Antenatal depression is an important public health issue affecting the physical and mental health of pregnant women and maternal-infant outcomes, with a global prevalence of 10% to 20%. Psychological capital, as a positive psychological resource of pregnant women, includes 4 core dimensions: Self-efficacy, hope, optimism, and resilience, and plays a critical role in coping with pregnancy-related stress and maintaining mental health. However, current research on antenatal depression and psychological capital remains insufficient, particularly with regard to exploration of their latent heterogeneous patterns. This study aims to identify latent joint profile types of psychological capital and antenatal depression among pregnant women using latent profile analysis (LPA), and to quantify the effects of social support, sleep quality, and exercise behavior on different types, so as to provide empirical evidence for the precision of psychological interventions during pregnancy. A cross-sectional survey design was adopted. From July to December 2023, an online survey platform was used to conduct investigations in tertiary hospitals in Hubei Province, Liaoning Province, and Guangdong Province (one hospital per province, 3 hospitals in total). A total of 772 valid questionnaires were obtained. Data were collected using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), the 12-item short version of the Psychological Capital Questionnaire (PCQ-12), the Multidimensional Scale of Perceived Social Support (MSPSS) for perceived social support, the Pittsburgh Sleep Quality Index (PSQI), and a self-designed questionnaire. LPA was used to identify latent profile types of psychological capital and antenatal depression. The optimal fitting model was determined based on the Bayesian Information Criterion (BIC), entropy, and the Lo-Mendell-Rubin (LMR) adjusted likelihood ratio test results. Multinomial logistic regression was applied to evaluate the effects of various factors on different latent types. The three-class model was the optimal fitting model. The comprehensive deprivation group (3.50%) showed the lowest levels of psychological capital and the most severe depressive symptoms; the functionally restricted group (33.94%) showed moderate psychological capital and relatively high depressive symptoms; and the positive adjustment group (62.56%) showed high psychological capital and low depressive symptoms. Univariate analysis showed statistically significant differences among the 3 latent classes in occupation, educational level, monthly income, frequency of alcohol consumption during pregnancy, frequency of exercise during and before pregnancy, relationship with husband, perceived social support, and sleep quality (all P<0.05). After controlling for covariates, each 1-point increase in perceived social support increased the probability of pregnant women entering the positive adjustment group rather than the comprehensive deprivation group by 13.0% [odds ratio (OR)=1.130, 95% confidence interval (CI) 1.091 to 1.171, P<0.001]. Pregnant women who rarely exercised during pregnancy were more likely to enter the comprehensive deprivation group rather than the positive adjustment group (OR=0.107, 95% CI 0.012 to 0.962, P=0.046). Pregnant women with higher perceived social support scores were more likely to enter the positive adjustment group rather than the functionally limited group (OR=1.075, 95% CI 1.058 to 1.091, P<0.001), while pregnant women with poor sleep quality were more likely to enter the functionally limited group rather than the positive adjustment group (OR=0.902, 95% CI 0.848 to 0.959, P<0.001). Pregnant women with higher perceived social support scores were more likely to enter the functionally limited group rather than the comprehensive deprivation group (OR=1.052, 95% CI 1.017 to 1.087, P=0.003). Significant heterogeneity exists in psychological capital and antenatal depression among pregnant women, and 3 latent classes with clinical and intervention significance can be identified. Social support is a key protective factor in promoting psychological resilience and preventing antenatal depression, while regular physical activity and good sleep also have independent predictive value. It is recommended that positive psychological resources be incorporated into pregnancy mental health screening systems, promoting a shift in service models from "disease-oriented" to "resource-oriented" and implementing stratified intervention strategies based on class characteristics. For the positive adjustment group, participation in community peer support networks can be encouraged, and they can be cultivated as key opinion leaders for mental health promotion. For the functionally limited group, priority should be given to improving sleep disorders, increasing physical activity, and strengthening social connections to prevent progression to high-risk states. For the comprehensive deprivation group, inclusion in high-risk case management pathways in prenatal care clinics is required, with early identification and multidisciplinary collaborative interventions to effectively reduce the risk of adverse psychological and pregnancy outcomes and improve overall maternal and infant health. 目的: 产前抑郁是影响孕产妇身心健康和母婴结局的重要公共卫生问题，全球患病率为10%~20%。心理资本作为孕妇的一种积极心理资源，包括自我效能感、希望、韧性与乐观4个核心维度，可在应对孕期压力、维持心理健康中发挥关键作用。然而，目前关于产前抑郁和心理资本的研究仍不足，尤其缺乏对其潜在异质性模式的探索。本研究旨在通过潜在剖面分析(latent profile analysis，LPA)识别孕妇在心理资本与产前抑郁上的潜在联合剖面类型，并量化社会支持、睡眠质量与运动行为对不同类型的影响，为实现孕期心理干预的精准化提供实证依据。方法: 采用横断面调查设计，于2023年7至12月通过在线调查平台在湖北省、辽宁省和广东省的三级医院(每个省1家医院，共3家医院)开展调查，最终得到有效问卷772份。采用中文版爱丁堡产后抑郁量表(Edinburgh Postnatal Depression Scale，EPDS)、心理资本问卷12项简版(Psychological Capital Questionnaire-12，PCQ-12)、多维度领悟社会支持量表(Multidimensional Scale of Perceived Social Support，MSPSS)、匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index，PSQI)量表及自编问卷收集数据。通过LPA识别心理资本和产前抑郁的潜在剖面类型，依据贝叶斯信息准则、熵值及罗-门德尔-鲁宾(Lo-Mendell-Rubin，LMR)校正似然比检验结果等确定最优拟合模型，并采用多项Logistic回归评估各因素对不同潜在类型的影响。结果: 3类模型为最优拟合模型。3类模型中的全面匮乏组(占比为3.50%)心理资本水平最低、抑郁症状最严重，功能受限组(占比为33.94%)心理资本水平中等、抑郁症状偏高，积极调节组(占比为62.56%)心理资本水平高、抑郁症状低。单因素分析结果显示，3个潜在类别在职业、学历、家庭人均月收入、孕期伴侣的饮酒频率、孕前运动频率、孕期运动频率、与丈夫的关系、领悟社会支持、睡眠质量方面的差异均有统计学意义(均P<0.05)。在控制协变量后，MSPSS评分每增加1分，孕妇进入积极调节组而非全面匮乏组的概率提高13.0%[比值比(odds ratio，OR)=1.130，95%置信区间(confidence interval，CI) 1.091~1.171，P<0.001];孕期很少运动者更可能进入全面匮乏组而非积极调节组(OR=0.107，95% CI 0.012~0.962，P=0.046);MSPSS评分高的孕妇更可能进入积极调节组而非功能受限组(OR=1.075，95% CI 1.058~1.091，P<0.001)，PSQI评分高(睡眠质量差)的孕妇更可能进入功能受限组而非积极调节组(OR=0.902，95% CI 0.848~0.959，P<0.001);MSPSS评分高的孕妇更可能进入功能受限组而非全面匮乏组(OR=1.052，95% CI 1.017~1.087，P=0.003)。结论: 孕妇在心理资本与产前抑郁表现上存在显著异质性，可识别出具有临床与干预意义的3个潜在类别。社会支持是促进心理韧性、预防产前抑郁的关键保护因素，规律的运动与良好睡眠亦具有独立预测价值。建议将积极心理资源纳入孕期心理健康筛查体系，推动从“疾病导向”向“资源导向”的服务模式转型，并实施基于类别特征的分层干预策略:对积极调节组，可鼓励其参与社区同伴支持网络，培育为心理健康促进的关键意见领袖;对功能受限组，应重点改善睡眠障碍、增加身体活动、强化社会联结，阻断其向高危状态转化;对全面匮乏组，需纳入孕期保健门诊高危个案管理流程，开展早期识别与多学科协同干预，以有效降低不良心理及妊娠结局风险，提升母婴整体健康水平。.
The widespread use of immune checkpoint inhibitors (ICIs) has led to breakthrough advances for patients with various advanced solid tumors. As the skin is an important target organ of immune responses, it is the most commonly affected site of treatment-related adverse events associated with ICIs, with a relatively high incidence of ICI-related skin toxicity events. Immune-related adverse events induced by ICIs are increasingly becoming a bottleneck limiting their clinical application. To collect post-marketing adverse events and medication errors related to drugs and therapeutic biological products and to evaluate real-world drug safety, the United States Food and Drug Administration (FDA) established the FDA Adverse Event Reporting System (FAERS) database. Based on the FAERS database, this study aims to systematically evaluate differences in the risk of skin toxicity events among different drug subtypes, cytotoxic-T-lymphocyte-associated antigen-4 inhibitors, programmed death-1 (PD-1) inhibitors, and programmed death-ligand 1 (PD-L1) inhibitors, and to explore the limitations and potential improvements of existing pharmacovigilance methods. Skin toxicity event data from the FAERS database between 2004 and 2024 were cleaned, standardized, and screened to identify adverse events associated with the target drugs. Pharmacovigilance signal detection methods, including the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method, were used for the signals of ICIs-related skin toxicity event in the data, with stratified analyses by age and sex. For the ROR method, a skin toxicity event reporting count ≥3 and a lower bound of the 95% confidence interval (CI) >1 were used as criteria for a positive signal; for the Bayesian method, the information component was used as the core parameter. Subsequently, a systematic statistical analysis of the frequencies of different types of adverse events induced by different drugs was conducted, and outcomes associated with different drugs were summarized. Pharmacovigilance signal detection methods were applied for data analysis. A total of 15 768 reports of skin-related adverse events were collected. The reported population was predominantly male, with most patients aged ≥65 years, and a higher proportion of cases from Europe and the United States. Among the reported indications, the 3 most common were malignant melanoma, non-small cell lung cancer, and metastatic melanoma. Most adverse events occurred within 30 days after drug administration, during which the number of reports was the highest. Using the two signal detection methods, positive signals were identified for 5 of the 8 target drugs: nivolumab (ROR=1.20, 95% CI 1.17 to 1.23), pembrolizumab (ROR=1.31, 95% CI 1.27 to 1.35), ipilimumab (ROR=1.82, 95% CI 1.74 to 1.90), atezolizumab (ROR=1.06, 95% CI 1.01 to 1.12), and tislelizumab (ROR=3.05, 95% CI 2.71 to 3.43). Further analysis showed that the PD-1 inhibitors pembrolizumab and nivolumab had higher numbers of reported cases of immune-mediated dermatitis, vitiligo, psoriasis, and other skin toxicity events than other ICIs. Comparison of outcomes of skin toxicity reactions caused by different drugs revealed that nivolumab-related cases had the highest numbers of reports of hospitalization, death, and life-threatening, followed by pembrolizumab. Five ICIs may induce skin toxicity events, which exhibit specific population characteristics, temporal patterns, and toxicity profiles. When using the PD-1 inhibitors nivolumab or pembrolizumab, particular vigilance is required for severe cutaneous toxicity to avoid unfavorable outcomes. Expanding the sample size and incorporating machine learning in the future may improve the precision and clinical translatability of signal detection, providing important evidence for optimizing clinical monitoring strategies for ICIs and establishing toxicity early-warning models. 目的: 免疫检查点抑制剂(immune checkpoint inhibitors，ICIs)的广泛应用使多种晚期实体肿瘤患者的治疗获得突破性进展。皮肤作为免疫应答的重要靶器官，是ICIs治疗相关不良事件最常累及的部位，ICIs相关皮肤不良事件发生率较高。ICIs引发的免疫相关不良事件正逐渐成为制约其临床应用的瓶颈问题。美国食品药品监督管理局(Food and Drug Administration，FDA)为收集上市后的药品及治疗性生物制品的不良事件及用药错误，评估真实世界的药物安全性，建立FDA不良事件报告系统(FDA Adverse Event Reporting System，FAERS)数据库。本研究以FAERS数据库为基础，拟对不同的药物亚型[细胞毒性T淋巴细胞相关抗原-4抑制剂、程序性死亡受体-1(programmed death-1，PD-1)抑制剂及程序性死亡受体配体-1(programmed death-ligand 1，PD-L1)抑制剂]的皮肤不良事件风险差异进行系统评估，并对现有的药物警戒方法的局限性和改进方向进行探讨。方法: 对FAERS数据库中2004至2024年的皮肤不良事件数据进行清洗、标准化及筛选，获得发生目标药品不良事件数据集。采用报告比值比(reporting odds ratio，ROR)法及贝叶斯法对数据的ICIs相关皮肤不良事件信号进行分析，并进行年龄及性别分层分析。ROR法采用皮肤不良事件报告数≥3例且95%置信区间(confidence interval，CI)下限>1作为阳性信号判定标准;贝叶斯法则以信息成分值为核心参数;接下来对不同药物引发的不同种类的不良事件发生频数进行系统的统计分析;最后总结不同药物的转归情况。结果: 共收集皮肤相关不良事件报告15 768例。报告人群以男性为主，年龄多集中于65岁以上，且以欧美地区患者占比较高。在所涉及的适应证中，最常见的3种为恶性黑色素瘤、非小细胞肺癌及转移性黑色素瘤。不良事件多发生在用药后30 d内，报告例数最多。通过ROR法及贝叶斯法，共识别出8种目标药物中5种具有阳性信号，分别为纳武利尤单抗(ROR=1.20，95% CI 1.17~1.23)、帕博利珠单抗(ROR=1.31，95% CI 1.27~1.35)、伊匹木单抗(ROR=1.82，95% CI 1.74~1.90)、阿替利珠单抗(ROR=1.06，95% CI 1.01~1.12)及替雷利珠单抗(ROR=3.05，95% CI 2.71~3.43)。进一步分析显示，PD-1抑制剂帕博利珠单抗与纳武利尤单抗报告免疫介导性皮炎、白癜风、银屑病等多种皮肤不良事件例数高于其他ICIs。对不同药物所致皮肤不良事件的转归情况进行比较发现，纳武利尤单抗相关病例中，住院、死亡及危及生命的报告数量均居首位，帕博利珠单抗次之。结论: 5种ICIs均可能诱发皮肤不良事件，其发生呈现特定人群特征、时序特征及毒性特征;使用PD-1抑制剂纳武利尤单抗或帕博利珠单抗时，需特别警惕重度皮肤毒性，避免引起不良转归。未来可扩大样本并引入机器学习，有望提升信号检测精度与临床可转化性，为优化ICIs临床监测方案及建立毒性预警模型提供重要循证依据。.
The China Alzheimer's Disease Report 2024 reveals that the number of deaths in China due to Alzheimer's disease (AD) and other types of dementia reached 320 715, accounting for 19.8% of global dementia-related deaths. The socioeconomic burden is increasingly prominent and poses a serious threat to the health of Chinese residents. This study aims to analyze the changes in the disease burden of dementias among Chinese residents from 1992 to 2021 and to predict future trends, so as to provide a reference for dementia prevention and control. Based on data from the Global Burden of Disease (GBD) Study 2021, Joinpoint regression models were used to analyze the incidence and age-standardized incidence rate, deaths and age-standardized mortality rate, disability-adjusted life year (DALY) and age-standardized DALY rate of senile dementia among Chinese residents aged 60 years and above from 1992 to 2021. Age-period-cohort models were used to analyze incidence and mortality under different effects. Bayesian age-period-cohort models were applied to predict the age-standardized incidence rate of dementias among Chinese residents from 2022 to 2031. From 1992 to 2021, the disease burden of senile dementia among Chinese residents increased year by year. The age-standardized incidence rate and age-standardized DALY rate showed fluctuating upward trends, while the age-standardized mortality rate declined. The average annual percent change (AAPC) of the age-standardized incidence rate, age-standardized mortality rate, and age-standardized DALY rate were 0.57%, -0.07%, and 0.09%, respectively (all P<0.05). From 2019 to 2021, the numbers of incident cases, deaths, and DALY of dementia among Chinese residents aged 60 years and above increased significantly, with higher values in females than in males. The age-period-cohort model indicated that incidence and mortality risks increased with age, with a marked increase after 70 years of age; incidence risk showed a "wave-like" pattern of increase-decrease-increase over periods, while mortality risk showed a trend of decrease followed by increase; incidence risk fluctuated upward across birth cohorts, whereas mortality risk fluctuated downward. Predictions from the Bayesian age-period-cohort model indicate that from 2022 to 2031, the age-standardized incidence rate of dementia in China may continue to increase, reaching 1 616.87 per 100 000 in the total population, 1 304.71 per 100 000 in males, and 1 809.09 per 100 000 in females by 2031. From 1992 to 2021, the disease burden of senile dementia in China has increased year by year, with a particularly heavy burden among older women. Senile dementia remains a major public health problem, and its disease burden may continue to increase in the future. It is recommended to promote early screening to promote early screening among high-risk populations and to enhance public awareness through extensive health education to reduce incidence risk and comprehensively improve the effectiveness of senile dementia prevention and control. 目的: 《中国阿尔茨海默病报告2024》显示，中国因阿尔茨海默病(Alzheimer’s disease，AD)及其他类型痴呆导致的死亡人数为320 715例，占全球相关死亡总数的19.8%，其社会经济负担日益突出，对中国居民健康构成严重威胁。本研究旨在分析1992至2021年中国居民老年痴呆症疾病负担的变化状况并预测其变化趋势，为老年痴呆症防控提供参考。方法: 基于2021年全球疾病负担研究(Global Burden of Disease，GBD)数据，采用联结点(Joinpoint)回归模型分析1992至2021年中国60岁及以上居民老年痴呆症的发病人数及标化发病率、死亡人数及标化死亡率、伤残调整生命年(disability-adjusted life years，DALY)及标化DALY率;采用年龄-时期-队列模型，分析不同效应下的发病率和病死率;采用贝叶斯年龄-时期-队列模型，对2022至2031年中国居民老年痴呆症的标化发病率进行预测。结果: 1992至2021年中国居民老年痴呆症的疾病负担逐年加重，标化发病率与标化DALY率波动上升，标化死亡率下降，标化发病率、标化死亡率、标化DALY率的平均年度变化百分比(average annual percent change，AAPC)分别为0.57%、-0.07%、0.09%(均P<0.05)。2019至2021年，中国60岁及以上居民老年痴呆症发病人数、死亡人数和DALY均显著增加，且女性高于男性。年龄-时期-队列模型显示其发病和死亡风险与年龄增长相关，70岁以上增幅显著;发病风险随时期推移呈先升后降再升的“波浪形”，死亡风险呈先降后升的变化趋势;发病风险随出生队列推移波动上升，死亡风险波动下降。贝叶斯年龄-时期-队列模型预测结果表明，2022至2031年中国的标化发病率可能将持续增长，至2031年，总人群、男性、女性的标化发病率可分别达1 616.87/10万、1 304.71/10万、1 809.09/10万。结论: 1992至2021年中国老年痴呆症的疾病负担呈逐年增加的趋势，尤其在老年女性中格外沉重，仍是重大的公共卫生问题，且未来其疾病负担可能持续加重。建议推动高危人群早期筛查，并通过广泛的健康教育提升公众认知，降低发病风险，全面提升老年痴呆症的防控效果。.
Given the high incidence, poor prognosis, and scarcity of high-quality multimodal research data for acral melanoma in the Chinese population, this study aims to build a representative multimodal disease-specific cohort to provide a high-quality data foundation for characterizing disease features and exploring mechanisms of prognosis. This single-center prospective cohort was constructed by consecutively enrolling melanoma patients with pathological confirmation at Xiangya Hospital of Central South University between April 2016 and September 2024, while excluding minors and pregnant or lactating women. A standardized dataset comprising 16 internationally aligned core modules was built following global ontologies and clinical data standards. Data governance integrated a hybrid automated extract-transform-load (ETL) and artificial intelligence (AI)-assisted architecture. Pathology narratives were processed using Transformer-based natural language processing (NLP) models to extract textual and morphologic features, while raw imaging data were handled with deep learning pipelines for pixel-level modeling. Data quality was ensured through dual clinical-engineering validation, and outcomes were adjudicated using RECIST 1.1 and CTCAE v5.0 criteria. The cohort included 1 036 melanoma patients, consisting of 514 males (49.614%) and 522 females (50.386%), with a mean age of (60.2±13.7) years. Among 898 patients with a known clinical subtype, 606 (67.483%) were acral melanoma, the dominant subtype. In 678 patients with complete Breslow thickness data, the median Breslow thickness was 3.25 mm. Of 612 patients with recorded Clark levels, 277 (45.261%) were Clark level IV, the most frequent category. Among 880 patients with available clinical TNM (cTNM) staging, 329 (37.386%) were stage II, representing the largest proportion; Driver mutation profiling showed BRAFV600E positivity of 21.786% (61/280) and c-KIT mutation rate of 9.459% (7/74). Regarding treatment patterns, 217 patients (20.946%) received immunotherapy and 59 (5.695%) received targeted therapy. In 372 patients with complete systematic follow-up, there were 129 deaths (34.677%) and 86 recurrence/metastasis events (23.118%). Acral subtype, Clark level IV, and stage III-IV cTNM patients represented the major at-risk groups for death and recurrence/metastasis. The cohort integrated 8 536 digital pathology whole-slide images (WSI), 5 084 raw imaging data complying with Digital Imaging and Communications in Medicine (DICOM) imaging encounters, over 350 000 structured clinical-molecular data points, and a total data volume of 20.5 TB. This melanoma-specific multimodal cohort captures population-specific clinical, imaging, digital pathology, and molecular features for the Chinese population. It establishes a scalable, governed real-world research resource to enable comparative-effectiveness studies, prognostic biomarker discovery, and future development of AI-assisted diagnostic and prognostic models. 目的: 中国人群肢端型黑色素瘤高发且预后不良，目前尚缺乏多模态高质量研究数据。本研究旨在构建具有中国人群代表性的多模态专病队列，为解析疾病特征及预后机制提供数据基础。方法: 采用单中心前瞻性研究设计，连续纳入中南大学湘雅医院2016年4月至2024年9月经病理学检查确诊的黑色素瘤患者为研究对象，排除未成年人、妊娠期及哺乳期女性。基于国际标准构建包含16个核心模块的标准化数据集。数据治理采用自动化抽取-转换-加载(extract-transform-load，ETL)流程与人工智能(artificial intelligence，AI)相结合的混合架构，利用基于Transformer的自然语言处理(natural language processing，NLP)模型提取病理文本特征等，并结合深度学习模型处理医学影像等像素级数据。采用临床与工程双重校验机制保证数据质量，随访结局评估遵循实体瘤疗效评价标准1.1版和常见不良事件评价标准5.0版。结果: 多模态专病队列共纳入1 036例黑色素瘤患者，男514例(49.614%)，女522例(50.386%)，年龄为(60.2±13.7)岁。在898例具有明确临床分型的患者中，肢端型黑色素瘤606例(67.483%)，为主要亚型。在拥有完整Breslow厚度数据的678例患者中，Breslow厚度中位数值为3.25 mm。在612例具有明确Clark分级数据的患者中，Clark分级IV患者277例(45.261%)，为主要分级。在880例具有明确临床TNM(clinical TNM，cTNM)分期数据的患者中，II期患者329例(37.386%)，比例最高。驱动基因检测结果显示，B-Raf原癌基因丝氨酸/苏氨酸蛋白激酶V600E突变(B-Raf proto-oncogene serine/threonine kinase，BRAFV600E)检出率为21.786%(61/280)，干细胞生长因子受体(stem cell growth factor receptor，c-KIT)突变检出率为9.459%(7/74)。在治疗模式上，全队列有217例(20.946%)患者接受免疫治疗，59例(5.695%)患者接受靶向治疗。在完成系统随访的372例患者中，共记录死亡事件129例(34.677%)，复发/转移事件86例(23.118%);肢端型、Clark分级IV及cTNM分期III~IV患者为死亡、复发/转移的主要群体。队列整合了8 536张数字病理全切片图像(whole slide images，WSI)及5 084例次符合医学数字成像与通信(digital imaging and communications in medicine，DICOM)标准的原始影像数据等深层多模态数据，结构化数据点超 35万个，数据库总数据量达20.5 TB。结论: 该多模态专病队列整合了中国人群特异的临床、影像、病理和分子信息等数据资源，为开展真实世界研究、挖掘预后生物标志物，以及开发AI辅助诊疗模型提供了重要的数据基础。.
Chronic salpingitis is an important cause of secondary infertility, tubal pregnancy, and chronic pelvic pain in women. Its pathological characteristics mainly include adhesion of the tubal mucosa, impaired ciliary motility, and luminal occlusion. Due to the difficulty in obtaining human biopsy tissues, establishing a stable, standardized animal model consistent with the pathological progression in humans is of great academic significance for investigating the pathogenesis of chronic salpingitis and screening therapeutic drugs. Currently, there is still a lack of unified, reliable, and cost-effective animal model for chronic salpingitis. This study aims to evaluate the effects of Chlamydia muridarum (CM) and mixed bacteria (MB) in inducing chronic salpingitis in SD rats and to optimize the parameters for MB modeling. The study consisted of 2 stages: pathogen model comparison and MB dose-effect evaluation. For pathogen model comparison, 30 SPF female SD rats were randomly divided into a control (CON) group, a CM group [inoculation concentration 2×107 inclusion forming units (IFU)/mL], and an MB group [inoculation concentration 3×10⁹ colony forming units (CFU)/mL]. A reproductive tract inoculation method was used to establish the model. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were performed on days 1, 7, 14, 21, and 28 after modeling to observe pathological morphology of the fallopian tube and ultrastructural changes in epithelial cilia and mitochondria. For MB dose-effect evaluation, 30 specific pathogen free female SD rats were divided into a normal group, a low-dose MB group (3×1010 CFU/mL), and a high-dose MB group (3×1011 CFU/mL). Serum tumor necrosis factor-α (TNF-α) levels were measured on days 7 and 14 after modeling using enzyme-linked immunosorbent assay (ELISA). Combined with histomorphological scoring under microscopy, inflammation severity was quantitatively evaluated. Both the CM group and MB group successfully induced typical manifestations of chronic salpingitis. Light microscopy showed interstitial edema of the fallopian tube, thickening of the tubal wall, and marked infiltration of lymphocytes and plasma cells. Under TEM, rats in the modeling groups exhibited characteristic organelle damage, including disordered ciliary arrangement, extensive ciliary collapse and shedding, indistinct axoneme structure, and significant mitochondrial swelling with cristae disruption or disappearance and vacuolar degeneration in the cytoplasm. Time-course comparison showed that on day 7 after modeling, the MB group exhibited a more pronounced inflammatory response than the CM group, characterized by increased neutrophil infiltration. Dose-effect analysis demonstrated that on day 14 after modeling, serum TNF-α levels were significantly elevated in the high-dose MB group (P<0.01), accompanied by aggravated fallopian tube tissue damage with typical chronic inflammatory changes. Both CM and MB models can effectively simulate the complete pathological process of chronic salpingitis in humans, from acute inflammatory response to chronic fibrosis, with relatively high success rates. However, the CM model requires stringent pathogen culture conditions, higher purchase and maintenance costs, and a longer experimental cycle. In contrast, the MB model uses mixed bacterial strains that are easier to obtain and less costly to prepare. This study confirmed that the MB protocol constructed at a concentration of 3×10¹¹ CFU/mL can stably induce morphological changes consistent with chronic inflammation in rats, and the expression of inflammatory factors shows good quantifiability and reproducibility. This model provides a standardized experimental platform with important academic value for basic research, clinical drug screening, and translational studies of chronic salpingitis. 目的: 慢性输卵管炎是导致女性继发性不孕、输卵管妊娠及慢性盆腔疼痛的重要诱因，其病理特征主要表现为输卵管黏膜粘连、纤毛运动功能障碍及管腔闭锁。由于临床研究受限于人体活检组织获取的困难，建立一种稳定、标准且符合人体病理演变过程的动物模型对探讨慢性输卵管炎发病机制及筛选治疗药物具有重要的学术价值。目前尚缺乏统一明确、成功率高且经济实用的慢性输卵管炎动物模型。本研究旨在评估鼠衣原体(Chlamydia muridarum，CM)与混合菌(mixed bacteria，MB)诱导SD大鼠慢性输卵管炎的效果，并筛选优化MB造模的最佳参数。方法: 本研究分为病原体模型比较和MB剂量效应评估2个阶段。病原体模型比较:选取30只SPF级雌性SD大鼠，随机分为对照(control，CON)组、CM组[接种浓度2×107包涵体形成单位(inclusion forming units，IFU)/mL]和MB组[接种浓度3×109菌落形成单位(colony forming units，CFU)/mL]。采用生殖道接种法造模，采用苏木精-伊红(hematoxylin and eosin，HE)染色及透射电子显微镜(transmission electron microscopy，TEM)分别于造模后第1、7、14、21、28天观察输卵管组织病理形态及上皮纤毛、线粒体等超微结构变化。MB剂量效应评估:选取30只无特定病原体级雌性SD大鼠分为正常组、低浓度MB组(3×10¹⁰ CFU/mL)及高浓度MB组(3×1011 CFU/mL)。采用酶联免疫吸附测定(enzyme-linked immunosorbent assay，ELISA)技术检测造模后第7、14天血清肿瘤坏死因子-α(tumor necrosis factor-alpha，TNF-α)水平，结合显微镜下的组织形态学评分对炎症程度进行客观的量化评估。结果: CM组与MB组均成功诱发了典型的慢性输卵管炎表现，光镜下可见输卵管间质水肿、管壁增厚及明显的淋巴细胞和浆细胞浸润。在TEM超微结构下，造模组大鼠表现出极具特征性的细胞器损伤，包括纤毛排列紊乱、大面积倒伏脱落，轴丝结构不清晰，以及细胞质内线粒体显著肿胀、嵴断裂消失甚至出现空泡样变。时效性对比显示，在造模后第7天，MB组表现出比CM组更显著的炎症反应，其特征为中性粒细胞浸润明显增多。剂量效应分析显示，在造模后第14天，高浓度MB组大鼠血清TNF-α水平显著升高(P<0.01)，且输卵管组织损伤程度加剧，呈现出典型的慢性炎症改变。结论: CM模型和MB模型均能有效模拟人类慢性输卵管炎从急性炎症反应向慢性纤维化演变的完整病理过程，且2种模型均具有较高的成功率。然而CM模型的病原体培养条件苛刻，购买及维护成本较高，实验周期较长。相比之下，MB模型所采用的混合菌菌株获取便捷、制备成本低廉，且在3×1011 CFU/mL这一特定浓度下构建的MB方案，不仅能够稳定诱导大鼠产生符合慢性炎症标准的形态学改变，而且其炎症因子的表达具有良好的可量化性与可重复性，为慢性输卵管炎的基础研究、临床药物筛选及转化医学研究提供了具有重要学术价值的标准实验载体。.
Spinal cord stimulation (SCS) is a commonly used treatment for refractory zoster-associated pain (ZAP). The conventional open-loop regulation mode mainly relies on patients' subjective feedback for manual parameter adjustment, whereas the clinical application of closed-loop SCS regulation remains immature and requires further optimization. Previous studies have shown that SCS can influence electroencephalography (EEG) functional connectivity. This study aims to investigate whether a support vector machine (SVM) based on EEG functional connectivity features can effectively identify different neuromodulation states of SCS. A total of 21 patients with ZAP who underwent SCS treatment were retrospectively included. Visual Analogue Scale (VAS) scores were recorded before SCS implantation, at discharge, and at 1, 3, and 6 months postoperatively. EEG data lasting 5-10 minutes were collected under SCS-on and SCS-off conditions. The EEG data were randomly divided into a training set and a test set at a ratio of 7∶3. Pearson correlation coefficient (PCC) and coherence (COH) between EEG feature channels were extracted to construct an SVM-based classification model. Model performance in distinguishing SCS-on and SCS-off EEG states was evaluated using accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Shapley additive explanations (SHAP) were used to interpret the SVM model by analyzing the contribution and direction of each EEG feature to the model prediction. SCS effectively alleviated pain in patients with ZAP. Compared with baseline, VAS scores were significantly reduced at discharge and at 1, 3, and 6 months after SCS treatment (all P<0.001). The classification performance of SVM with different kernel functions for identifying SCS neuromodulation states showed that the radial basis function kernel SVM achieved an accuracy of 0.912, sensitivity of 0.927, specificity of 0.893, and AUC of 0.972, whereas the linear kernel SVM achieved an accuracy of 0.677, sensitivity of 0.714, specificity of 0.665, and AUC of 0.744. SHAP analysis showed that the top 20 most influential features contributing to the classification results were all COH features. In the beta frequency band, the COH between electrode pairs O2-F8 and FP2-F7 contributed most strongly to the model prediction, and increases in these values were positively associated with the SCS-on state. In contrast, the COH of the P4-P8 electrode pair in the theta frequency band was closely associated with the SCS-off state. The SVM model based on EEG functional connectivity features can effectively identify different neuromodulation states of SCS in patients with ZAP. These findings suggest that SCS may induce alterations in brain functional connectivity and provide a basis for future studies on EEG-based closed-loop SCS regulation. 目的: 脊髓电刺激(spinal cord stimulation，SCS)是治疗难治性带状疱疹相关性疼痛(zoster-associated pain，ZAP)的常用方法。传统开环调控模式主要依赖患者主观反馈进行人工参数调节，而闭环调控模式的SCS临床应用尚不成熟，其优化与完善仍需进一步探索。已有研究发现SCS可影响脑电功能连接特征。本研究旨在探讨基于脑电功能连接特征的支持向量机(support vector machine，SVM)能否有效识别SCS的不同调控状态。方法: 回顾性纳入21例行SCS治疗的ZAP患者，记录置入SCS治疗前，出院时，术后1、3、6个月的疼痛视觉模拟评分法(Visual Analogue Scale，VAS)评分。采集SCS开启(SCS-on)和关闭(SCS-off)状态下5~10 min的脑电数据，将脑电数据按7∶3随机划分为训练集和测试集。提取脑电特征导联的皮尔逊相关系数(Pearson correlation coefficient，PCC)及相干性(coherence，COH)，构建基于SVM的分类模型。采用准确率、灵敏度、特异度及受试者操作特征曲线下面积(area under the curve，AUC)作为评估指标，验证模型对SCS-on与SCS-off 2种脑电状态的识别效果;采用夏普利加性解释(Shapley additive explanations，SHAP)方法分析各脑电特征对SVM模型预测的贡献度和作用方向。结果: SCS能够有效缓解ZAP患者的疼痛，患者经SCS治疗后，在出院时及术后1、3、6个月的VAS评分均显著低于治疗前，差异均有统计学意义(均P<0.001)。不同核函数SVM识别SCS调控状态的结果显示:径向基核SVM准确率为0.912，灵敏度为0.927，特异度为0.893，AUC为0.972;线性核SVM准确率为0.677，灵敏度为0.714，特异度为0.665，AUC为0.744。SHAP分析结果显示:对模型分类结果贡献最为显著的前20个关键特征均为COH特征;beta频段中O2-F8、FP2-F7电极对的COH对模型预测的贡献度最高，且二者数值的升高与SCS-on状态呈正相关;而theta频段P4-P8电极对的COH则与SCS-off状态密切相关。结论: 基于脑电功能连接特征的SVM模型能够识别ZAP患者SCS不同调控状态，提示SCS可能引起脑功能连接特征发生改变，为今后研究基于脑电闭环调控SCS提供了基础。.
Under the guidance of analogical thinking in traditional Chinese medicine (TCM), the "treating of skin with skin" therapy, using processed animal and plant skin-derived medicinal materials to treat skin diseases, has a long history but lacks scientific evidence-based support. This study aims to apply data mining and network pharmacology techniques to explore the prescription patterns and mechanisms of action of the "treating skin with skin" therapy, and to interpret its rationality, effectiveness, and scientific basis using modern scientific methods. Relevant literature from Chinese and English databases over the past 20 years was retrieved and integrated according to inclusion and exclusion criteria. Data were integrated and mined using software such as Excel, OriginPro 2021, and SPSS Modeler 18.0. Frequency analysis, cluster analysis, and association rule analysis were performed sequentially to summarize high-frequency plant skin-derived Chinese medicinal materials and extract the core prescription. Core prescription drugs and skin disease-related gene targets were obtained from drug and disease target databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and GeneCards. Intersection targets were identified using Venny 2.1.0, and core targets were further extracted. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted for the intersection targets, and finally a "core drug-component-target-pathway" network was constructed and visualized. Based on the inclusion and exclusion criteria, 563 eligible articles were ultimately included, from which 32 prescriptions were extracted, involving 21 plant skin-derived Chinese medicinal materials. Among them, 15 medicinal materials had a usage frequency exceeding 50%, with bitter, sweet, and cold properties predominating. Cluster analysis yielded 4 effective clusters. Cluster 1: Phellodendron cortex-Dictamni cortex; Cluster 2: Eucommia cortex-Mori cortex-Meliae cortex-Pseudolaricis cortex; Cluster 3: Moutan cortex-Poriae Cutis-Lycii cortex-Fraxini cortex-Acanthopanacis cortex-Benincasae Pericarpium; Cluster 4: Ailanthi cortex-Periplocae cortex-Erycibes cortex. Association rule analysis generated 92 association rules, with 4 strong links, 90 moderate links, and 10 weak links between herb pairs. Based on the association rules and linkage strength, the core prescription of the "treating skin with skin" therapy was summarized as "Phellodendri Cortex-Moutan Cortex-Dictamni Cortex-Benincasae Pericarpium-Poriae Cutis-Lycii Cortex." A total of 46 active ingredients were screened from this core prescription, involving 781 gene targets. A total of 2 537 skin disease-related gene targets were retrieved, yielding 212 intersection targets between the core prescription and the disease. PPI network analysis of the intersection targets showed 2 723 edges among 212 nodes, with an average node degree of 25.9 and an average local clustering coefficient of 0.554. The PPI network of core targets contained 50 nodes and 784 edges; the top three core nodes by degrees were interleukin-6 (IL-6; 116), tumor necrosis factor (TNF; 115), and interleukin-1 beta (IL-1β; 110). GO analysis yielded 732 biological process terms, with the top 3 being response to lipopolysaccharide, positive regulation of DNA-templated transcription, and positive regulation of microRNA (miRNA) transcription; 90 cellular component terms, with the top 3 being extracellular space, extracellular region, and chromatin; and 153 molecular function terms, with the top 3 being enzyme binding, nuclear receptor activity, and identical protein binding. KEGG analysis identified 166 enriched signaling pathways, with the top 3 being pathways in cancer, lipid and atherosclerosis, and the advanced glycation end products-receptor for advanced glycation end products pathway in diabetic complications. The visualized "core drug-component-target-pathway" network comprised 854 nodes and 1 911 edges, with a network centralization coefficient of 0.182 and a characteristic path length of 3.985; the top 3 nodes by degree were all drug components, namely vitamin E, vitamin B, and trigonelline. Guided by TCM analogical thinking, the core prescription of the "treating skin with skin" therapy exerts therapeutic effects on skin diseases through synergistic actions involving multiple components, multiple targets, and multiple pathways. Its effect is significant, the rationale is well founded, and its origins are well established. 目的: 中医类象思维下，以炮制后的动、植物皮类药物治疗皮肤病的“以皮治皮”疗法历史悠久，但缺乏科学循证依据。本研究拟运用数据挖掘和网络药理学技术，探析“以皮治皮”疗法的处方规律及作用机制，以现代科学方法阐释其合理性、有效性及科学性。方法: 检索近20年中、英文数据库中的相关文献，并依据纳入和排除标准对文献进行整理，通过Excel、OriginPro 2021、SPSS Modeler 18.0等软件对数据进行整合及挖掘，依次进行频次分析、聚类分析和关联规则分析，总结高频植物皮类中药并提炼核心处方;通过中药系统药理学数据库与分析平台、GeneCards等药物和疾病靶点数据库获取核心处方药物和皮肤病对应的基因靶点，通过Venny 2.1.0获取交集靶点，并进一步提取核心靶点;对交集靶点进行蛋白质-蛋白质相互作用(protein-protein interaction，PPI)网络分析、基因本体论(Gene Ontology，GO)功能富集及京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析，最终构建可视化的“核心药物-成分-靶点-通路”网络。结果: 依据纳入和排除标准，最终纳入合格文献563篇，提取处方32首，涉及皮类植物中药21味，其中15味中药使用频率超过50%，性味以苦、甘、寒为主。聚类分析得到4个有效聚类群，分别是类1:黄柏-白鲜皮;类2:杜仲-桑白皮-苦楝皮-土荆皮;类3:牡丹皮-茯苓皮-地骨皮-秦皮-五加皮-冬瓜皮;类4:椿皮-香加皮-海桐皮。关联规则分析得到92条关联规则，药对之间得到4个强链接、90个中等链接和10个弱链接;根据关联规则和链接程度，总结出“以皮治皮”疗法的核心处方为“黄柏-牡丹皮-白鲜皮-冬瓜皮-茯苓皮-地骨皮”。该核心处方共筛选出46个有效活性成分，涉及基因靶点781个，检索获取皮肤病相关基因靶点2 537个，得到核心处方与疾病交集靶点212个。交集靶点的PPI网络分析显示，212个节点间共有2 723条边，平均节点度值为25.9，平均局部聚类系数为0.554;核心靶点的PPI网络共包含50个节点，784条边，核心节点度值排位前3的分别是白细胞介素-6(interleukin-6，IL-6;116)、肿瘤坏死因子(tumor necrosis factor，TNF;115)和白细胞介素-1β(interleukin-1 beta，IL-1β;110)。GO分析得到的条目中涉及生物过程的有732条，排位前3的分别是对脂多糖的反应、DNA模板转录的正向调控及微RNA(microRNA，miRNA)转录的正向调控;细胞组成的有90条，排位前3的分别是细胞外空间、细胞外领域(胞外区)及染色质;分子功能的有153条，排位前3的分别是酶结合、核受体活性及相同蛋白质结合。KEGG分析共得到166条富集信号通路，排位前3的分别是癌症、脂质与动脉粥样硬化、糖尿病并发症中的晚期糖基化终产物-晚期糖基化终产物受体通路;“核心药物-成分-靶点-通路”可视化网络分析共包含854个节点，1 911条边，网络集中化系数为0.182，特征路径长度为3.985，度值排名前3的均是药物成分，分别为维生素E、维生素B和葫芦巴碱。结论: 在中医类象思维指引下，“以皮治皮”疗法的核心处方通过多成分、多靶点、多通路协同发挥皮肤病治疗作用，其效显著，理据充分，渊源有自。.
The occurrence, metastasis, and drug resistance of melanoma pose major challenges to patient prognosis, and predictive models capable of accurately forecasting patient outcomes and guiding treatment are still lacking. This study aims to develop predictive models for melanoma prognosis and drug sensitivity based on mechanisms of programmed cell death (PCD). Genes related to 19 PCD patterns were collected and integrated from gene set enrichment analysis (GSEA), the Kyoto Encyclopedia of Genes and Genomes (KEGG), relevant reviews, and published studies to establish a comprehensive PCD signature gene set. Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) skin cutaneous melanoma (SKCM) cohort were obtained, and 3 untreated Gene Expression Omnibus (GEO) datasets (GSE65904, GSE19234, and GSE100797) were included as external validation cohorts. In addition, immunotherapy cohorts PRJEB23709, GSE136961, and GSE215222 were collected to validate the predictive value for immunotherapy. Single-cell transcriptomic data (GSE115978 and GSE215120) were processed using Seurat for quality control, normalization, dimensionality reduction, clustering, and cell annotation; spatial transcriptomic data were obtained from 10× Genomics and combined with Cottrazm for spatial partitioning and SpaCET deconvolution. Cell-cell communication was evaluated using CellChat to assess secreted signaling, extracellular matrix (ECM)-receptor interactions, and cell contact-mediated communication patterns. Based on the TCGA training set, a machine learning strategy comprising 10 algorithms and 101 combinations was used to construct PCD-related prognostic signatures, and the optimal model was selected using the average concordance index (C-index) across multiple cohorts. Differential analysis, GSEA, CIBERSORT, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) were further applied to evaluate immune infiltration, calculate T-cell receptor (TCR) clonal diversity, cytolytic activity, and T-cell effector gene expression profiles, and to explore the association between the PCD score (PCDS) and drug sensitivity. The activities of the 19 PCD pathways differed significantly between normal skin and SKCM, suggesting that dysregulation is involved in melanoma progression. Mutation analysis showed that titin (TTN) and mucin 16 (MUC16) had the highest mutation frequencies. After controlling for collinearity and correlation screening, 314 candidate genes were obtained. Among the 101 model combinations, StepCox (backward)+Ridge performed best (average C-index across 4 cohorts=0.677). The PCDS constructed based on this model stably stratified prognosis: The high-PCDS group showed significantly worse survival in TCGA and 3 external validation cohorts and remained an independent prognostic indicator after adjustment for age, sex, stage, Breslow thickness, Clark level, and ulceration. Immune analyses indicated that high PCDS was associated with immunosuppression: Immune scores were reduced; CD8+ T cells, activated memory CD4+ T cells, plasma cells, and M1 macrophages were decreased, whereas M2 macrophages were increased. PCDS was significantly negatively correlated with immune checkpoint molecules, TCR Shannon index, cytolytic activity score (CYT), and T-cell effector gene expression profile (T-GEP), and was highest in the immune-desert subtype. Spatial transcriptomic and single-cell results suggested spatial and cellular heterogeneity of PCDS: PCDS was lower at boundary regions and negatively correlated with macrophage proportions; myeloid cells had the lowest overall PCDS, macrophages exhibited the strongest communication with T/natural killer (NK) cells, and after immunotherapy, macrophages were enriched with enhanced human leukocyte antigen (HLA)-A/B/C-CD8a-related interactions. In clinical applications, PCDS demonstrated greater robustness compared with 100 previously reported prognostic signatures and complemented hot-cold tumor classification by identifying high-risk patients even among "hot tumors". Validation in immunotherapy cohorts showed that PCDS was negatively associated with therapeutic benefit; high PCDS was more likely to be associated with non-response and poorer prognosis. Drug analyses suggested that PCDS was associated with sensitivity to multiple drugs and could be used for potential treatment stratification. PCDS is a cross-cohort robust tool for predicting melanoma prognosis and immunotherapy benefit, reflecting the degree of immunosuppression in the tumor immune microenvironment and myeloid/macrophage-related immunoregulatory features, and provides a basis for individualized risk stratification and potential drug selection. This study provides an in-depth elucidation of the regulatory mechanisms of PCD in the tumor immune microenvironment and offers an important theoretical foundation for personalized treatment decision-making in melanoma patients. 目的: 黑色素瘤的发生、转移及耐药性对患者预后构成重大挑战，目前尚缺乏能够准确预测患者结局并指导治疗的预测模型。本研究旨在基于程序性细胞死亡(programmed cell death，PCD)机制开发黑色素瘤预后和药物敏感性的预测模型。方法: 从基因集富集分析(gene set enrichment analysis，GSEA)、京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)、相关综述及已发表研究中收集并整合19种PCD模式相关基因，建立全面的PCD特征基因集。获取癌症基因组图谱(The Cancer Genome Atlas，TCGA)-皮肤黑色素瘤(skin cutaneous melanoma，SKCM)队列的转录组与临床数据，并纳入3个未经治疗的基因表达综合(Gene Expression Omnibus，GEO)数据集(GSE65904、GSE19234、GSE100797)作为外部验证队列;同时收集免疫治疗队列PRJEB23709、GSE136961与GSE215222用于验证其对免疫治疗的预测价值。单细胞转录组数据(GSE115978、GSE215120)采用Seurat进行质量控制、标准化、降维聚类与细胞注释，空间转录组数据来源于10×Genomics，并结合Cottrazm进行空间分区与SpaCET解卷积;细胞通信采用CellChat评估分泌信号、细胞外基质(extracellular matrix，ECM)-受体互作及细胞接触等通信模式。基于TCGA训练集，采用包含10种算法及101种组合的机器学习策略构建PCD相关预后特征，并以多队列平均一致性指数(C-index)筛选最优模型;进一步结合差异分析、GSEA、CIBERSORT与基于表达估计恶性肿瘤组织的基质细胞和免疫细胞(Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data，ESTIMATE)评估免疫浸润，计算T细胞受体(T-cell receptor，TCR)克隆多样性、细胞溶解活性与T细胞效应基因表达谱，并探索PCD评分(PCD score，PCDS)与药物敏感性的关联。结果: 19种PCD通路在正常皮肤与SKCM间的活性显著不同，提示PCD异常参与黑色素瘤进展;突变分析显示肌巨蛋白(titin，TTN)和黏蛋白16(mucin 16，MUC16)突变频率最高。经共线性控制与相关性筛选获得314个候选基因，在101种模型组合中，StepCox(backward)+Ridge表现最佳(4个队列平均C-index=0.677)。基于该模型构建的PCDS可稳定分层预后，高PCDS组在TCGA及3个外部验证队列中生存显著更差，且在校正年龄、性别、分期、Breslow厚度、Clark分级和溃疡等因素后仍为独立预后指标。免疫分析表明，高PCDS与免疫抑制相关:免疫评分降低，CD8+ T细胞、活化记忆CD4+ T细胞、浆细胞、M1型巨噬细胞均减少而M2型巨噬细胞增加;PCDS与免疫检查点分子、TCR Shannon指数、细胞溶解活性评分(cytolytic activity score，CYT)及T细胞效应基因表达谱(T-cell effector gene expression profile，T-GEP)均呈显著负相关，并在免疫荒漠型中最高。空间转录组与单细胞结果提示PCDS存在空间/细胞异质性:边界区PCDS更低且与巨噬细胞比例呈负相关;髓系细胞总体PCDS最低，巨噬细胞与T/自然杀伤(natural killer，NK)细胞通信最强，免疫治疗后巨噬细胞富集并增强人类白细胞抗原(human leukocyte antigen，HLA)-A/B/C-CD8a相关互作。临床应用上，PCDS在与既往100个预后特征比较中表现更稳健，并可补充“热-冷肿瘤”分型，在“热肿瘤”中仍能识别高风险患者。免疫治疗队列验证显示PCDS与疗效获益呈负相关，高PCDS更可能无应答且预后更差;药物分析提示PCDS与多种药物敏感性相关，可用于潜在治疗分层。结论: PCDS是一个跨队列稳健的黑色素瘤预后与免疫治疗获益预测工具，反映免疫微环境抑制程度及髓系/巨噬细胞相关免疫调控特征，并为个体化风险分层与潜在用药选择提供依据。深入解析PCD在肿瘤免疫微环境中的调控机制，可为黑色素瘤患者个性化治疗决策提供重要理论基础。.
Postpartum depression (PPD) is a common and serious mental disorder after childbirth, imposing a heavy burden on mothers, infants, and families. Abnormalities in the tryptophan-kynurenine (TRP-KYN) metabolic pathway are considered to be involved in its pathogenesis, but the role of quinolinic acid phosphoribosyltransferase (QPRT), a key downstream enzyme in this pathway, remains unclear. This study aims to explore the association between PPD in women undergoing cesarean section and QPRT gene polymorphisms, as well as other risk factors for PPD. A candidate gene association study design was adopted. From January 2024 to June 2025, full-term singleton pregnant women scheduled to undergo elective cesarean section under spinal anesthesia were recruited at the Third Xiangya Hospital of Central South University and Hunan Provincial Maternal and Child Health Hospital. At 42 days postpartum, postpartum depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Peripheral blood samples were collected and genomic DNA was extracted. Four QPRT single nucleotide polymorphism loci (rs1134700, rs2303255, rs9922666, and rs9933310) were selected for genotyping to analyze the association between these loci and PPD. Bioinformatics analysis and dual-luciferase reporter gene assays were performed to investigate the possible mechanism by which significant loci influence disease occurrence. A total of 362 women were ultimately included in the analysis, among whom 29 were diagnosed with PPD, with an incidence of 8.01%. Analysis of general data showed that comorbid hypertension or thyroid disease, inconsistency between neonatal sex and expectation, prenatal depression, prenatal self-harm ideation, domestic violence, poor marital and mother-in-law/daughter-in-law relationships, stressful life events, dissatisfaction with current life status, poor mood during pregnancy, and high stress during pregnancy were all risk factors for PPD in women undergoing cesarean section (all P<0.05). Genetic association analysis revealed that the QPRT rs9933310 A>G polymorphism was associated with PPD. Women carrying the rs9933310 GG or AG genotype had a 2.92-fold higher risk of PPD compared with women with the AA genotype (OR=2.92, 95% CI 1.18 to 6.99). Expression quantitative trait loci (eQTL) analysis suggested that the G allele at this locus was associated with downregulation of QPRT expression (AA>AG>GG). Multi-database queries indicated that the rs9933310 locus may have promoter and/or enhancer activity. In addition, JASPAR database prediction and experimental validation showed that the mutant (G) allele at the QPRT rs9933310 locus was more likely than the wild-type (A) allele to weaken promoter-enhancer activity at this locus, and resulted in loss of transcription factors Gata1, GATA2, GATA3, Gata4, Sox17, Sox2, Sox3, Sox6, and SRY, thereby regulating QPRT expression. Comorbid hypertension or thyroid disease, inconsistency between neonatal sex and expectation, prenatal depression, prenatal self-harm ideation, domestic violence, poor marital and mother-in-law/daughter-in-law relationships, stressful life events, dissatisfaction with current life status, poor mood during pregnancy, high stress during pregnancy, and mutation at the QPRT rs9933310 locus are all risk factors for PPD. The QPRT rs9933310 G allele is an independent risk factor for PPD in women undergoing cesarean section, and its pathogenic mechanism may involve downregulation of QPRT expression and disruption of TRP-KYN pathway homeostasis. QPRT has a potential role in the pathogenesis of PPD and may become a novel antidepressant target acting on the TRP-KYN pathway. 目的: 产后抑郁(postpartum depression，PPD)是分娩后常见且严重的精神障碍，对母亲、婴儿及家庭均造成沉重负担。色氨酸-犬尿氨酸(tryptophan-kynurenine，TRP-KYN)代谢通路异常被认为参与其发病机制，但该通路下游的关键酶——喹啉酸磷酸核糖基转移酶(quinolinic acid phosphoribosyltransferase，QPRT)的作用尚未阐明。本研究旨在探讨剖宫产产妇PPD与QPRT基因多态性的关联性，以及PPD的其他危险因素。方法: 采用候选基因关联研究设计。于2024年1月至2025年6月在中南大学湘雅三医院及湖南省妇幼保健院招募计划在腰麻下行择期剖宫产的足月单胎妊娠产妇。产后42 d时采用爱丁堡产后抑郁量表(Edinburgh Postnatal Depression Scale，EPDS)评估产妇产后抑郁水平。采集产妇外周血样本并提取基因组DNA，选取4个QPRT单核苷酸多态性位点(rs1134700、rs2303255、rs9922666和rs9933310)进行基因型检测以分析各位点与PPD的关联性，并通过生物信息学分析、双荧光素酶报告基因实验探究有意义位点影响发病的可能机制。结果: 最终362例产妇被纳入分析，其中29例被诊断为PPD，发病率为8.01%。一般资料分析显示:合并高血压或甲状腺疾病、新生儿性别与期望不一致、产前抑郁、产前有自我伤害想法、家庭暴力、不良的夫妻及婆媳关系、生活应激事件、对生活现状不满、孕期情绪差及压力大均为剖宫产产妇发生PPD的危险因素(均P<0.05)。遗传关联分析发现，QPRT rs9933310 A>G基因多态性与PPD具有关联性，携带至少一个G等位基因(GG或AG基因型)的女性患PPD的风险为AA基因型女性的2.92倍(OR=2.92，95% CI 1.18~6.99)。表达数量性状位点(expression quantitative trait loci，eQTL)分析提示，该位点G等位基因与QPRT表达下调相关(AA型>AG型>GG型)。多数据库查询结果显示rs9933310位点可能具有启动子和/或增强子活性。此外，JASPAR数据库预测及实验验证显示，QPRT rs9933310位点突变型(G)较野生型(A)更可能削弱了该位点的启动子增强子活性，并且缺失转录因子Gata1、GATA2、GATA3、Gata4、Sox17、Sox2、Sox3、Sox6和SRY，从而调控QPRT表达。结论: 合并高血压或甲状腺疾病、新生儿性别与期望不一致、产前抑郁、产前有自我伤害的想法、家庭暴力、不良的夫妻关系和婆媳关系、生活应激事件、对生活现状不满意、孕期心情差及孕期压力大、QPRT rs9933310位点突变均为PPD的危险因素。QPRT rs9933310 G等位基因是剖宫产产妇PPD的独立危险因素，其机制可能通过下调QPRT表达，影响TRP-KYN通路稳态。QPRT在PPD发病机制中具有潜在作用，有望成为作用于TRP-KYN通路的抗抑郁新靶点。.
With the intensification of global population aging, the incidence of depressive symptoms among older women has increased year by year, affecting their quality of life and physical and mental health. Therefore, investigating the impact of daytime napping behavior on depressive symptoms in older women, particularly the regulatory effects of napping on frailty status and inflammatory response, is of important clinical and public health significance. This study aims to explore the relationship between daytime napping behavior and depressive symptoms in older women, with a focus on the chain mediating roles of frailty status and C-reactive protein (CRP) between napping and depressive symptoms. This study used 5 waves of data from the China Health and Retirement Longitudinal Study (CHARLS), including 3755 female participants aged ≥45 years. First, descriptive statistics and difference analyses were used to summarize baseline characteristics of the participants. Second, Cox proportional hazards regression models were used to analyze the effects of napping habits and nap duration on depressive symptoms. To explore the biological mechanisms linking napping and depressive symptoms, path analysis was further conducted to examine the chain mediating roles of frailty status and CRP in the effect of napping on depressive symptoms. To control for potential confounding factors, all analyses were adjusted for multiple covariates, including age, education level, marital status, smoking, drinking, social participation, and physical exercise. Finally, subgroup analyses were conducted to further verify the moderating effects of different lifestyles on the impact of napping. Napping behavior was significantly associated with a lower risk of depressive symptoms, particularly among women with nap durations of 5 to 30 minutes, who had the lowest risk of depressive symptoms. Specifically, individuals with nap durations of 5 to 30 minutes had a lower risk of depressive symptoms (HR=0.750, 95% CI 0.637 to 0.883, P<0.001), whereas those with naps longer than 60 minutes did not show a significant reduction in depressive symptom risk (HR=0.934, 95% CI 0.811 to 1.076, P=0.347). Further path analysis showed that there is a total indirect effect between napping and depressive symptoms (β=-0.0219, P<0.05), and there is an overall effect between the two (β=-0.081, P<0.05), indicating that napping could indirectly alleviate depressive symptoms by slowing frailty progression and reducing CRP levels. Subgroup analysis showed that the protective effect of napping on depressive symptoms was more pronounced among women who did not smoke or drink, exercised regularly, and participated in social activities, suggesting that the psychological protective effect of napping depends on an individual's overall health behavior pattern. Daytime napping exerts a chain mediating effect on depressive symptoms in older women through frailty status and CRP levels. Moderate napping, especially short naps of 5 to 30 minutes, can effectively reduce the risk of depressive symptoms, and this effect may be achieved by improving physical function and alleviating frailty and inflammatory responses. 目的: 随着全球老龄化问题的加剧，老年女性抑郁症状的发病率逐年上升，影响其生活质量和身心健康。因此，研究午睡行为对老年女性抑郁症状的影响，特别是午睡对虚弱状态和炎症反应的调节作用，具有重要的临床和公共卫生意义。本研究旨在探讨午睡行为与老年女性抑郁症状的关系，重点分析虚弱状态和C反应蛋白(C-reactive protein，CRP)在午睡与抑郁症状之间的链式中介作用。方法: 采用中国健康与养老追踪调查(China Health and Retirement Longitudinal Study，CHARLS)的5期数据，涵盖3 755名年龄≥45岁的女性参与者。首先，通过描述性统计和差异性分析对参与者的基线特征进行整理。其次，采用Cox比例风险回归模型分析午睡习惯及午睡时长对抑郁症状的影响。为探讨午睡与抑郁症状之间的生物学机制，进一步使用路径分析方法，探索虚弱状态和CRP在午睡对抑郁症状影响中的链式中介作用。为排除潜在的混杂因素，所有分析均调整了年龄、教育程度、婚姻状况、吸烟、饮酒、社交、锻炼等多个协变量。最后，通过亚组分析进一步验证不同生活方式对午睡效应的调节作用。结果: 午睡习惯与较低的抑郁症状风险显著相关，尤其是午睡时长在5~30 min的女性群体，有抑郁症状的风险最低。具体而言，午睡时长为5~30 min的个体抑郁症状的风险较低(HR=0.750，95% CI 0.637~0.883，P<0.001)，而午睡超过60 min的个体未能显著降低抑郁症状的风险(HR=0.934，95% CI 0.811~1.076，P=0.347)。进一步的路径分析表明，午睡与抑郁症状之间存在总间接效应(β=-0.0219，P<0.05)，二者存在总体效应(β=-0.081，P<0.05)，表明午睡能够通过减缓虚弱状态和降低CRP水平间接减轻抑郁症状。亚组分析显示，午睡对抑郁症状的保护作用在不吸烟、不饮酒、积极锻炼和参与社交活动的女性群体中更加显著，这表明午睡行为的心理保护作用依赖于个体的整体健康行为模式。结论: 午睡行为通过虚弱状态和CRP水平在老年女性抑郁症状中起链式中介作用。适度午睡，尤其是5~30 min的短时午睡，能有效降低抑郁症状的风险，且这一效应通过改善身体功能、减缓虚弱状态和炎症反应实现。.
Accessory cavitated uterine malformation (ACUM) is a congenital Müllerian duct developmental anomaly. Clinically, it is commonly observed in young women presenting with progressive lower abdominal pain. Due to the small size of the lesions and insufficient awareness of this condition among clinicians, the rates of missed diagnosis and misdiagnosis are relatively high, often leading to delayed treatment. This study aims to explore the clinical characteristics, diagnostic and therapeutic approaches, and prognosis of ACUM, summarize relevant clinical experience, and provide references for clinical diagnosis and management. A retrospective analysis was conducted on the clinical data of 16 patients with ACUM who were admitted to the Department of Gynecology, the Third Xiangya Hospital of Central South University from May 2023 to November 2025. The collected data included age, clinical manifestations, medical history, menstrual and reproductive history, tumor markers, imaging findings, treatment methods, pathological results, and prognosis. The Kappa test was used to evaluate the diagnostic consistency between two auxiliary imaging modalities. The age at diagnosis ranged from 23 to 53 years [(32.00±7.56) years], and the disease duration ranged from 5 months to 12 years. All 16 patients presented with lower abdominal pain, including left lower abdominal pain in 6 cases, right lower abdominal pain in 3 cases, and ipsilateral pelvic pain in 2 cases. Dysmenorrhea occurred in 10 patients, pain initially associated with menstruation that later became non-menstrual pain occurred in 1 patient, and non-menstrual pain occurred in 5 patients. All 16 patients underwent gynecologic color Doppler ultrasonography. Lesions were located within the myometrium beneath the uterine cornual region of the left anterior uterine wall in 12 cases and the right anterior uterine wall in 4 cases. The nodules showed hypoechoic signals in 4 cases and mixed echogenicity in 12 cases. Clear boundaries were observed in 13 cases, while indistinct boundaries were observed in 3 cases. The maximum diameter of the nodules ranged from 17 to 38 mm [(28.31±6.04) mm] and the maximum diameter of the anechoic area within the cyst ranged from 5 to 29 mm [(18.63±6.77) mm]. Endometrium-like echoes within the cyst wall were detected in 12 cases. All 16 patients underwent pelvic magnetic resonance imaging (MRI) with plain and contrast-enhanced scans. The nodular lesions showed short T1 and long T2 signals in 7 cases, slightly shorter T2 signals with equal T1 values in 5 cases, equal T1 and T2 signals in 1 case, long T1 and short T2 signals in 2 cases, and long T1 and long T2 signals in 1 case. Among them, short T1 and long T2 signals were indicated within the nodules in 7 cases. The diagnostic coincidence rate for ACUM was 81.25% with gynecological ultrasonography and 56.25% with pelvic MRI. The agreement between the 2 diagnostic modalities was weak (Kappa=0.186, P=0.375). A total of 13 patients underwent cancer antigen 125 (CA125) testing, with values ranging from 12.90 to 91.80 U/mL. Among them, 10 cases had CA125≤35 U/mL and 3 cases had CA125> 35 U/mL. A total of 15 patients underwent laparoscopic resection of uterine lesions (including hysteroscopy in 6 cases), while 1 patient underwent laparoscopic total hysterectomy with bilateral salpingectomy due to advanced age and no reproductive requirement. Based on pathological examination combined with clinical and imaging findings, all 16 patients were diagnosed with ACUM, including 3 cases suspected of concomitant focal adenomyosis. The postoperative follow-up duration ranged from 2 to 28 months [(13.50±8.12) months]. Postoperative pain symptoms disappeared in 15 patients and were significantly relieved in 1 patient. 1 patient achieved full-term vaginal delivery after surgery. ACUM is a special type of obstructive disease that can easily be confused with cystic adenomyosis or cystic degeneration of uterine fibroids. When young women present with progressive lower abdominal pain, especially unilateral pain accompanied by referred pelvic pain, ACUM should be highly suspected. Three-dimensional gynecological ultrasonography and pelvic MRI are recommended for auxiliary diagnosis. Laparoscopic resection of uterine lesions is the preferred treatment for radical management of this condition, and hysteroscopy may be performed when necessary for differential diagnosis. 目的: 子宫附腔畸形(accessory cavitated uterine malformation，ACUM)是一种先天性苗勒管发育异常，临床上多见于年轻女性，常发生进行性下腹痛，由于病灶较小、医师对此类疾病缺乏充分的认识，漏诊及误诊率高，常导致治疗延误。本研究旨在探讨子宫附腔畸形的临床特征、诊治方式及预后情况，总结相关经验，为临床诊治提供更多参考依据。方法: 回顾性分析2023年5月至2025年11月在中南大学湘雅三医院妇科收治的16例ACUM患者的临床资料，包括年龄、临床表现、既往史、月经及生育史、肿瘤标志物、影像学检查、治疗方式、病理检查及预后情况等。采用Kappa检验进行2种辅助检查诊断的一致性检验。结果: 16例患者确诊年龄为23~53(32.00±7.56)岁，病程为5个月~12年。临床表现为下腹痛16例，其中左下腹痛6例、右下腹痛3例、伴同侧盆腔痛2例;月经期疼痛10例，经期疼痛后改为非经期疼痛1例，非经期疼痛5例。16例患者均行妇科彩色超声检查，病灶位于子宫左前壁宫角下方肌层内12例，位于子宫右前壁宫角下方肌层内4例，结节呈低回声4例，混合回声12例，边界清晰13例，边界欠清晰3例，结节最大径为17~38(28.31±6.04) mm，囊内无回声区最大径为5~29(18.63±6.77) mm，囊壁内可探及类内膜回声12例。16例患者均行盆腔磁共振成像(magnetic resonance imaging，MRI)平扫+增强检查，结节病灶呈短T1长T2信号7例，等T1稍短T2信号5例，等T1等T2信号1例，长T1短T2信号2例，长T1长T2信号1例，其中结节内呈短T1长T2信号7例。16例患者首先考虑诊断为ACUM的妇科超声的符合率为81.25%，盆腔MRI的符合率为56.25%，2种检查方法的判断一致性强度较弱(Kappa值=0.186，P=0.375)。13例行癌抗原125(cancer antigen 125，CA125)检测，数值为12.90~91.80 U/mL，其中≤35 U/mL的10例，>35 U/mL的3例。15例患者采用腹腔镜下子宫病损切除术(其中6例同时行宫腔镜检查)，1例因年纪大且无生育需求行腹腔镜下全子宫+双侧输卵管切除术。结合病理检查及临床、影像学资料，16例患者均诊断为ACUM，其中3例考虑合并局灶腺肌症。术后随访时长为2~28(13.50±8.12)个月，术后疼痛症状均消失15例，疼痛明显减轻1例，术后妊娠足月顺产1例。结论: ACUM是一种特殊的梗阻性疾病，容易与囊性腺肌病、子宫肌瘤囊性变等混淆，当临床上出现年轻女性进行性下腹痛，特别是偏侧性疼痛及伴随盆腔牵涉痛时，需高度怀疑ACUM，推荐采用三维妇科超声、盆腔MRI进行辅助诊断，首选腹腔镜下子宫病灶切除术来根治此类疾病，必要时行宫腔镜检查来鉴别诊断。.
Prenatal depression is one of the most common psychological disorders during pregnancy, with an incidence of approximately 19.7% in China, and the incidence is showing a significant upward trend. Prenatal depression seriously endangers maternal and infant health, may lead to self-injury and suicide, and has lasting effects on the health of offspring. Studies have shown that gut microbiota imbalance and disruption of the gut-brain axis can affect brain function and behavior and play an important role in the occurrence and development of depression. Significant changes occur in the gut microbiota of pregnant women during pregnancy, which may influence inflammation and metabolism. Gut microbiota play a key role in tryptophan metabolism; however, the mechanisms by which maternal gut microbiota regulate tryptophan metabolism to affect brain function and mood remain unclear. This study aims to clarify the role of plasma tryptophan in the relationship between gut microbiota and prenatal depression in pregnant women based on the gut-brain axis mechanism. A total of 73 pregnant women were included in the study. The Edinburgh Postnatal Depression Scale (EPDS) was used for assessment. According to the cutoff score (10 points), participants were divided into a prenatal depression group (pregnant women with prenatal depression) and a control group (pregnant women without prenatal depression). Demographic information, fecal samples, and plasma samples were collected. Gut microbiota sequencing was performed using 16S ribosomal RNA (rRNA) sequencing. Amino acid detection in plasma and feces was conducted using ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Data were analyzed using SPSS 26.0 and R software, and mediation model analysis was performed using SPSS PROCESS. There were no statistically significant differences in α-diversity or β-diversity of gut microbiota between the 2 groups (all P>0.05). Compared with the control group, plasma tryptophan levels were significantly higher in the prenatal depression group (t=-2.964, P<0.05). The abundances of Candidatus_Soleaferrea (β=-19.945, OR<0.001, 95% CI <0.001 to 0.002, P=0.004) and Enterococcus (β=-9.074, OR<0.001, 95% CI <0.001 to 0.183, P=0.016) were negatively correlated with prenatal depression, whereas the abundance of Lachnospiraceae_NC2004_group was positively correlated with prenatal depression (β=5.870, OR=354.354, 95% CI 1.248 to 100 619.527, P=0.042). Plasma tryptophan levels played a mediating role between Enterococcus abundance and prenatal depression. Depressive symptoms during pregnancy are associated with the composition of gut microbiota during pregnancy. Tryptophan, as a precursor of serotonin, may play a mediating role in this process, providing new insights for improving prenatal depression through interventions targeting gut microbiota or tryptophan metabolism. 目的: 产前抑郁是孕妇在怀孕期间最常见的心理障碍之一，在中国发生率约为19.7%，且发生率呈显著上升趋势。产前抑郁严重危害母婴健康，可引起自伤、自杀，而且持续影响子代的健康。有研究表明肠道菌群失衡及肠-脑轴紊乱会影响大脑功能和行为，在抑郁的发生和发展中起重要作用。孕妇孕期的肠道菌群会发生显著变化，可能对炎症、代谢等方面产生影响。肠道菌群在色氨酸代谢中扮演关键角色，但孕妇肠道菌群调节色氨酸代谢影响大脑功能和情绪的机制尚未完全阐明。本研究旨在基于肠-脑轴机制阐明血浆色氨酸在孕妇肠道菌群与产前抑郁关联中的作用。方法: 共纳入73名孕妇进行研究，采用爱丁堡产后抑郁量表(Edinburgh Postpartum Depression Scale，EPDS)对孕妇进行评估，根据评分分界值(10分)将其分为产前抑郁组(产前抑郁的孕妇)及对照组(无产前抑郁的孕妇)。收集研究对象的相关人口统计信息、粪便和血浆样本。肠道菌群测序使用了16S核糖体RNA(ribosomal RNA，rRNA)测序，血浆和粪便的氨基酸检测使用了超高效液相色谱-电喷雾电离串联质谱分析(ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry，UHPLC-ESI-MS/MS)技术。采用SPSS 26.0和R软件进行数据分析，使用SPSS PROCESS进行中介模型分析。结果: 2组间肠道微生物群的α多样性和β多样性差异均无统计学意义(均P>0.05)。与对照组相比，产前抑郁组的血浆色氨酸含量显著升高(t=-2.964，P<0.05)。Candidatus_Soleaferrea (β=-19.945，OR<0.001，95% CI <0.001~0.002，P=0.004)和Enterococcus (β=-9.074，OR<0.001，95% CI <0.001~0.183，P=0.016)的丰度与产前抑郁均呈负相关，而Lachnospiraceae_NC2004_group的丰度与产前抑郁呈正相关(β=5.870，OR=354.354，95% CI 1.248~100 619.527，P=0.042)。血浆色氨酸水平在Enterococcus和产前抑郁之间起中介作用。结论: 孕期的抑郁症状与孕期肠道菌群的组成有关，而色氨酸作为5-羟色胺的前体物质，可能在这一过程中起中介作用，为今后通过肠道菌群或色氨酸代谢干预改善产前抑郁提供新思路。.
Argininosuccinate synthase 1 (ASS1) is a key rate-limiting enzyme in the urea cycle and is highly conserved at the protein level. Its catalytic activity directly determines the efficiency of ammonia clearance. Hyperammonemia is a clinical syndrome caused by abnormally elevated blood ammonia levels and is characterized mainly by central nervous system dysfunction, with neurotoxicity and a high mortality rate. When liver function is impaired or key enzymes of the urea cycle are deficient, ammonia clearance is reduced, leading to ammonia accumulation and passage across the blood-brain barrier, resulting in disturbances of consciousness, coma, or even death. Among currently used ammonia-lowering agents, L-ornithine-L-aspartate (LOLA) can promote the urea cycle to reduce blood ammonia levels and protect the liver; however, high doses are prone to gastrointestinal adverse effects, limiting its clinical application. This study obtained biologically active human ASS1 protein through prokaryotic expression and analyzed its enzymatic kinetic properties, aiming to explore the ammonia-lowering effect of ASS1 combined with LOLA and to provide new ideas and potential enzymatic intervention strategies for the clinical treatment of hyperammonemia. The full-length open reading frame of human ASS1 was amplified by reverse transcription polymerase chain reaction (RT-PCR), and both the PCR product and the pET-28a vector were digested with restriction enzymes. After purification by agarose gel electrophoresis, the pET-28a-ASS1 prokaryotic expression vector was successfully constructed using homologous recombination technology. The recombinant plasmid was transformed into Escherichia coli, and expression of the 6×His-ASS1 recombinant protein was induced by isopropyl β-D-thiogalactopyranoside (IPTG). The protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography. In vitro enzyme activity assays were performed to verify the biological activity of the recombinant protein. An enzymatic reaction system using citrulline (Cit) and aspartate (Asp) as substrates was established to determine the optimal temperature and pH conditions for ASS1 activity and to further analyze its enzymatic kinetic parameters. A hyperammonemia mouse model was established in C57BL/6 mice by intraperitoneal injection of NH4Cl (400 mg/kg). The ammonia-lowering effects of ASS1 combined with LOLA were evaluated. Mice were randomly grouped, and 4 hours after modeling, ASS1, LOLA, or combined treatment was administered via the tail vein for 4 hours, followed by measurement of blood ammonia and urea levels. In addition, normal C57BL/6 mice were treated with combined ASS1 and LOLA for 24 hours, after which liver and renal function indices were assessed. The pET28a-ASS1 vector was successfully constructed using homologous recombination, and soluble recombinant ASS1 protein was obtained in a prokaryotic expression system. After purification and concentration by Ni-NTA affinity chromatography, the protein purity reached 95.4%±1.2%, with a concentration of (10.5± 0.8) mg/mL. In vitro enzyme activity assays systematically characterized the enzymatic properties of ASS1, showing an optimal reaction temperature of 37 ℃ and an optimal pH of 8.0. Using Asp and Cit as substrates, the enzymatic kinetic parameters were determined. The Km and kcat/Km values of ASS1 for Asp and Cit were (31.00±1.24) μmol/L and 2.07 L/(μmol·s), and (46.53±2.75) μmol/L and 1.35 L/(μmol·s), respectively. In vivo experiments showed that in an acute hyperammonemia mouse model induced by intraperitoneal injection of NH4Cl (400 mg/kg), ASS1 (50 mg/kg) reduced blood ammonia levels by 48.86% by accelerating the urea cycle. When ASS1 (50 mg/kg) was combined with low-dose LOLA (50 mg/kg), the ammonia-lowering efficiency was further enhanced, with a reduction of 76.31%, restoring blood ammonia levels to the normal range in hyperammonemic mice. Recombinant ASS1 protein obtained by prokaryotic expression exhibits stable and well-defined biological activity, with catalytic function significantly influenced by temperature and pH and displaying clear enzymatic kinetic characteristics. In an NH4Cl-induced mouse model of hyperammonemia, combined application of ASS1 and LOLA showed a more stable and effective ammonia-lowering effect than monotherapy, demonstrating good synergistic effects. These findings provide a new enzymatic intervention strategy for the treatment of hyperammonemia, lay a theoretical foundation for the development of combination ammonia-lowering therapies, and indicate potential application prospects. 目的: 精氨酸代琥珀酸合成酶1(argininosuccinate synthase 1，ASS1)是尿素循环的关键限速酶且蛋白质高度保守，其催化活性直接决定血氨的清除效率。高氨血症(hyperammonemia)是血氨异常升高引起的、以中枢神经系统功能障碍为主要表现的临床综合征，具有神经毒性和较高病死率。肝功能受损或尿素循环关键酶缺陷时，清除血氨能力下降，导致血氨蓄积并透过血脑屏障，引发意识障碍、昏迷甚至死亡。目前临床常用降氨药物中，门冬氨酸鸟氨酸(L-ornithine-L-aspartate，LOLA)可促进尿素循环降低血氨并保护肝，但高剂量易致胃肠道不良反应，限制其应用。本研究通过原核表达获得具有生物活性的人源ASS1蛋白，解析其酶促动力学特性，旨在探讨ASS1联合LOLA的降血氨作用，为临床高氨血症的治疗提供新的思路和潜在的酶学干预策略。方法: 通过逆转录聚合酶链式反应(reverse transcription polymerase chain reaction，RT-PCR)扩增获得人源ASS1的开放阅读框全长，并对该PCR产物及pET-28a载体进行酶切。经琼脂糖凝胶电泳回收纯化上述片段后，利用同源重组技术成功构建了pET-28a-ASS1原核表达载体。随后转化至大肠杆菌中表达并使用异丙基-β-D-硫代半乳糖苷(isopropyl β-D-thiogalactopyranoside，IPTG)诱导6×His-ASS1重组蛋白表达，采用镍柱亲和层析(nickel-nitrilotriacetic acid，Ni-NTA)进行蛋白质纯化。通过体外酶活实验验证重组蛋白的生物活性，构建以瓜氨酸(citrulline，Cit)和天冬氨酸(aspartate，Asp)为底物的酶促反应体系，测定ASS1的最适温度和最适pH反应条件，并进一步解析其酶促动力学参数。构建NH₄Cl(腹腔注射400 mg/kg)诱导的C57BL/6小鼠高氨血症模型，检测ASS1联合LOLA降血氨作用，随机分组，建模4 h后经尾静脉给予ASS1、LOLA或联合干预4 h，并检测血氨与尿素水平;另设ASS1和LOLA联合用药对C57BL/6正常小鼠给药24 h后检测肝功能及肾功能指标。结果: 采用同源重组技术成功构建并获得pET28a-ASS1载体，并在原核表达系统中获得可溶性重组蛋白ASS1;经Ni-NTA亲和层析纯化和浓缩后，蛋白质纯度达95.4%±1.2%，浓度为(10.5±0.8) mg/mL。在体外酶活实验中系统解析了ASS1的酶促反应特性，显示ASS1酶促反应的最适温度为37 ℃，最适pH值为8.0;结合底物Asp和Cit测定其酶促动力学参数，ASS1与Asp和Cit的Km和kcat/Km分别为(31.00±1.24) μmol/L，2.07 L/(μmol·s)和(46.53±2.75) μmol/L，1.35 L/(μmol·s);在体内实验中，通过腹腔注射400 mg/kg NH4Cl建立急性高氨血小鼠模型，ASS1(50 mg/kg)可通过加速尿素循环降低血氨浓度，使血氨浓度下降48.86%;ASS1(50 mg/kg)与低剂量LOLA(50 mg/kg)联合给药时，降氨效率进一步提升，血氨浓度下降76.31%，并可使高氨血症小鼠的血氨水平恢复至正常范围。结论: 通过原核表达获得的重组蛋白ASS1具有稳定且明确的生物活性，其催化功能受温度和pH条件显著影响，并呈现出清晰的酶促反应动力学特征。在NH₄Cl诱导的小鼠高氨血症模型中，ASS1与LOLA联合应用较单独用药表现出更稳定的降血氨效果，显示出良好的协同作用，为高氨血症的治疗提供了新的酶学干预思路，进而为发展联合降血氨策略奠定了理论依据，并具有潜在应用前景。.
The mechanism of abnormal eye movements in patients with cerebral small vessel disease (CSVD) remains unclear. This study aims to explore the potential link between eye movement in CSVD patients and the severity and distribution of white matter hyperintensities (WMH), and to evaluate the possibility of using eye movement assessment as a tool for specific diagnosis. This retrospective cross-sectional study was conducted at Xiangya Hospital, Central South University between September 7th, 2022 and October 27th, 2023, enrolling a total of 161 patients with CSVD. Demographic characteristics, past medical history, medication history, and imaging data were collected. The Montreal Cognitive Assessment (MoCA) was used to evaluate patients' cognitive function, and the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were used to assess patients' anxiety and depressive symptoms. All participants completed the EyeKnow Intelligent Eye Movement Analysis System within one week of enrollment, with data recorded on the following eye movement paradigms: saccade, smooth pursuit, fixation, and antisaccade. WMH were scored using both the Age-Related White Matter Change (ARWMC) scale and the Fazekas grading system. Based on the scores, patients were categorized into three severity groups (mild, moderate, severe). The Kruskal-Wallis rank sum test was used to analyze intergroup differences, while Spearman correlation analysis and multiple linear regression were used to explore the relationship between eye movement characteristics and WMH. Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the ability of eye movement characteristics to discriminate between patients with and without WMH in the five brain regions: frontal lobe, temporal lobe, parietal-occipital lobe, infratentorial region, and basal ganglia region. A weighted random forest model was developed to assess the performance of eye movement characteristics in predicting WMH severity at different locations. This study enrolled a total of 161 patients with CSVD. Baseline data were collected for all participants. According to the total ARWMC scores, patients were divided into a mild (0 to 10 points), a moderate (11 to 20 points), and a severe (21 to 30 points) WMH groups. The mild WMH group included 100 patients [66 males and 34 females, age (61.40±9.45) years]. The moderate WMH group included 46 patients [32 males and 14 females, age (63.72±8.77) years]. And the severe WMH group included 15 patients [12 males and 3 females, age (63.47±10.40) years]. Significant differences were observed among the 3 groups in MoCA scores (P=0.008), severity of cerebral microbleeds (CMB) (P<0.001), severity of basal ganglia perivascular spaces (BG-PVS) (P<0.001), and global cortical atrophy (GCA) grading system scores (P=0.003). Analysis of intergroup differences in eye movement characteristics revealed that with increasing WMH severity, the fastest saccade reaction time increased (P=0.008), the smooth pursuit deviation (P=0.013) and the number of fixation shifts (>2°) (P=0.025) decreased. In post-hoc pairwise comparisons, there were no significant differences in any eye movement characteristics between the moderate and severe WMH group (all P>0.05). Spearman correlation analysis demonstrated a strong positive correlation between the total Fazekas and total ARWMC scores (r=0.867, P<0.01), confirming their concordance for rating WMH severity. Additionally, MoCA scores were significantly negatively correlated with both the total Fazekas scores (r=-0.302, P<0.01) and the total ARWMC scores (r=-0.245, P<0.01). Multiple linear regression analysis based on the total ARWMC scores revealed that after adjusting for multicollinearity, oculomotor features including smooth pursuit initiation time (β=-0.001, P=0.009), smooth pursuit deviation (β=-1.212, P=0.001), number of fixation shifts (>2°) (β=-0.102, P=0.011), and mean reaction time of antisaccade (β=0.016, P=0.018) remained statistically significant predictors of cognitive function. After adjusting for gender, age, years of education, MoCA, HAMA, HAMD scores, and the presence of other imaging markers, the associations of smooth pursuit initiation time (β<0.001, P=0.010), smooth pursuit deviation (β=-1.066, P=0.002), and mean reaction time of antisaccade (β=0.013, P=0.034) with the outcome variable remained statistically significant. In the distribution of WMH locations, ROC curve analysis was conducted based on all eye movement characteristics to discriminate the presence of WMH in the whole brain, frontal lobe, temporal lobe, parietal-occipital lobe, and infratentorial region, with AUC values of 0.933, 0.928, 0.758, 0.784, and 0.881, respectively. For the basal ganglia region, binary logistic regression analysis showed no significant association, and therefore ROC curve analysis was not applicable. Using a weighted random forest method, the severity of WMH at different locations was further classified. After adjusting for gender, age, years of education, MoCA, HAMA, HAMD scores, and the presence of other imaging markers, the model's classification accuracy improved to 85.71% for the frontal lobe, 81.63% for the infratentorial region, and 75.51% for the parietal-occipital lobe. The eye movement performance of CSVD patients worsens with the increasing severity of WMH, especially in the frontal lobe and infratentorial region. Cognitive function exerts an influence on eye movement that appears largely independent of imaging changes. 目的: 脑小血管病(cerebral small vessel disease，CSVD)患者眼球运动异常的机制尚未明确。本研究旨在探讨CSVD患者眼球运动与白质高信号(white matter hyperintensity，WMH)严重程度及位置分布的潜在关系，探索眼球运动评估作为特异性诊断工具的可能性。方法: 采用横断面研究设计，纳入湘雅医院2022年9月7日至2023年10月27日共计161例门诊与住院CSVD患者为研究对象。采集患者人口学特征、既往史、用药史以及影像学数据;采用蒙特利尔认知评估量表(Montreal Cognitive Assessment，MoCA)评估患者的认知功能，分别采用汉密尔顿焦虑量表(Hamilton Anxiety Scale，HAMA)、汉密尔顿抑郁量表(Hamilton Depression Scale，HAMD)评估患者的焦虑、抑郁状态。所有患者在入组1周内完成EyeKnow智能眼动分析评价系统测试，记录眼球运动(间隔朝向扫视、平滑追踪、注视、反扫视)数据。基于年龄相关白质改变(age-related white matter changes，ARWMC)的量化评估与Fazekas分级2种评估方法对WMH进行评分，并根据严重程度进行分组。采用Kruskal-Wallis秩和检验进行组间差异分析，采用Spearman相关性分析、多元线性回归分析探讨眼球运动特征与WMH的相关性。针对全脑与额叶、颞叶、顶枕叶、幕下区、基底节区5个脑区是否存在WMH进行受试者操作特征(receiver operating characteristic，ROC)曲线分析，并采用基于加权随机森林的分析方法构建模型，评估眼球运动特征对不同位置WMH严重程度的分类准确率。结果: 本研究共纳入161例CSVD患者，均收集了基线资料。根据ARWMC总分将患者分为轻度WMH组(0~10分)、中度WMH组(11~20分)和重度WMH组(21~30分)。其中，轻度WMH组100例，男66例(66.00%)，女34例(34.00%)，年龄(61.40±9.45)岁;中度WMH组46例，男32例(69.57%)，女14例(30.43%)，年龄(63.72±8.77)岁;重度WMH组15例，男12例(80.00%)，女3例(20.00%)，年龄(63.47±10.40)岁。3组患者MoCA得分(P=0.008)、脑微出血(cerebral microbleeds，CMB)严重程度(P<0.001)、基底节区血管周围间隙(basal ganglia perivascular spaces，BG-PVS)严重程度(P<0.001)、全脑皮质萎缩(global cortical atrophy，GCA)分级系统评分(P=0.003)的差异均有统计学意义。眼动特征的组间差异分析结果显示，WMH严重程度越高，间隔朝向扫视最快反应时长越长(P=0.008)，平滑追踪偏移量(>4°)越小(P=0.013)，注视偏移(>2°)次数越少(P=0.025)，差异均有统计学意义。事后两两比较中，中度WMH组与重度WMH组患者眼动特征比较，差异均无统计学意义(均P>0.05)。Spearman相关性分析结果显示，Fazekas总分与ARWMC总分在评估WMH严重程度方面存在较好的一致性(r=0.867，P<0.01);MoCA与Fazekas总分(r=-0.302， P<0.01)、ARWMC总分(r=-0.245，P<0.01)均呈显著负相关。基于ARWMC总分的多元线性回归分析显示，在排除多重共线性后，眼动特征中的平滑追踪启动时长(β=-0.001，P=0.009)、平滑追踪偏移量(β=-1.212，P=0.001)、注视偏移(>2°)次数(β=-0.102，P=0.011)、反扫视平均反应时长(β=0.016，P=0.018)与结局变量的关联仍有统计学意义。在调整性别、年龄、受教育年限、MoCA、HAMA、HAMD以及是否存在其他影像学标志物后，平滑追踪启动时长(β<0.001，P=0.010)、平滑追踪偏移量(β=-1.066，P=0.002)、反扫视平均反应时长(β=0.013，P=0.034)与结局变量的关联仍具有统计学意义。在WMH位置分布中，基于所有眼动特征对全脑、额叶、颞叶、顶枕叶、幕下区是否存在WMH进行ROC曲线分析，其曲线下面积值分别为0.933、0.928、0.758、0.784、0.881;基底节区的二元Logistic回归分析结果无统计学意义，无法进行ROC曲线分析。基于加权随机森林算法进一步对不同位置WMH严重程度进行分类，在调整了人口学特征、MoCA、HAMA、HAMD以及其他影像学标志物后，模型对额叶、幕下区、顶枕叶的分类准确率分别提升至85.71%、81.63%、75.51%。结论: CSVD患者眼球运动表现随着WMH严重程度的加剧而愈发恶化，在额叶和幕下区尤为显著。认知水平可能在很大程度上独立于影像学改变而影响眼球运动表现。.
Prevention and treatment of perioperative acute kidney injury (AKI) remain a major focus in clinical practice. This study aims to investigate the role and underlying mechanism of sestrin2 (SESN2) in Erastin-induced ferroptosis of renal tubular cells and AKI in ICR mice. For in vitro experiments, human renal proximal tubular epithelial cells (HK-2) stably transfected with lentivirus were divided into three groups: control group, Erastin model group, and SESN2 intervention group. The control group was transfected with empty vector lentivirus (LV-Con). The Erastin model group was transfected with LV-Con and then treated with 10 μmol/L Erastin for 24 h. The SESN2 intervention group was transfected with SESN2-overexpressing lentivirus (LV-SESN2) followed by Erastin treatment. For in vivo experiments, after confirming successful establishment of the Erastin-induced AKI mouse model by measuring serum creatinine (SCr) and blood urea nitrogen (BUN), 18 healthy adult male ICR mice were randomly divided into three groups (n=6 per group): control group, Erastin model group, and SESN2 intervention group. The control group received tail vein injection of control virus (AAV9-Con). The Erastin model group received AAV9-Con followed by intraperitoneal injection of Erastin (30 mg/kg) after 4 weeks. The SESN2 intervention group received tail vein injection of SESN2-overexpressing virus (AAV9-Sesn2), followed by Erastin injection at the same dose after 4 weeks. Serum and renal tissues were collected 24 h after modeling. Enzyme-linked immunosorbent assay (ELISA) was used to measure lactate dehydrogenase (LDH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels in cell and tissue supernatants. Reactive oxygen species (ROS) levels were assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE) fluorescence staining. Malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe2+) levels were determined by colorimetric assays. Cell apoptosis was calculated using Annexin V-FITC/propidium iodide (PI), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and flow cytometry. The mRNA and protein expression levels of SESN2, nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and ferroptosis suppressor protein 1 (FSP1) were detected by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and Western blotting (WB). Compared with the in vitro/in vivo control groups, the Erastin model groups and SESN2 intervention groups showed significantly increased levels of LDH, IL-6, TNF-α, MDA, ROS, and Fe2+, along with significantly decreased GSH levels and increased apoptosis rates (all P<0.001). The mRNA and protein expression levels of GPX4 and FSP1 were significantly decreased, whereas those of SESN2 and Nrf2 were significantly increased (all P<0.001). Compared with the Erastin model groups, the SESN2 intervention groups exhibited significantly reduced levels of LDH, IL-6, TNF-α, MDA, ROS, and Fe2+, increased GSH levels, and decreased apoptosis rates (all P<0.001). In addition, the mRNA and protein expression levels of SESN2, Nrf2, GPX4, and FSP1 were significantly increased (all P<0.001). SESN2 exerts protective effects against Erastin-induced ferroptosis in renal tubular cells and ferroptosis-related AKI by activating the Nrf2 signaling pathway, upregulating ferroptosis-related molecules GPX4 and FSP1, and inhibiting oxidative stress, lipid peroxidation, and inflammatory responses. 目的: 如何防治围手术期常发生的急性肾损伤(acute kidney injury，AKI)一直是临床实践关注的核心。本研究旨在探讨应激诱导蛋白2(sestrin2，SESN2)在铁死亡诱导剂Erastin诱导的肾小管细胞铁死亡和ICR小鼠AKI中的作用及机制。方法: 体外试验方面，采用稳定转染慢病毒的人肾皮质近曲小管上皮细胞HK-2，分为体外对照组、Erastin体外模型组、SESN2体外干预组3组。体外对照组采用空载体慢病毒LV-Con进行转染;Erastin体外模型组转染LV-Con后给予10 μmol/L的Erastin，处理24 h;SESN2体外干预组转染SESN2过表达慢病毒LV-SESN2后，同样给予10 μmol/L的Erastin进行处理。体内试验方面，通过检测血肌酐(serum creatinine，SCr)和血尿素氮(blood urea nitrogen，BUN)水平验证和评估Erastin诱导的AKI小鼠模型的成功建立后，将18只健康成年ICR雄性小鼠随机分为体内对照组、Erastin体内模型组、SESN2体内干预组3组，每组各6只。体内对照组采用尾静脉注射空载对照病毒AAV9-Con;Erastin体内模型组采用尾静脉注射AAV9-Con，4周后腹腔注射Erastin(30 mg/kg);SESN2体内干预组采用尾静脉注射SESN2过表达病毒AAV9-Sesn2，4周后腹腔注射Erastin(剂量同Erastin体内模型组)。造模成功24 h后收集血清和肾组织。采用酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测细胞和组织的上清液乳酸脱氢酶(lactate dehydrogenase，LDH)、白细胞介素(interleukin，IL)-6及肿瘤坏死因子(tumor necrosis factor，TNF)-α水平。采用2’,7’-二氯二氢荧光素二乙酸酯(2’,7’-dichlorodihydrofluorescein diacetate，DCFH-DA)荧光探针法和二氢乙啶(dihydroethidium，DHE)荧光染色法检测活性氧(reactive oxygen species，ROS)的荧光强度。采用比色法检测丙二醛(malondialdehyde，MDA)、谷胱甘肽(glutathione，GSH)、亚铁离子(Fe2+)水平;采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶(Annexin V-fluorescein isothiocyanate/propidium iodide，Annexin V-FITC/PI)、原位末端转移酶标记法(terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling，TUNEL)和双染流式细胞术计算细胞凋亡率。采用实时反转录聚合酶链反应(real-time reverse transcription PCR，real-time RT-PCR)及蛋白质印迹法检测SESN2、核转录因子红系2相关因子2(nuclear factor-erythroid 2-related factor 2，Nrf2)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4，GPX4)和铁死亡抑制蛋白1(ferroptosis suppressor protein 1，FSP1)的mRNA及蛋白质表达情况。结果: 与体外/体内对照组相比，Erastin体外/体内模型组和SESN体外/体内干预组的LDH、IL-6、TNF-α、MDA、ROS、Fe2+水平均显著升高，GSH水平显著降低，细胞凋亡率显著增加(均P<0.001);GPX4、FSP1的mRNA和蛋白质表达水平均显著降低，SESN2及Nrf2的mRNA和蛋白质表达水平均显著升高(均P<0.001)。同时，与Erastin体外/体内模型组相比，SESN2体外/体内干预组中LDH、IL-6、TNF-α、MDA、ROS、Fe2+水平均显著降低，GSH水平显著升高，细胞凋亡率显著降低(均P<0.001)，SESN2、Nrf2、GPX4、FSP1的mRNA和蛋白质表达水平均显著升高(均P<0.001)。结论: SESN2可通过激活Nrf2信号通路，上调铁死亡相关分子GPX4和FSP1的表达，抑制氧化应激、脂质过氧化及炎症反应，从而减轻Erastin诱导的肾小管细胞铁死亡，对铁死亡相关AKI产生保护作用。.
Zoster-associated pain (ZAP) is an acute and chronic neuropathic pain condition caused by reactivation of varicella-zoster virus in sensory ganglia, which can severely impair patients' quality of life. Nerve block is one of the most commonly used interventional techniques in clinical practice and is often combined with various adjunctive agents to enhance therapeutic efficacy. However, these agents differ in mechanisms of action and levels of evidence, and due to differences in the pathological mechanisms at different stages of ZAP, there is currently a lack of systematic evaluation based on disease staging, resulting in insufficient precision in clinical decision-making. This study aims to systematically evaluate the clinical evidence for different adjunctive agents and clarify their application value at different stages of the disease course, thereby providing a reference for individualized treatment. Relevant literature published up to December 31, 2025, was systematically searched in PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform. Inclusion criteria were: 1) Patients diagnosed with acute herpes zoster (AHZ) or postherpetic neuralgia (PHN); 2) interventions involving drugs used as adjuncts in nerve blocks or local injections; 3) randomized controlled trials (RCT), prospective cohort studies, or case-control studies. Two reviewers independently performed literature screening and data extraction. Extracted data included first author, publication year, sample size, type of nerve blocks or local injections, type and dosage of adjunctive agents, and main outcome measures. The level of evidence was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria, and adjunctive agents were graded according to the highest level of evidence. A total of 29 clinical studies were included. Based on the level of evidence, adjunctive agents were categorized into level A and level B evidence groups. Among level A evidence agents, glucocorticoids relieve pain through potent anti-inflammatory effects, while botulinum toxin type A exerts analgesic effects by inhibiting the release of pain mediators and modulating neural signaling. Among level B evidence agents, platelet-rich plasma promotes nerve repair by releasing growth factors; medical ozone exerts effects through anti-inflammatory action and improvement of circulation; methylene blue provides long-term analgesia by ameliorating reversible demyelinating nerve injury; and vaccinia virus-inoculated rabbit inflammatory skin extract (Neurotropin) may regulate pain by activating descending inhibitory pathways. Based on disease stage, anti-inflammatory treatment (e.g., glucocorticoids) is recommended in the acute phase, whereas neuromodulation and nerve repair (e.g., botulinum toxin type A, platelet-rich plasma) are emphasized in the chronic phase. All adjunctive agents require careful consideration of their specific potential serious adverse events. The use of adjunctive agents in nerve blocks/local injections provides a multi-mechanistic and stage-specific therapeutic strategy for ZAP. Glucocorticoids and botulinum toxin type A have the highest level of supporting evidence. However, challenges remain, including heterogeneity in evidence levels and lack of standardized protocols. Future high-quality, large-scale randomized controlled trials, especially those comparing different adjunctive agents across disease stages, are needed to further optimize clinical treatment strategies. 目的: 带状疱疹相关性疼痛(zoster-associated pain，ZAP)是水痘-带状疱疹病毒在感觉神经节被重新激活后引起的急、慢性神经病理性疼痛，可严重影响患者的生活质量。神经阻滞作为临床最常用的介入治疗技术，常联合多种佐剂以增强疗效，但各类佐剂的作用机制各异、证据等级参差不齐，且由于ZAP不同病程阶段的病理机制存在差异，目前缺乏基于病程分期的系统梳理，导致临床选择缺乏精准依据。本研究旨在系统评价各类佐剂的临床证据，明确其在不同病程阶段的应用价值，为临床个体化治疗提供参考。方法: 系统检索PubMed、Web of Science、Cochrane Library、中国知网及万方数据知识服务平台自建库至2025年12月31日收录的相关文献。文献纳入标准:1)研究对象明确诊断为急性期带状疱疹(acute herpes zoster，AHZ)或带状疱疹后神经痛(postherpetic neuralgia，PHN);2)干预措施为药物作为神经阻滞佐剂或局部注射佐剂;3)随机对照试验(randomized controlled trial，RCT)、前瞻性队列研究或病例对照研究。由2名研究员独立进行文献筛选和资料提取，提取内容包括第一作者、发表年份、样本量、神经阻滞或局部注射类型、佐剂种类与剂量及主要结局指标等。采用牛津循证医学中心(Oxford Centre for Evidence-Based Medicine，OCEBM)标准对纳入研究进行证据等级评价，并依据最高证据等级对各类佐剂进行分级推荐。结果: 最终纳入临床研究文献29篇。依据证据等级，将佐剂分为A级证据佐剂和B级证据佐剂。在A级证据佐剂中，糖皮质激素通过强效抗炎作用缓解疼痛;A型肉毒毒素通过抑制疼痛介质释放及信号调制发挥镇痛作用。在B级证据佐剂中，富血小板血浆通过释放生长因子促进神经修复;医用臭氧通过抗炎及改善循环发挥作用;亚甲蓝通过改善可逆性神经髓鞘损伤实现长效镇痛;牛痘疫苗接种家兔炎症皮肤提取物则可能通过激活下行抑制通路调节疼痛。基于病程分期，急性期以抗炎(糖皮质激素)为主，慢性期以神经调控与修复(A型肉毒毒素、富血小板血浆等)为主。所有佐剂的应用均需警惕其特有的严重不良事件。结论: 神经阻滞/局部注射佐剂的应用为ZAP治疗提供了多机制、分阶段的干预策略，糖皮质激素和A型肉毒毒素拥有最高等级证据支持。当前佐剂应用面临证据等级不均、方案标准化不足等挑战，未来需开展更多高质量、大样本的随机对照试验，特别是针对不同病程阶段比较不同佐剂的优劣，以进一步优化临床治疗方案。.
Pulsed radiofrequency (PRF) treatment of the trigeminal ganglion via foramen ovale puncture for zoster-associated trigeminal neuralgia typically requires patient feedback during sensory and motor stimulation, and is usually performed under regional anesthesia (RA). However, under RA, patients often experience poor comfort due to pain and anxiety during puncture and PRF, and severe pain occurs when adjusting needle position or increasing output voltage. This often leads to lower-than-optimal treatment voltages, poor patient cooperation, and sometimes interruption or refusal of treatment. The Department of Anesthesiology at Xiangya Hospital, Central South University, has performed CT-guided trigeminal ganglion PRF under general anesthesia (GA) for zoster-associated trigeminal neuralgia. Currently, no studies directly compare the efficacy and safety of GA versus RA for this procedure. This study aims to compare GA and RA in terms of safety and efficacy for trigeminal ganglion PRF treatment of zoster-associated trigeminal neuralgia, providing clinical guidance for optimal anesthesia choice. Data were retrospectively collected for hospitalized and treated with trigeminal ganglion PRF for zoster-associated trigeminal neuralgia at Xiangya Hospital, Central South University, from July 2022 to January 2025. Patients were grouped according to the anesthesia method used during PRF: GA group and RA group. Baseline characteristics (demographics, comorbidities, disease features) were compared between groups. Pain was assessed using the Visual Analogue Scale (VAS) at 1 day, 1 month, 3 months, and 6 months postoperatively, and changes from baseline were analyzed. Patient satisfaction, total hospitalization duration, direct medical costs, and perioperative complications (hypertension, hypotension, bradycardia, tachycardia, etc.) were also compared. A total of 61 patients were included (GA group, n=29; RA group, n=32). Baseline characteristics were comparable between groups (all P>0.05). Two-way repeated measures analysis of variance showed a significant main effect of time [F(4, 295)=2 181, P<0.001], no significant main effect of group [F(1, 295)=1.377, P=0.241 5], and a significant interaction effect [F(4, 295)=4.821, P<0.001]. VAS scores at 1 day, 1 month, 3 months, and 6 months postoperatively were significantly lower than preoperative values in both groups (all P<0.05); differences between groups at all time points were not statistically significant (all P>0.05). Median hospitalization costs were 16 602 (14 904, 17 988) CNY for the GA group and 12 719 (8 709, 13 876) CNY for the RA group, with a significant difference (P<0.001). Median hospital stay was 6 (5, 7) days for both groups (P=0.606). Incidences of hypertension and tachycardia were significantly higher in the RA group than the GA group (both P<0.05). Other complications (facial swelling, dizziness, nausea, vomiting) did not differ significantly (all P>0.05). Patient satisfaction was higher in the GA group than the RA group (82.76% vs 56.25%, P=0.031). GA and RA provide comparable efficacy for trigeminal ganglion PRF in zoster-associated trigeminal neuralgia. However, GA significantly improves patient satisfaction and reduces cardiovascular stress without increasing other postoperative complications. PRF under GA is safe and feasible. 目的: 经卵圆孔穿刺三叉神经节脉冲射频(pulsed radiofrequency，PRF)治疗带状疱疹性三叉神经痛时，需在感觉运动刺激下根据患者反馈进行操作，临床上常采用局部麻醉(regional anesthesia，RA)。但在RA下穿刺与射频治疗过程中，疼痛与恐惧常导致患者舒适度下降，且在调节射频针位置及提高输出电压时患者疼痛感剧烈，进而导致治疗电压设置偏低，患者配合困难，甚至导致治疗中断或拒绝治疗。中南大学湘雅医院麻醉科开展了CT三维重建定位引导及全身麻醉(general anesthesia，GA)下三叉神经节PRF治疗带状疱疹性三叉神经痛。目前，尚无直接比较GA与RA 2种麻醉方式下该术式疗效的研究。因此，本研究拟比较GA与RA用于三叉神经节PRF治疗带状疱疹性三叉神经痛的安全性与有效性，以期为临床提供更优麻醉方案的选择依据。方法: 回顾性收集2022年7月至2025年1月期间于中南大学湘雅医院住院治疗，并接受三叉神经节PRF治疗的带状疱疹相关性三叉神经痛患者的资料。根据PRF治疗过程中所实施的麻醉方式，将患者分为GA组和RA组。比较2组患者的基线资料(人口学特征、合并症的发生情况、疾病特征)。比较2组患者术后1 d，以及术后1个月、3个月和6个月的疼痛视觉模拟评分法(Visual Analogue Scale，VAS)评分，及其与基线值的差异。此外，还比较了2组患者的满意率、住院总时长、直接医疗费用、围手术期并发症(高血压、低血压、心动过缓、心动过速等)发生率。结果: 纳入61例患者，其中GA组29例，RA组32例。2组基线特征比较差异均无统计学意义(均P>0.05)。双因素重复测量方差分析结果显示，时间主效应显著[F(4, 295)=2 181，P<0.001];组别主效应不显著[F(1, 295)=1.377，P=0.241 5];交互作用显著[F(4, 295)=4.821，P<0.001]。2组术后1 d、1个月、3个月、6个月的VAS评分均显著低于术前(均P<0.05);所有时间点2组VAS评分的差异均无统计学意义(均P>0.05)。GA组、RA组的住院费用分别为16 602(14 904，17 988)元、12 719(8 709，13 876)元，2组之间差异有统计学意义(P<0.001);GA组、RA组的住院时间分别为6(5，7) d、6(5，7) d，2组之间差异无统计学意义(P=0.606)。RA组高血压与心动过速发生率均显著高于GA组(均P<0.05)。面部肿胀、头晕、恶心和呕吐等并发症的发生率2组间比较差异均无统计学意义(均P>0.05)。GA组满意率显著高于RA组(82.76% vs 56.25%，P=0.031)。结论: GA与RA下行三叉神经节PRF治疗带状疱疹性三叉神经痛的疗效基本相当，但GA下实施PRF可显著提升患者满意度，降低心血管应激，且不增加其他术后并发症的发生风险。GA下行三叉神经节PRF安全可行。.
Postherpetic neuralgia (PHN) is a severe and distressing complication in elderly patients with herpes zoster and is associated with increased sympathetic nervous system activity. Spinal cord stimulation (SCS) implantation has been shown to effectively relieve PHN. In recent years, heart rate variability (HRV) analysis, as a reliable and objective indicator of autonomic nervous system (ANS) activity, has been widely used in the assessment of chronic pain. This study aims to investigate the clinical effects of SCS implantation on HRV in patients with PHN and its correlation with pain outcomes. A total of 28 patients who met the inclusion criteria and were treated in the Department of Pain Medicine, the Third Xiangya Hospital of Central South University between November 2023 and March 2024 were retrospectively included. All patients underwent SCS implantation. HRV parameters before and after SCS implantation were collected, including the standard deviation of all normal-to-normal intervals over 24 hours (SDNN), root mean square of successive differences (RMSSD), standard deviation of successive differences (SDSD), percentage of adjacent normal-to-normal intervals differing by more than 50 milliseconds (PNN50), low-frequency power (LF), high-frequency power (HF), the LF/HF ratio, and total power (TP) within 5 minutes across all frequency bands. Univariate linear regression analysis was performed to explore the correlations among HRV parameters before and after SCS treatment. After SCS implantation, the HRV time-domain indices SDNN, RMSSD, SDSD, and PNN50, as well as the frequency-domain indices LF, HF, and TP, were significantly increased (all P<0.05), while the change in LF/HF ratio was not statistically significant (P>0.05). SCS treatment also had positive effects on pain relief, improvement of negative emotions, and reduction of psychological stress (all P<0.05). Differences were observed among implantation segments. In patients receiving SCS implantation below the T8 thoracic segment, SDNN, LF, and HF decreased significantly (all P<0.05). Correlation analysis revealed that pain scores were significantly correlated with SDNN. Significant correlations were also observed among the HRV time-domain indices SDSD, RMSSD, and PNN50 (all P<0.05), whereas correlations among frequency-domain indices were relatively weak. The changes in time-domain and frequency-domain HRV indices showed a synergistic trend. Pain outcomes in patients with PHN are accompanied by synchronous changes in autonomic nervous system activity. SCS implantation can improve HRV stability in patients with PHN and contribute to better cardiac rhythm regulation. HRV measurement may serve as evidence reflecting ANS activity in patients with PHN. 目的: 带状疱疹后神经痛(postherpetic neuralgia，PHN)是一种带状疱疹老年患者严重而痛苦的并发症，与高交感神经活动有关，通过脊髓电刺激(spinal cord stimulation，SCS)置入可有效缓解PHN。近年来，心率变异性(heart rate variability，HRV)分析作为自主神经系统(autonomic nervous system，ANS)可靠、客观的反馈指标，被广泛应用于慢性疼痛的评估中。本研究旨在探讨SCS置入对PHN患者HRV的临床影响及其与疼痛结局的相关性。方法: 回顾性选取2023年11月至2024年3月在中南大学湘雅三医院疼痛科符合纳入标准的患者28例。所有患者均接受SCS置入治疗，获取SCS置入前后的HRV数据，包括连续24 h所有正常至正常(心搏)间隔的标准差(standard deviation of normal-to-normal intervals，SDNN)、差值的均方根(root mean square of successive interval differences，RMSSD)、差值的标准差(standard deviation of successive differences，SDSD)、相邻R-R间期差值>50 ms的个数所占百分比(percentage of adjacent normal-to-normal intervals that differ by more than 50 milliseconds，PNN50)、低频段功率(low-frequency power，LF)、高频段功率(high-frequency power，HF)、LF和HF比值(LF/HF)及5 min内所有频率总功率(total power，TP)。采用单因素线性回归分析探讨SCS治疗前后HRV指标的相关性。结果: SCS置入后，患者的HRV时域指标SDNN、RMSSD、SDSD、PNN50及频域指标LF、HF、TP均显著增加(均P<0.05)，LF/HF值的变化差异无统计学意义(P>0.05)。SCS治疗对疼痛缓解、负面情绪改善、精神压力下降均有积极作用(均P<0.05)。不同节段SCS置入存在差异，胸椎T8以下节段置入SCS后患者的SDNN、LF、HF显著降低(均P<0.05)。相关性分析显示，患者疼痛评分与SDNN具有显著相关性，HRV时域指标SDSD、RMSSD、PNN50间存在显著相关性(均P<0.05)，频域指标间相关性较低，且HRV时域与频域指标的变化呈协同促进趋势。结论: PHN患者疼痛结局与自主神经活动存在同步变化，SCS置入可改善PHN患者的HRV稳定性，有利于心脏节律的稳定。HRV测量可作为PHN患者ANS活动的证据。.
Ileal conduit diversion is currently the most commonly used urinary diversion method for patients undergoing radical cystectomy. Because intestinal reconstruction is involved, perioperative enteral nutrition intake is limited, placing patients at risk of malnutrition and affecting postoperative recovery and quality of life. Whole-process perioperative nutritional management is of great significance for promoting rapid postoperative recovery in such patients. This study aims to explore the effects of whole-process nutritional management intervention based on the information-knowledge-attitude-practice (IKAP) theory on nutritional status and quality of life in patients undergoing radical cystectomy for bladder cancer. A total of 69 patients who underwent radical cystectomy with ileal conduit diversion for bladder cancer in the Department of Urology, Third Xiangya Hospital of Central South University, between January 2022 and December 2024 were included. Patients were grouped according to admission time. Patients admitted between January 2022 and October 2023 were assigned to the control group (n=34) and received routine perioperative nutritional support for radical cystectomy with ileal conduit diversion. Patients admitted between November 2023 and December 2024 were assigned to the intervention group (n=35) and received whole-process nutritional management based on IKAP theory. Nutritional Risk Screening 2002 (NRS2002) score, Onodera's prognostic nutritional index (OPNI), and the third edition Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQ-C30) were compared between the 2 groups at 3 time points: day 1 after admission, 1 day before discharge, and 1 month after discharge. The incidence of postoperative related complications between the two groups was also compared. In both groups, the NRS2002 score at 1 month after discharge was lower than that at 1 day before discharge, and the intervention group had lower scores than the control group, with statistically significant differences (all P<0.05). The OPNI at 1 month after discharge was significantly higher than that at 1 day before discharge in both groups, and the intervention group had higher values than the control group, with statistically significant differences (all P<0.05). There was no statistically significant difference in the incidence of postoperative related complications between the 2 groups (all P>0.05). The EORTCQLQ-C30 scores in the intervention group were higher than those in the control group at 1 day before discharge and 1 month after discharge, with statistical significant differences (both P<0.05). Whole-process nutritional management based on IKAP theory can improve the nutritional status and prognosis of patients undergoing radical cystectomy with ileal conduit diversion and improve their quality of life. 目的: 回肠通道术是目前临床最为常用的根治性膀胱全切患者的尿流改道方式，因涉及肠道重建，围术期肠内营养摄入受限，患者存在营养不良风险，影响术后患者的康复及生活质量。围术期全程营养管理对促进此类患者术后快速康复具有重要意义。本研究旨在探讨基于信息-知识-信念-行为(information- knowledge-attitude-practice，IKAP)理论的全程营养管理干预对膀胱癌根治术患者营养状况及生活质量的影响。方法: 纳入2022年1月至2024年12月中南大学湘雅三医院泌尿外科收治的69例因膀胱癌行根治性膀胱全切加回肠通道术的患者。根据入院的先后顺序对患者进行分组，2022年1月至2023年10月收治的患者为对照组(n=34)，给予常规的根治性膀胱全切加回肠通道术围手术期营养支持;2023年11月至2024年12月收治的患者为干预组(n=35)，给予基于IKAP理论的全程营养管理。比较2组患者在入院第1天、出院前1 d、出院后1个月3个时间点的营养风险筛查(Nutrition Risk Screening 2002，NRS2002)评分、小野寺预后营养指数(Onodera’s prognostic nutritional index，OPNI)及第3版中文版欧洲癌症研究与治疗组织生活质量量表(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30，EORTCQLQ-C30)评分，并比较2组患者术后相关并发症的发生率。结果: 2组患者出院后1个月的NRS2002评分均低于出院前1 d，且干预组低于对照组，差异均有统计学意义(均P<0.05)。2组患者出院后1个月的OPNI均较出院前1 d明显升高，且干预组高于对照组，差异均有统计学意义(均P<0.05)。2组患者术后相关并发症发生率的差异均无统计学意义(均P>0.05)。干预组患者在出院前1 d、出院后1个月的EORTCQLQ-C30评分均高于对照组，差异均有统计学意义(均P<0.05)。结论: 基于IKAP理论的全程营养管理能改善根治性膀胱切除加回肠通道术患者的营养状况及预后，提高其生活质量。.
In recent years, the phenomenon of "hollow heart syndrome" has become increasingly prevalent among college students, characterized by persistent inner emptiness, lack of motivation, and a diminished sense of meaning. Even when external achievements are attained, individuals often fail to experience a sense of fulfillment and satisfaction. Such students may appear successful outwardly but remain trapped in confusion and meaninglessness, and may even frequently experience suicidal ideation. As a critical stage of psychological development, the college period involves the transition from identity diffusion to identity formation. Establishing a stable and clear self-identity during this stage is essential for developing a sustained sense of meaning in life. Therefore, this study aims to examine the relationship between self-concept clarity and meaning in life among college students using a longitudinal design, and to further investigate the moderating role of depressive symptoms in this relationship, thereby providing theoretical support for promoting meaning in life and empirical evidence for improving psychological crisis prevention and intervention systems. A longitudinal design was employed. A total of 387 college students from a comprehensive university were assessed twice at a four-week interval, with the two time points denoted as T1 and T2. The instruments included the Self-Concept Clarity Scale (SCCS), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Meaning in Life Questionnaire (MLQ). Cross-lagged analysis was conducted to examine the bidirectional relationship between self-concept clarity and meaning in life, and standardized regression coefficients (β) were calculated. Based on this, a two-step multiple regression analysis was used to test the moderating effects of depressive symptoms on the pathways from self-concept clarity to meaning in life and from meaning in life to self-concept clarity. For paths showing significant moderation, simple slope analyses were further conducted to explore the moderating patterns at different levels of depressive symptoms. Self-concept clarity at T1 significantly and positively predicted meaning in life at T2 (β=0.214, P<0.001), and meaning in life at T1 significantly and positively predicted self-concept clarity at T2 (β=0.211, P<0.001). Depressive symptoms significantly moderated only the predictive effect of self-concept clarity on meaning in life (P=0.035). Simple slope analysis showed that the effect sizes were 0.400 and 0.245 in the high and low depressive symptom groups, respectively. However, the moderating effect of depressive symptoms on the pathway from meaning in life to self-concept clarity was not significant (P=0.258). This is a reciprocal and mutually reinforcing relationship between self-concept clarity and meaning in life. Depressive symptoms play a moderating role in this relationship, such that higher levels of depressive symptoms strengthen the predictive effect of self-concept clarity on meaning in life. Therefore, in mental health education and intervention among college students, it is important to emphasize the coordinated development of self-concept and meaning construction, and to utilize the moderating role of depressive symptoms to optimize intervention strategies. For students with depressive tendencies, priority should be given to assessing and improving their identity status, promoting self-acceptance, integration, and identity consolidation. For students with unclear self-concept, timely assessment of depressive symptoms and early psychological intervention are recommended to reduce the negative cycle between self-concept and meaning in life and to promote psychological adaptation and healthy development. 目的: 近年来，“空心病”在大学生群体中较为普遍，其主要特征为个体长期处于内心空虚、动力匮乏和意义感缺失的状态，即使达成外在成就，仍难以获得内心的充实和满足。这类学生往往外在成就突出，但其内心仍受困于迷茫和无意义体验之中，甚至可能频繁出现自杀意念。大学阶段是个体心理发展的关键时期，个体承担着由自我同一性扩散向同一性确立过渡的重要发展任务，在此阶段构建稳定、清晰的自我同一性，对于形成持续的生命意义感具有至关重要的作用。本研究旨在探讨大学生群体中自我概念清晰度与生命意义感之间的关系，并进一步探究抑郁症状在二者关系中的调节作用，从而为促进大学生生命意义感的发展提供理论参考，为完善相关心理危机预防与干预体系提供实证依据。方法: 采用纵向研究设计，对一所综合性大学的387名大学生进行间隔4周的2次重复施测，第1次和第2次施测的时间点分别记为T1和T2。研究工具包括自我概念清晰度量表(Self-Concept Clarity Scale，SCCS)、流调用抑郁自评量表(Center for Epidemiological Survey-Depression Scale，CES-D)及生命意义量表(Meaning in Life Questionnaire，MLQ)。采用交叉滞后分析检验自我概念清晰度与生命意义感之间的双向关系，计算预测系数β，并在此基础上采用2步多元回归法检验抑郁症状得分在自我概念清晰度到生命意义感及生命意义感到自我概念清晰度路径上的调节作用。对调节效应显著的路径进行简单斜率分析，以揭示抑郁症状得分在自我概念清晰度影响生命意义感过程中的具体调节机制。结果: T1的自我概念清晰度可显著正向预测T2的生命意义感(β=0.214，P<0.001)，T1的生命意义感可显著正向预测T2的自我概念清晰度(β=0.211，P<0.001)。抑郁症状仅在自我概念清晰度对生命意义感的预测中起显著的调节作用(P=0.035)。简单斜率分析表明，在高抑郁症状水平和低抑郁症状水平条件下，自我概念清晰度对生命意义感的预测效应分别为0.400和0.245。在生命意义感对自我概念清晰度的预测路径中，抑郁症状的调节作用未达显著水平(P=0.258)。结论: 自我概念清晰度与生命意义感之间存在相互促进的关系，抑郁症状在二者关系中具有调节作用，表现为高抑郁症状会强化自我概念清晰度对生命意义感的预测效应。因此，在大学生群体的心理健康教育及干预实践中，应重视自我概念发展与意义感建构的协同作用，并利用抑郁症状的调节效应优化干预策略。对具有抑郁倾向的学生，可优先关注其自我同一性状态，促进其自我接纳、整合与同一性巩固;对出现自我概念模糊的学生，应及时评估其抑郁症状，实施早期心理干预，以减弱自我概念与意义感之间的消极循环，促进其心理适应与健康发展。.