To investigate the diagnosis rate of heparin-induced thrombocytopenia (HIT), the incidence of new thrombosis, the dynamic evolution pattern of platelets, and the clinical characteristics in patients with suspected HIT after cardiac surgery; and to evaluate the diagnostic value of HIT antibodies (HIT-Ab), 4T's score, and Lillo-Le Louet (LLL) score for HIT. A retrospective cohort study was conducted. A total of 307 patients with suspected HIT after cardiac surgery at Fuwai Hospital of the Chinese Academy of Medical Sciences from April 2023 to December 2024 were included. Clinical and laboratory data were collected. All patients underwent 4T's score, LLL score, and HIT-Ab testing. Patients were divided into the non-HIT group (n = 269) and the HIT group (n = 38) based on the final clinical diagnosis. The platelet evolution patterns and other clinical characteristics of the two groups were compared. HIT-Ab concentration was divided into four groups: negative (< 1.0 U/mL, n = 257), weakly positive (1.0-4.9 U/mL, n = 34), moderately positive (5.0-9.9 U/mL, n = 11), and strongly positive (≥ 10 U/mL, n = 5). Differences in the incidence of new thrombosis and the diagnosis rate of HIT among the groups were analyzed, and the diagnostic efficacy of HIT-Ab concentration, 4T's score, and LLL score for HIT was evaluated using receiver operating characteristic (ROC) curves. The diagnosis rate of HIT was 12.38% (38/307), and the incidence of new thrombosis in the HIT group was 63.16%, higher than the 34.57% in the non-HIT group (P < 0.001). Among HIT patients, 76.32% showed a biphasic decline pattern of platelets (pattern A), and their risk of HIT was significantly higher than that of patients with pattern B (odds ratio [OR] = 10.32, 95% confidence interval [CI]: 4.64-22.95). The incidence of new thrombosis increased stepwise with higher HIT-Ab concentration (32.7% in the negative group to 100% in the strongly positive group, P < 0.001), and the diagnosis rate of HIT increased from 0 in the negative group to 64.71% in the weakly positive group, reaching 100% in the moderate/strong positive group. The areas under the ROC curves for HIT-Ab concentration, 4T's score, and LLL score for diagnosing HIT were 0.996 (95% CI: 0.991-1.000), 0.799 (95% CI: 0.727-0.870), and 0.860 (95% CI: 0.811-0.908), respectively. When the HIT-Ab concentration was 1 U/mL, the diagnostic sensitivity and negative predictive value (NPV) were both 100%. Compared with the traditional diagnostic criteria for high-risk HIT populations (4T's score cutoff of 4, LLL score cutoff of 2), the optimal cutoff value of 4T's score selected by the maximum Youden index was 5, and the optimal cutoff value of LLL score was 3. The incidence of new thrombosis in patients with suspected HIT after cardiac surgery increases stepwise with higher HIT-Ab levels. The diagnostic value of the LLL score for HIT is superior to that of the 4T's score. HIT-Ab testing has high sensitivity and negative predictive value, making it a reliable tool for guiding early discontinuation of heparin and excluding HIT. Combining HIT-Ab concentration, platelet evolution pattern, and clinical scores helps more accurately identify HIT risk, initiate alternative anticoagulation therapy, and optimize anticoagulation management strategies. 探讨心脏外科术后疑似肝素诱导血小板减少症(heparin-induced thrombocytopenia, HIT)患者中HIT的确诊率、新发血栓发生率、血小板动态演变模式及临床特征;评估HIT抗体(hit-antibodies, HIT-Ab)、4T's评分和Lillo-Le Louet(LLL)评分对HIT的诊断价值。 采用回顾性队列研究,纳入2023年4月–2024年12月中国医学科学院阜外医院心脏外科术后疑似HIT患者307例,收集其临床与实验室数据。所有患者均接受4T's评分、LLL评分及HIT-Ab检测。根据最终临床诊断分为非HIT组(n=269)和HIT组(n=38),比较两组血小板演变模式及其他临床特征。根据HIT-Ab浓度分为四组:阴性组(<1.0 U/mL,n=257)、弱阳性组(1.0~4.9 U/mL,n=34)、中阳性组(5.0~9.9 U/mL,n=11)、强阳性组(≥10 U/mL,n=5),分析各组间新发血栓发生率及HIT确诊率等差异,并用受试者工作特征曲线(ROC曲线)评估HIT-Ab浓度、4T's评分和LLL评分对HIT的诊断效能。 HIT确诊率为12.38%(38/307),HIT组新发血栓率为63.16%,高于非HIT组34.57%(P<0.001)。76.32%HIT患者血小板呈双相下降模式(模式A),其发生HIT的风险显著高于模式B患者〔比值比(odds ratio, OR)=10.32, 95%置信区间(confidence interval, CI):4.64~22.95〕。新发血栓发生率随HIT-Ab升高阶梯式递增(阴性组32.7%→强阳性组100%,P<0.001),HIT确诊率从阴性组的0升至弱阳性组的64.71%,中/强阳性组确诊率达100%。HIT-Ab浓度、4T's评分和LLL评分诊断HIT的ROC曲线下面积分别为0.996(95%CI:0.991~1.000)、0.799(95%CI:0.727~0.870)和0.860(95%CI:0.811~0.908)。当HIT-Ab浓度为1 U/mL时,其诊断敏感度为100%,阴性预测值(negative predictive value, NPV)为100%。 与传统的HIT高危人群的诊断标准(4T's评分截断值为4分,LLL评分截断值为2分)相比, 以最大约登指数选定的4T's评分最佳截断值为5分,LLL评分最佳截断值为3分。 心脏术后疑似HIT患者新发血栓发生率随HIT-Ab水平升高呈阶梯上升趋势。LLL评分对HIT的诊断价值优于4T's评分。HIT-Ab检测具有较高的敏感度和阴性预测值,是指导早期停用肝素和排除HIT的可靠工具。结合HIT-Ab浓度、血小板演变模式及临床评分,有助于更精准地识别HIT风险、启动替代抗凝治疗及优化抗凝管理策略。
Based on the Global Burden of Diseases (GBD) 2021 data, this study systematically analyzed the trends in the disease burden of diabetic kidney disease (DKD) and predicted its burden over the next decade in 204 countries and regions worldwide from 1990 to 2021. Data on DKD from the GBD study spanning 1990 to 2021 were analyzed for trends using age-standardized rates (ASRs) and average annual percentage change (AAPC). The Joinpoint Regression Model (JRM) was applied to identify turning points, and the Autoregressive Integrated Moving Average (ARIMA) model was used to forecast future trends. Statistical analysis was performed using R software. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of global DKD from 1990 to 2021 showed substantial increases, with cumulative rises of 55.0% (95% CI: 42.3% to 69.8%, P < 0.001) and 57.3% (95% CI: 43.1% to 73.5%, P < 0.001), respectively. The age-standardized prevalence rate (ASPR) declined by 37.5% (95% CI: -45.2% to -28.8%, P < 0.001), while the age-standardized disability-adjusted life years (DALYs) rate rose by 56.2% (95% CI: 42.8% to 71.5%, P < 0.001). Noticeable disparities in disease burden were observed among countries and regions. Greenland experienced the largest increase in ASPR, whereas the United Kingdom had the most substantial decrease. Estonia had the highest rise in ASIR, while Ireland saw the greatest decline. The United States had the most pronounced increase in ASDR, while the Maldives had the largest decrease. East Asia had the highest number of current cases, while South Asia bore the heaviest burden of new cases and DALYs. The increase was more prominent in regions with a low socio-demographic index (SDI). Projections for the next decade (2022-2031) indicate that the global ASPR of DKD will increase by an average of 0.45% per year (95% CI: 0.21% to 0.69%), the ASIR will decrease by an average of 0.23% per year (95% CI: -0.47% to -0.01%), and the age-standardized DALYs rate will increase by an average of 1.12% per year (95% CI: 0.89% to 1.35%). The overall burden of the disease is expected to continue growing. The global burden of DKD is steadily increasing, and it is especially severe in regions with low SDI. It is essential to implement targeted prevention and control measures in high-burden areas to provide a scientific basis for allocating public health resources. 基于全球疾病负担(Global Burden of Diseases, GBD)2021数据,系统分析了1990–2021年全球204个国家和地区糖尿病肾病(diabetic kidney disease, DKD)的疾病负担趋势及未来十年预测。 GBD 1990–2021年DKD数据,采用年龄标准化率(age-standardized rates, ASRs)和平均年度百分比变化(average annual percentage change, AAPC)分析趋势,运用联结点回归模型(Joinpoint regression model, JRM)识别转折点,自回归积分移动平均模型(autoregressive integrated moving average, ARIMA)预测未来趋势,R软件实现统计分析。 1990–2021年全球DKD年龄标准化发病率(age-standardized incidence rate, ASIR)、年龄标准化死亡率(age-standardized death rate, ASDR)呈显著上升,累计分别上升55.0%〔95%置信区间(confidence interval, CI):42.3%~69.8%,P<0.001〕、57.3%(95%CI:43.1%~73.5%,P<0.001);年龄标准化患病率(age-standardized prevalence rate, ASPR)累计下降37.5%(95%CI:-45.2%~-28.8%,P<0.001);年龄标准化伤残调整寿命年(age-standardized disability-adjusted life years, DALYs)率累计上升56.2%(95%CI:42.8%~71.5%,P<0.001)。国家和地区间负担差异显著,格陵兰ASPR上升幅度最大,英国ASPR降幅最大;爱沙尼亚ASIR增幅最高,爱尔兰ASIR降幅最大;美国ASDR上升最显著,马尔代夫ASDR下降最明显。东亚现患病例数最多,南亚新发病例与DALYs负担最重,低社会人口指数(socio-demographic index, SDI)地区上升更显著。未来十年(2022–2031年)预测显示,全球DKD ASPR年均上升0.45%(95%CI:0.21%~0.69%),ASIR年均下降0.23%(95%CI:-0.47%~-0.01%),年龄标准化DALYs率年均上升1.12%(95%CI:0.89%~1.35%),疾病总负担仍将持续加重。 全球DKD疾病负担日益加重,低SDI地区尤为显著,亟需在高负担区域采取精准防控措施,为公共卫生资源配置提供科学依据。
To develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 33 aromatic primary amines in medical-grade thermoplastic polyurethane (TPU). The target compounds were extracted using 80% methanol and PBS solution containing 10% ethanol as the solvents. The 80% methanol extract was filtered through and diluted to one-fifth of the original concentration. The PBS extract was processed through an HLB solid-phase extraction column (3 mL, 60 mg, methanol and water equilibrium), eluted with 5 mL methanol, filtered, and diluted to 5 mL with methanol. Then, analysis was performed using UPLC-MS/MS. Chromatographic separation was performed using an Agilent InfinityLab Poroshell 120 EC-C18 column (150 mm × 3.0 mm, 2.7 μm) with methanol (A) and deionized water containing 0.1% formic acid (B) as the mobile phases. Gradient elution was conducted with a column temperature of 40 ℃, a flow rate of 0.2 mL/min, and an injection volume of 1 μL. Mass spectrometry analysis was performed using an electro-spray ionization (ESI) source in multiple reaction monitoring (MRM) positive ion mode. The standard curves, quantification limits, precision, recovery rates, and matrix effects of the method under different extraction conditions were evaluated. The 33 aromatic primary amines analyzed in the study showed good linearity (r > 0.998) within the 2-100 ng/mL concentration range. Detection limits ranged from 0.1 to 0.5 ng/mL, and quantification limits ranged from 0.3 to 1.7 ng/mL. Recovery rates for the 33 aromatic primary amines in 80% methanol samples ranged from 70.7% to 116.0%. Recovery rates for 31 aromatic primary amines in PBS samples containing 10% ethanol ranged from 74.9% to 113.8%. The intra-day and inter-day precision for different samples was both less than 10%, indicating good sample stability. Analysis of aromatic primary amine content in sample extracts using this method revealed that methylenedianiline (MDA) was detected in all 6 initially tested samples. Under simulated extraction at 37 ℃ and accelerated extraction at 60 ℃, 3 samples exhibited continuous or delayed MDA release. 2,4'-MDA was detected in 2 samples during the initial limit extraction phase and remained detectable in 1 sample under 60 ℃ accelerated aging conditions, but no release was observed under the 37 ℃ simulated physiological environment. 2,2'-MDA was detected only in two samples during initial limit extraction and was not released in subsequent simulated or accelerated extraction processes. The UPLC-MS/MS method demonstrates high sensitivity and accuracy, meeting the requirements for precise detection of 33 aromatic primary amines in medical-grade TPU and providing reliable technical support for risk assessment and quality control of aromatic primary amines in these materials and products. 建立超高效液相色谱-串联质谱法(ultra-high performance liquid chromatography-tandem mass spectrometry, UPLC-MS/MS),实现对医用热塑性聚氨酯(thermoplastic polyurethane, TPU) 中 33 种芳香伯胺含量的同时测定。 分别以80%甲醇和含10%乙醇的PBS溶液为溶剂提取目标化合物,80%甲醇浸提液过滤后稀释至原浓度的1/5;PBS浸提液经HLB小柱(3 mL,60 mg,甲醇+水平衡)处理后,5 mL甲醇洗脱,过滤后甲醇定容至5 mL,采用超高效液相色谱-串联质谱进行检测分析。色谱分离采用Agilent InfinityLab Poroshell 120 EC-C18色谱柱(150 mm×3.0 mm,2.7 μm),以甲醇(A)和含0.1%甲酸的去离子水(B)为流动相。梯度洗脱,柱温为40 ℃;流速为0.2 mL/min;进样体积为1 μL。质谱检测选用电喷雾离子源(electro-spray ionization, ESI),多反应监测(multiple reaction monitoring, MRM)正离子模式,考察该方法在不同浸提条件下的标准曲线与定量限、精密度、回收率及基质效应。 33种芳香伯胺在2~100 ng/mL浓度范围内线性关系良好(r>0.998),检出限为0.1~0.5 ng/mL,定量限为0.3~1.7 ng/mL;80%甲醇样本中33种芳香伯胺的回收率为70.7%~116.0%;含10%乙醇的PBS样本中31种芳香伯胺的回收率为74.9%~113.8%;本方法在不同样本中的日内、日间精密度均<10%,样品稳定性良好。采用本方法对样品浸提液中芳香伯胺含量进行分析,结果表明,在初始检测的6份样品中均检出MDA,且在37 ℃模拟浸提及60 ℃加速浸提条件下,共有3份样品持续或延迟释放出MDA;2,4'-MDA在初始极限浸提阶段于2份样品中检出,并在60 ℃加速老化条件下仍可在1份样品中检出,但在37 ℃模拟生理环境中未见释放;2,2'-MDA仅在初始极限浸提的2份样品中检出,在后续模拟及加速浸提过程中均未释放。 该UPLC-MS/MS 方法灵敏度高、准确度好,不仅可满足医用 TPU 中 33 种芳香伯胺的精准检测需求,更为该类材料及制品的芳香伯胺风险评估与质量控制提供了可靠技术支持。
As health and medical big data is elevated to a "national key strategic resource," its legal significance in public health governance, individual rights protection, and resource allocation optimization has become increasingly prominent. The World Health Organization (WHO) Global Strategy on Digital Health 2020-2027 states that digital health development should adhere to the principles of ethics, security, equity, and sustainability, with data governance serving as critical support for realizing the universal right to health. China has issued the Measures for Ethical Review and Service of Artificial Intelligence Technology (for Trial Implementation), which incorporates high-risk areas such as life and health, public order, and algorithmic decision-making into a full-process ethical review, thereby initially establishing a dual regulatory framework of "rule of law + ethics." However, a structural tension remains between technological logic and rule-of-law values. In the application of health and medical big data, multiple risks have gradually emerged, including de-anonymization failures, algorithmic discrimination, imbalances in data-related interests, and ethical misconduct. In light of this, from a scenario-based perspective, this paper systematically identifies the core legal risks and proposes regulatory pathways such as classified and graded protection, dynamic anonymization, algorithm auditing, and the return of public interests, aiming to safeguard human dignity and public health security in the digital era while unlocking the value of data. 随着健康医疗大数据被提升为“国家重要基础性战略资源”,其在公共健康治理、个体权利保障与资源配置优化中的法治意义日益凸显。世界卫生组织(World Health Organization, WHO)《全球数字健康战略(2020–2027年)》提出,数字健康发展应遵循伦理、安全、公平与可持续原则,将数据治理作为实现全民健康权的重要支撑;我国出台《人工智能科技伦理审查与服务办法(试行)》,将生命健康、公共秩序及算法决策等高风险领域纳入全流程伦理审查,初步构建“法治+伦理”的双重规制框架。然而,技术逻辑与法治价值之间仍存在结构性张力,健康医疗大数据应用中逐渐显现出匿名化失灵、算法歧视、数据利益失衡及伦理失范等多重风险。基于此,本文从场景化视角出发,系统识别核心法治风险,并提出分类分级保护、动态匿名化、算法审计及公共利益返还等规制路径,以期在释放数据价值的同时维护数字时代的生命尊严与公共卫生安全。
To investigate mitochondrial functional alterations in T lymphocytes of patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis, NMDAR-E) and their association with immune exhaustion. Twenty-five patients with NMDAR-E diagnosed in the Department of Neurology, West China Hospital, Sichuan University, between January and March 2025 (14 mild cases and 11 severe cases) and 16 healthy controls were enrolled. Flow cytometry was performed to characterize immune-cell distributions in paired peripheral blood and cerebrospinal fluid (CSF), and to evaluate the percentage of cells with low mitochondrial membrane potential (MMP-Low%), mitochondrial mass (MM), and PD-1 expression. In severe patients, the proportions of CD3+ and CD4+ T cells in CSF, the MMP-Low% of CD3+, CD4+, and CD8+ T cells (P < 0.01), and the MM of CD3+ (P < 0.01) and CD8+ T cells (P < 0.05) were all significantly higher than those in matched peripheral blood. Compared with healthy controls, the MMP-Low% of naïve and central memory CD4+ and CD8+ T-cell subsets in peripheral blood was significantly decreased (P < 0.05), whereas the proportion of PD-1-positive cells was significantly increased in CD4+naïve and central memory T-cell subsets (P < 0.01). CSF T cells in patients with anti-NMDAR encephalitis display a state of dysfunctional mitochondrial accumulation, suggesting a possible dysregulation of mitochondrial mass homeostasis under the central inflammatory milieu. Mitochondrial features of peripheral T cells indicate the presence of systemic immune exhaustion. The MMP-Low% of CSF CD8+ T cells and the peripheral blood lymphocyte percentage may serve as potential immunometabolic biomarkers for distinguishing disease severity in NMDAR-E. 探讨抗NMDAR脑炎(anti-N-methyl-D-aspartate receptor encephalitis, NMDAR-E)患者T淋巴细胞线粒体功能变化特征及其与免疫耗竭状态的相关性。 本研究纳入2025年1–3月在四川大学华西医院神经内科确诊的抗NMDAR脑炎患者25例(轻症14例,重症11例)及健康对照16名,采用流式细胞术检测患者外周血与脑脊液中免疫细胞分布,评估低线粒体膜电位细胞比例(low mitochondrial membrane potential, MMP-Low%)、线粒体质量(mitochondrial mass, MM)及PD-1表达水平。 重症患者脑脊液中CD3+和CD4+ T细胞占比、CD3+、CD4+和CD8+ T细胞的MMP-Low%以及CD3和CD8+ T细胞的MM均高于配对外周血(均P<0.05)。相比于健康对照,患者外周血CD4+和CD8+初始T细胞和中央记忆T细胞亚群MMP-Low%下降(P<0.05),同时CD4+初始T细胞和中央记忆T细胞亚群的PD-1阳性细胞比例上升(P<0.01)。 抗NMDAR脑炎患者脑脊液T细胞处于功能障碍性线粒体积聚状态,提示中枢炎症环境下T细胞线粒体质量稳态调控机制失衡。外周T细胞线粒体状态提示存在系统性免疫耗竭。脑脊液CD8+ T细胞MMP-Low%和外周血淋巴细胞占比可作为区分抗NMDAR-E脑炎患者病情轻重的潜在免疫代谢标志物。
To analyze the species distribution and in vitro susceptibility of pathogenic bacteria isolated from the lower respiratory tract of the patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to provide guidance for the treatment of pulmonary infections in this kind of patients. The AECOPD patients with suspected lower respiratory tract sample infection from January 2015 to December 2024 were included. The data of species identification and in vitro drug susceptibility testing results of pathogenic bacteria isolated from the lower respiratory tract were retrospectively collected. The detection rate, species distribution, in vitro susceptibility of predominant species, and ratios of multidrug-resistant (MDR) bacteria were compared among different sample types. Data were analyzed using WHONET 5.6 and SPSS 26.0 software. A total of 25253 lower respiratory tract samples from 3861 patients were included. The pathogen detection rates in sputum, aspirates and bronchoalveolar lavage fluids were 27.2% (6463/23722), 33.5% (135/403), and 48.9% (551/1128), respectively, with a statistically significant difference of detection rate (P < 0.001). Among the 3,824 non-repetitive strains, the ratio of the isolates recovered from outpatients and emergency patients to those from inpatients is 1∶6, and the ratio of the isolates from intensive care unit patients to those from other units is 1∶7. Gram-negative bacteria accounted for 93.1%, with the predominant species including Acinetobacter baumannii complex (23.7%), Pseudomonas aeruginosa (21.4%), Klebsiella pneumoniae (12.6%), Stenotrophomonas maltophilia (11.7%), and Escherichia coli (4.6%). Gram-positive bacteria accounted for 6.9%, with Staphylococcus aureus was the most common species (3.2%). Fastidious bacteria accounted for 6.4%, including Haemophilus influenzae (3.9%), Moraxella catarrhalis (1.6%), and Streptococcus pneumoniae (0.9%). The detection rate of methicillin-resistant S. aureus (MRSA) was 41.8%. The detection rates of carbapenem-resistant E. coli, K. pneumoniae, A. baumannii complex, and P. aeruginosa were 12.0% (21/175), 18.1% (87/480), 69.9% (635/908), and 29.3% (240/819), respectively. Compared with sputum, non-sputum specimens showed a higher detection rate of MDR bacteria (P < 0.01). Gram-negative bacteria were the predominant pathogenic bacteria detected from the low respiratory tract of AECOPD patients, with a low isolation rate of fastidious bacteria. Non-sputum samples exhibited a higher detection rate of MDR bacteria. 分析从慢性阻塞性肺病急性加重期(acute exacerbation of chronic obstructive pulmonary disease, AECOPD)患者下呼吸道分离病原菌的菌种分布及体外药物敏感性,为该类患者下呼吸道感染治疗提供参考。 纳入2015年1月–2024年12月AECOPD疑似发生下呼吸道感染的患者,回顾性收集从下呼吸道样本分离的病原菌菌种鉴定和体外药物敏感性检测结果,对比分析不同类型样本的病原菌检出率、菌种分布、主要菌种体外药物敏感性和多重耐药菌检出情况。采用WHONET 5.6和SPSS 26.0软件分析数据。 纳入的3861例患者送检下呼吸道样本25253份,痰液、气道分泌物和肺泡灌洗液的病原菌检出率分别为27.2%(6463/23722)、33.5%(135/403)和48.9%(551/1128),检出率差异有统计学意义(P<0.001)。共分离到非重复菌株3824株,门急诊患者和住院患者来源的细菌数量比为1∶6,重症监护病房和其他病房来源的细菌数量比为1∶7。分离株以革兰阴性菌为主(93.1%),鲍曼不动杆菌复合群检出率最高(23.7%),其次为铜绿假单胞菌(21.4%)、肺炎克雷伯菌(12.6%)、嗜麦芽窄食单胞菌(11.7%)和大肠埃希菌(4.6%);革兰阳性菌占比为6.9%,以金黄色葡萄球菌(3.2%)为主;苛养菌占比为6.4%,包括流感嗜血杆菌(3.9%)、卡他莫拉菌(1.6%)和肺炎链球菌(0.9%)。耐甲氧西林金黄色葡萄球菌检出率为41.8%(51/122),耐碳青霉烯类的大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌复合群和铜绿假单胞菌的检出率依次为12.0%(21/175)、18.1%(87/480)、69.9%(635/908)和29.3%(240/819)。与痰样本相比,非痰样本的多重耐药菌检出率更高(P<0.01)。 AECOPD患者下呼吸道检出病原菌中绝大多数为革兰阴性菌,苛养菌检出率较低,非痰样本的多重耐药菌检出率较高。
To investigate the factors influencing quality of life in patients with chemotherapy-induced peripheral neuropathy (CIPN) and to construct a risk prediction model. Patients with CIPN admitted to our hospital from January 2022 to December 2024 were selected. Based on the mean score of the Functional Assessment of Cancer Therapy-General (FACT-G) scale, 262 patients were divided into good quality of life group and poor quality of life group. Clinical data were compared between the two groups. Binary logistic regression was used to identify factors influencing quality of life, and a nomogram prediction model was constructed. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis. The 262 patients were divided into a good group (135 cases) and a poor group (127 cases) based on the mean FACT-G score of 84.65 ± 13.65. Multivariate analysis showed that marital status (odds ratio [OR] = 2.317, 95% CI: 1.037-5.176), renal dysfunction (OR = 2.635, 95% CI: 1.197-5.801), tumor TNM stage T2 (OR = 2.744, 95% CI: 1.095-6.878), stage T3 (OR = 0.301, 95% CI: 0.110-0.828), anxiety (OR = 2.763, 95% CI: 1.260-6.060), pain (OR = 4.651, 95% CI: 1.998-10.828), vomiting (OR = 3.459, 95% CI: 1.567-7.637), insomnia (OR = 5.215, 95% CI: 1.789-15.197), and somnolence (OR = 3.870, 95% CI: 1.387-10.795) were independent influencing factors for quality of life in CIPN patients (all P < 0.05).The nomogram prediction model was established based on the above factors. In the training cohort, the AUC of the ROC curve was 0.864 (95% CI: 0.813-0.915). The specificity and sensitivity corresponding to the optimal cut-off value were 0.827 (95% CI: 0.752-0.901) and 0.741 (95% CI: 0.648-0.834), respectively. In the validation cohort, the AUC was 0.803 (95% CI: 0.707-0.900), with a specificity of 0.703 (95% CI: 0.555-0.850) and a sensitivity of 0.738 (95% CI: 0.605-0.871) at the optimal cut-off value, suggesting good diagnostic efficacy of the model. The ideal curve aligns well with the calibration curve, and the Hosmer-Lemeshow test indicates that the model is well calibrated. Decision curve analysis demonstrated a high net benefit of the model within the range of 0.5 to 1.0. Marital status, renal dysfunction, tumor TNM staging, anxiety, pain, vomiting, insomnia, and somnolence are factors associated with a lower quality of life in patients with CIPN. The prediction model constructed based on these factors exhibits good discrimination and calibration, which can facilitate clinical assessment of quality of life in CIPN patients. 探讨化疗引起的周围神经病变(chemotherapy-induced peripheral neuropathy, CIPN)患者生活质量的影响因素,并构建风险预测模型。 选取2022年1月–2024年12月我院收治的CIPN患者作为研究对象。依据癌症治疗功能评价系统量表(Functional Assessment of Cancer Therapy-General, FACT-G)得分的平均值,将262例患者分为生活质量良好组与不良组。比较两组临床资料,采用二元logistic回归分析生活质量的影响因素,并构建列线图预测模型。通过受试者工作特征(receiver operating characteristic, ROC)曲线、校准曲线、Hosmer-Lemeshow拟合优度检验及决策曲线评估模型预测效能。 262例患者FACT-G平均得分为(84.65±13.65)分,其中良好组135例,不良组127例。多因素分析显示,婚姻状况〔比值比(odds ratio, OR)=2.317,95%置信区间(confidence interval, CI):1.037~5.176〕、肾功能异常(OR=2.635,95%CI:1.197~5.801)、肿瘤TNM分期T2(OR=2.744,95%CI:1.095~6.878)、T3(OR=0.301,95%CI:0.110~0.828)、焦虑(OR=2.763,95%CI:1.260~6.060)、疼痛(OR=4.651,95%CI: 1.998~10.828)、呕吐(OR=3.459,95%CI:1.567~7.637)、失眠(OR=5.215,95%CI:1.789~15.197)、嗜睡(OR=3.870,95%CI:1.387~10.795)是CIPN患者生活质量的独立影响因素(P<0.05)。基于上述因素构建的列线图预测模型在建模组中ROC曲线下面积(area under the curve, AUC)为0.864(95%CI:0.813~0.915),其ROC曲线最佳截断值对应的特异度为0.827(0.752~0.901)、灵敏度为0.741(0.648~0.834);在验证组中AUC为0.803(95%CI:0.707~0.900),最佳截断值对应的特异度为0.703(0.555~0.850)、灵敏度为0.738(0.605~0.871),提示模型诊断效能良好。理想曲线与校准曲线拟合良好,Hosmer-Lemeshow检验示模型校准度良好。决策曲线显示模型在0.5~1.0范围内具有较高的净收益。 婚姻状况、肾功能异常、肿瘤TNM分期、焦虑、疼痛、呕吐、失眠、嗜睡是CIPN患者生活质量较差的独立影响因素;基于这些因素构建的预测模型具有良好的区分度与校准度,可用于临床评估CIPN患者的生活质量。
To modify the non-antibacterial bioceramic root canal sealant iRoot SP with the quaternary ammonium salt dimethylaminododecyl methacrylate (DMADDM) and to develop a new type of sealant. The cytotoxicity of the modified root canal sealant was evaluated using the cell counting kit-8 (CCK-8). The solubility and flowability of the sealant were tested according to International Organization for Standardization (ISO) methods. The sealing ability and penetrability of the sealant were assessed by micro-computed tomography (micro-CT) and confocal laser scanning microscope (CLSM). The antibacterial activity of the sealant against Enterococcus faecalis biofilm was evaluated by colony-forming unit (CFU) counting, crystal violet staining, scanning electron microscope (SEM), and live/dead staining. When the DMADDM mass fraction was 0.625%, the modified sealant demonstrated good biocompatibility (P > 0.0125). The flowability (> 17 mm) and solubility (< 3%) of the sealant modified with 0.625% DMADDM met ISO standards and showed no significant difference compared with iRoot SP. DMADDM modification did not affect the sealing ability or penetrability of the sealant at different positions of the tooth root (P > 0.05). Antibacterial experiments showed that the modified sealant reduced the CFU count (0.518 ± 0.333 vs. 8.156 ± 0.011, P < 0.001) and the amount of biofilm (mean difference of 86.94%, 95% confidence interval: 74.82%-99.07%, P < 0.0001) of Enterococcus faecalis biofilm at the unaged stage. However, after 1 week of aging (7.327 ± 0.068 vs. 7.422 ± 0.035) or 4 weeks of aging (7.479 ± 0.065 vs. 7.581 ± 0.071), the CFU count of the modified sealant showed no significant difference from the iRoot SP group (P > 0.05). Live/dead staining and SEM also showed that the modified sealant could inhibit the formation of Enterococcus faecalis biofilm. iRoot SP modified with 0.625% DMADDM exhibited good biocompatibility, sealing ability, and penetrability, and significantly improved resistance to Enterococcus faecalis biofilm, providing a new approach for the antibacterial modification of bioceramic root canal sealants. 利用季铵盐甲基丙烯酸十二烷基二甲铵(dimethylaminododecyl methacrylate, DMADDM)对不具备抗菌性能的生物陶瓷类根管封闭剂iRoot SP进行改性,制备新型封闭剂。 通过细胞计数试剂盒-8(cell counting kit-8, CCK-8)评估改性根管封闭剂的细胞毒性,根据国际标准化组织(International Organization for Standardization, ISO)的方法测试封闭剂的溶解度和流动性。分别利用显微计算机断层扫描(micro-CT)及共聚焦激光扫描显微镜(confocal laser scanning microscope, CLSM)评估封闭性及渗透性。通过菌落形成单位(colony-forming unit, CFU)计数、结晶紫染色、扫描电镜(scanning electron microscope, SEM)及活死染色评估封闭剂对粪肠球菌生物膜的抗菌性。 DMADDM质量分数为0.625% 时,改性封闭剂显示出良好的生物相容性(P>0.0125)。经质量分数0.625%的DMADDM改性封闭剂的流动性(>17 mm)及溶解度(<3%)均符合ISO标准,且与iRoot SP相比差异无统计学意义(P>0.05)。DMADDM改性对封闭剂在牙根不同位置的封闭性及渗透性均无影响(P>0.05)。抗菌实验显示,未老化时改性封闭剂降低了粪肠球菌生物膜的CFU计数(0.518±0.333 vs. 8.156±0.011,P<0.001)及生物膜量(均值差为86.94%,95%可信区间:74.82%~99.07%,P<0.0001),但老化1周(7.327±0.068 vs. 7.422±0.035)或老化4周(7.479±0.065 vs. 7.581±0.071)后改性封闭剂的CFU计数与iRoot SP组无明显差异(P>0.05)。同时,活死染色及SEM显示改性封闭剂可以抑制粪肠球菌的生物膜形成。 质量分数为0.625% 的DMADDM改性后的iRoot SP表现出良好的生物相容性、封闭性和渗透性,显著改善了封闭剂抗粪肠球菌生物膜的能力,为生物陶瓷类根管封闭剂的抗菌改性提供了思路。
To explore the correlations between various insulin resistance (IR) assessment indicators and embryo quality and pregnancy outcomes during in vitro fertilization and embryo transfer (IVF-ET) in patients with polycystic ovary syndrome (PCOS). A retrospective cohort design was used, including PCOS patients who received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment for the first time from January 2019 to July 2022. Assessment indicators of insulin resistance (IR) based on fasting status (HOMA-IR, QUICKI, Li Guangwei Index, Bennett ISI), collectively referred to as static IR indicators, and assessment indicators based on the oral glucose tolerance test (OGTT) (area under the curve ratio, Matsuda Index, Gutt Index), collectively referred to as dynamic IR indicators, were selected. Patients were divided into the IR group (high level) and the non-IR group (low level) according to the median. Differences in the levels of various IR assessment indicators, embryo quality, and pregnancy outcomes were compared. The primary outcome indicators were the D3 high-quality embryo rate (high embryo rate), fresh cycle clinical pregnancy rate, cumulative pregnancy rate, and cumulative live birth rate; other outcomes were considered secondary indicators. A multivariate binary logistic regression model was used to adjust for confounding factors, and multiple comparison correction was applied to control false positives when analyzing the correlation between different levels of IR assessment indicators and embryo quality and pregnancy outcomes. A total of 571 PCOS patients were included, all of whom had fasting blood glucose and insulin data. Among these, 499 cases had complete OGTT data. Main outcome indicators: There was no statistical correlation between the levels of static IR indicators and the main outcome indicators. The levels of dynamic IR indicators (Gutt index) were associated with the pregnancy rate of good embryos, with an adjusted odds ratio (OR) of 0.88 (95% CI: 0.79-0.99, P = 0.035). The levels of the Matsuda index were associated with the cumulative pregnancy rate, with an adjusted OR of 0.61 (95% CI: 0.39-0.97, P = 0.036). Secondary outcome indicators: No statistically significant correlations were observed between the static IR indicators and dynamic IR indicators after multiple comparison correction. The Matsuda index and Gutt index based on OGTT are more sensitive than static fasting indicators in reflecting differences in reproductive outcomes among PCOS patients, and thus have significant clinical value. 探讨多种胰岛素抵抗(insulin resistance, IR)评估指标与多囊卵巢综合征(polycystic ovary syndrome, PCOS)患者体外受精-胚胎移植(in vitro fertilization and embryo transfer, IVF-ET)过程中胚胎质量及妊娠结局的相关性。 采用回顾性队列设计,纳入2019年1月–2022年7月期间首次接受体外受精/卵胞质内单精子注射(in vitro fertilization/intracytoplasmic sperm injection, IVF/ICSI)治疗的PCOS患者。选取基于空腹状态计算的IR评估指标(HOMA-IR、QUICKI、李光伟指数、Bennett ISI)(以上统称静态IR指标)以及基于口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)计算的IR评估指标(曲线下面积比、Matsuda指数、Gutt指数)(以上统称动态IR指标),依据中位数分为IR组(即高水平)和非IR组(即低水平),比较各种IR评估指标水平高低在胚胎质量和妊娠结局的差异。主要结局指标为D3优质胚胎率(简称优胚率)、新鲜周期临床妊娠率、累积妊娠率和累积活产率,其余为次要结局指标。采用多因素二元logistic回归模型校正因素,多重比较校正控制假阳性,分析不同IR评估指标高低水平与胚胎质量及妊娠结局的相关性。 共纳入571例PCOS患者,均包含空腹状态的血糖和胰岛素数据,其中499例具有完整的OGTT数据。主要结局指标:静态IR指标高低水平与主要结局指标均未呈现统计学关联;动态IR指标中的Gutt指数高低水平与优胚率有关,调整后比值比(odds ratio, OR)为0.88〔95%置信区间(confidence interval, CI):0.79~0.99,P=0.035〕;Matsuda指数高低水平与累积妊娠率有关,调整后OR为0.61(95%CI:0.39~0.97,P=0.036)。次要结局指标:静态IR指标和动态IR指标未观察到经多重比较校正后仍具有统计学意义的关联。 基于OGTT的Matsuda指数和Gutt指数较基于空腹的静态指标更敏感地反映了PCOS患者辅助生殖结局的差异,具有重要的临床应用价值。
To explore the efficacy of ganciclovir combined with recombinant human interferon α-1b in the treatment of viral encephalitis in children. 160 children with viral encephalitis admitted to third department of pediatrics of Xingtai People' s Hospital were selected, and divided into single group and combined group by random number table method, with 80 cases in each group. The single group was treated with ganciclovir, whereas the combined group was given ganciclovir combined with recombinant human interferon α-1b. Compare the time to recovery of symptoms in patients between groups. After 2 weeks of treatment, compare the clinical efficacy and EEG abnormalities between the two groups. The cerebral hemodynamics (mean blood flow velocity [Vm] and pulsatility index [PI] of anterior cerebral artery and posterior cerebral artery), neurological function (neuron specific enolase [NSE], neurotrophin3 [NT-3], nerve growth factor [NGF]), immune function (immunoglobulin A [IgA], IgG, IgE) and inflammatory factors (tumor necrosis factor α [TNF-α], interleukin β [IL-1β], interleukin 2 [IL-2]) before treatment and after 2 weeks of treatment were compared between groups, and the adverse reactions during treatment were recorded. The disappearance durations of fever, headache, vomiting, convulsion, disturbance of consciousness and meningeal irritation in combined group were shorter than those in single group (P < 0.05). After 2 weeks of treatment, the total effective rate of clinical efficacy was higher in the combined group than in the single group (P < 0.05), the abnormal rate of EEG in the combined group was lower than that in the single group (P < 0.05). There was no statistically significant difference in the clinical effective rate between subgroups with different disease severity between the two groups of children (P > 0.05). The Vm and PI of anterior cerebral artery and posterior cerebral artery and levels of NSE, NGF, IgA, TNF-α, IL-1β and IL-2 were decreased in both groups, and the indicators in combined group were lower compared to single group (all P < 0.05). The levels of NT-3, IgG and IgE in both groups were enhanced after 2 weeks of treatment, and the levels were higher in combined group (all P < 0.05). There was no significant difference in the total incidence rate of adverse reactions between groups (P > 0.05). Ganciclovir combined with recombinant human interferon α-1b can effectively treat viral encephalitis in children, improve cerebral hemodynamics and neurological function, enhance immune function, and relieve inflammatory response, and it dose not increase adverse reactions. 探究更昔洛韦联合重组人干扰素α-1b治疗小儿病毒性脑炎的疗效。 选取于邢台市人民医院儿三科接诊的160例病毒性脑炎患儿,以随机数字表法分为单一组和联合组,各80例。单一组给予更昔洛韦治疗,联合组给予更昔洛韦联合重组人干扰素α-1b治疗,比较组间患者恢复时间。治疗2周后,比较两组临床疗效和脑电图异常情况。治疗前和治疗2周后,比较两组脑血流动力学〔大脑前动脉、大脑后动脉平均血流速度(Vm)、搏动指数(PI)〕、神经功能〔神经元烯醇化酶(NSE)、神经营养因子3(NT-3)、神经生长因子(NGF)〕、免疫功能〔免疫球蛋白A(IgA)、IgG、IgE〕及炎症因子〔肿瘤坏死因子α(TNF-α)、白细胞介素β(IL-1β)、白细胞介素2(IL-2)〕水平,并记录治疗期间不良反应发生情况。 联合组发热、头痛、呕吐、惊厥、意识障碍、脑膜刺激征消失时间均短于单一组(P<0.05);治疗2周后,联合组临床疗效总有效率高于单一组(P<0.05),联合组脑电图异常率低于单一组(P<0.05);两组患儿不同疾病严重程度亚组之间的临床有效率差异无统计学意义(P>0.05);两组患儿大脑前动脉、大脑后动脉Vm、PI、NSE、NGF、IgA、TNF-α、IL-1β、IL-2水平均降低,联合组低于单一组(P均<0.05);治疗2周后,两组患儿NT-3、IgG、IgE水平升高,联合组高于单一组(P均<0.05);两组不良反应总发生率差异无统计学意义(P>0.05)。 更昔洛韦联合重组人干扰素α-1b可有效治疗小儿病毒性脑炎,改善患儿脑血流动力学及神经功能,增强免疫功能,缓解炎症反应,且不增加不良反应。
By introducing an attention enhancement mechanism and improving the post-processing strategy, the Faster Region-based Convolutional Neural Network (Faster R-CNN) is enhanced. The resulting improved Faster R-CNN method for wound detection (WD-IFRCNN) increases the accuracy and stability of wound detection. ① Algorithm construction: The 50-layer residual network (ResNet-50) is used as the backbone. In the fourth residual stage (convolutional stage 4, Conv4_x) and fifth residual stage (convolutional stage 5, Conv5_x), the fuzzy mask attention module (FMAM) and convolutional block attention module (CBAM) are embedded together to enhance the model's ability to represent features in key areas and blurry regions of the wound surface. At the same time, soft non-maximum suppression (Soft-NMS) replaces the traditional non-maximum suppression strategy to reduce missed detections in overlapping target scenarios. ② Algorithm validation: The experimental dataset consists of open-source wound images and clinically collected images, totaling 740 original images. After data augmentation, the dataset expands to 5920 images and is evaluated using ten-fold cross-validation. Model performance is assessed through internal validation, external validation, hyperparameter tuning, and ablation experiments, using metrics such as precision, recall, average precision, and F1 score. ① Internal validation showed that the model performs best when CBAM is embedded in both the Conv4_x and Conv5_x stages of ResNet-50. When ResNet-50-CBAM is used as the backbone, the model's detection performance surpasses that of VGG16 and ResNet-50. ② External validation showed that WD-IFRCNN achieves an precision of 92.31%, recall of 93.95%, average precision of 92.33%, and F1 score of 0.93. The average precision was 3.21%, 2.30%, 1.39%, 0.86%, 0.82%, 0.37%, and 0.63% higher than SSD, YOLOv4, YOLOv5, YOLOv8, DETR, RT-DETR, and FR-CNN-FPN, respectively. ③ Ablation experiments showed that CBAM, FMAM, and Soft-NMS each positively impact model performance, with the best results achieved when all are used together. WD-IFRCNN effectively enhances the model's ability to represent features in key areas and blurry regions of the wound surface, improves the accuracy and stability of wound detection, and demonstrates good adaptability to complex wound scenarios. It can provide technical support for clinical wound assessment and auxiliary diagnosis. 通过引入注意力增强机制和改进后处理策略,对更快的基于区域的卷积神经网络(faster region-based convolutional neural network, Faster R-CNN)进行改进,即用于创面检测的改进Faster R-CNN方法(wound detection method based on improved faster R-CNN, WD-IFRCNN),以提高创面检测的准确性和稳定性。 ①算法构建:以50层残差网络(50-layer residual network, ResNet-50)为主干网络,在第4残差阶段(convolutional stage 4, Conv4_x)和第5残差阶段(convolutional stage 5, Conv5_x)嵌入模糊注意力引导模块(fuzzy mask attention module, FMAM)协同的卷积块注意力模块(convolutional block attention module, CBAM),以增强模型对创面关键区域及边界模糊区域的特征表达能力;同时采用软非极大值抑制(soft non-maximum suppression, Soft-NMS)替代传统非极大值抑制策略,以减少重叠目标场景中的漏检。②算法验证:实验数据集由开源创面图像和临床采集图像构成,共740张原始图像,经数据增强后扩展至5920张,并采用十折交叉验证进行评估。通过内部验证、外部验证、超参数调优和消融实验,采用精确率、召回率、平均精确率和F1分数等指标对模型性能进行评价。 ①内部验证表明,同时在ResNet-50的Conv4_x和Conv5_x阶段嵌入CBAM时模型性能最佳;采用ResNet-50-CBAM作为主干网络时,模型检测效果优于VGG16和ResNet-50。②外部验证表明,WD-IFRCNN的精确率、召回率、平均精确率和F1分数分别达到92.31%、93.95%、92.33%和0.93,其中平均精确率较SSD、YOLOv4、YOLOv5、YOLOv8、DETR、RT-DETR和FR-CNN-FPN分别提高3.21%、2.30%、1.39%、0.86%、0.82%、0.37%和0.63%。③消融实验表明,CBAM、FMAM和Soft-NMS均对模型性能提升具有积极作用,三者联合时检测效果最佳。 WD-IFRCNN能够有效增强模型对创面关键区域及模糊边界区域的特征表达能力,提高创面检测的准确性和稳定性,对复杂创面场景具有较好的适应性,可为临床创面评估与辅助诊断提供一定的技术支持。
Mucormycosis is a life-threatening invasive fungal infection with high mortality, yet traditional diagnostic methods are limited by low positivity rates. This study aims to evaluate the diagnostic performance and clinical utility of metagenomic next-generation sequencing (mNGS) in mucormycosis. A retrospective analysis was conducted on 135 patients with mNGS results positive for Mucorales fungi at West China Hospital of Sichuan University from November 1, 2022, to October 31, 2024. Based on comprehensive clinical diagnostic criteria (including proven and probable cases), patients were classified into a confirmed mucormycosis group and a non-mucormycosis group. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of normalized read counts (lgRPM) from different specimen types. Fungal species distribution and laboratory parameters were compared between the two groups. Among the 135 patients with positive mNGS results for Mucorales, 100 (74.1%) were ultimately diagnosed with mucormycosis. ROC curve analysis revealed that the diagnostic performance of mNGS varied by specimen type. For blood specimens, the area under the curve (AUC) was 0.772, with a specificity of 87.5% at the optimal cutoff value of 0.11 RPM. For bronchoalveolar lavage fluid specimens, the AUC was 0.717, with a sensitivity of 76.5% at the optimal cutoff value of 0.02 RPM. Combined analysis of all specimens showed that at the optimal cutoff value of 0.08 RPM (approximately 8 reads/100M), the sensitivity and specificity were 62.0% and 71.4%, respectively. Species distribution analysis showed that the proportions of Cunninghamella elegans (11.0% vs. 2.9%) and Rhizomucor pusillus (9.0% vs. 2.9%) were significantly higher in the confirmed group than in the non-mucormycosis group (P < 0.05). Levels of C-reactive protein and interleukin-6 were also significantly higher in the confirmed group (P < 0.05). Notably, all seven renal perfusion fluid samples yielded false-positive mNGS results. mNGS technology can effectively improve the diagnostic yield for mucormycosis. However, results should be interpreted in conjunction with specimen type, read count, and clinical characteristics. BALF specimens offer high sensitivity, making them suitable for screening, while blood specimens demonstrate high specificity, making them valuable for confirmation. Positive results from low-biomass samples such as renal perfusion fluid warrant caution against false positivity. Fungal species identification and inflammatory markers may serve as adjunctive evidence for clinical diagnosis. 毛霉菌病是一种具有高致死率的侵袭性真菌感染,传统诊断方法因阳性率较低而受限。本研究旨在评估宏基因组二代测序(metagenomic next-generation sequencing, mNGS)在毛霉菌病诊断中的效能及临床应用价值。 回顾性分析2022年11月1日–2024年10月31日于四川大学华西医院接受mNGS检测且结果为毛霉目真菌序列阳性的135例患者。以临床综合诊断(包含确诊与临床诊断)为标准,将患者分为毛霉菌病确诊组与非毛霉菌病组。通过受试者工作特征(receiver operating characteristic, ROC)曲线评估不同标本类型mNGS序列数(lgRPM,即以10为底的对数转换每百万读数标准化值)的诊断效能,并比较两组患者的菌种分布及实验室指标。 135例mNGS毛霉菌阳性患者中,最终确诊毛霉菌病100例(74.1%)。ROC曲线分析显示,不同标本类型的mNGS诊断效能存在差异。血液标本的曲线下面积(area under the curve, AUC)为0.772,在最佳截断值(0.11 RPM)下,特异性为87.50%;支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)的AUC为0.717,在最佳截断值(0.02 RPM)下,敏感性为76.47%。所有标本合并分析显示,当RPM的最佳截断值为0.08(约8条reads/100M)时,诊断的敏感性和特异性分别为62.0%和71.4%。菌种分布分析显示,确诊组中雅致小克银汉霉(11.0% vs. 2.9%)和微小根毛霉(9.0% vs. 2.9%)的比例高于非确诊组(P<0.05)。确诊组的C反应蛋白和白细胞介素-6水平亦高于非确诊组(P<0.05)。值得注意的是,7例肾灌注液样本的mNGS结果均为假阳性。 mNGS技术可有效提升毛霉菌病的诊断阳性率,但其结果需结合标本类型、序列数及患者临床特征进行综合解读。BALF样本敏感性高,适合筛查;血液样本特异性强,适合确诊。肾灌注液等低生物量样本的阳性结果需警惕假阳性。菌种鉴定和炎症标志物可为临床诊断提供辅助依据。
Tumors represent a global public-health concern, accounting for approximately one-sixth of all fatalities worldwide annually. Attaining precise management of patients across all stages of diagnosis, treatment, and surveillance is not merely a significant challenge in contemporary clinical practice but also a crucial strategy for enhancing patient survival rates. In comparison with traditional testing approaches, liquid biopsy offers the benefits of being less invasive and enabling repeated sampling. Through the examination of biological specimens that can be readily and repeatedly obtained from the patient's body, liquid biopsy can furnish information throughout the entire continuum of disease diagnosis, treatment, and follow-up prognosis. Consequently, it emerges as a highly prospective substitute for tissue samples in the minimally invasive, real-time, and comprehensive monitoring of tumors in clinical contexts. This article conducts a systematic review of the common liquid biopsy markers in the oncology field and their latest detection technologies. It encompasses detection schemes for non-blood samples such as cerebrospinal fluid and feces. Moreover, it proposes a novel framework for the precise management of the entire tumor process based on "multi-marker combination + full sample coverage". The article further deliberates on a series of challenges currently encountered in developing liquid biopsy into a mature clinical testing project. These challenges include the standardization of sample testing procedures, the establishment of standardized reporting systems, and how to strike a balance between the popularity of detection methods and cost control, with the aim of promoting the development of liquid biopsy in tumor early screening, treatment innovation, and extensive application. We anticipate constructing a full-chain system spanning from basic research to transformational production and clinical application. We aim to develop an integrated detection platform, establish standardized reporting procedures and a well-established regulatory mechanism, offer patients full-cycle precise management from diagnosis to rehabilitation, and ultimately convert cancer from an "incurable disease" into a "preventable and controllable" chronic disease. 肿瘤是世界级公共卫生问题,导致了全球每年约六分之一的死亡。在诊断、治疗和监测的每个阶段实现对患者的精准化管理,既是当前临床实践中的一大挑战,也可作为提升患者生存率的重要策略。液体活检相较于传统检测具有创伤性小、可反复采样的优势。通过对患者身体易于重复获取的生物样本进行检测,液体活检能够在疾病诊断、治疗及预后随访全阶段提供信息,成为临床上实现对肿瘤微创、实时、全面监控的极具前景的组织样本替代方法。本文系统综述了肿瘤领域中常见的液体活检标志物及其最新检测技术,涵盖脑脊液、粪便等非血液样本的检测方案,并提出了基于“多标志物联合+全样本覆盖”的肿瘤全程精准管理新框架。文中也探讨了当前将液体活检发展为成熟临床检测项目所面临的一系列挑战,包括样本检测流程标准化、标准化报告制度的建立,以及如何平衡检测方法的普及性与成本控制等问题,以推动液体活检在肿瘤早筛、治疗革新与广泛应用方面的发展。我们期望通过构建从基础研究到转化生产、临床应用的全链条体系,开发一体化检测平台,建立标准化报告流程与完善监管机制,为患者提供从诊断到康复的全周期精准管理,最终使肿瘤从“不治之症”转变为“可防可控”的慢性疾病。
To systematically identify traditional Chinese medicine (TCM) compound formulas with anti-atherosclerosis (AS) potential using a screening platform based on multi-strain apoeb gene knockout zebrafish models for anti-atherosclerosis TCM compounds. Screening was conducted using a formula dictionary database, and compound formulas such as Dan Shen Fang, Shang Ni San, Jin Lingzi San, and Li Qi Hua Liang Tang were selected from 933 blood-activating and stasis-resolving formulas. Five strains of apoeb -/- zebrafish-AB, Tg(mpeg1:EGFP), Tg(lyzc:dsRed), Tg(gata1a:mCherry), and Tg(flk1:EGFP)-were fed a high-fat diet for 2 days, after which the AS model was established. DMSO (solvent control), rosuvastatin (western medicine positive control), compound Dan Shen Fang (TCM positive control), Shang Ni San, Jin Lingzi San, and Li Qi Hua Liang Tang were administered by bathing for 24 hours. Oil red O staining was used to detect lipid content, oxidative stress indicators, blood flow velocity, vascular endothelial cell damage, and the expression of inflammatory factors in zebrafish. The behavior patterns of inflammatory cells in zebrafish were observed, and the anti-AS efficacy of the Li Qi Hua Liang formulas was comprehensively evaluated. Compared with the AS model group, compound Dan Shen Fang and Shang Ni San improved lipid accumulation in the vascular lumen, reduced total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, decreased oxidative stress response, inhibited the recruitment of neutrophils and macrophages, repaired vascular endothelial damage, improved blood flow velocity, and reduced the expression of inflammatory factors, thereby alleviating AS, with statistically significant differences. Jin Lingzi San and Li Qi Hua Liang Tang had limited effects on AS. This platform provides an efficient and targeted tool for the screening and research evaluation of anti-atherosclerosis TCM compound formulas, accelerates the research progress of anti-atherosclerosis TCM compound formulas, and lays a foundation for subsequent drug development and clinical application. 利用基于多品系apoeb基因敲除斑马鱼模型的抗动脉粥样硬化(arterial atherosclerosis, AS)中药复方筛选平台,系统筛选出具有抗AS潜力的理气活血功效的中药复方。 基于方剂大辞典数据库进行筛选,从933首活血化瘀方剂中筛选出复方丹参方、手拈散、金铃子散、理气活血汤。采用AB、Tg(mpeg1:EGFP)、Tg(lyzc:dsRed)、Tg(gata1a:mCherry)、Tg(flk1:EGFP)5种品系apoeb-/-斑马鱼给予高脂饲料喂食2 d后构建AS模型,在此基础上给予DMSO(溶剂对照)、瑞舒伐他汀组(西药阳性对照)、复方丹参方组(中药阳性对照)、手拈散、金铃子散、理气活血汤药浴24 h,行油红O染色,检测血脂含量、氧化应激指标、血流速度、血管内皮细胞损伤情况以及炎症因子在斑马鱼体内表达情况,观察斑马鱼体内炎症细胞行为模式,综合评估理气活血方剂抗AS疗效。 与模型组比较,复方丹参方和手拈散可改善血管内脂质堆积,降低总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)含量,减少氧化应激反应,抑制中性粒细胞和巨噬细胞募集,修复血管内皮损伤,改善血流速度,降低炎症因子表达,从而减轻AS,差异有统计学意义;而金铃子散及理气活血汤对AS的改善效果有限。 该平台为抗AS中药复方的筛选和研究评价提供了一种高效性且靶向性较强的工具,加速推动抗AS中药复方的研究进程,为后续的药物开发和临床应用奠定了基础。
This article focuses on the legal transformation of medical ethics in China during the new era of socialism with Chinese characteristics, since the 18th National Congress of the Communist Party of China. By employing diachronic review and normative analysis, it systematically presents the internal logic and practical pathways of the field's evolution from fragmented self-regulation to integrated governance. Academically, the discipline has advanced through four stages: theoretical foundation and foreign introduction, practical shift and institutional exploration, critical reflection and systemic optimization, and legal-led, full-coverage advancement. Legally, a refined regulatory system has been established, centered on national laws and supported by specialized review regulations. In governance, a transition from passive response to proactive shaping has been achieved, with ethical review expanding across all domains of life science research, and procedural management and accountability fully incorporated into the rule of law. Looking ahead, it is essential to balance institutional rigidity with practical flexibility, contribute ethical wisdom to the Healthy China initiative, and offer a Chinese solution to global science and technology ethics governance. 本文聚焦党的十八大以来,中国特色社会主义新时代背景下我国医学伦理领域的法治化转型,通过历时性梳理与规范性分析方法,系统呈现其从分散自律向集成治理演进的内在逻辑与实践路径。学科层面,历经“理论奠基与域外引介—实践转向与建制探索—制度反思与体系优化—法治引领与全域覆盖”四阶段发展;法律层面,构建起以法律法规为核心,专项审查办法为支撑的精细化规范体系; 治理层面,实现从被动应对到主动塑造,审查范围走向全领域覆盖,流程管控与责任追究均纳入法治化轨道。未来,需进一步平衡制度刚性与实践弹性,为健康中国建设贡献伦理智慧,为全球科技伦理治理提供中国方案。
To analyze changes and correlations in the pregnancy characteristics of parturients and adverse birth outcomes of newborns in a tertiary grade A hospital from 2017 to 2022, and provide a basis for targeted prevention of adverse birth outcomes in newborns. Medical records of obstetric deliveries from January 1, 2017, to December 31, 2022, were retrospectively collected. Descriptive analysis was used to examine the pregnancy characteristics of parturients and adverse birth outcomes of newborns. Univariate and multivariate analyses were conducted to explore the relationship between these factors during this period. The final analysis included data from 93547 newborns and 88857 corresponding mothers. From 2017 to 2022, the number of mothers and newborns at our hospital showed an overall increasing trend. The main reproductive age for women in this region was concentrated between 30 and 34 years. The proportion of older mothers (≥ 35 years) showed a general downward trend, and this difference was statistically significant (χ 2 trend = 13.261, P < 0.001). Except for cesarean section, the risks of preterm birth, low birth weight (LBW), macrosomia, small for gestational age infant (SGA), and large for gestational age infant (LGA) in this region showed an overall downward trend, with statistically significant differences (P < 0.05). Multivariate logistic regression analysis showed that, compared with mothers under 30 years, the risk of cesarean section for newborns was 1.339 times higher in the 30-34 age group (adjusted odds ratio [aOR] = 1.339, 95% CI: 1.297-1.382) and 2.646 times higher in the ≥ 35 age group (aOR = 2.646, 95% CI: 2.532-2.765). For LGA risk, only mothers aged ≥ 35 years showed an increased risk for newborns (aOR = 1.111, 95% CI: 1.049-1.178, P < 0.001). The risks of cesarean section, preterm birth, and macrosomia in the multiparous group were 1.151 times (aOR = 1.151, 95% CI: 1.114-1.189), 1.558 times (aOR = 1.558, 95% CI: 1.486-1.633), and 1.595 times (aOR = 1.595, 95% CI: 1.527-1.688) those in the primiparous group, respectively, while the risk of SGA in the multiparous group was lower than in the primiparous group (aOR = 0.684, 95% CI: 0.655-0.715). The risks of cesarean section, macrosomia, and LGA in the in vitro fertilization (IVF) group were 2.295 times (aOR = 2.295, 95% CI: 2.170-2.427), 1.274 times (aOR = 1.274, 95% CI: 1.122-1.447), and 1.300 times (aOR = 1.300, 95% CI: 1.216-1.391) those in the natural conception group, respectively, but the risk of SGA was lower than in the non-IVF group (aOR = 0.774, 95% CI: 0.729-0.821). From 2017 to 2022, the characteristics of pregnant women in our hospital changed, and the risk of some adverse neonatal outcomes showed a decreasing trend during this period. Additionally, neonatal birth outcomes among different high-risk groups (women aged 35 or older, multiparous women, and women who conceived with assisted reproductive technology) exhibited distinct characteristics. 分析2017–2022年某三级甲等医院产妇的妊娠特征和新生儿不良出生结局的变化趋势和关联,为有针对性预防新生儿不良出生结局提供依据。 回顾性收集2017年1月1日–2022年12月31日期间产科分娩医疗记录数据。采用描述性分析方法对产妇妊娠特征和新生儿不良出生结局进行分析,并通过单因素和多因素分析,探讨此时期二者的关系。 最终分析共纳入93547例新生儿数据和对应88857例产妇数据。2017–2022年本院产妇和新生儿数量总体呈增加趋势。本地区女性的主要生育年龄集中于30~34岁,高龄产妇(≥35岁)占比整体呈下降趋势,差异有统计学意义(χ2趋势= 13.261,P<0.001)。除了剖宫产,本地区的早产、低出生体重(low birth weight, LBW)、巨大儿、小于胎龄儿(small for gestational age infant, SGA)和大于胎龄儿(large for gestational age infant, LGA)的发生风险整体呈下降趋势,差异有统计学意义(P<0.05)。多变量逻辑回归分析结果显示,与<30岁产妇组相比,30~34岁和≥35岁产妇年龄组的新生儿剖宫产发生风险升高,分别为1.339倍〔调整比值比(aOR)=1.339,95%置信区间(CI):1.297~1.382〕和2.646倍(aOR=2.646,95%CI:2.532~2.765),在LGA发生风险方面,仅≥35岁产妇年龄组的新生儿发生风险增高(aOR=1.111,95%CI:1.049~1.178,P<0.001);经产组剖宫产、早产和巨大儿的发生风险分别是初产组的1.151倍(aOR=1.151,95%CI: 1.114~1.189)、1.558倍(aOR=1.558,95%CI:1.486~1.633)和1.595倍(aOR=1.595,95%CI:1.527~1.688),而经产组SGA发生风险低于初产组(aOR=0.684,95%CI:0.655~0.715);体外受精(in vitro fertilization, IVF)组新生儿的剖宫产、巨大儿和LGA的发生风险分别是自然受孕组的2.295倍(aOR=2.295,95%CI:2.170~2.427)、1.274倍(aOR=1.274,95%CI:1.122~1.447)和1.300倍(aOR=1.300,95%CI:1.216~1.391),但SGA的发生风险反而低于非IVF组(aOR=0.774,95%CI:0.729~0.821)。 2017–2022年本院产妇妊娠特征发生改变,且此期间的部分新生儿不良出生结局发生风险呈现降低趋势。此外,不同高危人群(年龄≥35岁产妇、经产妇和辅助技术助孕产妇)的新生儿出生结局呈现差异化特征。
From the perspective of patients' self-identity, this article explores the correlations among coping strategies of adolescent patients with depression, parents' autonomous support, and self-identity, and also examines the mediating role of coping strategies. A total of 240 adolescent patients with depression from the First Hospital of Hebei Medical University were selected between August 2023 and July 2024. Basic information questionnaires, the Simplified Coping Style Questionnaire (SCSQ), the Parental Autonomy Support Scale (PASS), and the Self-Identity Scale (SIS) were used for the survey. Pearson correlation analysis was conducted to examine the relationships among coping styles of adolescent patients with depression, parental autonomy support, and self-identity. The SPSS macro program Process 4.1 was used to analyze the mediating role of coping styles between parental autonomy support and self-identity. A total of 240 questionnaires were distributed in this study, and 236 valid questionnaires were collected, resulting in a recovery rate of 98.33%. The mean score for positive coping strategies among 236 adolescent patients with depression was (19.45 ± 2.68) points, while the mean score for negative coping strategies was (18.97 ± 5.04) points. The mean PASS score was (42.73 ± 9.98) points, and the mean SIS score was (48.64 ± 7.73) points. Pearson correlation analysis showed that positive coping strategies were positively correlated with parental autonomous support and self-identity (r = 0.267, 95% CI: 0.154-0.381; r = 0.207, 95% CI: 0.098-0.317). Negative coping strategies were negatively correlated with parental autonomous support and self-identity (r = -0.173, 95% CI: -0.290 to -0.054; r = -0.153, 95% CI: -0.265 to -0.039). Parental autonomous support was positively correlated with self-identity (r = 0.182, 95% CI: 0.052-0.313). The bootstrap method confirmed three mediating paths: Path 1 (parental autonomous support → positive coping → self-identity) had an effect value of 0.070 (95% CI: 0.021-0.162), accounting for 17.68% of the effect; Path 2 (parental autonomous support → negative coping → self-identity) had an effect value of 0.020 (95% CI: 0.005-0.042), accounting for 5.05% of the effect; Path 3 (parental autonomous support → positive coping → negative coping → self-identity) had an effect value of 0.017 (95% CI: 0.005-0.033), accounting for 4.29% of the effect. The 95% confidence intervals did not include 0, indicating that the indirect effects were significant. Parental autonomous support can directly affect the self-identity of adolescent patients with depression and can also indirectly influence it through coping strategies. Positive coping strategies mediate the beneficial effect of parental autonomous support on self-identity and play a protective role. 基于患者的自我认同视角,探讨青少年抑郁症患者应对方式与父母自主支持、自我认同感的相关性及其中介效应。 选取2023年8月–2024年7月河北医科大学第一医院青少年抑郁症患者240例,采用基本信息调查表,简易应对方式量表(SCSQ)、父母自主支持量表(PASS)、自我认同感量表(SIS)进行问卷调查。Pearson相关分析青少年抑郁症患者应对方式、父母自主支持、自我认同感的相关性,并采用SPSS宏程序Process 4.1探究应对方式在父母自主支持与自我认同感间的中介作用。 本研究共发放问卷240份,有效问卷236份,回收率98.33%。236例青少年抑郁症患者积极应对方式得分(19.45±2.68)分,消极应对方式得分(18.97±5.04)分,PASS得分(42.73±9.98)分,SIS得分(48.64±7.73)分;Pearson相关性显示,积极应对方式与父母自主支持、自我认同感均呈正相关〔r=0.267,95%置信区间(CI):0.154~0.381;r=0.207,95%CI:0.098~0.317〕;消极应对方式与父母自主支持、自我认同感均呈负相关(r=-0.173,95%CI:-0.290~-0.054;r=-0.153,95%CI:-0.265~-0.039);父母自主支持与自我认同感呈正相关(r=0.182,95%CI:0.052~0.313)。Bootstrap法验证得出,中介路径为三条,路径1(父母自主支持→积极应对→自我认同感):效应值0.070,95%CI:0.021~0.162,效应占比17.68%;路径2(父母自主支持→消极应对→自我认同感):效应值0.020,95%CI:0.005~0.042,效应占比5.05%;路径3(父母自主支持→积极应对→消极应对→自我认同感):效应值0.017,95%CI:0.005~0.033,效应占比4.29%。95%CI均不包含0,间接效应成立。 父母自主支持既可以对青少年抑郁症患者自我认同感产生直接作用,又可通过应对方式间接作用于患者自我认同感,积极应对方式介导了父母自主支持对自我认同感的正面效应,起到了一定程度的保护作用。
To analyze the correlations between multimodal MRI examination parameters - apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and choline (Cho)/creatine (Cr)-and microvessel density (MVD) in patients with glioma, as well as the prognostic value of these parameters. The medical records of 200 patients diagnosed with glioma at our hospital from January 2019 to January 2024 were retrospectively analyzed. According to the WHO classification, patients were divided into a low-grade group (n = 122) and a high-grade group (n = 78). Patients were further divided into a good prognosis group (n = 114) and a poor prognosis group (n = 86). The Pearson correlation test was used to analyze the relationship between multimodal MRI parameters and MVD in glioma patients. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of multimodal MRI parameters and MVD for high-grade glioma and their predictive value for poor prognosis. The Hosmer-Lemeshow test was used to assess the goodness of fit of the model. The ADC value in the low-grade group was higher than in the high-grade group, while CBF, Cho/Cr, and MVD were lower in the low-grade group (P < 0.05). The ADC value in the good prognosis group was higher than in the poor prognosis group, while CBF and Cho/Cr values were lower in the poor prognosis group (P < 0.05). ADC was negatively correlated with MVD in glioma patients (r = -0.226, P = 0.001); CBF and Cho/Cr were positively correlated with MVD (r = 0.235 and 0.396, P = 0.001 and < 0.001, respectively). The AUCs of ADC, CBF, Cho/Cr, and MVD for diagnosing high-grade glioma were 0.870, 0.696, 0.926, and 0.950, respectively. The combined AUC of these four parameters was 0.997. For prognosis prediction based on multimodal MRI parameters, the combined AUC of ADC+CBF+Cho/Cr was 0.876, while the AUCs of ADC, CBF, and Cho/Cr alone were 0.718, 0.688, and 0.808, respectively. The Hosmer-Lemeshow test showed that the combined model (ADC + CBF + Cho/Cr) fit was good (χ 2 = 8.570, P = 0.380), indicating that the combined prediction model had high accuracy. ADC, CBF, and Cho/Cr have a weak correlation with MVD in glioma patients. The combination of these four parameters has high value in diagnosing high-grade glioma, and the combination of the first three parameters has higher predictive value for patient prognosis. 分析多模态MRI检查参数〔表观弥散系数(ADC)、脑血流量(CBF)、胆碱(Cho)/肌酸(Cr)〕与脑胶质瘤患者微血管密度(MVD)的相关性及其对预后的评估价值。 回顾性分析2019年1月–2024年1月间在我院确诊为脑胶质瘤的200例患者病历资料,以WHO为分级基础,Ⅰ~Ⅱ级为低级别组(n=122);Ⅲ~Ⅳ级为高级别组(n=78);以预后情况为依据,分为预后良好组(n=114)和预后不良组(n=86)。Pearson相关性检验多模态MRI检查参数与脑胶质瘤MVD之间的关系,受试者工作特征曲线(ROC)的曲线下面积(AUC)评价多模态MRI检查参数以及MVD对高级别脑胶质瘤患者的诊断价值及其预后不良的预测价值,最后Hosmer-Lemeshow检查评估模型的拟合度。 低级别患者ADC值高于高级别组,CBF、Cho/Cr以及MVD均低于高级别组(P<0.05)。预后良好组患者ADC值高于预后不良组,CBF以及Cho/Cr值均低于预后不良组(P<0.05)。脑胶质瘤患者ADC与MVD呈负相关(r=-0.226,P=0.001);CBF和Cho/Cr与MVD均呈正相关(r=0.235、0.396,P<0.001)。 ADC、CBF、Cho/Cr、MVD诊断高级别脑胶质瘤患者的AUC分别为0.870、0.696、0.926、0.950,四者联合的AUC为0.997。多模态MRI检查参数对脑胶质瘤患者预后的ROC曲线中,DC+CBF+Cho/Cr联合预测的AUC为0.876,ADC、CBF、Cho/Cr单独诊断的AUC分别为0.718、0.688、0.808。Hosmer-Lemeshow检验显示ADC+CBF+Cho/Cr联合预测模型拟合度良好(χ2=8.570,P=0.380),即ADC+CBF+Cho/Cr联合预测模型具有较高的精确度。 ADC、CBF、Cho/Cr与脑胶质瘤患者MVD具有弱相关性,四者联合诊断高级别脑胶质瘤患者的价值较高,前三者联合对患者预后的预测价值较高。
To analyze the microbiological characteristics of extrapulmonary nontuberculous mycobacterial (ENTM) infections in a tertiary hospital and to provide data to support clinical diagnosis and treatment of ENTM infections. A retrospective analysis was conducted on mycobacterial culture results from West China Hospital, Sichuan University from 2020 to 2023. A total of 68 confirmed cases of ENTM infection were enrolled, with all of which meeting the diagnostic criteria for extrapulmonary infection outlined in the Guidelines for the Diagnosis and Treatment of Nontuberculous Mycobacterial Disease (2020). Demographic data, strain distribution, and drug susceptibility test results were analyzed. Microbial species identification was performed using mass spectrometry, and drug susceptibility was assessed using the microbroth microdilution method. Among the 68 ENTM cases, the male-to-female ratio was 1 to 1.2, with individuals aged 40-59 years being the main affected group population. The most common sites of infection were the skin and soft tissues. The primary specimen source was pus (33.8%, 23 cases), followed by pathological tissues (26.5%, 18 cases). The Department of Infectious Diseases was the main source of confirmed cases (29.4%, 20 cases). Among the 68 EMTM cases, rapid-growing mycobacteria (RGM) accounted for 32.4% (22 cases), with Mycobacterium abscessus being the predominant species, while slowly-growing mycobacteria (SGM) accounted for 67.6% (46 cases), with Mycobacterium intracellulare and Mycobacterium marinum being the predominant species. RRGM exhibited higher minimum inhibitory concentration (MICs) for rifampicin and rifabutin but lower MICs for clarithromycin and amikacin. In contrast, SGM demonstrated low MICs for most antibiotics tested. In this study, ENTM infections most commonly involve the skin and soft tissues, with SGM being the predominant pathogens and Mycobacterium intracellulare being the dominant species. RGM shows susceptibility to clarithromycin and amikacin, which provides a basis for empirical anti-infective therapy. Although SGM exhibits low MICs to most tested antimicrobial agents, combination regimens remain necessary in clinical practice, and the risk of treatment failure should be thoroughly evaluated. 本研究旨在分析某三甲医院肺外非结核分枝杆菌(extrapulmonary nontuberculous mycobacterial, ENTM)感染的微生物学特征,为ENTM感染的临床诊疗提供数据支撑。 回顾性分析四川大学华西医院2020–2023年分枝杆菌培养结果,共纳入ENTM感染确诊病例68例,所有纳入病例均符合《非结核分枝杆菌病诊断与治疗指南(2020年版)》中肺外感染的诊断标准。分析纳入病例的人口学特征、菌种分布特征及药敏试验结果。采用质谱技术进行微生物菌种鉴定,采用微量肉汤稀释法进行药敏试验。 68例ENTM感染病例中,男女比例为1∶1.2,40~59岁为主要感染人群,感染部位以皮肤软组织最常见。标本主要来源为脓液(33.8%,23例),其次为病理组织(26.5%,18例);确诊患者主要来源于感染科(29.4%,20例)。68例ENTM中,快速生长型分枝杆菌(rapid-growing mycobacterial, RGM)占32.4%(22例),最常见菌种为脓肿分枝杆菌;缓慢生长型分枝杆菌(slowly-growing mycobacterial, SGM)占比67.6%(46例),最常见菌种为胞内分枝杆菌和海分枝杆菌。RGM对利福平、利福布汀等抗生素具有较高的最低抑菌浓度(minimal inhibitory concentration, MIC),对克拉霉素、阿米卡星具有较低MIC值;SGM对大多数抗生素均具有较低的MIC值。 本研究中ENTM感染最常累及皮肤软组织,病原菌以SGM为主,其中胞内分枝杆菌占据主导地位。RGM对克拉霉素和阿米卡星敏感,可为经验性抗感染治疗提供参考依据;SGM虽对多数受试药物表现出较低的MIC,但临床治疗时仍需采用联合用药方案,并充分评估治疗失败的风险。
To explore the pleiotropic molecular mechanisms by which atorvastatin (Ator) regulates atherosclerosis (AS) in ApoE-/- mice. Thirty 8-week-old male ApoE-/- mice were induced to develop atherosclerosis by a high-fat diet. They were randomly assigned to a control group (normal saline), a low-dose Ator group (5 mg/[kg·d]), and a high-dose Ator group (10 mg/[kg·d]), and received interventions for 10 weeks. The primary outcome indicators were assessed by Oil Red O and HE staining to measure the area of atherosclerotic plaques. Secondary outcome indicators included serum lipid levels detected by a blood chemical analyzer, Masson and Sirius Red staining combined with polarized light to assess plaque stability indicators (collagen fiber content, fibrous cap thickness), immunohistochemistry to detect the expression of α-smooth muscle actin (α-SMA) and CD68, fluorescence microplate reader to measure reactive oxygen species (ROS) levels, Western blot and RT-qPCR to detect protein and gene expression of inflammation, oxidative stress, apoptosis-related molecules, matrix metallopeptidase 7 (MMP-7), and guanine nucleotide-binding protein subunit α-13 (Gα13). Blood lipids and plaques: Ator reduced serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels (P < 0.05), and dose-dependently decreased the area of aortic lipid deposition and plaque area (Control group: plaque area [1.62 ± 0.15] mm², Low-dose group: [1.13 ± 0.06] mm², High-dose group: [0.83 ± 0.07] mm², P < 0.001). Plaque stability: Ator increased collagen fiber content (P < 0.001), increased fibrous cap thickness, upregulated α-SMA expression, and downregulated CD68 expression (P < 0.001). Oxidative stress: Ator remarkably diminished the levels of ROS in arterial tissue and malondialdehyde (MDA) in serum (P < 0.001). Molecular mechanism: Ator downregulated pro-inflammatory factors (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]), NLRP3, pro-apoptotic proteins (caspase-3, p53), inducible nitric oxide synthase (iNOS), and MMP-7; and upregulated anti-apoptotic protein Bcl-2, antioxidant proteins [mitochondrial deacetylase 3 (sirtuin 3, SIRT3)/superoxide dismutase 2 (SOD2)], and Gα13 (P < 0.001). The expression trends of these proteins and genes were consistent, with a more significant effect in the high-dose group. Atorvastatin exerts its anti-atherosclerotic effects by regulating blood lipids, inhibiting inflammatory responses, reducing oxidative stress, and regulating apoptosis. It also affects the expression of MMP-7 and Gα13. 探究阿托伐他汀(atorvastatin, Ator)调控ApoE-/-小鼠动脉粥样硬化(atherosclerosis, AS)的多效性分子机制。 30只8周龄雄性ApoE-/-小鼠经高脂饮食诱导AS模型后,随机分为对照组(生理盐水)、低剂量Ator组〔5 mg/(kg·d)〕和高剂量Ator组〔10 mg/(kg·d)〕,干预10周。主要结局指标为油红O、HE染色检测动脉粥样硬化斑块面积,次要结局指标包括血液化学分析仪检测血清血脂指标,Masson、天狼星红染色结合偏振光检测斑块稳定性相关指标(胶原纤维含量、纤维帽厚度),免疫组化法检测α-平滑肌肌动蛋白(alpha smooth muscle Actin, α-SMA)与CD68表达,荧光酶标仪检测活性氧(reactive oxygen species, ROS)水平,Western blot法、RT-qPCR法分别检测炎症、氧化应激、凋亡相关分子及基质金属蛋白酶7(matrix metallopeptidase 7, MMP-7)、G蛋白α13 亚基(guanine nucleotide-binding protein subunit α-13, Gα13)的蛋白与基因表达。 血脂与斑块:Ator降低血清低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、总胆固醇(total cholesterol, TC)、甘油三酯(triglycerides, TG)水平(P<0.05),并剂量依赖性减少主动脉脂质沉积面积和斑块面积〔对照组斑块面积(1.62±0.15) mm2,低剂量组(1.13±0.06) mm2,高剂量组(0.83±0.07) mm2,P<0.001〕。斑块稳定性:Ator提升胶原纤维含量(P<0.001)、增加纤维帽厚度,上调α-SMA表达、下调CD68表达(P<0.001)。氧化应激:Ator显著降低动脉组织ROS及血清丙二醛(malondialdehyde, MDA)水平(P<0.001)。分子机制:Ator下调促炎因子〔肿瘤坏死因子α (tumor necrosis factor-alpha, TNF-α)、白细胞介素(interleukin, IL)-6〕、NLRP3、促凋亡蛋白(caspase-3、p53)、诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)及MMP-7;上调抗凋亡蛋白Bcl-2、抗氧化蛋白〔线粒体去乙酰化酶3(sirtuin 3, SIRT3)/超氧化物歧化酶2(superoxide dismutase 2, SOD2)〕及Gα13(P<0.001)。上述蛋白与基因表达趋势一致,高剂量组效应更显著。 阿托伐他汀通过调节血脂、抑制炎症反应、减轻氧化应激、调控细胞凋亡,同时影响MMP-7和Gα13的表达,发挥抗AS的多效作用。