To construct AS1411 aptamer-modified mesoporous polydopamine (MPDA) nanoparticles co-loaded with doxorubicin (DOX) and catalase (AS1411-D/C-MPDA nanoparticles) targeting the tumor microenvironment and evaluate their efficacy in synergy with ultrasound for inhibiting Lewis lung carcinoma (LLC) cells. AS1411-D/C-MPDA nanoparticles were synthesized using a one-step assembly method, and their physicochemical properties were characterized. Cultured LLC cells were treated with free DOX, DOX-loaded MPDA nanoparticles or AS1411-D/C-MPDA nanoparticles with or without ultrasound exposures (frequency 1.0 MHz and intensity 1.0 W/cm²) for 3 min. The changes in viability, apoptosis, and migration and invasion abilities of the cells were assessed using CCK-8 assay, flow cytometry (Annexin V-FITC/PI staining), wound healing assay, and Transwell assay, respectively. The prepared AS1411-D/C-MPDA nanomaterials showed a uniform spherical morphology, a mean particle size of 183.36±15.99 nm, and DOX and catalase encapsulation efficiencies of (91.17±0.08)% and (29.59±0.2)%, respectively. The nanoparticles demonstrated good pH responsiveness to enable disintegration for promoting drug release, with a cumulative DOX release rate of (81.25±1.61)%. The nanoparticles possessed strong oxygen-generating capacity to alleviate cell hypoxia. AS1411-modified nanoparticles showed significantly enhanced cellular uptake by LLC cells. Compared with free DOX and DOX-MPDA nanoparticles combined with ultrasound, AS1411-D/C-MPDA in synergy with ultrasound induced higher levels of ROS in LLC cells, resulted in a higher cell apoptosis rate, and more efficiently reduced cell viability and suppressed cell migration and invasion. AS1411-D/C-MPDA nanoparticles combined with ultrasound allow targeted delivery of anticancer drugs and represent a promising strategy for synergistic treatment of lung cancer by integrating physical acoustics, pharmaceutical chemistry, and tumor microenvironment regulation. 目的: 针对肿瘤微环境构建一种能同时负载阿霉素（DOX）与过氧化氢酶（CAT）的AS1411适配体修饰的介孔聚多巴胺纳米颗粒（AS1411-D/C-MPDA），并探讨其联合超声对Lewis肺癌（LLC）细胞的协同治疗效果。方法: 通过一步组装法合成负载DOX和CAT并经AS1411适配体修饰的AS1411-D/C-MPDA，检测其物理特性;在细胞水平，将LLC细胞分为游离DOX组、DOX-MPDA组及AS1411-D/C-MPDA组及对应的超声组进行处理。超声参数设置为:频率1.0 MHz，强度1.0 W/cm²，持续时间3 min。通过CCK-8法检测细胞活性，流式细胞术（Annexin V-FITC/PI染色）分析细胞凋亡，划痕实验评估细胞迁移能力，以及Transwell实验评估细胞侵袭能力。结果: 成功制备AS1411-D/C-MPDA纳米材料，其呈大小均匀的球形颗粒，粒径为183.36±15.99 nm、包封率DOX（91.17±0.08）%，CAT（29.59±0.2）%，具有pH响应性，能裂解并促进药物释放，DOX释药率为（81.25±1.61）%，该纳米材料有较强的产氧能力，缓解了缺氧状态。AS1411修饰的纳米材料对LLC细胞的摄取显著增强。与游离DOX和DOX-MPDA联合超声相比，AS1411-D/C-MPDA联合超声能诱导LLC细胞产生更多的活性氧，从而诱导细胞凋亡，细胞活性明显降低、划痕愈合面积减小（0.097±0.010 mm2vs 0.278±0.001 mm2，P<0.01）及侵袭细胞数量减少（24.33±12.01个vs 352±4.36个，P<0.001）。结论: AS1411-D/C-MPDA联合超声通过靶向递送抗癌药物，有望成为物理声学、药物化学、微环境调控协同治疗肺癌的新策略。.
To investigate the protective effect of 1,3-dicaffeoylquinic acid (1,3-DA) against dextran sulfate sodium (DSS)-induced colitis in mice and its molecular mechanism. Fifty C57BL/6 mice were randomly divided into normal control group, DSS model group, 1,3-DA treatment group, PI3K inhibitor (LY294002), and 5-aminosalicylic acid (5-ASA; positive control) group. Except for those in the control group, the mice were given DSS to induce colitis and treated with daily intraperitoneal injections the indicated agents during modeling for 7 consecutive days. Colonic pathological phenotypes, inflammation, oxidative stress, and expressions of tight junction proteins and PI3K/Akt pathway proteins in the colon tissues of the mice were detected. In cultured intestinal epithelial NCM460 cells with H₂O₂-induced oxidative stress, the effects of 1,3-DA and 1,3-DA plus 740Y-P (a PI3K activator) were examined on intracellular oxidative stress and expressions of tight junction proteins. Treatment of the mice with 1,3-DA significantly alleviated DSS-induced body weight loss, colon shortening, elevation of disease activity index and mucosal injury, downregulated interferon‑γ and myeloperoxidase, upregulated superoxide dismutase, catalase and glutathione peroxidase, reduced malondialdehyde, increased zonula occludens-1 and claudin-1, and inhibited overexpressions of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt). In NCM460 cells, treatment with 1,3-DA significantly reduced H₂O₂-induced reactive oxygen species accumulation, increased zonula occludens-1 and claudin-1 expressions, and lowered p-PI3K and p-Akt expression. The protective effects of 1,3-DA was obviously attenuated by treatment with 740Y-P. 1,3-DA ameliorates DSS-induced colitis in mice and H₂O₂-mediated intestinal epithelial injury by inhibiting inflammation and oxidative stress and promoting repair of intestinal barrier function, which is closely related to inhibition of excessive PI3K/Akt pathway activation. 目的: 探讨1，3-二咖啡酰奎宁酸（1，3-DA）对葡聚糖硫酸钠（DSS）诱导小鼠结肠炎的保护作用及调控磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路的分子机制。方法: 体内构建DSS诱导的小鼠结肠炎模型，设置正常对照组、DSS模型组、1，3-DA干预组、PI3K抑制剂LY294002干预组及5-氨基水杨酸（5-ASA）阳性对照组，评估小鼠结肠炎病理表型，检测结肠组织炎症水平、氧化应激指标、肠上皮紧密连接蛋白及PI3K/Akt通路相关蛋白表达。体外采用过氧化氢（H2O2）诱导NCM460肠上皮细胞构建氧化应激损伤模型，设置对照组、模型组、1，3-DA干预组及1，3-DA联合PI3K激活剂740Y-P共处理组，检测细胞活性氧（ROS）生成、紧密连接蛋白与通路蛋白表达以验证调控机制。结果: 体内实验中，与DSS模型组相比，1，3-DA干预组小鼠体质量下降（P<0.001）、结肠长度缩短（P<0.001）、疾病活动指数（DAI）升高（P<0.001）及结肠黏膜病理损伤得到缓解，结肠组织促炎因子γ 干扰素（IFN-γ）（P<0.001）、髓过氧化物酶（MPO）表达显著下调（P<0.001），抗氧化酶:超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）活性含量明显上调（均P<0.001），脂质过氧化产物丙二醛（MDA）水平显著降低（P<0.001），肠上皮紧密连接蛋白:闭锁小带蛋白1（ZO-1）、闭合蛋白1（Claudin-1）的表达上调（P<0.001），同时磷酸化磷脂酰肌醇3-激酶（p-PI3K）与磷酸化蛋白激酶B（p-Akt）的表达上调受到显著抑制（均P<0.001）。体外实验中，与H₂O₂诱导的肠上皮细胞模型组相比，1，3-DA干预组细胞内ROS蓄积水平显著降低（P<0.001），紧密连接蛋白ZO-1、Claudin-1的表达显著上调（均P<0.001），p-PI3K（P<0.001）和p-Akt（P=0.014）的表达明显下降，且PI3K激活剂740Y-P与1，3-DA共处理后可部分逆转其对肠上皮细胞的保护作用。结论: 1，3-DA可通过抗炎、抗氧化应激、修复肠上皮屏障功能，减轻DSS诱导的小鼠结肠炎及H₂O₂介导的肠上皮细胞氧化应激损伤，其作用机制与抑制PI3K/Akt信号通路的过度异常激活密切相关。.
To evaluate the efficacy of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based antifungal susceptibility testing (MS-AFST) for rapid detection of fluconazole resistance in Candida tropicalis. C. tropicalis isolates from patients with bloodstream infections at West China Hospital of Sichuan University (2018-2023) were collected and identified by chromogenic culture and MALDI-TOF MS. Using Clinical and Laboratory Standards Institute broth microdilution (BMD) method as the reference standard, we compared the performance of the Sensititre YeastOne chromogenic antifungal susceptibility testing and optimized MS-AFST based on the minimum profile change concentration (MPCC). All the 41 isolates were confirmed as C. tropicalis, which showed an azole resistance rate of 36.59% and a proportion of non-wild-type strain of 68.29% with high cross-resistance to azoles. The categorical agreement (CA) and essential agreement (EA) between Sensititre YeastOne and CLSI BMD were both 100%, and their minimum inhibitory concentrations were highly correlated. The MPCC-based MS-AFST enabled rapid detection of fluconazole-resistant phenotype of C. tropicalis within approximately 3 h, demonstrating a CA of 92.68% and an EA of 90.24% both in comparison with the CLSI BMD reference method and Sensititre YeastOne; very major error\discrepancy occurred in two strains, and minor error\discrepancy occurred in one strain. MPCC-based MS-AFST enables rapid, reliable detection of fluconazole resistance in C. tropicalis with good agreement with the reference methods. However, classification errors remain, which should be improved by further technical optimization of this method and exploration of the underlying molecular mechanisms. 目的: 评估基于基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）的抗真菌药物敏感性试验（MS-AFST）快速检测热带念珠菌氟康唑耐药性的临床应用潜能。方法: 回顾性分析2018~2023年四川大学华西医院血流感染热带念珠菌的检出情况，并经念珠菌显色培养与MALDI-TOF MS行菌种鉴定。抗真菌药物敏感性试验以 CLSI 微量肉汤稀释法（BMD）为参考标准，对比评估 Sensititre YeastOne 显色药敏试验、优化前处理后基于最小谱图改变浓度（MPCC）的 MS-AFST 法检测氟康唑耐药性的一致性。结果: 本研究纳入的41分离株均为热带念珠菌，其唑类耐药率和非野生型菌株占比在36.59%~68.29%，且唑类高度交叉耐药。Sensititre YeastOne与CLSI BMD的分类一致性和基本一致性均为100%，二者最小抑菌浓度高度相关。基于MPCC的MS-AFST可以3 h左右快速检测热带念珠菌氟康唑耐药表型，与CLSI BMD参考方法和Sensititre YeastOne的分类一致性均为92.68%，基本一致性均为90.24%，极重大误差2株，小误差1株。结论: 基于 MPCC 的 MS-AFST 可快速检测热带念珠菌氟康唑耐药性，且与参考方法一致性较好，但仍存在分类错误，需进一步优化方法并探究其机制。.
To investigate the role of the SREBP-1/SCD1 pathway in mediating the protective effect of Tongxie Yaofang (TXYF) against 5-hydroxytryptamine (5-HT)-induced injury in BRL 3A cells. Fourteen SD rats were gavaged with TXYF for 7 consecutive days to prepare TXYF-medicated serum. BRL 3A cells in routine culture were examined for changes in cell viability using CCK-8 assay following treatment with different concentrations of 5-HT. In BRL 3A cells treated with 5-HT and different concentrations of the medicated serum, SOD, MDA, and ROS levels were measured, and mitochondrial membrane potential and cell morphology were evaluated using JC-1 staining and electron microscopy; autophagosomes and LC3B expression were detected with immunofluorescence staining, and the protein expression levels of Cyt-c, caspase-3, Gsk3β, Beclin-1, LC3 I/II, p62, SREBP-1, SCD1, and 5-HT2AR were analyzed using Western blotting. The optimal 5-HT concentration for modeling was 1.5 mmol/L. In 5-HT-treated cells, treatment with TXYF-medicated serum significantly reduced cellular ROS and MDA levels, increased SOD activities, lowered mitochondrial membrane potential, and alleviated mitochondrial swelling. The cells treated with TXYF-medicated serum also showed decreased expression levels of LC3B, MDC, Beclin-1, LC3 II/LC3 I, Cyt-c, SCD1 and 5-HT2AR and increased expressions of p62 and SREBP-1 without significant changes in caspase-3 and Gsk3β expressions. TXYF-medicated serum alleviate oxidative stress and autophagy dysfunction via the SREBP-1/SCD1 pathway to protect BRL 3A cells against 5-HT-induced injury. 目的: 研究SREBP-1/SCD1通路在5-HT致肝细胞BRL 3A细胞损伤中的作用，探讨痛泻要方含药血清对氧化应激损伤的保护作用及机制。方法: 制备含药血清及培养BRL 3A细胞:14只SD雄性大鼠予痛泻要方灌胃，每日1次，连续7 d，腹主动脉取血制备含药血清;用10%胎牛血清37 ℃、5%CO2饱和湿度条件下培养。CCK-8法检测不同浓度5-HT（0.2、0.5、1、1.5 mmol/L）处理 BRL 3A 细胞48、72、96 h后细胞存活率。细胞培养给药后进行超氧化物歧化酶（SOD）、丙二醛（MDA）含量检测，流式法检测细胞活性氧（ROS）含量。采用JC-1染色检测细胞线粒体膜电位变化，细胞电镜观察线粒体形态变化。免疫荧光法检测细胞自噬小体（由MDC特异性标记）及其标志蛋白LC3B，荧光显微镜下观察自噬体及其标志蛋白在细胞内的位置、表达情况及细胞核的形态变化。Western blotting法检测细胞Cyt-c、Caspase3、Gsk3β、beclin-1、LC3Ⅰ/Ⅱ、p62，SREBP-1、SCD1，5-HT2AR蛋白表达水平。结果: 通过CCK-8测定细胞最适宜的生长浓度为1.5 mmol/L（P<0.01）;与model组相比，TXYF组ROS含量显著降低（P<0.0001）、MDA含量降低（P<0.05）、SOD含量升高（P<0.01）。与model组相比，TXYF组线粒体膜电位降低，UR降低（P<0.001），LR升高（P<0.001）;在透射电子显微镜下可观察到TXYF组线粒体肿胀程度较model组明显减轻，大部分线粒体嵴结构形态恢复。与model组相比，TXYF组LC3B和MDC免疫荧光强度下降（P<0.05），自噬相关蛋白Beclin-1降低（P<0.05）、LC3Ⅱ/LC3Ⅰ降低、p62升高（P<0.01）;通过检测线粒体途径凋亡，TXYF组较model组Cyt-c降低（P<0.01），Caspase3及Gsk3β蛋白量降低但无统计学意义。与model组相比，TXYF组SREBP-1蛋白表达升高（P<0.05）、SCD1蛋白表达降低（P<0.01），5-HT2AR蛋白表达降低（P<0.05）。结论: 痛泻要方含药血清可能通过SREBP-1/SCD1通路，调节SOD活力与自噬功能来减轻氧化应激和脂质过氧化损伤，对5-HT诱导的BRL 3A细胞损伤具有保护调节作用。.
To explore the risk factors for early respiratory failure in patients with acute pancreatitis (AP) and develop an interpretable machine learning model to predict the need for invasive mechanical ventilation (MV) within 72 h of ICU admission. This retrospective cohort study was conducted using data of adult patients with acute pancreatitis from the MIMIC-IV database, excluding those receiving invasive MV at ICU admission. The primary outcome was initiation of invasive MV within 72 h after ICU admission. Multiple machine learning models were developed and internally validated, and the best-performing model was externally validated using the eICU-CRD database. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). A total of 517 patients with acute pancreatitis from the MIMIC-IV database were included, with 361 assigned to the training cohort and 156 to the internal testing cohort; 269 patients from the eICU-CRD database were included as the external validation cohort. The patients who developed early respiratory failure exhibited more severe organ dysfunction at ICU admission. The random forest model achieved an AUC of 0.908 in the training cohort, 0.733 in the internal testing cohort, and 0.681 in the external validation cohort. SHAP analysis identified sequential organ failure assessment (SOFA) score, use of vasoactive agents, and acute kidney injury (AKI) as the most important predictive factors. The interpretable machine learning model demonstrates moderate predictive performance in both the internal and external validation cohorts and can be used for early risk assessment of invasive MV in patients with acute pancreatitis. The key predictive variables primarily reflect multi-organ dysfunction consistent with the underlying pathophysiological mechanisms of acute pancreatitis. 目的: 探讨急性胰腺炎患者早期呼吸衰竭的风险预测因子，并利用可解释的机器学习模型，预测ICU入院后72 h内是否需要启动有创机械通气。方法: 基于MIMIC-IV数据库纳入急性胰腺炎成人患者进行回顾性队列研究。排除入ICU时已接受有创机械通气者，主要结局为入院后72 h内启动有创机械通气。构建多种机器学习模型并进行内部验证，选取表现最佳模型进行外部验证（eICU-CRD数据库）。采用SHapley 加法解释（SHAP）方法评估模型可解释性。结果: 纳入MIMIC-IV数据库517例急性胰腺炎患者，其中361例患者用于训练队列，156例患者用于内部测试队列。纳入eICU-CRD 269例急性胰腺炎患者作为外部验证队列。早期呼吸衰竭的患者在ICU入院时即表现出更显著的器官功能衰竭，且随机森林模型在训练集的AUC为0.908，在验证集的AUC为0.733，在外部验证集的AUC为0.681。序贯器官衰竭评分、血管活性药物使用及急性肾损伤是预测早期呼吸衰竭的关键因素。结论: 本研究构建的可解释机器学习模型在内外部验证中均显示出一定的预测效能，可用于评估急性胰腺炎患者早期有创机械通气风险。模型关键变量主要反映多器官功能衰竭状态，与疾病病理生理过程一致。.
To evaluate the efficacy of CD4/TGF-β bispecific antibody in a mouse model of peritoneal metastasis of melanoma. For drug safety testing, 20 human CD4 transgenic C57BL/6J mice were randomized into 4 groups (n=5) for intravenous injections of PBS or 2.5, 5, or 10 mg/kg CD4/TGF‑β bispecific antibody, and the changes in general condition, body weight and body temperature were observed. Another 20 transgenic C57BL/6J mice were randomized into two groups to receive intraperitoneal injection of magnetized B16F10-GL melanoma cells expressing green fluorescent protein and luciferase with or without application of a magnet (3 mm in diameter) to the right abdominal skin before cell injection. Three days later, each group was further divided into two groups for treatment with PBS or CD4/TGF-β bispecific antibody (300 μg) twice a week. In vivo imaging was performed at different time points to assess fluorescence distribution and intensity. On day 14, the mice were euthanized and tumor burden and dissemination were evaluated by gross observation, histopathological analysis, immunofluorescence staining, and RT-qPCR. Injection of the antibody did not produce any significant adverse effects in the mice. In the tumor-bearing mice, the application of a magnet significantly accelerated tumor development (3.80±1.79 vs 9.20±2.17 days; P=0.003) and resulted in precise and consistent tumor formation in the parietal peritoneum. Magnet application did not significantly affect survival of the mice but significantly prolonged the therapeutic window (4.60±1.95 vs 10.00±1.73 days; P=0.002). The mice treated with CD4/TGF‑β bispecific antibody had significantly reduced tumor burden irrespective of the inoculation approach, and showed dense encapsulation of the tumor foci by type III collagen, whereas minimal type III collagen deposition and abundant tumor cells were observed in PBS-treated mice. Treatment with the antibody significantly downregulated the expression of melanoma-associated gene MITF, and the reduction was more pronounced in the magnet group. The CD4/TGF‑β bispecific antibody shows significant antitumor efficacy and good safety in the mouse model of peritoneal metastasis of melanoma. 目的: 探讨新药CD4/TGF-β双特异性抗体对腹膜转移的恶性黑色素瘤的疗效。方法: 药物安全性试验:将20只C57BL/6J背景的人CD4转基因小鼠随机分为3个实验组与1个对照组（每组5只），分别给予2.5、5、10 mg/kg CD4/TGF-β双特异性抗体和等量的磷酸缓冲液，观察小鼠状态、体质量和体温变化。肿瘤模型与药物疗效对比:将20只C57BL/6J背景的人CD4转基因小鼠，随机均分为经典腹腔接种治疗（P4T）组、经典腹腔接种对照（P4U）组、磁力诱导细胞（MagIC）法腹膜接种治疗（M4T）组和MagIC法接种对照（M4U）组（每组5只）。每只小鼠于腹腔内接种5×106磁化的、携带绿色荧光蛋白和荧光素酶的小鼠恶性黑色素瘤细胞B16F10-GL，P4T和M4T组造模3 d后给予CD4/TGF-β双特异性抗体300 μg、每周2次治疗，而M4U和P4U组给予等量磷酸缓冲液。观察小鼠存活和一般情况，并在不同时间点，通过小动物活体成像系统监测体内荧光信号分布及强弱;造模14 d处死小鼠，以大体观察、病理切片、免疫荧光染色和RT-qPCR等方法观测肿瘤负荷和转移情况。结果: 药物安全性试验:各实验组小鼠活动度、体质量、体温变化与对照组相比无显著差异，未出现不良反应。M4U组和P4U组成瘤时间短（P=0.003）;M4U组于壁腹膜固定位置精准成瘤，组内模型鼠成瘤一致性强，而P4U组早期即在腹腔内广泛转移;两组存活时间无明显差异，但M4U组治疗窗口期较P4U组延长（P=0.002）。疗效对比:小动物活体成像显示，同期M4T组肿瘤负荷低于M4U组（P<0.0001），且M4T组肿瘤负荷显著低于P4T组（P=0.0239）;但P4T组肿瘤负荷下降与P4U组相比差异无统计学意义。病理和免疫荧光染色显示M4T和P4T治疗组瘤灶均被致密的Ⅲ型胶原包裹，而相应对照组的瘤灶仅有少数Ⅲ型胶原包裹其内部较多的肿瘤细胞;RT-qPCR显示M4T组和P4T组与各自对照组相比肿瘤负荷相关MITF基因表达量下降（P<0.05），且M4T组下降更明显（P<0.05）。结论: CD4/TGF-β双特异性抗体对黑色素瘤腹膜转移模型有显著疗效，为其进一步临床应用打下基础。.
To explore the risk factors for concomitant anxiety in patients with malignant gastrointestinal tumors based on machine learning algorithms. A total of 280 patients with malignant gastrointestinal tumors admitted to the First Affiliated Hospital of Bengbu Medical University from November, 2022 to April, 2023 were enrolled, and the collected data were re-analyzed between November ,2024 and April, 2025. According to Hospital Anxiety and Depression Scale (HADS-A) anxiety scores, the patients were divided into anxiety group (HADS-A score≥8) and non-anxiety group (<8). Six machine learning algorithms including Logistic Regression, Decision Tree, Random Forest, K-Nearest Neighbors, Support Vector Machine and Light Gradient Boosting Machine were used to predict anxiety. The performance of each model was assessed, and the factors affecting anxiety in these patients were identified by feature importance ranking and SHAP analysis by the optimal model. Among the 6 machine learning algorithms for predicting anxiety in patients with malignant gastrointestinal tumors, the Random Forest model showed the best performance with an accuracy of 0.73, precision of 0.48, recall of 0.86, specificity of 0.69, F1-Score of 0.62, and the area under the ROC curve (AUC) of 0.85, and was more accurate for identifying and classifying anxiety status in the target patients. According to the feature importance ranking by the optimal model, the top 10 key factors affecting anxiety in these patients were total cholesterol (0.0406), gender (0.0224), albumin (0.0157), platelet count (0.0152), white blood cell count (0.0121), retinol-binding protein (0.0116), total protein (0.0115), body mass index (0.0098), C-reactive protein (0.0096), and platelet distribution width (0.0095). The Random Forest model has good performance for predicting anxiety and screening key factors affecting anxiety in patients with malignant gastrointestinal tumors to facilitate its early identification and targeted intervention. 目的: 通过机器学习算法研究消化道恶性肿瘤患者在临床诊疗过程中伴发焦虑情绪的相关危险因素。方法: 收集2022年11月~2023年4月蚌埠医科大学第一附属医院280例消化道恶性肿瘤患者数据，并于2024年11月至2025年4月对数据进行再分析，依据医院焦虑抑郁量表将焦虑分量表评分≥8分的患者纳入焦虑组，<8分纳入非焦虑组;采用逻辑回归、决策树、随机森林、K-近邻、支持向量机、轻量梯度提升机6种机器学习算法预测焦虑情绪，比较各模型性能指标，并根据最优模型的特征重要性排序及SHAP分析结果，分析焦虑情绪影响因素。结果: 在预测消化道恶性肿瘤患者焦虑情绪的6种机器学习算法中，随机森林模型表现最优，其准确率为0.73、精确率为0.48、召回率为0.86、特异度为0.69、F1-Score为0.62、ROC曲线下面积为0.85，优于其他算法，对消化道恶性肿瘤患者焦虑情绪的识别分类更精准。根据最优模型的特征重要性排序，影响患者焦虑情绪的前10位关键因素依次为总胆固醇（0.0406）、性别（0.0224）、白蛋白（0.0157）、血小板计数（0.0152）、白细胞计数（0.0121）、视黄醇结合蛋白（0.0116）、总蛋白（0.0115）、BMI（0.0098）、C反应蛋白（0.0096）、血小板分布宽度（0.0095）。结论: 随机森林模型为消化道恶性肿瘤患者焦虑情绪提供了较好的预测性能及关键因素筛选，为临床医生早期识别与干预提供辅助决策。.
To investigate the effect of the petroleum ether fraction of Myrica nana roots (PEFM) for relieving spasmodic abdominal pain in mice and its underlying mechanism. The chemical profile of PEFM was analyzed using GC-MS. Forty Kunming mice were randomized into 5 groups for daily gavage with solvent, dicyclomine, or low-, medium-, and high-dose PEFM for 5 consecutive days, and their effects against neostigmine-induced spasmodic abdominal pain were evaluated. Serum cGMP levels and ileal PKG and p-VASP expressions of the mice were measured. Acute toxicity of PEFM gavage at different doses was assessed in another 32 Kunming mice by monitoring behavioral changes and organ indices. An isolated ileal model of ACh-induced spasm was used to observe the antispasmodic effect of PEFM and its main constituent, stigmast-4-en-3-one (ST), and the mediating roles of the NO/sGC/cGMP/PKG pathway, potassium channels, and calcium channels were investigated using specific inhibitors and a high-potassium-induced spasm model. Molecular docking was used to predict the interactions between compounds and targets. PEFM contained mainly steroidal compounds, with ST as the most abundant component (31.51%). PEFM at the medium and high doses significantly reduced abdominal pain frequency, prolonged pain latency, and increased serum cGMP and ileal p-VASP expression without producing significant acute toxicity. Both PEFM and ST exhibited concentration-dependent antispasmodic effects against ACh-induced contractions (EC50: 4.06 μg/mL and 0.53 μg/mL, respectively), which were inhibited by L-NAME, methylene blue, ODQ, and potassium channel blockers; they also strongly antagonized high potassium-induced contractions. Molecular docking confirmed stable binding of ST to PKG and p-VASP. PEFM has spasmolytic and analgesic effects in mice with neostigmine-induced spastic abdominal pain, mediated primarily by its main active component ST, which upregulates cGMP, enhances ileal VASP phosphorylation, activates NO/sGC/cGMP/PKG pathway, promotes opening of voltage-gated potassium channels, and antagonizes L-type calcium channels. 目的: 研究矮杨梅根石油醚部位（PEFM）对痉挛性腹痛小鼠的镇痛作用及机制。方法: 采用GC-MS鉴定PEFM的化学成分。采用新斯的明诱导的小鼠痉挛性腹痛模型评价PEFM的体内镇痛效果。将40只雄性KM小鼠按体质量随机分为空白对照组，双环维林组（25 mg/kg），PEFM低、中、高剂量组（100、200、400 mg/kg），8只/组。各组小鼠每日灌胃给予相应的溶媒或药物，连续5 d，末次给药45 min后，所有小鼠腹腔注射新斯的明（150 μg/kg）致痛，记录小鼠疼痛潜伏期和疼痛抑制率。取实验小鼠的血清和回肠组织，测量血清中cGMP的含量及回肠中p-VASP（ser157）蛋白表达量。采用小鼠经口灌胃急性毒性试验法评估PEFM的安全性。取雌雄各半的KM小鼠32只，按体质量随机分为空白组（0.5% CMC-Na溶液），PEFM低、中、高剂量组（1、2、4 g/kg），8只/组。连续14 d观察小鼠自主活动、行为变化及急性毒性体征，记录毒性反应出现时间与程度。试验结束后解剖并观察各脏器形态有无异常，计算各脏器指数。建立乙酰胆碱（ACh，10 μmol/L）诱导的大鼠离体回肠平滑肌痉挛收缩模型，以舒张率和收缩最大效应值为指标，测试PEFM和豆甾-4-烯-3-酮（ST）的解痉作用。使用NO合酶抑制剂（L-NAME，10 μmol/L）、鸟苷酸环化酶抑制剂（MB，30 μmol/L;ODQ，10 μmol/L）以及多种钾离子通道阻滞剂（GLIB，10 μmol/L;4-AP，2 mmol/L;CsCl，5 mmol/L;TEA，5 mmol/L）预孵育。通过高钾离子（80 mmol/L）诱导的痉挛模型评价PEFM及ST对L型电压门控钙通道的拮抗作用。采用AutoDock Vina 软件对主要成分ST与PKG、p-VASP（ser157）蛋白进行了分子对接。结果: GC-MS分析表明PEFM富含甾类成分，其中ST的含量最高，为31.51%。PEFM的急性毒性实验中未发现小鼠毒性反应，解剖后主要脏器体积、颜色、质地均未见明显异常，小鼠的脏器指数与对照组比较无显著性差异。PEFM中、高剂量能显著减少新斯的明诱导的小鼠痉挛性腹痛次数，并显著延长疼痛潜伏期（P<0.05）。ELISA检测结果表明，与溶媒对照组相比，PEFM的中、高剂量能显著提高血清中cGMP的含量（P<0.01）。Western blotting结果表明，双环维林及PEFM均可提高回肠组织中p-VASP的表达量（P<0.05）。PEFM和ST对Ach诱导的回肠平滑肌痉挛收缩均具有显著的解痉效应，其EC50分别为4.06 μg/mL和0.53 μg/mL。PEFM的活性可被L-NAME、MB、ODQ及4-AP显著抑制（P<0.05）。ST的解痉活性可被L-NAME、MB、ODQ、GLIB和TEA显著抑制（P<0.05）。PEFM和ST对高钾离子诱导的痉挛收缩均具有较好的解痉活性，其EC50分别为22.62 μg/mL和18.63 μg/mL。分子对接结果显示，ST能与PKG和p-VASP（ser157）两个核心靶蛋白稳定结合。结论: PEFM具有显著的解痉活性，对新斯的明诱导的痉挛性腹痛小鼠具有显著的镇痛效果，其作用机制可能与上调cGMP水平，增强回肠VASP磷酸化，激活NO/sGC/cGMP/PKG通路，开放电压门控钾通道及拮抗L型钙离子通道有关。ST为PEFM解痉镇痛的主要活性成分。.
To develop an interpretable machine learning model and web-based prediction tool for preoperative risk assessment of perineural invasion (PNI) in cervical cancer. A total of 845 cervical cancer patients undergoing radical surgery at Fourth Hospital of Hebei Medical University were retrospectively enrolled and divided into training and testing sets in a 7:3 ratio, with another 223 cervical cancer patients at Hebei Medical University Second Hospital during the same period serving as the external validation cohort. LASSO regression identified 13 preoperative predictors, which were incorporated into 7 machine learning algorithms. Model performance was evaluated using AUC and decision curve analysis. The optimal model was interpreted using SHAP values and deployed as a web-based prediction tool. Of the total of 1068 patients enrolled, 192 (17.98%) were diagnosed to have PNI. Thirteen preoperative features, namely lymphovascular space invasion (LVSI), depth of stromal invasion, lymph node metastasis (LNM), colposcopy-directed biopsy (CDB), tumor maximum diameter, carcinoembryonic antigen, SCC-Ag, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-albumin-neutrophil ratio (LANR), menopausal status, age, and histological type were selected. Comparison of model performance revealed that the Extreme Gradient Boosting (XGBoost) model resulted in the best efficacy in both the training and testing datasets with AUC of 0.962 and 0.923 (95% CI: 0.942-0.979 and 0.874-0.960), sensitivity of 0.873 and 0.767, and specificity of 0.939 and 0.942, respectively. Decision curve analysis demonstrated greater net benefit of the XGBoost model across a broader threshold range. The SHAP-XGBoost model showed excellent performance in external validation with an AUC of 0.924 and an accuracy of 0.933. The interpretable SHAP-XGBoost model effectively predicts PNI risk preoperatively. The predictive website derived from this model provides an useful tool to facilitate clinical decision-making in cervical cancer treatment. 目的: 建立术前预测宫颈癌患者术后周围神经浸润（PNI）发生风险的机器学习模型和线上预测器，实现临床诊疗决策制定的人工智能应用。方法: 回顾性纳入845例于河北医科大学第四医院接受根治性手术治疗的宫颈癌患者病理资料，以7∶3的比例分为训练集（n=593）和测试集（n=252）;同期纳入河北医科大学第二医院收治的223例宫颈癌患者组成外部验证集。LASSO筛选宫颈癌患者术后PNI发生相关术前特征变量，通过7种机器学习算法构建预测模型并通过ROC曲线下面积（AUC）和临床决策曲线（DCA）评价其预测效能及其在不同数据集的一致性。确定最优预测模型后进行SHAP解释，最终构建宫颈癌患者术后PNI发生风险的预测网站。结果: 共纳入1068例宫颈癌患者，其中192例（17.98%）患者术后病理结果呈现为PNI。LASSO回归分析共筛选:脉管间隙侵犯、间质浸润深度、淋巴结转移、阴道镜引导下穿刺活检、肿瘤最大直径、癌胚抗原、SCC-Ag、血小板/淋巴细胞比值、中性粒细胞/淋巴细胞比值、淋巴细胞*白蛋白/中性粒细胞比值、绝经情况、年龄和组织学类型等13个术前特征变量，7种算法对比，XGBoost模型在训练集和测试集中效能最佳，AUC分别为0.962和0.923，95% CI:0.942~0.979和0.874~0.960，敏感度为0.873、0.767，特异度为0.939、0.942。DCA分析结果同样显示XGBoost模型在较宽阈值范围内具有正向更大的净效益。基于SHAP可解释模型构建预测网站并进行外部验证，结果显示，该模型具有良好的泛化能力和预测准确性（AUC为0.924，准确率为0.933）。结论: 本研究开发的可解释性SHAP-XGBoost模型能够较好的预测宫颈癌患者术后周围神经浸润结局，基于该模型开发的预测网站可为宫颈癌诊疗决策制定提供辅助工具。.
To address the limitations of data storage and transfer caused by exponential growth of medical imaging data size, we propose a frequency-adaptive implicit neural compression (FAINC) method for medical images based on optimized implicit neural networks (INRs). A retrospective analysis was conducted on abdominal CT data from 356 patients in the KiTS19 and AVT datasets. We developed the FAINC method, a multi-subnetwork collaborative compression framework, which first evaluates the frequency-domain complexity of image blocks using the Spectral Sparsity Index (SSI), and then dynamically allocates them to subnetworks of different capacities through a frequency-domain gating mechanism. Compression output is achieved by combining parameter quantization with entropy coding. To assess its performance, the proposed method was compared with mainstream commercial compression standards (H.265/HEVC and JPEG2000), the implicit neural representation method NeRV, and the deep-learning-based compression method DVC. The FAINC method achieved the best reconstruction performance on both KiTS19 and AVT datasets at high compression ratios. At bitrates of BPV=0.32 and BPV=0.34, the FAINC method obtained the highest PSNR (47.03 and 50.76), the highest SSIM (0.9853 and 0.9930), and the lowest RMSE (0.0045 and 0.0029), achieving also a significantly higher subjective image quality score than other methods. Ablation studies demonstrated that the frequency-domain gating mechanism and dynamic parameter allocation contributed approximately 2.05 dB and 1.87 dB PSNR improvements, respectively. The proposed method substantially enhances image reconstruction quality at high compression ratios and outperforms the existing mainstream approaches in terms of structural fidelity and compression efficiency. The FAINC method provides a promising technical solution for efficient storage and low-bandwidth remote transfer of medical image data. 目的: 为解决在医学影像数据量呈指数级增长的背景下数据存储与传输受限问题，对隐式神经网络（INR）进行优化，提出频域自适应隐式神经网络（FAINC）的医学影像压缩方法。方法: 基于KiTS19和AVT数据集的356例患者CT数据进行回顾性分析，构建由多子网络协作的FAINC压缩方法。该方法通过光谱稀疏指数（SSI）评估数据块频域复杂度，接着采用频域门控机制将其动态分配至不同容量的子网络，最终结合参数量化与熵编码实现压缩输出。为验证性能，将所提方法与主流商业压缩标准（H.265/HEVC、JPEG2000）、隐式神经表示方法NeRV以及深度学习压缩方法DVC进行系统对比。结果: 在高压缩率时FAINC在KiTS19和AVT数据集均表现出最优重建性能。当比特率分别为BPV=0.32和BPV=0.34时，FAINC分别实现最高的PSNR（47.03和50.76）、最高的SSIM指标（0.9853和0.9930）以及最低的RMSE指标（0.0045和0.0029）。主观图像质量评分亦显著优于其他方法（P<0.05）。消融实验表明，频域门控与参数动态分配机制分别贡献约2.05dB和1.87dB的PSNR提升。结论: 实验结果证明，该方法在高压缩比下能够显著提高医学影像的重建质量，并在结构保真度和压缩效率方面优于现有主流方法。为医学影像的高效存储及低带宽远程传输提供技术支撑。.
To develop a TabMap image mapping and deep learning prediction framework that integrates medical prior knowledge to address the challenges of complex feature associations in tabular medical data and insufficient model interpretability in early ovarian cancer diagnosis. Based on clinical semantics, 36 medical diagnostic features were partitioned into 4 spatially continuous regions, namely the routine blood test partition, biochemical indicators partition, tumor markers partition, and other (coagulation, inflammation, and other clinical variables) partition. The Gromov-Wasserstein optimal transport algorithm was then employed to solve the optimal coupling between feature space and pixel space, thus generating TabMap images that preserve the topological structures. A lightweight convolutional neural network incorporating SE attention mechanism and global average pooling was designed to handle sample imbalance using class-weighted loss and weighted sampling strategies. Finally, class activation mapping (CAM) technique was utilized to visualize the model's decision-making process for interpretability analysis. Experiments on a real ovarian cancer dataset demonstrated that the proposed method achieved a test accuracy of 91.82% with a precision of 89.96%, recall of 89.45%, F1-score of 0.8970 and balanced accuracy of 88.51%, representing accuracy improvements of 8.26%-14.93% over traditional machine learning methods and 2.28%-13.60% over standard deep learning models. Interpretability analysis showed that the model exhibits pronounced activation patterns in the tumor-marker region as well as in coagulation-, inflammation-, and age-related zones, consistent with established clinical understanding. The feature-importance ranking further underscored the pivotal roles of CA125, HE4, and other key biomarkers in guiding the model's decisions. The proposed medical prior-guided TabMap method effectively integrates domain knowledge with data-driven learning, which enhances both its prediction performance and clinical interpretability. This strategy provides a novel approach for deep learning modeling of tabular medical data with good clinical potentials. 目的: 针对卵巢癌早期诊断中表格型医疗数据特征关联复杂、模型可解释性不足等问题，提出一种融合医疗先验知识的TabMap图像映射与深度学习预测框架。方法: 首先，根据临床语义将36个医疗诊断特征划分为血常规分区、生化指标分区、肿瘤标志物分区以及其他（凝血、炎症及临床变量）分区4个空间连续区域;其次，采用Gromov-Wasserstein最优传输算法求解特征空间与像素空间的最优耦合，生成保持拓扑结构的TabMap图像;然后，设计融合SE注意力机制和全局平均池化的轻量级卷积神经网络，通过类别加权损失和加权采样策略应对样本不平衡问题;最后，利用类激活映射技术可视化模型决策过程，实现可解释性分析。结果: 在真实卵巢癌数据集上的实验表明，本文方法的测试集准确率达到91.82%，精确率为89.96%，召回率为89.45%，F1分数为0.8970，平衡准确率为88.51%，相比传统机器学习方法准确率提升8.26%~14.93%，相比标准深度学习模型准确率提升2.28%~13.60%。可解释性分析显示，模型在肿瘤标志物分区以及凝血、炎症以及临床变量相关分区中呈现出明显的响应模式，与临床既有认知保持一致;特征重要性排序进一步强调了CA125、HE4等关键指标在模型决策中的核心作用。结论: 本研究提出的医疗先验引导TabMap方法有效融合了领域知识与数据驱动学习，在提升预测性能的同时增强了模型的临床可解释性，为表格型医疗数据的深度学习建模提供了新思路，具有良好的临床应用潜力。.
To explore mechanism of Wenshen Yangan Decoction (WSYG) for improving intestinal function in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Sixty male C57BL/6 mice were randomized equally into control group, MPTP group, low-, medium-, and high-dose WSYG groups (daily dose 10, 20 and 40 g/kg by gavage, respectively), and selegiline group. In all but the control group, the mice received intraperitoneal injections of MPTP (30 mg/kg) for 6 consecutive days to induce subacute PD. Motor function of the mice was assessed by the pole and open field tests, and striatal tyrosine hydroxylase (TH) expression, neuronal damage and intestinal histopathology were evaluated using immunohistochemistry, Nissl staining, and HE staining. Serum levels of diamine oxidase(DAO), D-lactic acid (D-LA), lipopolysaccharide (LPS), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK) were measured by ELISA, intestinal expressions of tight junction proteins zonula occludens-1 (ZO-1) and occludin were an alyzed by immuno fluorescence staining, and intestinal barrier permeability was assessed using FITC-dextran. WSYG, especially at the medium and high doses, significantly improved the performance of the mice in the behavioral tests. WSYG at all the 3 doses reduced neuronal damage and Nissl body loss in the striatum and substantia nigra, its medium and high doses significantly increased TH-positive neurons in the striatum. WSYG at the 3 doses significantly decreased serum FITC-Dextran (MW 4000) level, and medium- and high-dose WSYG markedly alleviated colonic inflammatory infiltration and edema, increased the chorionic crypt ratio, and reduced loss of ZO-1 and occludin. WSYG at all the 3 doses significantly increased serum VIP and CCK levels and decreased DAO, D-LA and LPS levels in the mice. WSYG effectively improve motor deficits and intestinal dysfunction in PD mice possibly by up-regulating intestinal VIP/CCK and down-regulating DAO/D-LA/LPS expressions to reduce intestinal barrier permeability, thereby alleviating dopaminergic neuronal damage. 目的: 探讨温肾养肝方（WSYG）对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病（PD）模型小鼠肠道功能影响及其作用机制。方法: 60只雄性C57BL/6J小鼠随机分6组（n=10）:对照组（Control）、MPTP组（MPTP）、WSYG低剂量组（MPTP+L，10 g·kg-1·d-1）、WSYG中剂量组（MPTP+M，20 g·kg-1·d-1）、WSYG高剂量组（MPTP+H，40 g·kg-1·d-1）和司来吉兰组（MPTP+S，10 mg·kg-1·d-1），对照组及MPTP组予以等量纯水灌胃。除对照组外，其余组采用连续6 d腹腔注射MPTP（30 mg·kg-1·d-1）构建亚急性PD模型。采用爬杆和旷场实验检测运动功能;免疫组化检测纹状体酪氨酸羟化酶（TH）水平，H E/尼氏染色观察神经元损伤;HE染色评估肠组织病理，ELISA检测二胺氧化酶（DAO）、D-乳酸（D-LA）、脂多糖（LPS）及血管活性肠肽（VIP） 、胆囊收缩素（CCK）水平，免疫荧光分析闭锁小带蛋白-1 （ZO-1）、闭合蛋白（Occludin），FITC-右旋糖酐（4000 MW）测定肠屏障通透性。结果: WSYG各组均显著缩短爬杆实验转身和总时间（P<0.0001）;中、高剂量提升旷场实验总距离及速度（P<0.05）。WSYG各组减轻黑质及纹状体区神经损伤及尼氏小体丢失;中、高剂量显著增加纹状体区TH阳性神经元（P<0.05）。WSYG各组显著降低血清FITC-右旋糖酐浓度（P<0.05）;中、高剂量缓解了结肠炎症浸润，提高绒隐比（P<0.05），减少ZO-1/Occludin缺失（P<0.05）;WSYG各组显著上调VIP、CCK水平，下调DAO、D-LA及LPS水平（P<0.05）。结论: 温肾养肝方不仅能有效缓解PD小鼠的运动障碍，还能缓解肠道功能紊乱，其作用可能与调节肠道生物活性物质（上调VIP/CCK，下调DAO/D-LA/LPS）、降低肠屏障通透性，进而减轻多巴胺能神经元损伤有关，且高剂量的疗效最为显著。.
To develop a bidirectional feature-mapping classification model for differential diagnosis of pneumonia. We collected chest X-ray (CXR) images from 1457 patients with pneumonia and 1456 healthy individuals. Radiomic features extracted from the segmentation masks using PyRadiomics were mapped into a latent shared space to construct the classification model using the bidirectional feature mapping classification model based on multi-constrained latent representation learning. The performance of the constructed model for differential diagnosis of pneumonia was evaluated using 5-fold cross-validation and compared with other feature-based classification models. Decision curve analysis was used for evaluating clinical utility of the model, and ablation experiments were performed to assess the contribution of each constraint module. The importance of the radiomics features was interpreted using the SHAP method, and a two-dimensional visualization experiment of the low-dimensional latent features obtained through the proposed mapping method was conducted to verify the feasibility and effectiveness of the model. The 5-fold cross-validation results showed that the proposed classification model had a positive predictive value of 0.796, a negative predictive value of 0.830, a specificity of 0.784, a sensitivity of 0.830, an accuracy of 0.811, and an area under the ROC curve of 0.893 for differential diagnosis of pneumonia. Decision curve analysis demonstrated a high net clinical benefit of the model within acceptable threshold probabilities. Ablation studies confirmed the essential role of the multi-constraint module, and the SHAP analysis revealed that the model focused primarily on clinically meaningful and medically interpretable features. The feature mapping method exhibited excellent performance in visual experiments to confirm the effectiveness of the proposed model. The proposed bidirectional feature mapping classification model demonstrates strong discriminative capability and high potential for differential diagnosis of pneumonia and shows obvious advantages over other classification models in pneumonia classification tasks. 目的: 构建一种基于多约束潜在表征学习的双向特征映射肺炎鉴别分类模型，并验证其判别性能、可解释性及临床可行性。方法: 收集了2913名患者（1457名阳性和1456名阴性）的胸部X线（CXR）图像，并使用开源影像组学工具PyRadiomics从掩码中提取影像组学特征。使用本研究提出的基于多约束潜在表征学习的双向特征映射分类模型，将CXR的影像组学特征映射到潜在共享空间并建立分类模型。采用五折交叉验证方法和阳性预测值（PPV）、阴性预测值（NPV）、特异性（SPE）、灵敏度（SEN）、准确率（ACC）、ROC曲线下面积（AUC）评价该分类模型的鉴别性能。将本研究所提出的模型与其他特征分类模型对于肺炎的鉴别能力进行定量比较。决策曲线分析（DCA）和消融实验评估各约束模块的贡献。采用 SHAP 方法对影像组学特征的重要性进行解释，以提升模型的可解释性。本研究提出特征映射方法得到的低维潜在特征进行样本散点可视化实验，验证本研究所提出的特征映射分类模型的可行性和有效性。结果: 五折交叉验证结果显示本研究所提出的基于多约束表征学习的双向特征映射分类模型在鉴别肺炎中的PPV、NPV、SPE、SEN、ACC、AUC分别为0.796、0.830、0.784、0.838、0.811、0.893，决策曲线显示在临床可接受阈值内具有更高净受益，消融实验验证多约束模块的关键作用，SHAP 分析表明模型关注的特征具有医学合理性，且特征映射方法在可视化实验中具有优秀的表现。结论: 基于多约束潜在表征学习的双向特征映射分类模型在鉴别肺炎中的应用具有较强的鉴别能力和较高的应用价值。与其他分类模型相比，本研究提出的分类模型在肺炎的鉴别分类任务中具有较大的优势。.
To identify Pediococcus acidilactici BPA03 strain isolated from healthy women's milk and evaluate its safety and probiotic properties. BPA03 strain was isolated from breast milk using dilution plating and streaking on MRS agar. Identification was performed using Gram staining, biochemical assays (BD card), 16S rRNA sequencing, and phylogenetic analysis. Safety assessment of the strain was conducted by evaluation of its hemolytic activity on blood agar, antibiotic susceptibility (Kirby-Bauer), and acute toxicity in zebrafish embryos. The probiotic properties of the bacterium were evaluated by measuring lactic acid production and assessing its protective effects against UV-induced photoaging and D-galactose-induced aging in zebrafish models. The BPA03 strain was Gram-positive with a spherical or ovoid shape, and identified as Pediococcus acidilactici. This strain showed no hemolytic activity and was sensitive to all the tested antibiotics (penicillin, ampicillin, and vancomycin). Growth curve analysis showed a lag phase of 2 h, a logarithmic phase starting from 4 to 12 h, and a stationary phase after 20 h in aerobic culture. Lactic acid concentration reached 23.6 mmol/L after culture for 8 h in MRS medium. In zebrafish embryos, BPA03 exhibited no significant acute toxicity, and the embryos showed a hatching rate above 95% even in the presence of 10⁸ CFU/mL BPA03 (LD₅₀>10⁸ CFU/mL). In UV-exposed zebrafish models, BPA03 obviously alleviated UV-induced caudal fin damage, significantly reduced reactive oxygen species and malondialdehyde levels, enhanced antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase), and downregulated mRNA expression of pro-inflammatory cytokines (IL‑1β, IL‑6, IL‑8, and TNF‑α). Pediococcus acidilactici BPA03 strain isolated from breast milk of healthy women exhibits good probiotic properties and safety. 目的: 对健康妇女乳汁中分离得到的菌株BPA03进行鉴定，并评价其安全性与益生特性。方法: 通过稀释平板涂布法和划线分离法在血琼脂培养基和MRS固体培养基上对乳汁中的菌株进行分离纯化和菌落形态观察;采用革兰氏染色鉴别菌株的形态与革兰氏阴阳性;采用BD鉴定卡对菌株BPA03进行生理生化性质的鉴定;结合16S rRNA测序与系统发育分析，对菌株BPA03进行了分子生物学鉴定;采用血琼脂平板检测菌株BPA03的溶血性;采用KB法检测菌株BPA03对抗生素的敏感性;使用生化分析仪检测其发酵液中的乳酸浓度;斑马鱼胚胎急性毒性实验评价其安全性;利用紫外线及D-半乳糖诱导的斑马鱼衰老模型，评价菌株BPA03的益生特性。结果: 菌株BPA03在MRS培养基上生长良好，菌落呈乳白色半透明、圆形、表面光滑、边缘整齐;该菌革兰氏染色为阳性，球形或卵圆形，多呈单、双或短链状排列，直径0.5~1.0 μm。菌株BPA03经形态学、生理生化及16S rRNA系统发育分析，被鉴定为乳酸片球菌。溶血性试验结果显示，该菌在血琼脂平板上无溶血环;药敏试验对青霉素、氨苄西林、万古霉素等测试抗生素均敏感。菌株BPA03成人血培养需氧瓶中35 ℃培养时，延滞期约2 h，对数生长期为4~12 h，20 h后进入稳定期，在MRS培养基中培养约8 h乳酸产量达到饱和终浓度为23.6 mmol/L。斑马鱼胚胎急性毒性实验表明，即使在10⁸ CFU/mL浓度下，胚胎孵化率仍高于95%，LD50>10⁸ CFU/mL，无显著急性毒性。在益生功能方面，BPA03在紫外线诱导的斑马鱼光老化模型中，能有效抑制尾鳍损伤并改善光老化;在D-半乳糖诱导的衰老模型中，BPA03能显著降低机体ROS与丙二醛（MDA）含量，提升超氧化物歧化酶（SOD）、过氧化氢酶（CAT）及谷胱甘肽过氧化物酶（GSH-Px）的抗氧化酶活性，并下调促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和肿瘤坏死因子-α（TNF-α）的mRNA表达水平（与模型组比较，P<0.05）。结论: 从健康妇女乳汁中分离得到的菌株BPA03被鉴定为乳酸片球菌，其具有良好的益生效应和安全性。.
To investigate the association between the red blood cell distribution width to hematocrit (RDW/HCT) ratio and 28-day all-cause mortality in patients with sepsis. A retrospective cohort study was conducted using the MIMIC-IV database (27 335 adult patients), and the eICU-CRD database was used for external validation (17 406 adult patients). The patients were grouped by RDW/HCT ratio quartiles. The primary outcome was 28-day all-cause mortality. Kaplan-Meier survival curves were used to assess the survival rates. Multivariable Cox regression and restricted cubic spline (RCS) analyses were performed to examine the association between RDW/HCT ratio and patient mortality. Subgroup analyses were conducted to assess the robustness of the findings. The 28-day mortality rates were 19.3% in the MIMIC-IV cohort and 16.0% in the eICU-CRD cohort. In the MIMIC-IV cohort, Kaplan-Meier analysis showed that a higher RDW/HCT ratio was associated with an increased risk of 28-day mortality in septic patients (log-rank P<0.0001). Multivariable Cox regression analysis suggested that an elevated RDW/HCT ratio was an independent risk factor for 28-day mortality in septic patients (HR=1.89, 95% CI: 1.52-2.36, P<0.001). RCS analysis showed a non-linear, U-shaped relationship between the RDW/HCT ratio and 28-day mortality of septic patients. No significant interactions were observed in subgroup analyses. The trends in the eICU-CRD validation cohort were consistent with those observed in the MIMIC-IV cohort. Conclusion Elevation of the RDW/HCT ratio is associated with an increased 28-day all-cause mortality rate in patients with sepsis. 目的: 探讨红细胞分布宽度/红细胞压积 （RDW/HCT） 比值与脓毒症患者28 d全因死亡率的相关性。方法: 使用MIMIC-IV数据库进行回顾性分析，并利用eICU-CRD数据库进行验证。分别从上述数据库中纳入27 335例及17 406例成年脓毒症患者。根据RDW/HCT比值四分位数分组，主要结局指标为28 d全因死亡率。采用Kaplan-Meier法评估各组生存率，利用多变量Cox回归模型和限制性立方样条（RCS）分析RDW/HCT比值与28 d死亡风险的相关性，并进行亚组分析。结果: MIMIC-IV队列和eICU-CRD队列脓毒症患者28 d死亡率分别为19.3%与16.0%。在MIMIC-IV队列中，Kaplan-Meier（K-M）生存曲线显示:RDW/HCT比值升高与28 d死亡风险增加相关（P<0.0001）。多变量Cox回归分析显示:RDW/HCT比值升高是28 d死亡的独立危险因素（HR=1.89，95% CI:1.52~2.36，P<0.001）。RCS分析显示RDW/HCT比值与28 d死亡率呈非线性“U”型关系。亚组分析未发现显著交互作用。eICU-CRD验证队列的结果趋势与MIMIC-IV数据库一致。结论: RDW/HCT比值升高与脓毒症患者28 d全因死亡率增加相关。.
To investigate the expressions of cofilin-1 (CFL1) and its phosphorylated form p-CFL1 in colon cancer, their relationship with clinicopathological features and patient prognosis, and their regulatory roles in colon cancer cell migration. The expression of CFL1 and p-CFL1 and their correlation with clinicopathological parameters were analyzed using the TCGA database and immunohistochemistry of colon cancer tissue microarrays. Kaplan-Meier survival analysis was used to explore the association of CFL1/p-CFL1 expression levels with survival of colon cancer patients. The localization of CFL1 and p-CFL1 in the nucleus and cytoplasm was observed using immunofluorescence staining. Wild-type (CFL1-WT) and nuclear localization signal mutant-type (CFL1-MUT) overexpression vectors were constructed and transfected into HCT116 cells, and the changes in cell migration were assessed using Transwell chamber migration assay. Transcriptome sequencing combined with KEGG enrichment analysis was performed to identify the differentially expressed genes and signaling pathways. Immunohistochemistry results showed significantly increased expressions of CFL1 and p-CFL1 in colon cancer tissues compared with the adjacent tissues (P<0.0001), and their expression levels were positively correlated (r=0.4753, P<0.0001). High expressions of CFL1 and p-CFL1 were significantly correlated with lymph node metastasis, advanced clinical stage, and shorter overall survival of the patients (P<0.05). Immunohistochemistry and immunofluorescence staining demonstrated localization of CFL1 and p-CFL1 in both the cytoplasm and nucleus. Functional experiments showed that overexpression of CFL1-WT and CFL1-MUT both promoted HCT116 cell migration, and CFL1-WT exhibited a stronger effect. KEGG analysis suggested that the genes regulated by CFL1-WT were significantly enriched in tumor metastasis-related pathways involving Ras, PI3K-Akt, and cell adhesion molecules. CFL1/p-CFL1 are highly expressed in colon cancer and can be potential biomarkers for poor prognosis. CFL1 overexpression further activates tumor metastasis-related signaling pathways through nuclear localization, thereby promoting colon cancer migration. 目的: 探究丝切蛋白1（CFL1）及其磷酸化形式p-CFL1在结肠癌中的表达情况，分析其与临床病理特征及预后的关系。揭示CFL1/p-CFL1调控结肠癌细胞迁移的分子机制，重点阐明其核定位在此过程中所发挥的作用及潜在机制。方法: 利用TCGA数据库、结肠癌组织芯片免疫组化分析CFL1和p-CFL1表达及临床病理参数相关性;应用Kaplan-Meier生存分析探究CFL1和p-CFL1表达水平与结肠癌患者生存期的关系;应用免疫荧光明确CFL1和p-CFL1在细胞核和细胞质的定位;构建野生型（CFL1-WT）与核定位信号突变型（CFL1-MUT）载体，在HCT116细胞中过表达，通过Transwell小室迁移实验检测细胞迁移能力;结合转录组测序与KEGG富集分析解析差异基因与信号通路。结果: 免疫组化结果显示，CFL1与p-CFL1在结肠癌组织中表达显著高于癌旁组织（P<0.0001），且二者表达呈正相关（r=0.4753，P<0.0001）。CFL1和p-CFL1高表达与淋巴结转移、临床分期晚及患者总生存期缩短相关（P<0.05）。免疫组化与免疫荧光显示CFL1/p-CFL1可定位于细胞质与细胞核。功能实验表明，过表达CFL1-WT与CFL1-MUT均能促进HCT116细胞迁移，且CFL1-WT作用更强。KEGG分析提示，CFL1-WT调控的基因显著富集于Ras、PI3K-Akt、细胞粘附分子等肿瘤转移相关通路。结论: CFL1/p-CFL1在结肠癌中高表达，是预后不良的潜在生物标志物。CFL1可通过核定位进一步激活肿瘤转移相关信号通路，从而促进结肠癌迁移。.
To investigate the mechanism of cephaeline for suppressing malignant biological behaviors of colorectal cancer (CRC). Network pharmacology was employed to identify the core targets and signaling pathways of cephaeline in CRC treatment. The binding between the key targets of CRC and cephaeline was simulated using molecular docking. CCK-8 assay was used to assess the viability of HCT116 and DLD-1 cells treated with 2-32 nmol/L cephaeline for 24, 48, and 72 h to determine the optimal treatment condition. The effects of cephaeline treatments (at 2 and 4 nmol/L in HCT116 cells and at 4 and 8 nmol/L in DLD-1 cells) for 48 h on cell proliferation, migration, invasion, epithelial‑mesenchymal transition (EMT), apoptosis, and expressions of RAS signaling pathway proteins were evaluated using colony-forming assay, wound healing assay, Transwell assays, and Western blotting. Network pharmacology analysis suggested that cephaeline inhibited CRC mainly by regulating the targets such as MAPK, VEGFA, and PDGFRB and modulating the Rap1, Ras, cAMP, and PI3K-Akt signaling pathways. Molecular docking results showed that the binding energies of cephaeline with PDGFRB and MAPK1 were less than -5 kcal/mol, indicating spontaneous and stable binding between them. In HCT116 and DLD-1 cells, treatment with cephaeline concentration-dependently suppressed the cell viability, proliferation, migration, and invasion, downregulated the expressions of PCNA, MMP9, VEGF-C, BCL-2, N-cadherin, vimentin, VEGF-A, PDGFRB, MYC, and MAPK1, and upregulated the expression levels of E-cadherin and BAX. Cephaeline suppresses malignant biological behaviors of CRC possibly by regulating the RAS signaling pathway. 目的: 探讨吐根酚碱（Cephaeline）抗结直肠癌（CRC）的潜在作用机制。方法: 利用网络药理学获取Cephaeline治疗CRC的核心靶点与信号通路，利用分子对接技术验证CRC关键靶点与Cephaeline的结合能力;以CCK-8法检测2~32 nmol/L Cephaeline处理24、48、72 h后HCT116和DLD-1细胞活力。据此设对照组（0 nmol/L）及低、高浓度组（HCT116:2、4 nmol/L;DLD-1:4、8 nmol/L）处理细胞48 h，通过平板克隆、划痕实验、Transwell和Western blotting分别评估细胞增殖、迁移、侵袭、凋亡、上皮间质转化、RAS信号通路及相关蛋白表达。结果: 经过网络药理学筛选，Cephaeline主要通过调控丝裂原活化蛋白激酶1（MAPK1）、血管内皮生长因子A（VEGFA）、血小板衍生生长因子受体β（PDGFRB）等靶点作用于Rap1 信号通路、Ras 信号通路、cAMP 信号通路、PI3K-Akt等信号通路来达到治疗结肠癌的目的。分子对接结果显示Cephaeline与PDGFRB、MAPK1等关键靶点结合能均小于-5 kcal/mol，表明二者可自发且稳定结合。体外实验中，与对照组相比，不同浓度Cephaeline处理后，可观察到以下结果:细胞活力、增殖能力、迁移能力及侵袭能力均随药物浓度的升高呈现降低趋势，表现出浓度依赖性抑制效应（P<0.05）;蛋白表达水平检测显示，增殖细胞核抗原、基质金属蛋白酶 9、血管内皮生长因子C、B细胞淋巴瘤-2蛋白、N-钙黏蛋白、波形蛋白、VEGF-A、PDGFRB、MYC原癌基因蛋白、MAPK1蛋白的表达水平出现下降，而E-钙黏蛋白、BCL2相关X蛋白蛋白的表达水平则呈现上升趋势（P<0.05）。结论: Cephaeline降低CRC的恶性生物学行为可能与RAS信号通路有关联。.
To construct a Transformer-based multimodal data encoding model for predicting hospital-acquired infections (HAI). Laboratory test data of 300 000 patients were extracted from the publicly available MIMIC-IV database. The laboratory data of 1172 patients and chest X-ray images from 274 of these patients were collected from Nanfang Hospital. A novel Transformer-based encoding model was developed to process the data, which was then connected to a machine learning classifier for predicting HAI. The radiomic and deep learning features were extracted from the chest X-ray images for predicting ventilator-associated pneumonia (VAP). These imaging features were subsequently integrated with the laboratory test data using a feature fusion algorithm. The model performance was evaluated by assessing the accuracy, the area under the ROC curve (AUC), sensitivity, and specificity. The proposed algorithm was quantitatively compared against traditional machine learning classifiers to validate its effectiveness and feasibility. The results demonstrated that the model developed in this study achieved an AUC of 0.989 in the internal validation set. In the external validation set, the optimal model for predicting HAI attained an AUC of 0.98, and following the integration of imaging features, the optimal model reached an AUC of 0.93 in the VAP prediction task, demonstrating superior performance over the baseline models. The Transformer-based model for processing laboratory test data has excellent predictive capability and good clinical applicability for HAI prediction with also good performance for predicting VAP. 目的: 构建一个基于Transformer的多模态数据编码模型用于预测医院获得性感染。方法: 收集公开医学数据库MIMIC-IV中300 000条患者的实验室检验数据，同时在南方医院收集1172例患者的实验室检验数据和其中274例患者的X线胸片。使用本研究提出的基于Transformer的编码模型处理数据并接入机器学习分类器对医院获得性感染（HAI）进行预测。提取X线胸片影像组学特征和深度特征，采用特征融合算法将其与实验室检验数据融合后对呼吸机相关性肺炎（VAP）进行预测。通过准确率 （ACC）、AUC、灵敏度 （SEN） 和特异度 （SPE）评价模型性能，并将本研究所提出算法与传统机器学习分类算法进行定量比较，验证模型的有效性和可行性。结果: 结果显示本研究所构建的模型在内部验证中AUC可达0.989;在外部验证中，在预测HAI问题上的最优模型的AUC达到0.98，在融合影像特征后预测VAP任务中，最优模型的AUC达到0.93，均高于预设的基线模型性能。结论: 基于Transformer的实验室检验数据处理模型在预测HAI的问题中具有优秀的预测能力和较高的临床应用价值，并拓展性的对HAI的亚型进行了预测，取得了较好的结果。.
To investigate the mechanism by which chronic iron overload induces diminished ovarian reserve (DOR) in mice. Forty female C57BL/6J mice with normal estrous cycles were randomly divided into 4 groups (n=10) for intraperitoneal injections of normal saline or iron dextran at 0.1, 0.5 or 1.0 g/kg once a week for 8 consecutive weeks. The changes in body weight and food intake of the mice were monitored weekly. Vaginal smears were used to assess estrous cycle changes of the mice, and wet weights of bilateral ovaries and uterus were recorded. Ovarian histopathology was evaluated by HE staining, iron deposition was detected by Prussian blue staining; serum levels of sex hormones (FSH, LH, E2, and AMH) and the levels of MDA and SOD in the ovarian tissue were determined, and reactive oxygen species (ROS) production was assessed on frozen sections of the ovarian tissue. Mitochondrial ultrastructural changes in the ovaries of the mice were observed with transmission electron microscopy, and ovarian expression levels of Fth1, Ftl, Cat, Gpx1, Tf and Tfr1 mRNAs and Tf, Tfr1, Ft, Fth1, Ftl and Gpx4 protein were detected. The mice receiving injections of 0.5 and 1.0 g/kg iron dextran exhibited disrupted estrous cycles, increased atretic follicles, decreased ovarian index, and increased uterine index with reduced AMH and E₂ levels and increased FSH and LH levels. The injections caused significant iron accumulation, oxidative stress, and obvious mitochondrial damage in the ovarian tissues, resulting also in downregulation of Tf, Tfr1, Gpx4, Gpx1 and Cat and upregulation of Ft, Ftl and Fth1 expressions. Iron dextran at 0.5 and 1.0 g/kg can induce chronic, dose-dependent iron overload in mice, which causes systemic iron metabolism disorders and disrupted iron homeostasis to trigger oxidative stress damage and endocrine dysfunction and ultimately induce DOR. 目的: 探讨慢性铁过载导致小鼠卵巢储备功能减退的机制。方法: 将40只动情周期正常的C57BL/6J雌性小鼠随机分为空白组（腹腔注射等体积生理盐水，OF组）、低铁剂组（0.1 g/kg，LF组）、中铁剂组（0.5 g/kg，MF组）、高铁剂组（1.0 g/kg，HF组），10只/组，除空白组外，其余组腹腔注射右旋糖酐铁，1次/周，持续8周，制备慢性铁过载小鼠模型。每周称量小鼠体质量、监测小鼠进食量;阴道脱落细胞涂片观察小鼠动情周期变化;称量小鼠双侧卵巢及子宫湿重;苏木精-伊红染色观察小鼠卵巢组织病理学改变;普鲁士蓝染色评估卵巢组织中铁离子的表达水平;ELISA测定血清性激素[卵泡刺激素、黄体生成素、雌二醇、抗缪勒氏管激素（AMH）];生化试剂盒检测卵巢组织中丙二醛和超氧化物歧化酶（SOD）水平;冰冻切片小鼠卵巢组织活性氧测试;透射电镜观察小鼠卵巢组织线粒体超微结构;Rt-qPCR检测卵巢组织中铁重链蛋白1（Fth1）、铁轻链蛋白（Ftl）、转铁蛋白（Tf）、转铁蛋白受体1（Tfr1）、过氧化氢酶（Cat）、谷胱甘肽过氧化物酶1（Gpx1）基因的表达;Western blotting检测卵巢组织Ft、Ftl、Fth1、Tf、Tfr1、谷胱甘肽过氧化物酶4（Gpx4）蛋白的表达。结果: 与空白组相比，其余3组小鼠动情周期不同程度的紊乱，MF、HF组闭锁卵泡数量增多，卵巢指数下降、子宫指数上升（P<0.05），血清AMH、雌二醇水平下降（P<0.05），卵泡刺激素、黄体生成素水平上升（P<0.05），卵巢间质铁沉积信号显著增多，SOD活性降低（P<0.001），丙二醛水平升高（P<0.01），活性氧荧光强度上升（P<0.05），氧化应激水平显著升高，卵巢组织受损线粒体数量增多，线粒体嵴减少甚至消失，卵巢组织Tf、Tfr1、Gpx4、Gpx1、Cat表达水平均下降（P<0.05），Ft与Ftl、Fth1表达升高（P<0.05）。结论: 0.5 g/kg和1.0 g/kg右旋糖酐铁成功诱导慢性浓度依赖性铁过载模型小鼠，慢性铁过载通过代偿性上调卵巢组织内Ft、Ftl和Fth1的表达，同时下调Tf和Tfr1、Gpx4的表达，导致小鼠体内铁代谢失常，铁稳态紊乱，出现氧化应激损伤和内分泌功能紊乱，进而诱发卵巢储备功能减退。.
To investigate the neuroprotective effect of gastrodin (GAS) against hypobaric hypoxia (HH)-induced brain injury in rats and the underlying mechanism. Twenty-four adult SD rats were randomized equally into normoxic control group, HH model group, low-dose (100 mg/kg) GAS group (HH+GAS-L group), and high-dose (200 mg/kg) GAS group (HH+GAS-H group). In the latter 3 groups, the rats were exposed to HH in a hypobaric oxygen chamber for 24 h to simulate the condition at an altitude of 6000 m, and GAS was administered intraperitoneally once daily for 7 days. Cerebral cortex tissues were collected for analysis of P53, SLC7A11, and GPX4 protein expressions using Western blotting and for determination of the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe²⁺). In cultured HT22 neurons exposed to oxygen-glucose deprivation (OGD), the effects of GAS (500 μmol/L), nutlin-3 (a P53 agonist; 10 μmol/L) or their combination were examined on ferroptosis-related protein expressions, intracellular ROS, lipid peroxidation, MDA, GSH, cell viability, mitochondrial membrane potential, and Fe²⁺ levels. In the rat models of HH, GAS treatment significantly inhibited P53 expression, upregulated SLC7A11 and GPX4 proteins, markedly reduced Fe²⁺, ROS, and MDA levels, and increased GSH content in the cerebral cortex. In cultured HT22 neurons, GAS treatment effectively alleviated OGD-induced cell ferroptosis as shown by decreased P53 expression, increased SLC7A11 and GPX4 expressions, and lowered levels of intracellular ROS generation, lipid peroxidation, and Fe²⁺ accumulation, along with obvious restoration of GSH levels, cell viability, and mitochondrial membrane potential. The protective effects of GAS was markedly attenuated by activation of the P53 pathway using nutlin-3. GAS produces neuroprotective effects against HH-induced brain injury in rats by inhibiting neuronal ferroptosis via regulating the P53/SLC7A11/GPX4 signaling pathway. 目的: 研究天麻素（GAS）对高原低压缺氧（HH）性脑损伤的神经保护作用，并探讨其机制是否与调节P53/SLC7A11/GPX4信号通路、抑制神经元铁死亡相关。方法: 体内实验选取24只成年SD大鼠，随机分为4组（n=6）:常压常氧对照组（Nor）、低压缺氧模型组（HH）、天麻素低剂量组（HH+GAS-L，100 mg/kg）、天麻素高剂量组（HH+GAS-H，200 mg/kg）。除对照组外，其余各组大鼠置于模拟海拔6000 m的低压氧舱中持续暴露24 h以建立HH模型。天麻素于造模后腹腔给药，1次/d。取第7天的脑皮层进行Western blotting检测P53、SLC7A11及GPX4蛋白表达，同时测定组织内活性氧标志物（DHE）、丙二醛（MDA）、谷胱甘肽（GSH）及亚铁离子（Fe²⁺）的含量。体外培养HT22神经元，分为:对照组（Control）、模型组（OGD）、天麻素干预组（OGD+GAS，500 μmol/L）、P53激动剂组（OGD+Nutlin-3，10 μmol/L）及联合处理组（OGD+GAS+Nutlin-3）。检测指标包括铁死亡相关蛋白表达、细胞内活性氧（DCFH-DA）、脂质过氧化（BODIPY-C11）、MDA、GSH、细胞存活率（CCK-8）、线粒体膜电位（JC-1）及亚铁离子（FerroOrange）。结果: 动物实验显示，与HH组相比，天麻素显著抑制P53表达，上调SLC7A11与GPX4蛋白水平（P<0.05），并显著降低脑皮层组织Fe²⁺、ROS和MDA含量，提高GSH水平（P<0.05）。细胞实验结果一致，天麻素有效减轻低压缺氧诱导的铁死亡，表现为P53表达下降，SLC7A11与GPX4表达升高（P<0.05），细胞内ROS生成、脂质过氧化和Fe²⁺蓄积被抑制，同时GSH含量、细胞活性和线粒体膜电位显著恢复（P<0.05）。而使用Nutlin-3激活P53信号通路后，天麻素的保护作用被明显逆转（P<0.05）。结论: 天麻素可能通过调控P53/SLC7A11/GPX4信号通路抑制神经元铁死亡，从而对高原低压缺氧性脑损伤发挥神经保护作用。.