To analyze the global trends, drivers, and health inequalities of non-alcoholic fatty liver disease (NAFLD) burden to identify key predictors of NAFLD-related mortality. Using data from the Global Burden of Disease (GBD) Study 2021, we extracted global measures of NAFLD from 1990 to 2021, and the trends were analyzed using joinpoint regression. Decomposition analysis was used to quantify the contributions of population growth, aging, and epidemiological changes. The health inequality was assessed using the concentration index. Using XGBoost-SHAP machine learning, the mortality predictors were identified, and two-sample Mendelian randomization was employed to test the causality for the key factors. All the analyses were conducted with data stratification by sex and the socio-demographic index (SDI). The global age-standardized disability-adjusted life years (DALYs) rate showed an increasing trend in both males (average annual percentage change [AAPC]=+0.34%) and females (AAPC=+0.05%). Decomposition analysis revealed that population growth was the primary driver of the global increase in DALYs, while population aging contributed to 52.37% of male deaths in high-SDI regions. Health inequality analysis showed a concentration index of -0.05 for DALYs in 2021, indicating a concentration of burden among low-SDI populations. Machine learning identified smoking (relative importance=100%) and advanced age (70-74 years: 60%) as the most critical predictors of mortality, and the model demonstrated good fit on the test set (R2=0.98). SDI-stratified analysis showed smoking and aging are the top two predictors across all SDI regions. Mendelian randomization further confirmed positive causal associations of smoking initiation (OR=1.35, P<0.05) and aging (proxied by frailty index, OR=2.01, P<0.05) with NAFLD risk. NAFLD burden is heavy globally with significant sex and socioeconomic inequalities. Smoking and advanced age are key risk factors for NAFLD, calling for integrated interventions for tobacco control, geriatric health management, and health equity promotion. 目的: 分析非酒精性脂肪性肝病（NAFLD）的全球负担趋势、驱动因素及健康不平等，利用可解释机器学习识别关键死亡风险因素，并通过孟德尔随机化验证其潜在因果关联。方法: 基于全球疾病负担（GBD）2021数据，提取1990~2021年NAFLD的发病率、患病率、死亡率、残疾调整生命年（DALYs）等指标。运用Joinpoint回归分析趋势，分解分析法量化人口增长、老龄化和流行病学变化的贡献，集中指数评估健康不平等，XGBoost-SHAP机器学习识别死亡预测因子，并使用双样本孟德尔随机化对关键因子进行因果验证;分析按性别和社会人口指数（SDI）分层。结果: 全球NAFLD年龄标准化DALY率在男性（平均年度百分比变化[AAPC]=+0.34%）和女性（AAPC=+0.05%）中均呈上升趋势。分解分析显示，人口增长是全球DALYs增加的主要驱动力，而在高SDI地区，人口老龄化对男性死亡的贡献度达52.37%。健康不平等分析显示，2021年DALYs的集中指数为-0.05，负担向低SDI人群集中。机器学习识别吸烟（相对重要性=100%）和高龄（70~74岁:60%）为最关键死亡预测因素，模型测试集拟合优度良好（R²=0.98）。SDI分层分析显示吸烟和老龄化在不同SDI区域均位列前两位。孟德尔随机化进一步验证了吸烟起始（OR=1.35，P<0.05）与衰老（以衰弱指数代理，OR=2.01，P<0.05）与NAFLD风险间的正向因果关联。结论: NAFLD负担沉重，存在性别与社会经济不平等。吸烟和高龄是关键风险因素，需制定整合烟草控制、老年健康管理与健康公平促进的针对性干预策略。.
To investigate the regulatory mechanism of Yiqi Jiedu Formula on immune microenvironment of hepatocellular carcinoma (HCC) in mice. Forty male BALB/c mice bearing subcutaneous Hep3B cell xenografts were randomized equally into model group (with normal saline treatment), Huachansu Tablet group, and low- (0.5 g/kg), medium- (1 g/kg), and high-dose (2 g/kg) Yiqi Jiedu Formula groups. All the mice received daily gavage of the corresponding treatments for 28 consecutive days, and the changes in tumor weight and volume were recorded every 7 days, and tumor inhibition rate was calculated after the final administration. Histopathological changes in the tumor tissues were observed with HE staining, and polarization of M1/M2 macrophages was analyzed with flow cytometry. The mRNA and protein expressions of iNOS, Arg-1, p65, and p50 in the tumor tissues were detected using q-PCR and Western blotting, and CD86 and CD206 protein expressions were observed with immunofluorescence staining. Serum levels of IL-4, IL-6, IL-10, IFN‑γ, TNF‑α, and TGF‑β1 of the mice were measured using ELISA. The mice in the 3 Yiqi Jiedu Formula groups showed significant reductions in tumor weight and volume with decreased tumor cell count, increased tumor cell apoptosis, increased percentage of M1 macrophages, and decreased percentage of M2 macrophages. The treatment obviously upregulated CD86 and downregulated CD206 expression in the tumor tissue, lowered the protein and mRNA expressions of iNOS, Arg-1, p65, and p50, reduced serum levels of IL-4, IL-10, TNF‑α, and TGF-β1, and increased serum levels of IL-6 and IFN-γ in the tumor-bearing mice. Yiqi Jiedu Formula effectively inhibits Hep3B cell xenograft growth in mice and induces a shift of M1/M2 ratio by promoting M1 polarization, thereby ameliorating the immunosuppressive tumor microenvironment and enhancing anti-tumor immunity possibly in association with inhibition of NF-κB signaling pathway overactivation. 目的: 探究益气解毒方对Hep3B肝癌小鼠模型中免疫微环境的调控机制。方法: 选取40只SPF级雄性小鼠，小鼠腋下注射Hep3B肿瘤细胞，建立异位小鼠模型，将小鼠随机分为模型组（生理盐水0.2 g/kg），华蟾素片组（0.22 g/kg），益气解毒方低（0.5 g/kg）、中（1 g/kg）、高（2 g/kg）剂量组，8只/组。连续灌胃给药28 d，每7 d记录各组小鼠瘤重、体积。给药结束后计算抑瘤率，通过HE染色观察小鼠肿瘤组织病理变化，流式细胞术检测肿瘤组织中M1/M2型巨噬细胞极化比例，免疫荧光术检测CD86、CD206蛋白表达，Western blotting检测小鼠瘤体组织中iNOS、Arg-1、p65、p50蛋白表达，q-PCR检测iNOS、Arg-1、p65、p50 mRNA表达，ELISA法检测血清IL-4、IL-6、IL-10、INF-γ、TNF-α、TGF-β1水平。结果: 与模型组比较，益气解毒方各组小鼠肿瘤质量、体积减小;肿瘤细胞数量减少，细胞核缩小，坏死区域增大;M1型巨噬细胞比例升高，M2型巨噬细胞比例降低;肿瘤组织中CD86表达上升，CD206表达下降;iNOS、Arg-1、p65、p50蛋白及mRNA表达降低;血清IL-4、IL-10、TNF-α、TGF-β1水平降低，IL-6、INF-γ水平升高（P<0.05）。结论: 益气解毒方能有效抑制Hep3B肝癌荷瘤小鼠肿瘤生长，逆转肿瘤相关巨噬细胞的极化状态，将M1/M2比例从M2主导调整至M1主导，从而改善肿瘤免疫抑制微环境，增强抗肿瘤效应，其作用机制可能与抑制NF-κB信号通路的过度激活有关。.
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 elucidate the neuroimmune regulatory mechanism of the circadian rhythm gene KLF10 as a biomarker for anxiety depressive disorder (ADD). The differentially expressed circadian rhythm genes were screened using human peripheral blood gene chip data from the GEO database (including 64 healthy individuals, 62 patients with major depressive disorder [MDD], and 59 with ADD) in conjunction with the MSigDB database. Weighted gene co-expression network analysis and machine learning models were employed to identify the core genes, followed by KEGG pathway enrichment analysis and evaluation of their diagnostic efficacy using ROC curves. In a male SD rat model of ADD induced by chronic restraint and corticosterone stress, the changes in depressive-like behaviors, hippocampal and amygdala pathologies, levels of inflammatory and pro-inflammatory cytokines, co-localization of KLF10 and p-p65 expression, and expression levels of NF‑κB/NLRP3 pathway molecules were examined following stereotactic AAV virus injection into the lateral ventricle for KLF10 overexpression. Compared with healthy individuals, the depressive patients showed differential expressions of 9 circadian rhythm genes. Compared with the MDD patients, the patients with ADD had significantly higher immune infiltration scores with upregulated NOD-like receptor and NF‑κB signaling pathways. The specific biomarker KLF10 demonstrated a diagnostic efficacy of 0.885. In the rat models of AOD, KLF10 overexpression significantly ameliorated depression- and anxiety-like behaviors, restored the balance between the pro- and anti-inflammatory cytokines, and improved hippocampal and amygdala pathologies. KLF10 overexpression also markedly upregulated NFKBIA mRNA, downregulated NLRP3 and RELA mRNAs, and reduced protein expressions of p-IκB‑α, p-p65, and NLRP3 in the brain tissues of the rats. KLF10 overexpression ameliorates ADD behaviors in rats by inhibiting hippocampal-amygdala inflammation via downregulating the NF‑κB/NLRP3 pathway, suggesting the potential of KLF10 as a diagnostic biomarker and therapeutic target for AOD. 目的: 解析昼夜节律基因KLF10作为焦虑性抑郁生物标志物的神经免疫调控机制。方法: 基于GEO数据库人源外周血基因芯片信息，纳入健康对照64例、抑郁组62例、焦虑性抑郁59例，结合MSigDB数据库筛选差异表达的昼夜节律基因。加权基因共表达网络分析和机器学习模型筛选核心基因，KEGG通路富集分析生物过程，采用ROC曲线评估诊断效能。将40只SPF级雄性SD大鼠按体质量均质化分为空白组、假手术组、模型组、KLF10过表达组，10只/组，通过脑立体定位-侧脑室注射腺相关病毒（AAV）构建KLF10过表达模型、慢性束缚联合皮质酮应激构建焦虑性抑郁大鼠模型。强迫游泳试验检测抑郁样行为，高架十字迷宫检测焦虑样行为;采用尼氏染色观察海马、杏仁核病理学改变，酶联免疫吸附法（ELISA）检测中枢及外周细胞因子白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白介素-10（IL-10）、转化生长因子-β（TGF-β）;免疫荧光染色观察KLF10与p-p65共定位表达;Western blotting及qRT-PCR检测NF-κB/NLRP3通路分子表达水平。结果: 抑郁患者较健康人群9个昼夜节律基因存在表达差异，焦虑性抑郁与单纯抑郁相比免疫浸润评分升高，KEGG涉及NOD样受体信号通路和NF-κB信号通路的上调。特异性生物标记物KLF10的诊断效能为0.885（P<0.001）。在体实验验证表明，焦虑性抑郁模型大鼠强迫游泳不动时间增加、高架十字迷宫开臂探索减少（P<0.05），中枢及外周促炎因子IL-1β、TNF-α含量升高，抗炎因子IL-10、TGF-β含量下降（P<0.05）;海马和杏仁核神经元排列紊乱、尼氏体减少。NF-κB/NLRP3通路各信号分子转录水平及关键蛋白表达升高（P<0.05）。过表达KLF10可显著改善大鼠抑郁样及焦虑样行为（P<0.05），恢复中枢和外周促炎/抗炎因子平衡，改善海马及杏仁核神经元排列，同时上调NF-κB/NLRP3通路抑制节点NFKBIA的转录（P<0.001），从而下调NLRP3、RELA的转录（P<0.05），降低p-IκB-α、p-p65、NLRP3蛋白的表达（P<0.05）。结论: KLF10通过下调NF-κB/NLRP3通路抑制海马-杏仁核炎症，改善抑郁及焦虑行为，可作为焦虑性抑郁诊断标志物与治疗靶点。.
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 establish a mouse model with the comorbidity of gastric dysfunction and depression mimicking clinical onset of the condition. Thirty male C57BL/6J mice were randomly divided into control, 14-day model, and 28-day model groups (n=10). The mice in the latter two groups were subjected to continuous combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 14 or 28 days. Gastric motility, gastric emptying and histopathological changes of the mice were evaluated using strain gauge sensors, in vivo imaging and HE staining, respectively, and behavioral tests were used to assess their depression-like behaviors. Serum corticotropin-releasing factor (CRF), brain-derived neurotrophic factor (BDNF), gastrin, motilin, and gastric nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels were measured by ELISA to explore the peripheral mechanisms. Compared with control mice, the mice in 14-day model group exhibited reduced body weight, food intake and gastric motility amplitude with delayed gastric emptying but showed no significant depression-like behaviors; in 28-day model group, these changes were further exacerbated, and significant depression-like behaviors were observed. Compared with 14-day model group, the 28-day model group displayed severer gastric dysfunction and depression-like behaviors. Compared with control group, exposure to complex stresses for 14 days significantly increased serum CRF and decreased BDNF, gastrin and motilin levels, increased gastric NOS and decreased gastric AChE level, which were worsened after a 28-day exposure. HE staining showed no obvious histological changes in the gastric mucosa in the two model groups. Combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 28 days can induced the comorbidity of gastric dysfunction and depression in mice, and abnormal changes in serum neurotransmitters, brain-gut peptides and vagus activity may partly participate in the pathogenesis of the comorbidity. 目的: 构建一种稳定可行的模拟临床发病的胃功能障碍与抑郁共病模型。方法: 将30只C57BL/6J雄性小鼠随机分为对照组、模型14 d组、模型28 d组（n=10）。模型组采用夹尾、冰生理盐水灌胃及不规则进食3种应激因素持续干预，对照组常规饲养。通过应力传感器记录胃动力、小动物活体成像评估胃排空、HE染色观察胃组织形态;旷场、高架十字迷宫、悬尾、强迫游泳和糖水偏好试验评价抑郁行为;ELISA检测血清中促肾上腺皮质激素释放因子（CRF）、脑源性神经营养因子（BDNF）、胃泌素（GAS）、胃动素（MTL）及胃组织中一氧化氮合酶（NOS）及乙酰胆碱酯酶（AchE）含量，分析共病发生的可能外周机制。结果: 与对照组相比，模型14 d组小鼠体质量和进食量下降，胃运动振幅降低和胃排空延迟（P<0.05），但各抑郁行为学指标均未出现明显变化（P>0.05）;模型28 d组小鼠体质量和进食量进一步下降、胃运动振幅降低和胃排空延迟加剧（P<0.01），同时出现小鼠旷场活动总距离及中央穿越时间和次数降低、进入开放臂次数和时间减少、悬尾与强迫游泳不动时间增加及糖水偏好下降等抑郁行为（P<0.01）;与模型14 d组比较，模型28 d组体质量和进食量下降，胃运动振幅降低和胃排空延迟明显（P<0.01），各抑郁行为学指标均出现变化（P<0.01）。ELISA结果显示，与对照组相比，模型14 d组血清BDNF降低和CRF升高（P<0.05），GAS和MTL减少，胃组织中NOS升高，AchE减少（P<0.01），模型28 d组小鼠血清CRF升高，BDNF、GAS、MTL减少，胃组织中NOS升高，AchE减少（P<0.01）;与模型14 d比较，模型28 d组血清CRF升高，BDNF、MTL、GAS进一步降低（P<0.01），胃组织中NOS上升（P<0.05）。HE染色显示，模型14、28 d组小鼠胃黏膜均未见器质性损伤。结论: 通过夹尾、冰生理盐水灌胃及不规则禁食3种应激干预28 d，成功构建一种稳定易复制的胃功能障碍与抑郁共病的动物模型，血清神经递质、脑肠肽水平紊乱或迷走神经活性异常等可能是胃功能障碍与抑郁共病的外周机制。.
To investigate the neuroprotective effects of formononetin (FMN) against hypoxic-ischemic brain damage (HIBD) in neonatal mice and the underlying mechanism. Twenty-four neonatal C57BL/6J mice were randomly divided (n=6) into sham-operated group, HIBD model group, HIBD+FMN-L (50 mg/kg) group, and HIBD+FMN-H (100 mg/kg) group. Mouse models of HIBD were established by left common carotid artery ligation followed by hypoxia (92% N₂, 8% O₂) for 40 min. FMN at the two doses was administered by intraperitoneal injection, and 3 days later, brain tissues from the cortical ischemic penumbra were collected for assessing expressions of ferroptosis-related proteins (P53, SAT1, and ACSL4) using Western blotting and immunofluorescence staining and for detecting the levels of Fe²⁺, superoxide, malondialdehyde (MDA), and glutathione (GSH). In cultured HT22 neurons with oxygen-glucose deprivation (OGD), the effects of 100 μmol/L FMN, 10 μmol/L Nutlin-3 (a P53 agonist), or their combination on expressions of ferroptosis proteins, intracellular Fe²⁺, reactive oxygen species (ROS), lipid peroxidation, GSH, mitochondrial membrane potential, and cell viability were evaluated. In the neonatal mouse models of HIBD, FMN treatment significantly suppressed the protein expression of P53, SAT1, and ACSL4, reduced Fe²⁺, ROS, and MDA levels and increased GSH content in the cortical ischemic penumbra. In HT22 neurons with OGD, FMN obviously alleviated OGD-induced ferroptosis as shown by lowered expressions of the key ferroptosis proteins, reduced Fe²⁺ accumulation and lipid peroxidation, and significant increases of GSH levels, mitochondrial membrane potential, and cell viability. Mechanistic experiments showed that activation of P53 signaling by Nutlin-3 markedly reversed the protective effects of FMN. FMN produces neuro-protective effects against HIBD in neonatal mice by mitigating neuronal ferroptosis, primarily through downregulation of the P53/SAT1/ACSL4 signaling pathway. 目的: 探讨刺芒柄花素（FMN）对新生小鼠缺氧缺血性脑损伤（HIBD）的神经保护作用，并阐明其机制是否与调控P53/SAT1/ACSL4信号通路以抑制神经元铁死亡有关。方法: 选取24只出生9~11 d的C57BL/6J新生小鼠，通过结扎左侧颈总动脉并置于低氧环境（92% N2，8% O2）中40 min以构建HIBD模型。造模成功后，将小鼠随机分为4组（n=6）:假手术组（Sham）、模型组（HIBD）、FMN低剂量治疗组（HIBD+FMN-L，50 mg/kg）和高剂量治疗组（HIBD+FMN-H，100 mg/kg）。腹腔注射给药，3 d后取脑皮层缺血半暗带组织进行检测。采用Western blotting和双重免疫荧光技术分析铁死亡通路关键蛋白P53、SAT1及ACSL4的表达水平;同时测定组织内亚铁离子（Fe²+）、超氧化物（DHE）、丙二醛（MDA）和谷胱甘肽（GSH）的含量，以评估铁死亡及相关氧化应激指标。体外选用HT22神经元，建立氧糖剥夺（OGD）模型并分组为:对照组（Control）、模型组（OGD）、FMN干预组（OGD+FMN，100 μmol/L）、P53激动剂Nutlin-3干预组（OGD+Nutlin-3，10 μmol/L）以及FMN与Nutlin-3联合处理组（OGD+FMN+Nutlin-3）。在药物预处理1 h及OGD处理6 h后，检测上述铁死亡相关蛋白，并利用特异性探针或生化方法评估细胞内Fe²+（FerroOrange）、活性氧（DCFH-DA）、脂质过氧化（BODIPY-C11、MDA）、GSH水平、线粒体膜电位（JC-1）及细胞活性（CCK-8）。结果: 体内实验结果表明，与HIBD组相比，FMN治疗能够显著抑制P53、SAT1和ACSL4的蛋白表达（P<0.05），并有效改善铁死亡相关生化指标，具体为Fe²+、ROS和MDA含量显著降低，同时抗氧化物质GSH水平得以恢复（P<0.05）。体外实验结果与体内发现相互印证，FMN处理缓解了OGD诱导的HT22细胞铁死亡，表现为铁死亡关键蛋白表达下调（P<0.05），Fe²+积聚、脂质过氧化和ROS水平受到抑制，并且GSH含量、线粒体膜电位及细胞活力得到显著改善（P<0.05）。机制验证方面，当使用Nutlin-3特异性激活P53信号后，FMN所产生的上述保护效应均被明显逆转或削弱（P<0.05），P53信号在FMN抑制铁死亡过程中发挥重要的上游调节作用。结论: 刺芒柄花素通过下调P53/SAT1/ACSL4通路介导的神经元铁死亡的途径，对新生小鼠HIBD产生神经保护效应。.
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 develop a hollow Cu9S8-based nanoparticles loaded with the photosensitizer IR780, investigate its photothermal and photodynamic (PTT-PDT) effects against esophageal cancer cells and analyze the underlying mechanisms. Hollow Cu9S8 nanoparticles were synthesized using a sacrificial-template strategy, and IR780 was encapsulated within a lauric acid matrix to serve as a phase-change material for preparing IR780@Cu9S8 composite nanoparticles. The composite nanoparticles were characterized for morphology and structural attributes using transmission electron microscopy, X-ray diffraction, and UV-visible spectroscopy. The effects of IR780@Cu9S8 on proliferation, invasion, and migration of esophageal cancer cells under near-infrared (NIR) irradiation (808 nm, 1.5 W/cm², 5 min) were assessed using CCK-8 assay, live/dead staining, reactive oxygen species, mitochondrial membrane potential assay, wound-healing assay, and Transwell assay. The in vivo PTT-PDT therapeutic efficacy and biosafety of IR780@Cu9S8 was evaluated in a mouse model bearing subcutaneous esophageal cancer xenografts. The synthesized IR780@Cu9S8 nanoparticles exhibited a uniform quasi-spherical morphology with a photothermal conversion efficiency of 44.0%. Under NIR irradiation, IR780@Cu9S8 produced pronounced synergistic PTT-PDT effects against KYSE150 cells, causing a significant reduction of cell viability and marked suppression of cell proliferation, migration, and invasion. In the tumor-bearing mice, IR780@Cu9S8 and 808 nm laser irradiation exhibited strong synergistic PTT-PDT effects and significantly inhibited tumor growth with a good biocompatibility. The IR780@Cu9S8 composite nanoparticles achieve synergistic PTT-PDT antitumor activity in esophageal cancer cells which can be a promising strategy for combined therapy and targeted drug delivery for esophageal cancer. 目的: 制备负载光敏剂IR780的中空Cu9S8复合纳米载药系统，探讨其对食管癌光热-光动力（PTT-PDT）的联合治疗效果及潜在作用机制。方法: 采用牺牲模板法制备具有中空结构的Cu9S8纳米颗粒，并利用相变材料月桂酸将光敏剂IR780进行包覆，构建复合纳米颗粒IR780@Cu9S8。通过透射电镜（TEM）、X射线衍射（XRD）、紫外-可见光谱（UV-Vis）等对其形貌与结构进行系统表征。通过CCK-8、细胞活死染色、ROS及线粒体膜电位检测、细胞划痕、Transwell等方法评估其在近红外（808 nm，1.5 W/cm²，5 min）激光照射下对食管癌细胞的增殖、侵袭、迁移等恶性行为的影响。通过构建小鼠食管癌同种移植模型，进一步评估IR780@Cu9S8复合纳米颗粒在体内PTT-PDT联合抗肿瘤疗效及生物安全性。结果: 本研究制备的IR780@Cu9S8复合纳米颗粒呈均一空心类球形结构，光热转换效率约为44.0%。在近红外照射下，IR780@Cu9S8可实现显著的PTT-PDT协同抗肿瘤疗效，KYSE150细胞活力下降（P<0.001），增殖、迁移和侵袭能力也得到抑制（P<0.001）。体内实验同样表明其可在808 nm激光照射后，具有PTT与PDT协同增效，可抑制荷瘤小鼠肿瘤体积的生长（P<0.001），同时具有良好的生物相容性。结论: IR780@Cu9S8复合纳米颗粒通过整合PTT与PDT的优势，实现光动力与光热效应的协同抗肿瘤作用，为食管癌的联合治疗及靶向药物递送研究提供了新策略。.
To investigate the mechanism by which Qingda Granules (QDG) inhibit apoptosis of hypertensive cerebral microvascular endothelial cells. Eighteen C57BL/6 mice were randomized into control group, angiotensin II (AngII) group, and Ang II+QDG group (n=6). The mice in the latter groups underwent subcutaneous implantation of a micropump for continuous infusion of Ang II (1000 ng·kg-1·min-1) to induce cerebral small vessel disease (CSVD) with daily gavage of saline or QDG (1.3 g/kg) for 4 weeks. Blood pressure of the mice was monitored weekly, cerebral microvascular morphology was assessed with HE staining, and the expressions of CD31, p53, cleaved caspase-3, cleaved caspase-9, Bcl-2 and Bax in the brain tissues were detected with immunohistochemistry and Western blotting. In a bEnd.3 cell model of oxygen and glucose deprivation/reoxygenation (OGD/R), the effects of QDG on cell viability and apoptosis were evaluated using CCK8 assay and Hoechst 33342 staining, respectively; the changes in mRNA expressions of P53, Bcl-2, and Bax and protein expressions of P53, Bcl-2, Bax, cleaved caspase-3 and cleaved caspase-9 were detected using RT-qPCR and Western blotting. Continuous infusion of Ang II resulted in significant elevation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the mice, causing also widening of the perivascular space of the cerebral microvasculature, reduction of CD31 and Bcl-2 expressions, and increases in the expressions of p53, Bax, cleaved caspase-3, and cleaved caspase-9. All these changes were significantly mitigated by treatment with QDG. In bEnd.3 cells, QDG treatment significantly attenuated OGD/R-induced apoptosis, increased Bcl-2 expression, and decreased expressions of P53, Bax, cleaved caspase-3, and cleaved caspase-9. QDG suppress apoptosis of cerebral microvascular endothelial cells in hypertensive rats by downregulating the P53 signaling pathway to alleviate cerebral microvascular endothelial injury caused by hypertension. 目的: 基于P53信号通路探讨清达颗粒 （QDG） 抑制高血压脑微血管内皮细胞凋亡的作用机制。方法: 利用血管紧张素Ⅱ（AngⅡ）构建高血压脑小血管病（CSVD）小鼠模型，分为Control组、AngⅡ组、AngⅡ+QDG组，6只/组，AngⅡ剂量为1000 ng/kg/min。造模后第1天开始给药，AngⅡ+QDG组给予清达颗粒（1.3 g/kg/d）灌胃，对照组和AngⅡ组给予生理盐水灌胃，1次/d，连续灌胃4周。每周用无创血压测量系统测量各组血压。利用HE染色观察脑微血管病理变化，免疫组化检测CD31、P53、cleaved caspase-3、cleaved caspase-9的表达;Western blotting检测Bcl-2、Bax的表达。利用氧糖剥夺再灌注（OGD/R）构建小鼠脑微血管内皮细胞 （bEnd.3） 损伤模型，将细胞分为Control组、QDG组、OGD/R组、OGD/R+QDG组。利用CCK-8确定细胞给药浓度;利用Hoechst 33342染色检测细胞凋亡，RT-qPCR检测P53、Bcl-2、Bax mRNA的表达，利用Western blotting检测P53、Bcl-2、Bax、cleaved caspase-3、cleaved caspase-9的表达。结果: 体内实验中，与Control组比较，AngⅡ组小鼠的收缩压、舒张压及平均动脉压均升高（P<0.05），脑微血管周围间隙增大，CD31、Bcl-2的表达降低，P53、Bax、cleaved caspase-3、cleaved caspase-9的表达升高（P<0.05）。与AngⅡ组比较，清达颗粒能降低高血压小鼠的收缩压、舒张压及平均动脉压的升高（P<0.05），改善高血压小鼠脑微血管的病理损伤，升高CD31、Bcl-2的表达（P<0.05），降低P53、Bax、cleaved caspase-3、cleaved caspase-9的表达（P<0.05）。在体外实验中，与Control组比较，OGD/R组的凋亡率升高，Bcl-2 mRNA表达降低，P53、Bax mRNA表达升高（P<0.05）;Bcl-2 蛋白表达降低，P53、Bax、cleaved caspase-3、cleaved caspase-9 蛋白表达升高（P<0.05）;与OGD/R组比较，清达颗粒能降低OGD/R诱导的bEnd.3细胞凋亡率，升高Bcl-2的mRNA表达，降低P53、Bax的mRNA表达（P<0.05）;升高Bcl-2的蛋白表达，降低P53、Bax、cleaved caspase-3、cleaved caspase-9的蛋白表达（P<0.05）。结论: 清达颗粒可能通过下调P53信号通路，抑制高血压脑微血管内皮细胞凋亡。.
To investigate the effect of niranthin (Nir) in mice with Crohn's disease (CD)‑like colitis and its therapeutic mechanism. In a mouse model of CD-like colitis induced using 2,4,6-trinitrobenzene sulfonic acid, the effects of niranthin on colitis symptoms were evaluated by measuring changes in disease activity index (DAI) score, body weight, colon length, and colonic pathologies. Intestinal barrier function and cell apoptosis were evaluated using AB-PAS staining, immunofluorescence staining, Western blotting, and TUNEL staining. The changes in Th1 and Th2 cells in the mesenteric lymph nodes and colonic TNF-α and IL-10 expression levels were determined with flow cytometry and ELISA. In lipopolysaccharide (LPS)-induced mouse colon organoids, the effects of niranthin on organoid budding number and barrier protein expressions were observed. Network pharmacology and in vivo experiments were employed to explore and verify the therapeutic mechanism of niranthin on colitis. In the mouse models of CD-like colitis, niranthin treatment obviously improved weight loss, DAI scores, and colorectal shortening and significantly reduced tissue inflammation scores, goblet cell loss, and intestinal epithelial cell apoptosis. Niranthin significantly increased the budding number in LPS-induced mouse colon organoids. In both mouse colon tissues and LPS-induced mouse colon organoids, niranthin obviously increased the expressions of ZO-1 and claudin-1, downregulated the expressions of cleaved caspase-3 and BAX, and upregulated Bcl‑2 expression. The niranthin-treated mouse models showed significantly ameliorated Th1/Th2 imbalance in the mesenteric lymph nodes, downregulated TNF‑α and upregulated IL‑10 levels in the colon tissues. Network pharmacology predicted that the therapeutic mechanism of niranthin for CD-like colitis involved the PI3K/AKT pathway, which was validated in the mouse models treated with niranthin and the PI3K/AKT pathway activator Recilisib. Niranthin ameliorates colitis in mice by antagonizing epithelial apoptosis and regulating Th1/Th2 balance via inhibiting the PI3K/AKT pathway. 目的: 探究珠子草素（Nir）对克罗恩病样结肠炎的作用与机制。方法: 建立2，4，6-三硝基苯磺酸（TNBS，2.5%）诱导的结肠炎小鼠模型，通过疾病活动度活动（DAI）评分、体质量改变、结肠长度、病理学检测评估结肠炎症状改变，AB-PAS、免疫荧光和免疫印迹评估肠屏障功能，TUNEL染色和免疫印迹评估细胞凋亡，流式细胞术分析肠系膜淋巴结中T淋巴细胞亚群（Th1/Th2）变化;ELISA检测TNF-α和IL-10表达水平变化。体外实验采用脂多糖诱导小鼠结肠类器官炎症模型，检测类器官出芽数及屏障蛋白表达。通过网络药理学和体内实验探索验证Nir拮抗结肠炎的潜在机制。结果: 体内实验显示，Nir可改善TNBS诱导结肠炎小鼠体质量下降、DAI升高、结直肠缩短等表型，降低组织炎症评分，减少杯状细胞丢失（P<0.05）及肠上皮凋亡细胞数量。体外实验表明，Nir能增加结肠类器官出芽数目（P<0.05）。免疫荧光和免疫印迹证实，Nir可恢复体内外实验结肠组织紧密连接蛋白（ZO-1、claudin-1）水平，下调促凋亡蛋白C-caspase3和BAX表达，上调抗凋亡蛋白Bcl-2（P<0.05）;流式细胞术显示，Nir可降低小鼠肠系膜淋巴结Th1比例，升高Th2比例，改善Th1/Th2失衡，同时下调结肠组织TNF-α、上调IL-10水平（P<0.05）;网络药理学预测Nir作用与PI3K/AKT通路相关;免疫印迹发现，Nir可下调p-PI3K、p-AKT和p-p65表达（P<0.05）。并且PI3K/AKT通路激活剂Recilisib可逆转Nir拮抗肠上皮细胞凋亡和调节Th1/Th2平衡的作用。结论: Nir通过拮抗肠上皮细胞凋亡与调控Th1/Th2平衡来改善克罗恩病样结肠炎，其作用机制与抑制PI3K/AKT通路活性，进而调控下游凋亡信号和炎症免疫分子表达有关。.
To evaluate the regulatory effects of Zhizichi Decoction on tryptophan metabolism, inflammation, and neurotrophic factor-related signaling pathways and its potential antidepressant effects in a rat model of depression induced by chronic unpredictable mild stress (CUMS). Adult male SD rat models of CUMS-induced depression were randomized into CUMS model group, fluoxetine group, low-dose Zhizichi Decoction group (LZZCD), and high-dose Zhizichi Decoction group (HZZCD) (n=10), with another 10 normal rats as the control group. After modeling, the rats received daily drug interventions via gavage for 4 weeks. Forced swimming test, tail suspension test, and voluntary activity recording were used to assess depressive-like behaviors of the rats. HE staining, Western blotting and ELISA were used to evaluate the changes in brain tissue pathologies, tryptophan metabolism, neurotransmitter levels, inflammation and brain-derived neurotrophic factor (BDNF)-related pathways of the rats. The rat models with CUMS showed significantly increased immobility and reduced swimming and struggling time. Both fluoxetine and Zhizichi Decoction at the two doses markedly alleviated depressive-like behaviors of the rat models, and high-dose Zhizichi Decoction produced the strongest ameliorating effect. Zhizichi Decoction treatment reduced brain injury scores of the rats, upregulated TPH2 and downregulated IDO, KMO, and MAO-A expressions in the hippocampus, causing also inhibition of the NF‑κB/NLRP3 pathway and increased hippocampal expressions of TrkB, p-CREB, p-AKT, and p-ERK. ELISA results demonstrated that Zhizichi Decoction treatment increased Trp, 5-HT, and 5-HIAA levels, decreased the levels of Kyn and inflammatory cytokines, and upregulated BDNF expression in the hippocampus of the rat models. Zhizichi Decoction alleviates depressive-like behaviors and brain pathologies in CUMS rats by regulating tryptophan metabolism, enhancing synthesis and reducing degradation of neurotransmitters, inhibiting inflammatory response, and upregulating the BDNF signaling pathway. 目的: 探讨栀子豉汤对慢性不可预见轻度应激（CUMS）大鼠抑郁症模型中色氨酸代谢途径、炎症相关信号通路和神经营养因子相关信号通路的调节作用，并评估其抗抑郁潜力。方法: 选用健康成年雄性SD大鼠建立CUMS模型，随机分为5组（n=10）:正常对照组、模型组、氟西汀组、栀子豉汤低剂量组和高剂量组。各组在建模后接受相应药物干预，持续4周。通过强迫游泳实验（FST）、悬尾实验（TST）、自愿活动记录、HE染色及组织损伤评分、Western blotting和ELISA检测，评估栀子豉汤对大鼠抑郁样行为、脑组织病理学、色氨酸（Trp）代谢、神经递质水平、炎症及脑源性神经营养因子（BDNF）相关通路的影响。结果: 与正常组相比，模型组不动时间延长，游泳和挣扎时间缩短（P<0.01）;与模型组相比，氟西汀组及栀子豉汤各剂量组均显著改善（P<0.01），高剂量组效果最显著（P<0.05）。HE染色显示，栀子豉汤降低脑组织损伤评分（P<0.01）。Western blotting显示，栀子豉汤上调TPH2并下调IDO、KMO、MAO-A（P<0.01），抑制NF-κB/NLRP3炎症通路并上调TrkB、p-CREB、p-AKT、p-ERK（P<0.01）。ELISA结果显示，栀子豉汤显著升高Trp、5-羟色胺、5-羟吲哚乙酸水平，降低犬尿氨酸及炎症因子肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）（P<0.01），并上调BDNF表达（P<0.01）。结论: 栀子豉汤通过调节色氨酸代谢途径、神经递质代谢（促进合成并减少分解）、炎症反应及BDNF信号通路，从而缓解CUMS大鼠的抑郁样行为和改善脑组织病理学损伤，具有潜在的抗抑郁作用。.
To explore the targets and molecular mechanisms mediating the inhibitory effect of myricetin against bladder cancer. The potential targets of myricetin were predicted using SwissTargetPrediction and SEA Search Server, bladder cancer-related targets were screened from TCGA transcriptome and FinnGen plasma proteome data, and the intersecting genes were obtained to identify the potential targets. A protein-protein interaction network was constructed, followed by GO and KEGG enrichment analyses. Molecular docking and dynamics simulations were performed to validate the binding between myricetin and the core targets. Amino acid residue virtual mutation was conducted to confirm the binding specificity of myricetin to HSP90AA1. Public single-cell transcriptomic and CRISPR screening data were analyzed to evaluate the cell-type specificity and functional essentiality of HSP90AA1. UM-UC-3 cells were used to examine the effects of myricetin on cell proliferation and migration and expressions of HSP90AA1 and PI3K-AKT pathway proteins. Thirty potential targets of myricetin against bladder cancer were obtained, and HSP90AA1 was identified as the central target. KEGG analysis indicated significant enrichment of the target genes in the PI3K-AKT signaling pathway. Molecular docking and dynamics simulations demonstrated high binding affinity and stable conformation between myricetin and HSP90AA1. Bioinformatics analysis suggested that HSP90AA1 was highly and specifically expressed in bladder cancer urothelial cells, and its high expression was correlated with poor progression-free survival of the patients. In UM-UC-3 cells, myricetin concentration-dependently inhibited cell proliferation and migration, and downregulated mRNA level of HSP90AA1 and protein expressions of HSP90AA1, p-PI3K, and p-AKT. Myricetin inhibits bladder cancer cell proliferation and migration possibly by targeting HSP90AA1 and regulating the PI3K-AKT signaling pathway, suggesting its potential as a therapeutic agent for bladder cancer. 目的: 基于网络药理学、计算生物学及体外实验，系统筛选并验证杨梅酮抑制膀胱癌的潜在作用靶点及其分子机制。方法: 通过Swiss Target Prediction与SEA Search Server平台预测杨梅酮作用靶点，基于TCGA转录组数据与FinnGen血浆蛋白质组数据筛选膀胱癌相关靶点，取交集获得杨梅酮抗膀胱癌潜在靶点，构建蛋白质相互作用网络，进行GO与KEGG富集分析。采用Discovery Studio 2019进行分子对接与分子动力学模拟验证杨梅酮与核心靶点的结合能力与稳定性。通过氨基酸残基虚拟突变验证杨梅酮特异性结合HSP90AA1。通过公开单细胞转录组数据及CRISPR筛选数据，分析核心靶点HSP90AA1在膀胱癌中的细胞特异性与功能必要性。采用CCK-8、克隆形成、划痕实验、qRT-PCR及Western blotting等方法，在UM-UC-3细胞中验证杨梅酮对细胞增殖、迁移能力的影响，并检测其对HSP90AA1及PI3K-AKT信号通路关键蛋白表达的调控作用。结果: 共筛选出30个杨梅酮抗膀胱癌潜在靶点，其中HSP90AA1被确定为最核心的靶点。KEGG富集分析提示这些基因显著富集于PI3K-AKT信号通路。分子对接与动力学模拟表明，杨梅酮与HSP90AA1蛋白具有较高的结合亲和力与稳定的结合构象。生物信息学分析显示，HSP90AA1在膀胱癌尿路上皮细胞中特异性高表达，是膀胱癌细胞的潜在治疗靶点，且其高表达与不良无进展生存期（PFS）显著相关。体外实验显示，杨梅酮可浓度依赖性地抑制UM-UC-3细胞的增殖与迁移（P<0.05），并下调HSP90AA1 mRNA及HSP90AA1、p-PI3K、p-AKT蛋白表达水平（P<0.05）。结论: 杨梅酮可能通过特异性靶向HSP90AA1，调控PI3K-AKT信号通路，从而抑制膀胱癌UM-UC-3细胞的增殖与迁移能力。.
To adapt the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA) to Chinese cultural contexts and assess its reliability and validity among Chinese adolescents. A total of 2103 vocational high school students (917 males and 1186 females; mean age 16.73±1.24 years) in Guangdong Province completed an online survey using the LSAS-CA. Item analysis and psychometric evaluations were conducted. The concurrent validity of the scale was assessed using the Social Anxiety Scale for Adolescents (SAS-A), Patient Health Questionnaire (PHQ-9), and Post-Event Processing Inventory-Trait (PEPI-T), and its discriminant validity was examined using the Rosenberg Self-Esteem Scale (RSES). Three months later, 210 of the students were retested to examine the test-retest reliability of LSAS-CA. The Chinese LSAS-CA retained 24 items (12 social interaction and 12 performance situations) for assessing anxiety and avoidance with a total of 48 scored responses. Confirmatory factor analysis was used for comparing fitting of 4 competing models (unidimensional, two-factor, bifactor, and higher-order models), and the bifactor model showed the best fit: anxiety bifactor model (χ²=3168.263, df=224, χ²/df=14.144, RMR=0.022, GFI=0.875, AGFI=0.832, PGFI=0.653, NFI=0.931, TLI=0.921, CFI=0.936, and RMSEA=0.079); avoidance bifactor model (χ²=3144.601, df=216, χ²/df=14.558, RMR=0.019, GFI=0.875, AGFI=0.826, PGFI=0.630, NFI=0.944, TLI=0.933, CFI=0.948, and RMSEA=0.080). The revised Chinese version of LSAS-CA has acceptable reliability and validity in the context of Chinese culture and provides a more convenient measurement tool for Chinese researchers to study adolescent social anxiety. 目的: 修订适合中国文化背景下使用的Liebowitz儿童和青少年社交焦虑量表（LSAS-CA），检验其在中国青少年中的信效度。方法: 使用LSAS-CA对广东省某职业高中的2103名学生（男生917人，女生1186人，平均年龄16.73±1.24岁）进行线上问卷调查，并进行项目分析和信效度检验;同时采用青少年社交焦虑量表（SAS-A）、病人健康问卷（PHQ-9）和特质性事后加工过程量表（PEPI-T）作为效标效度;采用自尊量表（RSES）进行区分效度检验。3个月后对其中210名学生重测，检验LSAS-CA的重测信度。结果: 中文版LSAS-CA共24个条目，包括12个社交互动情景和12个表现情景，分别评定焦虑和回避程度，共48个评分项。通过验证性因子分析，比较4个竞争模型（单维、双维、双因子模型以及高阶因子模型）的拟合情况。双因子模型更能解释量表结构:焦虑因子（χ²=3168.263，DF=224，χ²/DF=14.144，RMR=0.022，GFI=0.875，AGFI=0.832，PGFI=0.653，NFI=0.931，TLI=0.921，CFI=0.936，RMSEA=0.079）和回避因子（χ²=3144.601，DF=216，χ²/DF=14.558，RMR=0.019，GFI=0.875，AGFI=0.826，PGFI=0.630，NFI=0.944，TLI=0.933，CFI=0.948，RMSEA=0.080）模型拟合指数均尚可接受。结论: 本研究修订的中文版LSAS-CA在中国文化背景下表现出可接受的信效度，为国内学者研究青少年社交焦虑提供了更加便捷的测量工具，以促进研究进展与干预实践。.
To explore the regulatory effects of 3 Astragalus herb pairs (Astragalus-Salvia miltiorrhiza, Astragalus-Rehmannia glutinosa, and Astragalus-Dioscorea opposita) in QidanDihuang Granule on PTGS2-mediated lipid peroxidation in mice with diabetic kidney disease (DKD). Network pharmacology was used to screen active components and targets of Astragalus membranaceus, Salvia miltiorrhiza, Rehmannia glutinosa, and Dioscorea opposita in Qidan Dihuang Granule to construct herb pair-active component-target networks, followed by intersection analysis with DKD-related targets for PPI network construction and enrichment analysis. Molecular docking was used to verify the binding of the key active components to PTGS2. In 25 C57BL/6J mouse models of streptozotocin-induced DKD, the therapeutic effects of treatments with saline, irbesartan, and the 3 Astragalus herb pairs (n=5) for 8 weeks were tested, with 5 normal mice serving as the control group. Network pharmacology showed extensive intersections between the active components of each herb pair and DKD-related targets, with PTGS2 as the key target. The major active components exhibited good binding affinity to PTGS2. The DKD mouse models in Astragalus-Salvia miltiorrhiza and Astragalus-Rehmannia glutinosa groups, particularly those in the former group, showed significant improvements in body weight, fasting blood glucose, serum creatinine, urea nitrogen, and 24-h urinary albumin. The Astragalus-Dioscorea opposita pair only slightly improved blood glucose and creatinine without improving urea nitrogen or urinary albumin in the mouse models. The Astragalus-Salvia miltiorrhiza pair, but not the other two pairs, markedly reduced the elevation of PTGS2 expression, significantly enhanced SOD activity, reduced MDA content, and upregulated GPX4 expression in the mouse models, and the therapeutic effect was only moderate in Astragalus-Rehmannia glutinosa group and the poorest in Astragalus-Dioscorea opposita group. The 3 Astragalus herb pairs from Qidan Dihuang Granule can improve DKD in mice by reducing PTGS2-mediated lipid peroxidation, and the Astragalus-Salvia miltiorrhiza pair shows the strongest efficacy. 目的: 探究芪丹地黄颗粒中不同黄芪药对（黄芪丹参药对、黄芪地黄药对、黄芪山药药对）调节糖尿病肾病（DKD）小鼠PTGS2介导的脂质过氧化的不同影响。方法: 通过网络药理学方法筛选芪丹地黄颗粒中黄芪、丹参、生地黄和山药的活性成分及其作用靶点，构建药对-有效成分-靶点网络，并与DKD相关靶点进行交集分析，构建PPI蛋白互作网络和富集分析。利用分子对接技术验证关键活性成分与PTGS2的结合能力。通过动物实验评估不同黄芪药对对DKD小鼠的影响。30只小鼠随机分为6组（n=5），包括正常对照组、模型组、厄贝沙坦组（50 mg/kg/d）及3个黄芪药对组（黄芪丹参、黄芪地黄、黄芪山药，给药剂量均为6 g/kg/d）。除正常组外，其余各组采用链脲佐菌素（50 mg/kg）诱导DKD模型，造模成功后给予相应药物干预8周。结果: 网络药理学结果显示芪丹地黄颗粒中各药对的活性成分与DKD相关靶点存在广泛交集，PTGS2为关键靶点。主要活性成分与PTGS2具有良好的结合亲和力。与模型组相比，黄芪-丹参组和黄芪-地黄组小鼠的体质量、空腹血糖、血清肌酐、尿素氮和24 h尿白蛋白水平改善（P<0.05），其中黄芪-丹参组改善最显著;而黄芪-山药组仅在血糖和肌酐水平方面有轻微改善（P<0.05），对尿素氮和尿白蛋白无统计学差异（P>0.05）。PTGS2蛋白表达在模型组升高（P<0.01），黄芪-丹参组显著下调其表达（P<0.01）。黄芪-丹参组显著提高SOD活性（P<0.01），降低MDA含量（P<0.01）并上调GPX4表达（P<0.01）;黄芪-地黄组改善作用相对较弱，黄芪-山药组效果最差。结论: 芪丹地黄颗粒中3个黄芪药对可在一定程度上通过PTGS2介导的脂质过氧化改善糖尿病肾病，其中黄芪丹参药对效果最为显著。.
To evaluate the efficacy and safety of Q-switched Nd:YAG 1064 nm laser and topical 30% metformin lotion for treatment of chloasma in mice and explore the possible therapeutic mechanism of topical metformin for chloasma. Forty female healthy Kunming mice were randomly divided into normal group (n=16) and chloasma model group (n=24), and the latter group was further divided into control, laser treatment, metformin lotion treatment, and laser with metformin (Laser+Met) treatment groups (n=6). Chloasma was induced in the mouse models by medium-wave ultraviolet irradiation and intramuscular injection of progesterone. After 4 weeks of treatment, melanocyte count, melanin and tyrosinase activities of the mice were detected using immunohistochemistry and Western blotting, and the mRNA expressions of CRE/MITF signaling pathway-related proteins were detected with quantitative real-time PCR. The mouse models of chloasma receiving Laser+Met treatment had the lowest recurrence rate among the groups. After 4 weeks of treatment, melanocyte count and melanin and tyrosinase expressions, protein expressions of melanin and tyrosinase, and mRNA expressions of CREB1 and MITF in laser, metformin lotion, and Laser+Met groups were significantly reduced compared with those in the control group. Laser treatment and metformin lotion alone produced similar therapeutic effects in the mouse models, and the combined treatment achieved significantly better effects than either of them. Q-switched Nd:YAG 1064 nm laser combined 30% metformin lotion effectively shortens the treatment course and reduces recurrence rate of chloasma in mice with a good safety profile. The therapeutic effect of metformin lotion is mediated possibly by regulation of the cAMP/MITF signaling pathway and reduction of melanin and tyrosinase synthesis. 目的: 探讨Q开关Nd:YAG 1064 nm激光联合局部外用30%二甲双胍洗剂治疗黄褐斑小鼠模型的有效性及安全性，并初步探索外用二甲双胍治疗黄褐斑的可能机制。方法: 本研究以中波紫外线照射及黄体酮肌注建立黄褐斑小鼠模型。共选取SPF级雌性健康昆明小鼠40只将其随机分为两组，正常组16只，模型组24只;随后将24只模型组小鼠随机分成对照组（Control）、激光组（Laser）、二甲双胍组（Met）、激光联合二甲双胍组（Laser+Met），每组6只，各组疗程均为4周。通过免疫组化、蛋白质印迹法检测黑素细胞数量、黑色素及酪氨酸酶活性。采用实时荧光定量PCR法检测各组小鼠皮肤组织中CREB/MITF信号通路相关蛋白表达水平。结果: 治疗后，Laser+Met组小鼠复发率显著低于Met组、Laser组、Control组（χ2=8.914，P=0.03）;治疗4周后，免疫组化结果显示，与对照组相比较，激光组、二甲双胍组、联合组小鼠黑素细胞个数、黑色素及酪氨酸酶表达均明显降低（P<0.001）;其中，激光组与二甲双胍组之间差异无统计学意义（P>0.05），联合组与激光组、二甲双胍组之间差异有统计学意义（P<0.001）。蛋白质印迹法结果显示，与对照组相比较，激光组、二甲双胍组、联合组小鼠黑色素及酪氨酸酶蛋白表达均明显降低（P<0.001）;其中，激光组与二甲双胍组之间差异无统计学意义（P>0.05），联合组与激光组、二甲双胍组之间差异有统计学意义（P<0.001）。qRT-PCR结果显示，与对照组相比较，激光组、二甲双胍组、联合组小鼠CREB1、MITF表达均明显降低（P<0.001）;其中，激光组与二甲双胍组之间差异无统计学意义（P>0.05），联合组与激光组、二甲双胍组之间差异有统计学意义（P<0.001）。结论: Q开关Nd:YAG 1064 nm激光联合30%二甲双胍洗剂治疗黄褐斑小鼠，能够有效缩短治疗疗程，降低其复发率，安全性较高;其治疗机制可能与调控cAMP/MITF信号通路进而减少皮肤中的黑色素和酪氨酸酶合成有关。.
To screen key genes related to efferocytosis in osteoarthritis (OA) based on bioinformatics and machine learning methods, and explore their diagnostic value, immune microenvironment characteristics, and potential therapeutic targets of traditional Chinese medicines (TCM). OA-related datasets GSE55235, GSE55457, and GSE117999 were obtained from the GEO database. An efferocytosis-related gene set was retrieved from GeneCards. Differential expression analysis was performed to identify OA-related differentially expressed genes (DEGs) and their intersection with efferocytosis-related genes, followed by GO and KEGG enrichment analyses. Three machine learning algorithms (Random Forest, LASSO regression, and SVM) were used to screen feature genes, and their diagnostic efficacy was evaluated using ROC curves. qRT-PCR was used to validate the feature gene expressions in a rat OA model. Immune cell infiltration was analyzed using CIBERSORT, GSEA was used to explore the related pathways, and the Coremine database was utilized to predict TCMs associated with the feature genes. A total of 959 OA-related DEGs were identified, including 15 efferocytosis-related genes, which were enriched in leukocyte migration, extracellular matrix, and inflammatory pathways. Machine learning identified 3 feature genes, namely UCP2, EGLN3, and IL1B, which showed good diagnostic performance in both the training (GSE55235) and validation sets (GSE55457 and GSE117999) and varying expression patterns in the mouse models. Immune infiltration analysis showed significant differences in resting mast cells, resting memory CD4⁺ T cells, and activated mast cells between OA patients and healthy controls. The feature genes were closely associated with the adipocytokine signaling pathway, sulfur metabolism, and spliceosome pathway. A total of 100 TCMs were predicted, which were primarily herbs for tonifying deficiency, clearing heat, and promoting blood circulation, such as Lycium barbarum, Epimedium brevicornu, Rehmannia glutinosa, Sophora flavescens, Ligusticum chuanxiong, and Achyranthes bidentata. Efferocytosis-related genes play important roles in OA pathogenesis. UCP2, EGLN3, and IL1B have diagnostic value for OA. The predicted TCMs may serve as potential agents for OA prevention and treatment. 目的: 基于生物信息学与机器学习法，筛选骨关节炎中与胞葬作用相关的关键基因，探讨其诊断价值、免疫微环境特征及潜在中药治疗靶点。方法: 从GEO数据库获取骨关节炎数据集GSE55235、GSE55457和GSE117999，其中GSE55235作为训练集，GSE55457和GSE117999作为验证集。从GeneCards数据库获取胞葬相关基因集。通过差异表达分析筛选骨关节炎差异基因，并与胞葬基因取交集获得胞葬相关差异基因。对差异基因进行GO和KEGG富集分析。采用随机森林、LASSO回归和SVM三种机器学习算法筛选特征基因，并通过ROC曲线评估其诊断效能。通过qRT-PCR实验在大鼠骨关节炎模型中验证特征基因表达，利用CIBERSORT解析免疫细胞浸润情况，采用GSEA分析特征基因相关通路，运用Coremine数据库预测与特征基因相关的中药。结果: 共筛选出959个OA差异基因，其中15个与胞葬作用相关。GO和KEGG分析显示这些基因主要富集于白细胞迁移、细胞外基质、炎症通路等。机器学习筛选出UCP2、EGLN3和IL1B三个特征基因，其在训练集和验证集中均表现出良好的诊断能力。qRT-PCR显示部分特征基因表达趋势存在差异（P<0.05）。免疫浸润分析显示静止肥大细胞、休眠记忆CD4+ T细胞和活化的肥大细胞在骨关节炎患者和健康人群的浸润差异显著（P<0.05）。GSEA提示特征基因与脂肪细胞因子信号通路、硫代谢和剪接体通路密切相关。中药预测获得100味中药，以补虚、清热、活血化瘀类为主，包括枸杞子、淫羊藿、生地黄、苦参、川芎、牛膝等。结论: 胞葬相关基因在骨关节炎发病中起重要作用，UCP2、EGLN3、IL1B基因对骨关节炎具有诊断价值，预测出的枸杞子、淫羊藿、生地黄、苦参、川芎、牛膝等中药可能是防治骨关节炎的潜在药物。.
To investigate the mechanism by which aerobic exercise improves transverse aortic constriction (TAC)-induced heart failure in mice. Thirty male C57BL/6J mice were randomized into sham-operated group, TAC model group, and TAC with aerobic exercise (TACE) group. The mice in TACE group underwent a 4-week progressive treadmill training starting on day 3 following TAC modeling. Echocardiography and Masson's trichrome staining were used to assess cardiac function and myocardial fibrosis of the mice, respectively, and serum levels of BNP, TNF-α, IL-6, IL-1β, MDA, SOD, and GSH-Px were measured using ELISA. The mRNA and protein expressions of Hippo-YAP pathway components in the myocardial tissue were detected using RT‑PCR and Western blotting, respectively. Bioinformatics analysis was performed to explore the correlations among the measured indicators. Compared with those in TAC group, the mice in TACE group showed significantly reduced heart weight and heart weight/body weight ratio, increased left ventricular ejection fraction, left ventricular fractional shortening, and E/A ratio, reduced myocardial fibrosis, decreased BNP expression in both the serum and myocardial tissue, lowered serum levels of TNF‑α, IL‑6, IL‑1β, and MDA, and increased SOD and GSH-Px activities. The mRNA expressions of Mst1, Lats1, Lats2, and YAP1 were significantly downregulated in TACE group as compared with those in TAC group. Western blotting revealed decreased total protein expressions of Mst1/2, Lats1/2, and YAP and increased expression levels of phosphorylated Lats1/2 and phosphorylated YAP in TACE group. Correlation analysis suggested significant associations of oxidative stress markers and inflammatory factors with the expressions of the Hippo-YAP pathway components. Aerobic exercise improves cardiac function and attenuates cardiac remodeling in mice with TAC-induced heart failure possibly by suppressing oxidative stress and inflammation and modulating the Hippo-YAP pathway. 目的: 探讨有氧运动通过调控氧化应激、炎症与Hippo-YAP信号通路改善主动脉弓缩窄（TAC）诱导心力衰竭的作用机制。方法: 30只C57BL/6J雄性小鼠随机分为假手术组（Sham）、TAC模型组（TAC）及TAC+有氧运动组（TACE），10只/组。TACE组进行4周跑台有氧训练（强度递增）。干预后采用超声心动图评估心功能，Masson染色观察心肌纤维化，ELISA检测血清BNP、炎症因子（TNF-α、IL-6、IL-1β）及氧化应激指标（MDA、SOD、GSH-Px）。RT‑PCR与Western blotting分别检测心肌组织Hippo‑YAP通路相关基因及蛋白表达。通过生物信息学分析各指标相关性。结果: 与TAC组相比，TACE组心脏质量与心质量指数降低（P<0.01），左心室射血分数（LVEF）、左心室缩短分数（LVFS）及E/A比值升高（P<0.05），心肌纤维化减轻（P<0.05），血清与心肌BNP表达下降（P<0.05）。TACE组血清TNF‑α、IL‑6、IL‑1β及MDA水平降低（P<0.05），SOD与GSH‑Px活性升高（P<0.05）。RT‑PCR结果显示，TACE组心肌Mst1、Lats1、Lats2及YAP1 mRNA表达较TAC组下调（P<0.05）。Western blotting结果显示，TACE组心肌Mst1/2、Lats1/2及YAP总蛋白表达降低，而p‑Lats1/2与p‑YAP水平升高（P<0.05）。相关性分析提示氧化应激、炎症指标与Hippo‑YAP通路表达显著相关。结论: 有氧运动可改善TAC诱导的心力衰竭小鼠心功能，减轻心肌肥厚与纤维化，其保护作用可能与抑制氧化应激、炎症反应及调控Hippo‑YAP信号通路有关。.
To investigate the effect of silybin in inhibiting fibrosis after glaucoma filtration surgery and the underlying mechanism. Twenty-five healthy rabbits undergoing unilateral trabeculectomy on the left eye were randomly assigned into 5 groups for treatment with subconjunctival injections of sterilized water (control) or 50, 100, 200, and 250 μmol/L silybin for 7 consecutive days. Postoperative intraocular pressure (IOP) and filtration bleb morphology (Krofeld classification) were monitored. On day 28, tissues samples were harvested from the operated eyes for HE staining, Masson's trichrome staining, and immunofluorescence detection of fibronectin and collagen I. In cultured rabbit Tenon's capsule fibroblasts with TGF‑β1-induced fibrosis, the effects of silybin on autophagy and apoptosis were analyzed using Western blotting (LC3II/LC3I ratio and p62 expression) and flow cytometry. From postoperative day 7 to day 21, the rabbits with silybin treatment showed significantly lower IOP than those in the control group, and in the 200 and 250 μmol/L silybin groups, IOP reduction was maintained up to postoperative day 28. From postoperative day 14 to day 21, silybin dose-dependently increased the formation rate of functional filtering blebs, the 200 and 250 μmol/L silybin groups maintained more than 40% functional filtering blebs from postoperative day 14 to day 28. HE staining revealed obviously lessened inflammatory cell infiltration in silybin treatment groups compared with that in the control group. Masson's trichrome staining showed progressively reduced fibroblast numbers and collagen deposition in the silybin groups. Immunofluorescence staining confirmed that silybin dose-dependently reduced fibronectin and collagen I-positive cells. In cultured rabbit Tenon's capsule fibroblasts, silybin treatment effectively reversed TGF-β1-induced fibroblast fibrotic phenotype, increased the LC3II/LC3I ratio, decreased p62 expression, and promoted apoptosis of the fibroblasts. Silybin significantly inhibits postoperative fibrosis in rabbit models of glaucoma likely by activating cellular autophagy and inducing apoptosis to reduce fibroblast activation. 目的: 探讨水飞蓟宾在抑制青光眼术后纤维化的作用及其分子机制。方法: 体内动物实验:将25只健康新西兰兔随机分为对照组及不同浓度水飞蓟宾实验组（50、100、200、250 μmol/L），5只/组，左眼行小梁切除术后连续7 d进行结膜下注射。术后动态监测眼压和滤过泡形态（Krofeld分型），第28天取术眼组织进行HE、Masson染色，Fibronectin和Collagen I免疫荧光检测。体外实验:通过TGF-β1诱导兔Tenon囊成纤维细胞纤维化模型，结合Western blotting及流式细胞术分析水飞蓟宾对自噬（LC3II/LC3I、p62）与凋亡的调控作用。结果: 术后7~21 d，不同浓度水飞蓟宾实验组兔眼压均低于对照组（P<0.05）。200 μmol/L、250 μmol/L实验组兔眼压降低可维持至术后28 d（P<0.05）。术后14~21 d，随着水飞蓟宾浓度升高，功能性滤过泡数形成率升高（P<0.05），200、250 μmol/L水飞蓟宾组在术后28 d仍保持40%以上的功能性滤过泡（P<0.05）。HE和Masson染色显示，各实验组炎性细胞浸润程度和纤维细胞数量较对照组降低、胶原沉积呈浓度依赖性减少。免疫荧光实验显示，水飞蓟宾呈剂量依赖性减少Fibronectin与Collagen I阳性细胞数量（P<0.001）。体外实验显示，水飞蓟宾逆转TGF-β1诱导的成纤维细胞纤维化表型（P<0.01），上调LC3II/LC3I比值（P<0.0001），降低p62表达（P<0.0001），并促进细胞凋亡（P<0.0001）。结论: 水飞蓟宾可明显抑制青光眼术后纤维化，可能是通过激活细胞自噬及诱导细胞凋亡双重机制减少成纤维细胞活化。.
To investigate the mechanism by which Acorus tatarinowii Schott volatile oil (VOA) alleviates tic disorder (TD) in rats. Forty-eight 3-week-old SD rats were randomly divided into blank group (n=8) and TD model group with intraperitoneal injection of iminodipropionitrile (n=40). The rat models were further randomized into 5 groups (n=8) for treatment with daily gavage of saline (model group), tiapride (47.91 mg/kg) or VOA (51.12 mg/kg), intraperitoneal injection of TAK-242 (a TLR4 inhibitor; 3 mg/kg), or both VOA gavage and TAK242 injection for 28 days. Behavioral changes of the rats were assessed, and Nissl staining was used to observe neuronal morphology in the striatum. The levels of TNF-α, C1q, TGF-β, and VEGF in the serum and striatum were measured using ELISA. The mRNA and protein expressions of TLR4, MyD88, and NF‑κB p65 in the striatum were detected using RT-PCR and Western blotting, and NF‑κB p65 nuclear translocation and expressions of Iba1 (a MG-specific marker), CD86 and CD206 were analyzed using immunofluorescence staining. VOA treatment significantly reduced tic-like behavior scores and ameliorated striatal neuronal damage in the rat models, resulting also in lowered levels of TNF-α and C1q and increased levels of TGF-β and VEGF in both the serum and striatum, decreased mRNA and protein expression levels of TLR4, MyD88, and NF‑κB p65 in the striatum, and reduced nuclear translocation of NF‑κB p65. Immunofluorescence staining revealed significantly weakened expressions of Iba1 and CD86 and enhanced CD206 expression in the striatum of VOA-treated rats. All these ameliorative effects of VOA were significantly attenuated by treatment with TAK-242. VOA alleviates tic symptoms in rats by inhibiting microglia activation and polarization to reduce neuroinflammation possibly through suppression of the TLR4/MyD88/NF-κB signaling pathway. 目的: 探讨石菖蒲挥发油（VOA）通过TLR4/MyD88/NF-κB通路调控小胶质细胞（MG）抗抽动的机制。方法: 48只3周龄SD大鼠，随机分为空白组（n=8）和模型制备组（n=40），采用腹腔注射亚氨基二丙腈诱导TD模型，将模型制备组大鼠随机分为模型组、硫必利组（47.91 mg/kg）、VOA组（51.12 mg/kg）、TAK-242组（3 mg/kg）和VOA+TAK242组（51.12 mg/kg+3 mg/kg），每组8只，1次/d，干预28 d。干预结束后，评估大鼠行为学变化情况，采用尼氏染色观察纹状体神经元形态改变，ELISA法检测大鼠血清、纹状体中TNF-α、C1q、TGF-β、VEGF含量，RT-PCR、Western blotting法检测观察大鼠纹状体中TLR4、MyD88、NF-κB p65的mRNA和蛋白的表达情况，免疫细胞荧光染色检测NF-κB p65入核情况、MG特异性标志物Iba1、M1型、M2型标记蛋白CD86、CD206的表达水平。结果: 与模型组相比较，VOA组大鼠抽动样行为评分降低（P<0.01），纹状体神经元损伤改善;血清及纹状体中TNF-α、C1q水平降低（P<0.01）、TGF-β、VEGF水平升高（P<0.01）;纹状体中TLR4、MyD88、NF-κB p65 mRNA和蛋白相对表达量水平降低（P<0.01），NF-κB p65 入核减少（P<0.05），Iba1、CD86相对荧光强度减弱（P<0.01），Iba1、CD206相对荧光强度增强（P<0.01）。结论: VOA通过降低MG的活化及极化状态，进而抑制脑内炎症水平改善抽动症状，其作用机制可能与抑制TLR4/MyD88/NF-κB通路有关。.