BackgroundPulmonary arterial hypertension (PAH) shows significant clinical variability in older adults. Standard diagnostic methods often detect the disease late, creating a need for multiomics-based biomarker discovery. Integrating these with artificial intelligence (AI) can improve early screening and risk stratification, helping G20 countries tackle public health challenges linked to aging.MethodsUsing Global Burden of Disease 2023 data and multiomics evidence from adults aged 55 and older in G20 nations, we applied machine learning to assess age-sex disease burden patterns. Deep learning models assessed circulating biomarkers-microRNA profiles, plasma proteomic markers (GDNF and GDF-15), and metabolomic signatures-for predicting disease onset and progression across sociodemographic index (SDI) regions.ResultsIn 2023, the age-standardized PAH incidence rate among adults >= 55 in G20 countries was 1.33 per 100,000 people. AI analysis identified exosomal miR-223-3p and mitochondrial metabolic fingerprints as key early-warning signals, accumulating notably in ages 70-74. Elevated GDF-15 and IL-6 were linked to diagnostic delays in low-SDI areas (SHAP weight = 0.24). A metabolomic ratio of dodecatrienoic acid to sphingosine predicted PAH risk in women (AUC = 0.87). An XGBoost model incorporating these biomarkers enabled accurate risk stratification in high-burden countries such as India and Mexico (AUC = 0.92).ConclusionsWe systematically identified and validated novel multiomics biomarkers associated with aging and PAH. These support clinical translation via blood-based diagnostic kits using exosomal miRNA and proteomic markers, individualized prognostic models with metabolomic data, and tailored precision prevention strategies adaptable to diverse health systems-potentially enabling earlier intervention and improved PAH management.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a major global health issue strongly associated with obesity. Available treatments have significant limitations. The traditional Chinese medicine Huatan Qushi Huoxue (HTQSHX) granules represent a potential alternative therapeutic option. This study evaluates their effects and safety in patients with obesity-associated NAFLD.MethodsThis multicenter, randomized, double-blind, placebo-controlled, parallel-group trial recruited 248 patients with obesity-associated NAFLD from three clinical sites. Participants were randomized 1:1 to receive HTQSHX granules or placebo granules for 12 weeks. The primary outcome was the absolute change in hepatic fat fraction from baseline to week 12, as measured by MRI-proton density fat fraction (MRI-PDFF), which is recommended as a primary endpoint in early-phase NAFLD clinical trials for its precision and objectivity. Secondary outcomes included the proportion of patients achieving ≥30% relative reduction in MRI-PDFF-assessed hepatic fat fraction, serum liver enzyme indicators, glucose and lipid metabolism parameters, non-alcoholic steatohepatitis-related serum biomarkers, anthropometric measures, and serum metabolomics analysis.ResultsAmong 228 participants included in the modified intention-to-treat (mITT) analysis, the median hepatic fat fraction decreased from 16.15% at baseline to 12.12% in the HTQSHX group (median change: 3.27%), and from 15.64% to 14.95% in the placebo group (median change: 0.96%). The between-group difference in absolute change was statistically significant (−2.32%; 95% CI, −4.50 to −0.23; P = 0.029). The proportion of patients achieving a ≥30% relative reduction in hepatic fat fraction was significantly higher in the HTQSHX group than in the placebo group (41.23% vs. 20.18%; P < 0.001). The HTQSHX group also showed significantly greater improvements in serum alanine aminotransferase (P = 0.048), aspartate aminotransferase (P = 0.033), free fatty acids (P = 0.026), cytokeratin-18 fragment M30 (P < 0.001), soluble triggering receptor expressed on myeloid cells 2 (P < 0.001) and anthropometric parameters (body mass index, waist-to-hip ratio, body fat percentage). Metabolomics analysis of 30 HTQSHX-treated participants revealed that the formula restored multiple phospholipid levels and reduced markers of oxidative stress and mitochondrial dysfunction, with enrichment in fatty acid and sphingolipid metabolism pathways.ConclusionHTQSHX granules may represent a potentially beneficial therapeutic option for obesity-associated NAFLD, with observed effects including significant reduction in hepatic fat fraction and modulation of lipid metabolism and oxidative stress, alongside an acceptable safety profile. These findings warrant further investigation in longer-term studies.Clinical Trial Registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200060901.

BackgroundHepatitis B remains a global threat with significant disparities. This study provides a comprehensive assessment of its long-term burden, inequalities, and future trajectories to inform elimination strategies.MethodsUsing data from the Global Burden of Disease Study 2021, we analyzed age-standardized rates (ASRs) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We quantified socioeconomic inequalities using the slope index of inequality (SII) and concentration index, and projected future trends to 2035 using Bayesian age-period-cohort modeling.ResultsFrom 1990 to 2021, all ASRs declined annually (1.64%-1.81%). However, an estimated 68.5 million new infections and 291 million prevalent cases persisted in 2021. The burden was heavily concentrated in low-SDI regions (e.g., sub-Saharan Africa) and among males. Inequality analysis revealed narrowing absolute gaps but widening relative inequity. Projections indicate a continued decline in ASRs but a rise in absolute deaths by 2035, driven by an aging cohort with prevalent infections.ConclusionsDeep-seated socioeconomic inequality is the main barrier to elimination. Future efforts must accelerate prevention in high-burden settings while globally scaling up treatment and surveillance to address the legacy of past infections.

Background The global burden of non-alcoholic fatty liver disease (NAFLD) is parallel to the increasing obesity rates around the world. Phlegm stasis syndrome is a common traditional Chinese medicine syndrome type of obese NAFLD, which is often treated by resolving phlegm, dispelling dampness, and promoting blood circulation. This study mainly explores the clinical efficacy and safety of Huatan Qushi Huoxue Fang (HTQSHXF) granules in the treatment of obese NAFLD. Methods This is a multicenter, randomized, double-blind, placebo-controlled clinical trial that will recruit 248 obese NAFLD patients from three hospitals in China. Randomly allocate patients to either the HTQSHXF group or the placebo group in a 1:1 ratio. The intervention phase lasts for 12 weeks. The primary outcome will be the change in relative liver fat content from baseline to week 12 measured by Magnetic resonance proton density fat fraction (MRI-PDFF). The secondary outcomes will be Body fat percentage (BFR), Waist to hip ratio (WHR), Body Mass Index (BMI), Controlled attenuation parameter (CAP), Liver tiffness value (LSM), serum liver function, blood lipids, blood glucose, Free fatty acids (FFA), Cytokeratin 18-M30 (CK18-M30), and Cytokeratin 18-M65 (CK18-M65). The results will be monitored at baseline and 12 weeks of intervention. Adverse events that occur in this study will be promptly managed and recorded. Discussion This study will use more recognized quantitative methods to explore the efficacy and safety of HTQSHXF granules in treating obese NAFLD, providing clinical evidence for its translational application. Trial registration http://www.chictr.org.cn . Trial number: ChiCTR2200060901. Registered on 14 Jun 2022.

The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC). We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability. We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95

Ascites of liver cirrhosis is one of the serious complications of liver cirrhosis, which belongs to the category of "bulging" disease in Chinese medicine, and is one of the four major difficult diseases in Chinese medicine, namely, "wind, consumption, dropsy and diaphragm". At present, modern medicine has a single treatment measure for this disease, and the condition is easy to repeat, with poor prognosis and low quality of life of patients. In this paper, the research progress of Chinese medicine treatment of cirrhosis ascites in recent years is summarised by systematically collating and summarising the relevant literature on Chinese medicine treatment of cirrhosis ascites in recent years, and the research progress of Chinese medicine treatment of cirrhosis ascites in recent years is reviewed in terms of the etiology and pathogenesis of cirrhosis ascites, Chinese medicine internal treatment, Chinese medicine external treatment, and ethnic minority characteristic treatment, so as to provide reference for the subsequent modern clinical treatment of cirrhosis ascites in Chinese medicine.

Objective To investigate the effects of Huazhi Fugan granule on gastrointestinal function and intestinal microflora in mice with diabetic nonalcoholic fatty liver disease. Methods The nonalcoholic fatty liver disease model of spontaneous type 2 diabetes mellitus db/db mice was prepared and randomly divided into control group, model group,Huazhi Fugan granule group, fenofibrate group and cisapride group. Serological indexes detection and intestinal fecal gene sequencing were performed, and the pathological morphology of intestinal tissue was observed. Results Compared with the control group, the levels of total cholesterol（TC）, triglyceride（TG）, low-density lipoprotein cholesterol（LDL-C）, alanine transaminase（ALT） and aspartate transaminase（AST） in the model group increased, while the levels of high-density lipoprotein cholesterol（HDL-C） and insulin decreased; Huazhi Fugan granule had better effect than cisapride in reducing TG, LDL-C, and increasing HDL-C; the levels of ALT and AST in the Huazhi Fugan granule group, fenofibrate group and cisapride group were lower than those in the model group（P＜0.01）; the insulin level in the Huazhi Fugan granule group and fenofibrate group were higher than those in the model group（P＜0.0001）. The results of high-throughput sequencing showed that there were 8 main types of bacteria at the phylum taxonomy level, including Bacteroidota, Firmicutes,Actinobacteria and Verrucomicrobiota. Compared with the control group, the abundance of Bacteroidota in the Huazhi Fugan granule group, fenofibrate group and cisapride group was higher, while the abundance of Firmicutes was lower（P＜0.001）.In the model group, the intestinal tissue structure of mice was disordered, mucosa and submucosa were eroded, ulcers,bleeding and granulation tissue formation were found in severe parts, crypt structure was disordered, cryptitis and crypt abscess were found, glands were irregularly arranged and atrophied, there were a large number of inflammatory cells and granulocyte infiltration, and goblet cell was reduced; the Huazhi Fugan granule group and cisapride group showed varying degrees of improvement in lesions, while the reduction in lesions was not significant in the fenofibrate group. Conclusion Huazhi Fugan granule has certain advantages in reducing blood lipids, protecting liver and lowering enzymes, and improving insulin level, intestinal tissue structure, intestinal function and mucosal barrier.

中医对黄疸的认识由"以湿为主"逐渐发展为"瘀血致黄".薛敬东教授认为湿浊内阻,病久伤及血分,导致瘀血发黄,是黄疸发病的最重要因素,并从复方中药、单味中药进行了相关研究,结合临床提出清热利湿化瘀退黄、温阳燥湿消瘀消黄、滋阴活血利湿祛黄、益气利湿祛瘀退黄、养血和血行瘀退黄等不同从瘀论治的方法,临床治疗也取得了较好疗效.现从"湿瘀互结"阐述黄疸的病因病机、用药遣方特点,介绍薛教授治疗黄疸的经验.

目的:探讨自拟通腑醒脑开窍方中药直肠滴入治疗肝性脑病(HE)的疗效及对炎症因子、预后的影响.方法:选取2019年1月至2020年1月陕西省中医医院肝病科收治的HE患者80例,分为观察组和对照组两组,对照组患者(40例)采用常规治疗,观察组患者(40例)在对照组治疗的基础上联合应用通腑醒脑开窍方保留灌肠治疗,两组均以14 d为一疗程,比较两组总有效率及平均清醒时间,治疗前后数字连接试验完成时间(NCT)、数字符号试验评分(DST)、炎症因子(LPS、TNF-α、IL-6)、肝功能(TBil、ALT、AST)、血氨水平、终末期肝病MELD评分.结果:总有效率观察组为95％(38/40),优于对照组的80.00％(32/40);治疗后观察组患者平均清醒时间显著小于对照组(P＜0.05);治疗后观察组患者NCT-A、LPS、TNF-α、IL-6、TBil、ALT、AST、血氨、MELD评分水平低于对照组(P＜0.05);DST评分观察组高于对照组,差异具有统计数学意义(P＜0.05).结论:应用自拟通腑醒脑开窍方中药直肠滴入治疗肝性脑病临床效确切安全,有助于改善肝功能、降低血氨水平、提高患者预后,值得临床应用及进一步研究.

A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

目的:观察恩替卡韦联合乙转灵治疗乙型肝炎肝纤维化患者中医证候与瞬时弹性扫描(Fibroscan)检测肝脏硬度值(liver stiffness measurement,LSM)之间的相关性.方法:将80例乙型肝炎肝纤维化患者按单盲随机方法分成对照组和观察组,每组各40例,对照组予以恩替卡韦分散片治疗24周,观察组在对照组治疗基础上给予乙转灵片治疗24周,所有患者均整理中医证候积分和Fibroscan检测结果,按肝肾亏损、脾虚挟瘀型中医辨证标准进行分型,同时用LSM值的形式来表达肝脏瞬时弹性硬度值,并且分析中医证候与肝脏瞬时弹性硬度LSM值二者之间的关系.结果:观察组治疗12、24周时LSM值较治疗前显著下降(P＜0.05);对照组治疗24周时LSM值较治疗前明显下降(P＜0.05);与对照组比较,观察组12、24周时LSM值明显降低(P＜0.05);治疗24周时,观察组LSM值与中医证候积分均明显降低,且总有效率越高,LSM值越低.结论:恩替卡韦联合乙转灵治疗乙型肝炎肝纤维化患者疗效满意,且乙型肝炎肝纤维化患者Fibroscan检测LSM值与中医证候积分、总有效率之间存在相关性,且具有一致性,可判断肝纤维化病情,评估治疗效果,对肝纤维化诊治具有重要的临床意义.

目的 探讨泽茵丸联合常规西药治疗湿浊阻滞、瘀血内结型非酒精性脂肪性肝病(NAFLD)的效果.方法 选取 2020 年 1 月至2021 年 12 月陕西省中医医院肝病科收治的 86 例湿浊阻滞、瘀血内结型NAFLD患者为研究对象,按照随机数字表法将其分为对照组与观察组,各 43 例.对照组采用常规西药治疗,观察组在对照组基础上加泽茵丸治疗.比较两组的临床效果.结果 观察组的治疗总有效率高于对照组,差异具有统计学意义(P＜0.05).治疗后,观察组的超氧化物歧化酶(SOD)水平高于对照组,丙二醛(MDA)、乳酸脱氢酶(LDH)水平低于对照组,差异具有统计学意义(P＜0.05).治疗后,观察组的脂多糖结合蛋白(LBP)、瘦素(LEP)水平低于对照组,脂联素(ADPN)水平高于对照组,差异具有统计学意义(P＜0.05).结论 泽茵丸联合常规西药治疗湿浊阻滞、瘀血内结型NAFLD的效果满意,可调节SOD、MDA、LDH、LBP、LEP、ADPN水平,值得推广.

BACKGROUND AND STUDY AIM The mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms. MATERIALS AND METHODS A model of NAFLD-HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT-PCR were performed to analyze protein expression and measure mRNA expression levels, respectively. RESULTS Scoparone could ameliorate the pathological alterations observed in NAFLD-HCC mouse model. IHC analysis indicated an upregulation of NF-κB p65 expression in both NAFLD and NAFLD-HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF-κB target genes, including TNF-α, MCP-1, iNOS, COX-2, NF-κB, and MMP-9, which were originally elevated in the NAFLD-HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD-HCC model. CONCLUSION These findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD-associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF-κB signaling cascade.

目的:探究五苓散联合桃红四物汤对瘀血阻络型肝硬化腹水的治疗作用.方法:选取2019年3月至2020年6月我院收治的瘀血阻络型肝硬化腹水患者96例,采用随机数字表法分为西药组与中药组,西药组患者采用托伐普坦片(15 mg/d)、还原性谷胱甘肽(1.2 g/d)、呋塞米(80～160 mg/d)治疗,中药组患者在西药组患者治疗基础上加服五苓散合桃红四物汤,观察两组患者临床疗效、中医证候评分、肝功能变化,及出血并发症发生情况.结果:治疗后,中药组患者总有效率为87.50％高于西药组的70.83％(P<0.05),中医证候积分低于对照组(P<0.05),腹水消退时间短于西药组(P<0.05);治疗后,中药组患者丙氨酸氨基转移酶(ALT)、谷氨酰转移酶(GGT)、总胆红素(TBil)水平低于西药组(P<0.05),白蛋白(Alb)水平高于西药组(P<0.05);中药组、西药组患者出血并发症发生率分别为(18.75％vs 27.08％),差异无统计学意义(P>0.05).结论:五苓散联合桃红四物汤治疗瘀血阻络型肝硬化腹水效果确切,可有效改善患者肝功能,且不会增加出血风险.

目的 探讨补中益气汤对肝动脉化疗栓塞术(TACE)后患者疲劳指数和生活质量的影响.方法 选取2019年10月至2021年5月间陕西省中医医院收治的100例原发性肝癌患者,采用随机数表法分为研究组和对照组,每组50例.两组患者均采用TACE,对照组患者术后采用常规西医对症治疗,研究组患者术后在对照组基础上联合补中益气汤治疗,比较两组患者的疲劳指数、生活质量和治疗效果.结果 治疗前,两组患者的疲劳指数和生活质量比较,差异无统计学意义(P>0.05);治疗后,研究组患者的疲劳指数低于对照组,生活质量评分高于对照组,差异均有统计学意义(均P<0.05).研究组患者的疾病缓解率为96.0％,高于对照组的80.0％,差异有统计学意义(P<0.05).结论 原发性肝癌患者在TACE后行补中益气汤治疗,可提升患者的治疗效果,缓解疲劳指数,改善生活质量,建议临床借鉴.

目的 探讨芍仙萸颗粒对免疫性血小板减少症(immune thrombocytopenia,ITP)小鼠肝脾组织及辅助性T细胞(helper T cell,Th cell)17/调节性T细胞(regulatory T cell,Tregcell)免疫平衡的影响.方法 将30只C57BL/6小鼠随机分为对照组、模型组、芍仙萸颗粒低剂量组(5.85 g/kg)、高剂量组(11.7g/kg)和泼尼松组(5.4mg/kg),每组6只.检测各组小鼠免疫相关指标、Th17和Treg细胞数,计算Th17/Treg比值,并观察小鼠肝脏、脾脏的形态变化.结果 与对照组相比,模型组小鼠血小板计数下降,血小板相关免疫球蛋白(platelet-associatedi mmunoglobulin,PAIg)水平上升(P＜0.05);芍仙萸颗粒低、高剂量组血小板计数上升,PAIg水平下降(p＜0.05).与对照组相比,模型组小鼠白介素(interleukin,IL)-17和转化生长因子(transforming growth factor,TGF)-β1水平下降,IL-10水平上升(P＜0.05);芍仙萸颗粒低、高剂量组IL-17和TGF-β1水平上升,IL-10水平下降(p＜0.05).与对照组相比,模型组小鼠脾脏组织紊乱,白髓较大,红髓较小,髓索、髓窦内可见大量发育异常的巨核细胞,肝脏组织肿胀,肝小叶结构消失,汇管区及间质有大量炎症细胞浸润;芍仙萸颗粒低、高剂量组,肝脾组织病理改变较模型组显著改善,与泼尼松组疗效相当.与对照组相比,模型组小鼠Th17细胞数增加,而Treg细胞数减少,Th17/Treg比值上升(p＜0.05);芍仙萸颗粒低、高剂量组,两者比值对应下降(P＜0.05).结论 芍仙萸颗粒可显著增加ITP小鼠血小板数量,有效控制出血,并通过调节Thl7/Treg细胞免疫平衡对ITP小鼠的肝脾组织起到一定的保护作用.

探讨长安医学张氏肝病流派"补肝体强肝用"的学术思想.通过对临床诊治思路、临床医案的总结,探讨辨治臌胀的经验,为临床实践提供新思路.长安医学张氏肝病流派基于整体观念、脏腑学说理论,根据肝体阴用阳、肝肾同源、精血同源特点,提出"补肝体强肝用"的学术思想,用于治疗臌胀阴虚水停证、脾肾阳虚证、水湿内停证,效果较好.

目的 研究白花蛇舌草提取物(HDE)对肝癌QGY细胞增殖、凋亡的影响,并探讨其抗肿瘤的可能作用机制.方法 体外培养肝癌QGY细胞,分为对照组:RPMI-1640培养基培养;阳性对照组:全反式维甲酸(AT-RA)(5μmol/L);白花蛇舌草提取物(HDE)低、中、高剂量组:分别给予20、40、80 g/L HDE.四甲基偶氮唑盐比色法(MTT)检测细胞增殖能力,采用Hoechst33258荧光染色以及流式AnnexinV-FITC/PI双染法检测细胞凋亡率;通过蛋白质印迹法(Western blotting)检测增殖相关蛋白增殖细胞核抗原(PCNA)、凋亡相关蛋白B淋巴细胞瘤基因-2(Bcl-2)、Bcl-2相关X蛋白基因(Bax)、半胱氨酰天冬氨酸特异性蛋白酶3(caspase3)及JNK/p38MARK通路相关蛋白水平.结果 24、48 h时QGY细胞增殖抑制率,与对照组[(16.56±3.15)％、(19.27±3.33)％]同时间点比较,20、40、80 g/L HDE组[24 h(33.37±11.36)％、(47.57±13.62)％、(59.37±16.95)％,48 h(36.56±10.03)％、(50.59±13.87)％、(63.61±16.99)％]、阳性对照组[(60.43±17.09)％、(64.63±17.15)％]均显著升高(P<0.05).与对照组比较,20、40、80 g/L浓度HDE处理后QGY细胞凋亡率、Bax、caspase-3蛋白均显著升高(P<0.05),PCNA、Bcl-2蛋白、p-JNK/JNK、p-p38/p38表达降低(P<0.05),且均呈浓度依赖性,80 g/L HDE组细胞凋亡率、Bax、caspase-3、PCNA、Bcl-2蛋白、p-JNK/JNK、p-p38/p38表达与阳性对照组比较差异无统计学意义(P>0.05).结论 HDE可抑制肝癌QGY细胞增殖,促进QGY细胞凋亡,可能是通过抑制JNK/p38MARK通路活化进而发挥抗肿瘤作用.

目的:探讨化脂复肝颗粒在非酒精性脂肪性肝病(NAFLD)中对Kupffer细胞(KCs)TLR4/MyD88/NF-κB/NLRP3信号通路的影响.方法:将分离培养的KCs随机分为空白组、LPS干预组、LPS+空白血清组、LPS+化脂复肝组、高糖+对照组、高糖+LPS干预组、高糖+LPS+空白血清组、高糖+LPS+化脂复肝组,LPS干预浓度为100 ng/ml,高糖干预为于KCs培养基中另加入葡萄糖30 mmol/L.用CCK-8法检测各组KCs增殖情况;酶联免疫吸附法(ELISA)测定各组KCs培养基上清液中促炎因子TNF-α、IL-1β的含量;反转录实时荧光定量PCR(RT-qPCR)法检测各组KCs中TLR4、MyD88、NLRP3、Caspase-1、NF-κB p65、TNF-α、IL-1β的基因表达情况.结果:CCK-8检测显示,空白及高糖培养对照组KCs细胞不断增殖,长势良好;LPS+化脂复肝组与高糖+LPS+化脂复肝组KCs缓慢增殖,非高糖组KCs均较含高糖组KCs增殖速率更快;而LPS或高糖+LPS诱导模型组及各加空白血清组KCs于第6小时开始出现凋亡,含高糖组KCs均较非高糖组KCs凋亡速率更快.非高糖各组与含高糖各组中促炎因子TNF-α、IL-1β含量以及炎症相关基因(TLR4、MyD88、NLRP3、Caspase-1、NF-κB/p-65、TNF-α、IL-1β、IL-18)表达水平均呈相同变化趋势,且含高糖各组上述促炎因子及炎症相关基因表达水平均较非高糖组高.以非高糖组为例,LPS诱导模型组和LPS+空白血清组的促炎因子TNF-α与IL-1β含量均显著高于对照组(P<0.05),炎症相关基因TLR4、MyD88等的mRNA表达水平也均显著高于对照组(P<0.05),而LPS诱导模型组与LPS+空白血清组间上述各指标比较差异均无统计学意义(P>0.05);与LPS诱导模型组或LPS+空白血清组比较,LPS+化脂复肝组促炎因子TNF-α与IL-1β含量均显著降低(P<0.05),炎症相关基因TLR4、MyD88等的mRNA表达水平也均显著降低(P<0.05).结论:化脂复肝颗粒含药血清可改善KCs活力,有效减轻KCs炎症反应,减少KCs细胞焦亡的发生,具有显著的抗炎、抗氧化损伤及保肝作用,其作用机制可能与抑制TLR4/MyD88/NF-κB p65/NLRP3信号通路的激活相关.