Yu Gan Long Ameliorates Hepatic Fibrosis by Inhibiting PI3K/AKT,Ras/ERK and JAK1/STAT3 Signaling Pathways in CCl4-induced Liver Fibrosis Rats

Yu Gan Long(YGL)is a Chinese traditional herbal formula which has been reported to attenuate liver fibrosis for many years and we have explored its anti-fibrotic mechanism through blocking transforming growth factor(TGF-β)in the previous study.But the mechanisms associated with platelet-derived growth factor(PDGF)-BB remain obscure.In this study,we further investigated the mechanism of YGL reducing carbon tetrachloride(CCl4)-induced liver fibrosis in rats.Our results showed that YGL suppressed CCl4-induced upregulation of collagen IV(Col IV),type HI precollagen(PCHI),hyaluronuc acid(HA)and laminin(LN),which are implicated in liver fibrosis.Also,YGL reduced theα-smooth muscle actin(α-SMA)expression,which acts as the indicator of liver fibrosis.Furthermore,YGL decreased the serum levels of hepatic stellate cell(HSC)mitogen PDGF-BB and inflammation cytokines,including TNF-α,IL-1β,IL-6.Markers involved in liver fibrosis,such as Ras,p-Raf-1,p-ERK1/2,p-JNK,p-P38,p-PI3K,p-AKT,p-JAKl,p-STAT3 were downregulated significantly after treatment with YGL.Our results indicated that YGL ameliorated CCl4-induced liver fibrosis by reducing inflammation cytokines production,and suppressing Ras/ERK,PI3K/AKT,and JAK1/STAT3 signaling pathways,which provided further evidence towards elucidation of the anti-fibrotic mechanism of YGL.

Gan Shen Fu Fang ameliorates liver fibrosis in vitro and in vivo by inhibiting the inflammatory response and extracellular signalregulated kinase phosphorylation

BACKGROUND Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines.The Chinese herbal medicine,Gan Shen Fu Fang(GSFF)is composed of salvianolic acid B and diammonium glycyrrhizinate.In this study,we observed the effects of GSFF on liver fibrosis in vivo and in vitro in an attempt to provide some hope for the treatment.AIM To observe the effects of GSFF on liver fibrosis in vivo and in vitro and investigate the mechanism from the perspective of the inflammatory response and extracellular signal-regulated kinase(ERK)phosphorylation.METHODS Common bile duct-ligated rats were used for in vivo experiments.Hepatic stellate cells-T6(HSC-T6)cells were used for in vitro experiments.Hematoxylin and eosin staining and Masson staining,biochemical assays,hydroxyproline(Hyp)assays,enzyme-linked immunoasorbent assay and western blotting were performed to evaluate the degree of liver fibrosis,liver function,the inflammatory response and ERK phosphorylation.The CCK8 assay,immunofluorescence and western blotting were applied to test the effect of GSFF on HSC-T6 cell activation and determine whether GSFF had an effect on ERK phosphorylation in HSC-T6 cells.RESULTS GSFF improved liver function and inhibited liver fibrosis in common bile ductligated rats after 3 wk of treatment,as demonstrated by histological changes,hydroxyproline assays and collagen I concentrations.GSFF alleviated inflammatory cell infiltration and reduced the synthesis of pro-inflammatory cytokines[tumor necrosis factor-α(TNF-α)and interlukin-1β]and NF-κB.In addition,GSFF decreased ERK phosphorylation.In vitro,GSFF inhibited the viability of HSC-T6 cells with and without transforming growth factorβ1(TGF-β1)stimulation and decreased the synthesis of collagen I.GSFF had the greatest effect at a concentration of 0.5μmol/L.GSFF inhibited the expression ofα-smooth muscle actin(α-SMA),a marker of HSC activation,in HSC-T6 cells.Consistent with the in vivo results,GSFF also inhibited the phosphorylation of ERK and downregulated the expression of NF-κB.CONCLUSION GSFF inhibited liver fibrosis progression in vivo and HSC-T6 cell activation in vitro.These effects may be related to an alleviated inflammatory response and downregulated ERK phosphorylation.

Mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease based on network pharmacology and experimental verification

Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corresponding gene targets of each drug in Gan Dou Ling were obtained by using TCMSP database.The database of gene mutation and disease related gene was searched through the GeneCards database,DrugBank database,PharmGKB database and the DisGeNET database.After the intersection of drug and disease target genes.The STRING website was used to analyze the protein-protein interaction degree of target genes,and import the data to Cytoscape software 38.2 to analyze protein interaction network.The GO databases and KEGG databases were obtained in R language for enrichment analysis.On this basis,Masson staining were used to observe the degree of liver fibrosis in copper loaded mouse model,and the results of network pharmacological analysis were verified by Western Blot(WB).Results:A total of 108 drug disease intersection genes were analyzed by network pharmacology.Through PPI network analysis,JUN was found to be the key genes.The enrichment analysis of KEGG pathway showed that MAPK signal pathway was the important potential target pathways.Animal experiments showed that Gan Dou Ling could reduce liver fibrosis and inhibit the phosphorylation of P38,JNK and C-JUN in copper loaded mice.Conclusion:Gan Dou Ling may achieve the effect of treating WD liver fibrosis by inhibiting P38/JNK signaling pathway.

Randomized controlled trial of Qing Gan Huo Xue Prescription in the treatment of alcoholic liver cirrhosis

Objective:To evaluate the efficacy of Qing Gan Huo Xue Prescription(QGHXP)in the treatment of patients with alcoholic liver cirrhosis(ALC)of damp and heat stasis syndrome.Methods:A total of 69 patients with ALC were randomly divided into TCM group(n=35)and control group(n=34).The TCM group was given QGHXP 1 pack TID orally.Control group received polyene phosphatidylcholine capsule 456 mg TID for 24 weeks.The observation measurements are symptom efficacy rate,serum level of liver enzyme,and non-invasive liver cirrhosis evaluation,including liver stiffness measurement(LSM)examininged by FibroTouch,APRI score,FIB-4 index and Maddrey discriminant function.Results:The symptom efficacy rate of the experimental group and the control group was 85.70%and 61.80%(P=0.024).Liver enzyme levels(serum ALP,γ-GT,AST and ALT)of TCM group were lower than those of control group(P<0.05).LSM of TCM group was reduced after treatment,and was significant lower than control group(14.19±1.49)vs.(15.06±1.24)(P<0.05).The APRI scores,FIB-4 index and Maddrey discriminant functions of TCM group were lower than those of control group(P<0.05).Conclusion:QGHXP is an effective alternative for the treatment of damp and heat stasis syndrome of ALC in improving liver function and clinical symptoms.

调肝理脾法治疗肝胃郁热型难治性胃食管反流的临床研究

目的观察调肝理脾法治疗肝胃郁热型难治性胃食管反流病的临床疗效。方法选取2022年3月-2023年9月首都医科大学附属北京中医医院收治的肝胃郁热型难治性胃食管反流病患者共60例,随机分为2组,各30例。对照组给予奥美拉唑肠溶胶囊+调肝理脾方中药颗粒模拟剂治疗,治疗组给予调肝理脾方中药颗粒+奥美拉唑肠溶胶囊。比较治疗前后食管黏膜炎症改善情况、健康状况调查简表(SF-36)和胃食管反流病量表(GERD-Q)、症状及证候的疗效评价、复发率以及不良反应发生率。结果治疗后,治疗组胃镜下食管黏膜炎症改善有效率为93.33%,高于对照组(73.33%)(P<0.05);2组治疗后的SF-36评分显著升高,GERD-Q评分在治疗后显著降低,且治疗组SF-36评分高于对照组,GERD-Q评分低于对照组(P均<0.05);治疗后,治疗组中医证候评分显著低于对照组,治疗组的中医症候治疗率为96.67%,高于对照组80.00%(P均<0.05);治疗后,治疗组临床疗效为93.33%高于对照组73.33%(P<0.05);随访6个月后,治疗组未服药人数显著多于对照组(P<0.05);2组不良反应发生率无显著差异(P>0.05)。结论调肝理脾法可显著改善肝胃郁热型难治性胃食管反流病患者食管黏膜炎症、提高生活质量,改善中医证候及临床症状、复发性低,具有较好的临床治疗效果。

名中医陈锋从“肝主筋、为罢极之本”论治腰椎间盘突出症经验

腰椎间盘突出症主要由椎间盘各部分(包括髓核、纤维环及软骨板)出现不同程度的退行性改变,受外力作用的因素下,椎间盘的纤维环破裂,髓核组织从破裂处突出或脱出于后方或椎管内,刺激或压迫相邻脊神经根,产生腰部疼痛,一侧或双侧下肢麻木、疼痛等一系列临床症状。中医学通常把本病归纳在“腰痛”范畴,病因病机以肾虚为本,兼有外感风寒湿热或瘀血邪阻。陈锋教授认为肝脏亦为本病的核心病机之一,提出从“肝主筋,为罢极之本”溯发病之源,以肝不束筋骨致椎间盘退变为始、肝疏泄失司经不络属致腰背筋脉失常为标、肝筋劳损过度罢极不复致腰部筋力涣散为变的核心病机,日久腰背部气血失调、筋骨失衡发为本病。临证善于抓主症、辨主因、守病机,专病专药随症加减化裁,采用补肝养血、行气祛瘀为遣方思路,同时中药内服与外敷结合,注重手法推拿、腰背肌功能锻炼,发挥中医中药的临床价值。

从“肝藏魂”论肝主疏泄

“肝藏魂”是中医藏象理论中的重要内容,魂随神往来,为阳神。无论“罢极之本”或“肝主疏泄”,均体现肝“用阳”的生理特性,肝“用阳”实为肝藏魂(阳神)的外在表现。疏泄为肝最重要的生理功能,肝魂调控肝之疏泄发挥功能作用,魂安则疏泄正常;若魂不安则疏泄失常,继而诱发肝气逆、肝气郁两证。

基于GAN的医学图像仿真数据集生成算法

基于生成对抗网络(generative adversarial networks,GAN),提出了面向肝脏肿瘤CT图像仿真数据集生成深度学习算法.首先,将CT图像数据文件进行格式解析,单独保存为PNG格式的图像文件;然后,将肝脏病变区域统一标注为白色,并结合肝脏CT原图组成配对图片;最后,用生成对抗网络的pix2pix架构仿真生成病变肝脏图像.为将生成图像与目标图像进行定量分析、比较,本文采用了峰值信噪比和结构相似性作为模型的评价指标.实验结果表明,本文算法所生成的肝脏肿瘤CT仿真数据集的平均峰值信噪比为64.72 d B,平均结构相似性为0.9973,证明了所生成的仿真图像数据有着非常高的真实度.

龙江韩氏妇科对“肝肾同源”理论的传承应用

“肝肾同源”最早见于《易经》,医学概念源自《黄帝内经》。五行中肝属木,肾属水,水生木,肾为肝之母,肝为肾之子,肝肾同源,乙癸同源,精血互生互化,二者在生理上互相联系,病理上互相影响。龙江韩氏妇科历代医家重视“肝肾同源”理论,发展并应用于指导临床。龙江韩式妇科奠基人韩百灵教授,最早提出“肝肾学说”,其子韩延华教授作为代表性传承人,在韩百灵教授的理论思想指导下,创新性提出“肝主冲任”理论,并创立百灵育阴汤、补肾活血调经汤和百灵调肝汤等代表性方剂,运用于临床不孕症、闭经和月经先后不定期的治疗中,取得良效。本文围绕“肝肾同源”理论,追溯其起源,阐述韩氏妇科对其传承及应用,体现中医理论的传承和创新,为妇科同行提供借鉴。

基于“肝主疏泄”理论探讨肝脏维持血糖稳态的机制

糖尿病作为全球患病率增长最快的慢性病之一,是导致过早死亡、残疾和卫生系统成本增高的主要原因。糖尿病患者血糖调控机制受损且更易遭受外部因素影响而产生较大的血糖波动,现代研究证明血糖波动造成的血管损伤,使糖尿病并发症的发生风险增加,因此维持糖尿病患者的血糖稳态对延缓糖尿病并发症期及糖尿病的防治至关重要。肝主疏泄是肝脏最重要的生理功能之一,是维持各脏腑功能正常的基础,肝的疏泄对全身气机疏通和调畅的功能对机体平衡起着重要作用。文章基于中医典籍肝失疏泄理论与现代医学中肝组织的生理功能,总结现代医家的临床经验,从肝主疏泄与脾胃的运化、气血运行、水液代谢、情志角度综合分析肝主疏泄与血糖稳态机制的关系,并结合肝主疏泄与内分泌、神经、免疫系统内在物质表达的关系阐释肝主疏泄调节血糖波动的机制,为从肝助维持血糖稳态的中医临床治疗提供理论支持。

肝主生发的理论创新及其诊疗体系构建与应用

肝主生发的理论创新为肝脏及其相关病证的防治提供了中医肝藏象新的理论基础,“髓生肝”“髓失生肝”“补肾生髓成肝”是其重要知识体系,中医药调控发生发育及再生修复防治肝脏及其相关病证是其主要研究内容,在获得提高临床疗效的较高级别循证医学证据和明确疗效机制的基础上构建诊疗体系:病程进展的评估监测、识病辨证的诊疗标准、整体动态的防治方案和肝主生发的创新方药。该理论降低了慢性肝病患者肝硬化发生率,降低了肝癌发生风险及发生率,降低了肝衰竭的发生率,降低了慢加急性肝衰竭和慢性肝衰竭患者的病死率,减少或减轻了并发症,提高了艾滋病患者免疫功能重建能力,提高了患者生存质量,提高了中医药防治肝脏及其相关病证的能力和水平,体现其理论意义和临床价值。

基于“肝主筋膜”探讨椒梅汤对肛窦炎的治疗经验

肛窦炎是肛窦、肛门瓣、肛门腺内发生的急性或慢性炎症性疾病,反复炎症刺激极易造成患者排便不尽、坠胀、异物感以及疼痛。据相关文献报道,极大部分肛肠疾病均起源于肛窦炎,故肛窦炎的早期诊断和治疗非常重要。谢力子教授认为肛管直肠黏膜及周围的血管、淋巴等皆属于中医学“筋膜”范畴,“肝主筋膜”,故临床上常运用温肝散寒、柔肝缓急、酸敛肝阴之椒梅汤,从肝论治,以此缓解或治愈肛窦炎,为临床治疗肛窦炎提供了新思路。

针灸联合疏肝化瘀方治疗慢性乙型重型肝炎的效果观察

目的探讨针刺联合疏肝化瘀方在慢性乙型重型肝炎(chronic severe hepatitis B,CSHB)治疗中的应用价值。方法选取100例慢性乙型重型肝炎患者,随机分为西医组、针刺组、中药组和联合组,每组25例。西医组予以常规西医治疗,于此基础上,针刺组予以针刺治疗,中药组予以疏肝化瘀方,联合组予以针刺联合疏肝化瘀方治疗。观察4组临床疗效与安全性,比较4组治疗前、治疗1个月后、治疗6个月后中医症候积分、肝功能指标[谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)及γ-谷氨酰转肽酶(γ-glutamyl transpeptidase,GGT)]和T淋巴细胞亚群(CD^(4+)、CD^(8﹢)和CD^(4+)/CD^(8﹢))。结果联合组、中药组及针刺组总有效率均高于西医组(P<0.05);治疗1个月、6个月后,联合组、中药组及针刺组中医证候主症、次症积分及总积分低于西医组(P<0.05);治疗1个月、6个月后联合组ALT、AST、GGT水平及CD^(8﹢)低于中药组、针刺组和西医组,CD^(4+)及CD^(4+)/CD^(8﹢)高于中药组、针刺组、西医组(P<0.05);4组治疗期间均未出现不良反应。结论在西医常规治疗基础上,针刺联合疏肝化瘀方联合治疗CSHB可提高疗效,改善免疫功能与肝功能,缓解患者症状,且具有较高安全性。

基于“木曰敷和”理论探讨柔肝法治疗老年失眠症

肝主疏泄、藏血,在畅气机、统气血、燮阴阳方面发挥重要作用,文章从肝性柔润,“木曰敷和”角度出发,根据老年人脏腑柔弱、气血阴阳失调等病理特点,从肝论治老年失眠症,将其病机概括为木失敷和、气血怫郁、阴阳失衡。治疗主张柔肝胜于疏肝,从甘缓和中、养血柔肝,酸甘合阴、益肾柔肝,咸寒潜阳、降逆柔肝,辛润通络、化瘀柔肝4个方面探讨柔肝法应用,为治疗老年失眠症提供新思路,以期提高老年人生活质量。

基于《黄帝内经》探讨从肝主疏泄论治女性围绝经期潮热盗汗

潮热盗汗是女性围绝经期综合征的典型临床症状,严重干扰围绝经期女性的健康生活。女性在进入围绝经期后,出现潮热盗汗、情志不舒、月经不调、头晕目眩、眼目干涩等多种症状,而其中潮热盗汗因其多发于夜间,使人难以入眠,对女性造成严重困扰,故该文针对潮热盗汗进行分析探讨。目前西医对于其治疗多采用激素疗法,表现出明显的不良反应,且疗效有限。而从中医角度进行辨证论治,可减少产生不良反应,提高临床疗效。现中医临床多认为女性围绝经期潮热盗汗的发生与阴虚津亏密切相关,却易忽视肝失疏泄也是女性围绝经期发病的重要因素。该文基于《黄帝内经》及其他经典著作从生理、病理方面分析“肝主疏泄”理论,进一步探讨女性围绝经期的生理特点及潮热盗汗产生的病因病机,发现女性围绝经期产生潮热盗汗的重要原因在于肝失疏泄所导致的肝气郁结,气血瘀积化热,引起血热妄行、迫津外泄,以及肝失疏泄所引起的津液输布失常。故以此为依据,从恢复肝之疏泄功能进行论治,以疏肝理气为主要方法,柔肝滋阴、补肝养肾等为辅助手段,致力于为临床治疗女性围绝经期潮热盗汗提供学习和借鉴。

丹栀龙牡汤治疗心脏神经官能症撷粹

心脏神经官能症是心血管疾病的一种,由于发病机制不清、症状较多,西医以心理疗法、抗抑郁焦虑及对症治疗为主,疗效欠佳;而中医具有“整体观念”“辨证论治”的特点,可因人而异诊疗此病,在临床上取得了显著疗效。杨建新医师认为,本病属中医“郁病”“心悸”的范畴,病位主要涉及心、肝、脾三脏,与肝的关系最为密切,其中肝失疏泄最为关键,最常见的证型为肝郁脾虚型,以肝郁血虚脾弱、内有郁热为主要病机,以疏肝解郁、健脾养血、清热除烦、镇静安神为法,以丹栀龙牡汤为方治疗,疗效显著,在临床上取得了广大患者的尊敬和信赖。

肝宁方联合肝动脉化疗栓塞术治疗肝癌的疗效及对患者肝功能、氧化应激、炎症的影响

目的:分析肝宁方联合肝动脉化疗栓塞术治疗对肝癌患者临床疗效及肝功能、氧化应激、炎症的影响。方法:选择2022年1月—2023年2月我院收治的100例肝癌患者为研究对象,按照随机数字表法分为两组,对照组50例采用肝动脉化疗栓塞术治疗,联合组50例在对照组的基础上给予肝宁方治疗,对比两组患者临床疗效、肝功能、细胞因子水平、生活质量[肝胆肿瘤治疗功能评定(FACT-Hep)]、疲劳程度[简明疲劳量表(BFI)]情况。结果:治疗后,联合组总治疗效率为78.00%,高于对照组的56.00%(P<0.05)。治疗后,联合组总胆红素(TBIL)、谷草转氨酶(AST)、谷丙转氨酶(ALT)水平均低于对照组(P<0.05)。治疗后,联合组超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)及丙二醛(MDA)水平低于对照组,超氧化物歧化酶(SOD)水平高于对照组(P<0.05)。治疗后,联合组疲劳程度评分低于对照组,且生活质量评分高于对照组(P<0.05)。结论:肝宁方联合肝动脉化疗栓塞术可抑制肝癌患者氧化应激及炎症反应,改善肝功能,治疗效果显著。

从标本中气理论探讨“肝生于左,肺藏于右”的内涵

“肝生于左,肺藏于右”是中医中重要的理论问题,自提出以来就有很多解释,而这些解释也有不尽相同的地方,本文从五运六气中的标本中气理论出发,对“肝生于左,肺藏于右”的理论进行分析,提出了“肝生于左,肺藏于右”是指“肝主阳、肺主阴的功能”的观点,且其理论内涵对临床实践有较好的指导意义。

肝爽颗粒联合恩替卡韦治疗乙型肝炎肝硬化有效性和安全性的系统评价

目的系统评价肝爽颗粒联合恩替卡韦改善乙型肝炎肝硬化患者的有效性及安全性。方法计算机检索PubMed、中国知网、万方、维普等数据库,检索肝爽颗粒联合恩替卡韦治疗慢性乙型病毒性肝炎肝硬化的临床随机对照试验,由2名评价者独立评价纳入研究的方法学质量,应用RevMan 5.3软件进行Meta分析。结果共纳入25篇文献,Meta分析结果显示,肝爽颗粒联合恩替卡韦治疗乙型肝炎肝硬化,在e抗原转阴率[OR(95%CI)=3.08(1.84,5.16),P<0.01],乙型肝炎病毒-DNA[MD(95%CI)=-0.97(-1.38,-0.55),P<0.01];肝功能指标丙氨酸转氨酶[MD(95%CI)=-21.14(-28.38,-13.9),P<0.01],天冬氨酸转氨酶[MD(95%CI)=-2.1(-2.51,-1.69),P<0.01],白蛋白(ALB)[MD(95%CI)=5.23(4.47,6.00),P<0.01],总胆红素[MD(95%CI)=-10.75(-12.45,-9.05),P<0.01];肝纤维化指标透明质酸[MD(95%CI)=-40.68(-48.39,-32.97),P<0.01],层黏连蛋白[MD(95%CI)=-27.11(-31.99,-22.24),P<0.01],Ⅲ型前胶原[MD(95%CI)=-29.06(-32.64,-25.49),P<0.01],Ⅳ型胶原[MD(95%CI)=-27.74(-28.88,-19.64),P<0.01]等方面均优于恩替卡韦治疗,差异具有统计学意义(P<0.05)。2组患者不良反应发生率的差异无统计学意义(P>0.05)。结论肝爽颗粒联合恩替卡韦治疗慢性乙型肝炎肝硬化与单用恩替卡韦相比其疗效显著。

肝爽颗粒对慢性乙型病毒性肝炎患者免疫功能及肝功能的影响

目的:探讨肝爽颗粒对慢性乙型病毒性肝炎(CHB)患者免疫功能及肝功能的影响。方法:择取医院接诊的80例CHB患者,用随机数表法分成对照组与治疗组,各40例患者。对照组患者予西医常规治疗,治疗组患者在此基础上予肝爽颗粒治疗,持续6个月后对比两组疗效、肝功能、炎性反应及免疫功能。结果:治疗组患者总有效率高于对照组(P<0.05);治疗后,两组患者天冬氨酸氨基转移酶(AST)、γ-谷酰氨转肽酶(GGT)与丙氨酸氨基转移酶(ALT)均降低,且治疗组患者AST、GGT、ALT值更低(P<0.05);两组患者白介素-6(IL-6)、转化生长因子-β(TGF-β)与肿瘤坏死因子-α(TNF-α)均降低,且治疗组患者TGF-β、TNF-α、IL-6值更低(P<0.05);两组患者CD8+值均降低,CD4+、CD3+值均增高,且治疗组患者CD8+、CD4+、CD3+改善更优(P<0.05)。结论:肝爽颗粒治疗CHB疗效确切,可减轻患者炎性反应,提高免疫力,改善肝功能。