Prediction and validation of molecular biological mechanism of Fuzheng Huayu capsule in the treatment of liver cancer

Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly treat liver cancer remains largely unknown.This study aims to investigate the molecular mechanism underlying the potential of FZHY in treating liver cancer.Methods:A network pharmacological analysis was performed using the Traditional Chinese Medicine Systems Pharmacology database to identify FZHY compounds and targets.Disease targets were searched using the Genecards database,and transcriptome data was downloaded from the NCBI database.Gene Ontology analysis was conducted using the DAVID database,and Kyoto Encyclopedia of Genes and Genomes analysis was based on KOBAS and bioinformatics methods.The Swissdock database was used for molecular docking.In cell experiments,the half inhibitory concentration(IC50)of FZHY was determined using the CCK8 method.The effects of FZHY on cell viability,apoptosis,and mitochondrial membrane potential were evaluated using a fluorescence microscope and flow cytometry.The molecular mechanism of FZHY in treating liver cancer was verified using quantitative polymerase chain reaction.Results:A total of 127 compounds and 184 proteins were identified as potential active ingredients and putative liver cancer-related targets.Additionally,1,899 liver cancer targets,279 transcriptome targets,and 3 pathways(p53 signaling pathway,apoptosis and PI3K-Akt pathway)were collected.The FZHY-targets-liver cancer interaction network was constructed.IC50 of FZHY lyophilized powder solution to liver cancer was 5.13 mg/mL(IC50=5.13 mg/mL).FZHY treatment led to an increase in the ratio of cell apoptosis and induced mitochondrial membrane potential damage,resulting in an increase in the number of dead cells.The expression levels of CCNB1 and BIRC5 were induced with FZHY treatment,while the expression levels of AKR1C3 and IGF2 were reduced.Conclusion:FZHY promotes apoptosis of liver cancer cells by acting on the p53 signaling pathway,apoptosis,and PI3K-Akt pathway.CCNB1,BIRC5,AKR1C3,and IGF2 are potential target proteins for FZHY in treating liver cancer.

Effects of Fuzheng Huayu Capsules combined with nucleoside antiviral drugs on liver and kidney function, serum inflammatory factors, TLR-4, TGF-β1 and aspartate aminotransferase-platelet ratio index in patients with HBV infection and decompensated liver

Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.

Fuzheng Huayu Capsule Improves Survival in Patients with HepatitisB-related Cirrhosis and Overt Hepatic Encephalopathy

Objective:Fuzheng Huayu(FZHY)capsules exert anti-liver fibrosis and cirrhosis effects.This study aimed to determine the effect of FZHY on the 6-month survival rate of patients with overt hepatic encephalopathy(OHE)and hepatitis B-related cirrhosis(HBC).Methods:A total of 517 patients with OHE and HBC treated between January 2008 and July 2018 were enrolled.Patients were divided into the FZHY(n=129)and control groups(n=388),and the 6-month survival rates were compared between the two groups.Propensity score matching(PSM)was used to reduce the bias caused by confounding factors.Results:In multivariable regression analysis,FZHY therapy was an independent protective factor of 6-month survival.After PSM(1:2),the FZHY and control group comprised 126 and 252 patients,respectively.The 6-month survival rate was remarkably higher in the FZHY group than in the control group(P<0.005).FZHY users,especially those with a model for end-stage liver disease score>20 and Child-Pugh class C,benefited significantly from FZHY therapy.Conclusions:Adjuvant therapy with FZHY may be associated with improved survival in patients with OHE and HBC.However,further clinical studies are required to validate our findings.

Huayu capsule enhances limb-catching capability of rats with experimental open traumatic brain injury

BACKGROUND： It is hard to cure the open traumatic brain injury （TBI）, especially for the brain functional recovery after brain injury. In this regard, traditional Chinese medicine （TCM） has a wide prospect. OBJECTIVE： To observe the effect of Huayu capsule on limb-catching capability of rat models of open TBI, and investigate its possible mechanism. DESIGN： Randomized and controlled study. SETTING： Grade 3 Pharmacological Laboratory of TCM, State Administration of TCM, Chengdu University of TCM. MATERIALS： This study was performed from October 2005 to January 2006. Fifty Sprague-Dawley rats of either gender, aged 3 months old, weighing from 190 to 220 g, were involved in this study. Huayu capsule was made and supplied by the Department of TCM Processing of Chengdu University of TCM, Lot No. 050121; Xuefuzhuyu oral liquid was manufactured by Jilin Aodong Yanbian Pharmaceutical Industry Co.,Ltd., Lot No. 050406. METHODS： Open right parietal lobe TBI rat models were made as described in references. The involved rat models were randomized into 5 groups according to gender and body mass： model group, high-, middle-, low-dose Huayu capsule groups and Xuefuzhuyu oral liquid group, with 10 rats in each. Rats in the model group were administrated with distilled water of 5 mL/kg; Rats in the high-, middle- and low-dose Huayu capsule groups were administrated with 1.030, 0.515, 0.258 g/kg raw herbs; Rats in the Xuefuzhuyu oral liquid group were administrated with Xuefuzhuyu oral liquid of 5 mL/kg, intragastrically once a day for 7 days successively for all after recovering consciousness from anesthetization. ① One hour after administration on the 6^th day, rats in each group were placed on a 100 cm fine straight iron wire paralleling to the ground and 20 cm above the operational table. The time of the rats keeping on the wire was counted and it indicated the nerve-muscle catching capability. The longer the remained time, the better the nerve-muscle catching capability.② Twenty-four hours after the administration on the 7^th day, the samples of the whole brain were carefully taken out and stained by toluidine blue for observing the morphology of cells in the injured brain tissue. ③ The nerve cells in 4 visual fields from 4 directions （upper, lower, left, right） of injured area of brain tissue were counted. The amount was the total number of the four visual fields. The nerve cells in the injured brain tissue were measured by the same way. ④ On the basis of nerve cell counting, the content of Nissl＇s body in the corresponding nerve cells was measured. MAIN OUTCOME MEASURES： ①Nerve-muscle catching capability. ②Histopathomorphological examination of the injured areas in brain. ③Measurement of nerve cells and macrophages in the injured areas of brain. ④Measurement of content of Nissl＇s body in the injured areas of brain. RESULTS： All the 50 rats were involved in the final analysis. ①The catching time of rats in the high- and middle-dose Huayu capsule groups as well as Xuefuzhuyu oral liquid group was extended to （ 23.6 ± 10.12 ）, （ 18.6 ± 8.17 ） and （22.6 ± 9.43） s, respectively, which was significantly higher than that in the model group [ （12.1 ± 4.15） s, P 〈 0.05 - 0.01 ]. ② The injured areas of brain tissue of rats in the Huayu capsule-treated groups and Xuefuzhuyu oral liquid group were decreased to different extents. The nerve cells adjacent to brain injured area were increased. ③ The number of macrophages around the brain injured area of rats in the high- and middle-dose Huayu capsule groups as well as Xuefuzhuyu oral liquid group was 63.9 ± 7.99, 59.7 ± 7.41 and 62.9 ± 7.37, respectively, which was significantly larger than that in the model group （49.2 ± 8.00, P 〈 0.01 ） . The number of nerve cells adjacent to brain injured area of rats in the high-, middle-, and low-dose Huayu capsule groups as well as Xuefuzhuyu oral liquid group was 86.2 ± 25.93, 93.5 ± 31.79, 92.1 ± 14.54 and 125.2 ±34.25, respectively, which was significantly larger than that in the model group （62.5 ± 16.98, P 〈 0.05 -0.01 ） .④ The total area, the total and integral absorbance, the average gray degree of Nissl＇s body in the cytoplasm of nerve cells of rats in the Huayu capsule-treated groups and Xuefuzhuyu oral liquid group were all significantly increased （P 〈 0.05 - 0.01）. CONCLUSION： Huayu capsule at different doses can promote the limb-catching capability of rat models of open TBI to different extent. This promoting effect may be related to increasing macrophages in the injured area, lessening the apoptosis of nerve cells and increasing the content of Nissl＇s body in the nerve cells.

Impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis

Background:Fuzheng Huayu tablet is a traditional Chinese medicine(TCM)used for the treatment of liver fibrosis and cirrhosis.However,whether the combination with Fuzheng Huayu tablet could affect the antiviral efflcacy of nucleos(t)ide remains a concern.The objective of this trial was to explore the impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis.Methods:A prospective,randomized control trial was conducted.Patients with compensated hepatitis B cirrhosis were randomly divided into the treatment group(entecavir capsule plus Fuzheng Huayu tablet)and the control group(entecavir capsule plus simulant of Fuzheng Huayu),and followed up for 48 weeks.The dynamic changes of HBV DNA load,the rate of serological conversion of HBeAg,liver function,renal function and liver stiffness measurement(LSM)were monitored.The general clinical data and adverse events were also recorded.Results:There was no significant difference in the rate of virological response and cumulative virological response between the treatment group and the control group(P>0.05).After 48 weeks of treatment,the HBeAg seroconversion rate,biochemical response rate and LSM value were 21.05%and 4.76%(P=0.164),86.96%and 65.96%(P=0.017),9.5 kpa and 10.6 kpa(P=0.827)in the treatment group and the control group,respectively.No serious adverse events related to the study therapy occurred during the trial.Conclusions:The antiviral entecavir combined with Fuzheng Huayu tablet did not affect the antiviral efflcacy of entecavir,but could improve the rate of biochemical response,and had a tendency to improve the rate of serological conversion of HBeAg and liver fibrosis in patients with hepatitis B cirrhosis.Fuzheng Huayu tablet is clinically safe for patients with hepatitis B cirrhosis.

Seropharmalogical Effects of Fuzheng Huayu decoction on rat Ito cell morphology and functions in culture

IM To investigate the mechanisms of antiliver fibrosis actions of Fuzheng Huayu (FZHY, strengthen the body resistance and promote blood circulation) decoction.METHODS Ito cells were isolated from rats and cultured, the sera were collected from the normal rats after administration of FZHY decoction and added to the subcultured cells. Ito cell morphology was observed under the contrast microscopy, cells viability was measured by Pro incorporation, proliferation by TdR incorporation and MTT colorimetric assay, collagen synthesis rate by Pro incorporation and collagenase digestion. The effects of FZHY decoction on Ito cell morphology and functions were observed.RESULTS The rat serum containing FZHY decoction had no influence on Ito cell morphology, but could improve the cell viability. It could markedly inhibit Ito cell proliferation and collagen synthesis, these effects tend to be drug dose and drug sera concentration dependent.CONCLUSION Seropharmalogical method can be efficiently used to investigate the pharmacological mechanism of antifibrotic traditional Chinese herbs and formulae. The inhibition of Ito cell proliferation and collagen synthesis may be one of the major mechanisms of the antifibrosis actions in FZHY decoction.

Effects of Fuzheng Huayu 319 recipe on liver fibrosis in chronic hepatitis B

AIM To investigate clinic effects of Fuzheng Huayu 319 recipe (319 recipe) on liver fibrosis in chronic hepatitis B.METHODS Ninety-five patients with chronic hepatitis B were divide into the treated (63 cases) and control (32 cases) group, and orally administrated with 0.5g 319 capsule or 0.5g Dahuang Zhachong pill tid for 3 months, respectively. The liver functions and serological fibrotic markers were observed before and after treatment, 12 cases in the treated group were examined with liver biopsy.RESULTS Three hundreds nineteen recipe could remarkably decreased serum ALT level and total bilirubin and significantly improve serum albumin and A/G ratio. Its effects were better than Dahuang Zhachong pill. Before treatment, patients' serum monamine oxidase activities, tissue inhibitor of metalloproteinase (TIMP)-1, procollagen type Ⅲ and laminin were all higher than those of health peoples. These levels decreased remarkably after treatment, and urine hydroxyproline level increased significantly (P＜0.001-0.05). Compared with the control, the improvement in treated group was better than that in the control except TIMP-1. According to the scoring system for staging of chronic hepatitis, the fibrotic extents of 7 cases among 12 cases examined by liver biopsy decreased remarkably (1 case decreased by 3 scores, 5 by 2 scores, 1 by 1 score).CONCLUSION Fuzheng Huayu 319 recipe had good therapeutic effects on chronic hepatitis B, it could reverse the development of liver fibrosis to some extent. In general its effects were better than that of Dahuang Zhachong pill.

扶正化瘀胶囊对肝纤维化发展的影响

目的探讨扶正化瘀胶囊(FZHY)对肝纤维化发展的影响。方法CCK-8法检测FZHY对LX-2细胞活性的影响。RT-qPCR和Western blot法测定LX-2转染TGF-β或/和给予FZHY后α-SMA水平。选取2022年1月至2022年12月在上海第九人民医院接受抗病毒治疗的慢性乙型肝炎患者80例作为研究对象,分为对照组和治疗组,治疗组每日口服扶正化瘀胶囊1.5 g,一日3次,瞬时弹性成像检查各组治疗前后瞬时肝弹性F值。结果FZHY明显抑制LX-2生长,并与剂量呈正相关(P<0.05)。过表达TGF-β后α-SMA mRNA明显增加(57.14±4.81),与对照组相比差异显著(P<0.001)。同时予10%或20%FZHY时,α-SMA mRNA不同程度降低(37.42±3.65及21.79±0.496),与TGF-β组相比,α-SMA mRNA降低差异有统计学意义(P<0.05,P<0.001)。Western blot显示,FZHY能部分抵消TGF-β引起的α-SMA表达上调。治疗组瞬时肝弹性F值较干预前有所下降,但差异无统计学意义(P>0.05)。结论FZHY可通过影响LX-2细胞增殖、调节α-SMA表达来实现抗纤维化作用。

夏橘化瘀胶囊治疗气虚血瘀型冠状动脉旁路移植术后再发心绞痛的临床效果

目的 探讨夏橘化瘀胶囊治疗气虚血瘀型冠状动脉旁路移植术后再发心绞痛的临床效果。方法 选取2021年1月至12月山东省潍坊市中医院收治的70例行冠状动脉旁路移植术后再发心绞痛患者为研究对象,采用随机数字表法将其分为对照组和观察组,各35例。对照组采用西医常规治疗,观察组采用西医常规治疗+夏橘化瘀胶囊,两组均连续治疗3个月。比较两组中医证候疗效,比较两组治疗前后心绞痛发病频率、持续时间、西雅图心绞痛量表评分、N-末端B型利钠肽前体(NT-pro BNP)、超敏C反应蛋白(hs-CRP)水平,同时记录患者相关安全性指标。结果 观察组中医证候疗效优于对照组(P<0.05)。治疗后,两组心绞痛发病频率少于治疗前、持续时间短于治疗前,且观察组心绞痛发病频率少于对照组、持续时间短于对照组(P<0.05)。治疗后,两组西雅图心绞痛量表各项评分均高于治疗前,且观察组高于对照组(P<0.05)。治疗后,两组血清NT-pro BNP、hs-CRP水平低于治疗前,且观察组低于对照组(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 夏橘化瘀胶囊对冠状动脉旁路移植术后再发心绞痛有明显改善作用,且安全性较高,具有重要的临床应用价值。

扶正化瘀散结法联合西药治疗厌食-恶病质综合征有效性的Meta分析

目的系统评价扶正化瘀散结法联合西药治疗厌食-恶病质综合征的有效性。方法系统检索维普(VIP)、中国知网(CNKI)、万方数据知识服务平台(Wan Fang)、中国生物医学文献数据库(CBM)、PubMed、Web of Science、Embase数据库、Cochrane Library数据库,利用Jadad、Cochrane协作网RCT质量评价标准对纳入文献的研究质量进行评价,Meta分析提取数据。结果1)共纳入17个随机对照研究(RCT),患者1423例,纳入研究质量一般;2)Meta分析合并RR值包括体重变化[RR=1.36,95%CI(1.08,1.71),P=0.009]、KPS评分变化[RR=1.44,95%CI(1.29,1.60),P<0.00001]、进食量变化[RR=1.33,95%CI(1.15,1.55),P=0.0002]、白蛋白变化[MD=3.01,95%CI(2.10,3.93),P<0.00001]以及血红蛋白变化[MD=10.74,95%CI(1.91,19.58),P=0.02]。结论本研究证实扶正化瘀散结法在厌食-恶病质综合征应用的有效性优于单纯西药治疗或结合营养支持治疗。

扶正化瘀片联合多烯磷脂酰胆碱治疗慢性乙肝肝硬化患者的疗效

目的:探讨扶正化瘀片联合多烯磷脂酰胆碱治疗慢性乙肝肝硬化患者的疗效及其对肝功能、肝纤维化和血清指标的影响。方法:选取106例慢性乙肝肝硬化患者,按照治疗方式不同分为对照组和研究组,每组各53例。对照组给予常规治疗和多烯磷脂酰胆碱治疗;研究组在对照组基础上给予扶正化瘀片治疗,两组均治疗24周。比较两组患者的疗效、肝功能、肝纤维化指标、血清指标水平及不良反应发生情况。结果:研究组的临床总有效率为96.23%,高于对照组的83.02%(P<0.05)。治疗后,两组患者的总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、透明质酸酶(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(IV-C)、层粘连蛋白(LN)、D二聚体(D-D)、总胆汁酸(TBA)水平均降低(P<0.05),且研究组均低于对照组(P<0.05);两组患者的白蛋白(ALB)、胆碱酯酶(CHE)水平均升高(P<0.05),且研究组高于对照组(P<0.05),两组不良反应总发生率无统计学差异(P>0.05)。结论:扶正化瘀片联合多烯磷脂酰胆碱治疗慢性乙肝肝硬化患者疗效显著,可有效改善患者肝功能,减轻肝纤维化,调节D-D、TBA及CHE的表达水平,并具有较好的安全性。

扶正透邪解毒化瘀方对多重耐药铜绿假单胞菌肺炎老年大鼠炎症损伤的影响

目的探讨扶正透邪解毒化瘀方对多重耐药铜绿假单胞菌(MDRPA)肺炎老年大鼠不同时相炎症损伤的影响。方法将老年SD大鼠分为空白组、模型组、西药组、中药组、中药提前给药组、中西医结合治疗组,除空白组外使用经口气管插管法进行MDRPA肺炎造模,观察各组大鼠死亡保护率、生命延长率;在感染后不同时间点取大鼠血清及肺组织标本,应用ELISA试剂盒测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)水平,光镜下观察肺组织支气管、肺泡等结构;在感染后第3日取肺组织标本,电镜下观察各组肺组织超微结构。结果中药提前给药组和中西医结合治疗组可提高死亡保护率和生命延长率。中西医结合治疗组可明显降低MDRPA肺炎老年大鼠血清中促炎因子TNF-α水平,升高抑炎因子IL-10水平,其作用强度明显优于西药组,且可明显减少肺组织炎症细胞浸润和充血水肿,明显减轻肺泡结构的破坏。中药提前给药组可在炎症反应早期升高血清抑炎因子IL-10水平,降低促炎因子TNF-α水平。结论扶正透邪解毒化瘀方对老年MDRPA肺炎大鼠有着较高的死亡保护率和生命延长率,与头孢他啶联合治疗可纠正MDRPA感染后紊乱的炎症状态,减轻炎症损伤。中药提前给药可对MDRPA感染后造成的炎症损伤起到保护与治疗作用,对维持机体免疫稳态具有重要意义。

恩替卡韦联合扶正化瘀片治疗乙型肝炎肝硬化患者疗效研究

目的探讨恩替卡韦联合扶正化瘀片治疗乙型肝炎肝硬化患者的疗效。方法2018年8月~2022年12月我院收治的乙型肝炎肝硬化患者122例,被随机分为对照组61例和观察组61例,分别给予恩替卡韦或恩替卡韦联合扶正化瘀片治疗52 w。采用PCR法检测血清HBV DNA载量,采用电化学发光法检测血清HBeAg和HBsAg水平,使用Fibroscan 502型弹性测量仪行肝脏硬度检测(LSM)。结果在治疗52 w末,观察组血清HBV DNA转阴率为96.7%,与对照组的93.4%比,差异无统计学意义(P>0.05),而血清ALT复常率为98.4%,显著高于对照组的85.2%(P<0.05);观察组血清HBsAg和HBeAg水平分别为(826.1±152.6)IU/mL和(194.5±33.8)IU/mL,均显著低于对照组【分别为(1005.3±207.5)IU/mL和(245.6±51.5)IU/mL,P<0.05】;观察组血清ALT、AST和LSM分别为(49.6±7.3)U/L、(39.2±6.1)U/L和(9.2±2.1)kPa,均显著低于对照组【分别为(66.9±10.7)U/L、(52.8±8.7)U/L和(11.8±3.0)kPa,P<0.05】。结论应用恩替卡韦联合扶正化瘀片治疗乙型肝炎肝硬化患者在抗病毒的同时能帮助改善肝功能指标,减轻肝纤维化程度,值得临床进一步研究。

扶正透邪解毒化瘀方对不同时间点老年肺炎大鼠炎症及免疫功能的影响

目的:探讨扶正透邪解毒化瘀方对多重耐药铜绿假单胞菌肺炎老年大鼠炎症反应与免疫功能的态影响。方法:将实验老年大鼠随机分为空白对照组、模型对照组、西药对照组、中药组、中药提前给药组、中西医结合观察组,动态观察不同时间点各组老年大鼠炎症指标的变化及淋巴细胞增殖水平的变化。结果:中药提前给药组及中西医结合观察组疗效显著,中药组对感染早期的炎症水平改善明显;中西医结合观察组可使T淋巴细胞增殖能力趋于正常;中药提前给药组、中西医结合观察组能抑制感染后B淋巴细胞的增殖并使其趋于正常。结论:扶正透邪解毒化瘀方能够调节感染早期老年大鼠机体过度的免疫炎症反应,中西医结合治疗能够纠正多重耐药铜绿假单胞菌感染后紊乱的免疫状态,中药提前给药能够对多重耐药铜绿假单胞菌感染后的炎症反应及免疫紊乱起到一定的预防及治疗作用。

扶正化瘀方对肝硬化小鼠模型肝细胞消亡与再生的影响

目的探讨扶正化瘀方对纤维化肝脏肝细胞消亡与再生的影响,及其药物促进肝细胞再生的作用机制。方法以CCl4腹腔注射6周诱导建立肝硬化小鼠模型。正常对照组9只,模型组10只,索拉非尼组10只,扶正化瘀方组10只。自造模第4周起,扶正化瘀方组、索拉非尼组分别给予4.8 g/kg、4 mg/kg小鼠体质量相应药物灌胃,连续3周;正常组和模型组给予等体积羧甲基纤维素钠。检测血清肝功能;METAVIR评分系统评价肝组织炎症及纤维化分期;天狼星红染色和肝组织羟脯氨酸含量评价胶原沉积量;免疫组化检测Ⅳ型胶原、CD31与CD32b、Ki67、CyclinD1、谷氨酰胺合成酶(GS)、Wnt2以及HGF蛋白的表达;Western Blot检测肝组织Wnt2、LRP6、β-catenin、p-β-catenin、CyclinD1表达。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与模型组比较,扶正化瘀方组和索拉非尼组血清ALT、AST水平和肝组织羟脯氨酸含量均降低(P值均<0.01),METAVIR评分减低(P值均<0.05);Ⅳ型胶原、CD31表达减少(P值均<0.05),CD32b表达增加(P<0.01);肝组织实质病变消亡数量减少,Ki67、CyclinD1表达上升(P值均<0.01);Wnt2、LRP6、β-catenin、CyclinD1蛋白表达水平上调、p-β-catenin表达显著下调(P值均<0.05);肝组织CD32b与Wnt2共染阳性细胞显著增多。结论扶正化瘀方可通过抑制肝窦毛细血管化,改善肝窦内皮细胞Wnt2外分泌功能,激活肝细胞再生相关Wnt/β-catenin信号通路,最终逆转肝硬化。

扶正化瘀片联合抗病毒药物治疗乙肝肝硬化失代偿期患者的临床疗效及对其肝脏硬度、肝纤维化的影响

目的观察扶正化瘀片联合抗病毒药物治疗乙肝肝硬化(Liver cirrhosisi,LC)失代偿期患者的临床疗效及对其肝脏硬度、肝纤维化的影响。方法选取2020年5月—2022年5月期间淮安市第四人民医院收治的乙肝LC失代偿期患者共260例,按随机数字表法分为对照组和观察组,每组各130例。对照组给予恩替卡韦分散片治疗,观察组在对照组基础上加服扶正化瘀片,均治疗24周。观察比较两组患者治疗前后中医证候积分[胁痛、胁下痞块、面色晦暗、口干不欲饮、乏力]、肝功能[总胆红素(Total bilirubin,TBil)、谷草转氨酶(Alanine aminotransferase,AST)、谷丙转氨酶(Aspartate aminotransferase,ALT)、白蛋白(Albumin,ALB)]、血清肝纤四项[层黏连蛋白(Laminin,LN)、Ⅲ型前胶原(Procollagen typeⅢ,PCⅢ)、IV型胶原(IV collegen,CIV)、透明质酸(Hyaluronic acid,HA)]、肝脾影像学[脾静脉内径、门静脉内径、脾脏厚度、肝脏瞬时弹性硬度(Liver stiff-ness measurement,LSM)]及Th1/Th2型细胞因子[白细胞介素-4(Interleukin-4,IL-4)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-18(Interleukin-18,IL-18)、干扰素-γ(Inferferon-γ,IFN-γ)]指标变化情况,评估抗病毒效果[乙肝病毒脱氧核糖核酸(Hepatitis B virus-deoxyribonucleic acid,HBV-DNA)载量及转阴率、乙肝e抗原(Hepatitis B e antigens,HBeAg)转阴率]及临床疗效。结果治疗后两组患者胁痛、胁下痞块、面色晦暗、口干不欲饮和乏力证候积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组胁痛、胁下痞块、面色晦暗、口干不欲饮和乏力证候积分均明显低于对照组,统计学有显著性差异(P<0.05)。治疗后两组患者肝功能TBil、AST、ALT水平均较治疗前降低,ALB水平均较治疗前升高,差异有统计学意义(P<0.05);且观察组TBil、AST、ALT水平均明显低于对照组,ALB水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者肝纤四项LN、PCШ、CIV和HA指标水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组患者肝纤四项LN、PCШ、CIV和HA指标水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者脾静脉内径、门静脉内径、脾脏厚度和LSM指标均较治疗前降低,差异有统计学意义(P<0.05);且观察组脾静脉内径、门静脉内径、脾脏厚度和LSM指标均明显低于对照组,差异有统计学意义(P<0.05)。治疗后观察组患者IL-4、IL-6水平较治疗前降低,IL-18、IFN-γ水平较治疗前升高,差异有统计学意义(P<0.05);对照组Th1/Th2型细胞因子水平与治疗前比较,差异无统计学意义(P>0.05);且观察组IL-4、IL-6水平明显低于对照组,IL-18、IFN-γ水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后观察组HBV-DNA载量低于对照组。观察组HBV-DNA转阴率59.23%(77/130)和HBeAg转阴率56.15%(73/130)明显高于对照组41.54%(54/130)、38.46%(50/130),差异有统计学意义(P<0.05)。治疗后观察组总有效率93.85%(122/130)明显高于对照组81.54(106/130),差异有统计学意义(P<0.05)。结论扶正化瘀片与抗病毒药物联合治疗能够改善乙肝LC失代偿期患者症状和肝功能,降低肝脏硬度和肝纤维化程度,维持Th1/Th2型细胞因子平衡。

黄体酮胶囊与化瘀清热法对子宫内膜息肉切除术后疗效与生活质量的影响

目的:探讨黄体酮胶囊与化瘀清热法对子宫内膜息肉切除术后疗效与生活质量的影响。方法:选取2017年6月—2022年6月江南大学附属医院收治的102例宫腔镜子宫内膜息肉切除术后患者为研究对象,按1︰1比例随机分为研究组和对照组,每组51例。对照组接受黄体酮胶囊治疗,研究组在此基础上联合应用化瘀清热法。比较两组治疗前后子宫内膜厚度、月经异常情况、炎症因子水平、生活质量(SF-36),统计两组疗效及术后复发率。结果:治疗3个月后,研究组患者的子宫内膜厚度显著恢复,月经异常情况、炎症因子水平、生活质量均显著优于对照组,差异均有统计学意义(P<0.05),术后12个月内研究组总复发率显著低于对照组,差异有统计学意义(P<0.05)。结论:黄体酮胶囊联合化瘀清热法可显著提高宫腔镜子宫内膜息肉切除术后患者疗效及生活质量,明显降低复发率。

贞芪扶正胶囊和贞芪扶正汤剂在辅助治疗晚期非小细胞肺癌化疗患者中的应用效果

目的探讨贞芪扶正胶囊和贞芪扶正汤剂在辅助治疗晚期非小细胞肺癌(NSCLC)化疗患者中应用效果。方法将2021年1月—2023年2月收治接受化疗的晚期NSCLC 100例,随机分为胶囊组、汤剂组各50例。胶囊组给予贞芪扶正胶囊,汤剂组给予贞芪扶正汤剂。比较2组临床疗效、化疗毒副反应及治疗前后肿瘤标志物[胃泌素释放肽前体(Pro-GRP)、血清鳞状细胞癌抗原(SCC)、细胞角蛋白片段19(CYFRA21-1)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)]、细胞免疫功能(CD3+、CD4+、CD8+、CD4+/CD8+)、体液免疫功能(IgA、IgM、IgG)、生存情况[Karnofsky行为状态评分(KPS)]、癌因性疲乏程度量表(PFS-R)评分。结果2组均无脱落病例。胶囊组客观缓解率、疾病控制率[22.00%(11/50)、92.00%(46/50)]与汤剂组[26.00%(13/50)、94.00%(47/50)]比较差异无统计学意义(P>0.05)。2组治疗后SCC、Pro-GRP、CEA、CYFRA21-1、NSE均低于治疗前(P<0.05);2组CD3+、CD4+、CD8+、CD4+/CD8+及IgA、IgM、IgG水平组间、组内比较差异无统计学意义(P>0.05)。2组治疗后KPS评分均高于治疗前,PFS-R评分均低于治疗前(P<0.05)。2组毒副反应发生率比较差异无统计学意义(P>0.05)。结论贞芪扶正汤和贞芪扶正胶囊应用于晚期NSCLC化疗辅助治疗效果相似,均能改善患者免疫功能,减轻患者癌因性疲乏,抑制肿瘤标志物表达,二者具有等效性。

Beneficial Effects of Traditional Chinese Medicine Fuzheng Huayu on the Occurrence of Hepatocellular Carcinoma in Patients with Compensated Chronic Hepatitis B Cirrhosis Receiving Entecavir:A Multicenter Retrospective Cohort Study

Background and Aims:The application of antifibrotic drugs to treat patients with chronic liver diseases who are receiving antiviral therapies for hepatocellular carcinoma(HCC)has not been established.Here,we aimed to assess the impact of the Traditional Chinese Medicine Fuzheng Huayu(FZHY)on the occurrence of HCC in patients with hepatitis B virus-related compensated cirrhosis receiving the antiviral drug entecavir(ETV).Methods:A multicenter retrospective cohort study was performed.Compensated liver cirrhosis patients were divided into the ETV+FZHY group or the ETV group according to treatment.The cumulative incidence of HCC was analyzed using Kaplan-Meier and log-rank tests.Propensity score matching was used for confounding factors.Stratified analysis and Cox regression were used to determine the effects of FZHY on the occurrence of HCC and liver function decompensation.Results:Out of 910 chronic hepatitis B patients,458 were in the ETV+FZHY group and 452 were in the ETV group.After propensity score matching,the 5-year cumulative incidence of HCC was 9.8%in the ETV+FZHY group and 21.8%in the ETV group(p<0.01).The adjusted hazard ratio for HCC was 0.216(0.108,0.432)when FZHY treatment was>36 months.Age,diabetes,alanine aminotransferase,-glutamyl transpeptidase,albumin,hepatitis B e-antigen,and fibrosis 4 score were associated with the occurrence of HCC.FZHY decreased the risk of HCC in patients aged>45 years with a hepatitis B virus DNA level of2,000 IU/l.Conclusion:Adjunctive FZHY treatment reduced HCC occurrence in patients with hepatitis B virus cirrhosis who were treated with ETV,possibly due to the antifibrotic properties of FZHY.

清肝化滞汤方联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝炎患者肝纤维化和脂肪变的疗效

目的分析清肝化滞汤方联合多烯磷脂酰胆碱治疗非酒精性脂肪性肝炎(NASH)的疗效。方法选取2021年6月至2023年6月浙江省湖州市第一人民医院收治的106例NASH患者,采用随机数字表法分组,对照组(53例)给予多烯磷脂酰胆碱胶囊治疗,研究组(53例)在对照组基础上联合清肝化滞汤方治疗,对比2组临床疗效、生化指标、炎性因子、肝纤维化及脂肪变指标。结果研究组有效率94%,较对照组79%高(χ^(2)=5.267,P<0.05);研究组治疗后总胆红素(TBIL)、三酰甘油(TG)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平较对照组低(t=3.736、1.994、2.109、2.054,P<0.05);研究组治疗后白细胞介素(IL)-18、IL-37及IL-6水平较对照组低(t=9.067、1.998、2.056,P<0.05);研究组治疗后肝脏硬度值(LSM)、层黏连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)及脂肪衰减参数(CAP)水平较对照组低(t=2.235、2.099、18.770、2.044,P<0.05)。结论清肝化滞汤方联合多烯磷脂酰胆碱可提高NASH患者的临床疗效,降低血清TBIL、TG、ALT及AST水平,减轻机体炎性反应,并改善脂肪变及肝纤维化程度。