论著

尼达尼布联合格隆溴铵治疗合并肺纤维化的慢性阻塞性肺疾病患者的效果及对肺功能影响

Efficacy and effect on pulmonary function of nintanib combined with glycopyrrolate in the treatment of chronic obstructive pulmonary disease with pulmonary fibrosis

:513-519
 
      目的 合并肺纤维化的慢性阻塞性肺疾病(COPD)是COPD的特殊亚型,患者兼具气流受限与肺组织纤维化病理特征,临床症状更严重、肺功能下降更快,且现有单一治疗方案难以同时改善气流受限与纤维化进展,预后较差。基于此,本研究旨在分析尼达尼布联合格隆溴铵治疗合并肺纤维化的COPD患者的效果及对肺功能的影响,为优化临床治疗方案提供依据。方法 选取2022年3月—2024年12月收治的96例合并肺纤维化的COPD患者,采用前瞻性随机对照研究设计,应用随机数字表法分为试验组与对照组。所有患者均采取常规治疗,对照组48例采取尼达尼布治疗,试验组采取尼达尼布联合格隆溴铵治疗。两组均治疗24周后,比较治疗前后症状评分、肺功能、纤维化指标、炎症指标,并分析两组治疗安全性。结果 治疗后,两组CAT评分、mMRC评分及VAS降低(P<0.05);且与对照组比较,试验组CAT评分、mMRC评分及咳嗽VAS评分较低(P<0.05)。治疗后,两组FVC、FEV1、DLCO及FEV1/FVC比值均较治疗前改善(P<0.05);且与对照组比较,试验组FVC、FEV1、DLCO及FEV1/FVC比值较优(P<0.05)。治疗后,两组血清KL-6、SP-D水平及CT纤维化评分均降低(P<0.05);且与对照组比较,试验组血清KL-6、SP-D水平及CT纤维化评分较低(P<0.05)。治疗后,两组血清IL-6、TNF-α及TGF-β1水平降低(P<0.05);且与对照组比较,试验组血清IL-6、TNF-α及TGF-β1水平较低(P<0.05)。试验组总不良反应发生率为8.33%(4/48),对照组为10.42%(5/48),两组比较差异无统计学意义(P>0.05)。结论 尼达尼布联合格隆溴铵治疗合并肺纤维化的COPD效果良好,可减轻患者临床症状,改善肺功能与肺纤维化,降低机体炎症反应,安全性较高。

   Objective To analyze the effects of the combination of nintedanib and glycopyrrolate in treating chronic obstructive pulmonary disease(COPD)patients with associated pulmonary fibrosis and its impact on lung function,providing a basis for optimizing clinical treatment strategies.Methods Ninety-six COPD patients with pulmonary fibrosis admitted from March 2022 to December 2024 were selected,and divided into experimental group and control group using a random number table method.Using a prospective randomized controlled study design,all patients received conventional treatment,with 48 cases in the control group receiving treatment with nintedanib and the experimental group receiving treatment with nintedanib combined with glycopyrrolate bromide.After 24 weeks of treatment in both groups,the symptom scores,lung function,fibrosis indicators,and inflammation indicators were compared before and post-treatment,and the drug safety of the two groups was analyzed.Results Post-treatment,CAT score,mMRC score and VAS decreased in both groups(P<0.05).Compared with the control group,CAT score,mMRC score and cough VAS score were lower in the experimental group(P<0.05).Post-treatment,FVC,FEV1,DLCO and FEV1/FVC ratio of both groups improved compared with that before treatment(P<0.05).Compared with the control group,FVC,FEV1,DLCO and FEV1/FVC ratio of the experimental group were better(P<0.05).Post-treatment,serum KL-6,SP-D levels and CT fibrosis scores of both groups decreased(P<0.05).Compared with the control group,serum KL-6,SP-D levels and CT fibrosis scores of the experimental group were lower(P<0.05).Post-treatment,serum IL-6,TNF-α and TGF-β1 levels in both groups decreased(P<0.05).Compared with the control group,serum IL-6,TNF-α and TGF-β1 levels in the experimental group were lower(P<0.05).The incidence of total adverse reactions in the experimental group was 8.33%(4/48),and that in the control group was 10.42%(5/48).There was no difference between the two groups(P>0.05).Conclusions The combination of nintedanib and glycopyrrolate has a significant effect on the treatment of COPD complicated with pulmonary fibrosis,which can alleviate its clinical symptoms,improve lung function and pulmonary fibrosis,reduce the body’s inflammatory response,which is relatively safe.

基于“痰瘀互结”探讨双细胞互作在心肌纤维化中的机制

Mechanism of Macrophage-Fibroblast Interaction in Myocardial Fibrosis Based on the Theory of “Intermingled Phlegm and Blood

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心肌纤维化是心力衰竭等心血管疾病演化过程中的关键性病理改变,该病的进展机制依赖巨噬细胞与成纤维细胞的相互调控。现有现代医学研究证实巨噬细胞可凭借M1、M2表型极化行为介导炎症反应与组织修复过程,成纤维细胞能够分化形成肌成纤维细胞并推动细胞外基质异常沉积,两类细胞可依托TGF-β/Smad、CSF-1/CSF-1R等信号通路构建相互调控的作用网络并介导心肌纤维化恶化。中医痰瘀互结病机理论指出痰浊与瘀血可相互滋生、交织阻滞,是各类慢性迁延性疾病的关键发病基础。本文以中医痰瘀互结理论为研究切入点,剖析该病机理论与巨噬细胞、成纤维细胞交互作用的内在关联,整合现代医学关于两种细胞交互作用的现有研究成果,深入分析细胞互作在心肌纤维化发病过程中的协同机制与病理关联,旨在为心肌纤维化的中西医协同防治提供理论依据,为相关动物实验及临床应用研究筑牢研究基础。
Myocardial fibrosis is a key pathological change in the progression of cardiovascular diseases such as heart failure. The progression mechanism of this disease relies on the reciprocal regulation between macrophages and fibroblasts. Current modern medical research has confirmed that macrophages can mediate inflammatory responses and tissue repair processes through M1 and M2 phenotypic polarization behaviors, and fibroblasts can differentiate into myofibroblasts and promote abnormal extracellular matrix deposition. The two types of cells can construct a reciprocal regulatory network through signaling pathways such as TGF-β/Smad and CSF-1/CSF-1R, thereby mediating the deterioration of myocardial fibrosis. The theory of phlegm and blood stasis intermingling in traditional Chinese medicine suggests that phlegm turbidity and blood stasis can mutually generate and interweave to cause obstruction, serving as a key pathological basis for various chronic and persistent diseases. This article takes the traditional Chinese medicine theory of phlegmblood stasis intermingling as a research entry point, analyzes the intrinsic relationship between this pathological theory and the interaction of macrophages and fibroblasts, integrates existing modern medical research findings on the interaction between the two cell types, and deeply analyzes the synergistic mechanisms and pathological correlations of cellcell interactions in the pathogenesis of myocardial fibrosis. The aim is to provide a theoretical basis for the integrated traditional Chinese and Western medicine prevention and treatment of myocardial fibrosis, and also to lay a solid research foundation for related animal experiments and clinical application studies.

基于“痰瘀互结”探讨双细胞互作在心肌纤维化中的机制

Mechanism of Macrophage-Fibroblast Interaction in Myocardial Fibrosis Based on the Theory of “Intermingled Phlegm and Blood Stasis”

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心肌纤维化是心力衰竭等心血管疾病演化过程中的关键性病理改变,该病的进展机制依赖巨噬细胞与成纤维细胞的相互调控。现有现代医学研究证实巨噬细胞可凭借M1、M2表型极化行为介导炎症反应与组织修复过程,成纤维细胞能够分化形成肌成纤维细胞并推动细胞外基质异常沉积,两类细胞可依托TGF-β/Smad、CSF-1/CSF-1R等信号通路构建相互调控的作用网络并介导心肌纤维化恶化。中医痰瘀互结病机理论指出痰浊与瘀血可相互滋生、交织阻滞,是各类慢性迁延性疾病的关键发病基础。本文以中医痰瘀互结理论为研究切入点,剖析该病机理论与巨噬细胞、成纤维细胞交互作用的内在关联,整合现代医学关于两种细胞交互作用的现有研究成果,深入分析细胞互作在心肌纤维化发病过程中的协同机制与病理关联,旨在为心肌纤维化的中西医协同防治提供理论依据,为相关动物实验及临床应用研究筑牢研究基础。
Myocardial fibrosis is a key pathological change in the progression of cardiovascular diseases such as heart failure. The progression mechanism of this disease relies on the reciprocal regulation between macrophages and fibroblasts. Current modern medical research has confirmed that macrophages can mediate inflammatory responses and tissue repair processes through M1 and M2 phenotypic polarization behaviors, and fibroblasts can differentiate into myofibroblasts and promote abnormal extracellular matrix deposition. The two types of cells can construct a reciprocal regulatory network through signaling pathways such as TGF-β/Smad and CSF-1/CSF-1R, thereby mediating the deterioration of myocardial fibrosis. The theory of phlegm and blood stasis intermingling in traditional Chinese medicine suggests that phlegm turbidity and blood stasis can mutually generate and interweave to cause obstruction, serving as a key pathological basis for various chronic and persistent diseases. This article takes the traditional Chinese medicine theory of phlegmblood stasis intermingling as a research entry point, analyzes the intrinsic relationship between this pathological theory and the interaction of macrophages and fibroblasts, integrates existing modern medical research findings on the interaction between the two cell types, and deeply analyzes the synergistic mechanisms and pathological correlations of cellcell interactions in the pathogenesis of myocardial fibrosis. The aim is to provide a theoretical basis for the integrated traditional Chinese and Western medicine prevention and treatment of myocardial fibrosis, and also to lay a solid research foundation for related animal experiments and clinical application studies.

非重型肺源性ARDS患者发病后30 d内发生肺纤维化的风险因素及构建的Logistic风险预测模型对肺纤维化发生的预测效能

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目的 探讨非重型肺源性急性呼吸窘迫综合征(ARDS)患者发生肺纤维化的影响因素,并构建Logistic回归模型,以筛选高危患者,指导临床制定针对性干预方案。方法 前瞻性选取2022年1月~2024年12月于本院诊治的134例非重型肺源性ARDS患者为研究对象,依据发病后30 d内是否发生肺纤维化将其分为发生组58例、未发生组76例。比较两组临床资料,并通过多因素Logistic回归分析肺纤维化发生的影响因素。构建Logistic回归模型,并分析该模型对肺纤维化发生的预测价值。结果 多因素Logistic回归分析显示病程中出现休克、脓毒症、吸烟史、肺动脉高压及血清白细胞介素-8(IL-8)、低氧诱导因子-1α(HIF-1α)、Clara细胞分泌蛋白16(CC-16)、成纤维细胞生长因子(FGF-2)水平为肺纤维化发生的独立危险因素(P<0.05);Logistic回归模型预测肺纤维化发生的AUC值为0.871,敏感度、特异度分别为77.59%、84.21%,Hosmer-Lemeshow检验该模型与观测值拟合度良好,且Bootstrap检验显示该模型具有良好的区分度。结论 病程中出现休克、脓毒症、吸烟史、肺动脉高压及血清IL-8、HIF-1α、CC-16、FGF-2水平为非重型肺源性ARDS患者发生肺纤维化的独立危险因素,基于上述危险因素构建Logistic回归模型,该模型预测肺纤维化发生具有良好的预测效能,临床可依据上述因素采取针对性干预方案,以降低肺纤维化发生率。
综述

Wnt/β-catenin信号通路在心肌纤维化中的作用研究进展

Research progress on the role of Wnt / β-catenin signaling pathway in myocardial fibrosis

:85-90
 
Wnt/β-catenin信号通路是一种在胚胎发育,细胞增殖分化、迁移,干细胞更新等中起关键作用的蛋白质家族。Wnt/β-catenin信号通路的失调常常会导致各种严重的疾病,例如肿瘤、心脏疾病、肺部疾病、肝脏疾病、骨骼疾病、神经疾病等。大量研究表明,Wnt/β-catenin信号通路在心肌纤维化发病机制中起重要作用,本文结合最新研究成果,从心肌纤维化相关疾病的角度对Wnt/β-catenin通路进行综述,为预防心肌纤维化提供新的思路,进一步达到防治心血管疾病的目的。
The Wnt/β-catenin signaling pathway is a family of proteins that play a key role in embryonic development,cell proliferation and differentiation,migration,stem cell renewal,etc.Dysfunctions of Wnt/β-catenin signaling pathway often lead to various serious diseases,such as tumor,heart,lung,liver,bone and neurological diseases,etc.Numerous studies have shown that the Wnt/β-catenin signaling pathway plays an important role in the pathogenesis of cardiac fibrosis.This article,in combination with the latest research findings,presents a review of the Wnt/β-catenin pathway from the perspective of myocardial fibrosis-related diseases,in order to provide new ideas for preventing myocardial fibrosis and achieving the goal of combating cardiovascular disease.
论著

复方甘草口服液联合泼尼松治疗特发性肺间质纤维化急性加重期患者的疗效及安全性研究

Study on the efficacy and safety of compound licorice oral liquid combined with prednisone in the treatment of patients with acute exacerbation of idiopathic pulmonary interstitial fibrosis

:1177-1182
 
目的 探讨复方甘草口服液联合泼尼松治疗特发性肺间质纤维化急性加重期患者的疗效。方法 选取张掖市第二人民医院2020年1月—2023年10月收治的128例特发性肺间质纤维化急性加重期患者,应用随机数字表法分为两组,每组各64例。对照组采取泼尼松治疗,观察组采取复方甘草口服液联合泼尼松治疗。对比其临床疗效,治疗前后血清肺纤维化指标及炎症因子水平,最后对比其不良反应发生率。结果 观察组总有效率93.75%,高于对照组的79.69%(χ2=5.490,P=0.019);治疗前两组层黏连蛋白(LN)、Ⅲ型前胶原肽(PC-Ⅲ)、透明质酸(HA)对比差异无统计学意义(P>0.05),治疗后两组患者LN、PC-Ⅲ、HA均降低,观察组[(89.25±7.61)μg/L;(68.33±7.68)mg/L;(81.53±8.54)μg/L]低于对照组[(96.17±8.34)μg/L;(75.68±8.25)mg/L;(95.68±9.25)μg/L],对比差异有统计学意义(t1=4.903,P1<0.001;t2=5.217,P2<0.001;t3=8.992,P3<0.001);治疗前两组患者肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)、IL-10、转化生长因子(TGF-β1)对比差异无统计学意义(P>0.05),治疗后两组TNF-α、IL-4、IL-10、TGF-β1水平降低,观察组[(61.94±8.24)ng/L;(4.43±1.17)ng/mL;(65.49±13.24)g/L;(114.73±13.12)pg/mL]低于对照组[(75.52±9.43)ng/L;(6.31±1.28)ng/mL;(79.27±9.38)g/L;(147.76±15.46)pg/mL],对比差异有统计学意义(t1=8.675,P1<0.001;t2=8.673,P2<0.001;t3=6.794,P3<0.001;t4=13.032,P4<0.001);两组不良反应发生率对比差异无统计学意义(7.81% vs 6.25%,χ2=0.120,P=0.730)。结论 复方甘草口服液联合泼尼松治疗特发性肺间质纤维化急性加重期疗效显著,可辅助延缓患者肺纤维化发展进程,减轻机体炎症反应,安全性较高。
Objective To investigate the efficacy of compound licorice oral liquid combined with prednisone in patients with acute exacerbations of idiopathic pulmonary interstitial fibrosis. Methods A total of 128 patients with acute exacerbation of idiopathic pulmonary interstitial fibrosis admitted to Zhangye Second People's Hospital from January 2020 to October 2023 were divided into two groups by random number table method,with 64 patients in each group.The control group received prednisone treatment,while the observation group received compound licorice oral liquid combined with prednisone treatment.Compare its clinical efficacy,serum pulmonary fibrosis indicators and inflammatory factor levels before and after treatment,and finally compare its incidence of adverse reactions. Results The total response rate in the observation group was 93.75%,which was higher than the 79.69% in the control group(χ2=5.490,P=0.019).There was no difference between the two groups of LN,PC-III,and HA(P>0.05),LN,PC-III and HA were decreased in both groups,while the observation group[(89.25±7.61)μg/L;(68.33±7.68)mg/L;(81.53±8.54)μg/L] was lower than the control group[(96.17±8.34)μg/L;(75.68±8.25)mg/L;(95.68±9.25)μg/L],the contrast difference was statistically significant(t1=4.903,P1<0.001;t2=5.217,P2<0.001;t3=8.992,P3<0.001).There was no difference in TNF-α,IL-4,IL-10,and TGF-β1 between the two groups before treatment(P>0.05),lower levels of TNF-α,IL-4,IL-10,and TGF-β1 in the two patient groups after treatment,the observation group[(61.94±8.24)ng/L;(4.43±1.17)ng/mL;(65.49±13.24)g/L;(114.73±13.12)pg/mL] was lower than the control group[(75.52±9.43)ng/L;(6.31±1.28)ng/mL;(79.27±9.38)g/L;(147.76±15.46)pg/mL],the contrast difference was statistically significant(t1=8.675,P1<0.001;t2=8.673,P2<0.001;t3=6.794,P3<0.001;t4=13.032,P4<0.001).There was no difference in the incidence of adverse effects between the two groups(7.81% vs 6.25%,χ2=120,P=0.730). Conclusions The combination of compound licorice oral liquid and prednisone has a significant therapeutic effect on the acute exacerbation of idiopathic pulmonary interstitial fibrosis.It can assist in delaying the progression of pulmonary fibrosis in patients,reducing the body's inflammatory response,and has high safety.
论著

血浆置换治疗抗MDA5阳性皮肌炎伴肺间质纤维化临床疗效及安全性分析

Clinical efficacy and safety analysis of plasmapheresis for anti-MDA 5 positive dermatomositis with lung interstitial fibrosis

:1166-1171
 
目的 探讨血浆置换联合泼尼松(PDN)联合环磷酰胺(CTX)治疗抗黑色素瘤分化相关基因5(MDA5)抗体阳性皮肌炎(DM)伴肺间质纤维化(ILD)患者疗效及安全性。方法 回顾性分析2014年6月—2023年6月普洱市人民医院诊断的MDA5阳性DM伴ILD患者40例,其中治疗组20例,采用血浆置换联合PDN 1 mg/kg每日1次口服,4周后减量,每周减总量10%,CTX 1 g每月1次静脉滴注,共6次治疗;另20例设为对照组,采用PDN 1 mg/kg每日1次口服,4周后减量,每周减总量10%,CTX 1 g每月1次静脉滴注,共6次治疗,分别于治疗后3月、6月检测一氧化碳弥散量(DLCO)、第1秒用力呼气量(FEV1),血清铁蛋白(SF)、C-反应蛋白(CRP)、涎液化糖链抗原(KL-6)、MDA5转阴率行疗效评估。结果 在治疗3个月和6个月时,两组患者的DLCO、FEV1、SF、CRP、KL-6、MDA5转阴率等指标的完全缓解率不一致。其中,3个月时,治疗组上述指标的完全缓解率依次为95%、85%、90%、90%、90%、85%,对照组依次为15%、20%、20%、15%、0%、0%。两组患者在治疗3个月的DLCO、FEV1、SF、CRP、KL-6水平和MDA5转阴数均有所不同。其中治疗组的DLCO、KL-6、CRP水平均较对照组降低(P<0.01),治疗组FEV1水平较对照组升高(P<0.01),治疗组SF水平较对照组降低(P<0.05),两组治疗6个月时,治疗组上述指标缓解率依次为95%、85%、90%、90%、90%、85%,对照组依次为20%、25%、20%、20%、20%、5%。两组患者在DLCO、FEV1、SF、CRP、KL-6水平以及MDA5转阴数和死亡例数方面比较差异均有统计学意义,其中治疗组的DLCO、KL-6和CRP水平均较对照组降低(P<0.01),治疗组FEV1水平较对照组升高(P<0.01),SF水平治疗组较对照组降低(P<0.05)。结论 在MDA5抗体阳性DM伴ILD患者治疗中,给予血浆置换联合PDN、CTX治疗,可以提高疗效,降低病死率。
Objective To explore the effect of plasmapheresis combined with prednisone(PDN)plus cytoxan(CTX)on patients with anti-melanoma differentiation-associated gene 5(MDA 5)antibody-positive dermatomyositis(DM)with interstitial lung disease(ILD). Methods The data of 40 patients with MDA 5 positive DM and ILD diagnosed in the People's Hospital of Pu'er City from June 2014 to June 2023 were retrospectively was analyzed.Twenty patients of the treatment group were treated with plasmapheresis combined with PDN 1mg / kg once daily,which was reduced by 10% per week after 4 weeks.The other 20 patients of the control group were treated with PDN 1mg / kg once daily,which was reduced after 4 weeks by 10% per week,and CTX 1g once per month.diffusing capacity of the lungs for carbon monoxide(DLCO),forced expiratory volume in the first second(FEV1),serum ferritin(SF),C-reactive protein(CRP),Krebs Von den Lungen-6(KL-6)and MDA5 negative conversion rate were measured at 3 and 6 months after treatment,respectively. Results At 3 and 6 months of treatment,complete remission rates of DLCO,FEV1,SF,CRP,KL-6,MDA 5 conversion and other indicators were inconsistent.Among them,at 3 months,the complete response rate of the above indicators in the treatment group was successively:95%,85%,90%,90%,90% and 85%.The control group was 15%,20%,20%,15%,and 0%,0%.Statistical analysis showed that the levels of DLCO,FEV1,SF,CRP,KL-6 and MDA 5 significantly varied at 3 months of treatment.Pairwise comparison of LSD found that the DLCO,KL-6 and CRP levels in the treatment group were significantly lower than the control group(P<0.01),the FEV1 level in the treatment group was significantly higher(P<0.01),and the SF level in the treatment group was significantly lower(P<0.05).After 6 month of treatment,the complete response rate of the above indicators in the treatment group were 95%,85%,90%,90%,90% and 85%,and the complete response rate of the above indicators in the control group was 20%,25%,20%,20%,20% and 5%.Statistical analysis showed the levels of DLCO,FEV1,SF,CRP,KL-6 for the amount of MDA 5 and the number of deaths between two groups were significantly different.Further pairwise comparison of LSD showed that the DLCO,KL-6 and CRP levels in the treatment group were significantly lower compared with the control group(P<0.01),the FEV1 level was significantly increased compared with the control group(P<0.01),and the SF treatment group was significantly decreased compared with the control group(P<0.05). Conclusions In the treatment of patients with MDA 5 antibody positive DM with ILD,the treatment of plasmapheresis combined with PDN and CTX can significantly improve the efficacy and reduce the mortality rate.
专家综述

纳米载体药物用于缓解慢性肾脏病纤维化的研究进展

Recent advances in nanomedicines for alleviating chronic kidney disease fibrosis

:1-10
 
慢性肾脏病是一类具有高发病率、高死亡率的慢性疾病群。临床上一般采用血液透析和肾脏移植治疗终末期的慢性肾脏病。研究表明,小分子药物或核酸类药物在慢性肾脏病治疗中极具潜力,但是缺乏特异性导致肾脏纤维化治疗效果有限,亟需开发新的治疗策略。纳米载体因具有良好的理化性质,被广泛应用于生物医学领域。本文综述了近年来纳米载体递送小分子或核酸类药物在慢性肾脏病中的研究进展。
Chronic kidney disease (CKD) is a series of chronic disease groups associated with high morbidity and mortality. Hemodialysis and kidney transplantation are the only choices for end-stage renal disease. According to the literature report, it is shown that small molecule and nucleic acid drugs have great potential in CKD treatments with an unsatisfied therapeutic efficacy because of the lack of specific targeting. Thus, it is necessary to develop a new strategy. Nanocarriers have been widely used in biomedical fields due to their excellent physical and chemical properties. In this review, we have summarized the recent advances in applying functional nanocarriers to deliver the small molecules and nucleic acid drugs in the treatment of CKD.
论著

基于网络药理学预测黄甲软肝颗粒抗肝纤维化作用及验证研究

Prediction of anti-hepatic fibrosis effect of Huangjia Ruangan Granules based on pharmacology network and its verification

:119-127
 
目的 利用网络药理学技术,分析黄甲软肝颗粒治疗肝纤维化的作用网络,以及黄甲软肝颗粒治疗肝纤维化的潜在作用机制,并在体内动物实验进行初步验证。方法 采用中药系统药理学分析平台中寻找黄甲软肝颗粒中10味中药相关的化学成分和作用靶点,通过GeneCards等数据库筛选肝纤维化疾病相关的靶标;对药物与疾病靶点相映射得到黄甲软肝颗粒治疗肝纤维化的作用靶点,运用cytoscape将疾病靶点与复方活性成分靶点的交集-交集部分对应的活性成分”构建“C(成分)-T(靶点)”作用网络。将交集靶点利用 DAVID数据库进行GO富集分析和KEGG富集分析,以获得其潜在作用机制。最后,通过黄甲软肝颗粒防治CCl4导致SD大鼠肝纤维化的体内实验进行初步验证,考察末次给药后大鼠体质量和肝脏指数,采用微板法检测SD大鼠血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平,苏木精-伊红染色观察肝脏病理学变化。结果 预测筛选得到黄甲软肝颗粒共有117个潜在活性成分,266个活性成分对应靶点,161个交集靶点,关键成分有槲皮素、山奈酚、丹参酮IIA、芒柄花黄素等,关键靶点有PTGS2、PTGS1、NCOA1、ACHE、HTR、RXRA、ADRB2、IL1B等。GO 分析共包含 960条富集结果,其中生物过程845 条,分子功能 63条,细胞组成 52 条;KEGG 分析共得出68条通路,与本次研究较相关的通路主要包括TNF信号通路、Toll样受体信号通路、Rap1信号通路、胞质DNA传感途径、ErbB信号通路、VEGF信号通路等。体内动物实验研究表明,黄甲软肝颗粒能显著降低大鼠的肝脏指数和血清ALT、AST,改善肝组织病理学指标。结论 黄甲软肝颗粒可通过多成分、多途径、多靶点协同发挥治疗肝纤维化的作用,本研究为黄甲软肝颗粒治疗肝纤维化疾病的物质基础、作用机制及临床应用的进一步研究奠定基础。
Objective To analyze the effective network of Huangjia Ruangan Granules in treating liver fibrosis and its potential mechanism by using network pharmacology, and preliminary verify by animal in vivo experiments. Methods From the Chinese Medicine System Pharmacology Analysis Platform, we searched for the chemical constituents and targets of 10 Chinese herbs in Huangjia Ruangan Granules, and screened the targets related to liver fibrosis diseases through GeneCards and other databases. The drug and disease target were mapped to the target of Huangjia Ruangan Granules for the treatment of liver fibrosis, and the active component corresponding to the intersection of the disease target and the compound active component target was constructed using cytoscape “C (component)-T (target)” action network. The intersection target was used for GO enrichment analysis and KEGG enrichment analysis with DAVID database to obtain its potential mechanism of action. Finally, through the in vivo experiment of using Huangjia Ruangan Granules to prevent and treat CCl4 leaded liver fibrosis in SD rats, the rats' body weight and liver index after the last dose were recorded, and the levels of aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of SD rats were detected by the microplate method, hematoxylin-eosin staining were used to observe liver pathological changes. Results Predictive screening showed that Huangjia Ruangan Granules had 117 potential active ingredients, 266 active ingredients corresponded to targets, and 161 intersection targets. The key ingredients was quercetin, kaempferol, tanshinone IIA, formononetin, etc. The key targets were PTGS2, PTGS1 NCOA1, ACHE, HTR, RXRA, ADRB2, IL1B, etc. GO analysis showed a total of 960 enrichment results, including 845 biological processes, 63 molecular functions, and 52 cell compositions; KEGG analysis revealed a total of 68 pathways, the related pathways included TNF signaling pathway, Toll-like receptor signaling pathway, Rap1 signaling pathway, cytoplasmic DNA sensing pathway, ErbB signaling pathway and VEGF signaling pathway, etc. In vivo animal experiments had shown that Huangjia Ruangan Granules could significantly reduce the liver index and serum ALT and AST levels of rats, and improve liver histopathological indicators. Conclusions Huangjia Ruangan Granules treated liver fibrosis through multi-component, multi-pathway and multi-target synergy. This research laid the groundwork for the material basis, mechanism and clinical application of Huangjia Ruangan Granules in treating liver fibrosis diseases.
论著

I131联合TSH抑制治疗对术后中高危组甲状腺乳头状癌患者心肌纤维化及心房颤动的影响

Impact of I131 combined with thyroid-stimulating hormone for suppressive treatment on myocardial fibrosis and atrial fibrillation in patients with papillary thyroid

:40-44
 
目的 探讨I131联合促甲状腺激素(TSH)抑制治疗对术后中高危组甲状腺乳头状癌(PTC)患者心肌纤维化及心房颤动(AF)的影响。方法 选取2016年8月—2017年8月南华大学附属第一医院收治的因PTC行甲状腺双侧腺叶全切术或近全切除术患者69例,根据复发危险度分层分为中危组(49例)和高危组(20例), 两组患者均行I131 联合TSH抑制治疗,治疗后嘱患者3个月进行1次复诊或自觉不适及时复诊,观察患者心血管系统症状、心房颤动及心肌纤维化发生情况,患者治疗前后可溶性基质溶素-2(sST2)、生长分化因子-15(GDF-15)、半乳糖凝集素-3 (GAL-3)及血清乳酸脱氢酶(LDHA)含量变化。结果 I131联合TSH抑制治疗后患者心房颤动发生率和心肌纤维化相关指标水平明显高于治疗前,且高危组患者治疗后心房颤动发生率和心肌纤维化相关指标水平高于中危组,差异均有统计学意义(P<0.05)。结论 I131联合TSH抑制治疗会增加PTC患者心肌纤维化和心房颤动的发生概率,且高危组PTC患者心肌纤维化和房颤的发生率高于中危组。
Objective To investigate the impact of I131 combined with thyroid-stimulating hormone(TSH) for suppressive treatment on myocardial fibrosis(MF) and atrial fibrillation(AF) in patients with papillary thyroid (PTC). Methods 69 patients with PTC undergoing total or subtotal thyroidectomy admitted into First Affiliated Hospital of University of South China from Aug. 2016 to Aug. 2017 were selected and divided into middle-risk group (49 cases) and high-risk group (20 cases) according to the recurrence risk stratification. Two groups of patients were given I131 combined with thyroid-stimulating hormone for suppressive treatment. The patients were instructed to undergo a follow-up visit every 3 months after treatment or whenever felt unwell. The incidences of cardiovascular system symptoms, atrial fibrillation and myocardial fibrosis, changes of contents of serum soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), galectin-3 (GAL-3) and lactate dehydrogenase A (LDHA) were observed. Results After I131 combined with thyroid-stimulating hormone suppressive treatment, the incidences of atrial fibrillation and myocardial fibrosis after treatment were higher than that before treatment, and the incidences of atrial fibrillation and myocardial fibrosis of high-risk group were higher than those of the middle-risk group, with statistically significant differences (P<0.05). Conclusion Combined use of I131 and thyroid-stimulating hormone for suppressive treatment can increase the incidences of atrial fibrillation and ventricular remodeling of patients with PTC, and the incidences of high-risk group were higher than those of the middle-risk group.
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