Research Survey of Animal Model of Hepatic Fibro-sis Integrated with Western Medicine Diseases and Traditional Chinese Medicine^TCM~)Syndrome

Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.

基于hACE2转导建立SARS-CoV-2 spike假病毒感染病证结合的小鼠病毒肺炎模型

目的建立与评价一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型。方法30只KM种小鼠随机分为空白组、对照组及实验1组、实验2组、实验3组,每组各6只。每天把KM小鼠置于模拟寒湿环境中4 h,将表达hACE2的重组腺相关病毒(pAAV-hACE2)采用改良悬挂法气管内给药转导至肺组织,继以新型冠状病毒(SARS-CoV-2)spike假病毒采用相同的气管内给药方式造模。观察各组小鼠一般情况,检测体重变化、肺指数、血清炎性因子及肺部病理变化。结果免疫组化法显示h ACE2在小鼠肺组织中有效表达;在寒湿环境中给予SARS-CoV-2 spike假病毒后,实验组小鼠表现出类似疫毒犯肺证候的体征;且同样喂养条件和时间下,与空白组和对照组小鼠比较,实验组小鼠出现体重下降;实验1、2、3组小鼠出现肺指数显著增大(P<0.05或P<0.01),血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)显著升高(P<0.01),肺组织病理改变明显。结论本研究成功建立了一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型。

Clinical treatment of myasthenia gravis with deficiency of spleen and kidney based on combination of disease with syndrome theory

OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG patients with a deficiency of both spleen and kidney were randomly divided into an treatment group (n=30) treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide) and a control group (n= 30) treated with Jianjining granules. The dosage of the three drugs was reduced over the course of treatment. After 3 and 6 months of treatment, the curative effect was evaluated with the muscle weakness severity scale (MWSS). RESULTS: The MWSS score after treatment declined significantly in both groups. The score in the treatment group was much lower than that in thecontrol group (P<0.05). The total effective rate was 63.33% (19/30) in the treatment group and 36.67% (11/30) in the control group after 3 months of treatment, and 80.00% (24/30) and 50.00% (15/30), respectively, after 6 months of treatment. The obvious and total effective rates in the treatment group were much higher than those in the control group (P<0.05). After 6 months of treatment, there were no obvious differences (P>0.05) in the obvious and effective rates between the 2 groups. However, the total effective rate in the treatment group was much higher than that in the control group (P<0.01). CONCLUSION: Using the theory on the combination of disease with syndrome, we found that the curative effect of Jianjining and Western Medicine on MG patients with deficiency of both spleen and kidney is worth further exploration.

Disease-Syndrome Combination Clinical Study of Psoriasis:Present Status,Advantages,and Prospects

Psoriasis is an immune-abnormal,chronic,proliferative skin disease determined by polygenic inheritance and induced by a number of environmental factors.It causes worldwide concern because of its high-prevalence,harmful and incurable characteristics.Over the years,Chinese medicine（CM） treatment of psoriasis has accumulated a wealth of clinical experience.Disease-syndrome combination, which achieves more satisfactory clinical effect,is the basis to highlight the special CM advantages in treating psoriasis.In this paper,we review the advantages of treating psoriasis with the combination of disease and syndrome,analyze the prospects of research on treating psoriasis combining disease with syndrome.We also make a point that there are several key points for the clinical research of combination of disease and syndrome.It can be expected that carrying out clinical research on the combination of disease and syndrome will help improve the clinical efficacy of medical treatment of psoriasis,which will be the main direction of research in the future.

Risk factors of postoperative cerebral hyperperfusion syndrome and its relationship with clinical prognosis in adult patients with moyamoya disease

Background To investigate the incidence,risk factors,and clinical prognosis of cerebral hyperperfusion syndrome(CHS)after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis(STA-MCA/EDAS)in adult patients with moyamoya disease(MMD).Methods The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed.According to CHS diagnosis,MMD patients were divided into CHS and non-CHS group.Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed.Results A total of 12 patients(7.5%)developed postoperative CHS,of which 4 patients(2.5%)presented with cerebral hemorrhage.Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere(OR=3.04,95%CI=1.02-9.03,P=0.046)and left operated hemisphere(OR=5.16,95%CI=1.09-21.34,P=0.041)were independent risk factors for CHS.The other variables,such as age,gender,presentation,hypertension,diabetes,smoking,mean mRS score on admission,modified Suzuki stage and pre-infarction stage on surgical hemisphere,and bypass patency,had no association with postoperative CHS(P>0.05).At final follow-up with average 38 months,there were 18 out of 133 patients(13.5%,4.91%per person year)presented with newly developed complications.There was no significant difference between newly developed complications,mean mRS scores,and Kaplan-Meier curve of stroke-free survival in patients with and without CHS(P>0.05).Conclusion The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS,which could not affect the clinical prognosis if treated timely and properly.The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Combined liver-kidney transplantation for rare diseases

Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.

RF、抗CCP抗体、SP-A以及SP-D对类风湿关节炎合并间质性肺病的预测价值

目的探讨RF、抗CCP抗体、SP-A以及SP-D对类风湿关节炎(rheumatoid arthritis,RA)合并间质性肺病(interstitial lung disease,IL-D)的预测价值。方法选取2020年12月—2021年12月在顺德和平外科医院治疗的180例RA-ILD患者作为RA-ILD组,同期选取了102例单纯RA患者作为RA组。比较两组类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体、表面活性蛋白(SP)-A及SP-D,并绘制受试者工作特性曲线(ROC)获取曲线下面积(AUC),评估各指标对RA-ILD的预测价值。随访患者6个月时间,根据病情转归情况将RA-ILD组分为两个亚组,即好转组(132例)和进展组(48例),比较两个亚组患者的RF、抗CCP抗体、SP-A、SP-D水平。采用Pearson检验分析RF、抗CCP抗体、SP-A、SP-D与肺间质病变评分的相关性。结果RA-ILD组患者RF、抗CCP抗体、SP-A、SP-D水平均显著高于RA组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,RF(AUC=0.741)、抗CCP抗体(AUC=0.663)、SP-A(AUC=0.825)、SP-D(AUC=0.804)均对RA-ILD具有显著的预测价值(P<0.05)。好转组患者的RF、抗CCP抗体、SP-A、SP-D水平均显著低于进展组,差异有统计学意义(P<0.05)。Pearson相关性检验分析结果显示,RF、抗CCP抗体、SP-A、SP-D与肺间质病变评分均呈现正相关性(r=0.378、0.516、0.526、0.388,P<0.05)。结论RF、抗CCP抗体、SP-A以及SP-D对RA-ILD具有显著的诊断和预后评估价值,可作为病情随访监测的血清学指标。

基于治未病理论灸药同治对实体恶性肿瘤化疗患者骨髓抑制的预防作用

目的:基于治未病理论探讨灸药同治对实体恶性肿瘤化疗患者骨髓抑制的预防作用。方法:选取2019年1月至2022年1月于武汉科技大学附属武汉亚心总医院接受治疗的实体恶性肿瘤化疗患者120例作为研究对象,采用随机数字表法分为对照组和观察组,每组60例。对照组常规接受化疗,观察组化疗前连续3 d给予灸药同治(艾灸+加味八珍汤)。比较治疗前、化疗后7 d 2组患者中医证候积分、血常规[血红蛋白(Hb)、白细胞计数(WBC)、血小板计数(PLT)、中性粒细胞计数(NEUT)]、生命质量[卡诺夫斯凯计分(KPS)、中国癌症患者生命质量(QOL_(2))调查问卷],比较化疗后7 d 2组患者骨髓抑制情况[发生率、严重程度、重组人粒细胞集落刺激因子(rhG-CSF)使用情况]。结果:化疗后7 d,2组患者中医证候积分升高,但观察组低于对照组(P<0.05);Hb、WBC、PLT、NEUT、KPS评分及QOL_(2)评分降低,但观察组高于对照组(均P<0.05);观察组骨髓抑制发生率、rhG-CSF使用率低于对照组,0、Ⅰ度比例高于对照组(均P<0.05)。结论:基于治未病理论,灸药同治能够改善实体恶性肿瘤化疗患者临床症状及血常规,提高患者生命质量,减少骨髓抑制的发生。

基于病证结合特点的绝经后骨质疏松症动物模型分析

绝经后骨质疏松症(PMOP)病证结合动物模型在中医药研究中应用较多,但建立方法各式各样且缺乏统一的评价标准。文章从中医学和现代医学临床角度出发,就目前PMOP模型动物选择、构建方法和模型动物与临床吻合度进行对比,结合病证结合动物模型构建思路,从PMOP病证结合动物模型的构建和进一步完善评价方法进行归纳总结,以期为PMOP实验研究提供新思路。

基于数据挖掘的胆石症动物模型特点及应用分析

目的对现有胆石症动物模型进行整理归纳,探索可更好反映中西医临床病证特点,满足中医药临床与基础研究发展需要的动物模型。方法检索中国知网、万方、维普、SinoMed、PubMed等数据库,对国内外胆石症相关实验研究的动物模型进行搜集和整理,对模型的动物种类、造模方法、造模周期、检测指标和阳性药等数据进行统计和分析。结果纳入的128篇文献中,胆石症模型的动物种类以豚鼠、家兔和C57BL/6小鼠为主。使用最多的造模方法为高脂饲料法,饲料喂养周期集中在8周。高频检测指标为成石率、总胆固醇、磷脂、总胆红素、总胆汁酸等。较多使用的干预方式为中药复方、西药和单味中药或提取物,西药干预以熊去氧胆酸(Ursodeoxycholic acid,UDCA)为主,中药干预以中药复方为主,还包括针灸、运动、饮食等其他干预方式。实验设立阳性对照药多为UDCA。结论随着胆石症动物模型的不断完善和发展,目前有较多种造模方法都较好地模拟了胆石症中西医临床表现特点,但也存在一定局限性。该文分析结果可为胆石症模型的选择、应用和完善提供参考。

加味柴胡加龙骨牡蛎汤治疗情志病热郁少阳证的临床疗效

目的探讨加味柴胡加龙骨牡蛎汤治疗情志病热郁少阳证的临床疗效。方法选取2021年9月—2023年11月南京中医药大学太仓附属医院、江苏省中医院收治的情志病热郁少阳证患者245例,按照随机数字表法将其分为对照组120例与治疗组125例。对照组采用草酸艾司西酞普兰片治疗,治疗组患者在对照组基础上加用加味柴胡加龙骨牡蛎汤治疗,两组疗程均为6周。比较两组临床疗效,治疗前及治疗2、4、6周后核心症状总积分、中医证候积分,治疗前及治疗6周后汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表24项(HAMD-24)、匹兹堡睡眠质量指数(PSQI)各维度评分及其总分,不良反应发生率。结果治疗组临床疗效优于对照组(P<0.05)。治疗方法与时间在核心症状总积分、中医证候积分上存在交互作用(P<0.05);治疗方法、时间在核心症状总积分、中医证候积分上主效应显著(P<0.05)。治疗组治疗4、6周后核心症状总积分及治疗2、4、6周后中医证候积分低于对照组(P<0.05)。治疗6周后,治疗组躯体性焦虑维度评分,焦虑/躯体化、绝望感维度评分及HAMD-24总分,睡眠障碍、催眠药物使用维度评分低于对照组(P<0.05)。对照组不良反应总发生率与治疗组比较,差异无统计学意义(P>0.05)。结论加味柴胡加龙骨牡蛎汤治疗情志病热郁少阳证的疗效确切,可有效减轻患者核心症状、病情程度及躯体症状,减轻睡眠障碍及催眠药物依赖程度,且临床安全性较高。

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

基于《黄帝内经》病证结合思想探讨疾病循证病机-证治体系研究模式

深度挖掘《黄帝内经》病证结合思想,《黄帝内经》首开辨病论治之先河,在此基础上,又将辨病与脏腑辨证、病因辨证、经络辨证及六经辨证有机结合,开启了病证结合思想的萌芽,为后世病机、证候、治则治法理论的发展奠定了坚实的理论基础。基于病机、证候、治法、方药之间的内在联系性与统一性,提出病证结合是循证病机-证治体系的立论基础,循证病机-证治体系以疾病为研究基础,以病机为核心要素,以临床疗效为评价标准,“基于疗效,评价病机”是构建疾病循证病机-证治体系的关键。在疾病循证病机-证治体系的构建过程中,借鉴循证医学系统评价的方法,通过“以方测证、验证病机”的方式,为循证病机-证治体系的构建提供思路。

基于国医大师郭子光“人-症-病-证”体系探析慢性萎缩性胃炎临床辨治路径

慢性萎缩性胃炎(Chronic Atrophic Gastritis,CAG)中常见的肠上皮化生、异型增生属于胃癌前状态。中医在逆转肠上皮化生及异型增生方面具有治疗优势。笔者系国医大师郭子光教授学术传承人,在郭师学术思想指导下,初步提出基于“人-症-病-证”体系慢性萎缩性胃炎临床辨治路径。以病为纲,抓住CAG“脾气胃阴亏虚,湿热瘀阻胃络”的共性核心病机;兼顾个性,结合患者不同证型的个性病机。以“益气养阴,清热燥湿,和胃通络”为基本治则,创制了“益胃复萎”方这一验方,基于此方,分型分期加减论治。病证结合,最大化地优化临床疗效,更能发挥中医特色优势。

百合地黄汤及其类方在肿瘤治疗中的应用

肿瘤进展及化疗、放疗、手术各种治疗过程中患者常发生的不适症状(例如抑郁、心烦、食欲时好时坏、呕吐、口苦、小便色黄、身体虚弱)与百合病类似。仲景病证结合思路也适用于肿瘤治疗。例如,百合地黄汤加减治疗非小细胞肺癌及放射性肺炎、百合类方治疗肿瘤相关性抑郁焦虑、百合知母汤加减治疗乳腺癌术后心烦夜寐难安及肿瘤并发出血,百合滑石散加减治疗直肠癌术后抑郁兼小便灼热、百合滑石代赭汤加减治疗胃癌。以百合地黄汤为主方的病证结合思路在运用到肿瘤治疗时需注意明辨证型,抓住主症,病证结合。此外,对于百合地黄汤的其他类方(百合鸡子汤、百合洗方、栝蒌牡蛎散)目前虽未见肿瘤临床文献报道,但亦可应用于今后临床实践中,从而提高患者生活质量。

江泳教授病证结合分人分型分期辨治带状疱疹

带状疱疹以剧烈疼痛为其特点,严重影响患者生活。西医治疗虽起效较快但使疼痛降低至初始程度一半时较易产生不良反应,且在预防及控制其并发症方面效果不佳。江泳教授以病为纲,认为带状疱疹以肝络血虚,热毒湿浊瘀滞肝络为其共性核心病机,结合患者不同证型的个性病机进行分型论治。江教授以“柔肝泻火,解毒除湿,通络止痛”为基本治则,创制“泻毒通络”方为基础验方,分人分型分期加减治疗带状疱疹,她认为病证结合辨治带状疱疹,可以最大化地优化临床疗效,更能发挥中医特色优势。

病证结合动物模型宏观表征指标评价方法研究进展

动物实验在中医药的发展中起重要作用,病证结合动物实验更是实现中医药现代化的必经之路。近年来,随着病证结合动物实验的不断发展,动物模型的建立与评价体系均在不断完善,然而其模型的宏观指标评价仍有很大不足,多数实验仅通过观察法来判断动物的宏观体征,常具有主观性且缺乏科学性。因此,通过文献综述方法系统地整理了目前病证结合动物模型各证候宏观表征评价指标的进展,并提出各宏观指标定量评价模式,认为此模式为动物实验发展路上的可行且必要途径,同时结合实验室行为学设备等来探索证候定量的测量方法,以期通过专业的仪器设备来评价证候指标,进而解决动物实验模型指标评价的关键问题,完善宏观指标评价标准,推动病证结合动物实验进一步的发展。

胃癌前病变病证结合动物模型研究进展

中医药在胃癌前病变(precancerous lesions of gastric cancer,PLGC)诊疗中发挥着重要作用,病证结合动物模型是进行PLGC相关实验研究的前提。文章从模型动物选择、胃癌前病变疾病模型和病证结合模型三方面,对近年来PLGC病证结合模型的制备方法进行了归纳分析,介绍了脾胃虚弱、胃阴不足、肝胃气滞、脾胃湿热和胃络瘀血5个常见PLGC病证结合模型的造模方法,并对当前模型制备中存在的问题提出了思考与展望。

病证结合骨质疏松模型大鼠骨骼的生物力学性能分析

背景:肾虚是骨质疏松症的最主要病机,对肾阳虚、肾阴虚与骨质疏松的关系研究有利于病证结合临床诊疗模式的发展。目的:评价右归丸对肾阳虚、肾阴虚大鼠股骨生物力学性能的影响差异,从生物力学角度论证骨质疏松症病证结合、因证施药的科学性。方法:手术摘除60只雌性SD大鼠双侧卵巢建立骨质疏松模型,10周后将大鼠随机分为肾阴虚组(n=30)和肾阳虚组(n=30),肾阳虚组臀部肌肉注射氢化可的松注射液,肾阴虚组灌胃甲状腺片混悬药液,1次/d,连续14 d。造模结束后,每组取20只灌胃右归丸混悬液,1次/d,连续12周,剩余10只作为对照不灌胃。灌胃结束后使用Micro-CT扫描测量股骨微结构参数,在力学试验机上对股骨分别进行三点弯曲、有限元仿真、股骨头压缩及表面压痕分布实验。结果与结论:①Micro-CT扫描显示,与肾阴虚组比较,肾阴虚+右归丸组股骨骨密度、骨体积分数、骨表面密度、骨小梁数量、骨小梁分离度升高(P<0.05);与肾阳虚组比较,肾阳虚+右归丸组股骨骨体积分数、骨表面密度、骨小梁数量及骨小梁厚度升高(P<0.05);②三点弯曲实验显示,与肾阳虚组相比,肾阳虚+右归丸组股骨弹性模量、最大抗弯强度和弯曲断裂强度均降低(P<0.05),韧性提高(P<0.05);③有限元仿真显示,右归丸能显著提高肾阳虚组大鼠股骨抗骨折能力,对肾阴虚组大鼠不产生明显作用;股骨头压缩实验显示,右归丸可增强肾阳虚组大鼠股骨头抵抗形变的能力,但右归丸对肾阴虚组和肾阳虚组大鼠股骨头表面性能的影响无显著区别;④结果表明,右归丸可增强肾阳虚骨质疏松骨骼生物力学性能,但对肾阴虚骨质疏松骨骼无显著影响。

脾虚证动物模型研究述评

中医界运用现代科学方法进行相关研究已有多年历史,在病证动物模型上颇有收获。本文对脾虚证动物模型发展历程进行回顾,对动物选择、造模方法、评价指标、消化系统病证结合模型进行总结和评论。模型动物多选用以大鼠为代表的小型啮齿类。目前,多基于病因病机造模,而较少使用化学药物与物理因素造模,复合因素造模法最常见。评价指标则分为中医证型指标、与“脾”功能和特性有关量化指标,以及方剂反证。功能性腹泻/消化不良为代表的脾虚证病证结合模型是目前研究的重心。脾虚证动物模型研究成绩斐然的同时仍存在许多不足,如缺乏脾虚证模型行业标准和共识,评价指标缺乏系统性和整体性,脾虚理论的现代阐释缺乏统一,学界亟需解决上述问题以促进发展。