Guideline for the diagnosis and treatment of rheumatoid arthritis with integrated traditional Chinese medicine and Western medicine to increase efficiency and reduce toxicity

Rheumatoid arthritis imposes a huge disease burden.Existing practice guidelines do not meet the needs of integrated traditional Chinese medicine and Western medicine in the treatment of rheumatoid arthritis.We established a guideline working group consists of a steering committee,a secretary group,an evidence evaluation group,a consensus group and a review group and developed a guideline following the guidance of the World Health Organization Handbook and the Chinese Medical Association.The guideline includes 35 recommendations which reached consensus by the two rounds Delphi surveys.These recommendations were formulated to address the following themes of most concern to clinician:diagnostic imaging,disease staging,traditional Chinese medicine syndromes,effectiveness and toxicity of integrated traditional Chinese medicine and Western medicine.

Reflections on the Toxicity and Safety of Traditional Chinese Medicine Combined with the Cases of Nephrotoxicity and Hepatotoxicity

This paper analyzes the relationship between toxicity and safety of traditional Chinese medicine(TCM)based on the cases of current nephrotoxicity and hepatotoxicity,and summarizes the literature on hepatotoxicity and nephrotoxicity.It is found that the main reasons for the toxic reaction of TCM are own factors of drugs,irregular administration of medicine and individual difference.However,as long as the"quality"and"quantity"of TCM are guaranteed,the toxicity of TCM can be controlled within the safety range.

Advances in Research of Toxic Traditional Chinese Medicines in the Treatment of Malignant Tumors

Combating poison with poison is an important method of traditional Chinese medicine to treat malignant tumors.This study reviews the experimental research on anti-tumor effects of toxic traditional Chinese medicines in recent years.It summarizes the action mechanism of toxic traditional Chinese medicines for the treatment of malignant tumors,including:inhibiting tumor cell proliferation and angiogenesis,inducing tumor cell apoptosis and differentiation,reversing tumor cell multidrug resistance(MDR),inhibiting tumor cell invasion and metastasis,and enhancing the body's immune functions.Finally,it discusses the research and development prospects of toxic traditional Chinese medicines as new anti-tumor drugs.

Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment

BACKGROUND Ribonucleotide reductase(RR)is a key enzyme in tumor proliferation,especially its subunit-RRM2.Although there are multiple therapeutics for tumors,they all have certain limitations.Given their advantages,traditional Chinese medicine(TCM)monomers have become an important source of anti-tumor drugs.Therefore,screening and analysis of TCM monomers with RRM2 inhibition can provide a reference for further anti-tumor drug development.AIM To screen and analyze potential anti-tumor TCM monomers with a good binding capacity to RRM2.METHODS The Gene Expression Profiling Interactive Analysis database was used to analyze the level of RRM2 gene expression in normal and tumor tissues as well as RRM2's effect on the overall survival rate of tumor patients.TCM monomers that potentially act on RRM2 were screened via literature mining.Using AutoDock software,the screened monomers were docked with the RRM2 protein.RESULTS The expression of RRM2 mRNA in multiple tumor tissues was significantly higher than that in normal tissues,and it was negatively correlated with the overall survival rate of patients with the majority of tumor types.Through literature mining,we discovered that berberine,ursolic acid,gambogic acid,cinobufagin,quercetin,daphnetin,and osalmide have inhibitory effects on RRM2.The results of molecular docking identified that the above TCM monomers have a strong binding capacity with RRM2 protein,which mainly interacted through hydrogen bonds and hydrophobic force.The main binding sites were Arg330,Tyr323,Ser263,and Met350.CONCLUSION RRM2 is an important tumor therapeutic target.The TCM monomers screened have a good binding capacity with the RRM2 protein.

A Brief Discussion on the Toxicity of Traditional Chinese Medicine

With the wide application of traditional Chinese medicine in the world,the related reports on the toxicity of traditional Chinese medicine are increasing,which makes the safety of traditional Chinese medicine receive wide attention.This paper analyzes the toxicity of traditional Chinese medicine with a fair and scientific attitude,in order to promote the benign and sustainable development of traditional Chinese medicine.

Metabolomics and its application in the evaluation of toxicity of traditional Chinese medicine

Metabolomics is a newly developed discipline following genomics,transcriptomics,and proteomics.It is based on the theory of systems biology,supported by modern spectroscopy analysis technology and is analyzed by the external stimulation of organisms.By analyzing the overall changes of metabolites with low molecular weight in organism after being stimulated by the outside world,we can understand the physiological and pathological state of organism,and finally clarify the essence of biological changes of organism.In recent years,metabolomics has developed rapidly.It has been widely used in early toxicity screening of lead compounds,preclinical toxicity of drugs and toxicity evaluation of clinical drugs.The in-depth interpretation of metabolomics results is also developing.This article reviewed the progress of metabolomics technology and its application in the study of toxicity evaluation of traditional Chinese medicine.

Research progress on the regulation of androgen receptor signaling pathway in the treatment of prostate cancer by traditional Chinese medicine monomers

The prevalence of prostate cancer in males worldwide is increasing every year.Androgen and androgen receptor drive the development of prostate cancer and are important targets for the treatment of prostate cancer.A growing number of reports indicate that the traditional Chinese medicine has a clear advantage in the prevention and treatment of prostate cancer.This article provides an overview of the in vitro and in vivo studies of different traditional Chinese medicine monomers acting on the androgen receptor-signaling pathway in prostate cancer.

Research progress of traditional Chinese medicine monomers in intervening colorectal cancer by regulating MAPK signaling pathway

The incidence rate and mortality rate of colorectal cancer in China are increasing year by year.Finding effective therapeutic strategies and interventions,especially exploring“highly effective and low toxic”drugs to prevent“inflammation-cancer”transformation,treat primary tumors,prevent tumor metastasis and reduce the toxicity and increase efficiency of existing therapies has become a hot topic of domestic and foreign scholars.The advantage of traditional Chinese medicine in the treatment of colorectal cancer is to reduce the postoperative recurrence rate,improve patients’symptoms and the quality of life of“tumor survivors”and prolong the survival time.This paper summarizes the tumor treatment strategies and research prospects of traditional Chinese medicine targeting mitogen activated protein kinase by sorting out the mechanism of traditional Chinese medicine extracts or effective components intervening colorectal cancer by regulating mitogen activated protein kinase signal pathway in tumor cells in recent years.

Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine

某些药物在体内代谢过程中会生成反应性代谢物,并与体内的大分子物质结合产生毒副作用.这些亲电代谢产物或中间体,具有化学不稳定性和较短的半衰期,往往不易被检测到.谷胱甘肽作为天然的亲核物质,可以捕获亲电的反应性代谢产物,与之形成GSH共价结合物.利用液质联用技术对GSH结合物进行检测和分析,即可快速筛查和发现中药潜在毒性物质.本文简要介绍了谷胱甘肽捕获反应性代谢物的原理,列举了近年来 LC-MS 检测 GSH 结合物的定性和定量分析方法,例如用于检测谷胱甘肽特征碎片的中性丢失扫描、前体离子扫描和多反应监测等方法,并就该技术在一些含有吡咯里西啶生物碱类 （阿多尼弗林碱、毛果天芥菜碱）、呋喃类（黄独乙素）、醌类（黄樟素）中药毒性物质的发现进行了综述.概而述之,基于GSH 捕获反应性代谢物的 LC-MS 检测方法,可快速、灵敏地发现中药潜在的毒性反应性代谢物,具有较好的应用前景.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer,characterized by excessive deposition of the extracellular matrix.In the past,hepatic fibrosis was thought to be a static and irreversible pathological process.In recent years,with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level,more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process.Therefore,it is particularly important to find an effective,simple,and inexpensive method for its prevention and treatment.Traditional Chinese medicine(TCM)occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions,low cost,and multi-target effectiveness.A large number of research results have shown that TCM monomers,single herbal extracts,and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis.Oxidative stress(OS)is one of the key factors in the occurrence and development of hepatic fibrosis.Therefore,this article reviews the progress in the understanding of the mechanisms of TCM monomers,single herbal extracts,and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years,in order to provide a reference and basis for drug therapy of hepatic fibrosis.

A systematic review of treating Helicobacter pylori infection with Traditional Chinese Medicine

AIM: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of Helicobacter pylori (H pylori) infection. METHODS: We electronically and manually searched electronic databases, references lists and conferences compilations, and included all randomized clinical trials comparing the treatment of H pylori using TCM with proton pump inhibitor or colloidal bismuth subcitratebased triple therapy as controls. The Jadad score was used to assess trial quality, H pylori eradication rate and the incidence of side effects were taken as outcome measurements, and heterogeneity analysis, meta-analysis and funnel plot analysis were conducted. RESULTS: Sixteen trials were included. The Jadad scores of all the trials were not more than 2. Clinical heterogeneity and substantial statistical heterogeneity existed among the trials (P = 0.001, I 2 = 59%) and meta-analysis was not conducted. The average eradication rates following TCM and triple therapy were 72% and 78% and the incidence of side effects were 2% and 29%, respectively. The funnel plot was obviously asymmetric. CONCLUSION: Available evidence is not convincing enough to show that TCM has the same efficacy as triple therapy in H pylori treatment. TCM may be safer than triple therapy. TCM should not be recommended as monotherapy in H pylori infection.

Study progress in therapeutic effects of traditional Chinese medicine monomer in severe acute pancreatitis

Severe acute pancreatitis (SAP) is a common acute abdomen clinical problem characterized by high mortality, mul-tiple complications, complicated pathogenesis and difficult treatment. Recent studies found traditional Chinese medicine (TCM) monomers have markedly good effect for treating SAP. Many TCM monomers can inhibit pancreatin, resist inflammation, im-prove microcirculation and immunoloregulation, etc. to block the pathological progress of SAP in multiple ways, reduce com-plications and lower mortality with rapid effects. It is significant for enhancing SAP treatment to deeply understand the current situation in TCM monomers for treating SAP and take precious references therein. This article summarizes the treating effects and mechanisms of TCM monomers for SAP in recent years.

Safety Research in Traditional Chinese Medicine: Methods, Applications, and Outlook

Traditional Chinese medicine (TCM) is a medical system that has collected and summarized abundant clinical experience over its long history of more than 2000 years. However, the frequent occurrence of TCM-induced adverse reactions has hindered the modernization and internationalization of TCM, while attracting increasing attention from around the world. Unlike chemical drugs and biological agents, the difficulties involved in research on the toxicity and safety of TCM mainly include the complexity of its components and the unpredictability of drug–body interactions. Much of TCM, which has overall therapeutic effects, has the typical mechanisms of multiple components, multiple pathways, and multiple targets. While considering the gradualness and unpredictability of TCM toxicity, the ambiguity of toxicants and safe dosage, and individual differences during long-term TCM administration, we have systematically established key techniques for the toxicity assessment of TCM. These techniques mainly include TCM toxicity discovery in an early phase, based on a combination of drug toxicology genomics and metabolomics;methods to identify dose–toxicity relationships in TCM;and integrated techniques for the exploration of TCM interactions, such as fast-screening tests based on drug-metabolizing enzymes and receptor pathways. In particular, we have developed a new technical system for TCM safety evaluation using molecular toxicology, which has been validated well in research on TCM compatibility contraindication, quality control, and allergen discovery. The application of this key technical platform is introduced here in detail. This application includes model organisms, toxicant biomarkers, a magnetic suspension technique, and the application of network toxicology and computational toxicology in research on the toxicity of Fructus toosendan, Semen cassiae, Polygonum multiflorum, and Fructus psoraleae.

中药单体川楝素介导hsa-circ-0025583/hsa-miR-671-5p/SYNGR2轴调控乳腺癌生长的分子机制研究

目的 探究中药单体川楝素介导的hsa-circ-0025583/hsa-miR-671-5p/SYNGR2轴调控乳腺癌生长的分子机制。方法 选取南通第三人民医院乳腺外科于2020年4月—2022年4月收治的乳腺癌患者40例为研究对象,患者均在医院进行手术,取患者乳腺癌及癌旁组织作为实验材料,采用定量荧光聚合酶链反应(quantitative polymerase chain reaction, qPCR)对其hsa-circ-0025583及SYNGR2的表达水平进行测定;取乳腺癌细胞株T47D细胞,加入不同浓度的川楝素,比较不同浓度川楝素对细胞增殖的抑制率;对所选乳腺癌细胞株系进行预处理,A组不进行特殊处理,B组中加入0.5μmol/L的川楝素,C组对乳腺癌细胞进行转染,敲除hsa-miR-671-5p,并向其中加入0.5μmol/L的川楝素,比较其hsa-circ-0025583及SYNGR2的表达水平,上述实验重复3次。结果 与正常癌旁组织相比较,乳腺癌组织中提取的hsa-circ-0025583及SYNGR2 mRNA表达水平均降低,差异有统计学意义(P<0.05)。hsa-circ-0025583及SYNGR2 mRNA在乳腺癌组织中均低表达,具有正相关性(r=0.965,P<0.05)。随着川楝素浓度的升高,乳腺癌细胞增殖的抑制率逐渐升高,且与0μmol/L浓度组比较均具有统计学意义(P<0.05)。对数据进行处理,得出乳腺癌细胞在24 h及48 h的半数抑制浓度分别为0.78μmol/L、0.49μmol/L。与A、C组相比较,B组的hsa-circ-0025583及SYNGR2 mRNA的表达水平明显升高,差异有统计学意义(P<0.05);但A、C组间比较,差异无统计学意义(P>0.05)。与A、C组相比较,B组24 h及48 h侵袭细胞数量明显降低,差异有统计学意义(P<0.05);但A、C组间侵袭细胞数量比较,差异无统计学意义(P>0.05)。结论 川楝素通过介导hsa-circ-0025583/hsa-miR-671-5p/SYNGR2轴调控hsa-circ-0025583及SYNGR2水平,进而影响乳腺癌细胞的增殖及侵袭能力,抑制乳腺癌细胞的生长。

中医药治疗卵巢癌的机制研究进展

卵巢癌具有难检测、难治疗、复发率高等临床特点,是致死率最高的妇科恶性肿瘤之一。早期症状隐匿,发现时多已进展至晚期,手术后铂类药物化疗是目前的主要治疗手段,但长期使用会产生耐药性,且不良反应极多。近年来,随着中医学的不断进步和发展,中药已成为目前抗卵巢癌研究的热点。笔者在国内外数据库中检索相关研究论文,发现中药具有抑制卵巢癌细胞增殖、促进细胞凋亡、逆转耐药性等作用机制,主要作用在PI3K/Akt/mTOR、Wnt/β-catenin、Notch、NF-κB、MAPK信号通路。

飞龙掌血茎和根不同炮制品对小鼠的急性毒性试验

旨在了解飞龙掌血[Toddalia asiatica(Linn)Lam.]茎和根不同炮制对小鼠急性毒性作用。130只KM小鼠适应性喂养3 d后,随机分为13组,包括溶媒组和12个药物试验剂量组(1个药材茎生品组和5个茎炮制组,1个根生品组和5个根炮制组,其中5种药材炮制品包括水煮制品、水洗制品、水蒸制品、酒蒸制品和酒炙制品)。溶媒组小鼠按40 mL/kg给予纯净水灌胃,给药3次,间隔4~5 h;茎各炮制品试验组小鼠按40 mL/kg灌胃,给药3次,间隔4~5 h;根各炮制品试验组小鼠按30 mL/kg灌胃,给药2次,间隔4~5 h,记录给药后各组小鼠14 d的主要临床症状、体重变化,并统计死亡率。结果表明,飞龙掌血及各炮制品可对小鼠产生急性毒性作用,临床中毒症状有自主活动减少、安静怠动、俯卧和翻正反射消失。炮制品组与溶媒组比较,在14 d内茎和根各炮制品均可致小鼠体重明显降低,且死亡率显著高于溶媒组(P<0.05或P<0.01);而与生品组比较,茎和根的5种炮制品在14 d内对小鼠体重的影响不显著,可有效降低小鼠的死亡率,其中以水煮法效果最佳。水煮、水洗、水蒸、酒蒸、酒炙炮制方法可以减小飞龙掌血茎和根(生品)对小鼠的毒性作用,但对小鼠体脂影响不显著。

益气活血中药对化疗患者心脏功能的影响

目的探讨肿瘤治疗相关心血管毒性(CTR-CVT)的早期监测指标及益气活血类中药对CTR-CVT的预防作用。方法选取2019年1月至2022年1月该院行抗肿瘤治疗且经病理学诊断确诊的恶性肿瘤患者40例,将其按照1∶1比例随机分为对照组及治疗组,对照组接受化疗,治疗组在化疗基础上联合益气活血中药。比较2组心肌酶谱[α-羟丁酸脱氢酶(α-HBDH)、乳酸脱氢酶(LDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、谷草转氨酶(AST)]、B型脑钠肽(BNP)、肌钙蛋白Ⅰ(CTNⅠ)、左心室射血分数(LVEF)水平,并对心电图异常及心血管不良事件发生情况进行分析。结果对照组化疗后CK、CK-MB、α-HBDH、LDH、BNP水平高于化疗前,AST、CTNⅠ低于化疗前,差异无统计学意义(P>0.05)。治疗组化疗后α-HBDH、LDH、BNP、AST、CK、CK-MB、CTNⅠ水平与化疗前比较,差异无统计学意义(P>0.05)。2组化疗后BNP、α-HBDH、LDH水平比较,差异有统计学意义(P<0.05),但AST、CK-MB、CK、CTNⅠ水平比较,差异无统计学意义(P>0.05)。2组化疗后LVEF水平及心血管不良事件发生情况比较,差异有统计学意义(P<0.05)。2组化疗后心肌酶谱指标、BNP水平、CTNⅠ水平及心电图异常情况比较,差异无统计学意义(P>0.05)。结论心肌酶谱、BNP、CTNⅠ可以作为CTR-CVT的早期监测指标。益气活血类中药在一定程度上具有预防CTR-CVT的作用,其可以改善患者心脏功能及BNP、LVEF水平,降低心血管不良事件发生率。

Network toxicology and LC-MS-based metabolomics:New approaches for mechanism of action of toxic components in traditional Chinese medicines

Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines(TCMs).In this study,we reviewed the application of network toxicology based on LC-MS metabolomics,mainly in the study of toxic components and the toxicity mechanism of TCMs,which provides new ideas and methods for the further study of the toxicity mechanism of TCMs.

中药单体调控非受体型酪氨酸激酶抗肿瘤的研究进展

癌症严重威胁人类的生命健康,致癌基因的过度活化是导致癌症患者治疗和预后不佳的主要原因,这些过度活化的致癌基因多为蛋白酪氨酸激酶(PTK)。在众多的PTK中,非受体酪氨酸激酶(NRTK)是一类重要的信号分子,作为细胞内信号通路转导的主要驱动者,调控细胞增殖、迁移等过程。以NRTK为靶点已成为抗肿瘤药物开发的重点和难点。中药以其多途径、多环节、多靶点、低毒等特性,在肿瘤的治疗和辅助治疗中发挥巨大的优势,至今已发现多种中药单体可抑制NRTK发挥抗肿瘤作用。该文对NRTK主要成员Src、Jak、Abl和Fak家族在肿瘤中的作用进行概述,并归纳总结了作用于这些成员的中药单体,旨在为靶向NRTK的抗肿瘤治疗提供理论基础,为寻找NRTK的中药单体抑制剂提供参考。

中药单体调控“细胞自噬”防治皮瓣坏死

背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chinese Medicine (TCM),Autophagy,Skin flaps”为中英文检索词,由第一作者检索2010年1月至2022年10月发表在中国知网与PubMed数据库的相关文献,文献初筛共检索到相关文献196篇,以纳入和排除标准进行筛选,通过阅读文献标题与摘要进行质量评估,最终归纳整理55篇文献进行综述。结果与结论:(1)细胞自噬的调控是由AMPK/mTOR和PI3K/AKT等信号通路介导的,激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。(2)中药单体中的萜类化合物(桦木酸、穿心莲内酯、三七三萜和梓醇)、酚类化合物(白藜芦醇、姜黄素和天麻素)、酚酸类化合物(丹酚酸B)及类固醇类化合物(拟人参皂甙F11)可通过调控相关信号通路激活细胞自噬来缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,促皮瓣存活。(3)文章通过总结中药单体调控细胞自噬防治皮瓣坏死的研究进展,为临床上中药防治皮瓣坏死、促进皮瓣愈合提供参考与理论依据。