Appropriate medical practice—natural forces and medical intervention

FAN Daiming

[Abstract] Medical practice is the most important step in fulfilling the medical purposes of medical theory. Appropriate medical practice not only can help treat and prevent diseases, but also is beneficial to the maintenance and promotion of health. Appropriate medical practice requires full knowledge of the natural forces that maintain the human body. Medical intervention should be considered as a last resort. Appropriate medical practice should respect the human body’s natural forces and understand the needs and limitations that can be endured by the body’s natural forces, instead of ignoring or even damaging, suppressing, or replacing these forces.

[Key words] Natural force;  Medical intervention;  Medical practice

试论医学的正确实践——自然力与医学干预

[摘要]医学实践是将医学理论实现医学目的之最重要的步骤。正确的医学实践不仅有助于疾病的诊治和预防，而且有利于健康的维护和促进。正确的医学实践应充分认识和维护人体的自然力，医学干预是不得已而为之，要尊重人体自然力，要根据人体自然力发展的需要和可能承受的限度，而不是不顾自然力，甚至任意伤害、抑制或取代自然力。

[关键词]自然力； 医学干预； 医学实践

A neglected complication of COVID-19: liver injury

LAN Tian, LIANG Xiaolin,…,GUO Jiao*

[Abstract]Coronavirus disease-2019 (COVID-19) not only causes substantial respiratory pathology, but also results in several extrapulmonary manifestations, including thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologicillnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Recent reports showed about 2%~11% of patients with COVID-19 had underlying chronic liver disease. Here we review the liver-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for liver injury in COVID-19.

[Key words]COVID-19; SARS-CoV-2; Liver injury; Pathophysiology; Therapy

未被重视的新冠病毒感染并发症——肝损伤

[摘要]冠状病毒病-2019 (COVID-19)不仅可引起大量的呼吸病状，还可导致多种肺外表现，包括血栓并发症、心肌功能障碍和心律失常、急性冠状动脉综合征、急性肾损伤、胃肠道症状、肝细胞损伤、高血糖和酮症酸中毒、神经系统疾病、眼部症状和皮肤并发症等。考虑到传染性冠状病毒SARS-CoV-2的进入受体ACE2在多个肺外组织的表达，病毒相关组织直接损伤是一种可能的损伤机制。此外，内皮损伤和血栓形成、免疫反应失调和ace2相关通路适应不良都可能导致COVID-19的这些肺外表现。近期报告显示，约2%~11%的COVID-19患者存在潜在的慢性肝病。在此，我们对COVID-19患者的肝脏特异性病理生理、表现和管理方面进行了综述，以帮助临床医生和科学家识别和监测COVID-19肝脏损伤，并为COVID-19肝损伤制定研究重点和治疗策略。

[关键词]COVID-19;  SARS-CoV-2;  肝损伤;  病理生理学;  治疗

Boundary and scope: the dilemma of Chinese herbal medicine practice in the US concerning incidents during the COVID-19 pandemic

CHEN Yemeng*

[Abstract]During COVID-19 pandemic, Chinese herbal medicine practices in the United States face challenges for Chinese herbal products application. The FDA has issued at least seven warning letters for alleging these products help to prevent, treat, mitigate, diagnose, or cure coronavirus disease 2019. Although Chinese herbal medicine has been imported to America for about two hundred years, the Chinese herbal products are categorized as dietary supplements and Chinese herbal medicine practices have limited scope and larger boundaries, which push the Unites States with Chinese herbal medicine practices far more behind. A CLAP (Compliance, Lobby, Adaptation, and Promotion) action plan is proposed to advance Chinese herbal medicine development in America.

[Key words] Chinese Herbal Medicine; Dietary Supplement; Dilemma; COVID-19; United States

边界与范围:新冠肺炎疫情期间美国中草药实践的困境

[摘要]2019新型冠状病毒病(COVID-19)大流行期间，美国中草药应用面临挑战。虽然中草药进口到美国已有200多年的历史，但中草药产品被归类为膳食补充剂，中草药实践范围有限、所受限制很大，这使得美国的中草药实践远远落后于美国发展。一项名为CLAP(合规、游说、适应和促进)的行动计划被提出，以促进美国的中草药发展。

[关键词]中草药； 膳食补充剂； 困境； COVID-19； 美国

Research progress of traditional Chinese medicine influencing macrophage polarization

GAO Shuang,CHEN Zhesheng,…, LI Jing*
[Abstract] Recently, with advancements in science and technology, humans have found that macrophages play essential roles in many diseases, which has become a new focus of research on disease diagnosis and treatment. As traditional Chinese medicine is one of the main tools for disease prevention and treatment, research on its macrophage polarization deserves attention. In this paper, we summarized the effects of traditional Chinese medicine on macrophage polarization in areas such as inhibition of M1 macrophage polarization, inhibition of M2 polarization, and effects on reversal of M1/M2 macrophage phenotype.

[Key words] Traditional Chinese medicine; Macrophages; Polarization; M1 macrophage; M2 macrophage

中医药影响巨噬细胞极化的研究进展

[摘要]近年来，随着科学技术的发展，人们发现巨噬细胞在许多疾病中都发挥着重要作用，成为疾病诊疗研究的新的出发点。中医药作为疾病防治的主要手段之一，在巨噬细胞极化方面的研究值得关注。本文从抑制M1型巨噬细胞方向极化、抑制M2型巨噬细胞方向极化及影响M1/M2型巨噬细胞表型逆转方面，概述了中医药对巨噬细胞极化的影响。

[关键词]中医药； 巨噬细胞； 极化； M1型巨噬细胞； M2型巨噬细胞

Comparative study of liposomes and liposomes-in-polymer hydrogel as transdermal carriers for improving the topical delivery of imperatorin

BAN Junfeng,MO Zhenjie,…,LV Zhufen*

[Abstract]Objective A novel imperatorin (IMP)-liposome-hydrogel formulation was developed to increase skin permeation efficiency and improve the bioavailability of IMP after topical delivery. Methods IMP loading into liposomes was optimized, and liposomes were entrapped in a polymer hydrogel consisting of carbomer. Liposomes were also used as a control formulation. The physical properties and percent encapsulation efficiency were evaluated. The adhesive strength of the gel was tested. The in vitro percutaneous permeability, percutaneous penetration mechanism, and irritant evaluation were investigated. Results Compared to liposomes, the preparation of IMP-liposomes-gel has excellent adhesion properties and sustained drug release on the skin surface. Conclusion These findings suggest developing liposome gels for potential percutaneous drug carrier systems.

[Key words] Imperatorin;  Liposomes;  Liposome gel;  Encapsulation efficiency;  Percutaneous penetration mechanism; Irritant evaluation

欧前胡素脂质体及其凝胶局部经皮递药的比较研究

[摘要]目的 以中药白芷中的有效成分欧前胡素为模型药物，制备其脂质体及脂质体-水凝胶新剂型，以期提高局部用欧前胡素的经皮渗透效率和生物利用度。方法 以欧前胡素脂质体为对照。对欧前胡素脂质体及脂质体-水凝胶的物理性能、包封率、凝胶的胶凝强度，体外透皮性、透皮机制及刺激性进行评价。结果 与脂质体相比，制备的欧前胡素-脂质体-水凝胶具有良好的皮肤表面黏附性能和药物渗透性。结论 以脂质体水凝胶有望成为复方中药经皮递药的新型载体。

[关键词]欧前胡素； 脂质体； 脂质体水凝胶； 经皮递药； 刺激性评价

Network pharmacology-based investigation into the mechanism of action of TongxieYaofang decoction in the treatment for ulcerative colitis

MAI Yuyi,LIN Yujian,SHI Jun*,…

[Abstract] Objective  Network pharmacology techniques were used to predict the key active compounds and targets of TongxieYaofang decoction in treating ulcerative colitis (UC) and exploring the potential multicomponent, multitarget, and multipathway mechanism. Also, peroxisome proliferator-activated receptor-γ (PPAR-γ) in cancer pathways was selected for animal testing. Methods The chemical components of the four herbs in TongxieYaofang decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), whereas the other relevant information was obtained from the literature. Targets of the active compounds were obtained from the TCMSP and SwissTargetPrediction. Meanwhile, the UC targets were searched and screened from GeneCards and DisGeNET and intersected with targets of the active compounds in TongxieYaofang decoction. The obtained common targets were imported into the STRING database to build the target protein-protein interaction network. Cytoscape software was used to construct the network diagram of single herb-active compounds-targets of TongxieYaofang decoction. The common targets of the drug and disease received the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological functions and metabolic pathways of the drug and predict its potential mechanism of action in treating UC. Molecular docking was conducted for the top 3 and 5 relevant proteins using AutoDock software and verified in animal testing: UC rat models were established and received 22 g/kg alcohol extract of TongxieYaofang decoction through intragastric administration for 28 days. The colonic mucosa damage index was assessed. PPAR-γ protein expression was detected by immunohistochemistry. Results Fifty-three UC-related potential active compounds and 168 potential targets were obtained. Paeoniflorin in Radix Paeoniae Alba and wogonin in Radix Sileris might be the key compounds of TongxieYaofang decoction in treating UC. Cyclooxygenase-2 (PTGS2), the most highly associated with active compounds, might be an important therapeutic target. GO and KEGG enrichment analyses showed that the efficacy of TongxieYaofang decoction involved various molecular functions and biological processes and might achieve the collaborative treatment for UC through multiple pathways, such as cancer pathways, tumor necrosis factor signaling pathway, Toll-like receptor signaling pathway, and phosphatidylinositol 3-kinase/Akt signaling pathway. The molecular docking results demonstrated that active compounds had a favorable binding activity with the target AR. TongxieYaofang decoction could significantly increase PPAR-γ expression in UC rats (P < 0.05), verifying part of the predicting outcomes of network pharmacology. Conclusion  TongxieYaofang decoction is featured with the multicomponent, multitarget, multipathway collaborative treatment for UC. This study has predicted the potential active compounds and key targets and preliminarily clarified the potential material base for the efficacy and mechanism of this drug.

[Key words] TongxieYaofang decoction;  Ulcerative colitis; Paeoniflorin; Wogonin; Cyclooxygenase-2; Peroxisome proliferator-activated receptor-γ

基于网络药理学探究痛泻要方治疗溃疡性结肠炎作用机制研究  

[摘要]目的 运用网络药理学技术预测痛泻要方治疗溃疡性结肠炎（ulcerative colitis，UC）的主要活性成分和作用靶点，探讨其多成分-多靶点-多通路的潜在作用机制；并选取癌症通路中的过氧化物酶体增殖物激活受体（PPAR-γ）进行动物实验验证。方法 利用中药系统药理数据库与分析平台（TCMSP）收集痛泻要方中4味中药的化学成分，并通过文献资料加以补充；通过TCMSP及SwissTargetPrediction数据库获取活性成分的作用靶点；同时从GeneCards、DisGeNET数据库对UC靶点进行检索及筛选，与痛泻要方的活性成分靶点进行交集，筛选出的共同靶点导入STRING数据库构建靶点蛋白-蛋白相互作用（PPI）网络；运用Cytoscape软件构建痛泻要方“单味药-活性成分-作用靶点”网络关系图，对药物-疾病共同靶点进行GO分析和KEGG通路富集分析，分析其参与的生物功能与代谢通路，预测痛泻要方治疗UC的潜在作用机制。采用AutoDock软件对相关度前3的蛋白与相关度前5的成分进行分子对接，并进一步采用动物实验进行验证：复制大鼠UC模型，22 g/kg痛泻要方醇提物灌胃给药28 d，评价大鼠结肠黏膜损伤指数，采用免疫组化检测PPAR-γ蛋白表达水平。结果 在痛泻要方中，共筛选出53个与UC相关的潜在活性成分和168个潜在作用靶点，其中白芍的芍药苷（paeoniflorin）、防风的汉黄芩素（wogonin）可能是痛泻要方治疗UC的关键成分，而靶点环氧化酶-2（PTGS2）与活性成分的关联最多，提示这可能是重要的治疗靶点。GO和KEGG富集分析结果表明，痛泻要方发挥药效涉及多方面的分子功能与生物过程，可能通过癌症通路、肿瘤坏死因子信号通路、Toll样受体信号通路和磷脂酰肌醇3'-激酶信号通路等多条通路协同治疗UC。分子对接结果表明活性成分与靶点AR具有较好的结合活性。痛泻要方可显著升高UC大鼠PPAR-γ（P＜0.05）的表达量，验证了网络药理学的部分预测结果。结论 痛泻要方具多成分、多靶点、多通路协同作用治疗UC的作用特点，并预测了其可能的活性成分和关键靶点，初步阐明其潜在的药效物质基础和作用机制。

[关键词]痛泻要方； 溃疡性结肠炎； 芍药苷； 汉黄芩素； 环氧化酶-2； 过氧化物酶体增殖物激活受体

A network pharmacology study on the main active constituents and key pharmacological pathways of Shaoyao Gancao Decoction on Osteoarthritis

LI Qiuyue, HOU Chengzhi, …, WEI Xu*

[Abstract]Objective This study identifies the active constituents and molecular mechanism of Shaoyao Gancao decoction (SGD) in the treatment of osteoarthritis (OA) and provides new ideas and targets for the prevention and treatment of OA with traditional Chinese medicine (TCM).

Methods The chemical constituent profile of SGD was identified by UHPLC-Q-TOF assay. Based on the candidate active compounds, combining LC-MS with the TCM database, putative targets of SGD drug-like chemical constituents were predicted using TCMSP. The targets of disease were obtained from the Gene database. Subsequently, the compound-target network was constructed and the core potential targets were screened out by a Cytoscape plug-in.

Results Thirty-two bioactive compounds of 87 drug-like chemical constituents of SGD were identified by UHPLC-Q-TOF: 279 genes were found to be the putative targets of these compounds. In a protein-protein interaction (PPI) network, according to the comprehensive analysis of the topological parameters, 62 key targets were found. Subsequently, 23 core genes were further screened out by the cytohubba plug-in of Cytoscape resulting from a synthesis of 11 algorithms. Functional enrichment analysis suggested that SGD exerted its pharmacological effects in OA by modulating multiple pathways. Eighteen active components, 23 key targets and eight key regulatory pathways were identified, among which, CCND1, MYC, MAPK8, INS, EGF, serpine1, and AGE-RAGE signaling pathway are new targets (non-OA genes) and new mechanisms. Conclusion This study systematically and comprehensively studied bioactive compounds and core targets and pathways of SGD on OA by LC-MS-MS and network pharmacology. These results suggest that SGD is likely to treat OA by regulating metabolic pathways, which provides important information and direction for further research.

[Key words] Shaoyao Gancao Decoction (SGD); Osteoarthritis (OA); Network Pharmacology; Pharmacological pathways

基于网络药理学的芍药甘草汤治疗骨关节炎的主要活性成分鉴定及关键药理途径研究

[摘要]目的  研究芍药甘草汤(SGD)治疗骨关节炎(OA)的活性成分及分子机制，为中医药防治OA提供新思路和新靶点。方法 采用UHPLC-Q-TOF法对其进行化学成分鉴定。基于候选活性化合物，结合LC-MS和TCM数据库，利用TCMSP预测SGD药物样化学成分的推定靶标。从基因数据库中获得疾病靶点。构建了化合物-靶标网络，并通过Cytoscape插件筛选出核心潜在靶标。结果 经UHPLC-Q-TOF鉴定，鉴定出32种活性化合物，其中279个基因为这些化合物的靶基因。在蛋白质-蛋白质相互作用(PPI)网络中，根据拓扑参数的综合分析，发现62个关键靶点。利用Cytoscape的cytohubba插件，合成了11种算法，进一步筛选出23个核心基因。功能富集分析表明SGD通过调节多种途径发挥其在OA中的药理作用。其中，CCND1、MYC、MAPK8、INS、EGF、serpine1和age - age signaling pathway是新的靶点(非OA基因)和新的机制。结论 本研究采用LC-MS-MS和网络药理学方法，系统、全面地研究了SGD对OA的生物活性化合物及核心靶点和通路。结果提示SGD可能通过调节代谢途径治疗OA，为开展进一步研究提供了重要参考。

[关键词]芍药甘草汤; 骨关节炎(OA); 网络药理学; 药理通路