With the in-depth implementation of Opinions of the Central Committee of the Communist Party of China and the State Council on promoting the inheritance, innovation, and development of TCM and Special provisions for the registration administration of TCM, the evidence system of registration, review, and evaluation of TCM, which integrates TCM theory, human use experience, and clinical trials(hereinafter referred to as "three combinations"), has broken through the traditional evaluation model and established a research and development pathway aligns with the characteristics of TCM, and has become a pivotal reform driving the research and development of new TCM drugs. Against this backdrop, experts and representatives from hospitals and enterprises of research and development have developed this consensus through multiple rounds of discussions, aiming to provide a reference for the scientific design, standardized conduct and efficient advancement of clinical trials for new TCM drugs under this system. Centering on human use experience, this consensus elaborated on rational clinical trial planning strategies according to the evidence level of human use experience, the innovative design approaches of trials based on human use experience, the integration and optimized application of domestic and international regulations and technical guidelines, and a full-process communication mechanism and an efficient collaborative framework with clearly defined roles of three parties. It is expected to promote the high-quality development of new TCM drugs in research and development and better meet clinical needs.

AbstractDenosumab is a human IgG2 monoclonal antibody against receptor activator of nuclear factor kappa‐B ligand (RANKL) for the treatment of osteoporosis and bone loss. HLX14 is a proposed biosimilar of denosumab. This randomized, parallel‐group, two‐part, phase I study aimed to compare the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 with reference denosumab in Chinese healthy adult male participants. In Part 1, participants were randomized 1:1 and given HLX14 or reference denosumab sourced from the European Union (EU). In double‐blind Part 2, participants were randomized 1:1:1:1 to receive HLX14 or denosumab sourced from the United States, EU, or China. All study drugs were administered via subcutaneous injection at a single dose of 60 mg. The primary endpoints were area under the serum drug concentration–time curve from time 0 to the last concentration‐quantifiable time t (AUC0–t), maximum serum drug concentration (Cmax), and area under the serum drug concentration–time curve from time 0 to infinity (AUC0–inf). Twenty‐four participants were randomized in Part 1 and 228 in Part 2. The 90% confidence intervals of geometric mean ratio of AUC0–t, Cmax, and AUC0–inf between HLX14 and denosumab from different sources fell within the pre‐specified similarity margins of 0.80–1.25 (AUC0–t, 0.91–1.13; Cmax, 0.91–1.13; AUC0–inf, 0.91–1.12), demonstrating pharmacokinetic similarity. No notable difference was observed among treatment groups in pharmacodynamics, safety, or immunogenicity. HLX14 demonstrated highly similar pharmacokinetic characteristics with comparable pharmacodynamics, safety, and immunogenicity to denosumab, supporting its further investigation as a potential denosumab biosimilar.

Aim and Objective:: Traditional Chinese Medicine prescribes Yantiao Formula (YTF; peach kernel, mirabilite, Angelica sinensis, Radix Scrophulariae, raw rhubarb, Radix Paeoniae, Flos Lonicerae, Forsythia, and Ophiopogon japonicus) to treat sepsis. Clinically, it reduced the inflammatory response of sepsis. It also reduced lung damage by decreasing the level of TNF-α in septic rats' serum. Using network pharmacology analysis, we investigated the efficacy network and mechanism of YTF in treating sepsis. Materials and Methods:: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine (BATMAN-TCM) combined with literature to collect the main components in YTF and their targets. DisGeNET and GENECARDS databases were used for sepsis-related targets. Cytoscape 3.7.1 software was used to construct the herbcomponent- target and ingredient-target-disease interaction protein-protein interaction networks of YTF. The jvenn was used to perform the intersection of YTF targets and sepsis targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed． We also created a sepsis rat model using cecal ligation and perforation and stimulated alveolar macrophages (NR8383) with endotoxin to investigate the mechanisms of YTF. Results:: GO, and KEGG enrichment analysis revealed that these targets involved mineralocorticoid secretion, aldosterone secretion, active regulation of chronic inflammatory response, the exogenous coagulation pathway, and other pathophysiology. It was linked to various inflammatory factors and the MAPK pathway. YTF inhibits the p38MAPK pathway and decreases TNF- α, IL-6, and CXCL8 levels. Conclusion:: YTF has a multi-component, multi-target, and multi-channel role in treating sepsis. The primary mechanisms may involve inhibiting the p38MAPK pathway to reduce the inflammatory response.

AbstractThe purpose of this study was to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SN1011, a novel Bruton tyrosine kinase (BTK) inhibitor, and food effects in healthy subjects. In this phase I trial, subjects received single ascending doses (SADs) of SN1011 (100 to 800 mg), multiple ascending doses (MADs) of SN1011 (200 to 600 mg), or placebo q.d. Additionally, 12 subjects randomly received a single dose of SN1011 600 mg under fasting states and then fed states, vice versa. Safety was assessed per Common Terminology Criteria for Adverse Events version 5.0. Pharmacokinetic parameters were calculated by noncompartmental analysis and BTK receptor occupancy in peripheral blood monocytes was determined. Seventy‐one healthy subjects were dosed in five SAD cohorts, three MAD cohorts, and one food effect cohort, with 57 receiving SN1011 and 14 receiving placebo. No serious adverse events (AEs) were reported. There was no correlation between AE occurrences and SN1011 exposure. The three most frequent AEs with SN1011 were increased blood triglycerides, decreased neutrophil count, and decreased leucocyte count. SN1011 exhibited a dose‐proportional increase in maximum plasma concentration and area under the time concentration curve following single and multiple dose administrations, with an accumulation ratio of 1.5 to 2.2 after multiple dose administrations. No difference in SN1011 exposure was observed between fed states. BTK receptor occupancy remained above 83% over 24 h after single administration and remained above 80% for the MAD groups for 10 days of continuous q.d. administration. SN1011 was well‐tolerated and safe after single or multiple exposures to healthy subjects, supporting further clinical development of SN1011 for treatment of autoimmune diseases.

基于现代医家关于帕金森病的因机证治论述并结合自身临床经验,蒋健教授认为本病病机为本虚标实,本虚主要在于肝肾气血亏虚,标实主要在于痰湿瘀血阻络、内风发动,临床往往本虚标实同时存在,内风夹痰瘀多贯穿于帕金森病的发病始终.蒋健教授常用活络丹、逐风汤、刷痰丸化裁治疗本病,紧紧抓住补益肝肾、祛痰化湿、活血化瘀、舒筋活络、搜风剔络、熄风解痉止颤六大主线,善用虫类药,敢用大剂量,治风先治血,多原则灵活配伍,取得了较好疗效.

Background: Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified. Purpose: To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy. Methods: The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl4-induced hepatic fibrosis model. Results: Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of alpha-SMA; cycloastragenol, calycosin 7-O-beta-D glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl4-induced hepatic fibrosis. Conclusion: Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.

水肿是体内水液潴留,泛滥肌肤,表现为以头面、眼睑、四肢、腹背,甚至全身浮肿为特征的病证[1],是人体体液在组织间隙内的蓄积,多与心源性、肾源性、肝源性、炎症性、内分泌等疾病相关,此外还有营养不良性水肿、特发性水肿等[2].《景岳全书·肿胀》云:"盖水为至阴,故其本在肾;水化于气,故其标在肺;水惟畏土,故其制在脾."指出水肿病机与肺、脾、肾三脏功能失调有关,故一般治疗水肿多从肺脾肾着手.

Since the end of 2019, the spread of the corona virus disease 2019 (COVID-19) has caused serious economic shocks and social impacts. The development of clinical trials of drugs has also brought many difficulties and challenges. Based on the particularity of the population and process of the Phase I clinical trials of the drug, it caused us to think about the management of the subjects in the Phase I clinical trials under the influence of the COVID-19. It proposes various strategies from the different stages of subject recruitment, screening, and admission, to subject education, diet management, and observation of adverse events. It aims to discuss how to protect the safety and rights of subjects better under the normalization of epidemic prevention and control, strengthen the risk control of clinical trials, and ensure the successful completion of trials.

蒋健教授通过多年临证总结认为,灼口综合征(BMS)常见"火证"、瘀血阻络证及肝气郁结证等,提出"郁证性舌觉异常"的新概念.常用治则包括滋阴泻火、活血化瘀、疏肝解郁等,主张辨识郁证并从郁论治."火证"者,实火重在清热泻火,虚火重在养阴生津,虚实相兼则当滋阴泻火并举.对于难辨难治者,临证采用试验性用药治疗,以探明有效方药.

目的 利用数据挖掘及文献研究,汇总分析溃疡性结肠炎(UC)中医药内服及灌肠治疗的方药规律.方法 检索中国知网学术期刊全文数据库、万方数据库、维普数据库收录的近10年公开发表的中医药治疗UC的临床研究文献,建立文献研究数据库,对涉及的方剂、中药的功效类别、频次频率等进行统计,再对核心用药进行关联规则和网络图的数据挖掘分析.结果 ①最终纳入相关文献339篇,涉及内服方剂50个,以乌梅丸使用最多,关联规则亦显示“乌梅-附子-黄连”强关联;常用药物167味,其中补虚药占31.11％、清热药占20.15％,使用频率在10％以上者有甘草、黄连、白术、白芍、党参、当归、木香、茯苓、黄芩、黄芪、白头翁、陈皮、乌梅等26味;关联规则显示健脾益气类中药强关联.②灌肠方剂16个,以白头翁汤使用最多,关联规则亦显示“白头翁-秦皮-黄柏-黄连”强关联;常用药物123味,其中清热药占39.17％、止血药占17.72％,使用频率在10％以上的中药有黄连、白及、黄柏、地榆、白头翁、黄芩、苦参、败酱草等17味;网络图显示“白头翁-黄连-黄柏-白及-地榆”强关联;中成药5种,锡类散使用最多.③黄连在内服和外用中药关联规则和网络图中均表现出与其他药物的强关联.结论 UC的中医药内服治疗重在健脾益气扶正、清热燥湿祛邪,以乌梅丸最为常用;局部灌肠治疗以清热解毒燥湿、收敛止血、化腐生肌为主,以白头翁汤及锡类散最为常用;综合内服和灌肠中药,最常用的药物是黄连.

目的 分析慢性萎缩性胃炎的中医证型分布及幽门螺杆菌(Hp)感染、胃黏膜病理变化情况.方法 收集338例慢性萎缩性胃炎患者的相关资料,分析中医证型分布及Hp感染、胃黏膜病理变化情况.结果 ①慢性萎缩性胃炎患者以脾胃虚弱证最为多见(23.4％),其余依次为脾胃湿热证(20.7％)、肝胃气滞证(19.2％)、胃阴不足证(13.3％)、肝胃郁热证(12.1％)、胃络瘀血证(11.2％).②338例慢性萎缩性胃炎患者中,Hp阳性率为55.3％,各中医证型中脾胃湿热证患者Hp阳性率最高(72.9％);不同中医证型Hp阳性率差异有统计学意义(P＜0.01).③在胃黏膜活动性炎症方面,总检出率为53.8％,各中医证型中脾胃湿热证患者活动性炎症检出率最高(71.4％),其中中度、重度活动性炎症占比分别为37.1％和27.1％;不同证型患者胃黏膜组织活动性炎症程度差异有统计学意义(P＜0.05).④在胃黏膜组织萎缩方面,脾胃虚弱证患者胃黏膜组织中度、重度萎缩占比最高,分别为43.0％和27.8％;不同证型患者胃黏膜组织萎缩程度差异有统计学意义(P＜0.05).⑤不同证型患者胃黏膜组织慢性炎症、肠化生程度及低级别上皮内瘤变检出率差异无统计学意义(P＞0.05).结论 慢性萎缩性胃炎患者最常见的中医证型为脾胃虚弱,脾胃虚弱型患者胃黏膜组织中度、重度萎缩发生率较高;脾胃湿热与Hp感染密切相关,脾胃湿热型患者胃黏膜活动性炎症程度较重.

本文通过颤证的治疗案例,介绍蒋健教授对此病证的证候识别要点、观察组方原则及其用药经验.基于古今医家关于颤证因机证治论述并结合自身临床经验,蒋健教授认为震颤本质上为风病,风夹痰瘀是其最为常见的基本病机;治疗上重视联合运用祛痰除湿、活血化瘀、祛风熄风3原则为主进行治疗;观察组方三原可根据不同患者的不同情况灵活应用,每获良效.

结合蒋健教授治疗唇风的案例分析其治疗该病的临床经验.认为其病机为外感风燥热毒、内生脾胃湿热,以中药内服配合外敷法治疗唇风,常用药物分疏风散热、清热解毒(燥湿)、运脾化湿、滋阴润燥等不同类型.

本文通过验案介绍蒋健教授关于“郁证脾胃病”的临床经验及其学术观点.郁证性脾胃病的临床特征为:脾胃病类症状因情志致病因素引起,并兼有情志类、脾胃病类以及脾胃病以外纷繁多彩的躯体表现;无器质性胃肠疾病或以其不能合理解释患者症状;症状怪异不合常理;从郁论治或辅助从郁论治有效.郁证性脾胃病的治疗需遵从四个原则:从郁论治药物疗法和情志疗法相结合;解郁治本与郁证脏腑定位结合;从郁辨证论治与辨证论治相结合;从郁论治与从痰论治、从瘀论治相结合.郁证性脾胃病以郁证为本、脾胃病类表现为标,故从郁论治为治其本,针对脾胃病类症状的治疗为治其标.

Through analyzing the current situation and coverage controversy of Chinese clinical trial insurance,this paper stated that the attending insurance rate in domestic clinical trials was entirely low.The sponsors,clinical trial institutions,investigators and insurance companies paid attention of different levels to clinical trial insurance.Therefore,the risk awareness of drug/medical device clinical trials should be enhanced.It is necessary to give impetus to clinical trial insurance system,during which all parties need to make a joint effort including government departments,ethics committees,sponsors,clinical trial institutions,investigators and insurance companies.

目的:解读药物临床试验数据现场核查要点,以规范药物临床试验过程.方法:从通用内容、人体生物等效性/人体药动学试验数据现场核查要点、Ⅱ、Ⅲ期临床试验数据和疫苗临床试验数据现场核查要点3个方面解读核查要点,分析现场检查的注意事项.结果:目前,我国各期药物临床试验的质量距离比较严格的核查要点还有一定的差距,申办者、合同研究组织、研究者、药物临床试验机构都应该进一步学习相关法规,提高临床试验质量,确保上市后的药品安全.结论:以药物临床试验数据现场核查要点为标准,并严格执行该标准将是保证试验数据真实、完整、规范的重要途径.

Objective Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype. Methods A pharmacokinetics interaction study was carried out in three groups with CYP2D6*1/*1 ( n = 6), CYP2D6*1/*10 ( n = 6), and CYP2D6*10/*10 ( n = 6) genotypes. Each participant received a single oral dose of dextromethorphan (15 mg) followed by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15 mg dextromethorphan in the last day. Blood samples (0–24 h) and urine samples (0–12 h) were collected at baseline and after the administration of Zuojin Pill, and the samples’ concentration of dextromethorphan and its main metabolite dextrorphan was determined. Results Compared to baseline values, co-administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC 0-24 of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49∼3.61) and 1.71-fold (1.42∼2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57-fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes, respectively. In contrast, no significant change was observed in these pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype. Conclusion These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.

Ⅰ期临床试验是新药人体试验的起始阶段，目的是观察人体对新药的耐受程度和药代动力学特征，为制订给药方案提供依据[1]。我院Ⅰ期临床试验研究室是国家食品药品监督管理局(SFDA)首批认定的国家药物临床试验基地之一，成立至今已开展了包括口服片剂、混悬液、滴眼液、静脉注射制剂、外用贴剂及气雾吸入剂等各种途径给药的Ⅰ期临床试验项目，其中静脉制剂给药的护理管理最为复杂，其安全性管理尤为重要。现将静脉制剂在Ⅰ期临床试验中的护理管理体会总结如下。

临床研究协调员是药物临床试验中的重要组成部分，在试验的管理和协调中具有举足轻重的作用。该文拟通过介绍临床研究协调员的职责，并探讨现有的管理模式及其利弊，从而阐明临床研究协调员在临床试验质量保证体系中的作用，为提高临床试验质量提供借鉴。