从新型冠状病毒肺炎的寒疫病机探析清肺排毒汤的组方机制

在《新型冠状病毒肺炎诊疗方案(试行第六版)》中推荐的清肺排毒汤,临床观察疗效显著。笔者拟探讨新型冠状病毒肺炎(COVID-19)的寒疫病机以及清肺排毒汤的方药组成机制,认为该方能疏解表里、通调三焦,具有宣肺行气、透邪解毒、润燥化湿、逐水泻热的功效,切合COVID-19寒、燥、湿的病机特点,且能有效的针对症状进行治疗,应推广全国各地广泛使用以遏制疫情蔓延。     

中药治疗肝肾阴虚证绝经后骨质疏松的Meta分析

目的系统评价中成药和汤剂治疗肝肾阴虚证绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)的疗效及安全性。方法计算机检索CNKI、CBM、VIP、万方数据库、PubMed、Embase、Cochrane图书馆,检索自建库以来至2019年9月23日的文献,按照纳排标准,收集调补肝肾法治疗PMOP的临床对照试验,依据Cochrane Handbook for Systematic Reviews of Interventions(version 5.35)进行质量评估,并使用RevMan5.3软件进行Meta分析。结果纳入9篇文献,9个研究。与常规治疗的中成药和西药相比,在降低中医证候积分[分别为MD=-3.74,95%CI(-4.86,-2.62),P<0.01;MD=-2.05,95%CI(-2.26,-1.84),P<0.01]、提高血清雌激素[分别为SMD=0.69,95%CI(0.21,1.17),P<0.01;SMD=0.37,95%CI(0.01,0.74),P=0.04]方面,单用调补肝肾法可能优于常规治疗;在临床症状疗效有效率[分别为RR=1.03,95%CI(0.90,1.17),P=0.68;RR=1.24,95%CI(0.94,1.63),P=0.13]、提高腰椎骨密度[分别为MD=0.01,95%CI(-0.03,0.05),P=0.65;MD=0.03,95%CI(-0.01,0.07),P=0.12]指标方面,与常规治疗组相比,无显著性差异。无纳入文献提示单用或联合应用以调补肝肾为治法选用的中成药和汤剂出现不良反应。结论中成药和汤剂在改善肝肾阴虚PMOP患者腰脊疼痛、腰膝酸软无力等的症状及提高血清雌激素方面,具有一定的治疗作用,具有较好的安全性。     

Clinical application of Aconitum carmichaelii Debx. (Fu Zi in Chinese) by traditional Chinese medicine physicians--A cross-sectional questionnaire survey in Beijing

ObjectiveTo investigate clinical application of aconite root (Aconitum carmichaelii Debx.; hereinafter “aconite”) by traditional Chinese medicine (TCM) physicians in TCM hospitals in Beijing and explore the specific use of aconite and the effect of different doses on decoction time.MethodsThis was a cross-sectional study using two-stage sampling. Questionnaires were administered among TCM physicians from TCM hospitals in Beijing between September 2020 and August 2021. The questionnaire mainly included general demographics, clinical backgrounds of TCM physicians, and clinical application of aconite. The data analyses were performed using SPSS 20.0.ResultsA total of 387 questionnaires were collected, of which 385 were valid. Of the 385 participating TCM physicians, 331 (85.97%) used aconite in clinical practice. The top three medical diagnoses treated with aconite were heart failure, diarrhea without cause, and chronic gastritis. The TCM pattern treated most frequently with a high dose of aconite was spleen-kidney yang deficiency, and the TCM pattern treated most frequently with a low dose was spleen yang deficiency, while spleen-kidney yang deficiency was treated most frequently with a common dose of aconite. The top three common formulas were Sini decoction, Mahuang Xixin Fuzi decoction, and Zhenwu decoction. Hei Shun Pian was the most common herbal pieces of aconite. The highest frequency of the maximum dose of aconite was 15 g, that of the minimum dose was 3 g, and that of the common dose was 10 g. There was a certain correlation between decoction time and the dose of aconite. Most TCM physicians advised their patients to take medicine twice a day.ConclusionIn this study, we refined and quantified the use of aconite and enriched the exploration of the clinical application of aconite besides its provisions in the Pharmacopoeia of the People's Republic of China.     

Postmarketing safety evaluation: depside salt injection made from Danshen (Radix Salviae Miltiorrhizae)

ObjectiveTo systematically examine the postmarketing safety of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), identify the potential risk factors, and ensure its clinical safety.MethodsWe examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae). Data from I-IV clinical drug trials, hospital information systems (HIS), and spontaneous reporting systems (SRS) were also analyzed.ResultsThe effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached more than 80%. The median lethal dose (LD50) calculated by the Bliss method was 1.49 g/kg, with 95% confidence intervals of 1.29–1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions (ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen (Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.ConclusionThis study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.     

基于真实世界中刺五加注射液应用于心血管病的复杂网络分析＊

为分析真实世界刺五加注射液治疗心管病的联合用药治疗方案，提取全国19家三甲医院信息系统（HIS）数据库中使用刺五加注射液治疗心血管疾病患者的一般信息、中西医诊断信息、医嘱记录，采用Tabu算法挖掘不同子结构之间的关系，并用复杂网络分析将结果可视化。全国19家医院5904例患者纳入分析，优效人群为2595，占44%。刺五加注射液治疗心血管疾病常与西药的抗心绞痛药、抗心律失常药、心血管扩张药、抗血栓药、降血脂药及中药祛瘀剂联合应用，使用频次最高的是单硝酸异山梨酯和中药的速效救心丸。优效人群的联合用药方案中不仅有对症治疗，还有针对基础病的用药，在临床中取得较为理想的疗效。通过对不同子结构之间关系的深入分析，可以为联合用药以及研发用药提供支持和借鉴。     

TNF inhibitors – Mechanisms of action,approved and off-label indications

Tumor necrosis factor inhibitors (TNFi) belong to the group of biologic drugs, holding presently top positions on lists of most profitable products for pharmaceutical companies. Although current indications for TNFi include only selected diseases with an established role of immune dysfunction in their pathogenesis, studies on new indications are being carried out all over the world. The most important aspect of TNFi therapy is a targeted therapeutic approach, allowing to avoid a wide range of side effects associated with treatment with nonspecific immunosuppressive agents. Results of the trials on TNFi in the approved indications are widely accessible and analyzed elsewhere, both in primary publications as well as in systematic reviews and meta-analyses. Here we aim to discuss their mechanisms of action, and approved, as well as off-label indications of TNFi. In addition, we present comprehensive evidence on TNFi in treatment of rheumatoid arthritis (RA); the first authorized and probably most extensively developed indication for the majority of TNFi.     

Establishment of safety evidence for Xingxue Shuxuening injection

OBJECTIVE： To systematically investigate the safety of Xingxue Shuxuening injection（SXN） in preand post-marketing, and to ensure clinical drug safety.METHODS： Strict quality control in raw herb selection and production processes was adopted and pharmacology research on SXN was performed by the drug manufacturing company, Heilongjiang ZBD Pharmaceutical Co., Ltd. We systematically reviewed the safety literature of Xingxue SXN. Adverse drug reaction（ADR） data of the drug, extracted from Spontaneous Reporting System（SRS）, and clinical characters based on 20 hospital information systems（HIS） in China, were analyzed. Large-scale prospective safety monitoring and Risk Minimization Action Plans（Risk MAPs） of XingxueSXN were carried out.RESULTS： The quality of SXN was stable and controllable when it was produced. Drug toxicology studies found no effect on rabbits with hemolytic or condensed, local stimulation and muscle stimulation, and no allergic reactions in guinea pigs. The ADRs of Xingxue SXN were dizziness, phlebitis,and vomiting based on SRS data. The injection did not conform to instructions in clinical practice when we analyzed HIS database, and patient＇s abnormal blood urea nitrogen levels may be related to the drug, when analyzed using the propensity score method. A nested case-control study was designed and performed to analyze the influencing factors of suspected allergic reactions to SXN. The study showed that patients with an allergy history were more prone to allergic reactions（P〈0.001）,and some medicine combinations could cause allergic reactions.CONCLUSION： These studies have established a body of evidence on Xingxue SXN safety, and provide a good model for Chinese medicine injection for clinical safety. The Xingxue SXN production process and toxicology research indicate the safety of the injection. However, the use of the injection is not consistent with instructed clinical practice.Xingxue SXN causes ADRs perhaps from inappropriate usage or its     

Phenotype-dependent alteration of pathways and networks reveals a pure synergistic mechanism for compounds treating mouse cerebral ischemia

Aim:

Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.

Methods:

Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.

Results:

In phenotype analysis, UA, JA, and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.

Conclusion:

The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.     

不同肥胖表型者中医体质特点分析研究

背景　有研究表明肥胖者和代谢紊乱者的中医体质类型存在一定的相似性,但是不同肥胖者发生代谢紊乱的风险不完全相同,是否中医体质为其内在原因？目前尚不可知。目的　探究不同肥胖表型者中医体质特点。方法　从2012年6月-2014年1月北京同仁医院、安徽中医药大学第一附属医院以及广东省中医院珠海医院治未病中心健康体检人群1 814例数据库中,排除年龄<18岁者、分析变量存在缺失值及体质量过轻和超重者,纳入1 267例体质量正常和肥胖样本进行分析。根据代谢正常/异常及体质量正常/肥胖组合形成4种代谢肥胖表型,即代谢正常体质量正常表型（MHNW）、代谢异常体质量正常表型（MUNW）、代谢正常肥胖表型（MHO）、代谢异常肥胖表型（MUO）。采用中医体质量表评价中医体质,采用最小二乘回归法（控制社会人口学因素及行为习惯因素）计算不同肥胖表型者9种中医体质（平和质、气虚质、阳虚质、阴虚质、痰湿质、湿热质、血瘀质、气郁质、特禀质）得分。结果　1 267例调查对象中,MHNW 584例（46.1%）,MUNW 207例（16.3%）,MHO 174例（13.7%）,MUO 302例（23.9%）。不同肥胖表型者平和质、阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者平和质得分高于MHNW和MUNW者,阳虚质得分低于MHNW和MUNW者;MHO和MUO者痰湿质得分高于MHNW和MUNW者（P<0.05）。男性不同肥胖表型者平和质、阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者平和质得分高于MHNW和MUNW者,阳虚质得分低于MHNW和MUNW者;MUNW、MHO和MUO者痰湿质得分高于MHNW者（P<0.05）。女性不同肥胖表型者阳虚质、痰湿质得分比较,差异均有统计学意义（P<0.05）;其中MUO者阳虚质得分低于MHNW者,MHO者痰湿质得分高于MHNW和MUNW者,MUO者痰湿质得分高于MUNW者（P<0.05）。结论　代谢状况相近的情况下,肥胖者痰湿质、平和质倾向更高,阳虚质倾向更低;体质量相近的情况下,不同代谢状况者未表现出明显的体质差异。但男性和女性情况有所不同,男性肥胖者和代谢异常者均表现为较高的痰湿质倾向;女性仅有肥胖者表现为较高的痰湿质倾向,而代谢异常者未发现较高的痰湿质倾向。     

肾主生殖的生物学基础

从形态、位置和毗邻的角度来看,中医的肾藏就是生物学之肾脏;从功能上看,肾藏不完全等同于肾脏,但是中医学肾主生殖功能与生物学生殖-内分泌系统相关。因此,可以通过对肾主生殖功能异常症状的生理病理解释,获得肾主生殖的生物学基础。肾藏的生物学基础一是主男性生殖之肾藏:①睾丸、附睾、输精管、射精管、尿道、阴茎、阴囊;②分泌器官:睾丸、附睾、前列腺、精囊、尿道球腺。二是主女性生殖之肾藏:①卵巢、输卵管、子宫、阴道、外阴;②分泌器官:腺垂体、卵巢、黄体、肾上腺、胎盘、乳房。肾精的生物学基础一是主男性生殖之肾精:①具有遗传基因的生殖细胞(精子)及其母细胞;②促性腺激素、雄激素、胰岛素样因子3、降钙素基因相关肽、雄激素结合蛋白;③附属性腺产生的分泌液。二是主女性生殖之肾精:①具有遗传基因的生殖细胞(卵子)及其母细胞;②促性腺激素(促卵泡素和黄体生成素)、雌激素、孕激素、雄激素、催产素、催乳素、前列腺素、人绒毛膜促性腺激素;③卵泡壁溶解酶。