中医药靶向调节p53介导的铁死亡机制研究进展

铁死亡是一种新发现的非凋亡调节性细胞死亡形式，以铁依赖性的脂质过氧化物及活性氧（ROS）累积为主要特征。p53是一种抑癌基因，可以通过介导多种关键细胞基因的转录调控，诱导细胞周期阻滞、凋亡、自噬和衰老，进而维持基因组稳定性。新近研究发现p53还可通过影响铁代谢、多不饱和脂肪酸（PUFAs）代谢、氨基酸代谢和烟酰胺腺嘌呤二核苷酸磷酸盐（NADPH）介导的多种细胞代谢过程，调控铁死亡，参与肿瘤、神经系统疾病、心血管疾病、肝病、肾病等疾病的病理进展。该文对p53介导的铁死亡在相关疾病转归中的作用机制及其影响因素进行了系统综述，同时追踪了中医药靶向调节p53介导的铁死亡防治肿瘤、脑卒中、急性心肌梗死、慢性心力衰竭、动脉粥样硬化、溃疡性结肠炎、佐剂性关节炎等疾病的研究进展，以期为相关疾病的防治提供新思路。     

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma

Lessons Learned

• A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies.
• This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.

BackgroundThis study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical‐grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV).MethodsThis study was an open‐label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m² capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1–4 and days 8–11 every 21‐day cycle. The primary endpoint was 6‐month survival rate, and secondary endpoints were progression‐free survival, overall survival, disease control rate, and safety.ResultsThirty‐nine subjects completed the study with a 46.2% stable disease rate. The median progression‐free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6‐month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen (not otherwise specified), fatigue, increased aspartate aminotransferase, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha‐fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome.ConclusionOur data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.     

基于知识图谱构建和定性访谈法探析张忠德教授辨治间质性肺病临床特征与方药规律＊

目的 构建个性化知识图谱技术和定性访谈法结合，进一步挖掘张忠德教授辨治间质性肺疾病临证特征与用药规律。方法 采用回顾性分析，系统收集张忠德教授广东省中医院门诊2010年8月至2020年8月治疗间质性肺疾病病历，按照诊断标准、纳入标准、排除标准，严格筛选后，通过广东省中医院大数据挖掘团队中医药大数据智能处理与知识服务系统进行数据挖掘分析，并通过多元化视觉定性访谈法，将定量与定性分析有效结合。结果 共筛选出347首方，共141味药物，常用药物频次 ≥ 84次的药物有10味，其中党参、麦芽、黄芪、紫菀、白术等为核心用药，通过症状与药物推理知识地图显示，党参、炒麦芽、黄芪、大枣、太子参、山萸肉、巴戟天等为主要治疗用药；临证遣方用药知识关联分析，得知咳嗽、耳鸣、心悸、水肿、头痛、胸闷、恶寒等为多见，针对咳嗽，首选紫苏子、橘红、桂枝等温肺降气通阳之品等；频繁聚集显示，常用药对炒麦芽-炒白术、黄芪-党参、黄精-菟丝子、前胡-紫菀、炙枇杷叶-浙贝母等；聚类分析结果得到4组关系密切的聚类新药物组合；以脾为中轴，肺肾共扶为主的“平调五脏论”，分期阶梯辨治间质性肺疾病。结论 张忠德教授认为间质性肺疾病，虚实夹杂为多见，应从肺、脾、肾着手，采用平调五脏论分期阶梯辨治，用药配伍精简，以和为贵，以平为期。     

基于数据挖掘的中药辅助化疗治疗晚期结直肠癌的用药规律文献研究＊

目的 分析中药复方辅助化疗治疗晚期结直肠癌的用药规律。方法 借助中国知网、万方数据、重庆维普以及中国生物医学文献数据库数据平台，搜索晚期结直肠化疗并中药经方治疗等相关文献，进行质量评价，剔除低质量文献，罗列组方建立Excel数据库，进行高频药物及其性味归经的描述性统计，基于SPSS Statistics 26.0关联规则及因子分析，SPSS Modeler 18.0聚类分析，Cytoscape软件直观网络图，进行数据挖掘整理与分析。结果 研究纳入相关文献148篇，处方155首，药物191味，用药总频次1823次，核心中药27味（使用频率 ≥ 10%），以白术所用最广。性味以甘温为首，归经以脾经为最。以置信度95%、支持度15%、提升度 > 1进行关联规则分析得到常用三药组合17组。聚类分析以欧式平方距离24为标准得到潜在聚类方剂3个。结论 中药复方用药以清补健脾，甘温扶正；平解邪毒，调气畅腑；肝脾同调，肺胃同治为规律，正合晚期结直肠癌化疗后脾虚毒恋、痰瘀互结之证。研究归纳出中药辅助化疗治疗晚期结直肠癌的用药组方规律，予以临床一定的理论依据及借鉴意义。     

隗继武教授临证用药经验

隗继武教授在长期的临床、教学、科研中积累了丰富的经验,善于通过调理脾胃治疗疑难杂病,他紧抓脾胃特点,重视辨证用药、药物配伍及脏腑关系,用药审慎求精,临床疗效显著。     

High serum neurofilament levels among Chinese patients with aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders

BackgroundSerum neurofilament light chain (sNfL) is a promising biomarker for neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS), but there is limited validation data in specific ethnic and disease groups.ObjectiveTo investigate the levels of sNfL in a cohort of Chinese patients with NMOSD and compare sNfL levels in patients with different disease courses and treatments.MethodsWe analysed sNfL levels in 153 Chinese patients with NMOSD (n = 51) and MS (n = 102) using single-molecule array (Simoa) technology. The sNfL levels were compared with those of 71 healthy controls from two centres in southern China. For each disease, we assessed correlations between sNfL and disease phases and treatments.ResultsHigher levels of sNfL were found in the patients with NMOSD [17.97 (10.55–27.94) pg/mL] and MS [15.83 (8.92–25.67) pg/mL] compared to healthy controls [10.09 (7.19–13.29) pg/mL, p < 0.001]. No significant differences were found between the AQP4-IgG-positive NMOSD group and OCB-positive MS group.ConclusionssNfL measured by Simoa technology is a potential candidate blood biomarker for the diagnosis and disease monitoring of NMOSD in Chinese patients, warranting further prospective and multicentre studies.     

Potential advantages of a combination of Chinese Medicine and bone marrow mesenchymal stem cell transplantation for removing blood stasis and stimulating neogenesis during ischemic stroke treatment

Combined treatment of ischemic stroke with Chinese medicine and exogenous bone marrow mesenchymal stem cell (BMSC) transplantation may improve the removal of blood stasis and stimulation of neogenesis.Chinese medicines that remove blood stasis not only promote blood circulation but also calm the endopathic wind,remove heat,resolve phlegm,remove toxic substances and strengthen body resistance.The medicinal targeting effect of Chinese medicine can promote the homing of BMSCs,and the synergistic therapeutic effects of drugs can contribute to BMSC differentiation.As such,exogenous BMSC transplantation has potential advantages for neogenesis.Chinese medicines and exogenous BMSCs provide complementary functions for the removal of blood stasis and stimulation of neogenesis.Therefore,a combination of Chinese medicine and transplantation of exogenous BMSCs may be particularly suited to ischemic stroke treatment.     

养脑安神法治疗考前紧张综合征86例

目的观察养脑安神丸治疗考前紧张综合征临床疗效。方法将考前紧张综合征172例随机分为治疗组和对照组,治疗组给予养脑安神丸,3～4g/次,3次/天,口服,连服6周;对照组给予逍遥丸,8粒/次,2次/天,口服。两组考试结束后,随访并判定疗效。结果治疗组、对照组总有效率分别为90.69%、67.45%,疗效治疗组为优(P<0.01)。结论养脑安神丸对考前紧张综合征有良好的治疗作用。