老年良性阵发性位置性眩晕复发及死亡的临床研究

目的：探讨老年良性阵发性位置性眩晕（Benign paroxysmal positional vertigo,BPPV）复发及死亡的危险因素，为临床控制危险因素、减少复发及降低死亡风险发生提供理论依据。方法：回顾性连续纳入我院2013年12月30日至2018年9月23日明确诊断为良性阵发性位置性眩晕住院患者共1 366例，根据年龄是否大于等于65岁分为老年组和非老年组，其中老年组570例，非老年组796例。收集患者临床基本资料，并进行随访，以复发或出院后任何原因死亡为主要不良心血管事件（Major adverse cardiovascular events,MACE）进行记录。结果：与非老年组比较，老年组女性比例较低，高血压病、糖尿病、冠心病比例较高，入院收缩压较高，尿素氮、肌酐、尿酸水平较高，TC、LDL-c水平较低，TBiL、DBiL水平较高，颈部血管斑块发生率较高，MACE发生率较高（P均<0.05）。单因素Logistic回归分析结果显示：吸烟（OR=1.844,P=0.012,95%CI 1.143～2.975）、高血压（OR=1.597,P=0.012,95%CI 1...     

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol

Kaempferol is a natural flavonol that possesses various pharmacological activities,including anti-arthritis effects,yet the underlying mechanisms remain controversial.To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol,collagen-induced arthritis(CIA)mice were treated with kaempferol intragastrically(200 mg·kg^−1·d^−1)and intraperitoneally(20 mg·kg^−1·d^−1).Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index,arthritis index,paw thickness,and inflammatory factors;the bioavailability(1.5%,relative to that of the intraperitoneal injection)and circulatory exposure of kaempferol(Cmax=0.23±0.06 ng/mL)and its primary metabolite kaempferol-3-O-glucuronide(Cmax=233.29±89.64 ng/mL)were rather low.In contrast,the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects,although it achieved a much higher in vivo exposure.The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut.Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level,whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice.A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan,fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice.In conclusion,we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism,which are potentially responsible for the anti-arthritis activities of kaempferol.     

自然杀伤细胞免疫检查点抑制剂在癌症治疗中的研究进展

近年来许多研究证实免疫检查点抑制剂在多种癌症治疗中的潜力。自然杀伤细胞（natural killer cell，NK）是固有免疫系统的重要组成部分，在肿瘤免疫监视中发挥重要作用。其作用效应依赖于其与抑制和（或）激动受体的结合，无需主要组织相容性复合体（major histocompatibility complex，MHC）便能有效杀伤肿瘤。NK细胞对实体和血液肿瘤有巨大的杀伤潜力，已被越来越多的研究证实是肿瘤免疫治疗的理想靶点。NK细胞上一些新发现的免疫检查点受体被证实在肿瘤微环境中介导NK细胞的功能障碍，是理想的肿瘤免疫治疗靶点。本文将重点论述近年来新发现的免疫检查点受体在调节NK细胞功能中的作用及其在肿瘤免疫治疗中的潜在应用。      

Annual advances of integrative pharmacology in 2019

Representative studies concerning the pharmacology of traditional medicine and active herbal products have been summarized over the past 12 months.This annual integrative pharmacology review encompasses research articles published during 2019 on the bioactive compounds and extracts used in traditional medicine.Reports highlighting the pharmacology progress of traditional medicine were specifically introduced,including artemisinin for cancer cell sensibility and induction to ferroptosis,rutin for neuroinflammation suppression,Ginseng Radix et Rhizoma for gut microbiota regulation against obesity,green tea and Pu-erh tea for metabolic syndrome,and marine-derived oligosaccharide(GV-971)from brown algae for anti-dementia.Moreover,novel TCM molecular targets and pharmacological mechanisms were trialed against different human diseases,including cancers,cardiovascular,cerebrovascular diseases,diabetes,and metabolic diseases.Notably,herb-derived bioactive products have become important treatment alternatives for cancer research in 2019.Cardiovascular and cerebrovascular diseases,together with diabetes and metabolic diseases,are ongoing research areas for traditional medicine.Moreover,inflammation and infectious disease are also attracting more attention by researchers,which might have been influenced by seasonal influenza or HIV/Ebola viral infections.Further traditional medicine investigations are required in neurodegenerative diseases,depression,and mental diseases.Taken together,the findings of the integrative pharmacology review in 2019 provide a vast number of novel lead compounds or drug candidates for future clinical agent development and also details a novel series of attractive therapeutic targets and molecular mechanisms for human diseases.     

The cancer-testis gene,MEIOB,sensitizes triple-negative breast cancer to PARP1 inhibitors by inducing homologous recombination deficiency

Objective:The newly defined cancer-testis(CT)gene,MEIOB,was previously found to play key roles in DNA double-strand break(DSB)repair.In this study,we aimed to investigate the effects and mechanisms of MEIOB in the carcinogenesis of triple-negative breast cancers(TNBCs).Methods:The Cancer Genome Atlas database was used to quantify the expression of MEIOB.Cox regression analysis was used to evaluate the association between MEIOB expression and the prognosis of human TNBC.The effects of MEIOB on cell proliferation and migration in TNBCs were also assessed in vitro.Patient-derived xenograft(PDX)models were used to assess the sensitivity of breast cancers with active MEIOB to PARP1 inhibitors.Results:We confirmed MEIOB as a CT gene whose expression was restricted to the testes and breast tumors,especially TNBCs.Its activation was significantly associated with poor survival in breast cancer patients[overall,hazard ratio(HR)=1.90(1.16–2.06);TNBCs:HR=7.05(1.16–41.80)].In addition,we found that MEIOB was oncogenic and significantly promoted the proliferation of TNBC cells.Further analysis showed that MEIOB participated in DSB repair in TNBCs.However,in contrast to its function in meiosis,it mediated homologous recombination deficiency(HRD)through the activation of poly ADP-ribose polymerase(PARP)1 by interacting with YBX1.Furthermore,activated MEIOB was shown to confer sensitivity to PARP inhibitors,which was confirmed in PDX models.Conclusions:MEIOB played an oncogenic role in TNBC through its involvement in HRD.In addition,dysregulation of MEIOB sensitized TNBC cells to PARP inhibitors,so MEIOB may be a therapeutic target of PARP1 inhibitors in TNBC.     

重视门静脉高压症脾切除断流术后门静脉系统血栓的诊治

正脾切除贲门周围血管离断术(脾切除断流术)是临床上治疗门静脉高压症的主要术式,能够有效降低门静脉压力,对于上消化道出血的止血效果确切并且能够增加入肝血流,改善患者的肝功能。然而,脾切除术后门静脉系统血栓形成(postsplenectomy-portal vein system thrombosis,PS-PVST)的发生率很高[1-5]。PS-PVST的存在将导致门静脉压力再次升高,引起反复发作的腹水和静脉曲张出血。若不及时进行干预治疗,病情进一步发展将引起肝内缺血,诱发急性肝衰竭和肝性脑病,严重威胁患者生命。此外,肠系膜上静脉     

早期高危子宫内膜癌“夹心模式”序贯放化疗的疗效分析

目的评估“化疗-放疗-化疗”的“夹心模式”序贯放化疗在早期高危子宫内膜癌患者中疗效及可行性。方法回顾性分析2004年1月至2015年12月于北京大学人民医院行分期手术,分期(FIGO 2009)Ⅰ~Ⅱ期,且术后行“夹心疗法”的内膜癌患者,分析其临床病理特征,复发、生存及副反应。结果40例纳入研究,平均年龄(57±7)岁;随访51~182个月,仅1例术后66个月发生远处复发,其余均无瘤生存;5年总生存率及无疾病生存率均100%;无疾病生存期(178.7±3.3)m(95%CI:172.3~185.1);16例出现化疗副反应,仅1例发生Ⅲ度骨髓抑制;8例出现放疗副反应,其中1例发生左侧输尿管狭窄,其余为Ⅰ~Ⅱ度副反应。结论“夹心疗法”应用于早期高危内膜癌具有较好疗效,副反应可耐受。因病例数有限,有待积累病例,进一步总结。     

反向离子对色谱法测定氨甲苯酸片的含量

目的:建立反向离子对色谱法测定氨甲苯酸片中氨甲苯酸含量的方法。方法:采用Agilent 5TC-C18 150mm×4.6μm色谱柱,用甲醇-0.005mol?L-1的十二烷基硫酸钠溶液（用磷酸调节pH值至3.0）=55:45为流动相,流速1.0mL?min-1,柱温30℃,检测波长226nm。结果:氨甲苯酸在约1.0～0.02mg?mL-1的浓度范围内线性关系良好（r=0.9999）;平均回收率为99.96%,RSD为0.15%（n=9）,样品测定误差<0.1%。结论:本法经方法学验证,可用于氨甲苯酸片的质量控制。