SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters

Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface.     

Two new bisamides from the leaves of Aglaia perviridis

Two new bisamides, aglaiamides A (1) and B (2), along with three known ones (3–5), were isolated from the leaves of Aglaia perviridis. Their structures were established on the basis of detailed spectroscopic analyses.     

浙江省2007－2017年罕见病住院病例特征分析

目的 分析2007-2017年浙江省24 388例罕见病住院病例特征，为制定罕见病防控策略提供依据。方法 收集2007-2017年浙江省10家三级甲等（三甲）医院罕见病住院病例资料和各年度住院数，进行描述性统计分析。结果 罕见病病例共24 388例，占住院总例数的2.69‰（24 388/9 054 201），病例数居前3位的疾病类型依次为"血液和造血器官疾病以及某些涉及免疫机能的异常"（占32.81%，8 001/24 388）、"先天性畸形、变形和染色体异常"（占24.87%，6 065/24 388）和"神经系统疾病"（占19.01%，4 635/24 388）；2007-2017年罕见病病例数呈逐年增长趋势，年均增幅19.69%，而罕见病例数占同期住院总例数比例仅在2016-2017年明显上升，各类型罕见病时间分布呈不同特征；罕见病的病例数男女性别比为1.35：1（13 990/10 398），男女性别比最高的3类疾病依次为"消化系统疾病"（4.45：1，1 180/265）、"损伤、中毒和外因的某些其他后果"（3.51：1，281/80）和"神经系统疾病"（2.26：1，3 213/1 422）；各年龄段罕见病类型、各类型罕见病年龄分布均呈不同特征；病例数居前10位的疾病占全部罕见病例数的53.55%（13 060/24 388），其中前3位疾病分别为成人粒细胞缺乏症（14.41%，3 515/24 388）、皮质基底核退化症（7.60%，1 854/24 388）和亨诺克-舍恩莱因紫癜（6.01%，1 466/24 388）。结论 本研究分析的浙江省2007-2017年24 388例罕见病住院病例的特征资料，是推动我国罕见病的研究、监测或登记数据库构建、制定防控策略的参考依据。     

重症肌无力相关抗体的研究进展

作为一种累及神经肌肉接头的自身免疫性疾病,重症肌无力(myasthenia gravis,MG)的发病机制与自身免疫性抗体密切相关。关于MG相关抗体,研究最多且最为明确的是乙酰胆碱受体抗体(acetylcholine receptor antibody,AChR-Ab),由于存在AChR-Ab阴性的MG患者,近年来学者们开始热衷于研究AChR-Ab以外的其他抗体,如肌肉特异性酪氨酸激酶抗体、低密度脂蛋白4抗体等,并进行相应治疗方案的探索。该文对MG相关抗体的研究进展进行综述,为今后治疗该病提供临床依据和参考。     

医疗器械口咽通气道产品注册的常见问题及改进建议

近年来,医疗器械口咽通气道产品的注册数量日益增加,针对该产品的相关咨询也逐渐增多。但该产品暂无相关的注册技术审查指导原则,以致该产品的注册申报资料经常出现一些共性问题。现根据医疗器械口咽通气道产品相关法规和标准,对日常工作中遇到的常见问题进行归纳,分析该产品注册申报中的技术审评要求及共性问题,并给出对策或建议。     

替考拉宁在中国成人患者中的群体药动学研究

目的建立中国成年患者的替考拉宁(teicoplanin,TEC)群体药动学(population pharmacokinetics,PPK)模型,考察TEC药动学参数的影响因素。方法前瞻性收集139例革兰阳性球菌感染患者静脉注射TEC后的222份常规监测血药浓度和相关信息,采用一级消除的一室模型进行数据拟合,并应用非线性混合效应模型(nonlinear mixed effect model,NONMEM)程序建立PPK模型。采用Bootstrap、正态预测分布误差法(normalized predictive distribution error,NPDE)进行最终模型评价。利用蒙特卡洛模拟法对给药方案进行优化。结果确定了肌酐清除率(creatinine clearance,CLcr)、白蛋白(albumin,ALB)为影响TEC清除率的主要因素。最终模型为:CL(L·h^-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2。验证表明,模型稳定、有效,且有较好的预测效能。对于不同ALB和CLcr的多数患者起始负荷剂量400 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案可达有效治疗谷浓度。严重感染者需调整负荷剂量至800 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案来确保血药浓度达到15 mg·L^-1以上。结论本实验报道了CLcr、ALB对TEC清除率有显著影响,所建模型对TEC在中国成人患者中实现个体化给药具有重要应用价值。     

针刺京骨穴联合推拿治疗背肌筋膜炎临床研究

目的探讨针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效。方法将2016年10月—2018年10月收治的背肌筋膜炎患者86例纳入研究,采用随机数字表法分组。对照组43例予以推拿治疗,观察组43例予以针刺京骨穴联合推拿治疗。比较2组患者的治疗总有效率、VAS评分及Oswestry功能障碍指数、痊愈所用时间。结果观察组治疗总有效率为95.3%,而对照组仅为81.4%,差异有统计学意义(P<0.05);2组治疗后VAS评分、Oswestry功能障碍指数均有下降,观察组上述指标低于对照组,差异有统计学意义(P<0.05);观察组痊愈所用时间短于对照组,差异有统计学意义(P<0.05)。结论针刺京骨穴联合推拿治疗背肌筋膜炎的临床疗效突出,可缓解背部疼痛、恢复功能活动,并缩短了愈合时间,提高了生活质量,值得一定的临床推广。     

MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.     

脑血管疾病后Holmes震颤的临床、影像和电生理特点

目的 总结脑血管疾病后Holmes震颤的临床、影像和电生理特点。 方法 回顾性分析2015年8月-2019年8月就诊于首都医科大学附属北京天坛医院的4例脑血管疾病 所致Holmes震颤患者，对其临床、影像及电生理资料进行分析总结。 结果 4例患者中2例由高血压性脑出血引起，另外2例分别由脑动静脉畸形和脑海绵状血管瘤破裂 出血引起。Holmes震颤出现于原发病后1～24个月，表现为病灶对侧肢体震颤，以上肢多见。头颅MRI 检查显示2例患者病灶仅累及丘脑，2例同时累及丘脑和中脑。震颤分析显示静止、姿势、意向及持物 1000 g几种状态下震颤的峰频率均在2.6～3.8 Hz，意向状态震颤半宽功率高于静止状态。主动肌与 拮抗肌在静息时以同步收缩为主，姿势、意向和持物时以交替收缩为主。3例接受普拉克索治疗均有 不同程度缓解。 结论 Holmes震颤多由累及中脑、丘脑部位脑血管疾病引起，表现为2～4 Hz低频震颤，意向状态震 颤明显，部分患者多巴胺受体激动剂治疗有效。