“调任通督”法针刺治疗围绝经期潮热的随机对照研究＊

目的 观察“调任通督法”针刺治疗围绝经期潮热的临床疗效和安全性。方法 将符合纳入标准的72例围绝经期潮热患者，按照1∶1的比例随机分为治疗组（针刺组）和对照组（等待组）。治疗组取穴百会、印堂、神庭、关元、气海、中脘、阴郄、太溪、复溜、三阴交。针刺治疗每次持续30 min，每周2次，连续治疗6周。对照组为等待组，试验期间仅给予同针刺组相同的健康宣教，两组分别于治疗前、治疗第3周、治疗第6周以及第10周随访评估其潮热频率和程度，以及更年期生活质量量表（Menopause-specific quality of life questionnaire，Men-QoL）的变化情况，同时记录针刺不良事件的发生。结果 ①潮热频率及潮热程度：在治疗后及随访时，针刺组较等待组有明显改善，差异具有统计学意义（P < 0.01）。与治疗前相比，针刺组第3周即出现了潮热频率明显下降的趋势（P < 0.01），治疗后以及随访期针刺组潮热频率及潮热程度均较治疗前有明显统计学差异（P < 0.01）。而等待组在各时间点潮热频率及潮热程度均无统计学差异（均P > 0.05）。②围绝经期生活质量量表：治疗后针刺组在Men-QoL总分、血管舒缩功能评分、社会心理、体能状况较等待组比较均有统计学差异（均P < 0.01）。在随访期，针刺组在Men-QoL社会心理以及体能方面明显改善，差异均具有统计学意义（P < 0.01，P < 0.05）。两组Men-QoL性功能在治疗后及随访期均无统计学差异（P > 0.05）。与治疗前相比，在治疗后及随访期，针刺组Men-QoL总分、血管舒缩功能、社会心理、体能状况均有统计学差异（均P < 0.05），在Men-QoL性功能方面无统计学差异（P > 0.05）。等待组在Men-QoL总分及四个域方面均无明显改善，无统计学意义（均P > 0.05）。结论 调任通督法针刺治疗围绝经期潮热安全有效，且对围绝经期生活质量有所改善。     

Biomechanical behavior of brain injury caused by sticks using finite element model and Hybrid-III testing

Objective: To study the biomechanical mechanism of head injuries beaten with sticks, which is common in the battery or assaultive cases. Methods: In this study, the Hybrid-III anthropomorphic test device and finite element model (FEM) of the total human model for safety (THUMS) head were used to determine the biomechanical response of head while being beaten with different sticks. Total eight Hybrid-III tests and four finite element simulations were conducted. The contact force, resultant acceleration of head center of gravity, intracranial pressure and von Mises stress were calculated to determine the different biomechanical behavior of head with beaten by different sticks. Results: In Hybrid-III tests, the stick in each group demonstrated the similar kinematic behavior under the same loading condition. The peak values of the resultant acceleration for thick iron stick group, thin iron stick group, thick wooden stick group and thin wooden stick group were 203.4 g, 221.1 g, 170.5 g and 122.2 g respectively. In finite element simulations, positive intracranial pressure was initially observed in the frontal comparing with negative intracranial pressure in the contra-coup site. Subsequently the intracranial pressure in the coup site was decreasing toward negative value while the contra-coup intracranial pressure increasing toward positive values. Conclusions: The results illustrated that the stiffer and larger the stick was, the higher the von Mises stress, contact force and intracranial pressure were. We believed that the results in the Hybrid-III tests and THUMS head simulations for brain injury beaten with sticks could be reliable and useful for better understanding the injury mechanism.     

基于医院信息系统的乳腺癌临床特征及中西医用药特征分析

目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征，为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统（Hospital Information System，HIS）中，出院诊断为“乳腺癌”的患者用药信息，采用SAS9.3统计软件，对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者，平均年龄（50.93者，平均年龄）岁；多以门诊入院，入院病情以“一般”为主;合并疾病主要为高血压，骨肿瘤，联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主；中医辨证以痰瘀互结证，气阴两虚证，肝气淤滞证，脾气亏虚证型最为常见，临床清热解毒剂、益气扶正剂，活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗，联用药物广泛，临床治疗基本符合临床指南。     

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.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.