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.     

晚期肺癌化疗患者医院感染的病原学与危险因素分析

目的研究晚期肺癌化疗患者发生医院感染的病原学特点,分析其危险因素,降低晚期肺癌化疗患者医院感染率。方法选择2012年1月-2015年12月收治的532例晚期肺癌化疗患者为研究对象,采集患者痰液或呼吸道分泌物标本进行细菌培养,应用SAS 9.3软件进行统计分析,并分析晚期肺癌化疗患者发生医院感染的危险因素。结果 125例晚期肺癌化疗患者发生医院感染,感染率为23.50%,其主要感染部位为呼吸道、胃肠道、口腔黏膜,分别占52.00%、15.20%、14.40%;共分离病原菌104株,其中革兰阴性菌51株占49.04%、革兰阳性菌30株占28.85%、真菌23株占22.11%;logistics回归显示,住院时间长、接受侵入性操作、使用抗菌药物是晚期肺癌化疗患者发生医院感染的危险因素。结论晚期肺癌化疗患者医院感染率较高,主要病原菌以革兰阴性菌为主,通过缩短患者住院时间、减少侵入性操作、合理使用抗菌药物等措施,降低晚期肺癌化疗患者医院感染的发生。     

单抗N糖分析系统适用性对照品的建立

目的建立单抗N糖分析方法的系统适用性对照品,并设定相应的系统适用性要求。方法利用液质联用(LC-MS)仪对N糖系统适用性对照品进行N糖型的表征鉴别,并对对照品进行稳定性评价。结合方法特点和验证数据,对系统适用性要求进行设定。结果建立的系统适用性对照品具有良好的稳定性,其糖型涵盖了单抗主要的N糖型种类。针对3种药典拟收录的单抗N糖分析方法,设定了以下系统适用性要求,包括:图谱与典型图谱相似、G1F(1,6)和G1F(1,3)的分离度应满足具体要求、G0F%应在规定的范围内、G0F保留时间的RSD应≤4%。结论建立了单抗N糖系统适用性对照品,可配合3种2020年版《中国药典》拟收录的N糖分析方法使用。     

柴芍六君子汤治疗消化性溃疡的随机平行对照研究

目的:观察柴芍六君子汤治疗消化性溃疡的临床症状改善、胃镜疗效、组织学炎症改善等方面的疗效。方法:采用随机平行对照方法对经胃镜检查确诊为消化性溃疡患者进行分析,对照组给予埃索美拉唑治疗,治疗组在上述治疗的基础上予柴芍六君子汤,疗程6周。结果:两组临床总有效率、血清胃泌素(Gas)比较均有统计学意义。结论:柴芍六君子汤治疗消化性溃疡能够发挥协同作用、增强疗效,降低不良反应,值得推广。     

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。     

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.     

Craving-induced effects of different drug cues on persons abstaining from heroin

Background: The key factors of inducing drug cravings in persons abstaining from drug use remain a focus of addictions research. Given the accumulating evidences, the scope of cues investigated in the cue-reactivity paradigm has increased considerably. Yet, few studies have examined the effects of the intensity and endurance of different types of cues on their ability to induce craving. This study investigated differences among drug-cue words, negative physiological-cue words, and negative social-cue words in the induction of drug cravings among persons abstaining from heroin.

Methods: The sample consisted of 149 male abstinent heroin abusers from four addiction rehabilitation centers in China. Based on their abstinence lengths, they were labeled as short-term, medium-term, and long-term abstainer participants respectively. All participants completed a stress-imagery task and rated craving by visual analog scale.

Results: There was a significant interaction of cue type and abstinence length. There was no difference on the craving induced by three types of cue words in the short-term group. In the medium-term group, craving induced by negative social-cue words was significantly stronger than that by negative physiological-cue words, but not that by drug-cue words. In the long-term group, the craving induced by negative social-cue words remained the strongest, significantly stronger than that by both drug-cue words and negative physiological-cue words.

Conclusion: Negative social-cue words presented in the current study retain the ability to induce craving in heroin abstainers; this finding suggests that negative social cues encountered under more general circumstances could be a risk factor for relapse.     

外泌体在肿瘤转移前微环境形成中的作用

肿瘤的转移前微环境（pre-metastatic niche，PMN）特指原发肿瘤灶为肿瘤细胞远处播散和定植准备的微环境，此微环境的六个特征包括炎症、免疫抑制、血管生成/血管通透性、亲器官性、重编程和淋巴管生成。PMN形成的关键成分包括肿瘤源性分泌因子、细胞外囊泡（含外泌体）、骨髓源性细胞、免疫抑制细胞和宿主基质细胞等，其中，外泌体作为细胞间重要的信使，在肿瘤PMN的形成中具有重要作用。本综述就外泌体在肿瘤PMN形成中的作用进行探讨。     

胆囊结石合并急性胰腺炎患者实施早期 LC 的安全性及有效性分析

〔摘 要〕 目的：探讨胆囊结石合并急性胰腺炎患者实施早期腹腔镜胆囊切除术（LC）安全性及有效性。方法：回顾性 分析 2017 年 1 月至 2019 年 3 月解放军联勤保障部队第 900 医院收治的胆囊结石合并急性胰腺炎患者 100 例临床资料，依据 手术时机分为观察组与对照组，各 50 例，对照组采用延期 LC，观察组采用早期 LC，对两组患者的一般资料、手术结果、 相关酶检测结果进行比较。结果：观察组患者的手术时间、住院费用、住院天数、手术出血量均少于对照组，差异具有统计 学意义（P ＜ 0.05）；术后第 6 天，两组患者的尿淀粉酶、谷草转氨酶、谷丙转氨酶、碱性磷酸酶比较，差异均无统计学意 义（P ＞ 0.05）。结论：胆囊结石合并急性胰腺炎患者采用早期 LC 治疗，患者术后恢复效果较好，且安全性较高。