Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

EBUS-TBNA超声内镜对纵隔肿大淋巴结良恶性的鉴别诊断价值

目的:分析超声内镜引导下经支气管针吸活检(endobronchial ultrasound-guided transbronchial needle aspiration，EBUS-TBNA)术中肿大纵隔淋巴结的超声图像特点，探讨EBUS-TBNA超声内镜对纵隔淋巴结良恶性的鉴别诊断价值，以期提高EBUS-TBNA对纵隔淋巴结恶性病变的活检率。方法:回顾性分析2014年10月至2018年11月行EBUS-TBNA患者的超声内镜图像。我们使用以下EBUS超声内镜特征来预测淋巴结的良恶:回声，长轴长度，短轴长度，纵横比，形态，边界，淋巴门有无，淋巴结内血流信号分级。将超声检查结果与最终病理结果或临床随访结果进行比较。采用SPSS 20.0软件进行统计学分析，采用logistic回归分析评价肿大淋巴结EBUS-TBNA超声内镜下的特征与良恶性的相关性，以 P<0.05 为标准判定差异有统计学意义。结果:对130例纵隔淋巴结肿大患者的227个淋巴结进行回顾性分析，67.4%的肿大淋巴结被证实为恶性转移。Logistic回归分析显示回声、长轴及短轴的长度、正常淋巴门结构的消失是诊断恶性淋巴结的独立预测因素。结论:纵隔恶性淋巴结具有一定的超声特征，可以通过这些超声特征提高EBUS-TBNA对纵隔恶性淋巴结的检出率。     

The potential mechanism of Bupleurum against anxiety was predicted by network pharmacology study and molecular docking

Metabolic Brain Disease - Bupleurum chinense DC. (Chaihu) is a traditional Chinese medicine (TCM) used in the treatment of anxiety. But the anxiolytic mechanisms of bupleurum are still unclear....     

河南省非订单定向全科住院医师规范化培训结业学员的就业状况及影响因素研究

背景 全科医生数量和质量是人力资源管理的两个重要维度，其中，医生数量的新增、保持和流失，是全科人力动态规划、管理和评价的重要考量，也是全科住院医师规范化培训（简称全科住培）的绩效指标。探讨全科住培学员的就业状况及影响因素，可以为今后住培政策和激励机制的制定提供参考，但目前针对非订单定向全科住培学员的相关研究较为缺乏。 目的 了解河南省非订单定向全科住培学员的就业状况，分析学员结业后未从事全科医学相关工作的原因，从而为完善培训管理和人力资源激励机制提供参考。 方法 于2021年8月，采用分层随机整群抽样法，在河南省选取2014—2017年入培且已结业的非订单定向全科住培学员326例进行问卷调查。问卷由课题组自行设计，主要内容为学员的基本信息、全科住培情况、目前工作情况及结业后从事与未从事全科医学相关工作的原因。问卷通过"问卷星"平台发放，由学员自行填写。 结果 共发放问卷326份，回收有效问卷271份（83.1%）。结业后，从事全科医学相关工作者77例（28.4%），从事非全科医学相关工作者194例（71.6%）。多因素Logistic回归分析结果显示，年龄、文化程度、生源类型、全科住培基地所在区域是学员结业后是否从事全科医学相关工作的影响因素（P<0.05）。与结业后未从事全科医学相关工作的学员相比，结业后从事全科医学相关工作学员注册为全科医学专业的比例更高〔70.1%（54/77）比32.0%（62/194），P<0.05〕，在乡镇卫生院/社区卫生服务中心执业的比例更高〔49.4%（38/77）比6.2%（12/194），P<0.05）〕。194例未从事全科医学相关工作的学员中，从事内科学工作者78例（40.2%），从事急诊及危重症医学工作者33例（17.0%），从事外科学工作者17例（8.8%）。不选择从事全科医学相关工作的前3位原因分别为：单位安排〔34.5%（67/194）〕，所在单位没有全科医学科〔29.9%（58/194）〕，薪酬低〔26.8%（52/194）〕。 结论 非订单定向全科住培学员选择从事全科医学相关工作的比例较低，年龄、文化程度、生源类型及基地所在区域是影响因素。建议加大全科医学理念宣传，加快综合医院全科医学科建设，提高全科医生薪酬待遇，以此增加全科医生的职业吸引力。     

A Well-Balanced Positivity-Preserving Quasi-Lagrange Moving Mesh DG Method for the Shallow Water Equations

A high-order, well-balanced, positivity-preserving quasi-Lagrange moving mesh DG method is presented for the shallow water equations with non-flat bottom topography. The well-balance property is crucial to the ability of a scheme to simulate perturbation waves over the lake-at-rest steady state such as waves on a lake or tsunami waves in the deep ocean. The method combines a quasi-Lagrange moving mesh DG method, a hydrostatic reconstruction technique, and a change of unknown variables. The strategies in the use of slope limiting, positivity-preservation limiting, and change of variables to ensure the well-balance and positivity-preserving properties are discussed. Compared to rezoning-type methods, the current method treats mesh movement continuously in time and has the advantages that it does not need to interpolate flow variables from the old mesh to the new one and places no constraint for the choice of a update scheme for the bottom topography on the new mesh. A selection of one- and two-dimensional examples are presented to demonstrate the well-balance property, positivity preservation, and high-order accuracy of the method and its ability to adapt the mesh according to features in the flow and bottom topography.     

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。     

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.