钙离子通道蛋白TRPV6及其相关疾病的研究进展

瞬时受体电位亚家族V成员6 (Transient Receptor Potential Channel Subfamily V Member 6, TRPV6) 是一种钙离子高度选择性离子通道，在多种组织中均有表达，控制细胞顶端钙离子的进入，在维持钙稳态中发挥重要作用。TRPV6功能异常会影响体内钙稳态，进而引发新生儿骨骼发育异常、甲状旁腺功能亢进、骨与软骨代谢异常、肾结石和高尿钙症、 以及炎症性肠病和慢性胰腺炎等多种疾病。近年来研究也表明，TRPV6的上调与多种肿瘤的侵袭性增加有关，具有作为肿瘤检测的标志物以及治疗靶点的潜力。本综述将聚焦于TRPV6与其在相关疾病中发挥的作用，旨在为TRPV6作为药物靶点实现临床转化提供理论依据。     

接受选择性淋巴结照射的食管鳞癌患者预后和失败模式的分析

目的探讨接受选择性淋巴结照射(ENI)的食管鳞癌患者预后和失败模式。方法回顾性分析2005年1月至2012年12月河北医科大学第四医院收治的179例符合入组条件的食管鳞癌患者,分析肿瘤局部相关因素预测患者预后的价值,分析影响患者近期疗效、预后的影响因素,并对影响患者总生存率(OS)、无进展生存率(PFS)和复发的指标分别进行单因素和多因素分析。结果全组患者1、3、5年OS和PFS分别为77.1%、40.1%、26.0%和62.6%、30.6%、20.3%。多因素分析结果显示声音嘶哑、cN分期、cTNM分期、GTV-横径(GTV-D)和GTV-体积/长度(GTV-V/L)为影响患者OS的独立性影响因素(P<0.05);声音嘶哑、cTNM分期和近期疗效为影响患者PFS的独立性影响因素(P<0.05)。全组有75例(41.9%)患者出现复发,61例(34.1%)远处转移,其中19例(10.6%)为合并复发和远处转移。75例复发患者中64例(85.3%)患者为单纯食管复发,4例(5.3%)为单纯淋巴结复发,另7例(9.3%)患者为食管合并淋巴结复发。治疗后达完全缓解(CR)的63例患者中有18例患者出现复发,其中仅有2例患者出现淋巴结复发;logistic多因素分析结果显示患者周边组织/器官受侵、GTV-D和近期疗效为影响患者复发的独立性影响因素(P<0.05)。结论食管鳞癌患者接受ENI确实可行,其失败主要模式仍为食管复发;治疗前声音嘶哑、GTV-D和GTV-V/L较大、临床分期较晚和近期疗效不佳为患者预后较差的指标;肿瘤周边组织受侵、GTV-D和近期疗效是影响患者失败的独立性因素。     

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.     

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....     

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.     

外周血miR-150-5p、SOCS1 mRNA对类风湿关节炎“病”“证”诊断意义的初步探讨＊

目的 探讨类风湿关节炎患者外周血miR-150-5p、细胞因子信号抑制因子1（suppressor of cytokine signaling 1，SOCS1）mRNA的表达及对类风湿关节炎（Rheumatoid Arthritis，RA）疾病诊断、中医证型判断的意义。方法 纳入符合诊断标准的RA患者57例及健康对照组19例，根据《22个专业95个病种中医诊疗方案》有关RA的中医证候诊断标准，判断RA的中医证型。qPCR检测RA患者及健康对照组miR-150-5p、SOCS1mRNA的相对表达水平，同时检测血常规、肝功能、肾功能等常规指标。双荧光素酶分析方法判断两者是否存在靶向关系。统计分析miR-150-5p、SOCS1 mRNA对RA疾病的诊断意义及其与中医证型的相关性。结果 RA患者外周血miR-150-5p的相对表达水平下调，低于正常人群（t = -19.019，P < 0.05）；其表达水平随疾病活动度升高，有下降趋势；患者外周血SOCS1 mRNA的相对表达水平上调，低于正常人群（t = 5.333，P < 0.05）；其表达水平随疾病活动度升高，有上升趋势。MiR-150-5p与SOCS1 mRNA有靶向结合关系（P < 0.05）。通过AUC曲线比较，miR-150-5p的相对表达水平区分RA的敏感性及特异性分别为98.1%、92.1%（AUC = 0.972，P < 0.05）；SOCS1 mRNA的相对表达水平无法区分RA（AUC = 0.472，P > 0.05）。RA患者中miR-150-5p的相对表达水平低于3.06，RA患者风湿痹阻证、寒湿痹阻证的相对风险分别为8.33、250.00（P < 0.05）。结论 miR-150-5p、SOCS1 mRNA在RA患者中有差异性表达，且有靶向结合关系。miR-150-5p可能是RA的疾病诊断及中医风湿痹阻证、寒湿痹阻证证型诊断的潜在生物标志物。