七叶一枝花甾体皂苷种类及含量差异研究进展＊

重楼是我国传统的名贵中药，七叶一枝花为历版《中国药典》收载的重楼药材两个基原植物之一，具有清热解毒、消肿止痛、活血化瘀等功效，其主要活性成分为甾体皂苷类物质。由于重楼市场需求量剧增和七叶一枝花成药时间较长，导致大量依靠人工种植。然而，人工种植过程中产地、采收年限和采收月份都会影响七叶一枝花的甾体皂苷含量。本文系统地总结了七叶一枝花中主要活性成分甾体皂苷的种类，以及不同产地、不同生长年限及不同采收月份的七叶一枝花根茎中甾体皂苷含量差异的研究现状，以期为进一步研究七叶一枝花品质差异、野生资源驯化及规范化种植提供参考。     

Effect of Replacement of Wharton Acellular Jelly With FBS on the Expression of Megakaryocyte Linear Markers in Hematopoietic Stem Cells CD34+

Objective: Animal environments for the growth of stem cells cause the transmission of some diseases and immune problems for the recipient. Accordingly, replacing these environments with healthy environments, at least with human resources, is essential.  One of the media that can be used as an alternative to animal serums is Wharton acellular jelly (AWJ).  Therefore, in this study, we intend to replace FBS with Wharton jelly and investigate its effect on the expression of megakaryocyte-related genes and markers in stem cells. Materials and Methods: In this study, cord blood-derived CD34 positive HSCs were cultured and expanded in the presence of cytokines including SCF, TPO, and FLT3-L. Then, the culture of expanded CD34 positive HSCs was performed in two groups: 1) IMDM culture medium containing 10% FBS and 100 ng / ml thrombopoietin cytokine 2) IMDM culture medium containing 10% AWJ, 100 ng / ml thrombopoietin cytokine.  Finally, CD41 expressing cells were analyzed with the flow cytometry method. The genes related to megakaryocyte lineage including FLI1 and GATA2 were also evaluated using the RT-PCR technique.  Results: The expression of CD41, a specific marker of megakaryocyte lineage in culture medium containing Wharton acellular jelly was increased compared to the FBS group. Additionally, the expression of GATA2 and FLI1 genes was significantly increased related to the control group. Conclusion: This study provided evidence of differentiation of CD34 positive hematopoietic stem cells from umbilical cord blood to megakaryocytes in a culture medium containing AWJ.     

阿克替苷通过激活血红素加氧酶-1抑制H_(2)O_(2)诱导的视网膜神经节细胞氧化损伤北大核心

目的研究阿克替苷对视网膜神经节细胞(RGC-5)的保护作用及其机制。方法将RGC-5细胞分为对照组、H_(2)O_(2)组、阿克替苷+H_(2)O_(2)组(1μmol·L^(-1)、10μmol·L^(-1)、30μmol·L^(-1)阿克替苷分别预处理细胞2 h),MTT法检测各组细胞活力;后续实验阿克替苷+H_(2)O_(2)组选择阿克替苷30μmol·L^(-1)作为治疗浓度,荧光探针H2DCF-DA检测活性氧(ROS)产生和罗丹明123检测线粒体膜电位,Western blot检测各组细胞中Bcl-2、Bcl-2/Bax、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达。机制研究中首先用不同浓度阿克替苷单独处理RGC-5细胞24 h,Western blot检测血红素加氧酶-1(HO-1)蛋白表达水平,进一步锌原卟啉(ZnPP)预处理RGC-5细胞1 h,而后30μmol·L^(-1)阿克替苷单独预处理后与200μmol·L^(-1)H_(2)O_(2)共孵育24 h,通过MTT法测定细胞活力。结果与对照组相比,H_(2)O_(2)组中细胞活力明显降低(P<0.01)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组中10μmol·L^(-1)、30μmol·L^(-1)阿克替苷预处理可显著提高细胞活力(P<0.05、P<0.01)。与对照组相比,H_(2)O_(2)组RGC-5细胞ROS生成明显增加,线料体膜电位显著降低,同时Bcl-2/Bax比值降低和Caspase-3蛋白相对表达量增加(均为P<0.05)。与H_(2)O_(2)组相比,阿克替苷+H_(2)O_(2)组RGC-5细胞ROS生成减少,线粒体膜电位增加,Bcl-2/Bax比值提高,Caspase-3蛋白相对表达量减少(均为P<0.05)。与阿克替苷未处理组相比,阿克替苷剂量依赖性诱导HO-1蛋白的表达,与阿克替苷+H_(2)O_(2)组相比,加入ZnPP后细胞活力降低(P<0.01),说明HO-1抑制剂ZnPP降低了阿克替苷对H_(2)O_(2)损伤的抑制作用。结论阿克替苷能够通过上调HO-1表达抑制H_(2)O_(2)诱导的RGC-5氧化应激损伤。     

流动人口基层医疗卫生机构首诊现状及影响因素分析

目的:了解流动人口基层首诊现状及其影响因素,为推进流动人口分级诊疗提供实证参考依据。方法:基于2017年全国流动人口动态监测调查数据中82734名最近1次患病(负伤)流动人口数据,利用SPSS 25.0统计软件分析其基层首诊情况及影响因素。结果:82734名最近1次患病(负伤)流动人口中首选到基层医疗卫生机构就诊15936人,基层首诊率仅为19.3%;二分类logistic回归分析结果显示:年龄≥65岁、农业户口、流动时间0~5年、患慢性病、至少参加1项医疗保险,居住地到最近医疗服务机构所需时间≤15 min的流动人口患病后更愿意选择到基层首诊。学历大专及以上、家庭月均收入>10000元、市跨县、东北地区、不愿意落户、自评健康状况为不健康的流动人口患病后更不愿意选择到基层首诊。结论:流动人口患病(负伤)后选择到基层首诊率较低,年龄、受教育程度、户口类型、家庭月均总收入、流动时间、流动范围、流入地区域、落户意愿、自评健康状况、是否患慢性病、有无参加医疗保险、居住地到最近医疗服务机构所需时间是影响流动人口患病(负伤)后选择到基层首诊的主要因素。     

A Coupled FEM-BEM Approach for the Solution of the Free-Boundary Axi-Symmetric Plasma Equilibrium Problem

In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric plasma equilibrium problem. The proposed method, obtained from an improvement of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium problem in unbounded domains by discretizing only the plasma region; the external conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github. om/matteobonotto/ FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against experimental data from RFX-mod device, and numerical equilibria of an ITER-like device.     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。     

A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

The impact of preoperative immune checkpoint inhibitors on kidney and bladder cancer surgeries: a systematic review☆

Therapies based on the use of immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, and durvalumab, have proven effective in the treatment of metastatic urological neoplasms. Recently, it has been hypothesized that the use of this type of treatment prior to surgery could lead to an increased difficulty in renal and bladder surgeries. The literature concerning this topic, however, is still scarce and non-consensual. In our systematic review, we used the PRISMA guidelines methodology to search the pertinent literature available up to June 18, 2020 in PubMed. Additionally, we searched the related grey literature in the abstracts of the meetings of the American Society of Clinical Oncology (ASCO), American Society of Clinical Oncology Genitourinary (ASCO-GU), European Society of Medical Oncology (ESMO), and American Urological Association (AUA) from 2015 to 2020. We were able to find only 16 publications that addressed the use of ICIs prior to surgery in kidney and bladder neoplasms. The results were conflicting, and usually the issue of surgical difficulties after the use of ICIs was not directly approached. We hope that our publication may raise the awareness towards the need to further investigate the effects of neoadjuvant ICIs on surgical outcomes in urologic cancers.