Gut bacteria affect the tumoral immune milieu: distorting the efficacy of immunotherapy or not？

ABSTRACT

Immunotherapy using immune-checkpoint inhibitors is revolutionizing oncotherapy. However, the application of immunotherapy may be restricted because of the lack of proper biomarkers in a portion of cancer patients. Recently, emerging evidence has revealed that gut commensal bacteria can impact the therapeutic efficacy of immune-checkpoint inhibitors in several cancer models. In addition, testing the composition of gut bacteria provides context for prediction of the efficacy and toxicity of immunotherapy. In this review, we discuss the impacts of gut commensal bacteria on the tumoral immune milieu, highlighting some typical bacteria and their associations with immunotherapy.     

急性脑血管病的多系统并发症

分析１８５例急性脑血管病的严重并发症，以探讨多脏器系统衰竭（ＭＯＳＦ）的临床特点。结果显示４７例无脏器系统衰竭，４７例为单脏器系统衰竭（ＳＯＳＦ），９１例为ＭＯＳＬ即有１３８例出现单或多个脏器系统衰竭（ＯＳＦ）。５０％病例发生脑疝及合并ＯＳＦ，其中合并单脏器系统衰竭（ＳＯＳＦ）者３９例，ＭＯＳＦ者５３例；有２５％病例死于ＯＳＦ而非脑疝，其中３８例为ＭＯＳＦ，８例为ＳＯＳＦ。好发生衰竭的脏器系统依次为胃＞代谢＞肺＞心＞肾＞血液。梗塞组和出血组的第１个脏器系统发生衰竭的平均时间分别为２４小时和１２．５小时；第２个脏器系统平均时间分别为４天和２４小时。ＯＳＦ的发生与性别、原患病及脑干受损有关，但与病灶大小、数量及血肿破入脑室无关。因此，脑原性多脏器系统衰竭存在独特的临床特点及发病机制。     

Trace amines: identification of a family of mammalian G protein-coupled receptors.

Tyramine, beta-phenylethylamine, tryptamine, and octopamine are biogenic amines present in trace levels in mammalian nervous systems. Although some "trace amines" have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues. Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors. We have demonstrated that two of these receptors bind and/or are activated by trace amines. The cloning of mammalian GPCRs for trace amines supports a role for trace amines as neurotransmitters in vertebrates. Three of the four human receptors from this family are present in the amygdala, possibly linking trace amine receptors to affective disorders. The identification of this family of receptors should rekindle the investigation of the roles of trace amines in mammalian nervous systems and may potentially lead to the development of novel therapeutics for a variety of indications.     

白藜芦醇对人结肠癌细胞上皮间质转化的抑制作用

目的观察白藜芦醇(Resveratrol,Res)对人结肠癌细胞HCT-8上皮间-质转化(EMT)的影响,初步探讨其可能存在的机制。方法取对数生长期的人结肠癌HCT-8细胞,采用不同浓度的白藜芦醇(0、40、80、120μmol/L)对细胞分别进行干预24、48、72 h;MTT法检测不同时间Res对HCT-8细胞增殖活性的影响;细胞黏附试验检测Res对HCT-8细胞黏附能力的影响;Transwell小室试验检测Res对HCT-8细胞迁移和侵袭能力的影响;进一步采用蛋白免疫印迹法和qRT-PCR分别检测Res对HCT-8细胞中蛋白激酶B(AKT)、磷酸化蛋白激酶B(P-AKT)、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)和mRNA表达的影响。结果 Res(浓度为40、80、120μmol/L)在干预后24、48、72 h均可以明显抑制HCT-8细胞的增殖活性(P<0.05)。与空白对照组相比,细胞的同种黏附能力增强,异种黏附能力降低,差异有统计学意义(P<0.05)。与空白对照组相比,Res 120μmol/L对细胞迁移和侵袭能力均具有明显的抑制作用(P<0.05),Res 120μmol/L作用HCT-8细胞48 h后,HCT-8细胞中上皮间质标志性蛋白E-钙黏蛋白(E-cadherin)和mRNA的相对表达量增加(P<0.05),而AKT蛋白的表达无明显变化(P>0.05),P-AKT蛋白的表达明显减少(P<0.05);N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)和mRNA的相对表达量显著减少,差异有统计学意义(P<0.05)。结论白藜芦醇通过调控细胞EMT抑制人结肠癌HCT-8细胞的迁移和侵袭能力,其作用机制可能受PI3K/AKT信号通路的调控。     

严重急性呼吸综合征冠状病毒2疫情期间儿童肾脏病房感染防控思维导图

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的疫情已经持续了近2个月,现处于疫情胶着的状态。因儿童SARSCoV-2感染症状不典型,慢性肾脏疾病(CKD)患儿是高危感染人群,儿童肾脏专科病房的管理在复工、返校压力下,面临疫情防控的新挑战,国家临床研究中心肾脏病房、重庆市医学会儿科专委会肾脏学组,为进一步做好肾脏专科病房的疫情防控工作,结合目前疫情和相关防控建议,推荐SARS-CoV-2疫情期间儿童肾脏病房感染防控思维导图,以供儿童肾脏专科病房参考。     

急性脑梗死后抑郁患者血清iNOS,MIP-1 α水平变化及其临床意义

目的 探讨急性脑梗死后抑郁(Post-stroke depression,PSD)患者血清诱导型一氧化氮合酶(Inducible nitric oxide synthase,iNOS)、巨噬细胞炎性蛋白-1α(Macrophage inflammatory protein-1α,MIP-1α)水平变化及其临床意义。方法 收集2017年6月-2020年4月本院收治的143例急性脑梗死患者为研究对象,根据患者发病后1个月内是否发生PSD分为PSD组(n=42)和非PSD组(n=101),并于同期随机选取60例体检健康者为对照组; 采用酶联免疫吸附法检测各组血清iNOS,MIP-1α水平,绘制受试者工作特征(Receptor operating characteristic,ROC)曲线评估其对PSD的预测价值。结果 PSD组和非PSD组血清iNOS,MIP-1α水平高于对照组,且PSD组高于非PSD组(P<0.05); 随着抑郁程度的加重,PSD组患者血清iNOS,MIP-1α水平逐渐升高(P<0.05); 经Pearson积矩相关分析显示,PSD组患者血清iNOS,MIP-1α水平与HAMD评分呈正相关(r=0.692、0.658,P<0.05)。ROC曲线显示,iNOS水平预测PSD的AUC为0.862,灵敏度、特异性分别为83.33%、86.14%; MIP-1α水平预测PSD的AUC为0.832,灵敏度、特异性分别为78.57%、81.19%; iNOS联合MIP-1α水平预测PSD的AUC为0.902,灵敏度、特异性分别为88.10%、91.09%。结论 PSD患者血清iNOS,MIP-1α水平异常升高,并与病情严重程度密切相关,早期联合检测可作为预测急性脑梗死患者PSD发生风险的生化指标。     

Geometric classification of the carotid siphon: association between geometry and stenoses

Purpose

The development of intracranial internal carotid artery (ICA) stenoses may be associated with the morphology of the siphon. The aim is to quantitatively characterize the geometry of ICA, and develop a classifier of the ICA shape in relation to the location and incidence of stenoses.

Methods

The ICA geometry from 74 subjects was analyzed by means of image-based computational techniques. The siphon was split into two bends, and was described in terms of curvature radius, radius of vessel, angle of bending, and length. Differences of geometry between ICA classes were assessed in control group, consisted of 30 subjects without stenoses. In stenosed group, the association between the ICA classes and the incidence of stenoses were investigated and validated by hemodynamic simulation.

Results

The curvature radius and angle of the posterior bend were significantly different between ICA classes, as well as the angle between the two bends. An innovative classifier was developed with the three geometric parameters. The ICA classification was found associated with the incidence of stenoses at the siphon.

Conclusions

Geometric factors relative to the ICA were correlated with the location and incidence of stenoses at the siphon. The present work has potential implications in the quest for hemodynamic factors contributing to the initiation and progression of intracranial ICA stenoses.     

Molecular characteristics and evolutionary analysis of field Marek’s disease virus prevalent in vaccinated chicken flocks in recent years in China

Marek’s disease is a highly contagious, oncogenic, and immunosuppressive avian viral disease. Surveillance of newly registered Marek’s disease virus (MDV) isolates is meaningful for revealing the potential factors involved in increased virulence. Presently, we have focused on the molecular characteristics of all available MDVs from China, including 17 new Henan isolates. Based on Meq, gE, and gI genes, we found that most Chinese isolates contain conserved amino acid point mutations in Meq, such as E⁷⁷, A¹¹⁵, A¹³⁹, R¹⁷⁶, and A²¹⁷, compared to USA virulent MDVs. However, the 59-aa or 60-aa insertions are only found in a few mild MDVs rather than virulent MDVs in China. Further phylogenetic analysis has demonstrated that a different genotype of MDV has been prevalent in China, and for virulent MDVs, their recent evolution has possibly been geographically restricted. Our study has provided more detailed information regarding the field MDVs circulating in China.     

腰椎手术Wiltse入路准确进入多裂肌与最长肌间隙的解剖学基础

目的　探讨腰椎手术Wiltse入路的解剖学基础,提高该入路的稳定性和可操作性。 方法　成人标本20具,通过解剖观察双侧竖脊肌腱膜与多裂肌的关系;最长肌与竖脊肌腱膜的关系;多裂肌和最长肌间隙是否清晰,是否存在稳定的解剖标志;竖脊肌腱膜表面及其深面是否还存在其它结构可作为多裂肌和最长肌之间隙的解剖标志。 结果　多裂肌虽有少许纤维与竖脊肌腱膜相连接,仍可视为在竖脊肌腱膜上无起点;在腰部,最长肌在竖脊肌腱膜形成起点,起点的内缘自内上向外下斜行,并发出筋膜向深部延伸副突、横突,由此形成多裂肌与最长肌之间的分隔;在所有20具标本的左右两侧,以此隔膜为解剖标志向深部钝性分离,直接、顺利到达关节突;在竖脊肌腱膜表面未发现任何可作为多裂肌和竖脊肌间隙标志的解剖结构,剥离竖脊肌腱膜后在最长肌和多裂肌表面亦未发现可定位二者间隙的解剖标志;在多裂肌和最长肌间隙内,最长肌的内侧面可见清晰的节段神经及伴随血管。 结论　竖脊肌腱膜在最长肌内侧向深部的延续是腰椎手术Wiltse入路准确进入多裂肌和最长肌间隙的可靠解剖标志。     

强脉冲光联合Nd:YAG激光治疗黄褐斑疗效观察

目的:探讨强脉冲光联合Nd:YAG激光治疗黄褐斑的疗效。方法:60例患者按治疗方法不同分成3组:强脉冲光组、Nd:YAG激光组、联合组（强脉冲光联合Nd:YAG激光组）,每组20例患者,观察3组患者疗效和副作用。结果:3组之间疗效两两比较采用Mann-Whitney秩和检验,强脉冲光组和激光组疗效无显著差异,而联合组疗效显著好于强脉冲光组（Z=7.123, P=0.024）和激光组（Z=6.024, P=0.030）。3组患者治疗后均无出现色素沉着加重、色素脱失病等不良反应。强脉冲光组和激光组的满意度无显著差异,而联合组的满意度显著好于强脉冲光组（Z=7.361, P=0.029）和激光组（Z=6.831, P=0.027）。结论:强脉冲光联合Nd:YAG激光治疗黄褐斑是一种安全有效的治疗方法,值得临床推广。