祛瘀通络脑泰汤结合循环灸对脑梗死急性期肢体痉挛状态的治疗效果及机制探讨

目的评价祛瘀通络脑泰汤结合循环灸对脑梗死急性期患者肢体痉挛状态的治疗效果及机制探讨。方法选择2018年1月—2020年1月医院收治的急性脑梗死患者95例,依据治疗方法的不同,分为试验组(48例)和参照组(47例),参照组依据《中国急性缺血性脑卒中诊治指南2014》给予西医规范治疗。试验组在参照组治疗的基础上,口服祛瘀通络脑泰汤结合循环灸治疗。两组均治疗2周。比较两组治疗前后中医证候积分、治疗疗效,比较治疗前后美国国立卫生研究院卒中量表(NIHSS)、Barthel指数(BI)、运动肌群肌张力评定量表(Ashworth)、血清脑源性神经影响因子(BDNF)和γ-氨基丁酸(GABA)含量。结果试验组治疗疗效较参照组高(P<0.05);试验组治疗后半身不遂、口舌歪斜、言语謇涩、头晕目眩、舌苔黄腻和脉象弦滑等中医证候积分低于参照组(P<0.05);试验组治疗后NIHSS评分、Ashworth评分低于参照组,BI评分高于参照组(P<0.05);试验组治疗后血清BDNF和GABA含量高于参照组(P<0.05)。结论祛瘀通络脑泰汤结合循环灸对脑梗死急性期肢体痉挛患者治疗效果确...     

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma

PurposeThe molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes.MethodsIn the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations.ResultsSeventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates.ConclusionsDifferent inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.     

荔枝核总皂苷体外抗乙型肝炎病毒的作用

0 引言 我国属乙型病毒性肝炎高流行区,2004年中国疾病预防控制中心调查显示我国HBsAg感染率高达9．09％．目前,尚没有理想的治疗慢性乙型肝炎的药物．我国有数千年应用中草药治疗疾病的传统和经验,从中已发现了不少抗乙型肝炎病毒（HBV）的药物．荔枝核是无患子科植物荔枝（Litchi chinensis Sonn）的成熟种子,又名荔仁或荔核,味甘、微苦,归肝、肾经,具有行气散结、祛寒止痛的功效．其化学成分包括皂苷、蒜质和脂肪酸等多种物质．研究发现,荔枝核黄酮类提取物对乙肝病毒HBsAg,HBeAg以及HBVDNA有明显的抑制作用．但荔枝核皂苷是否具有抑制HBV的作用,目前尚未见文献报道．我们采用HepG2．2．15细胞为靶细胞,观察不同浓度荔枝核总皂苷体外对HBV的抑制作用．     

脑白质病变MRI视觉分级方法的比较

目的:比较7种常用的脑白质病变(WMLs)MRI视觉分级方法,评价各分级之间的相关性和一致性,并计算两两间相互转化的参数.方法:随机选取50例MRI T2-FLAIR显示有不同程度WMLs患者,由两名医师分别用7种分级方法对其WMLs进行评分. 视觉分级间的相关性评价采用Spearman 等级相关分析,不同评估者之间的一致性分析采用Kappa检验,通过回归分析计算各分级间相互转化的参数.结果:不同视觉分级在WMLs评分上均有较强的相关性(相关系数rs: 0.579～0.917, P＜0.05). 除Schelten(modilified)分级和Ylikoski分级外,其它分级在不同观察者间的一致性好(κ＞0.585). 除Aharon-Peretz J分级和De Groot JC分级外,通过回归分析得出了其它5个分级间相互转化的参数,其确定系数R2的范围为0.5856～0.8892.结论:7种不同白质病变的MRI视觉分级间有较好的相关性,而不同评估者间Aharon-Peretz J分级的一致性最好.     

Drug D,a Diosgenin Derive,Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD^-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.     

一种海洋来源ETP类化合物GQQ-ZML-2抑制H358细胞增殖作用与机制的研究

摘要：目的 探究化合物GQQ-ZML-2对H358细胞(KRASG12C)的增殖抑制作用并初步研究其作用机制。方法 采用磺酰罗丹明B法（SRB法）测定GQQ-ZML-2对不同KRAS突变的肿瘤细胞的细胞毒;采用流式细胞术检测细胞周期和细胞凋亡;利用荧光探针DCFH-DA检测细胞内总活性氧（ROS）水平;Western Blotting检测相关信号蛋白的表达水平;结果 GQQ-ZML-2选择性抑制H358细胞增殖,以浓度依赖的方式抑制克隆形成并将细胞周期阻滞于G2/M期而诱导细胞凋亡。机制研究表明GQQ-ZML-2引起KRAS G12C依赖的ROS产生,抑制AKT/mTOR和JAK2/STAT3信号通路。结论 GQQ-ZML-2是一种新型的具有选择性抑制H358细胞增殖作用的海洋来源化合物,其作用机制可能与诱导KRASG12C依赖的ROS增加相关。本文研究为开发新型的拮抗具有KRASG12C突变肿瘤的药物提供了实验依据。     

血管化淋巴结皮瓣移植治疗下肢淋巴水肿的研究进展

下肢淋巴水肿的治疗是临床研究中的难点和重点。严重的下肢淋巴水肿对患者的生存质量影响极大。近年来,血管化淋巴结皮瓣移植作为一种新兴的手术方式,对重度下肢淋巴水肿具有较好的治疗效果。本文对血管化淋巴结皮瓣移植的作用机制、手术方式、辅助手段、常见并发症等方面的研究进展进行综述。     

山东中医药大学附属医院引进博士研究生发展现状分析

目的:了解山东中医药大学附属医院近年来引进的博士研究生的发展现状。方法:采用调查问卷的方法对医院近年来引进且入院满1年的博士研究生进行调查,统计其入院后的科研产出及工作状况,通过内容分析法分析其工作以来遇到的问题及困惑。结果:缺少科研支持、职能部门管理不到位、科室管理不够科学等是造成博士研究生发展困惑的因素,医院在高层次人才培养意识、高层次人才培养机制、高层次人才科研支持力度、对引入的外校高层次人才的人文关怀与心理疏导方面存在不足。结论:医院应增强高层人才培养的意识、健全人才培养的机制、强化人才培养与梯队建设方案的落实监督、为高层次人才提供科研支持、增强对引进高层次人才的人文关怀与心理疏导等,改变高层次人才发展环境。     

TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.Electronic supplementary materialThe online version of this article (10.1007/s12264-021-00662-3) contains supplementary material, which is available to authorized users.