基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

Lack of ceramide synthase 2 suppresses the development of experimental autoimmune encephalomyelitis by impairing the migratory capacity of neutrophils

Ceramide synthases (CerS) synthesise ceramides of defined acyl chain lengths, which are thought to mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed a significant elevation of CerS2 and its products, C24-ceramides, in CD11b⁺ cells (monocytes and neutrophils) isolated from blood. This result correlates with the clinical finding that CerS2 mRNA expression and C24-ceramide levels were significantly increased by 2.2- and 1.5-fold, respectively, in white blood cells of MS patients. The increased CerS2 mRNA/C24-ceramide expression in neutrophils/monocytes seems to mediate pro-inflammatory effects, since a specific genetic deletion of CerS2 in blood cells or a total genetic deletion of CerS2 significantly delayed the onset of clinical symptoms, due to a reduced infiltration of immune cells, in particular neutrophils, into the central nervous system. CXCR2 chemokine receptors, expressed on neutrophils, promote the migration of neutrophils into the central nervous system, which is a prerequisite for the recruitment of further immune cells and the inflammatory process that leads to the development of MS. Interestingly, neutrophils isolated from CerS2 null EAE mice, as opposed to WT EAE mice, were characterised by significantly lower CXCR2 receptor mRNA expression resulting in their reduced migratory capacity towards CXCL2. Most importantly, G-CSF-induced CXCR2 expression was significantly reduced in CerS2 null neutrophils and their migratory capacity was significantly impaired. In conclusion, our data strongly indicate that G-CSF-induced CXCR2 expression is regulated in a CerS2-dependent manner and that CerS2 thereby promotes the migration of neutrophils, thus, contributing to inflammation and the development of EAE and MS.     

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology

BACKGROUND Helicobacter pylori(H.pylori)infection is known to prevent the occurrence of gastroesophageal reflux disease(GERD)by inducing gastric mucosal atrophy.However,little is known about the relationship between atrophic gastritis(AG)and GERD.AIM To confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODS Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included.The grade of reflux esophagitis was evaluated according to the Los Angeles classification.Endoscopic AG(EAG)was categorized into six grades.Serologic AG(SAG)was defined as pepsinogen I≤70 ng/m L and pepsinogen I/II ratio≤3.0.The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTS In total,4684 individuals with GERD were compared with 21901 healthy controls.In multivariate logistic regression analysis,advanced age,male sex,body mass index>23 kg/m2,presence of metabolic syndrome,current smoking,and alcohol consumption were associated with an increased risk of GERD.Seropositivity for H.pylori immunoglobulin G antibodies was associated with a decreased risk of GERD.There was an inverse correlation between the extent of EAG and occurrence of GERD:Odds ratio(OR),1.01[95%confidence interval(CI):0.90-1.14]in C1,0.87(0.78-0.97)in C2,0.71(0.62-0.80)in C3,0.52(0.44-0.61)in O1,0.37(0.29-0.48)in O2,and 0.28(0.18-0.43)in O3.Additionally,the extent of EAG showed an inverse correlation with the severity of GERD.The presence of SAG was correlated with a reduced risk of GERD(OR=0.49,95%CI:0.28-0.87,P=0.014).CONCLUSION The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD.AG followed by H.pylori infection may be independently protect against GERD.     

2例胰岛素自身免疫综合征临床病例分析

通过回顾分析我院2例确诊为胰岛素自身免疫综合征(IAS)患者的临床资料,并复习相关文献,总结发病机制及治疗方法,探讨IAS患者的临床特点,提高对低血糖症的诊治水平。     

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

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