Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

Evaluation of efficacy and safety of esmolol in treating patients with septic shock: A protocol for systematic review and meta-analysis

Background:In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks.Methods:A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered.Results:The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment.Conclusion:Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock.Ethics and dissemination:Ethical permissions are not required as prepublished data are used.OSF registration number:DOI 10.17605/OSF.IO/SKEZ7     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

Efficacy and safety of transcatheter arterial chemoembolization-lenvatinib sequential therapy for patients with unresectable hepatocellular carcinoma: a single-arm clinical study

BackgroundRepeated transcatheter arterial chemoembolization (TACE) could cause ischemia of the tumor tissue and increases production of angiogenic factors in patients with hepatocellular carcinoma (HCC). Lenvatinib can inhibit the expression of angiogenic factors induced by ischemia after TACE and reduce angiogenesis and tumor recurrence. TACE-lenvatinib sequential therapy may improve clinical outcomes. There have been few investigations of TACE-lenvatinib sequential therapy for the treatment of unresectable HCC. We aimed to evaluate the efficacy and safety of TACE-lenvatinib sequential therapy for unresectable HCC.MethodsFrom May 2018 to May 2021, 53 consecutive patients who underwent TACE-lenvatinib sequential therapy were retrospectively reviewed. Of these, 30 patients who met the inclusion criteria were selected. Lenvatinib treatment started within 1 or 2 weeks after TACE at a dose of 8 or 12 mg once daily. Treatment response was assessed using dynamic magnetic resonance imaging (MRI) according to the modified response evaluation criteria in solid tumor (mRECIST). Blood tests were also performed at every response evaluation. Patients with complete response (CR) or partial response (PR) and stable disease (SD) received continuous lenvatinib therapy, and patients with progressive disease (PD) received repeated TACE. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were calculated. Statistical analysis was performed using the Kaplan-Meier method.ResultsThe median age was 58.5±9.1 years, and 16.7% (5/30) of patients were female. A total of 12 patients were categorized as Barcelona Clinic Liver Cancer (BCLC) Stage B and 18 were BCLC Stage C. The mean follow-up time was 15.7 months. The ORR was 76.7% (23/30), and the DCR was 96.7% (29/30). The median PFS was 6.1 months, and the median OS was 20.7 months. The most common lenvatinib-related AE was rash, and the most common TACE-related AE was elevated aspartate aminotransferase (AST). No treatment-related mortality was observed.ConclusionsFrom our findings, TACE-lenvatinib sequential therapy may prolong OS and PFS in patients with unresectable HCC, and the side effects are acceptable. The efficacy and safety of the sequential therapy should be confirmed in multiple center randomized controlled trials (RCTs) with a large sample and sufficient follow-up period.     

40例原发性胃肠道弥漫大B细胞淋巴瘤临床特征、细胞来源与预后分析

背景与目的:原发性胃肠道弥漫大B细胞淋巴瘤(primary gastrointestinal diffuse large B-cell lymphoma,PGI-DLBCL)的发病部位及其临床表现与胃肠道其它肿瘤性疾病难以鉴别,误诊率较高,且其标准治疗的方法仍未确定。本研究旨在分析PGI-DLBCL的临床特征、肿瘤细胞来源及预后,并探讨有效的联合治疗方法。方法:分析我院1998～2007年诊治的40例PGI-DLBCL,应用Kaplan-Meier法、log-rank检验和Cox回归模型对其临床资料和实验室检测结果进行生存分析及单因素和多因素预后分析。通过免疫组化染色分析34例患者的肿瘤细胞来源。治疗方法包括联合化疗、手术 联合化疗及放疗、单纯手术等,联合化疗方案为CHOP及CHOP样方案。结果:40例PGI-DLBCL患者中,年龄10～89岁中位年龄56.5岁,男女比例1.86∶1,胃与肠道的发病比率为1.05∶1。预后分析可追访病例38例中,死亡12例(31.6%),3年和5年生存率均为64.7%。9例多部位发病的患者中,8例(88.9%)在3年内死亡。9例(26.5%)肿瘤细胞来源于生发中心(germinal center,GC),25例(73.5%)来源于非生发中心(non-germinal center,non-GC)。单因素预后分析发现肿瘤细胞来源、国际预后指数(international prognosis index,IPI)、B症状对生存率的影响有显著性(P<0.05)。Cox多因素预后分析显示血清乳酸脱氢酶(LDH)升高组患者的死亡风险是LDH正常组的2.87倍。结论:PGI-DLBCL发病以中年男性为主,多部位发病是该类患者死亡的重要原因。肿瘤细胞来源、IPI、B症状对预测患者生存和指导治疗有重要作用,其中初诊时血清LDH水平升高是本组患者的独立预后因素。     

基于人工智能的骨龄辅助评价系统对四川地区完全性生长激素缺乏症患儿骨龄研究

目的 探讨采用基于“人工智能(AI)的骨龄辅助评价系统(上海初云医疗科技有限公司与四川大学华西第二医院合作开发)”(以下简称为AI系统)对完全性生长激素缺乏症(CGHD)患儿诊断及骨龄评价准确性。方法 选择2014年7月至2019年11月,于四川大学华西第二医院确诊的66例来自四川地区CGHD患儿为研究对象,纳入研究组。选择同期于病例收集医院儿童保健科进行骨龄测定的67例来自四川地区身高达标儿童作为对照,纳入对照组。对每例受试儿进行左手腕关节正位X射线摄片骨龄测定,由2位医师采用《TW₂骨龄评分法中国未成年人南方标准》(以下简称为TW₂CHN)》与《TW₃骨龄评分法标准》(以下简称为TW₃),盲法评价受试儿TW₂CHN-桡、尺、掌指骨(RUS)与TW₂CHN-腕骨(carpal)、TW₂CHN-20、TW₃-RUS及TW₃-carpal骨龄(以下简称为5种传统骨龄),以及以同性别、年龄身高达...     

HPLC法测定舒金克喘胶囊中盐酸麻黄碱的含量

目的:测定舒金克喘胶囊中盐酸麻黄碱的含量。方法:用HPLC法测定,色谱条件:Hypersil ODS2 C18分析柱(150 mm×4．6 mm,5μm);流动相:1 000 ml水中加入磷酸二氢钾1．36 g、三乙胺3 ml,甲醇110 ml,加磷酸调pH 3-3．5,检测波长218 nm,流速1．0 ml·min-1,室温操作。结果:盐酸麻黄碱在0．119 6-1．196 0μg范围具良好线性:平均回收率为98．90％(RSD=1．70％,n=6)。结论:方法快速准确,样品处理简便易行。     

胆红素对离体培养大鼠耳蜗基底膜的药理效应观察

目的观察胆红素对离体培养的新生SD大鼠耳蜗器官的损伤效应。方法健康新生3日龄SD大鼠18只,雌雄不限,分离其双侧的内耳共得到耳蜗器官组织36个,体外培养,12h后换液。选择贴壁、存活良好的组织30个入选实验,并随机分为两组(15个/组):实验组于贴壁第二天开始进行胆红素处理,对照组加入相应体积的生理盐水。处理后24h,实验组和对照组同时终止培养,并对其进行固定、免疫组织化学染色,共聚焦显微镜观察毛细胞及螺旋神经节神经元的形态变化并计数,统计对比。结果胆红素组离体培养的耳蜗器官中螺旋神经节神经元胞体及其树突纤维与对照组相比有明显的减少,内外毛细胞形态完整,数量无明显变化。结论大鼠耳蜗器官螺旋神经节神经元对胆红素的毒性敏感,而内外毛细胞对其毒性相对不敏感。