Bioinformatics Analyses of Potential miRNA-mRNA Regulatory Axis in HBV-related Hepatocellular Carcinoma

Aims: We aimed to explore the crucial miRNA-mRNA axis through bioinformatics analysis and provide evidences for the development of pathophysiological mechanisms and new therapies for HBV-related HCC.Methods: MiRNA ({"type":"entrez-geo","attrs":{"text":"GSE76903","term_id":"76903"}}GSE76903) and mRNA ({"type":"entrez-geo","attrs":{"text":"GSE77509","term_id":"77509"}}GSE77509) dataset were used to screen differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs) using R software. Overlapping genes between DE-mRNAs and target genes of DE-miRNAs were identified as candidate genes. Hub genes were obtained via cytohubba analysis. The expression at protein and mRNA levels and prognostic value of hub genes were evaluated based on The Cancer Genome Atlas (TCGA) data. Key miRNA-mRNA axes were constructed according to predicted miRNA-mRNA pairs. MiRNA expression and prognostic role were respectively identified using starBase v3.0 and Kaplan-Meier plotter database. Real-time PCR was performed to verify the expression of crucial miRNAs and mRNAs. Coexpression of crucial miRNA and mRNA were analyzed using starBase v3.0.Results: CDK1, CCNB1, CKS2 and CCNE1 were screened as hub genes, which were significantly upregulated at protein and mRNA levels. These up-regulated hub genes were also significantly associated with poor prognosis. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 were screened as critical miRNA-mRNA axes. Critical miRNAs were decreased in HCC, which indicates unfavourable prognosis. QPCR results showed that crucial miRNAs were decreased, whereas critical mRNAs were increased in HBV-related HCC. A reverse relationship between miRNA and mRNA in crucial axis was further verified.Conclusion: This study identified several miRNA-mRNA axes in HBV-related HCC. Hsa-mir-195-5p/CDK1, hsa-mir-5589-3p/CCNB1 and hsa-let-7c-3p/CKS2 might serve as potential prognostic biomarkers and therapeutic targets for HBV-related HCC.     

Lactose-riched Mongolian mare's milk improves physical fatigue and exercise performance in mice

Fatigue may cause the efficiency of the organ in human body to decrease, which may affect the daily life and exercise performance of the general people and athletes. Mare''s milk powder (MMP) is a lactose rich supplement. The research of the study is to evaluate the whether MMP has anti-fatigue effect. Forty male ICR mice were randomly divided into four group to receive vehicle or MMP by oral gavage at 0 (Vehicle), 0.27 (MMP-1X), 0.54 (MMP-2X), 1.35 (MMP-5X) g/kg/day for 14 days. The forelimb grip of the MMP-2X, and MMP-5X group were significantly higher than the vehicle group. The swim-to-exhaustion times of the MMP-1X, MMP-2X, and MMP-5X group were significantly greater than the vehicle group. Glycogen levels in liver and muscle were significantly larger in the MMP-1X, MMP-2X, and MMP-5X groups than the vehicle group. Receive MMP supplement for 14 days can promoting exercise performance and amelioration of exercise-induced fatigue.     

Exploration of the relationship between tumor mutation burden and immune infiltrates in colon adenocarcinoma

Background: Tumor mutation burden (TMB) was correlated with the immunotherapeutic response in various malignancies. We aimed to evaluate the TMB immune signature in colon adenocarcinoma (COAD).Methods: Gene expression profile, mutation and clinical data of COAD patients were obtained from The Cancer Genome Atlas (TCGA) database. The samples were divided into high and low TMB level groups to identify differentially expressed genes (DEGs). Functional enrichments analyzes were performed to identify the biological functions of the DEGs. Then, immune cell infiltration signatures were calculated by the CIBERSORT algorithm. Finally, Cox proportional hazard model was constructed to estimate the prognostic value of the identified immune-related genes.Results: Gene set enrichment analysis in the high-TMB level group showed that DEGS were enriched in immune-related pathways, such as antigen processing and presentation, Toll-like receptor signaling and natural killer cell-mediated cytotoxicity. A higher infiltration level of CD8+ T cells, CD4+ T cells, activated NK cells , M1 Macrophages and T follicular helper cells was observed in the high-TMB level group. Furthermore, a Cox regression model combined with survival analysis based on the expression level of four identified prognostic genes was constructed, validated anf revealed that higher risk-score levels conferred poor survival outcomes in COAD patients.Conclusions: Our data demonstrate that the high TMB levels are associated with an immune signature in COAD and deepen the molecular understanding of TMB function in tumor immunotherapy.     

Successful intervention with Chinese herbal medicine for hyperthyroidism: Two case reports and a literature review

BackgroundHyperthyroidism, the excessive production of thyroid hormones, is most commonly attributed to autoimmune dysfunction such as Graves’ disease. Western medical treatment of hyperthyroidism includes antithyroid medications, radioiodine, and thyroidectomy, all of which are associated with side effects. We describe the successful treatment of two patients with Graves’ disease who used Chinese herbal medicine (CHM) with or without Western medicine.Case presentationBoth cases (a 50-year-old female [case 1] and a 56-year-old male [case 2]) received the Chinese herbal formula Jia Wei Xiao Yao San (JWXYS) as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas. Elevated thyroid hormone levels were restored to normal after 10 months of treatment in case 1 and 8 months in case 2. Neither patient experienced any complications or side effects during CHM treatment. Notably, symptoms and thyroid hormone levels have remained well controlled in both patients over 1 year of follow-up until the time of this report. To explore the possible mechanisms involved in CHM treatment of hyperthyroidism, we searched biomedical literature databases and reviewed the literature up to June 2020.ConclusionsAs for the hyperthyroidism almost was controlled by Western medicine instead of CHM, we report that JWXYS as well as Prunella vulgaris, Fritillaria thunbergii, and Crassostrea gigas was a safe and effective formula and we propose that CHM may be considered as either a first choice or combination therapy to control hyperthyroidism.     

Increased intracranial hemorrhage of mechanical thrombectomy in acute ischemic stroke patients with atrial fibrillation

Journal of Thrombosis and Thrombolysis - The impact of atrial fibrillation (AF) on outcomes of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is controversial, and with a paucity of...     

清热透邪法在新冠肺炎中的应用＊

目前新冠肺炎中医归属于“疫病”“瘟疫”范畴。其病因为疫戾邪气从口鼻而入，病理特点主要涉及湿、热、毒、瘀、浊、虚6个方面，但对于其病邪的性质，中医学界尚无完全统一认识。呈现百花齐放百家争鸣状态，此次疫病，王灿晖教授认为部分患者虽极早期或早期疠气挟夹寒湿为患，但速传于肺，以致出现高热、咳嗽、苔黄腻等肺热之征，秉承“祛邪为第一要义”，笔者临床根据王灿晖教授理论观点，施以“清热透邪”之法，获得良好效果，并列举典型案例，以期丰富中医药治疗新冠肺炎的理论与实践。     

构建靶向血管内皮生长因子受体2可调控活性的嵌合抗原受体T细胞及其体外功能验证

目的构建靶向血管内皮生长因子受体2(VEGFR2)可调控活性的小分子门控嵌合抗原受体T(smgCAR-T)细胞系统并在体外验证其抗肿瘤和可调节活性。方法采用基因全长合成和磷酸钙转染法构建smgCAR-T及其阳性(CAR+-T)和阴性(CAR--T)对照细胞。同时构建表达VEGFR2的小鼠结直肠癌细胞(MCA38VEGFR2+)。验证并筛选构建成功的细胞后再体外验证CAR-T细胞靶向结合能力。在不同的效靶比下检测白细胞介素-2和肿瘤坏死因子-γ的浓度来评估CAR-T细胞的体外分泌功能,用乳酸脱氢酶浓度评估CAR-T细胞的体外抗肿瘤活性。组间的比较采用t检验或单因素方差分析。结果基因测序和流式细胞术证实CAR-T细胞和靶细胞构建成功。与对照组比较,CAR+-T细胞+MCA38VEGFR2+组具有最强的靶细胞杀伤能力。在smgCAR-T细胞+MCA38VEGFR2+组中,随着C16-(S)-3-甲基吲哚雷帕霉素(Rapalog)滴度升高靶细胞杀伤率逐渐升高;当Rapalog为40 nmol/L时杀伤率达到最大值,为(66.25±13.20)%。分别向smgCAR-T细胞+MCA38VEGFR2+细胞组(A和B组)加入40 nmol/L的Rapalog后,在24 h时可观察到两组杀伤率出现同步升高[(44.25±6.24)%比(49.25±5.56)%,t=1.197,P>0.05],差异无统计学意义。在置换培养基后,再次添加了Rapalog的A组中观察到靶细胞杀伤率升高明显;而未再次添加Rapalog的B组中靶细胞杀伤率升高缓慢;此时,A和B组杀伤率差异有统计学意义[(89.00±3.16)%比(56.50±6.61)%,t=8.873,P<0.01]。结论构建的smgCAR-T细胞在体外展现出一定的抗肿瘤活性,且其活性受小分子化合物Rapalog的可逆调控。     

基于CiteSpace的中药溯源研究热点可视化分析＊

目的 归纳梳理中药溯源领域的研究现状和热点，分析发展趋势。方法 检索知网，万方，维普等中文文献数据库中2003年-2020年7月与中药溯源相关的文献并进行整理和归纳。使用CiteSpace 5.5 R2进行文献关键词，作者，机构的共现分析，获取对应知识图谱。结果 整理后共收集到196篇文献，通过分析，有三个团队在中药溯源领域内有稳定合作关系；机构之间合作较少且存在地域性，研究成果存在断档；热点关键词为质量追溯，物联网，区块链，二维码等。结论 中药溯源领域现处于稳定起步阶段，发文数量逐年趋于稳定，中药溯源系统与区块链，物联网，DNA条形码技术的融合，质量追溯体系的构建是相关研究的热点。NB-IoT，EPC编码等物联网技术在中药溯源系统中的运用未来将会受到更多学者关注。