反义端粒酶基因表达对肝癌细胞生长抑制的研究

目的：观察端粒酶基因hTRT反义表达对癌细胞生物学行为的影响,探讨人端粒酶逆转录酶反义基因治疗对肝癌细胞恶性表型的逆转作用.方法：含620bp端粒酶反义hTRT基因的PBSTRT质粒用Sal Ⅰ、BamH Ⅰ酶切后,插入真核表达载体pCDNA3 BamH Ⅰ、Xho Ⅰ酶切位点,构建成含反义hTRT基因的真核表达重组子.反义hTRT基因转染肝癌细胞株HepG1-6,观察其对肿瘤细胞生长的影响.结果：成功构建hTRT反义真核表达载体,并导入肝癌细胞株HepG1-6中,获表达hTRT反义基因的细胞系（HepG1-6/pCDNA3-反义hTRT）,该细胞系出现显著生长抑制现象,端粒酶活性明显下降,G0/G1期细胞增加,S和G2M期细胞减少,而HepG1-6/pCDNA3细胞则无明显变化.结论：反义hTRT基因治疗可以明显抑制HepG1-6细胞的增殖,部分细胞受阻于G1期,提示hTRT基因可以作为治疗肿瘤的靶基因.     

Efficacy and safety evaluation of acupuncture in the treatment of impaired glucose regulation: A protocol for systematic review and meta-analysis

Background:Impaired of glucose regulation belongs to the stage of prediabetes, which is a state of glucose metabolism between diabetes and normal blood glucose. The prevalence of prediabetes in people over 20 years old in China is significantly higher than that in diabetic patients. If no measures are taken to prevent the transition from prediabetes to diabetes, the number of diabetic patients in China will further increase. This study conducted a meta-analysis of the effectiveness of acupuncture in the treatment of impaired glucose regulation by collecting relevant literatures.Methods:Nine electronic databases: PubMed, EMBASE, Cochrane library, Web of Science, Google Scholar, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific and Journal Database, Wan Fang database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched for randomized clinical trails of acupuncture for impaired glucose regulation. The screening process will be developed by 2 independent reviewers, and meta-analysis will be performed with RevMan (V5.3.5) software.Results:This meta-analysis further confirmed the benefits of acupuncture in the treatment of impaired of glucose regulation.Conclusion:This study will provide a high-quality evidence of the efficacy and safety of acupuncture on patients with impaired glucose regulation.PROSPERO registration number:INPLASY202170058.Ethics and dissemination:This systematics review will evaluate the efficacy and safety of acupuncture in the treatment of impaired of glucose regulation. Since all the data included were published, the systematic review did not require ethical approval.     

The pectic polysaccharide from Bupleurum falcatum L. enhances immune-complexes binding to peritoneal macrophages through Fc receptor expression

Binding of glucose oxidase-anti-glucose oxidase complexes (GAG), a model of immune complexes, to macrophages was enhanced by treatment with an acidic pectic polysaccharide, bupleuran 2IIb, from Bupleurum falcatum L. GAG binding to macrophages by bupleuran 2IIb increased in a dose-dependent fashion, and was abolished when the Pronase^®-treated macrophages were incubated with bupleuran 2IIb. The GAG binding enhancing activity of bupleuran 2IIb was reduced by periodate oxidation but not Pronase^® digestion of bupleuran 2IIb. When bupleuran 2IIb was digested with endo-polygalacturonase, the resulting enzyme resistant carbohydrate portion showed potent activity. Scatchard analysis indicated enhanced expression of the Fc receptor (FcR) on the surface by the action of bupleuran 2IIb. The enhancement of GAG binding by bupleuran 2IIb was inhibited by the presence of actinomycin D or cycloheximide. Bupleur-2IIb-stimulated cells showed enhanced expression of both FcRI and FcRII mRNA, which were measured as PCR products. These results suggested that the endo-polygalacturonase resistant carbohydrate portion of bupleuran 2IIb is important for the expression of the activity, and that the activity of bupleuran 2IIb on GAG binding was mediated by receptors for polysaccharide on the cells. The up-regulation of the Fc receptor by bupleuran 2IIb was also suggested to mediate by de novo synthesis of the receptor protein.     

中文版老年人睡眠类药物使用情况调查问卷的跨文化调适

目的 对英文版老年人睡眠类药物使用情况调查问卷进行翻译,形成中文版问卷,并测量问卷的心理计量学特征。方法 与源问卷作者取得联系获得授权,采用Brislin翻译模型汉化形成修订版问卷。采用项目区分度（极端组比较法及积差相关系数）进行项目分析;采用专家测评法进行内容效度分析;探索性因子分析及验证性因子分析进行结构效度分析;问卷信度采用Cronbach α系数表示。结果 中文版问卷共有12条目,问卷Cronbach α系数为0.76,重测信度系数ICC=0.97;内容效度（S-CVI/Ave）为0.98;利用探索性因子分析对问卷提取公因子,特征值≥1的公因子有3个,对总方差的累计贡献率为56.56%,结构方程模型结果显示调整卡方值=3.75、拟合优度指数=0.89、比较拟合指数=0.86、调整后拟合优度指数=0.84、递增拟合指数=0.86、近似误差均方根=0.09,模型拟合度良好。结论 修订的中文版老年人睡眠类药物使用情况调查问卷具有良好的信效度,为医疗卫生人员评估老年人睡眠类药物使用情况提供工具,为卫生保健体系制定策略提供参考依据。     

Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality

Background and aimsHyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality.Methods and resultsNHANES datasets (cycles 2003–2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12–2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18–2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66–3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50–20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56–3.16, p < 0.001).ConclusionAlone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.     

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study

Background and aimsThe associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)].Methods and resultsWe used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65–0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50–0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88–0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01–0.60; p = 0.012).ConclusionOur MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.     

Anticancer potentiating effect and downregulation of PD-L1 expression: Study on the 2-[(p-fluorophenyl)amino]-6-substituted-9H-purine analogues as novel CHK1 inhibitors

In this study, a series of 2-[p-fluorophenyl]-6-substituted-9H-purine analogues were designed and synthesized as CHK1 inhibitors, among which compound b22 was the most potent. b22 exhibited nearly no antiproliferative activity toward HT29 cells and displayed a significant antitumor potentiating effect on HT29 cells when treated in combination with gemcitabine (Gem). A time-dependent assay found that treatment with Gem for 8 h before adding b22 achieved the optimal effect. Furthermore, the immunofluorescence and qPCR results demonstrated that b22 can remarkably reverse the upregulation of PD-L1 induced by Gem, which suggested dual effects of b22 in antitumor potentiation and antitumor immunity.