Background: Asthma is a complex polygenic disease in which gene-environment interactions are important. The gene encoding tumour necrosis factor alpha (TNFa) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNFa-308 gene promoter (substitution GRA, designated as TNF1 and TNF2) in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Methods: To address the inconsistent findings in studies of the association of the polymorphism of TNFa-308 gene promoter with susceptibility to asthma, a systematic review was undertaken of the published data and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to October 2005. Data were extracted using standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Fifteen eligible studies, comprising 2409 patients with asthma and 3266 controls, were included in the meta-analysis. Using the random effects model, the pooled result showed that the TNF2 allele is associated with overall susceptibility to asthma (OR 1.37, 95% CI 1.02 to 1.84, p = 0.04). The ORs for asthma susceptibility in TNF2 homozygote individuals were significantly increased at 2.01 (95% CI 1.26 to 3.20, p = 0.009) and 1.51 (95% CI 1.02 to 2.22, p = 0.041) compared with TNF1 homozygotes and TNF2/1 heterozygotes, respectively. In addition, the pooled OR for asthma risk in TNF2/1 heterozygotes was also significantly higher than that in TNF1/1 homozygotes (OR 1.47, 95% CI 1.01 to 2.13, p = 0.045). Conclusions: The TNF2 allele confers a significant risk for developing asthma. A large scale case-control study is needed to clarify the functional effect of the polymorphism of the TNFa gene in the pathogenesis of asthma.

Extracellular vesicles (EVs) can regulate the polarization of macrophages in a variety of inflammatory diseases by mediating intercellular signal transduction and affecting the occurrence and development of diseases. After macrophages are regulated by EVs, they mainly show two phenotypes: the proinflammatory M1 type and the anti-inflammatory M2 type. A large number of studies have shown that in diseases such as mastitis, inflammatory bowel disease, Acute lung injury, and idiopathic pulmonary fibrosis, EVs promote the progression of the disease by inducing the M1-like polarization of macrophages. In diseases such as liver injury, asthma, and myocardial infarction, EVs can induce M2-like polarization of macrophages, inhibit the inflammatory response, and reduce the severity of the disease, thus indicating new pathways for treating inflammatory diseases. The EV/macrophage axis has become a potential target for inflammatory disease pathogenesis and comprehensive treatment. This article reviews the structure and function of the EV/macrophage axis and summarizes its biological functions in inflammatory diseases to provide insights for the diagnosis and treatment of inflammatory diseases.

Background: Zaoren Anshen capsules (ZRAS) have been widely used to treat patients with insomnia. However, the efficacy and safety of ZRAS for insomnia treatment is not entirely clear. Therefore, it is necessary to clarify the effect of ZRAS for the treatment of insomnia by a systematic meta-analysis. Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases and performed a manual search to retrieve relevant articles (available through January 2019) describing randomized controlled trials (RCTs) of ZRAS for the treatment of insomnia. The quality of the selected articles was assessed with the Cochrane risk-of-bias tool. A meta-analysis of the selected articles was performed with RevMan 5.3 software. Results: A total of 13 articles including 1175 patients were included in the study. Overall, our results showed that ZRAS was slightly higher than that of the conventional Western medicine for insomnia in terms of clinical efficacy rate; but there was no statistical difference between the 2 groups (relative risk [RR] = 1.03, 95% confidence interval [CI] = [0.97, 1.09], P = .34). However, it should be noted that ZRAS treatment causes far fewer adverse reaction than treatment with conventional Western medicine (RR = 0.20, 95% CI = [0.14, 0.28], P < .00001). Conclusion: Our results suggested that ZRAS is an effective and safe treatment for insomnia, especially in adverse reaction. However, multi-regional and well-designed RCTs studies are needed in the future to validate the results.

Background/PurposeCurrently, there are no effective tools to accurately assess acute biliary pancreatitis (ABP) risk in patients with gallstones. This study aimed to develop an ABP risk nomogram in patients with symptomatic gallstones.MethodsWe conducted a retrospective nested case-control study and data on 816 conservatively treated patients with symptomatic gallstones admitted to The First Affiliated Hospital of Harbin Medical University between January 6, 2007 and January 22, 2016 were retrospectively collected. We conducted a propensity-score matched (PSM) analysis based on follow-up time in a ratio of 1:4 between ABP group (n=65) and non-ABP group (n=260). These matched patients were randomly divided into study cohort (n=229) and validation cohort (n=96) according to a ratio of 7:3. In the study cohort, independent risk factors for ABP occurrence identified using Cox regression were included in nomogram. Nomogram performance and discrimination were assessed using the concordance index (C-index), area under the curve (AUC), calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). The model was also validated in the validation cohort.ResultsNomogram was based on 7 independent risk factors: age, diabetes history, gallbladder wall thickness, gallstone diameter, coexisting common bile duct (CBD) stones, direct bilirubin (DBIL), and white blood cell count (WBC). The C-index of nomogram was 0.888, and the 10-year AUCs of nomogram was 0.955. In the validation cohort, nomogram still had good discrimination (C-index, 0.857; 10-year AUC, 0.814). The calibration curve showed good homogeneity between the prediction by nomogram and the actual observation. DCA and CIC demonstrated that nomogram was clinically useful.ConclusionsThe ABP risk nomogram incorporating 7 features is useful to predict ABP risk in symptomatic gallstone patients.

Sympathetic-induced vasoconstriction is mediated by various adrenergic receptor (AR) subtypes located on membranes of vascular smooth muscle cells (VSMC) located on the arterial wall, but is mostly attributed to activation of the α 1D -AR. In order to study interaction and crosstalk among AR genes, we induced post-transcriptional silencing of the α 1D -AR gene in cultured VSMC using the RNAi technique. A pSEC neo expression plasmid vector containing a small interfering RNA (siRNA) sequence selected to bind to the targeted mRNA of the α 1D -AR gene was transfected into cultured VSMC from rat aorta. The RNA expression of all AR-subtype genes was assessed by Q-RT-PCR and the α 1D and α 2A -AR proteins quantified by Western blot. In siRNA transfected cells, the α 1D -AR protein levels decreased by 55%, 69% and 75% at 24h, 48h and 72h, respectively (p < 0.03-0.01) with progressive increases in its gene expression by 50%-61% and concurrent increase in α 2A -AR protein peaking at 48 h. Decreases were noted in expression of the α 1A, α 2A , and β 3 AR genes. We conclude that post-transcriptional silencing of the α 1D -AR gene leads to significant decrease in receptor protein despite reactive increase in gene expression. However, suppression of one AR leads to reactive changes in other subtypes, indicating that cross-talk among related genes, whose products have overlapping functions, may partly offset anticipated effects in vivo.