Nomogram Model for Predicting the Risk of Multidrug-Resistant Bacteria Infection in Diabetic Foot Patients.

OBJECTIVE: This study established an individualized nomogram for predicting the risk of multidrug-resistant bacterial (MDRB) infection in patients with the diabetic foot (DF), and providing a reference for clinical prevention and treatment. METHODS: A total of 199 DF patients admitted to the hospital from July 2015 to December 2018 were included in this study. The pathogenic bacteria at the site of infection were detected and the factors affecting the occurrence of MDRB infection in DF patients summarized. The R software was used to draw the nomogram, and the Bootstrap Method used to internally verify the model. The calibration curve and the Harrell's Concordance Index (C-index) were used to evaluate the predictive effect of the nomogram model. RESULTS: Logistic regression analysis showed that age, course of diabetes, previous use of antibacterial drugs, types of antibacterial drugs, and osteoporosis were risk factors for multidrug-resistant infections in DF (P<0.05). The area under the receiver operating characteristic curve (AUC, Area Under Curve) of the nomogram model after internal verification was 0.773 (95% CI: 0.704-0.830). The mean absolute error between the predicted probability of infection in the nomogram and the actual occurrence of MDRB was 0.032, indicating that the nomogram model had good forecasting efficiency and stability. CONCLUSION: The risk factors for multidrug-resistant infections in DF are age, course of diabetes, previous use of antibacterial drugs, types of antibacterial drugs used, and osteoporosis. The nomogram model drawn on these risk factors has good predictive accuracy and can assist medical staff in formulating targeted infection prevention strategies for patients.

The relevance of MTHFR C677T, A1298C, and MTRR A66G polymorphisms with response to male infertility in Asians: A meta-analysis.

Although published studies have reported the association between MTHFR C677T (rs 1801133), A1298C (rs 1801131), and MTRR A66G (rs1801394) polymorphisms and male infertility in Asian populations, the results are conflicting. In order to accurately evaluate the relevance, a meta-analysis was performed.We searched for potential studies in 4 databases, containing PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang database until May 31, 2018. The summarized odds ratio (OR) with 95% confidence intervals (95% CI) were calculated to evaluate the relevance in 5 genetic models. The heterogeneity test, sensitivity analysis, and publication bias test was performed by Review Manager 5.3 software.Overall, 22 case-control studies with 5049 cases and 4157 controls were included in this meta-analysis, which contained 20 studies of MTHFR C677T polymorphism, 12 studies of MTHFR A1298C polymorphism and 4 studies of MTRR A66G polymorphism. The results indicated that MTHFR C677T, A1298C, and MTRR A66G polymorphisms were significantly associated with male infertility in Asian populations (Dominant model: MTHFR CC + CT vs TT: OR = 0.60, 95% CI (0.53, 0.67), P <.00001; MTHFR AA + AC vs CC: OR = 0.62, 95% CI (0.49, 0.79), P = .0001; MTRR AA + AG vs GG: OR = 0.60, 95% CI (0.45, 0.81), P = .001. Recessive model: MTHFR CC vs CT + TT: OR = 0.67, 95% CI (0.61, 0.74), P <.00001; MTHFR AA vs AC + CC: OR = 0.79, 95% CI (0.70, 0.88), P <.0001; MTRR AA vs AG + GG: OR = 0.70, 95% CI (0.56, 0.88), P = .002. Heterozygote model: MTHFR CC vs CT: OR = 0.74, 95% CI (0.67, 0.82), P <.00001; MTHFR AA vs AC: OR = 0.83, 95% CI (0.73, 0.93), P = .002; MTRR AA vs AG: OR = 0.76, 95% CI (0.60, 0.92), P = .02. Homozygote model: MTHFR CC vs TT: OR = 0.48, 95% CI (0.41, 0.56), P <.00001; MTHFR AA vs CC: OR = 0.61, 95% CI (0.39, 0.93), P = .02; MTRR AA vs GG: OR = 0.51, 95% CI (0.36, 0.72), P = .0001. Allele model: MTHFR C vs T: OR = 0.70, 95% CI (0.66, 0.75), P <.00001; MTHFR A vsC: OR = 0.82, 95% CI (0.71, 0.95), P = .01; MTRR A vs G: OR = 0.76, 95% CI (0.66, 0.88), P = .00003). Stratified analyses by geographical location and source of controls showed the same results. Sensitivity analyses indicated that the final consequences of this meta-analysis were stable, and the publication biases test had not found obvious asymmetry.This meta-analysis indicates that MTHFR C677T, A1298C, and MTRR A66G polymorphisms are the risk factors with susceptibility to male infertility in Asians.

Xanthatin induces apoptosis by activating endoplasmic reticulum stress in hepatoma cells.

Hepatocellular carcinoma (HCC) has high incidence and mortality in patients with chronic liver diseases worldwide. However, there are limited chemotherapeutic agents for HCC in clinic. Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancers, but little is known about its effects on HCC and the underlying mechanism. Here, we evaluated the antitumor effects of xanthatin on human hepatoma cells. We found that xanthatin caused morphological changes and reduced cell viability in three HCC cell lines in concentration- and time-dependent manners. Xanthatin at 10 µM significantly arrested cell cycle at the G2/M checkpoint, and at 40 µM significantly arrested cell cycle at the S phase in hepatoma cells. Additionally, xanthatin induced apoptosis associated with activation of caspase-3 in hepatoma cells, but did not apparently induce apoptosis in human normal LO2 hepatocytes. We also demonstrated that the three primary signaling pathways of unfolded protein response (UPR) were activated by xanthatin to different extents. Notably, the PERK/eIF-2α/ATF4 axis was most significantly activated by xanthatin. More importantly, both xanthatin and tunicamycin, an endoplasmic reticulum stress (ERS) inducing compound, increased the levels of CHOP and cleaved-caspase-3 in HepG2 cells, but their effects were significantly abolished by siRNA-mediated knockdown of CHOP. Further experiments validated that xanthatin more potently activated ATF4 by promoting its nuclear translocation in hepatoma cells. Taken together, we discovered that xanthatin induced apoptosis in human hepatoma cells by activating ERS. Our current data revealed a novel mechanism for xanthatin as a promising anti-tumor candidate for HCC therapy.

PXR polymorphisms have impact on the clinical efficacy of clopidogrel in patients undergoing percutaneous coronary intervention.

BACKGROUNDS: Clopidogrel is widely used in Coronary Heart Disease (CHD) patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic events. However, clopidogrel response variability (CRV) may affect the patients' clinical outcomes. The current data have shown that genetic factors play an important role in CRV. The aim of this research is to investigate the association of pregnane X receptor (PXR, also called NR1I2) genetic polymorphisms with the clinical efficacy of clopidogrel in patients undergoing PCI. METHODS: A total of 384 patients undergoing PCI were recruited and treated with dual antiplatelet therapy (DAPT) for 12 months. The plasma concentration of clopidogrel carboxylic acid metabolites (CLPM) was measured by High Performance Liquid Chromatography (HPLC). The maximum aggregation rate (MAR) of platelet were measured by PL-11 analyzer. PXR genetic polymorphisms were determined by Sequenom MassArray system. The clinical outcomes were observed by readmission, outpatient and calling back interview within 12 months after PCI. RESULTS: Among all 384 patients, a total of 153 patients were occurred with major adverse cardiovascular events (MACE), 29 patients were occurred with bleeding events, the other patients had a favorable prognosis. The polymprphisms of PXR rs3814057A > C [OR(95%CI): 0.71(0.527-0.957), P = 0.024], rs3814058T > C [OR (95%CI): 1.395(1.034-1.883), P = 0.029] and rs6785049 A > G [OR(95%CI): 0.724 (0.535-0.979), P = 0.036] were significantly associated with MACE. The haplotype h1 (GCC) was associated with a higher risk of MACE [OR (95%CI): 1.385 (1.028-1.866), P = 0.031]. Whereas, the haplotype h2 (AAT) was associated with a lower risk of MACE [OR (95%CI): 0.711(0.525-0.962), P = 0.027]. CONCLUSIONS: The genotypes and haplotypes of PXR rs3814057, rs3814058 and rs6785049 have impact on the MACE in clopidogrel treated patients after PCI.

The peroxisome proliferators activated receptor-gamma agonists as therapeutics for the treatment of Alzheimer's disease and mild-to-moderate Alzheimer's disease: a meta-analysis.

Alzheimer's disease (AD) is a devastating neurodegenerative disease and there is no effective therapy for it. Peroxisome proliferators activated receptor-gamma (PPAR-γ) agonists is a promising therapeutic approach for AD and has been widely studied recently, but no consensus was available up to now. To clarify this point, a meta-analysis was performed. We searched MEDLINE, EMBASE, Cochrane Central database, PUBMED, Springer Link database, SDOS database, CBM, CNKI and Wan fang database by December 2014. Standardized mean difference (SMD), relative risk (RR) and 95% confidence interval (CI) were calculated to assess the strength of the novel therapeutics for AD and mild-to-moderate AD. A total of nine studies comprising 1314 patients and 1311 controls were included in the final meta-analysis. We found the effect of PPAR-γ agonists on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) scores by using STATA software. There was no evidence for obvious publication bias in the overall meta-analysis. There is insufficient evidence of statistically incognition of AD and mild-to-moderate AD patients have been improved who were treated with PPAR-γ agonists in our research. However, PPAR-γ agonists may be a promising therapeutic approach in future, especially pioglitazone, with large-scale randomized controlled trials to confirm.