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.

[Relationship between ER-α36 and Akt in PC12 cells exposed to glucose deprivation].

ER-α36 is a novel 36-kDa variant of ER-α. A large of evidence demonstrated that ER-α36 responded to membrane-initiated estrogen signaling pathways which were involved in the physiological and pathological process in many kinds of cells. In this study, knock-down of ER-α36 expression in pheochromocytoma (PC12) cells (named as PC12-36L cells) by using the shRNA method was used to evaluate the relationship between ER-α36 and Akt in neurons under glucose deprivation. The effect of ER-α36 on outgrowth of PC12 cells, as well as the neuroprotective effect of ER-α36 on injured PC12 cells exposed to glucose deprivation was observed by using MTT assay, Western blot and Annexin V/PI staining et al. The results showed that, (1) Glucose deprivation induced by MEM treatment for 6 h reduced survival rate and increased apoptotic rate in PC12 cells significantly compared to control group (P < 0.01); and it produced a decrease in the expression of Glut-4 protein (P < 0.01); (2) The expression level of ER-α36 was decreased significantly at 3 h of glucose deprivation, and then increased, while phosphorylation of Akt participated in the glucose deprivation was increased at first and then reduced; LY294002 (PI3K inhibitor) contributed to decreased expression of ER-α36, and suppressed the activation of Akt; (3) The rate of apoptosis was significantly increased in PC12-36L cells after glucose deprivation compared with that in wild type PC12 cells (P < 0.01). Furthermore, phosphorylation of Akt was decreased and Caspase-3 was increased by glucose deprivation in PC12-36L cells compared with those in wild type PC12 cells. The study reveals that phosphorylation of Akt is associated with ER-α36 in PC12 cells exposed to glucose deprivation, and both are involved in the regulation of stress responses.

[Diverse expression of ER-α36, a novel variant of ER-α, in hippocampus and cortex of neonatal and adult rats].

ER-α36, a novel variant of ER-α, is expressed in breast, uterus, digestive tract, respiratory tract etc. The aim of the present study was to investigate the distribution and expression of ER-α36 in the central nervous system (CNS). Here, we comparatively analyzed the expression pattern of ER-α36 in the hippocampus and cortex of neonatal (1-day-old) and adult (12-week-old) Sprague-Dawley (SD) rats by using immunohistochemistry/immunocytochemistry analysis and Western blot. The results showed that ER-α36 was expressed both in hippocampus and cortex of adult rats, but mainly distributed in pyramidal neurons. ER-α36 was mainly located on the cytomembrane of hippocampal and cortical neurons from neonatal rats. Compared with the cortical neurons, the hippocampal neurons showed lower ER-α36 protein expression in the neonatal rats, but exhibited higher level of ER-α36 in the adult rats. Furthermore, the adult rats showed higher levels of ER-α36 expression in both hippocampus and cortex compared with the neonatal rats. These results suggest that ER-α36 might be involved in the regulation of membrane-initiated estrogen signaling throughout the postnatal development of diverse brain regions, and thus will be a potential target for the treatment of degenerative diseases in nervous system.

[Knock-down of ERα36 impacts the expression of differentiation protein in PC12 cells].

ERα36 is a novel subtype of estrogen receptor alpha (ERα) known to play an important role in breast cancer development and widely expressed in normal tissues and cells including nerve cells. However, the expression and function of ERα36 in nerve cells have not been well elucidated. To examine whether ERα36 is involved in differentiation of nerve cells, the differentiated and undifferentiated PC12 (PC12D and PC12unD) cells were used. Transfection of ERα36-shRNA plasmid into PC12 cells was performed to establish the ERα36 gene knock-down cells model. Immunocytofluorescence and Western blot were used to analyze the expression of Nestin, ß-tubulinIII and Neu-N in the PC12 cells. The results showed that ERα36 was expressed in both cell types. Compared with PC12D cells, PC12unD cells showed higher expression of Nestin and lower expression of ß-tubulinIII. ERα36-shRNA-mediated knock-down of ERα36 expression enhanced the expression of ß-tubulinIII and Neu-N, but attenuated Nestin expressions in PC12unD cells; ERα36 knock-down in PC12D cells mediated Nestin, ß-tubulinIII and Neu-N in a contrary manner. These results indicate that ERα36 knock-down appear to be associated with inhibiting differentiation in differentiated cells and promoting differentiation in undifferentiated cells, suggesting that ERα36 is a dual regulator in nerve differentiation.

Highly active carbonaceous nanofibers: a versatile scaffold for constructing multifunctional free-standing membranes.

Translating the unique characteristics of individual nanoscale components into macroscopic materials such as membranes or sheets still remains a challenge, as the engineering of these structures often compromises their intrinsic properties. Here, we demonstrate that the highly active carbonaceous nanofibers (CNFs), which are prepared through a template-directed hydrothermal carbonization process, can be used as a versatile nanoscale scaffold for constructing macroscopic multifunctional membranes. In order to demonstrate the broad applicability of the CNF scaffold, we fabricate a variety of CNF-based composite nanofibers, including CNFs-Fe(3)O(4), CNFs-TiO(2), CNFs-Ag, and CNFs-Au through various chemical routes. Importantly, all of them inherit unique dimensionality (high aspect ratio) and mechanical properties (flexibility) of the original CNF scaffolds and thus can be assembled into macroscopic free-standing membranes through a simple casting process. We also demonstrate the wide application potentials of these multifunctional composite membranes in magnetic actuation, antibiofouling filtration, and continuous-flow catalysis.