XRCC3 Thr241Met polymorphism and ovarian cancer risk: a meta-analysis

Genetic polymorphism of X-ray repair crosscomplementing group 3 (XRCC3) Thr241Met has been implicated to alter the risk of ovarian cancer, but the results are controversial. In order to get a more precise result, a meta-analysis was performed. All eligible studies were identified through an extensive search in PubMed, Excerpta Medica Database (Embase), Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature Database before August 2013. The association between the XRCC3 Thr241Met polymorphism and ovarian cancer risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CIs). Finally, a total of four publications including seven studies with 3,635 cases and 5,473 controls were included in our meta-analysis. Overall, there was no association between XRCC3 Thr241Met polymorphism and risk of ovarian cancer under all five genetic models in overall population (T vs. C: OR = 0.99, 95 % CI = 0.960–1.03, P = 0.752; TT vs. CC: OR = 1.00, 95 % CI = 0.91–1.10, P = 0.943; TC vs. TT: OR = 0.97, 95 % CI = 0.92–1.04, P = 0.396, Fig. 1; TT vs. TC/CC: OR = 1.00, 95 % CI = 0.91–1.12, P = 0.874; TT/TC vs. CC: OR = 0.98, 95 % CI = 0.94–1.03, P = 0.486). In the subgroup analysis according to ethnicity, the results suggested that XRCC3 Thr241Met polymorphism was not associated with the risk of ovarian cancer in Caucasians population. No significant association was found between the XRCC3 Thr241 Met polymorphism and the risk of ovarian cancer. Given the limited sample size and ethnicities included in the meta-analysis, further large scaled and well-designed studies are needed to confirm our results

Association of MDR1 G2677T polymorphism and leukemia risk: evidence from a meta-analysis

In the light of the relationship between the MDR1 G2677T polymorphism and the risk of leukemia remains inclusive or controversial. For better understanding of the effect of MDR1 G2677T polymorphism on leukemia risk, we performed a meta-analysis. Eligible studies were identified through a search of electronic databases such as PubMed, Excerpta Medica Database (Embase), Cochrane Library, and Chinese Biomedical Literature Database (CBM). The association between the MDR1 G2677T polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95 % confidence intervals (95 % CI). A total of seven publications including eight studies with 1,229 cases and 1,097 controls were included in the meta-analysis. There was no association between MDR1 G2677T polymorphism and leukemia risk in all of five models in overall populations (T vs. G: OR = 1.00, 95 % CI = 0.88–1.12, P = 0.914; TT vs. GG: OR = 0.97, 95 % CI = 0.75–1.26, P = 0.812; TG vs. GG: OR = 1.00, 95 % CI = 0.92–1.08, P = 0.939; TT vs. TG/GG: OR = 0.98, 95 % CI = 0.67–1.43, P = 0.906; TT/TG vs. GG: OR = 1.00, 95 % CI = 0.95–1.06, P = 0.994). However, the significant association was found in others (Table 2) under the homozygote model (TT vs. GG: OR = 0.68, 95 % CI = 0.48–0.94, P = 0.020) and recessive model (TT vs. TG/GG: OR = 0.63, 95 % CI = 0.43–0.92, P = 0.016). In the subgroup analysis, according to the type of leukemia, significant association was found between MDR1 G2677T polymorphism and myeloid leukemia but not lymphoblastic leukemia (TT vs. GG: OR = 0.66, 95 % CI = 0.46–0.95, P = 0.026; TT vs. TG/GG: OR = 0.56, 95 % CI = 0.38–0.84, P = 0.005). The results suggested that there was no association between MDR1 G2677T polymorphism and leukemia risk in overall populations, but significant association was found in others populations (Asians and Africans), and myeloid leukemia indicated that G2677T polymorphism might be a protective factor in the susceptibility of myeloid leukemia and in Asians and Africans

Research Progress of Each Cell Signaling Pathway in Renal Interstitial Fibrosis and Anti-Fibrotic Intervention Countermeasures

Interstitial fibrosis is a common pathological feature of various progressive renal diseases, andthis result is mainly caused with the activation of renal interstitial innate cells (fibroblasts, pericytes, immune cells, mesenchymal stem cells, etc.) and the massive expression and deposition of extracellular matrix（ECM）. According to statistics,chronic kidney disease and interstitial renal fibrosis affect half of the world's adults over the age of 70 and 10% of the population.Although there are currently no drugs or other means to halt this process, as more and more key players affecting fibrosis are identified, this provides new research directions for anti-fibrotic therapy. In this review, we highlight the relationship between renal interstitial lamina propria and the progression of interstitial fibrosis and describe new advances in anti-fibrotic strategies.Finally,we hope to provide new ideas for the treatment of interstitial renal fibrosis

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX2 (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91phoxsiRNA. Conclusion: Knockdown of gp91phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model

Scheduling distributed energy resources and smart buildings of a microgrid via multi-time scale and model predictive control method

To schedule the distributed energy resources (DERs) and smart buildings of a microgrid in an optimal way and consider the uncertainties associated with forecasting data, a two-stage scheduling framework is proposed in this study. In stage I, a day-ahead dynamic optimal economic scheduling method is proposed to minimise the daily operating cost of the microgrid. In stage II, a model predictive control based intra-hour adjustment method is proposed to reschedule the DERs and smart buildings to cope with the uncertainties. A virtual energy storage system is modelled and scheduled as a flexible unit using the inertia of building in both stages. The underlying electric network and the associated power flow and system operational constraints of the microgrid are considered in the proposed scheduling method. Numerical studies demonstrate that the proposed method can reduce the daily operating cost in stage I and smooth the fluctuations of the electric tie-line power of the microgrid caused by the day-ahead forecasting errors in stage II. Meanwhile, the fluctuations of the electric tie-line power with the MPC based strategy are better smoothed compared with the traditional open-loop and single-period based optimisation methods, which demonstrates the better performance of the proposed scheduling method in a time-varying context

Kinetics of the neutralising antibody response in patients with hand, foot, and mouth disease caused by EV-A71: A longitudinal cohort study in Zhengzhou during 2017-2019

BACKGROUND: Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health. Kinetics of the neutralising antibody (NAb) response in EV-A71 infected HFMD patients remains unclear. The ideal sampling time of paired serum samples for serological diagnosis of EV-A71 infection is not well defined. METHODS: HFMD inpatients admitted to Henan Children's Hospital between February 15, 2017 and February 15, 2018 were enrolled. Serial serum samples collected during hospitalisation and up to 1.5 years after discharge were tested for NAb against EV-A71. Random intercept modelling with B-spline was conducted to characterize the kinetics of the EV-A71 NAb response over time after illness onset. FINDINGS: A total of 524 serum samples from 264 EV-A71 RNA positive HFMD inpatients were collected. NAb titres of EV-A71 infected patients were estimated to increase from 40 (95% CI: 9-180) at the day of onset to the peak of 2417 (95% CI: 1859-3143) at day 13, then remained above 1240 until 26 months. For serological diagnosis of EV-A71 infection, if at least a 4-fold rise in titre was used as the criteria, the acute phase serum should be collected at 0-4 days, the corresponding convalescent serum should be collected 14.9 days (95% CI: 9.1-23.8) after illness onset. INTERPRETATION: EV-A71 infection induced a strong and persistent humoral immune response in HFMD patients. The findings provide a scientific support for determining the collection time of paired serum samples for serological diagnosis of EV-A71 infected HFMD patients. FUNDING: National Science Fund for Distinguished Young Scholar