Background Gestational diabetes mellitus (GDM) increased risk of perinatal complications for both the women and the fetuses. The association between the vitamin D receptor (VDR) gene polymorphism and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. Moreover, we aimed to explore their combined effects on the risk of GDM. Methods Pregnant women who had prenatal examinations at 24 to 28 weeks’ gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood samples were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted on the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and associations with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM. Results Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P < 0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P > 0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P > 0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs. Conclusions The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.

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Purpose The aim of the study was to find out the associations of Melatonin receptor 1B ( MTNR1B ) genetic variants with gestational diabetes mellitus (GDM) in Wuhan of central China. Patients and Methods A hospital-based case–control study that included 1679 women was carried out to explore the associations of MTNR1B single nucleotide polymorphisms (SNPs) with GDM risk, which were analyzed through logistic regression analysis by adjusting age, pre-pregnancy BMI and family history of diabetes. Multifactor dimensionality reduction was applied to determine gene–gene interactions between SNPs. Results MTNR1B SNPs rs10830962, rs10830963, rs1387153, rs7936247 and rs4753426 were significantly associated with GDM risk ( P <0.05). The rs10830962/G, rs10830963/G, rs1387153/T, and rs7936247/T were risk variants, whereas rs4753426/T was protective variant for GDM development. Fasting plasma glucose (FPG) and 1h-plasma glucose (PG) were significantly different among genotypes at rs10830962 and rs10830963, whereas 2h-PG levels were not. Gene–gene interactions were not found among the five SNPs on GDM risk. Conclusion MTNR1B genetic variants have significant associations but no gene–gene interactions with GDM risk in central Chinese population. Furthermore, MTNR1B SNPs have significant relationships with glycemic traits.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a local ablative technique for the clinical treatment of solid tumors, including locally advanced and unresectable PDAC, by intratumorally delivering high-intensity electric pulses to permanently disrupt cell membranes and induce cell death. But the distribution of electric field is uneven within the tumor, and in some regions, tumor cells only experience temporary perturbation to their cell membrane, a phenomenon denoted as reversible electroporation (RE). These tumor cells may survive and therefore are the main culprit of tumor relapse after IRE. We herein showed that RE, although not killing tumor cells, induced DNA double-strand breaks and activated DNA damage repair (DDR) responses. Using reactive oxygen species-sensitive polymeric micelles coloaded with Olaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and AZD0156, an inhibitor of ataxia telangiectasia mutated (ATM), the resultant nanoformulation (M-TK-OA) disrupted both homologous recombination and nonhomologous end joining signaling of the DDR response and impaired colony formation in pancreatic cancer cells after RE. The combination of IRE and M-TK-OA significantly prolonged animal survival in both subcutaneous and orthotopic murine PDAC models and elicited CD8 + T cell-mediated antitumor immunity with a sustained antitumor memory. The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.

Background: Gestational diabetes mellitus (GDM) increased risk for perinatal complications to both the women and the fetuses. The association between the vitamin D receptor (VDR) gene and GDM has not been thoroughly investigated in Chinese pregnant women. Therefore, we aimed to determine whether VDR gene single nucleotide polymorphisms (SNPs) rs154410, rs7975232, rs731236, rs2228570 and rs739837 contribute to GDM risk in Wuhan, China. In addition, we aimed to explore their combined effect on the risk of GDM. Methods: Pregnant women who had prenatal examination at 24 to 28 weeks’ gestation in our hospital from January 15, 2018 to March 31, 2019 were included in this case-control study. After exclusion, a total of 1684 pregnant women (826 GDM patients and 858 non-diabetic controls) were recruited. The clinical information and blood sample were collected by trained interviewers and nurses. Genotyping of candidate SNPs was conducted by the Sequenom MassARRAY platform. Statistical analyses including t-test, ANOVA, chi-square test and logistic regression were performed to the data with SPSS Software to evaluate differences in genotype distribution and association of genotypes with GDM risk. Multifactor dimensionality reduction method was used to explore the gene-gene interactions on the risk of GDM. Results: Differences in age, pre-pregnancy BMI, family history of diabetes and previous history of GDM between the case and control groups were statistically significant (P<0.05), whereas no significant differences were found in height, gravidity, parity, and age of menarche (P>0.05). There were no significant differences at genotype distributions of the examined VDR gene SNPs (P>0.05). After adjusting by age, pre-pregnancy BMI, family history of diabetes, the results of logistic regression analysis showed no associations of the five SNPs with GDM in all the four genotype models(P>0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the five examined VDR gene SNPs. Conclusion: The VDR gene SNPs rs154410, rs7975232, rs731236, rs2228570 and rs739837 showed neither significant associations nor gene-gene interactions with GDM in Wuhan, China.