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Pengsheng Li,1,2,&ast; Haiyan Wang,2,3,&ast; Jinping Feng,2 Gengdong Chen,1,2 Zixing Zhou,1,2 Xiaoyan Gou,2,3 Shaoxin Ye,1,2 Dazhi Fan,1,2 Zhengping Liu,1,2 Xiaoling Guo2 1Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, People’s Republic of China; 2Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, People’s Republic of China; 3Biobank, Foshan Fetal Medicine Research Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoling GuoDepartment of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University Email fsguoxl@163.comPurpose: Prenatal depressive symptoms are an important mental health problem during pregnancy. We aimed to explore the moderating role of social support on the association between perceived stress and prenatal depressive symptoms.Materials and Methods: A cross-sectional study was conducted at an obstetrics clinic. A total of 1846 women completed a self-administered questionnaire, with a response rate of 91.8%.Results: Of the 1846 participants, 28.2% reported prenatal depressive symptoms (Edinburgh postnatal depression scale score ≥ 9). After adjusting for demographic characteristics, gestational age, exercise, and passive smoking, both perceived stress (adjusted odds ratio (AOR): 1.210, 95% confidence interval (CI): 1.178– 1.242) and social support (AOR: 0.950, 95% CI: 0.932– 0.968) were associated with prenatal depressive symptoms. Moreover, social support had a moderating effect on the association between perceived stress and prenatal depressive symptoms (p < 0.001), and pregnant women with low social support were more likely to be affected by stress and experience prenatal depressive symptoms.Conclusion: Our study suggests that higher social support reduces the impact of stress on pregnant women, which in turn, decreases the risk of prenatal depressive symptoms. Therefore, interventions aimed at improving social support should be considered for the prevention and treatment of prenatal depressive symptoms.Keywords: prenatal depressive symptoms, stress, social support, moderation

Background Previous evidence has suggested that lower gestational vitamin D levels might increase the risks of adverse pregnancy and birth outcomes. The results remain inconsistent and require further exploration. Methods A total of 2814 Chinese mother-infant pairs were included in this retrospective cohort study. Serum concentrations of 25(OH)D were reviewed in early pregnancy (16.3 ± 2.3 weeks). Outcomes of maternal gestational diabetes mellitus (GDM), cesarean section, fetal distress, preterm birth, low birth weight (LBW), and macrosomia were extracted from the medical records. Cox regression analysis was used to explore these associations. Results In total, 19.3% of mothers were pregnant at an advanced age (≥35 years), and 40.3% of pregnant women had vitamin D deficiency (HR) (95% CI) per standard deviation (SD) increase of serum 25(OH)D concentrations was 0.86 (0.779, 0.951) for GDM, 0.844 (0.730, 0.976) for preterm birth, and 0.849 (0.726, 0.993) for LBW. Similar protective associations were found for GDM, cesarean section, and preterm birth for a better vitamin D status when compared with vitamin D deficiency. Conclusion Higher early pregnancy vitamin D was associated with a lower risk of GDM, cesarean section, preterm birth, and LBW.

ObjectivePreviously, we found that the presence of maternal serum metals before the 24th week of gestation prospectively increased fasting plasma glucose (FPG) at 24–28 weeks. We further explored the prospective association between levels of metals and neonatal outcomes and assessed the mediating effects of FPG on these relationships.MethodsA total of 7,644 pregnant women were included in a retrospective cohort study, and the relationships between metals [manganese (Mn), copper (Cu), lead (Pb), zinc (Zn), and magnesium (Mg)] and birth outcomes were explored. Quantile and linear regressions were performed to detect the shifts and associations between metals and neonatal size distribution focused on the 10th, 50th, and 90th percentiles. Mediation analysis was performed to assess the mediating effect of FPG on metals and birth outcomes.ResultsAfter adjustment, a 50% increase in Mn and Zn levels was related to a 0.136-cm (95% CI: 0.067–0.205) and 0.120-cm (95% CI: 0.046–0.193) increase in head circumference, respectively. Based on head circumference distribution, the magnitude of the association with Mn was smaller at the upper tail, while the magnitude of correlation with Zn was greater at the upper tail. A 50% increase in Mn and Zn levels was related to a 0.135-cm (95% CI: 0.058–0.212) and 0.095-cm (95% CI: 0.013–0.178) increase in chest circumference, respectively. The magnitude of the association with Mn increased with increasing chest circumference, while the magnitude of correlation with Zn decreased with increasing chest circumference. FPG explained 10.00% and 17.65% of the associations of Mn with head and chest circumference. A positive indirect effect of Zn associated with head circumference (0.004, 95% CI: 0.002–0.006) and chest circumference (0.005, 95% CI: 0.003–0.008) through FPG was also observed, and the estimated proportion of the mediating effect was 13.79% and 26.32%, respectively.ConclusionMaternal serum Mn and Zn levels before the 24th week of gestation may prospectively increase the circumference of the neonatal head and chest. FPG at 24–28 weeks had positive mediating effects on these relationships. Further research is needed to identify a balance between maternal blood glucose and birth size.

Background The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. Methods A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. Results We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p Conclusions Our data demonstrated that neuraxial anesthesia is associated with better maternal and neonatal outcomes during cesarean delivery in women with placenta previa.

Jiaming Rao,1 Dazhi Fan,1 Zixing Zhou,1 Xin Luo,1 Huiting Ma,1 Yingchun Wan,1 Xiuyin Shen,1 Dongxin Lin,1 Huishan Zhang,1 Yan Liu,2 Zhengping Liu1,2 1Foshan Fetal Medicine Institute, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 2Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of ChinaCorrespondence: Zhengping Liu; Yan LiuFoshan Fetal Medicine Institute and Department of Obstetrics, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Renminxi Road 11, Foshan, Guangdong, 528000, People’s Republic of ChinaTel +86 757 82969878Fax +86 757 82969772Email liuzphlk81@outlook.com; liuyan20102011@163.comBackground: To compare the maternal and neonatal outcomes of placenta previa (PP) with and without coverage of a uterine scar in Foshan, China.Methods: A retrospective cohort study comparing all singleton pregnancies with PP was conducted at a tertiary, university-affiliated medical center from 1 January 2012 to 31 April 2017 in Foshan, China. Demographic, clinical and laboratory data were extracted from electronic medical records (EMRs). Maternal and neonatal outcomes of PP with and without coverage of a uterine scar were compared by statistical method.Results: There were 58,062 deliveries during the study period, of which 726 (1.25%) were complicated PP in singleton pregnancies and were further classified into two groups: the PP with coverage of a uterine scar group (PPCS, n=154) and the PP without coverage of a uterine scar group (Non-PPCS, n=572). Overall, premature birth (< 37 weeks, 67.5% vs 54.8%; P=0.019), cesarean section (100% vs 97.6%; P=0.050), intraoperative blood loss > 1000 mL (77.9% vs 16.0%; P< 0.001) or > 3000mL (29.9% vs 3.0%; P< 0.001), bleeding within 2-24 hours after delivery (168.2± 370.1 ml vs 49.9± 58.4 ml; P< 0.001), postpartum hemorrhage (48.7% vs 15.7%; P< 0.001), transfusion (34.6% vs 16.1%; P< 0.001), hemorrhage shock (7.8% vs 1.9%; P< 0.001), hysterectomy (2.6% vs 0.5%; P=0.019), fetal distress (35.7% vs 12.1%; P< 0.001) and APGAR score at 1 min (15.2% vs 7.1%; P=0.002) had a significant difference between PPCS group and Non-PPCS group. After grouping by whether complicated with placenta accreta spectrum disorders (PASD), we found that PPCS was significant associated with more intraoperative blood loss > 1000mL, intraoperative blood loss > 3000mL, bleeding within 2– 24 hours after delivery and fetal distress than the Non-PPCS group.Conclusion: The PPCS group had poorer maternal and neonatal outcomes than the Non-PPCS group after grouping by whether pregnancies complicated with PASD or with different placental positions.Keywords: placenta previa, placenta accreta spectrum disorders, pregnancy outcomes, uterine scar, hysterectomy, cesarean section

Persistent high-risk HPV infection is considered as a major cause of cervical cancer. Nevertheless, only some infected individuals actually develop cervical cancer. The RIG-I pathway in innate immunity plays an important role in antivirus response. Here, we hypothesized that altered function of mitochondrial antiviral signaling protein (MAVS) and mitochondrial TNF receptor–associated factor 3(TRAF3), key molecules downstream of the viral sensors RIG-I, may impair their ability of clearing HPV and thereby influence the risk for cervical precancerous lesions. To investigate the effects of MAVS and TRAF3 polymorphisms on susceptibility to cervical precancerous lesions, 8 SNPs were analyzed in 164 cervical precancerous lesion cases and 428 controls. Gene–environment interactions were also calculated. We found that CA genotype of rs6052130 in MAVS gene were at 1.48 times higher risk of developing cervical precancerous lesion than individuals with CC genotype (CA vs. CC: ORadjusted = 1.48, 95% CI, 1.02–2.16). In addition, a significant synergetic interaction between high-risk HPV infection and rs6052130 was found on an additive scale. A significantly decreased risk of cervical precancerous lesions for the TC genotype of rs12435483 in the TRAF3 gene (ORadjusted = 0.67, 95% CI, 0.45–0.98) was also found. Moreover, MDR analysis identified a significant three-locus interaction model, involving high-risk HPV infection, TRAF3 rs12435483 and number of full-term pregnancies. Our results indicate that the MAVS rs6052130 and TRAF3 rs12435483 confer genetic susceptibility to cervical precancerous lesions. Moreover, MAVS rs6052130–mutant individuals have an increased vulnerability to high-risk HPV-induced cervical precancerous lesions.

Background Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. Methods This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. Results The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18–5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07–3.47). Conclusions The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

Background Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. Methods This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. Results The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84–7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86–6.45), transfusion (OR 5.97, 95% CI 4.15–8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83–44.49), a more estimated blood loss (β 601.85, 95%CI 458.78–744.91), and a longer length of hospital stay after delivery (β 0.54, 95%CI 0.23–0.86) were found in the vertical skin incision group. Conclusions Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.

Objective: To explore the prospective correlation between serum metals before 24 weeks’ gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women. Methods: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose. Results: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks’ gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 μmol/L (95% CI: 0.033–0.070) and 0.059 μmol/L (95% CI: 0.040–0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: −0.017 to −0.008), 0.028 mmol/L (95% CI: −0.049 to −0.007), and 0.036 mmol/L (95% CI: −0.057 to −0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (−0.010 mmol/L, 95% CI: −0.021 to 0.001), however, it showed a protective effect at the upper tail (−0.034 mmol/L, 95% CI: −0.049 to −0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P

A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPLcGAS = 35.40%, CPLMAVS = 24.26%, and CPLTRAF3 = 96.76%) were significantly higher than those in the control (ControlcGAS = 31.87%, ControlMAVS = 21.16%, and ControlTRAF3 = 96.26%, PcGAS< 0.001, PMAVS< 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, Pa = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06–3.69, Pa = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.

No recommendations are available for gestational weight gain (GWG) in underweight women with twin pregnancies. We aimed to evaluate whether underweight women with twin pregnancies should gain more weight than normal-weight women in order to optimize perinatal outcomes.This retrospective cohort study compared the GWG and perinatal outcomes among normal-weight and underweight women who gave birth to viable twins between 2015 and 2018 at the Maternal and Child Health Hospital in Foshan, China. Gestational weight gain (GWG) was categorized as adequate or inadequate GWG, based on the US Institute of Medicine 2009 guidelines for normal-weight women (≥ 0.46 kg/week). The outcomes of interest included spontaneous preterm birth (sPTB)37 weeks,35 and32 weeks, small for gestational age (SGA), gestational hypertensive disorder (GHD), gestational diabetes mellitus (GDM), birth weight discordance (BDW) ≥20%, neonatal intensive unit (NICU) admission and neonatal respiratory distress syndrome (NRDS). Propensity score matching (PSM, in a 1:1 ratio) was utilized to minimize the effects of confounders on the differences in the two cohorts. Multivariable logistic models were also used to verify the results from PSM analysis.There were 475 normal-weight and 111 underweight women included in the analysis. Our results suggested that the incidence of adequate GWG was comparable between underweight and normal-weight women (37.5% vs. 45.1%, P = 0.141). The prevalence of GDM was significantly lower among underweight women (9.9%) than among normal-weight women (20.4%) (P = 0.010). There was no evidence of differences in other perinatal outcomes between the two groups. 102 underweight women and 102 normal-weight women were included in PSM analyses. There was a lower incidence of GDM in underweight women than in normal-weight women, but the difference was not significant (9.8% vs. 18.6%, P = 0.071). No evidence of any differences in the other outcomes, including sPTB, GHD, BWD≥20%, SGA, NICU admission and NRDS, was found between the underweight and normal-weight women. Multivariable logistic regression models yielded similar results.For Chinese twin pregnant women with twin pregnancies, our data does provide evidence to suggest underweight women need to gain more weight than normal-weight women to optimize perinatal outcomes. Future studies with larger number of underweight women with twin gestations are warranted to establish an optimal range of GWG.

Objective: To explore the size and shape association of OGTT values with adverse pregnancy complications among women with gestational diabetes mellitus (GDM) in Southern Han Chinese population and further analyze their mediating effects with maternal age in outcomes.Methods: 6,861 women with GDM were included in the study. Logistic regression was used to identify the correlations between OGTT values and adverse pregnancy outcomes of GDM. Restricted cubic spline nested logistic regression was conducted to investigate potential non-linear and linear associations. Mediating effect among maternal age, OGTT and adverse outcomes were explored.Results: Women with GDM had a mean age of 31.83, and 24.49% had advanced maternal age (≥35 years). In logistic regression with adjustment, compared with lower OGTT0 ( 0.05) were observed between OGTT0 and HDP, preterm, neonatal hyperbilirubinemia, and macrosomia in both maternal age groups (

The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case–control study to estimate risk factors of cervical precancerous lesions. The gene–environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58–0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35–0.73, P

Dengue is an arthropod-borne infectious disease caused by dengue virus (DENV) infection and transmitted by Aedes mosquitoes. Approximately 50–100 million people are infected with DENV each year, resulting in a high economic burden on both governments and individuals. Here, we conducted a systematic review and meta-analysis to summarize information regarding the epidemiology, clinical characteristics, and serotype distribution and risk factors for global dengue outbreaks occurring from 1990 to 2015. We searched the PubMed, Embase and Web of Science databases through December 2016 using the term “dengue outbreak.” In total, 3,853 studies were identified, of which 243 studies describing 262 dengue outbreaks met our inclusion criteria. The majority of outbreak-associated dengue cases were reported in the Western Pacific Region, particularly after the year 2010; these cases were primarily identified in China, Singapore and Malaysia. The pooled mean age of dengue-infected individuals was 30.1 years; of the included patients, 54.5% were male, 23.2% had DHF, 62.0% had secondary infections, and 1.3% died. The mean age of dengue patients reported after 2010 was older than that of patients reported before 2010 (34.0 vs. 27.2 years); however, the proportions of patients who had DHF, had secondary infections and died significantly decreased after 2010. Fever, malaise, headache, and asthenia were the most frequently reported clinical symptoms and signs among dengue patients. In addition, among the identified clinical symptoms and signs, positive tourniquet test (OR = 4.86), ascites (OR = 13.91) and shock (OR = 308.09) were identified as the best predictors of dengue infection, DHF and mortality, respectively (both P < 0.05). The main risk factors for dengue infection, DHF and mortality were living with uncovered water container (OR = 1.65), suffering from hypotension (OR = 6.18) and suffering from diabetes mellitus (OR = 2.53), respectively (all P < 0.05). The serotype distribution varied with time and across WHO regions. Overall, co-infections were reported in 47.7% of the evaluated outbreaks, and the highest pooled mortality rate (2.0%) was identified in DENV-2 dominated outbreaks. Our study emphasizes the necessity of implementing programs focused on targeted prevention, early identification, and effective treatment.

Aims To evaluate the effects of TRAF6 and NLRX1 polymorphisms and their interactions with environmental factors on the susceptibility of type 2 diabetes mellitus (T2DM) vascular complications in a southern Han Chinese population. Methods Five single nucleotide polymorphisms (SNPs) were genotyped in a case-control study to estimate risk factors of T2DM vascular complications. Gene-gene and gene-environment interactions and haplotype associations were also estimated. Results The CA genotype of the NLRX1 rs4245191 was identified as a risk factor for T2DM macrovascular complications and diabetic cerebral infarction (OR=2.88, 95% CI=1.15–7.22, P =0.024; OR=4.00, 95% CI=1.04–15.38, P =0.043, respectively). A significantly lower T allele frequency in the TRAF6 rs16928973 was observed in T2DM patients with both microvascular and macrovascular complications compared with patients without any complication under the allelic model (T vs. C: OR=0.36, 95% CI=0.14–0.98, P =0.038). No significant differences in haplotypes, gene-gene interactions and gene-environment interactions were observed among T2DM vascular subgroup patients. Conclusions Our study provides evidence that the NLRX1 rs4245191 polymorphisms influence the risk of T2DM macrovascular complications and diabetic cerebral infarction.

Toll-like receptor 4 (TLR4), one of the key immune system effectors, plays a main role in immune recognition of cervical cancer. Micro-RNAs are involved in regulation of multiple important genes in the progression of cervical cancer. A case-control study of 592 people was conducted from Yun’an County, Yunfu City, Guangdong Province, China. Cervical fall off epithelia were collected to detect human papilloma virus (HPV), followed by Thin Prep cytology test (TCT). Moreover, extraction of DNA from peripheral blood were performed for genotyping from the 296 patients and another 296 age-matched healthy control subjects. Logistic regression was used to determine the risk genotypes for susceptibility to cervical precancerous lesion, and multifactor dimensionality reduction (MDR) was further employed to preliminarily investigate the gene-environment interaction on risk of cervical precancerous lesion. Gene expression of miRNA-140 from serum was done by real-time PCR. We investigated whether target sites of TLR4 gene polytheisms (rs11536896 T>C, rs7873784 G>C) of miR-140 were associated with cervical precancerous lesion risk. The alleles C>A of SNP rs11536896 were significantly different in ASCUS in comparison of case group and control group with HPV infection. The presence of the allele C was associated with a higher risk of developing ASCUS lesion in HPV negative women (OR: 1.75, 95%CI:1.20-2.54, p = 0.003). There was statistically significant difference between the expression of miRNA 140 and the susceptibility to cervical precancerous lesion, in which there is down-regulation of the miRNA-140 in case group (T=6.73i¼ŒP=0.007). Gene-environment interaction analysis by MDR software revealed an association among rs7873784 and hrHPV infection and more types of infected HPV (p < 0.0001, OR: 25.48; 95%Cl: 5.20-124.84). Collectively, these results suggested that rs11536896 and rs787378 from TLR4 gene were associated with risks of cervical precancerous lesion. Thus, this miRNA-140 and SNPsi¼ˆrs11536896rs787378i¼‰ of TLR4 gene could be considered as a potential molecular mechanism and biomarker for detecting and diagnosing cervical cancer in early time