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The aim of this study was to assess the prevalence and trends of congenital hydrocephalus (CH) using a large population-based sample with cases retrieved from the Liaoning Birth Defects Registry, which included 14 cities, over a 10-year period. CH prevalence, percent change, average change, and contribution rates of each city were calculated. Statistical analysis was performed using a Poisson regression model. There was a total of 3008 CH cases among 3,248,954 live births during the observational period (9.26 cases/10,000 live births). On average, the prevalence of CH had significantly decreased by 11.84% each year ( P < 0.01). The three leading cities with the highest prevalence of CH were Chaoyang (13.73/10,000), Huludao (13.18/10,000), and Fuxin (12.71/10,000), while Yingkou (6.06/10,000), Dalian (6.27/10,000), and Anshan (6.56/10,000) had the lowest prevalence. Notably, significantly decreasing trends were observed in 10 (71.4%) of these 14 cities. In addition, the cities of Fushun, Shenyang, and Dalian had contributed to more than one-third of the decreasing trend in Liaoning province. In conclusion, this study provides evidence of the decreasing prevalence of CH over a 10-year period (2006-2015) in Liaoning province. Preventative efforts should be strengthened to further reduce the risk of CH in these high prevalence areas., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities caused by an altered systemic host response to infection, has become the main cause of death among patients admitted to the intensive care units. Recently, genome-wide expression analysis revealed that over 80% of the essential genetic elements were altered in critically ill patients. Notably, non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, have been proven to play essential roles in innate immunity, mitochondrial dysfunction and organ dysfunction. In this review, we introduced the biogenesis of non-coding RNAs briefly and summed up different kinds of non-coding RNAs in regulation of sepsis, which could provide a more comprehensive understanding about pathogenesis of the disease. Additionally, we summarized the limitations of current biomarkers and then recommended some non-coding RNAs as novel potential biomarkers for sepsis and sepsis-induced organ dysfunction. Besides, we also introduced some problems and challenges that need to be overcome during the clinical application of non-coding RNAs. Future research should focus on elucidating their molecular mechanisms, particularly long non-coding RNAs as well as circular RNAs and sepsis, to further understanding of the disease process. With the in-depth understanding of the mechanism of sepsis, non-coding RNAs provide a new insight into sepsis and could become the novel therapeutic targets in the future., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

The goal of this study was to assess the prevalence and trends of anencephaly on the basis of a large population-based cases identified by the Liaoning Birth Defects Registry, which included 14 cities over a 10-year period. Anencephaly prevalence, percent change, average changeand the contribution rates of each city were calculated. Statistical analysis was undertaken on the basis of a Poisson regression model. A total of 1600 anencephaly cases were collected during the observational period (4.92/10,000 live births). On average, the prevalence decreased 10.15% each year; this overall time trend was statistically significant (P<0.01). The top three leading cities were Huludao (10.33 per 10,000 live births), Chaoyang (8.56 per 10,000 live births) and Fuxin (6.36 per 10,000 live births). In contrast, Anshan (2.64 per 10,000 live births), Dalian (2.79 per 10,000 live births) and Yingkou (3.46 per 10,000 live births) were the cities with the lowest prevalence. Of note, significantly decreasing trends were observed in half of these cities (n=7). Additionally, Benxi, Yingkou and Dalian were the major cities contributing to over one third of the decreasing trend in Liaoning province. In conclusion, this study provided evidence of the decreasing prevalence of anencephaly from 2006 to 2015 in Liaoning province. In the future, prevention efforts should be strengthened to further reduce the risk of anencephaly in areas with high rates., Competing Interests: COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests.

The present study sought to assess the time trends of spina bifida on the basis of cases identified by the Liaoning Birth Defects Registry in 14 cities from 2006 to 2015. We calculated the prevalence of spina bifida, percent and average change of time trends, and contribution rates of each city. Poisson regression model was used to find the line of best fit for spina bifida prevalence by year, with year as a continuous independent variable. From 2006 to 2015, a total of 2,029 spina bifida cases were identified from 3,248,954 live births (6.25/10,000 live births). We observed statistically significant decreasing trend of overall time trend (11.57% each year). Chaoyang, Fuxin, and Huludao were the top three leading cities, with 14.30/10,000 live births, 9.70/10,000 live births, and 9.20/10,000 live births, respectively. Inversely, the bottom three cities with lowest prevalence were Anshan (2.64/10,000 live births), Dandong (3.43/10,000 live births), and Dalian (3.45/10,000 live births). Of note, we observed significant decreasing trends in over half of these cities (n = 8). In addition, the decreasing trend of overall time trend could be mainly attributed to cities of Shenyang, Fushun, and Jinzhou which accounted for nearly one third. In summary, our study suggested a decreasing time trend of spina bifida during the past decade in the Liaoning province. The findings of this study provide evidence that the nationwide folic acid supplement program has been an effective strategy to prevent spina bifida.

Recent genome-wide association studies have established the association between EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population. However, recent studies reported inconsistent results in Asian population. Here, we performed a systematic review and meta-analysis to evaluate the impact of rs597668 on AD risk in Asian population using a total of 8686 samples including 2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154 controls in European population to evaluate the potential heterogeneity between East Asian and European populations. In East Asian population, we identified no potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we identified positive association between rs597668 and AD risk with P=0.023, OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In summary, all these findings indicate that rs597668 C allele is a risk factor for AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian population.

To evaluate the time trends in the prevalence of neural tube defects and all their subtypes as well as to identify the epidemiological characteristics of these malformations documented in the Liaoning Province of northeast China from 2006 to 2015. This was a population-based observational study using data from 3,248,954 live births as well as from 6217 cases of neural tube defects, 1,600 cases of anencephaly, 2,029 cases of spina bifida, 404 cases of encephalocele, and 3,008 cases of congenital hydrocephalus from 14 cities in Liaoning Province from 2006 to 2015. All analyses were conducted using SPSS software. During the observational period, the prevalence of neural tube defects, anencephaly, spina bifida, encephalocele, and congenital hydrocephalus was 19.1, 4.9, 6.2, 1.2, and 9.3 per 10,000 live births, respectively. Significantly decreasing trends were observed in the prevalence of all these malformations except for encephalocele. Notably, relatively higher prevalence rates were found in isolated compared with non-isolated malformations, with significant differences in selected characteristics (e.g., prognosis status, gestational age, and birth weight) between isolated and non-isolated cases of these malformations. The prevalence of neural tube defects showed a downward trend in Liaoning Province from 2006 to 2015. However, more attention should be focused on non-isolated cases in the future because of the severe clinical manifestations. Future prevention efforts should be strengthened to reduce the risk of these malformations, especially the non-isolated subtype, in areas with high prevalence.

Complications in women with multiple gestation pregnancy have not been studied in China. We aimed to establish a database of women with multiple gestation pregnancy and investigate the complications related to multiple pregnancy. We conducted a cross-sectional study that included 3246 women with multiple gestation pregnancy and who had multiple live-birth deliveries; the women were registered at ten maternal-fetal medicine centers in China in 2013. All participants completed a detailed questionnaire that included basic demographic information, history of gestation and abnormal fetal development, risk factors during pregnancy, and pregnancy outcomes. Overall, 1553 (47.8%) women experienced pregnancy complications; these women were more likely to have lower height and less education than women who did not experience complications. However, women who experienced complications had a higher twin birth rate and were more likely to have received regular antenatal care and assisted reproductive technology than women without complications (P < 0.05). Notably, preterm birth was a primary complication in multiple pregnancy (n = 960). In conclusion, pregnancy complications, especially preterm birth, were relatively common in women with multiple gestation pregnancy. The findings from this cross-sectional study in China may be used as a foundation for investigating risk factors for complications in women with multiple gestation pregnancy in the future., Competing Interests: The authors have no competing financial interests to declare.

To investigate the rate and time trends of neonatal mortality from 1997 to 2014 in Shenyang, which were previously rarely reported upon by developing countries, data on 4719 neonatal deaths (0-28 days) and 970,583 live births from the Shenyang Women and Children Health Care Centre were analyzed. Neonatal mortality rates (per 1000 live births), percent change, and annual percent change (APC) were calculated. During the observation period, neonatal mortality in Shenyang significantly decreased by 7.04%, 8.33%, and 5.35% per year overall, in urban and rural areas, respectively. When grouped by category of neonatal death, the time trends of three categories showed statistically significant decreases: congenital malformations (APC = -9.97%), diseases of the perinatal period (APC = -6.04%), and diseases of the respiratory system (APC = -8.52%). Congenital malformations, diseases of the respiratory system, and diseases of the nervous system and sense organs were the three major contributors to the aforementioned decreasing trend, which accounted for 58.71% in overall areas. Among selective causes of neonatal death, the neonatal mortality rates of pneumonia, congenital heart disease, preterm birth and low birth weight, birth asphyxia, and intracranial hemorrhage of the newborn significantly decreased 7.87%, 7.32%, 2.47%, 11.04%, and 10.68% per year, respectively. In summary, neonatal mortality rates decreased in Shenyang during the 17-year study period. Future studies are warranted to further investigate the factors contributing to the neonatal mortality trends in China.

In vivo and in vitro studies have indicated the link of cholesterol consumption and endometrial cancer risk, however, previous observational studies have yielded inconsistent results. Additionally, a previous meta-analysis published in 2007 found limited evidence of aforementioned association. Therefore, we performed the dose-response meta-analysis to address this concern. Studies were identified using the PubMed, EMBASE and Web of Science databases from the database inception to the end of June 2015 as well as by examining the references of retrieved articles. Two authors independently performed the eligibility evaluation and data extraction. The summary risk estimates and 95% confidence intervals (CIs) were summarized by the random-effects models. One cohort and nine case-control studies were included in the dose-response analyses. Risk of endometrial cancer increased by 6% for 100 mg/day increment in the dietary consumption of cholesterol (Odds ratio (OR) = 1.06; 95% CI = 1.00-1.12), with significant heterogeneity (I2 = 64.2, P = 0.003). When stratified by study design, the result was significant in case-control studies (OR = 1.07; 95% CI = 1.01-1.13). Additionally, although the direction of the associations were consistent in the subgroup analyses stratified by study characteristics and adjustment for potential confounders, not all of them showed statistical significance. In summary, findings of the present dose-response meta-analysis partly support the positive association between dietary cholesterol consumption and risk of endometrial cancer. Since only one cohort study was included, more prospective studies and pooled analysis of observational studies are warranted to confirm our findings in the future.

Although evidence from epidemiological studies evaluating the association between cigarette smoking during pregnancy and preeclampsia risk has been systematically reviewed, the findings have been out of date. To further clarify the relationship, we conducted this comprehensive meta-analysis of prospective studies. We searched PubMed and Web of Science up to August 2015 to identify prospective studies that evaluated the association between cigarette smoking during pregnancy and preeclampsia risk. Random-effects models were used to estimate summarized relative risk (RR) and 95% confidence intervals (CIs). Seventeen prospective studies involving 62,089 preeclampsia patients from a total of approximately 1.8 million subjects were included. Overall, there was a significant negative association between smoking during pregnancy and incidence of preeclampsia (RR = 0.67, 95% CI: 0.60-0.75), with significant heterogeneity (I2 = 91.7%). Such an inverse association was also detected in strata of subgroup analyses according to study location, study sample size, parity of populations, singleton pregnancy, and adjustment for potential confounders including maternal age, diabetes mellitus, chronic hypertension, body mass index, and gender of infant. In summary, this meta-analysis suggests that smoking during pregnancy is inversely associated with incidence of preeclampsia. Further large scale multi-center prospective studies are warranted to validate our findings.

The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54-0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53-0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43-0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48-1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.

The associations between dietary fat and fatty acid (FA) intakes and epithelial ovarian cancer (EOC) risk have been inconsistent in previous studies. We conducted a meta-analysis of epidemiological studies to evaluate these associations. We identified relevant studies by searching PubMed, EMBASE, and Web of Science databases. We used random-effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Overall, the search yielded 20 studies (1 pooled analysis of 12 cohort studies, 5 cohorts, and 14 case-control studies). The summary RR for EOC for the highest versus lowest categories of total dietary fat intake was 1.12 (95%CI= 0.95-1.33; I2 = 77.4%; n = 14). The RRs were not significant when fats were divided into plant-based fats (RR = 0.93, 95%CI = 0.77-1.13; n = 6), animal-based fats (RR = 1.15, 95%CI = 0.95-1.39; n = 8), dairy-based fats (RR = 1.02, 95%CI = 0.88-1.18; n = 3), saturated FAs (RR = 1.04, 95%CI = 0.93-1.17; n = 12), monounsaturated FAs (RR = 0.98, 95%CI = 0.84-1.13; n = 10), polyunsaturated FAs (RR = 0.96, 95%CI = 0.81-1.12; n = 10), and trans-unsaturated FAs (RR = 1.15, 95%CI = 0.98-1.36; n = 3). Similar non-significant results were also observed in most of the subgroup and sensitivity analyses. The findings of this meta-analysis suggest a lack of evidence for associations between dietary fat and FA intakes and EOC risk. Further analyses should be conducted to assess the associations with other types of fat, and the results should be stratified by tumor invasiveness and EOC histology.

Epidemiological studies have provided controversial evidence of the association between dietary fatty acids intake and endometrial cancer risk. The continuous update project of World Cancer Research Fund failed to focus on this issue. To address this inconsistency, we conducted this dose-response meta-analysis based on epidemiological studies published up to the end of June 2015 identified from PubMed, EMBASE and Web of Science. Two authors independently performed the eligibility evaluation and data extraction. Random-effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Fourteen epidemiological studies (4 cohort and 10 case-control studies) were included in this dose-response meta-analysis. The summary RR for an intake increment of 10g/day was 1.02 (95% CI = 0.97-1.08; I2 = 66.0%) for saturated fatty acids, 0.98 (95% CI = 0.96-1.001; I2 = 0%) for monounsaturated fatty acids, and 1.00 (95% CI = 0.95-1.06; I2 = 0%) for polyunsaturated fatty acids intake. Non-significant results were observed in the majority of subgroup analyses stratified by study characteristics and adjustment for potential confounders in analyses of aforementioned associations. In conclusion, results from this dose-response meta-analysis provided limited evidence that dietary saturated, monounsaturated, and polyunsaturated fatty acids consumption was associated with endometrial cancer risk. Further studies, especial prospective designed or pooled studies are warranted to confirm our findings.