Environmental tobacco smoke increased risk of gestational diabetes mellitus: A birth cohort study in Sichuan, China.

INTRODUCTION: Studies on the relationship between environmental tobacco smoke (ETS) and gestational diabetes mellitus (GDM) are limited. In this study, we aimed to clarify the association between ETS at different trimesters of pregnancy and the risk of GDM among non-smoking pregnant women. METHODS: A total of 16,893 non-smoking mothers from the Southwest Birth Cohort, China, were included in the final analyses. Exposure and outcome measures included self-reported ETS status at different trimesters of pregnancy and GDM diagnosis. Multivariable logistic regression models were constructed to estimate the association between ETS and GDM. RESULTS: The prevalence of ETS exposure was 25.7%. Compared with no ETS, ever ETS had an increased risk of GDM, with an adjusted odds ratio (95% confidence intervals) of 1.21 (1.09, 1.33). The association remained consistent at different trimesters of pregnancy ETS exposure. In the last trimester and with continuous ETS exposure, the risk of GDM increased significantly with the increase in the duration of the exposure. The risk of GDM associated with ever ETS during pregnancy significantly increased in mothers over 30 years old and pre-pregnancy overweight (P for interaction <0.05). CONCLUSIONS: ETS exposure at different trimesters of pregnancy was associated with an increased risk of GDM among non-smoking pregnant women. These findings emphasise the importance of preventing ETS exposure during pregnancy.

Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Analysis of characteristics and forecast of unintentional injury deaths of children under age 5 from 2013 to 2019 in Sichuan, China.

OBJECTIVE: Through the study of death characteristics and trend prediction, it is hoped that key populations, regions and seasons can be identified, thereby providing evidence support for the efficient prevention and control management of unintentional injury deaths. METHOD: We collected information on 8630 unintentional deaths of children under age 5 from local surveillance systems, analyzed by chi-square test and predicted by the seasonal ARIMA model. RESULTS: About 33.1% of child deaths were under the age of 1, 60.5% were boys, 37.6% were in urban areas, 2.6% were among ethnic Tibetans, 6.8% were among ethnic Yi, and 46.6% died inside houses. The top three of total deaths were accidental drowning (35.0%), accidental suffocation (32.7%) and traffic accident (15.5%). The ratio of males to females in traffic accidents (1.28:1) and poisoning (1.30:1) deaths was relatively lower than accidental falls (1.62:1) and drowning (1.85:1). The causes of death ratio in rural and urban areas were: drowning (1.83:1), poisoning (1.75:1), suffocation (1.62:1), traffic (1.41:1), and falling (1.24:1). Children's deaths of ethnic minority groups of Tibetan and Yi increased year by year (χ2=75.261, P< 0.001). Tibetan and Yi groups had the most deaths in summer, and Han in winter (χ2=29.093, P< 0.001). Accidental suffocation accounted for 78.2 percent of the total unintentional deaths of children under age 1. And drowning accounted for only 2.4 percent. The model SERIMA (1, 1, 2) (2, 0, 0) [12] is suitable for describing and predicting unintentional injury deaths of children under age 5. CONCLUSION: We should combine death surveillance with qualitative investigation or in-depth quantitative investigation to further analyze unintentional injury deaths in children.

Ethnic disparity in pneumonia-specific mortality among children under 5 years of age in Sichuan Province of Western China from 2010 to 2017.

BACKGROUND: To reveal the ethnic disparity in the pneumonia-specific mortality rates of children under the age of 5 years (PU5MRs) and provide suggestions regarding priority interventions to reduce preventable under-five-years-of-age deaths. METHODS: Data were obtained from the Direct Report System of Maternal and Child Health in Sichuan. The Cochran-Armitage trend test was used to assess the time trend. The Cochran-Mantel-Haenszel test and Chi-square test were used to examine the differences in the PU5MRs among different groups. RESULTS: The PU5MRs in the minority and nonminority counties decreased by 53.7 and 42.3% from 2010 to 2017, respectively. The PU5MRs of the minority counties were 4.81 times higher than those of the nonminority counties in 2017. The proportion of pneumonia deaths to total deaths in Sichuan Province increased from 11.7% in 2010 to 15.5% in 2017. The pneumonia-specific mortality rates of children in the categories of 0-28 days, 29 days-11 months, and 12-59 months were reduced by 55.1, 38.8, and 65.5%, respectively, in the minority counties and by 35.5, 43.1, and 43.7%, respectively, in the nonminority counties. CONCLUSIONS: PU5MRs declined in Sichuan, especially in the minority counties, while ethnic disparity still exists. Although the PU5MRs decreased more for the minority counties as a fraction of all mortality, the absolute number of such deaths were higher, and therefore more children in these counties continue to die from pneumonia than from the non-minority counties. Priority should be given to strategies for preventing and controlling child pneumonia, especially for postneonates, in the minority counties.

Disparities in health system input between minority and non-minority counties and their effects on maternal mortality in Sichuan province of western China.

BACKGROUND: The maternal mortality rate (MMR) markedly decreased in China, but there has been a significant imbalance among different geographic regions (east, central and west regions), and the mortality in the western region remains high. This study aims to examine how much disparity in the health system and MMR between ethnic minority and non-minority counties exists in Sichuan province of western China and measures conceivable commitments of the health system determinants of the disparity in MMR. METHODS: The MMR and health system data of 67 minority and 116 non-minority counties were taken from Sichuan provincial official sources. The 2-level Poisson regression model was used to identify health system determinants. A series of nested models with different health system factors were fitted to decide contribution of each factor to the disparity in MMR. RESULTS: The MMR decreased over the last decade, with the fastest declining rate from 2006 to 2010. The minority counties experienced higher raw MMR in 2002 than non-minority counties (94.4 VS. 58.2), which still remained higher in 2014 (35.7 VS. 14.3), but the disparity of raw MMR between minority and non-minority counties decreased from 36.2 to 21.4. The better socio-economic condition, more health human resources and higher maternal health care services rate were associated with lower MMR. Hospital delivery rate alone explained 74.5% of the difference in MMR between minority and non-minority counties. All health system indicators together explained 97.6% of the ethnic difference in MMR, 59.8% in the change trend, and 66.3% county level variation respectively. CONCLUSIONS: Hospital delivery rate mainly determined disparity in MMR between minority and non-minority counties in Sichuan province. Increasing hospital birth rates among ethnic minority counties may narrow the disparity in MMR by more than two-thirds of the current level.

Expansion of T follicular helper cells is associated with disease progression in rat experimental membranous nephropathy model.

BACKGROUND: T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses, but the functional role of Tfh cells in the pathogenesis of idiopathic membranous nephropathy (IMN) remains unclear. OBJECTIVES: This study aimed to establish a rat experimental membranous nephropathy model, investigate the phenotypic characteristics of Tfh cells, and analyze a clinically significant correlation between Tfh cells. MATERIAL AND METHODS: Passive Heymann nephritis (PHN) rats were induced by immunizing Sprague Dawley rats with anti-Fx1A serum. The frequency of Tfh and B cell subsets was analyzed with flow cytometry (FC). The serum concentration of interleukin-21 (IL-21), the relative mRNA expression levels of IL-21 and B cell lymphoma 6 (Bcl-6) in spleen mononuclear cells (MNCs), and the kidney infiltration of CD4+ T cells and IL-21 were assessed. The potential correlations among these measures were analyzed. RESULTS: In comparison with the control group, significantly increased percentages of Tfh cells, inducible T cell co-stimulator-positive (ICOS+) Tfh cells, and mRNA expression of Bcl-6 were detected in the spleen of PHN rats. Elevated IL-21 expression was detected in the serum and kidneys. Remarkably, the percentage of splenic ICOS+ Tfh cells was positively correlated with 24 h urine protein concentrations (r = 0.676, p = 0.011) in PHN rats. CONCLUSION: These data indicate that ICOS+ Tfh cells contribute to development of IMN, and they might be potential therapeutic targets for IMN.

Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy.

CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

[Retracted] MicroRNA­655 inhibits cell proliferation and invasion in epithelial ovarian cancer by directly targeting vascular endothelial growth factor.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell invasion assay data shown in Figs. 2C and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 1878­1884, 2018; DOI: 10.3892/mmr.2018.9090].

Maternal periconceptional folic acid supplementation reduced risks of non-syndromic oral clefts in offspring.

Maternal periconceptional folic acid supplementation (FAS) has been documented to be associated with decreased risk of nonsyndromic oral clefts (NsOC). However, the results remain inconclusive. In this population-based case-control study of 807 singletons affected by NsOC and 8070 healthy neonates who were born between October 2010 and September 2015 in Chengdu, China, we examined the association of maternal FAS with the risk of nonsyndromic cleft lip with or without cleft palate (NsCL/P), and cleft palate (NsCP). Unconditional logistic regression analysis was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidential intervals (CI). Significant associations were found between maternal periconceptional FAS and decreased risk of NsCL/P (aOR = 0.41, 95% CI 0.33-0.51). This protective effect was also detected for NsCL (aOR = 0.42, 95% CI 0.30-0.58) and NsCLP (aOR = 0.41, 95% CI 0.31-0.54). Both maternal FAS started before and after the last menstrual period (LMP) were inversely associated with NsCL/P (before LMP, aOR = 0.43, 95% CI 0.33-0.56; after LMP, aOR = 0.41, 95% CI 0.33-0.51). The association between NsCP and maternal FAS initiating before LMP was also found (aOR = 0.52, 95% CI 0.30-0.90). The findings suggest that maternal periconceptional FAS can reduce the risk of each subtype of NsCL/P in offspring, while the potential effect on NsCP needs further investigations.

[Detection of JAK2V617F and CALR Gene Mutations by Multiplex of Patients with Myeloproliferative Neoplasms PCR-Capillary Electrophoresis].

OBJECTIVE: To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN). METHODS: The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit. RESULTS: JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%. CONCLUSION: It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

Unintentional injury mortality among children under age five in urban and rural areas in the Sichuan province of west China, 2009-2017.

This study analysed trends in the unintentional injuries specific mortality rates among children under age five (UI-specific U5MRs) in urban and rural areas in the Sichuan province of western China. Data were obtained from the National Health Statistics Survey System. The Cochran-Armitage trend test was used to analyse the trends in UI-specific U5MRs and the proportion of unintentional injury deaths to total deaths. The Poisson regression model was used to compare the UI-specific U5MRs between rural and urban areas. The overall UI-specific U5MRs decreased from 3.8 to 1.7 per 1,000 live births from 2009 to 2017, with an average annual decline in the rates of 8.78% and 10.05% in urban and rural areas, respectively. The UI risk of death in rural areas was approximately 1.95 times that in urban areas (95% CI: 1.73-2.18; p < 0.01). A total of 49.9% of all the children in the study did not receive any treatment before death caused by UI. The UI-specific U5MRs significantly declined in Sichuan province from 2009 to 2017, but large disparities in UI-specific U5MRs in urban and rural areas still exist. Reducing the U5MRs due to UI should be a major public health concern in western China.

All-cause child mortality in minority and non-minority areas in Sichuan Province in Western China, 2008-2017.

This study aimed to evaluate the disparity in the under-five mortality rate (U5MR) between minority and non-minority areas in Sichuan Province in Western China. Data for this study was obtained from the National Health Statistics Survey System. The Cochran-Armitage trend test was used to analyze the time trend of the U5MR. We conducted Poisson regression model to compare the differences of U5MRs between minority and non-minority areas. The U5MR in Sichuan province was reduced by 62.19% from 2008 to 2017, with the minority and non-minority areas reduced by 60.48% and 65.39%, respectively. The under-five mortality risk in minority areas was approximately 1.791 times (95% CI: 1.790-1.793; P < 0.01) that in non-minority areas. The primary cause of death of children under-five years old in minority areas was the respiratory disease, which was significantly higher than that in non-minority areas (P all < 0.01). The U5MR significantly declined both in minority and non-minority areas in Sichuan Province in Western China from 2008 to 2017. However, disparities still existed between minority and non-minority areas. Respiratory diseases were the main causes of death in minority areas and corresponding rates were higher than those in non-minority areas.

MicroRNA­655 inhibits cell proliferation and invasion in epithelial ovarian cancer by directly targeting vascular endothelial growth factor.

In recent years, microRNAs (miRNAs/miRs) have been shown to be deregulated in epithelial ovarian cancer (EOC). Their deregulation has been suggested to be involved in EOC formation and progression through the regulation of the expression of numerous cancer­related genes. Hence, it is of great importance to further determine the detailed roles and underlying mechanisms of miRNAs involved in EOC and to identify novel targets for diagnosis, prognosis and treatment of patients with EOC. In this study, the expression of miR­655­3p (miR­655) was significantly downregulated in EOC tissues and four EOC cell lines. After miR­655 was restored, functional assays revealed that cellular proliferation and invasion were considerably reduced in EOC. Additionally, vascular endothelial growth factor (VEGF) A was identified as a direct target gene of miR­655 in EOC cells. Furthermore, VEGF knockdown could mimic the tumour­suppressive roles of miR­655 overexpression in EOC cells. Moreover, the introduction of VEGF abrogated the effects of miR­655­induced proliferation and invasion inhibition in EOC cells. Altogether, these findings indicated that miR­655 may inhibit EOC cell proliferation and invasion by repressing VEGF. Thus, the miR­655/VEGF pathway could serve as a novel therapeutic target for patients with EOC.

[Trend analysis on mortality and the mortal causes among children under 5 in Sichuan province, from 2001 to 2013].

OBJECTIVE: To study the mortality of children under five and the causes of death together with related trend of dynamics, from 2001 to 2013 in Sichuan province. METHODS: Using the Children Death Monitoring Network under five in Sichuan province to obtain basic data. Descriptive statistics and chi-square were used to describe the mortalities in children and infants as well as the causes of death, in both rural and urban areas of Sichuan province. RESULTS: In Sichuan province, the mortality of children under five decreased from 35.30‰ in 2001 to 11.77‰ in 2013. In 2013, mortality in the rural areas was 2.37 times more than that in the urban area. The proportion of neonatal deaths among the mortality in children under five was 44.72%. Pneumonia, congenital heart diseases and premature or low birth weigh were the top three causes of death for children under five. Among them, the top three causes of death for urban area were congenital heart disease, drowning, and premature or low birth weight/birth asphyxia. Meanwhile, the top three causes of death in rural areas were pneumonia, premature birth/low birth weight and birth asphyxia. Overall, the mortality rates of birth asphyxia, pneumonia and low birth weight gradually decreasd but drowning, diarrhea and traffic accidents fluctuated. CONCLUSION: The mortality of children under five in Sichuan province was 13‰, which had already met the goal set for the year 2020. However, reducing the mortality in rural areas, narrowing the gap between urban and rural areas seemed the main part of the future endeavor while focus of prevention should be adjusted according to the causes of death.

16S ribosomal DNA clone libraries to reveal bacterial diversity in anaerobic reactor-degraded tetrabromobisphenol A.

Microorganisms able to rapidly degrade tetrabromobisphenol A (TBBPA) were domesticated in an anaerobic reactor and added to gradually increased concentrations of TBBPA. After 240 days of domestication, the degradation rate reached 96.0% in cultivated batch experiments lasting 20 days. The optimum cultivating temperature and pH were 30°C and 7.0. The bacterial community's composition and diversity in the reactor was studied by comparative analysis with 16S ribosomal DNA clone libraries. Amplified rDNA restriction analysis of 200 clones from the library indicate that the rDNA richness was high (Coverage C 99.5%) and that evenness was not high (Shannon-Weaver index 2.42). Phylogenetic analysis of 63 bacterial sequences from the reactor libraries demonstrated the presence of Betaproteobacteria (33.1%), Gammaproteobacteria (18.7%), Bacteroidetes (13.9%), Firmicutes (11.4%), Chloroflexi (3.6%), Actinobacteria (0.6%), the candidate division TM7 (4.2%) and other unknown, uncultured bacterial groups (14.5%). Comamonas, Achromobacter, Pseudomonas and Flavobacterium were the dominant types.