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Showing papers by "National Health and Family Planning Commission published in 2016"


Journal ArticleDOI
01 Dec 2016-Cell
TL;DR: It is demonstrated that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice, and suggests that ZikV infection, under certain circumstances, can eventually lead to male infertility.

414 citations


Journal ArticleDOI
TL;DR: The development and operation of the new national mortality surveillance system is described, which is expected to yield representative provincial estimates of mortality in China for the first time.
Abstract: In China, sample-based mortality surveillance systems, such as the Chinese Center for Disease Control and Prevention's disease surveillance points system and the Ministry of Health's vital registration system, have been used for decades to provide nationally representative data on health status for health-care decision-making and performance evaluation. However, neither system provided representative mortality and cause-of-death data at the provincial level to inform regional health service needs and policy priorities. Moreover, the systems overlapped to a considerable extent, thereby entailing a duplication of effort. In 2013, the Chinese Government combined these two systems into an integrated national mortality surveillance system to provide a provincially representative picture of total and cause-specific mortality and to accelerate the development of a comprehensive vital registration and mortality surveillance system for the whole country. This new system increased the surveillance population from 6 to 24% of the Chinese population. The number of surveillance points, each of which covered a district or county, increased from 161 to 605. To ensure representativeness at the provincial level, the 605 surveillance points were selected to cover China's 31 provinces using an iterative method involving multistage stratification that took into account the sociodemographic characteristics of the population. This paper describes the development and operation of the new national mortality surveillance system, which is expected to yield representative provincial estimates of mortality in China for the first time.

206 citations


Journal ArticleDOI
18 Nov 2016-PLOS ONE
TL;DR: Smartphone apps offered moderate benefits for T2DM self-management, however, more research with valid study designs and longer follow-up is needed to evaluate the impact of mHealth apps for diabetes care and self- management.
Abstract: Background Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients.

198 citations


Journal ArticleDOI
TL;DR: The origin and overview function of lncRNAs is summarized; the roles of l NCRNAs in cervical cancer in terms of prognosis and tumor progression, invasion and metastasis, apoptosis, and radio-resistance are highlighted; and the molecular mechanisms of lNCRNAsin cervical cancer are outlined.
Abstract: Cervical cancer contributed the second highest number of deaths in female cancers, exceeded only by breast cancer, carrying high risks of morbidity and mortality. There was a great need and urgency in searching novel treatment targets and prognosis biomarkers to improve the survival rate of cervical cancer patients. Many long non-coding RNAs (lncRNAs) were emerging as pivotal regulators in various biological processes and took vitally an effect on the oncogenesis and progression of cervical cancer. In this review, we summarized the origin and overview function of lncRNAs; highlighted the roles of lncRNAs in cervical cancer in terms of prognosis and tumor progression, invasion and metastasis, apoptosis, and radio-resistance; and outlined the molecular mechanisms of lncRNAs in cervical cancer from the aspects of the interaction of lncRNAs with proteins/mRNAs (especially in HPV protein) and miRNAs, as well as RNA N-methyladenosine (m6A) methylation of lncRNAs. Meanwhile, the application of lncRNAs as biomarkers in cervical cancer prognosis and predictors for metastasis was also discussed. An overview of these researches will be valuable for broadening horizons into mechanisms, selection of meritorious biomarkers for diagnosis as well as prognosis, and future targeted therapy of cervical cancer.

172 citations



Journal ArticleDOI
TL;DR: HBV prevalence in men in rural China has changed from highly endemic into intermediate endemic in the past two decades, however, the absolute number of HBV-infected men and the susceptible population is still very large.
Abstract: Summary Background Hepatitis B virus (HBV) infection is highly endemic (7–8% prevalence) in rural China, causing high mortality and societal burden. Data from men of reproductive age is scarce and last reported in 2006. We assessed the seroepidemiology of men in rural China, aiming to provide updated baseline data for the prevalence of HBV infection. Methods We established prevalence of HBV infection from data gathered through a nationwide population-based study of Chinese rural men aged 21–49 years. Data were obtained from a physical check-up programme for couples of reproductive age, the National Free Preconception Health Examination Project, that covered 31 provinces from 2010–12. We tested serological samples with ELISA and categorised participants' HBV status based on presence of HBsAg, anti-HBV core antibody (anti-HBc), and anti-HBV surface antibody (anti-HBs). Findings 2 030 083 men were recruited into the database from Jan 1, 2010, to Dec 31, 2012, and 1 966 013 men provided serum samples for analysis. 124 274 men (6%) tested positive for HBsAg, 178 559 (9%) tested positive for anti-HBc, and 583 923 (30%) tested positive for anti-HBs. Isolated anti-HBs (an indicator of vaccine-mediated immunity) were present in 527 566 men (27%). And 1 234 127 men (63%) were negative for all HBV makers (susceptible population). HBsAg prevalence was higher in men aged 25–39 years (6·35–6·47%) than in other age groups (5·54–5·78%; p Interpretation HBV prevalence in men in rural China has changed from highly endemic into intermediate endemic in the past two decades. However, the absolute number of HBV-infected men and the susceptible population is still very large. Funding Chinese Association of Maternal and Child Health Studies.

156 citations


Journal ArticleDOI
TL;DR: It is demonstrated that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.
Abstract: Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death.

110 citations


Journal ArticleDOI
TL;DR: Results indicated that the hypothalamic-pituitary-testis (HPT) axis was disturbed and serum testosterone, LH and FSH levels were decreased following DEHP exposure, and taken together, DEHP-disturbed HPT axis and induced 5α-Reductase 2 contribute to the reduction of serum testosterone level.

75 citations


Journal ArticleDOI
TL;DR: The results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers.
Abstract: The metastasis-associated lung adenocarcinoma transcript 1(MALAT1), a member of the long non-coding RNA (lncRNA) family, has been reported to be highly enriched in many kinds of cancers and to be a metastasis marker and a prognostic factor. In this study, we found that MALAT1 expression levels were significantly increased in cervical cancer (CC) cells and tissues. The down-regulation of MALAT1 by shRNA in CC cells inhibited the invasion and metastasis in vitro and in vivo. Microarray analysis showed that the knockdown of MALAT1 up-regulated the epithelial markers E-cadherin and ZO-1, and down-regulated the mesenchymal markers β-catenin and Vimentin. This regulation was further confirmed by subsequent observation from RT-PCR, western blot, and immunofluorescence results. Meanwhile, the transcription factor snail, which functions to modulate epithelial–mesenchymal transition (EMT), was also down-regulated at both transcript and protein levels by MALAT1 down-regulation. In addition, we found that MALAT1 expression levels were positively related to HPV infection in cervical epithelial tissues by microarray analysis. Taken together, these results suggest that MALAT1 functions to promote cervical cancer invasion and metastasis via induction of EMT, and it may be a target for the prevention and therapy of cervical cancers.

75 citations


Journal ArticleDOI
TL;DR: It is suggested that the combination of Notch inhibition and Wnt activation can significantly promote SC proliferation and increase the number of regenerated HCs in mouse utricle.
Abstract: This work sought to determine the crosstalk between the Notch and Wnt signaling pathways in regulating supporting cell (SC) proliferation and hair cell (HC) regeneration in mouse utricles. We cultured postnatal day (P)3 and P60 mouse utricles, damaged the HCs with gentamicin, and treated the utricles with the γ-secretase inhibitor DAPT to inhibit the Notch pathway and with the Wnt agonist QS11 to active the Wnt pathway. We also used Sox2-CreER, Notch1-flox (exon 1), and Catnb-flox (exon 3) transgenic mice to knock out the Notch pathway and activate the Wnt pathway in Sox2+ SCs. Notch inhibition alone increased SC proliferation and HC number in both undamaged and damaged utricles. Wnt activation alone promoted SC proliferation, but the HC number was not significantly increased. Here we demonstrated the cumulative effects of Notch inhibition and Wnt activation in regulating SC proliferation and HC regeneration. Simultaneously inhibiting Notch and overexpressing Wnt led to significantly greater SC proliferation and greater numbers of HCs than manipulating either pathway alone. Similar results were observed in the transgenic mice. This study suggests that the combination of Notch inhibition and Wnt activation can significantly promote SC proliferation and increase the number of regenerated HCs in mouse utricle.

66 citations


Journal ArticleDOI
TL;DR: It is found that most AAVs infect both neonatal and adult inner ear, with different specificities and expression levels, and the inner ear cochlear sensory epithelial region is most frequently targeted for gene delivery.
Abstract: The mammalian inner ear consists of diverse cell types with important functions. Gene mutations in these diverse cell types have been found to underlie different forms of genetic hearing loss. Targeting these mutations for gene therapy development represents a future therapeutic strategy to treat hearing loss. Adeno-associated viral (AAV) vectors have become the vector of choice for gene delivery in animal models in vivo. To identify AAV vectors that target inner ear cell subtypes, we systemically screened 12 AAV vectors with different serotypes (AAV1, 2, 5, 6, 6.2, 7, 8, 9, rh.8, rh.10, rh.39, and rh.43) that carry a reporter gene GFP in neonatal and adult mice by microinjection in vivo. We found that most AAVs infect both neonatal and adult inner ear, with different specificities and expression levels. The inner ear cochlear sensory epithelial region, which includes auditory hair cells and supporting cells, is most frequently targeted for gene delivery. Expression of the transgene is sustained, and neon...

Journal ArticleDOI
TL;DR: Lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy and observations indicate lycorine as an effective autophagic inhibitor and reveal that Lycorine alone or in combination with bortezomib is a potential therapeutic strategy.
Abstract: Multiple myeloma (MM) is largely incurable and drug-resistant. Novel therapeutic approaches such as inhibiting autophagy or rational drug combinations are aimed to overcome this issue. In this study, we found that lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy. We identified High mobility group box 1 (HMGB1), an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment and as a critical mediator of lycorine activity. Gene expression profiling (GEP) analysis showed that higher expression of HMGB1 is linked with the poor prognosis of MM. This correlation was further confirmed in human bone marrow CD138+ primary myeloma cells and MM cell lines. Mechanistically, proteasomal degradation of HMGB1 by lycorine inhibits the activation of MEK-ERK thereby decreases phosphorylation of Bcl-2 resulting in constitutive association of Bcl-2 with Beclin-1. In addition, we observed higher HMGB1 expression in bortezomib resistant cells and the combination of bortezomib plus lycorine was highly efficient in vitro and in vivo myeloma models as well as in re-sensitizing resistant cells to bortezomib. These observations indicate lycorine as an effective autophagy inhibitor and reveal that lycorine alone or in combination with bortezomib is a potential therapeutic strategy.

Journal ArticleDOI
TL;DR: The observed diversity in the P. ovale curtisi surface antigens supports consideration that the two parasites be given species status, and a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family are described.

Journal ArticleDOI
TL;DR: DEHP-caused oxidative stress and Mdm2 downregulation contribute to p53 activation, and the p53-dependent apoptotic pathway plays critical and indispensable roles in DEHP-induced hepatotoxicity, while the Fas/FasL pathway does not involve in this molecular event.

Journal ArticleDOI
TL;DR: It is shown that Wnt activation followed by Notch inhibition strongly promotes the mitotic regeneration of new HCs in both normal and neomycin-damaged cochleae while partially preserving the SC number.
Abstract: Hair cell (HC) loss is the main cause of permanent hearing loss in mammals. Previous studies have reported that in neonatal mice cochleae, Wnt activation promotes supporting cell (SC) proliferation and Notch inhibition promotes the trans-differentiation of SCs into HCs. However, Wnt activation alone fails to regenerate significant amounts of new HCs, Notch inhibition alone regenerates the HCs at the cost of exhausting the SC population, which leads to the death of the newly regenerated HCs. Mitotic HC regeneration might preserve the SC number while regenerating the HCs, which could be a better approach for long-term HC regeneration. We present a two-step gene manipulation, Wnt activation followed by Notch inhibition, to accomplish mitotic regeneration of HCs while partially preserving the SC number. We show that Wnt activation followed by Notch inhibition strongly promotes the mitotic regeneration of new HCs in both normal and neomycin-damaged cochleae while partially preserving the SC number. Lineage tracing shows that the majority of the mitotically regenerated HCs are derived specifically from the Lgr5+ progenitors with or without HC damage. Our findings suggest that the co-regulation of Wnt and Notch signaling might provide a better approach to mitotically regenerate HCs from Lgr5+ progenitor cells.

Journal ArticleDOI
TL;DR: Circulating microRNAs may be involved in URSA pathogenesis and provide a promising new diagnostic biomarker for URSA, which is speculated to regulate URSA by targeting immune, apoptosis, and angiogenic gene functions.

Journal ArticleDOI
TL;DR: This work hypothesized that epithelial microRNAs (miRNAs) are involved in airway eosinophilia, a pivotal feature of asthma, and studied the role of epithelial cells in this condition.
Abstract: SummaryBackground Airway eosinophilic inflammation is a pivotal feature of asthma. Epithelial cells play critical roles in airway eosinophilia. We hypothesized that epithelial microRNAs (miRNAs) are involved in airway eosinophilia. Objective This study investigated the associations between epithelial and plasma miR-181b-5p and airway eosinophilic inflammation, and the possible mechanism by which miR-181b-5p participates in eosinophilic inflammation. Methods Epithelial miRNAs expression was profiled by miRNA array in eight subjects with asthma and four healthy controls. Epithelial miR-181b-5p expression was confirmed by quantitative PCR in the subjects for array experiment and another cohort including 21 subjects with asthma and 10 controls. Plasma miR-181b-5p was determined by quantitative PCR in 72 subjects with asthma and 35 controls. Correlation assays between epithelial and plasma miR-181b-5p expression and airway eosinophilia were performed. The target of miR-181b-5p, SPP1, was predicted by online algorithms and verified in BEAS-2B cells. The role of miR-181b-5p in epithelial proinflammatory cytokine expression was examined in an in vitro system. Results Epithelial miR-181b-5p expression was decreased in subjects with asthma. Epithelial miR-181b-5p levels were inversely correlated with sputum and bronchial submucosal eosinophilia. Plasma miR-181b-5p was decreased and correlated with epithelial miR-181b-5p in subjects with asthma. There was a strong inverse correlation between plasma miR-181b-5p and airway eosinophilia in subjects with asthma. Plasma miR-181b-5p was increased after inhaled corticosteroids treatment. We verified that SPP1 is a target of miR-181b-5p. In human bronchial epithelial cells, miR-181b-5p regulated IL-13-induced IL-1β and CCL11 expression by targeting SPP1. Dexamethasone restored IL-13-induced miR-181b-5p down-regulation and suppressed IL-13-induced SPP1, IL-1β and CCL11 expression. Conclusions and Clinical Relevance Epithelial and plasma miR-181b-5p are potential biomarkers for airway eosinophilia in asthma. MiR-181b-5p may participate in eosinophilic airway inflammation by regulating proinflammatory cytokines expression via targeting SPP1.

Journal ArticleDOI
TL;DR: The NMEP in China has been successfully implemented thus far and the malaria map has shrunk dramatically, and the priorities for malaria elimination are interventions to block transmission at border areas, management of imported malaria cases, preventing malaria reintroduction, capacity building, and sustainability of malaria surveillance and response.
Abstract: Remarkable progress has been made towards the elimination of malaria in China since the National Malaria Elimination Programme (NMEP) was launched in 2010 The incidence of locally-acquired malaria cases has declined rapidly and endemic areas have also dramatically shrunk In total, 3 078 malaria cases were reported in 2014, but only 56 cases were indigenous In order to further promote the elimination programme, we reviewed the progress of and experiences associated with malaria elimination in China, and identified the challenges and priorities for the next stage of the programme Data were collected from the web-based China Information System for Disease Control and Prevention, and the China Annual Report of Malaria Elimination The progress towards the elimination of malaria from 2010 to 2014 was measured During the implementation of the NMEP from 2010 to 2014, local malaria incidence has declined continuously, only remaining in the Yunnan Province and Tibet Autonomous Region in 2014 By the end of 2015, 756 % (1 636/2 163) of the malaria-endemic counties passed the sub-national elimination assessment The main challenges are cases of border malaria and imported malaria from other countries Sustainable support and investment from the government, the establishment of an effective surveillance and response system, and risk assessments for the potential reintroduction of malaria are priorities for the next stage of the elimination programme The NMEP in China has been successfully implemented thus far and the malaria map has shrunk dramatically The priorities for malaria elimination are interventions to block transmission at border areas, management of imported malaria cases, preventing malaria reintroduction, capacity building, and sustainability of malaria surveillance and response

Journal ArticleDOI
TL;DR: This study provides novel insights into the heterogeneity of obesity and has the potential to impact the optimization of the intervention options and regimens in the management of pediatric obesity.
Abstract: Context: Available data related to the metabolically healthy obesity (MHO) phenotype are mainly derived from studies in adults because studies during childhood are very limited to date. Objective: The objective of the study was to determine the prevalence of MHO in Chinese children and to investigate environmental and genetic factors impacting on MHO status. Design: This was a cross-sectional study. Participants: A total of 1213 children with a body mass index at the 95th percentile or greater aged 6–18 years were included in this study. Participants were classified as MHO or of metabolically unhealthy obesity based on insulin resistance (IR) or cardiometabolic risk (CR) factors (blood pressure, lipids, and glucose). Twenty-two genetic variants previously reported from genome-wide association studies of obesity and diabetes plus the environmental factors of lifestyle, socioeconomic status, and birth weight was assessed. Results: The prevalence of MHO-IR and MHO-CR were 27.1% and 37.2%, respectively. Waist...

Journal ArticleDOI
TL;DR: Results suggest that the lower selenium status in Guide County still remains, and that DON contamination in the wheat flour may be involved in the fluctuating high prevalence rates of KBD in children in the KBD endemic Guide County in Qinghai Province.
Abstract: The aim of this study was to determine the levels of selenium, T-2 toxin, and deoxynivalenol (DON) contamination in Kashin–Beck disease (KBD) areas and provide information for understanding the high prevalence of KBD in Qinghai Province. A total of 183 subjects were chosen in a KBD-prevalent county (Guide County) and a non-KBD county (Huangzhong County) in Qinghai Province, northwestern China, and the samples of wheat flour, soil, drinking water and blood, urine, and hair of children were collected from these residents. The selenium concentrations from all these sources were determined using atomic fluorescence spectrophotometry. The levels of T-2 toxin and DON contamination in the wheat flour samples were assayed using HPLC-MS/MS. The average selenium content in the soil, drinking water, and wheat flour samples from KBD areas were 26.93 ± 10.06 μg/kg, 0.097 ± 0.038 μg/L, and 9.50 ± 7.17 μg/kg, respectively. Among these, the selenium levels in the drinking water and wheat flour samples from the KBD endemic county were significantly lower than those from the non-KBD county. For the selenium nutrient status, only the hair selenium concentration of children from the KBD endemic county was significantly lower than that from the non-KBD county. The contents of T-2 toxin in all wheat samples were below the detection limit (0.4 μg/kg). The levels of DON contamination in wheat flour samples from KBD and non-KBD children’s households within the KBD endemic county were relatively higher, with average levels of 302 ± 49 and 280 ± 48 μg/kg, respectively. The DON level of wheat flour samples from the children’s households in the non-KBD county was significantly lower than that from the KBD endemic county. These results suggest that the lower selenium status in Guide County still remains. While the selenium nutritional status of the local children has improved to some extent, partly due to the introduction of food produce from nonlocal areas. DON contamination in the wheat flour may be involved in the fluctuating high prevalence rates of KBD in children in the KBD endemic Guide County in Qinghai Province.

Journal ArticleDOI
TL;DR: This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast and provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale.
Abstract: Scaling-up of high-cell-density fermentation (HCDF) of Pichia pastoris from the lab or pilot scale to the demonstration scale possesses great significance because the latter is the final technological hurdle in the decision to go commercial. However, related investigations have rarely been reported. In this paper, we study the scaling-up processes of a recombinant P. pastoris from the pilot (10 to 100-L) to the demonstration (1,000-L) scales, which can be used to convert 7-β-xylosyl-10-deacetyltaxol into 10-deacetyltaxol by the β-xylosidase for semi-synthesis of Taxol. We demonstrated that a pure oxygen supplement can be omitted from the HCDF if the super atmospheric pressure was increased from 0.05 to 0.10 ± 0.05 MPa, and we developed a new methanol feeding biomass-stat strategy (0.035 mL/g/h) with 1% dissolved oxygen and 100 g/L initial induction biomass (dry cell weight). The scaling-up was reproducible, and the best results were obtained from the 1,000-L scale, featuring a shorter induction time and the highest enzyme activities and productions, respectively. The specific growth and specific production rates were also determined. This study lays a solid foundation for the commercial preparation of 10-deacetyltaxol through the recombinant yeast. It also provides a successful paradigm for scaling-up HCDF of P. pastoris to the demonstration scale.

Journal ArticleDOI
TL;DR: The extensive proliferation of SCs and the subsequent mitotic hair cell (HC) generation is achieved through a genetic reprogramming process involving activation of β-catenin to upregulate Wnt signaling, deletion of Notch1 to downregulate Notch signaling, and overexpression of Atoh1 in Sox2+ SCs in neonatal mice cochleae.
Abstract: The generation of hair cells (HCs) from the differentiation of proliferating supporting cells (SCs) appears to be an ideal approach for replacing lost HCs in the cochlea and is promising for restoring hearing after damage to the organ of Corti. We show here that extensive proliferation of SCs followed by mitotic HC generation is achieved through a genetic reprogramming process involving the activation of β-catenin to upregulate Wnt signaling, the deletion of Notch1 to downregulate Notch signaling, and the overexpression of Atoh1 in Sox2+ SCs in neonatal mouse cochleae. We used RNA sequencing to compare the transcripts of the cochleae from control mice and from mice with β-catenin activation, Notch1 deletion, and β-catenin activation combined with Notch1 deletion in Sox2+ SCs. We identified the genes involved in the proliferation and transdifferentiation process that are either controlled by individual signaling pathways or by the combination of Wnt and Notch signaling. Moreover, the proliferation of SCs induced by Notch1 deletion disappears after deleting β-catenin in Notch1 knock-out Sox2+ cells, which further demonstrates that Notch signaling is an upstream and negative regulator of Wnt signaling. SIGNIFICANCE STATEMENT We show here that the extensive proliferation of supporting cells (SCs) and the subsequent mitotic hair cell (HC) generation is achieved through a genetic reprogramming process involving activation of β-catenin to upregulate Wnt signaling, deletion of Notch1 to downregulate Notch signaling, and overexpression of Atoh1 in Sox2+ SCs in neonatal mice cochleae. By comparing the transcripts of the cochleae among controls, β-catenin activation, Notch1 deletion, and β-catenin activation combined with Notch1 deletion group, we identified multiple genes involved in the proliferation and transdifferentiation process that are either controlled by individual signaling pathways or by the combination of Wnt and Notch signaling. This provides a better understanding of the mechanisms behind mitotic HC generation and might provide new approaches to stimulating mitotic HC regeneration.

Journal ArticleDOI
TL;DR: HIV incidence is still alarmingly high among Chinese MSM and stronger HIV intervention strategies should be implemented, in particular targeting young, less educated and syphilis-infected MSM.
Abstract: Background: The national annually reported proportion of men who have sex with men (MSM) among people living with HIV (PLWH) is growing in China. To better inform the public health sector how to improve HIV prevention strategies, it is necessary to understand the current level of HIV incidence and its correlates. Methods: Google Scholar, PubMed, Web of Science and three major Chinese electronic publication databases (http://qikan.cqvip.com/, http://g.wanfangdata.com.cn/, http://www.cnki.net/, respectively) were searched for studies reporting HIV incidence. Comprehensive Meta-Analysis (CMA) 2.0 statistical software (Biostat, Inc. Englewood, NJ, USA) was used to calculate the pooled HIV incidence and perform subgroup-analysis to find correlates for HIV seroconversion in Chinese MSM. Random effects modelling was then conducted. Results: Twenty-five eligible studies were included in this meta-analysis. The calculated pooled HIV incidence was 5.61/100 person years (PY), with an increasing trend over time (3.24/100PY, 5.29/100PY, 5.50/100PY in 2005-2008, 2009-2011, 2012-2014 respectively, χ2 test for trend P = 0.04). Subgroup analyses indicated that age <25 years (rate ratio (RR) = 1.85), junior college education and below (RR = 1.87), having ≥ 2 male sexual partners in past 6 months (RR = 2.50), baseline syphilis infection (RR = 2.99), homosexual orientation (RR = 1.91), preferred bottom/versatile roles in anal sexual intercourse (RR = 2.33), and having unprotected anal intercourse in the past 6 months (RR = 2.16) significantly increased the risk for HIV seroconversion (each P < 0.05). Uncircumcised MSM had a marginal statistically significant higher HIV incidence (RR = 3.35, P = 0.051). Conclusion: HIV incidence is still alarmingly high among Chinese MSM. Stronger HIV intervention strategies should be implemented, in particular targeting young, less educated and syphilis-infected MSM.

Journal ArticleDOI
TL;DR: The possible mechanisms for the co-infection of EBV and HPV during tumorigenesis are addressed and the probability of one patient infected with these two distinct types of viruses is increasing.
Abstract: Viral infections contribute to approximately 12% of cancers worldwide, with the vast majority occurring in developing countries and areas. Two DNA viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), are associated with 38% of all virus-associated cancers. The probability of one patient infected with these two distinct types of viruses is increasing. Here, we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.

Journal ArticleDOI
01 Jul 2016-BMJ Open
TL;DR: Underweight prepregnant women appeared to be at a greater risk of developing adverse pregnancy outcomes in China's rural areas, and the prevalence of underweight individuals in a very large population significantly increased.
Abstract: Objective Unhealthy maternal weight before pregnancy increases the risk of various adverse pregnancy outcomes. We conducted a nutrition survey to provide baseline data on the prepregnant nutritional status of mothers in order to better understand the association between prepregnancy maternal body mass index (BMI) and adverse pregnancy outcomes. Design A large, prospective, population-based cohort study. Setting Data from the National Free Preconception Health Examination Project (NFPHEP) in China during 2010–2012. Participants 536 098 pregnant women out of 2 120 131 were evaluated. Primary and secondary outcome measures The primary adverse pregnancy outcomes included preterm birth (PTB), low birth weight (LBW), spontaneous miscarriage (SM), ectopic pregnancy (EP) and stillbirth (SB). A χ 2 test was used to compare the prevalence of each BMI category during 2010–2012. Univariable and multiple logistic regression analyses were performed to assess the association between prepregnancy BMI and various adverse pregnancy outcomes. Results Between 2010 and 2012, the average BMI decreased from 21.31 to 21.16, while underweight prevalence increased from 10.40% to 14.14%. An age-stratified subgroup analysis indicated that the underweight prevalence increased from 13.52% to 17.02% among women aged 21–24 and from 10.72% to 13.71% among women aged 25–34. Overweight prevalence increased from 9.84% to 10.75% (25–34 years) and from 17.10% to 19.20% (35–49 years). Obesity prevalence increased from 2.17% to 2.42% and from 4% to 4.2% among women aged 25–34 and 35–49 respectively. Prepregnancy underweight was associated with PTB, LBW and SM; overweight women had an increased risk of LBW; obese women had a higher risk of LBW, SM, EP and SB. Conclusions While the average prepregnancy BMI decreased, the prevalence of underweight individuals in a very large population significantly increased. The abnormal prepregnancy BMIs were associated with increased risks of adverse pregnancy outcomes. Most notably, underweight prepregnant women appeared to be at a greater risk of developing adverse pregnancy outcomes in China9s rural areas.

Journal ArticleDOI
TL;DR: The present study suggested that IL-2, may play role in the arrhythmia by regulating the expression of SCN3B and sodium current density.
Abstract: In the initiation and maintenance of arrhythmia, inflammatory processes play an important role. IL-2 is a pro-inflammatory factor which is associated with the morbidity of arrhythmias, however, how IL-2 affects the cardiac electrophysiology is still unknown. In the present study, we observed the effect of IL-2 by qRT-PCR on the transcription of ion channel genes including SCN2A, SCN3A, SCN4A, SCN5A, SCN9A, SCN10A, SCN1B, SCN2B, SCN3B, KCNN1, KCNJ5, KCNE1, KCNE2, KCNE3, KCND3, KCNQ1, KCNA5, KCNH2 and CACNA1C. Western blot assays and electrophysiological studies were performed to demonstrate the effect of IL-2 on the translation of SCN3B/scn3b and sodium currents. The results showed that transcriptional level of SCN3B was up-regulated significantly in Hela cells (3.28-fold, p = 0.022 compared with the control group). Consistent results were verified in HL-1 cells (3.73-fold, p = 0.012 compared with the control group). The result of electrophysiological studies showed that sodium current density increased significantly in cells which treated by IL-2 and the effect of IL-2 on sodium currents was independent of SCN3B (1.4 folds, p = 0.023). Western blot analysis showed IL-2 lead to the significantly increasing of p53 and scn3b (2.1 folds, p = 0.021 for p53; 3.1 folds, p = 0.023 for scn3b) in HL-1 cells. Consistent results were showed in HEK293 cells using qRT-PCR analysis (1.43 folds for P53, p = 0.022; 1.57 folds for SCN3B, p = 0.05). The present study suggested that IL-2, may play role in the arrhythmia by regulating the expression of SCN3B and sodium current density.

Journal ArticleDOI
TL;DR: Although the vast majority of imported malaria cases were due to P. falciparum, the increase in other rare Plasmodium species originating from sub-Saharan Africa and Southeast Asia should be closely monitored at all levels of health providers focusing on diagnosis and treatment of malaria.
Abstract: Following initiation of China’s National Malaria Elimination Action Plan in 2010, indigenous malaria infections in Jiangsu Province decreased significantly. Meanwhile imported Plasmodium infections have increased substantially, particularly Plasmodium ovale and Plasmodium malariae. Given the risk for malaria resurgence, there is an urgent need to understand the increase in imported P. ovale and P. malariae infections as China works to achieve national malaria elimination. An observational study of imported malaria cases in Jiangsu Province, China was carried out for the period of 2011–2014. A total of 1268 malaria cases were reported in Jiangsu Province from 2011 to 2014. Although imported Plasmodium falciparum cases (n = 1058) accounted for 83.4 % of all reported cases in Jiangsu, P. ovale cases (14, 19, 30, and 46) and their proportion (3.7, 9.6, 8.8, and 13.0 %) of all malaria cases increased over the 4 years. Similarly, P. malariae cases (seven, two, nine, and 10) and proportion (1.9, 1.0, 2.6, and 2.8 %) of all malaria cases increased slightly during this time. A total of 98 cases of Plasmodium ovale curtisi (47/98, 48 %) and Plasmodium ovale wallikeri (51/98, 52 %) were identified as well. Latency periods were significant among these Plasmodium infections (p = 0.00). Also, this study found that the latency periods of P. ovale sp., P. malariae and Plasmodium vivax were significantly longer than P. falciparum. However, for both P. ovale curtisi and P. ovale wallikeri infections, the latency period analysis was not significant (p = 0.81). Misdiagnosis of both P. ovale and P. malariae was greater than 71.5 and 71.4 %, respectively. The P. ovale cases were misdiagnosed as P. falciparum (35 cases, 32.1 %), P. vivax (43 cases, 39.4 %) by lower levels of CDCs or hospitals. And, the P. malariae cases were misdiagnosed as P. falciparum (ten cases, 35.7 %), P. vivax (nine cases, 32.1 %) and P. ovale sp. (one case, 3.6 %). Geographic distribution of imported P. ovale sp. and P. malariae cases in Jiangsu Province mainly originated from sub-Saharan Africa such as Equatorial Guinea, Nigeria, and Angola. Although the vast majority of imported malaria cases were due to P. falciparum, the increase in other rare Plasmodium species originating from sub-Saharan Africa and Southeast Asia should be closely monitored at all levels of health providers focusing on diagnosis and treatment of malaria. In addition to a receptive vector environment, long latency periods and misdiagnosis of P. malariae and P. ovale sp. increase the risk of re-introduction of malaria in China.

Journal ArticleDOI
TL;DR: High rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among MSM in China and targeted interventions to address high-risk MSM including those having multiple partners, history of recreational drug use and syphilis or HSV-2 infection seemed to be the need of the hour.
Abstract: Recent upsurge of new HIV infections among men who have sex with men (MSM) is a major concern in China. Paucity of national-level information regarding the burden and predictors of this progressive epidemic of new infections called for a multi-centric, timely and comprehensive investigation. Mixed methods were used to recruit MSM from seven cities in China between 2012 and 2013. Recent and established HIV infections were estimated by Western Blot and BED HIV-1 capture enzyme immunoassay. Syphilis and herpes simplex virus-2 (HSV-2) were also tested. A total of 4496 eligible MSM were recruited. The majority was aged ≤35 years (77.5 %), migrants (60.3 %), never married (69.8 %), and played receptive role in anal sex (70.5 %). The HIV prevalence was 9.9 %, and 41.9 % were recently infected, with sensitivity/specificity adjusted HIV incidence of 8.9 (95 % CI: 7.6-10.2)/100 Person-Years. The prevalence of history HSV-2 and syphilis were 12.5 % and 8.5 %, respectively. Recent HIV infection was associated with having multiple male partners (aOR = 1.4, 95 % CI 1.1-1.9), recreational drug use (aOR = 2.2, 95 % CI 1.6-3.0), anal bleeding (aOR = 2.1, 95 % CI 1.4-3.0), syphilis infection (aOR = 2.8, 95 % CI 1.9-4.3) and history HSV-2 infection (aOR = 2.3, 95 % CI 1.5-3.3). High rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among MSM in China. Targeted interventions to address high-risk MSM including those having multiple partners, history of recreational drug use and syphilis or HSV-2 infection seemed to be the need of the hour.

Journal ArticleDOI
TL;DR: This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care.
Abstract: Many risk factors associated with adverse pregnancy outcomes can be identified and modified preconceptionally. Despite a broad consensus that preconception care should be provided to all couples of reproductive age, it has not been integrated in routine healthcare. There are several barriers to its implementation, and even in the most resourceful countries, it is only provided to some select high-risk groups, rather than being an organized healthcare service provision to all. Recently, China seems to be leading the way by implementing preconception care nationwide in all rural areas. Its National Free Preconception Health Examination Project is a unique model of comprehensive preconception care. Advantages of this ambitious project are now becoming evident and benefiting the most vulnerable sections of Chinese society. This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care.

Journal ArticleDOI
01 May 2016-Medicine
TL;DR: A meta-analysis aimed at further illustrating the prognostic power of DNMT3A R882 mutations in AML patients and predicted worse RFS and OS among the subgroups of patients under age 60 and over age 60.