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Abstract Introduction Metformin and statins are considered as potential agents for prevention of breast cancer, however, existing evidence does not uniformly substantiate this claim, and the data is scarce concerning their interaction in relation to breast cancer risk. This study aims to investigate whether the effect of metformin on breast cancer incidence varied by statin use among women with type 2 diabetes mellitus (T2DM). Methods This study included women with T2DM, without a history of cancers, and followed up for more than one year from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) for the period 1998–2014. The dataset was structured using a person-time approach, where the cumulative medication usage was annually updated for each person. The extended Cox proportional hazards models were employed, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results During a median follow-up of 5 years, 515 of 29,498 women received a breast cancer diagnosis. Each additional year of metformin or statins use corresponded to a decrease in breast cancer incidence, while the magnitude attenuated over time. Noteworthily, statin use modified the effect of metformin on breast cancer incidence. For instance, after 5 years of follow-up, one-year increase of metformin use among women who used statins for 3 years was linked to a substantially reduced breast cancer risk (HR, 95% CI: 0.88, 0.84–0.93), however, there was no significant decrease in risk for those non-statins users (HR, 95% CI: 0.96, 0.89–1.04). Conclusions Extending metformin or statin usage by one year conferred breast cancer protection in women with T2DM. Enhanced protective effect of metformin was observed among those who also use statins. These results suggest the potential of combined metformin and statin therapy as promising breast cancer prevention strategies.

PurposePotentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs).MethodsThis 3-year (2015–2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP.ResultsThe prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50–1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46–1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95–2.03) and musculoskeletal system and connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31–1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63–1.66).ConclusionAmong older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population.

Abstract BackgroundThe relation between climate change and human health has become one of the major worldwide public health issues. However, the evidence for low-latitude plateau regions is limited, where the climate is unique and diverse with a complex geography and topography. ObjectivesThis study aimed to evaluate the effect of ambient temperature on the mortality burden of nonaccidental deaths in Yunnan Province and to further explore its spatial heterogeneity among different regions. MethodsWe collected mortality and meteorological data from all 129 counties in Yunnan Province from 2014 to 2020, and 16 prefecture-level cities were analyzed as units. A distributed lagged nonlinear model was used to estimate the effect of temperature exposure on years of life lost (YLL) for nonaccidental deaths in each prefecture-level city. The attributable fraction of YLL due to ambient temperature was calculated. A multivariate meta-analysis was used to obtain an overall aggregated estimate of effects, and spatial heterogeneity among 16 prefecture-level cities was evaluated by adjusting the city-specific geographical characteristics, demographic characteristics, economic factors, and health resources factors. ResultsThe temperature-YLL association was nonlinear and followed slide-shaped curves in all regions. The cumulative cold and heat effect estimates along lag 0‐21 days on YLL for nonaccidental deaths were 403.16 (95% empirical confidence interval [eCI] 148.14‐615.18) and 247.83 (95% eCI 45.73‐418.85), respectively. The attributable fraction for nonaccidental mortality due to daily mean temperature was 7.45% (95% eCI 3.73%‐10.38%). Cold temperature was responsible for most of the mortality burden (4.61%, 95% eCI 1.70‐7.04), whereas the burden due to heat was 2.84% (95% eCI 0.58‐4.83). The vulnerable subpopulations include male individuals, people aged

A high performance liquid chromatography-ultraviolet (HPLC-UV) fingerprint method for the overall chemical analysis of edible mushrooms was established based on Auricularia heimuer for the first time, and then applied to analyze 60 batches of A. heimuer, Auricularia cornea, Auricularia cornea ʻYu Muerʼ and Tremella fuciformis. A total of 9 characteristic peaks of A. heimuer, 11 characteristic peaks of A. cornea, 6 characteristic peaks of A. cornea ʻYu Muerʼ, and 9 characteristic peaks of T. fuciformis were designated. Then, a combinatory analysis, including similarity evaluation, hierarchical cluster analysis and principal component analysis, revealed the chemical consistency and difference between samples from the same and different species. The HPLC fingerprint method established in this paper could be used to characterize the components of A. heimuer, A. cornea, A. cornea ʻYu Muerʼ, and T. fuciformis and discriminate the 4 edible mushrooms effectively in combination with pattern recognition analysis.

Background: Angiogenesis plays a critical protective role in myocardial ischemia-reperfusion injury (MIRI); however, therapeutic targeting of associated genes remains constrained. To bridge this gap, we conducted bioinformatics analysis to identify pivotal angiogenesis-related genes in MIRI, potentially applicable for preventive and therapeutic interventions. Methods: We collected two mouse heart I/R expression datasets (GSE61592 and GSE83472) from Gene Expression Omnibus, utilizing the Limma package to identify differentially expressed genes (DEGs). Angiogenesis-related genes (ARGs) were extracted from GeneCards, and their overlap with DEGs produced differentially expressed ARGs (ARDEGs). Further analyses included Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and disease ontology to explore biological functions. Weighted gene correlation network analysis (WGCNA) was used to investigate molecular modules linked to MIRI. Additionally, a protein–protein interaction (PPI) network was constructed to pinpoint hub genes relevant to MIRI. Receiver operating characteristic curves were used to assess the diagnostic efficacy of these hub genes for MIRI. An ischemia-reperfusion injury model was established using human cardiac microvascular endothelial cells (HCMECs), with the expression of hub genes validated within this experimental framework. Results: We identified 47 ARDEGs, 41 upregulated and 6 downregulated. PPI network analysis revealed suppressor of cytokine signaling 3 (Socs3), C-X-C motif chemokine ligand 1 (Cxcl1), interleukin 1 beta (Il1b), and matrix metallopeptidase 9 (Mmp9) as hub genes. Receiver operating characteristic (ROC) curve analysis demonstrated strong diagnostic potential for Socs3, Cxcl1, Il1b, and Mmp9. In vitro validation corroborated the mRNA and protein expression predictions. Conclusions: Our study highlights the pivotal role of Socs3, Cxcl1, Il1b, and Mmp9 in MIRI development, their significance in immune cell infiltration, and their diagnostic accuracy. These findings offer valuable insights for MIRI diagnosis and treatment, presenting potential molecular targets for future research.

Helicobacter pylori (H. pylori) eradication is pivotal for alleviating gastric mucosal inflammation and preventing the progression of gastric diseases. While antibiotic-based therapies have achieved significant success in H. pylori eradication, challenges such as antibiotic resistance, drug toxicity, side effects, nonadherence, inapplicability, and disruption of gastrointestinal microflora have emerged. Updated therapies are urgently needed to suppress H. pylori. Nature has provided multitudinous therapeutic agents since ancient times. Natural products can be a potential therapy endowed with H. pylori eradication efficacy. We summarize the basic information, possible mechanisms, and the latest research progress of some representative natural products in H. pylori eradication, highlighting their safety, accessibility, efficiency, and ability to overcome limitations associated with antibiotic application. This review highlights the potential therapeutic advantages of incorporating ethnomedicine into anti-H. pylori regimens. The findings of this review may provide insights into the development of novel natural products and expand the therapeutic options available for H. pylori eradication.

Aim: This study aimed to identify the association of chronic polypharmacy and potentially inappropriate medications (PIMs) with adverse health outcomes (AHOs) in community-dwelling older adults with diabetes in China.Methods: A 2-year retrospective cohort study was conducted using 11,829 community-followed older adults with diabetes and medical records from 83 hospitals and 702 primary care centers in Shenzhen, China. Chronic polypharmacy and PIMs were identified from prescription records using Beers’ criteria, and their associated AHO was analyzed using multivariable logistic regression analysis.Results: The prevalence of chronic polypharmacy and at least one PIM exposure was 46.37% and 55.09%, respectively. The top five PIMs were diuretics, benzodiazepines, first-generation antihistamines, sulfonylureas, and insulin (sliding scale). Chronic polypharmacy was positively associated with all-cause hospital admission, admission for coronary heart disease, admission for stroke, admission for dementia, and emergency department visits. Exposure to PIMs was positively associated with all-cause hospital admission, admission for heart failure (PIMs ≥2), admission for stroke (PIMs ≥3), emergency department visits, bone fracture, constipation, and diarrhea.Conclusion: Chronic polypharmacy and PIMs were prevalent in older adults with diabetes in Chinese communities. Iatrogenic exposure to chronic polypharmacy and PIMs is associated with a higher incidence of different AHOs. This observational evidence highlights the necessity of patient-centered medication reviews for chronic polypharmacy and PIMs use in older patients with diabetes in primary care facilities in China and draws attention to the caution of polypharmacy, especially PIM use in older adults with diabetes in clinical practice.

Abstract Background Tibetan medicine has been used in clinical practice for more than 3800 years. Zuozhu-Daxi (ZZDX), a classic traditional Tibetan medicine, has been proved to be effective in the treatment of digestive diseases, such as chronic gastritis, gastric ulcer, etc. Helicobacter pylori (H. pylori), one of the most common pathogenic microbes, is regarded as the most common cause of gastritis. Researching on the effects of ZZDX on H. pylori-induced gastric mucosa inflammation could provide more evidences on H. pylori treatment and promote the development of Tibetan medicine. This study aimed to explore whether ZZDX could rescue H. pylori-induced gastric mucosa inflammation and its mechanism. Methods Male C57BL/6 mice were infected with H. pylori, and orally treated with ZZDX to rescue gastric mucosa inflammation induced by H. pylori infection. Pathology of gastric mucosa inflammation was evaluated under microscopy by hematoxylin–eosin (HE) staining. The infection status of H. pylori was evaluated by immunohistochemical (IHC) staining. The reactive oxygen species (ROS) level in serum was evaluated using a detection kit. IL-1α, IL-6, and PGE2 expression levels in serum were measured using ELISA. IL-1α, IL-8, TNF-α, and NOD1 expression levels in gastric tissues were measured using real-time PCR. RNA sequencing and gene certification of interest were performed to explore the mechanisms in vivo and in vitro. Results The results showed that ZZDX could significantly inhibit H. pylori-induced gastric mucosa inflammation using HE staining. IL-1α, IL-6, and PGE2 expression levels in serum were significantly decreased after treatment with ZZDX. ZZDX treatment significantly decreased the mRNA expression of IL-8 induced by H. pylori infection in gastric tissues. Elovl4, Acot1 and Scd1 might be involved in the mechanisms of ZZDX treatment. However, the H. pylori infection status in the gastric mucosa was not reduced after ZZDX treatment. Conclusions ZZDX reversed gastric mucosal injury and alleviated gastric mucosa inflammation induced by H. pylori infection.

Abstract Background There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. Methods The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Participants’ demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. Results In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. Conclusions In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

Introduction: Paternal smoking associated with childhood overweight and obesity has been a concern, but studies have not investigated smoking exposure and smoking details. We investigated the association of exposures from paternal smoking as well as smoking details on offspring overweight/obesity. Methods: A total of 4,513 children (aged 7–8 years) in Shenzhen were enrolled. Four different exposures from paternal smoking as well as smoking quantity, duration of smoking, and age of starting smoking details were the exposure variables and demographic characteristics, and circumstances of birth, dietary intake, lifestyle, and nonpaternal-smoking exposure were covariates in the logistic regression analysis to determine the effect of paternal smoking on childhood overweight/obesity, estimating odds ratios (ORs), and 95% confidence intervals (CIs). Results: Paternal smoking was positively associated with childhood overweight/obesity (p < 0.05). Moreover, only preconception exposure, and both pre- and postconception exposure were significantly associated with childhood overweight/obesity (OR 1.54 [95% CI: 1.14–2.08] and OR 1.73 [95% CI: 1.14–2.61], respectively), restricted to boys but not girls. Furthermore, for children with only preconception paternal-smoking exposure, the dose-response relation was positive between smoking quantity, duration of smoking, age at starting, and overweight/obesity for boy offspring (p trend 0.05). Conclusions: Our findings suggest that paternal smoking is associated with boys’ overweight/obesity, and this association may be due to the paternal-smoking exposure before conception rather than the postnatal exposure to paternal smoking. Reducing paternal-smoking exposure before conception might help reduce overweight/obesity in boys.

Abstract Background The incidence rates of obesity and gestational diabetes mellitus (GDM) are increasing in parallel. This study aimed to evaluate the relationship between different obesity indices, including prepregnancy body mass index (preBMI), the first-trimester abdominal circumference (AC), and first-trimester abdominal circumference/height ratio (ACHtR), and GDM, and the efficacy of these three indices in predicting GDM was assessed. Methods A total of 15,472 pregnant women gave birth to a singleton at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Prepregnancy weight was self-reported by study participants, body height and AC were measured by nurses at the first prenatal visit during weeks 11 to 13+6 of pregnancy. GDM was diagnosed through a 75-g oral glucose tolerance test at 24–28 gestational weeks. Using receiver operator characteristic (ROC) curve analysis, we evaluated the association between obesity indices and GDM. Results A total of 1912 women (12.4%) were diagnosed with GDM. Logistic regression analysis showed that AC, ACHtR, and preBMI (P

Abstract Aims Opioid addiction is a major public health issue, yet its underlying mechanism is still unknown. The aim of this study was to explore the roles of ubiquitin–proteasome system (UPS) and regulator of G protein signaling 4 (RGS4) in morphine‐induced behavioral sensitization, a well‐recognized animal model of opioid addiction. Methods We explored the characteristics of RGS4 protein expression and polyubiquitination in the development of behavioral sensitization induced by a single morphine exposure in rats, and the effect of a selective proteasome inhibitor, lactacystin (LAC), on behavioral sensitization. Results Polyubiquitination expression was increased in time‐dependent and dose‐related fashions during the development of behavioral sensitization, while RGS4 protein expression was not significantly changed during this phase. Stereotaxic administration of LAC into nucleus accumbens (NAc) core inhibited the establishment of behavioral sensitization. Conclusion UPS in NAc core is positively involved in behavioral sensitization induced by a single morphine exposure in rats. Polyubiquitination was observed during the development phase of behavioral sensitization, while RGS4 protein expression was not significantly changed, indicating that other members of RGS family might be substrate proteins in UPS‐mediated behavioral sensitization.

Abstract The ultra-low head pump stations often have bidirectional demand of water delivery, so there is a risk of runaway accident occurring in both conditions. To analyze the difference of the runaway process under forward runaway condition (FRC) and backward runaway condition (BRC), the whole flow system of a horizontal axial flow pump is considered. The Shear-Stress Transport (SST) k–ω model is adopted and the volume of fluid (VOF) model is applied to simulate the water surface in the reservoirs. Meanwhile, the torque balance equation is introduced to obtain the real time rotational speed, then the bidirectional runaway process of the pump with the same head is simulated. In addition, the vortex transport equation and swirl number are proposed to reveal the flow characteristics during the runaway process. The results show that the runaway process can be divided into five stages: the drop, braking, rising, convergence and runaway stages, according to the changing law of torque curve. In the rising stage, the pressure difference on the blade surface continues to increase, which contributes to the abnormal torque increase. In this stage, the flow hits the pressure surface (PS) at a faster speed enlarging the pressure on PS, and the flow separation takes place on the suction surface (SS) weakening the pressure on SS. During the convergence and runaway stage, the pulsation amplitude of torque and axial force under FRC is obviously larger than those under BRC. This is because the rotation frequency of the vortex rope is the same as main pressure fluctuation frequency in impeller under FRC, which enhances the pulsation amplitude. Whereas the vortices are broken due to the inhibitive effect from guide vanes under BRC.

ObjectiveTo analyze pregnancy complications and outcomes of mothers with obesity or gestational diabetes mellitus (GDM).Methods15065 mothers were categorized into four and three groups by pre-pregnancy body mass index (preBMI) and abdominal circumference (AC), respectively, or divided into GDM or non-GDM groups. Logistic regression analysis was utilized to identify independent factors associated with pregnancy complications and outcomes.ResultsThe overweight and obesity groups accounted for 16.0% and 4.0% of the total population, respectively. GDM incidence rate was 12.3%. The overweight and obesity groups (pre-pregnancy body mass index [preBMI] ≥ 24 kg/m2) were at higher risks for GDM, hypertensive disorders of pregnancy (HDP), gestational proteinuria, postpartum hemorrhage, preterm delivery, fetal malformation or stillbirth, neonatal asphyxia, large for gestational age (LGA), shoulder dystocia, and increased cesarean section rate. Similar results were obtained with AC grouping. GDM pregnant women had higher risks of HDP, preterm delivery, small for gestational age (SGA), LGA, and increased cesarean section rate.ConclusionPeople with obesity had a higher risk of adverse pregnancy outcomes. The recommended preBMI is 19.2-22.7 kg/m2. The recommended AC at 11-13+6 gestational weeks is 74.0-84.0 cm, and that value in normal preBMI is 74.0-82.0 cm.

Placenta accreta spectrum (PAS) is a high-risk obstetrical complication associated with significant morbidity and mortality. Here the authors discover a uniquely high prevalence of circulating trophoblasts clusters in PAS and explore their diagnostic potential to augment current diagnostic modalities for the early detection of PAS.

AimsPotentially inappropriate medications had been found associated with adverse drug events such as falls, emergency department admissions and hospital readmissions. There is lack of information about the prevalence of potentially inappropriate medications and associated chronic conditions in older patients with diabetes in China. This study aimed to assess the prevalence of potentially inappropriate medications in older adults with diabetes in an outpatient visitation setting and the association with polypharmacy due to comorbidities.Materials and methodsThis was a 3-year repeated cross-sectional study which conducted in outpatient setting of 52 hospitals in Shenzhen, China, using 2019 Beers criteria. The prevalence of potentially inappropriate medications, polypharmacy and comorbidities in older adults with diabetes in an outpatient setting was expressed as percentages. Logistic models were used to investigate the association between potentially inappropriate medication exposure and age, sex, polypharmacy and comorbidities.ResultsAmong the 28,484 older adults with diabetes in 2015, 31,757 in 2016 and 24,675 in 2017, the prevalence of potentially inappropriate medications was 43.2%, 44.88% and 42.40%, respectively. The top five potentially inappropriate medications were diuretics (20.56%), benzodiazepines (13.85%), androgens (13.18%), non-steroidal anti-inflammatory drugs (12.94%) and sulfonylureas (6.23%). After adjustment for age and polypharmacy, the probability of potentially inappropriate medication exposure was associated with chronic gastrointestinal diseases, followed by osteoarthritis and rheumatoid arthritis, chronic pulmonary disease, chronic kidney disease, tumor, dementia, chronic liver disease, hypertension, cardiovascular disease, cerebrovascular disease and hyperlipemia.ConclusionPotentially inappropriate medications were common in older patients with diabetes in an outpatient visitation setting. Higher probability of potentially inappropriate medication exposure was associated with the comorbidity chronic gastrointestinal diseases as well as osteoarthritis and rheumatoid arthritis. To ensure that iatrogenic risks remain minimal for older adults with diabetes, the clinical comorbidities should be considered.

As a common vector-borne disease, dengue fever remains challenging to predict due to large variations in epidemic size across seasons driven by a number of factors including population susceptibility, mosquito density, meteorological conditions, geographical factors, and human mobility. An ensemble forecast system for dengue fever is first proposed that addresses the difficulty of predicting outbreaks with drastically different scales. The ensemble forecast system based on a susceptible-infected-recovered (SIR) type of compartmental model coupled with a data assimilation method called the ensemble adjusted Kalman filter (EAKF) is constructed to generate real-time forecasts of dengue fever spread dynamics. The model was informed by meteorological and mosquito density information to depict the transmission of dengue virus among human and mosquito populations, and generate predictions. To account for the dramatic variations of outbreak size in different seasons, the effective population size parameter that is sequentially updated to adjust the predicted outbreak scale is introduced into the model. Before optimizing the transmission model, we update the effective population size using the most recent observations and historical records so that the predicted outbreak size is dynamically adjusted. In the retrospective forecast of dengue outbreaks in Guangzhou, China during the 2011-2017 seasons, the proposed forecast model generates accurate projections of peak timing, peak intensity, and total incidence, outperforming a generalized additive model approach. The ensemble forecast system can be operated in real-time and inform control planning to reduce the burden of dengue fever.

Two new species, Catathelasma laorentou and C. subalpinum, are described on the basis of morphological characters, phylogenetic evidence, host preferences and geographic distributions. A taxonomic key to the known species in China is also provided to facilitate identification. Based on samples from temperate Asia, Europe and North America, the phylogeny of Catathelasma was reconstructed using the internal transcribed spacer (ITS) region, the large subunit (LSU) of the ribosomal DNA and the translation elongation factor 1-α (TEF1).The phylogenetic results showed that Catathelasma contains two monophyletic clades: the /subalpinum clade and the /imperiale clade. The Asian species C. laorentou and C. subalpinum are closely related to the North American C. sp. (labelled as C. ventricosum in GenBank) in the /subalpinum clade, whereas C. imperiale and C. singeri are closely related in the /imperiale clade.

Backgrounds: Evidence is scarce on the relation between maternal exposure to ambient air pollution during pregnancy and fetal growth in developing countries. Moreover, the current evidence is inconsistent. We aimed to investigate the association of trimester-specific exposure to air pollution with risk of being born small for gestational age (SGA) and birth weight-markers of fetal growth-among Chinese term births. Methods: This retrospective population-based cohort study consisted of 2,567,457 singleton term live-births from January 1, 2014 to December 31, 2017 across 123 Chinese districts and counties. Personal exposure to ambient air pollutants including carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), particulate matter with aerodynamic diameter

Abstract Aims To evaluate the utility of glycated haemoglobin A1c (HbA1c) alone and in combination with haematocrit (HCT) for screening gestational diabetes mellitus (GDM) between 12–16 gestational weeks. Methods This prospective study was carried out in the Obstetrics and Gynaecology Hospital of Fudan University from November 2014 to February 2015. In total, 690 pregnant women between 20 and 35 years old were included in this study. All subjects received a routine blood examination for HbA1c and HCT at 12–16 gestational weeks (gw) and a 75-g oral glucose tolerance test at 24–28 gw. Threshold values for the diagnosis of GDM were a plasma glucose concentration of 5.1 mmol/L after fasting, 10.0 mmol/L at 60 min, and 8.5 mmol/L at 120 min. Receiver operating characteristic curves were used to evaluate the diagnostic performance of HbA1c with or without HCT. Results One hundred seven women were diagnosis with GDM at 24–28 gw. An HbA1c cutoff value 38.8%) for the screening of GDM, the area under the receiver operating characteristic curve was 0.604 (95% [CI] 0.509, 0.701). Conclusions Whether the adoption of HbA1c as a screening test for GDM would benefit pregnant women remains to be determined. However, combining HbA1c with HCT for the screening of GDM may be a useful tool to predict GDM.

China experienced an unprecedented outbreak of dengue fever in 2014, and the number of cases reached the highest level over the past 25 years. Traditional sentinel surveillance systems of dengue fever in China have an obvious drawback that the average delay from receipt to dissemination of dengue case data is roughly 1–2 weeks. In order to exploit internet search queries to timely monitor dengue fever, we analyzed data of dengue incidence and Baidu search query from 31 provinces in mainland China during the period of January 2011 to December 2014. We found that there was a strong correlation between changes in people’s online health-seeking behavior and dengue fever incidence. Our study represents the first attempt demonstrating a strong temporal and spatial correlation between internet search trends and dengue epidemics nationwide in China. The findings will help the government to strengthen the capacity of traditional surveillance systems for dengue fever.

Cannabis is one of the most important industrial crops distributed worldwide. However, the phylogeographic structure and domestication knowledge of this crop remains poorly understood. In this study, sequence variations of five chloroplast DNA (cpDNA) regions were investigated to address these questions. For the 645 individuals from 52 Cannabis accessions sampled (25 wild populations and 27 domesticated populations or cultivars), three haplogroups (Haplogroup H, M, L) were identified and these lineages exhibited distinct high-middle-low latitudinal gradients distribution pattern. This pattern can most likely be explained as a consequence of climatic heterogeneity and geographical isolation. Therefore, we examined the correlations between genetic distances and geographical distances, and tested whether the climatic factors are correlated with the cpDNA haplogroup frequencies of populations. The “isolation-by-distance” models were detected for the phylogeographic structure, and the day-length was found to be the most important factor (among 20 BioClim factors) that influenced the population structures. Considering the distinctive phylogeographic structures and no reproductive isolation among members of these lineages, we recommend that Cannabis be recognized as a monotypic genus typified by Cannabis sativa L., containing three subspecies: subsp. sativa, subsp. Indica, and subsp. ruderalis. Within each haplogroup which possesses a relatively independent distribution region, the wild and domesticated populations shared the most common haplotypes, indicating that there are multiregional origins for the domesticated crop. Contrast to the prevalent Central-Asia-Origin hypothesis of C. saltiva, molecular evidence reveals for the first time that the low latitude haplogroup (Haplogroup L) is the earliest divergent lineage, implying that Cannabis is probably originated in low latitude region.

In China, dengue remains an important public health issue with expanded areas and increased incidence recently. Accurate and timely forecasts of dengue incidence in China are still lacking. We aimed to use the state-of-the-art machine learning algorithms to develop an accurate predictive model of dengue.Weekly dengue cases, Baidu search queries and climate factors (mean temperature, relative humidity and rainfall) during 2011-2014 in Guangdong were gathered. A dengue search index was constructed for developing the predictive models in combination with climate factors. The observed year and week were also included in the models to control for the long-term trend and seasonality. Several machine learning algorithms, including the support vector regression (SVR) algorithm, step-down linear regression model, gradient boosted regression tree algorithm (GBM), negative binomial regression model (NBM), least absolute shrinkage and selection operator (LASSO) linear regression model and generalized additive model (GAM), were used as candidate models to predict dengue incidence. Performance and goodness of fit of the models were assessed using the root-mean-square error (RMSE) and R-squared measures. The residuals of the models were examined using the autocorrelation and partial autocorrelation function analyses to check the validity of the models. The models were further validated using dengue surveillance data from five other provinces. The epidemics during the last 12 weeks and the peak of the 2014 large outbreak were accurately forecasted by the SVR model selected by a cross-validation technique. Moreover, the SVR model had the consistently smallest prediction error rates for tracking the dynamics of dengue and forecasting the outbreaks in other areas in China.The proposed SVR model achieved a superior performance in comparison with other forecasting techniques assessed in this study. The findings can help the government and community respond early to dengue epidemics.

Three previously undescribed biflavonoids, oxytrodiflavanone A (1), and oxytrochalcoflavanones A,B (2,3), were isolated from the aerial part of Oxytropis chiliophylla, together with their putative biosynthetic monomers, i.e., (2S)-5,7-dihydroxyflavanone (4), (2S)-7-hydroxyflavanone (5), and 2′,4′-dihydroxychalcone (6). The structures of these compounds were elucidated by a combination analysis of spectroscopic data. The cytotoxic activities of all the isolated compounds against PC-3 human prostate cancer cell line are also presented.

Eight azukisapogenol triterpene glycosides, including five new compounds, oxychiliotriterpenosides A–E (1–5), two new methyl glucuronide derivatives that proved to be artifacts, oxychiliotriterpenoside E-glucuronic acid methyl ester (6) and myrioside B-glucuronic acid methyl ester (7), and a known one, myrioside B (8), was isolated from the aerial part of Oxytropis chiliophylla Royle. Their structures were elucidated based on extensive spectroscopic analyses and chemical methods. Triterpene glycosides were first obtained from O. chiliophylla, and those containing a galactose unit (1, 2, 5 and 6) and diglucosidic or triglucosidic linkage at C-29 (1–4), were reported from Oxytropis species for the first time, which might be recognized as a chemotaxonomic feature of O. chiliophylla. All isolated compounds were evaluated for their anti-inflammatory activities against NO production using lipopolysaccharide (LPS)-induced RAW 264.7 cells, but no compounds showed potent inhibition on NO production.

Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

In Guiyu, an electronic waste recycling site near Shantou, Guangdong province, China, primitive ways of e-waste processing have caused severe cadmium and lead pollution to the local residents. However, the possible effects of cadmium or lead pollution to genomic integrity of the local residents have not been investigated. We examined the possible relationship between cadmium and lead concentrations in placenta and placental telomere length in Guiyu and compared the data with that of a non-polluted town. Graphite furnace atomic absorption spectrometry and real-time PCR were used to determine placental cadmium and lead concentrations, and placental telomere length. We found that placental cadmium concentration was negatively correlated with placental telomere length (r = -0.138, p = 0.013). We also found that placental cadmium concentration of 0.0294 µg/g might be a critical point at which attrition of placental telomere commenced. No significant correlation between placental lead concentration and placental telomere length was detected (r = 0.027, p = 0.639). Our data suggest that exposure to cadmium pollution during pregnancy may be a risk factor for shortened placental telomere length that is known to be related to cancer development and aging. Furthermore, grave consequence on the offspring from pregnancies in e-waste polluted area is indicated.

Chronic obstructive pulmonary disease (COPD), which is a common respiratory disorder with high morbidity and mortality globally, has a complex pathogenesis that is not fully understood. Some circular RNAs (circRNAs) have been recognized to serve as miRNA sponges for regulating target RNA transcripts during the processes of human diseases. In the present study, we aimed to investigate novel circRNA-associated biomarkers for COPD, 245 differentially expressed circRNAs were identified, including 111 up-regulated and 134 down-regulated circRNAs. These candidate circRNAs were enriched in inflammation-associated pathways (such as mTOR, B-cell receptor, and NF-κB signaling pathways) via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A combination of two circRNAs (up-regulated hsa circ 0067209 and down-regulated hsa circ 0000673) demonstrated good diagnostic value (area under the receiver operating characteristic curve [AUC] = 0.866) for COPD by receiver operating characteristic curve (ROC) analysis and qRT-PCR validation. Subsequently, hsa-miR-8082 and hsa-miR-1248 were identified as targets for hsa circ 0067209 and hsa circ 0000673, respectively, via bioinformatics analysis and a dual-luciferase reporter assay, and the combination of these two miRNAs displayed better diagnosis potential for COPD (AUC = 0.967) than each other. Evaluation of COPD-related mRNA profiles revealed that the up-regulated genes ABR and TRPM6 were predicted downstream targets for hsa circ 0067209/hsa-miR-8082, whereas the down-regulated gene RORC was a predicted downstream target for hsa circ 0000673/hsa-miR-1248. In summary, hsa circ 0067209 and hsa circ 0000673 have potential as novel diagnostic biomarkers of COPD. In addition, competing endogenous RNA networks of hsa circ 0067209/hsa-miR-8082/ABR/TRPM6 and hsa circ 0000673/hsa-miR-1248/RORC may play critical regulation roles for COPD pathogenesis. [ABSTRACT FROM AUTHOR]