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Fast and accurate identification of mine water source is the key condition to prevent and control mine water damage. This study takes Mindong No.1 Mine in grassland mining area of east China as the research area, collects a variety of mine water source samples, and analyzes the hydro-chemical characteristics of different types of water samples by drawing Piper three-line diagram and Gibbs diagram and ionic proportional coefficients diagram, and qualitatively identifies several types of mine water source. In addition, the proportion of mine water source is quantitatively analyzed by the calculation of hydrogen and oxygen isotopes. The hydro-chemical type of mine indirect water sources (atmospheric precipitation, surface water, quaternary diving and aquifer water I) is HCO3-Ca, and the hydro-chemical type of aquifer water II is HCO3-Ca mixed with HCO3-Na. The hydro-chemical types of aquifer III water and mine gushing water are both HCO3-Na type, and aquifer III water is the main recharge source of mine gushing water. The formation of Ca2+, Na+ and HCO3− in groundwater and mine water is controlled by rock weathering, and mainly comes from the dissolution of silicate minerals such as potassium feldspar, albite and calcium feldspar. Combined with the calculation of isotope tritium content, the relative average age of water in the Quaternary, I aquifer, II aquifer and III aquifer is 18.48, 57.88, 69.24, 69.24 years, respectively. The average age of mine water gushing is 69.24 years, and the average values of δD and δ18O of mine water are closest to aquifer II and aquifer III water. Mine water gushing is mainly a mixture of aquifer II and III water, accounting for 11.1% and 89.9% of the total mine water gushing, respectively. The mixing ratio is about 1∶9.

The water–rock interactions significantly affect the dissolution and release of dissolved organic matter (DOM) during the reinjection of mine water into the underground reservoir. In this study, the surface characteristics and chemical composition of the natural medium from the open-pit coal mine were characterized. The waste consists mainly of quartz-dominated sandstone (43.64%) and mudstone dominated by sanidine (76.36%). During the 35-day experiment, two protein-like, one humus-like, and one fulvic acid-like substances were identified by PARAFAC. It was observed that the type of aqueous medium significantly affected the variational trend of DOM. Compared to the artificial medium, the fluorescence intensity of waste materials in the waste dump increased significantly during the reinjection process. Therefore, a positive correlation was observed between the fraction of mudstone in the aqueous medium and the DOM composition, mainly due to the dissolution of polycyclic aromatic hydrocarbon substances from the mudstone. The results revealed that the natural water storage medium had a certain water storage feasibility when compared with the expensive artificial medium. However, the fraction of mudstone in the water storage medium should be controlled to minimize the release of organic matter into the environment. HIGHLIGHTS The evolution law of DOM in the underground storage of mine water has been elucidated first.; The water storage medium in sandstone and mudstone was divided, and the influence of mineral composition on the evolution of water quality separately was studied.; The variation patterns of different components of DOM in mine water were scientifically analyzed using three-dimensional fluorescence spectroscopy combined with the parallel factor method.;

To explore impact of the propensity to coronavirus disease 2019 (COVID-19) vaccine/vaccination on influenza vaccination from willingness to behavior after COVID-19 pandemic among older adults in rural China. A combined study involving a cross-sectional survey for the willingness of influenza vaccination, a health education momentary intervention and a community intervention program were conducted from September 11th to 16th, 2023 among rural older adults in China. Totally 3138 individuals were investigated in this study with 1923 (61.3%) willing to receive influenza vaccination. After the momentary intervention, 47.8% (582/1215) individuals changed to be willing to receive influenza vaccination. There were 1440 (78.8%) vaccinated. The influenza vaccination willingness rate was significantly higher in the participants willing to receive COVID-19 vaccine booster dose vaccination than the participants unwilling to (69.4% vs. 37.7%, adjusted OR [aOR] = 2.671, 95% CI 2.211–3.227, p

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third doses is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from the Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28 and 61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61 and 214 days after the second dose 87,067 (64.1%) infants were vaccinated with the third dose between 151 and 180 days after the second dose. The time interval distribution varied across the four provinces or municipalities (p

The Hengduan Mountains in Southwest China are currently facing a recurring and escalating threat of forest fires, posing a significant challenge to vegetation restoration efforts given the ecological value of this region. However, the effects of artificial restoration compared to natural regeneration on vegetation recovery dynamics have been less explored. This study focused on two sites in the Hengduan Mountains, primarily composed of conifer forests. One site employed a mix of artificial restoration measures, including tree planting, aerial grass seeding, and fertilizer application. The other site, which is relatively drier and colder, relied on natural regeneration. Four fire events in these two sites were compared to examine the effects of artificial restoration on vegetation recovery using remotely sensed data from Landsat and MODIS. Fire severity was classified using the differenced Normalized Burn Ratio (dNBR) and validated with field samples. Vegetation greenness loss and recovery trajectory were quantified using the near-infrared reflectance of vegetation (NIRv). The effects of artificial restoration were further analyzed after employing unburnt controls to minimize the impact of climate fluctuations. Results showed that fire severity mapping achieved an overall accuracy of 82%. The average NIRv loss across the four fires was 30%, 49%, and 69% in areas of low, moderate, and high severity, respectively. In low severity areas, natural and artificial recovery rates were similar, at 21% and 26% respectively, three years post-fire. In moderate severity areas, artificial restoration achieved a 46% recovery rate compared to 31% for natural recovery. In high severity areas, artificial restoration resulted in a 63% recovery rate versus 45% for natural recovery. Although the differences in recovery patterns may also be attributed to inherent variations in the vegetation composition, physical environment, and their interactions, this study suggests that high severity areas benefit significantly from artificial intervention for rapid recovery. Future studies should include more controlled experiments at the plot scale to further elucidate the processes of vegetation response to different artificial restoration measures.

Abstract Background While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. Results The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy − Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the − 600 to − 1200 segment, in which the four SNPs were located. Conclusions The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Introduction: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. Objectives: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. Methods: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. Results: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. Conclusions: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

Abstract CUL4B, a crucial scaffolding protein in the largest E3 ubiquitin ligase complex CRL4B, is involved in a broad range of physiological and pathological processes. While previous research has shown that CUL4B participates in maintaining intestinal homeostasis and function, its involvement in facilitating intestinal recovery following ionizing radiation (IR) damage has not been fully elucidated. Here, we utilized in vivo and in vitro models to decipher the role of CUL4B in intestinal repair after IR-injury. Our findings demonstrated that prior to radiation exposure, CUL4B inhibited the ubiquitination modification of PSME3, which led to the accumulation of PSME3 and subsequent negative regulation of p53-mediated apoptosis. In contrast, after radiation, CUL4B dissociated from PSME3 and translocated into the nucleus at phosphorylated histones H2A (γH2AX) foci, thereby impeding DNA damage repair and augmenting p53-mediated apoptosis through inhibition of BRCA1 phosphorylation and RAD51. Our study elucidated the dynamic role of CUL4B in the repair of radiation-induced intestinal damage and uncovered novel molecular mechanisms underlying the repair process, suggesting a potential therapeutic strategy of intestinal damage after radiation therapy for cancers.

Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1–TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown. Here, we show that Tmc7 is specifically expressed in the testis and that it is required for acrosome biogenesis during spermatogenesis. Tmc7−/− mice exhibited abnormal sperm head, disorganized mitochondrial sheaths, and reduced number of elongating spermatids, similar to human oligo-astheno-teratozoospermia. We further demonstrate that TMC7 is colocalized with GM130 at the cis-Golgi region in round spermatids. TMC7 deficiency leads to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome. Moreover, upon loss of TMC7 intracellular ion homeostasis is impaired and ROS levels are increased, which in turn causes Golgi and endoplasmic reticulum stress. Taken together, these results suggest that TMC7 is required to maintain pH and ion homeostasis, which is needed for acrosome biogenesis. Our findings unveil a novel role for TMC7 in acrosome biogenesis during spermiogenesis.

Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the APC gene, leading to the formation of benign polyps. Despite the well-established role of APC, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood. In this investigation, we generated a murine model by crossing ApcMin/+ mice with Cul4bΔIEC mice to achieve specific deletion of Cul4b in the gut epithelium against an ApcMin/+ background. By employing histological methods, RNA-sequencing (RNA-seq), and flow cytometry, we assessed alterations and characterized the immune microenvironment. Our results unveiled that CUL4B deficiency in gut epithelium expedited ApcMin/+ adenoma formation. Notably, CUL4B in adenomas restrained the accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). In vivo inhibition of MDSCs significantly delayed the growth of CUL4B deleted ApcMin/+ adenomas. Furthermore, the addition of MDSCs to in vitro cultured ApcMin/+; Cul4bΔIEC adenoma organoids mitigated their alterations. Mechanistically, CUL4B directly interacted with the promoter of Csf3, the gene encoding granulocyte-colony stimulating factor (G-CSF) by coordinating with PRC2. Inhibiting CUL4B epigenetically activated the expression of G-CSF, promoting the recruitment of MDSCs. These findings offer novel insights into the tumor suppressor-like roles of CUL4B in regulating ApcMin/+ adenomas, suggesting a potential therapeutic strategy for CRC initiation and progression in the context of activated Wnt signaling.

Sea buckthorn pomace is often discarded as a by-product during the sea buckthorn processing stage. Consequently, its richness in dietary fiber is usually overlooked. In this study, soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were extracted from sea buckthorn pomace using ultrasound combined with the enzyme method. The optimal values of the independent variable were determined by a combinatorial design and a response surface optimization test with SDF/IDF as the dependent variable, prepared as follows: 5% enzyme addition, ultrasonic power of 380 W, enzymatic time of 30 min, and alcoholic precipitation liquid ratio of 4:1. Under these conditions, the SDF/IDF ratio was 17.07%. The structural characterization and hypoglycemic activity of the two dietary fibers were then compared. The results show that two dietary fibers have respective structures and functional groups of fibers. SDF was less crystalline than IDF, and its structure was looser. Furthermore, the hypoglycemic activity of SDF was significantly better than IDF’s (p < 0.05). The glucose adsorption capacity of SDF was 1.08–1.12 times higher than that of IDF. SDF inhibited α-amylase and α-glucosidase by 1.76 and 4.71 times more than IDF, respectively. These findings provide a reference for improving the utilization of sea buckthorn processing by-products.

Abstract Regulation of alternative splicing (AS) enables a single transcript to yield multiple isoforms that increase transcriptome and proteome diversity. Here, we report that spliceosome component Usp39 plays a role in the regulation of hepatocyte lipid homeostasis. We demonstrate that Usp39 expression is downregulated in hepatic tissues of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) subjects. Hepatocyte-specific Usp39 deletion in mice leads to increased lipid accumulation, spontaneous steatosis and impaired autophagy. Combined analysis of RNA immunoprecipitation (RIP-seq) and bulk RNA sequencing (RNA-seq) data reveals that Usp39 regulates AS of several autophagy-related genes. In particular, deletion of Usp39 results in alternative 5’ splice site selection of exon 6 in Heat shock transcription factor 1 (Hsf1) and consequently its reduced expression. Importantly, overexpression of Hsf1 could attenuate lipid accumulation caused by Usp39 deficiency. Taken together, our findings indicate that Usp39-mediated AS is required for sustaining autophagy and lipid homeostasis in the liver.

In order to solve the problem of difficult solid-liquid separation in the treatment of mine water containing suspended solids, based on the theory of nuclear crystal coagulation induced granulation, the process of “micro flocculation multi stage filtration” of mine water is studied through laboratory experiments. First of all, through the adjustment of reagent dosage and water conservancy conditions, the suspended particles and flocculants are induced to form a copolymer to form a floc settling time curve, and the floc granulation and densification are completed through the selection of optimal parameters. Secondly, four filter media of quartz sand, artificial zeolite, active carbon and aeolian sand are selected to investigate the effects of different media types and particle sizes on the removal efficiency of pollutants, and the physical and chemical reactions generated at the solid-liquid interface are analyzed. Finally, field tests are carried out in typical mines to verify the removal effect of the process on different pollution components. The results show that (1) the sedimentation time can be greatly reduced by adding polyaluminum chloride of 200 mg/L and diatomite of 200 mg/L in the micro flocculation stage. (2) The turbidity removal rate of 1−2 mm quartz sand in the multi-stage filtration stage can reach 97.9%, while the artificial zeolite in the four filter media is the best for the removal of inorganic ions. The removal rates of \begin{document}${\rm{SO}}_4^{2 -} $\end{document}, \begin{document}${\rm{HCO}}_3^- $\end{document} and Na+ in the filtered water can reach 25.5%, 44.1% and 69.9%, respectively. The micro flocculation multi-stage filtration process formed through the research results can greatly reduce the residence time in the process of mine water treatment and improve the solid-liquid separation efficiency. On this basis, the selection of natural diatomite as nucleating agent instead of polyacrylamide can effectively inhibit the generation of acrylamide monomer and reduce environmental risks. In addition, the process has a certain removal effect on inorganic ions. It is good application value for the treatment of mine water containing suspended solids.

To explore the mechanism of the FRZB gene in hair follicle development by regulating the Wnt/β-catenin signalling pathway, Angora rabbits were selected to collect back skin samples for the experiment. The action mechanism is understood by cell culture and transfection, apoptosis and proliferation assays and TOP/FOP Flash Wnt Reporting System methods. The results showed that the interference and overexpression of the FRZB gene in rabbit dermal papilla cells indicated that overexpression could inhibit the expression of SFRP2, BMP4, and WNT2 genes (P

Abstract Background Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. Methods Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. Results Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. Conclusions Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Abstract Background The growing trend of ageing population has become a worldwide concern. In comparison with the youth, older people are more likely to suffer from multimorbidity and polypharmacy, both of which are associated with adverse outcomes and increased healthcare costs. This study aimed to investigate the status of multimorbidity and polypharmacy in a large sample of hospitalized older patients aged 60 years and over. Methods A retrospective cross-sectional study was conducted among 46,799 eligible patients aged 60 years and over, who were hospitalized from January 1, 2021 to December 31, 2021. Multimorbidity was defined as the presence of 2 or more morbidities in one patient during the stay in hospital, and polypharmacy as prescription of 5 or more different oral medications. Spearman rank correlation analysis was used to assess the relationship of factors with the number of morbidities or oral medications. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated from logistic regression models to determine the predictors for polypharmacy and all-cause death. Results The prevalence of multimorbidity was 91.07% and increased with age. The prevalence of polypharmacy was 56.32%. Older age, polypharmacy, prolonged length of stay (LOS), higher cost on medications were significantly associated with an increased number of morbidities (all P

Objective To examine social region-specific characteristics and transition-differentiation of driving factors for multidimensional health poverty (MHP) in China for providing a reference to precise poverty alleviation and effective governance of health poverty. MethodsWe collected nationwide data from four rounds of the China Health and Retirement Longitudinal Survey (CHARLS) conducted in 2011, 2013, 2015, and 2018 and other relevant data from the China Statistical Yearbook and the China Health and Family Planning Statistical Yearbook of 2012, 2014, 2016, and 2019 and from the Global Burden of Disease Network in 2019. Based on a self-established theoretical framework of MHP associated with three dimensional components of health capability-right-risk, we selected 13 indicators covering the three dimensional components as the driving factors of MHP and used geographic detectors to explore the characteristics of independent and coupled effect of the driving factors and analyze differences in spatial distribution of the driving factors. ResultsCompared with those in 2011, 2013, and 2015, the ranking of three health capability dimension factors (gross domestic production [GDP] per capita, urbanization rate, and annual hospitalization rate of residents) increased in 2018; while the ranking of three health right dimension factors (per capita expenditure on both social security and employment and the number of public health education programs) decreased; the effect of health right empowerment on preventing the occurrence of health poverty increased. The analysis on differences in spatial distribution of driving factors during 2011 – 2018 showed that urban unemployment rate was a main driving factor for MHP in eastern region; while, the main driving factor for MHP in central region was the concentration of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) three years ago and the MHP was driven jointly by multiple factors with regard to health capability-right-risk. The analyses on interactive effect of the driving factors revealed bivariate interactive enhancement effect on MHP among GDP per capita and urbanization rate as factors of health capability dimension and government health expenditure ratio, per capita expenditure on social security and employment, and the number of beds in health care institutions versus per 1 000 population as factors of health right dimension; the joint effect of driving factors regarding to health capability and health right reduced the occurrence MHP; the interaction between PM2.5 concentration three years ago (a health risk indicator) and two health capability indicators (annual hospitalization rate of residents and elderly dependency ratio in 2011/2013/2018) also showed bivariate interactive enhancement effect on MHP. ConclusionThe prevalence of MHP is of spatially and temporally heterogeneous pattern across social regions in China and is driven by the coupling of multidimensional factors, suggesting that comprehensive strategies need to be developed for effective health poverty management.

ObjectiveTo explore spatiotemporal non-stationarity in health poverty prevalence and its influencing factors among middle-aged and elderly residents in China for providing evidence to promote comprehensive and effective management on health poverty alleviation in the populations. MethodsThe data of the analysis were extracted from four rounds of China Health and Retirement Longitudinal Survey (CHARLS) conducted in 2011, 2013, 2015, and 2018 across China, which collected the information on 37 296 households with family members aged ≥ 45 years. Other relevant data were extracted from the China Statistical Yearbook of 2012, 2014, 2016, and 2019, the China Health and Family Planning Statistical Yearbook of 2012 and 2016, the China Tertiary Industry Statistical Yearbook of 2014 and 2019, and from the Global Burden of Disease Network in 2019. Based on the self-developed indexes for measurement of multidimensional health poverty (MHP), we used the ordinary least squares model (OLS), the geographically weighted regression model (GWR), the temporally weighted regression model (TWR), and the geographically and temporally weighted regression model (GTWR) to model the impacts of influencing factors on health poverty among the middle-aged and elderly residents during the period. The spatiotemporal modes of the estimation coefficients in the optimal model were further described. ResultsAfter adjusting for fixed effects of year and region, the global OLS regression results showed that the MHP index increased with the increment of the prevalence of non-communicable diseases (NCDs) and disabilities, gross domestic production (GDP) per capita, average out-of-pocket medical expenditure, and mean annual concentration of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) in previous 3 years; but the index decreased with the increment of population density, the coverage of basic medical insurance, and the number of nurses per 10 000 population. Among all partial regression models constructed, GWR fitted the survey data best, with the increased R2 from 70.57% to 88.68% and the decreased sum of squares of the residuals from 797.791 to 585.277 compared with the global OLS regression model. The impacts of the eight covariates mentioned above on MHP index were non-stationary based on the results of GWR modeling; the aggravating impact of NCDs prevalence rate on MHP index was much stronger for Inner Mongolia Autonomous Region (Inner Mongolia) and the four provinces including Hebei, Shanxi, Yunnan, and Guizhou; the aggravating impact of disability prevalence rate on MHP index was much more stronger for Jiangsu, Anhui, and Henan province; the alleviating impact of population density on MHP index was stronger for the five provinces of Heilongjiang, Jilin, Liaoning, Shandong, and Shanxi and much more stronger for Inner Mongolia, Gansu and Hebei provinces, and Beijing municipality; both the alleviating impact of the coverage rate of basic medical insurance and the number of nurses versus 10 000 population and the aggravating impact of GDP per capita on MHP index were the strongest for Xinjiang Uygur Autonomous Region, Qinghai province, and Gansu province; the aggravating impact of average out-of-pocket medical expenditure on MHP index was much more stronger for Henan, Anhui and Jiangsu province; the aggravating impact of mean annual PM2.5 concentration in previous 3 years on MHP index attenuated gradually from a central region including Beijing municipality, Hebei province and Inner Mongolia to the surrounding area of whole Bohai rim region. ConclusionThere is a spatial non-stationarity for the impacts of multiple factors on health poverty among middle-aged and elderly residents in China. Partial weighted regression analysis could be adopted to examine the non-stationarity in studies on improving administrative efficiency of regional health poverty reduction.

ObjectiveTo establish an index system with three dimensions of health capacity, right and risk and multidimensional indexes for the measurement of household health poverty. MethodsAn indicator system for evaluating health poverty was preliminary established through reviewing 225 relevant studies published in Chinese or English from 1983 till 2023. Delphi qualitative interview and two rounds of consultation were conducted among 10 senior experts working in regions with higher prevalence of health poverty or better implementation of healthy poverty alleviation to screen the identified indicators. The weights of the selected indicators were calculated using hierarchical analysis and a set of multidimensional health poverty indexes was constructed using the key performance indicator method and the Alkire-Foster method. ResultsFor the two rounds of expert consultation, the positive coefficient was 100% and the authority coefficients were 0.8145 and 0.8667; the coordination coefficients of the experts′ opinions on the second/third level indicators were 0.342/0.233 and 0.487/0.353 for the first and second round of consultation, respectively (all P < 0.05), indicating a good coordination between the expert opinions. According to the results of the expert consultations and qualitative interviews, a health poverty evaluation index system was constructed; the index system includes 3 primary, 11 secondary, 39 tertiary indicators covering the three dimensions (health right, capability and risk) for health poverty measurement; in addition, 10 specific indicators were screened out from all the indicators for the measurement of multidimensional health poverty using key performance indicator method and double threshold method based on Alkire-Foster model. ConclusionThe study establishes the index system and multidimensional indexes for household-based measurement on health poverty and multidimensional health poverty and the index system could provide a reference to the promotion of healthy poverty alleviation in China.

ObjectiveTo examine spatial and temporal distribution patterns of household-based multidimensional health poverty (MHP) indexes among middle-aged and elderly populations in China, and to provide evidence to precise elimination of MHP in the populations. MethodsThe data of the analysis were extracted from four rounds of China Health and Retirement Longitudinal Survey (CHARLS) conducted in 2011, 2013, 2015, and 2018 across China, which collected the information of residents aged ≥ 45 years in 37 296 households on demographics, income and consumption, family structure, economic support, health status, health service utilization and medical insurance. The MHP was assessed and deconstructed with self-established health poverty evaluation index system and multidimensional health poverty measurement index (MHPI) covering three dimensional components (health right, health capability and health risk) of MHP. The year- and region-specific distribution of MHPI were described. ResultsFor all the middle-aged and elderly residents surveyed in 2011, 2013, 2015, and 2018, the health MHPI were 0.320, 0.326, 0.349, and 0.29 and the MHP prevalence were 69.7%, 69.0%, 71.9%, and 63.0%, respectively. The mean values of index measuring the contribution of health right, health capacity and health risk to MHP were 0.143, 0.450 and 0.416 for all the residents surveyed in the four rounds of CHARLS study. The results of regional decomposition analysis on MHPI showed that following six provincial-level administrative divisions (PLADs) could be assessed as with severe prevalence of health poverty in 2011: Guizhou, Gansu, Xinjiang Uygur Autonomous Region (Xinjiang), Sichuan, Anhui, and Jilin, with the mean MHPI of 0.365, 0.364, 0.395, 0.377, 0.402, and 0.413,respectively; in 2013, the six PLADs assessed as having severe prevalence of health poverty were Yunnan, Qinghai, Inner Mongolia Autonomous Region (Inner Mongolia), Sichuan, Anhui, and Guizhou and the mean MHPI for those PLADs were 0.359, 0.361, 0.381, 0.378, 0.389, and 0.402; while in 2015 the number of PLADs with severe prevalence of health poverty increased to 16, including Yunnan (mean MHPI = 0.395), Xinjiang (0.388), Qinghai (0.448), Sichuan (0.406), Inner Mongolia (0.39), Anhui (0.388), Chongqing (0.391), Guizhou (0.373), Tianjin (0.370), Heilongjiang (0.366), Guangxi (0.362), Shandong (0.362), Jiangxi (0.359), Jilin (0.355), Fujian (0.351), and Liaoning (0.350); but in 2018, only 3 PLADs (Sichuan, Guizhou, and Yunnan, with the mean MHPI of 0.352, 0.352, and 0.351) could be assessed as with severe prevalence of health poverty. ConclusionAccording to this analysis, both mean index and prevalence of health poverty declined generally among middle-aged and elderly populations in China during 2011 – 2018; there were regional differences in health poverty prevalence and the multidimensional health poverty was more severe in southwest region.

The border area between Mongolia and Shaanxi is the core area for China’s energy security. However, a large number of mine water produced in the process of coal mining contains a variety of pollution components. Only by finding out the sources and characteristics of pollution components can we deal with and utilize mine water resources more scientifically and reasonably, which is also in line with the requirements of high-quality de-velopment of the Yellow River region. Based on the investigation of the geological, hydrogeological and coal mining disturbance conditions in the border area between Mongolia and Shaanxi, the hydrogeochemical charac-teristics of coal seam roof aquifer and the characteristics of typical pollution components in mine water were studied, and the sources of these typical pollution components were analyzed. The results showed that the border area between Mongolia and Shaanxi was located in the Yishan slope. According to the coal seam buried depth conditions, it could be divided into shallow buried area, medium deep buried area and deep buried area. The mine water in the shallow buried area came from all aquifer water of the coal seam roof, and the mine water in the medium deep buried area came from aquifer water of the Yan’an formation and the Zhiluo Formation (divided into complete bedrock section and weathered bedrock section) of the coal seam roof. The concentration of TDS in the Quaternary and Jurassic groundwater in the shallow buried area and the medium deep buried area was lower than 1 000 mg/L. The mine water in the deep buried area came from the aquifer water of the Jurassic Yan’an Formation and Zhiluo Formation in the roof of the coal seam. The Jurassic aquifer was relatively closed and stagnant. The long-term water rock interaction led to the concentration of TDS in groundwater upper than 1 000 mg/L, and the main exceeding standard components were Na+, Ca2+ and \begin{document}${\rm{SO}}_4^{2-} $\end{document}. The pollution components in mine water included two categories: one was from the roof aquifer water, and the long-term water rock interaction led to the entry of ion components into mine water. The other came from the underground production activities of coal mines. The release of coal cuttings, dust and oil led to the dissolution of suspended solids, nitrogen, organic matter and other pollution into mine water. The concentration of TDS in mine water in the shallow and medium deep buried areas was lower than 1 000 mg/L, which is mainly weakly alkaline HCO3-Ca water, and the main cation and anion (including Na+, Ca2+, Cl−, \begin{document}${\rm{SO}}_4^{2-} $\end{document}) basically did not exceed the standard. The TDS concentration in the mine water in the deep buried area (including the Xiaojihan coal mine) was 1 824.00−3 684.00 mg/L, which was slightly higher than that in the roof water. The increase of Na+ and \begin{document}${\rm{SO}}_4^{2-} $\end{document} ion concentration accounted for the largest proportion, which was mainly due to the further water rock interaction in the goaf. The concentration of COD in mine water of most coal mines exceeded the standard, but the TOC concentration and UV254 value were low, it showed that the organic matter in the mine water was mainly suspended. The 3DEEM spectrum detection results showed that the dissolved organic matter was mainly natural amino acids and humus, the fluorescence intensity of all kinds of organic matter was low, and there were few organic pollutants in mine water.

Abstract Background Standardized patient (SP) simulations are well-recognized patterns for practicing clinical skills and interactions. Our previous study showed that a simulation program using occupational SP for Traditional Chinese Medicine (OSP-TCMs) was efficient, however, a high cost and time-intensive nature have limited its use. TCM postgraduates trained as student SPs (SSP-TCMs) present a potentially cost-effective alternative. The purpose of this study was to examine and determine whether SSP simulation offered more benefits over didactic training alone for improving clinical competency among TCM medical students, and conduct a multifaceted analysis comparing SSP-TCMs and OSP-TCMs. Methods This was a prospective, single-blinded, randomized controlled trial. Fourth-year TCM undergraduates were recruited as trainees from the Clinical Medical School, Chengdu University of TCM. Data were collected from September 2018 to December 2020. Trainees were randomly divided into the three following groups: traditional method training group, OSP-TCM training group, and SSP-TCM training group (1:1:1). At the end of a 10-week curriculum, trainees received a two-station examination comprising a systematic online knowledge test and an offline clinical performance examination. Post-training and post-exam questionnaires were administered to collect feedback from these trainees. Results Students assigned to the SSP-TCM training and OSP-TCM training groups received favorable marks for the “systematic knowledge test” and “TCM clinical skills” (2018, Pa=0.018, Pb=0.042; 2019, Pa=0.01, Pb=0.033; 2020, Pa=0.035, Pb=0.039) compared to the TM trainees. Additionally, trainees in the intervention groups demonstrated a positive post-training edge in scores of “medical records” (2018, Pa=0.042, Pb=0.034; 2019, Pa=0.032, Pb=0.042; 2020, Pa=0.026, Pb=0.03) and “TCM syndrome differentiation and therapeutic regimen” (2018, Pb=0.032; 2019, Pa=0.037, Pb=0.024; 2020, Pa=0.036, Pb=0.043). For the simulation encounter assessment given by SP-TCMs, OSP-TCM trainees and SSP-TCM trainees scored higher than TM trainees (2018, Pa=0.038, Pb=0.037; 2019, Pa=0.024, Pb=0.022; 2020, Pa=0.019, Pb=0.021). For the feedback questionnaires, the students in TM group provided less positive feedback for training efficacy and test performance compared to those in the SSP-TCM and OSP-TCM groups. The trainees responded that the training effect of clinical simulations was similar between the SSP-TCM and OSP-TCM groups. SSP-TCMs were more responsive to unexpected emergencies (Pa=0.022, Pb>0.05) and more likely to encourage questioning (Pa=0.029, Pb>0.05) but tended to provide implied hints (Pc=0.015) and utilize medical jargon (Pc=0.007) as compared to OSP-TCMs. Conclusion Simulation training for SSP-TCMs and OSP-TCMs showed great benefits for enhancing clinical competency. SSP-TCM simulation was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation.

ABSTRACTAlthough changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Abstract Background Air pollution has been identified as related to the diseases of susceptible population, but the spatial heterogeneity of its economic burden and its determinants are rarely investigated. The issue is of great policy significance, especially after the epidemic of COVID-19, when human are facing the joint crisis of health and environment, and some areas is prone to falling into poverty. Methods The geographical detector was adopted to study the spatial distribution characteristics of the incidence of catastrophic health expenditure (ICHE) for older adults in 100 rural areas in China at the prefecture-city level. The health factors, sociological factors, policy factors and environmental factors and their interactions are identified. Results First, most health service factors had strong explanatory power for ICHE whether it interacts with air pollution. Second, 50 single-factor high-risk areas of ICHE were found in the study, but at the same time, there were 21 areas dominated by multiple factors. Conclusion The different contributions and synergy among the factors constitute the complex mechanism of factors and catastrophic health expenditure. Moreover, during this process, air pollution aggravates the contribution of health service factors toward ICHE. In addition, the leading factors of ICHE are different among regions. At the end, this paper also puts forward some policy suggestions from the perspective of health and environment crisis in the post-COVID-19 world: environmental protection policies should be combined with the prevention of infectious diseases; advanced health investment is the most cost-effective policy for the inverse health sequences of air pollution and infectious diseases such as coronavirus disease 2019 (COVID-19); integrating environmental protection policy into healthy development policy, different regions take targeted measures to cope with the intertwined crisis.

Abstract Background China’s medical insurance schemes and poverty alleviation policy at this stage have achieved population-wide coverage and the system's universal function. At the late stage of the elimination of absolute poverty task, how to further exert the poverty alleviation function of the medical insurance schemes has become an important agenda for targeted poverty alleviation. To analyse the risk of catastrophic health expenditure (CHE) occurrence in middle-aged and older adults with vulnerability characteristics from the perspectives of social, regional, disease, health service utilization and medical insurance schemes. Methods We used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database and came up with 9190 samples. The method for calculating the CHE was adopted from WHO. Logistic regression was used to determine the different characteristics of middle-aged and older adults with a high probability of incurring CHE. Results The overall regional poverty rate and incidence of CHE were similar in the east, central and west, but with significant differences among provinces. The population insured by the urban and rural integrated medical insurance (URRMI) had the highest incidence of CHE (21.17%) and health expenditure burden (22.77%) among the insured population. Integration of Medicare as a medical insurance scheme with broader benefit coverage did not have a significant effect on the incidence of CHE in middle-aged and older people with vulnerability characteristics. Conclusions Based on the perspective of Medicare improvement, we conducted an in-depth exploration of the synergistic effect of medical insurance and the poverty alleviation system in reducing poverty, and we hope that through comprehensive strategic adjustments and multidimensional system cooperation, we can lift the vulnerable middle-aged and older adults out of poverty.

To improve the freeze-drying survival rate of Lactobacillus casei LTL1361 in the vacuum freeze-drying process, the single factor and Plackett-Burman designs were first conducted to verify the main factors affecting the freeze-drying survival rate of Lactobacillus casei LTL1361. According to the experimental results, the artificial network coupling genetic algorithm was constructed using the Box Behnken design. The artificial network coupled genetic algorithm (BP-GA) model was constructed to simulate and predict the lyophilized protective agent formulation of Lactobacillus casei LTL1361. The results showed that the three main factors affecting the lyophilisation survival rate of the strain were: Alginate, glutamic acid and mannitol, which were selected by single-factor and Plackett-Burman tests, and the three factors and the base skim milk were identified as the optimisation conditions for subsequent optimisation tests. The BP-GA model was used to find the optimum concentration of protectant for Lactobacillus casei LTL1361, which was 10.3% skim milk, 0.8% glutamic acid, 6.7% alginate and 4.0% mannitol, and the maximum lyophilisation survival rate of the strain was 89.56%. Using the BP-GA model, this study explored a probiotic lyophilisation protectant formulation with a high lyophilisation survival rate, and provided a reference for the preparation of lyophilised formulations of highly active strains and the development of commercial direct-injection ferments.

Altered expression of splicing factors can contribute to tumour progression. Here the authors show that splicing factor BUD31 enhances ovarian cancer progression by promoting exon inclusion in the anti-apoptotic BCL2 family member, BCL2L12.

Brain-inspired deep spiking neural network (DSNN) which emulates the function of the biological brain provides an effective approach for event-stream spatiotemporal perception (STP), especially for dynamic vision sensor (DVS) signals. However, there is a lack of generalized learning frameworks that can handle various spatiotemporal modalities beyond event-stream, such as video clips and 3D imaging data. To provide a unified design flow for generalized spatiotemporal processing (STP) and to investigate the capability of lightweight STP processing via brain-inspired neural dynamics, this study introduces a training platform called brain-inspired deep learning (BIDL). This framework constructs deep neural networks, which leverage neural dynamics for processing temporal information and ensures high-accuracy spatial processing via artificial neural network layers. We conducted experiments involving various types of data, including video information processing, DVS information processing, 3D medical imaging classification, and natural language processing. These experiments demonstrate the efficiency of the proposed method. Moreover, as a research framework for researchers in the fields of neuroscience and machine learning, BIDL facilitates the exploration of different neural models and enables global-local co-learning. For easily fitting to neuromorphic chips and GPUs, the framework incorporates several optimizations, including iteration representation, state-aware computational graph, and built-in neural functions. This study presents a user-friendly and efficient DSNN builder for lightweight STP applications and has the potential to drive future advancements in bio-inspired research.

Abstract Background The high incidence of catastrophic health expenditure (ICHE) among middle-aged and elderly population is a major deterrent for reducing the financial risk of disease. Current research is predominantly based on the assumption of spatial homogeneity of nationwide population characteristics, ignoring the differences in regional characteristics. Thus, our study aimed to explore the impact of various influencing factors on the ICHE from a spatiotemporal perspective. Methods We used data from the China Health and Retirement Longitudinal Study (waves 1 to 4), to conduct a retrospective cohort study across 28 provinces, from 2011 to 2018. We measured regional incidences of catastrophic health expenditure using methods recommended by the World Health Organization. Ordinary least squares (OLS) and geographical and temporal weighted regression (GTWR) were used as the global and local estimation models, respectively. The Fortheringham method was used to test the spatiotemporal non-stationarity. Results National ICHE showed a gradual increase from 2011 to 2015, but suddenly decreased from 2015 to 2018, also showing the spatial heterogeneity. And the southwest area and Hebei showed persistently high ICHE (Qinghai even reached the highest value of 27.5% in 2015). Out-of-pocket payment, gross domestic product, PM2.5, ageing, incidence of non-communicable diseases and disabilities, number of nurses, and health insurance coverage in the global estimation passed the significance test, and the GTWR model showed a better model fit (0.769) than the OLS model (0.388). Furthermore, except for health insurance coverage, all seven variables had spatiotemporal non-stationarity among their impacts on ICHE. Conclusion In this longitudinal study, we found spatiotemporal non-stationarity among the variable relationships, supporting regional governments’ adoption of regional-target policies. First, after the completion of universal health insurance coverage, the spatiotemporal non-stationarity of the prevalence of non-communicable diseases and disability and ageing should be the focus of the next phase of health insurance design, where improvements to compensation coverage and benefit packages are possible policy instruments. Second, the governance and causes of catastrophic health expenditure need to be laid out from a macro perspective rather than only from the individual/household perspective, especially for the potential impact of economic development, air pollution and nursing resources.

Growth and development of hair follicles (HF) is a complex and dynamic process in most mammals. As HF growth and development regulate rabbit wool yield, exploring the role of genes involved in HF growth and development may be relevant. In this study, the coding sequence of the Angora rabbit (Oryctolagus cuniculus) WIF1 gene was cloned. The length of the coding region sequence was found to be 1140 bp, which encodes 379 amino acids. Bioinformatics analysis indicated that the WIF1 protein was unstable, hydrophilic and located in the extracellular region, contained a putative signal peptide and exhibited a high homology in different mammals. Moreover, WIF1 was significantly downregulated in the high wool production in the Angora rabbit group. Overexpression and knockdown studies revealed that WIF1 regulates HF growth and development-related genes and proteins, such as LEF1 and CCND1. WIF1 activated β-catenin/TCF transcriptional activity, promoted cell apoptosis and inhibited cellular proliferation. These results indicate that WIF1 might be important for HF development. This study, therefore, provides a theoretical foundation for investigating WIF1 in HF growth and development.

Abstract Background As the fifth-largest global mortality risk factor, air pollution has caused nearly one-tenth of the world’s deaths, with a death toll of 5 million. 21% of China’s disease burden was related to environmental pollution, which is 8% higher than the US. Air pollution will increase the demand and utilisation of Chinese residents’ health services, thereby placing a greater economic burden on the government. This study reveals the spatial impact of socioeconomic, health, policy and population factors combined with environmental factors on government health expenditure. Methods Spearman’s correlation coefficient and GeoDetector were used to identify the determinants of government health expenditure. The GeoDetector consist of four detectors: factor detection, interaction detection, risk detection, and ecological detection. One hundred sixty-nine prefecture-level cities in China are studied. The data sources are the 2017 data from China’s Economic and Social Big Data Research Platform and WorldPOP gridded population datasets. Results It is found that industrial sulfur dioxide attributed to government health expenditure, whose q value (explanatory power of X to Y) is 0.5283. The interaction between air pollution factors and other factors will increase the impact on government health expenditure, the interaction value (explanatory power of × 1∩× 2 to Y) of GDP and industrial sulfur dioxide the largest, whose values is 0.9593. There are 96 simple high-risk areas in these 169 areas, but there are still high-risk areas affected by multiple factors. Conclusion First, multiple factors influence the spatial heterogeneity of government health expenditure. Second, health and socio-economic factors are still the dominant factors leading to increased government health expenditure. Third, air pollution does have an important impact on government health expenditure. As a catalytic factor, combining with other factors, it will strengthen their impact on government health expenditure. Finally, an integrated approach should be adopted to synergisticly governance the high-risk areas with multi-risk factors.

Measurement(s) 12-lead electrocardiogram Technology Type(s) EKG or ECG Monitor Device

Abstract Objective Middle-aged and older adults are more likely to suffer from chronic diseases because of their particular health characteristics, which lead to a high incidence of catastrophic health expenditure (CHE). This study plans to analyse the different factors affecting CHE in middle-aged and older adults with chronic diseases, target the vulnerable characteristics, and suggest groups that medical insurance policies should pay more attention to. Methods The data used in this study came from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database. The method of calculating the CHE was adopted from the World Health Organization (WHO). The logistic regression was used to determine the family characteristics of chronic disease in middle-aged and older adults with a high probability of incurring CHE. Results The incidence of CHE in middle-aged and older adults with chronic disease was highest in sub-poverty level families (26.20%) was lowest in wealthier level families (20.07%). Households with malignant tumours had the highest CHE incidence under any circumstances, especially if the householder had been using inpatient service in the past year. Among the comparison of CHE incidence in different types of medical insurance, the Urban and Rural Residents’ Basic Medical Insurance (URRBMI) was the highest (27.46%). The incidence of CHE was 2.73 times (95% CI 2.30–3.24) and 2.16 times (95% CI 1.81–2.57) higher among people who had used inpatient services in the past year or outpatient services in the past month than those who had not used them. Conclusions Relatively wealthy economic conditions cannot significantly reduce the financial burden of chronic diseases in middle-aged and older adults. For this particular group with multiple vulnerabilities, such as physical and social vulnerability, the high demand and utilization of health services are the main reasons for the high incidence of CHE. After achieving the goal of lowering the threshold of universal access to health services, the medical insurance system in the next stage should focus on multiple vulnerable groups and strengthen the financial protection for middle-aged and older adults with chronic diseases, especially for patients with malignant tumours.

To explore the potential quantitative relationship between dietary characteristics and physical health indicators of the long-lived population in Guangxi, the longevous in Guangxi (Fengshan County, Donglan County, Shanglin County, Dahua County, and Cenxi City) and some of their descendants were recruited from 2016 to 2018. A semi-quantitative food frequency questionnaire (FFQ) was used to investigate their diet, routine physical examination indicators and blood sample analysis data of the long-lived population were collected, and the weight of the corresponding indicators obtained was calculated by the entropy weight method. Health composite index (HCI) was further introduced to conduct a comprehensive evaluation of health indicators, and stochastic forest regression algorithm was used to model the relationship between volunteers' food and nutrient intake and HCI, to explore the quantitative relationship between each parameter. The results of the model were evaluated by ‘Accuracy’. The results showed that BMI, hemoglobin, triglyceride and C-reactive protein were significantly different in different age groups. There were significant differences in food component intake and nutrient intake among different age groups (P

The meningococcal meningitis (MM) vaccine reduces the incidence of MM significantly; however, outbreaks still occur in communities with high vaccine coverage. We aimed to analyze the driving factors of infection from a community outbreak. A total of 266 children aged 9 to 15 years old from the three junior high schools of Tongzi county were identified. We documented infection cases using laboratory tests and analyzed attack rates, infection rates and risk factors for transmission. The index case in School A was identified, and the attack rate in School A was 0.03%. Children showed a significantly low infection rate of MenC in School A (13.2% vs. 19.5% in total children, p = 0.002), while exhibiting significantly high infection rates of MenA in School B (44.1% vs. 24.8% in total children, p < 0.001) and MenB in School C (11.1% vs. 4.1% in total children, p = 0.015). The infection rate of MenA for females (30.0%) was higher (p = 0.055) than for males (19.9%). In School A, 63.19% of children were vaccinated against MenC, while in School B the rate was 42.65% and in School C, it was 59.26%. Three male MenC infection cases were detected as breakthrough infection cases in addition to the index case. The findings suggest that the current full-course immunization has limited long-term effectiveness and is inefficient in preventing the transmission of MM among older children.

Abstract The recombinase RAD51 catalyzes the DNA strand exchange reaction in homologous recombination (HR) during both mitosis and meiosis. However, the physiological role of RAD51 during spermatogenesis remains unclear since RAD51 null mutation is embryonic lethal in mice. In this study, we generated a conditional knockout mouse model to study the role of RAD51 in spermatogenesis. Conditional disruption of RAD51 in germ cells by Vasa-Cre led to spermatogonial loss and Sertoli cell-only syndrome. Furthermore, tamoxifen-inducible RAD51 knockout by UBC-CreERT2 confirmed that RAD51 deletion led to early spermatogenic cells loss and apoptosis. Notably, inducible knockout of RAD51 in adult mice caused defects in meiosis, with accumulated meiotic double-strand breaks (DSBs), reduced numbers of pachytene spermatocytes and less crossover formation. Our study revealed an essential role for Rad51 in the maintenance of spermatogonia as well as meiotic progression in mice.

Background: Chinese herbal medicine (CHM) has the advantage of being safe and effective and has been widely used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM) with hyperuricemia (HUA), but its overall efficacy and safety remain unclear. This study aimed to evaluate the efficacy and safety of CHM for the treatment of T2DM with HUA based on randomized controlled trials (RCTs) to provide clinical evidence.Methods: The protocol evaluated in this study is registered with PROSPERO (CRD42022351519). As of November 2022, eight databases were searched, and RCTs of CHM for the treatment of T2DM with HUA were included. Outcome indicators observed included fasting blood glucose (FBG), 2-h postprandial glucose (2hPG), glycated hemoglobin (HbA1c), uric acid (UA), triglycerides (TG), total cholesterol (TC), overall effectiveness, and adverse events. Utilizing Review Manager 5.4, Stata V14.0, and GRADEpro, the included studies were evaluated, and the quality of the evidence was determined.Results: 18 RCTs covering 1,311 patients were included in this study. The results of the study demonstrated that the combination of CHM and western medicine (WM) was more effective in treating patients with T2DM with HUA than WM alone, with significant improvements in FBG (weighted mean differences (WMD) = −0.60.95% confidence interval (CI) [−0.81, −0.40], p < 0.00001), 2hPG (WMD = −1.12.95% CI [−1.64, −0.60], p < 0.0001), HbA1c (WMD = −0.80.95% CI [−1.04, −0.56], p < 0.00001), UA (WMD = −53.47.95% CI [−67.45, −39.48], p < 0.00001), TG (WMD = −0.56.95% CI [−0.74, −0.38], p < 0.00001), TC (WMD = −0.49.95% CI [−0.65, −0.33], p < 0.00001), and overall effective rate (risk ratio (RR) = 1.29.95%CI [1.13, 1.48], p = 0.0002). The quality of evidence for all outcomes was low.Conclusion: Compared with WM alone, the combination of CHM and WM was more effective in treating patients with T2DM with HUA, with significant improvements in glucose metabolism, uric acid, and lipids. However, further evaluation by high−quality RCT results is needed due to the low quality and high heterogeneity of the evidence.Systematic Review Registration: [https://systematicreview.gov/], identifier [CRD42022351519].

Abstract Nonsmall cell lung cancer (NSCLC) is one of the most commonly diagnosed and lethal cancers characterized by relatively low overall cure and poor survival rates with great challenge for consistent effective clinical treatment. Here we demonstrated that the antifungal sertaconazole displays potent anti‐NSCLC effect by promoting apoptosis in vitro and in vivo. Further studies found that sertaconazole induces complete autophagic flux, which contributes to sertaconazole‐induced apoptosis and subsequent growth suppression in NSCLC cells. Further studies demonstrated that sertaconazole provokes TNF receptor type 1 associated death domain protein (TRADD) expression via stabilizing it from ubiquitination‐mediated degradation, which results in Akt dephosphorylation and thereby triggers proapoptotic autophagy in NSCLC cells. Moreover, we found that TRADD suppression reverses sertaconazole‐induced proapoptotic autophagy and relieves growth suppression, indicating the vital role of TRADD‐regulated proapoptotic autophagy in the anti‐NSCLC activity of sertaconazole. In summary, our findings suggest that sertaconazole could be a highly promising anti‐NSCLC drug by triggering proapoptotic autophagy via stabilizing TRADD, which may provide a new potential therapeutic option for patients with NSCLC.

Introduction: Anal fistula is one of the commonest ailments seen by anorectal surgeons as surgery is currently the preferred treatment for it. Diabetes mellitus is a risk factor that can lead to slow wound healing after anal fistula surgery. Because of the large postoperative wound surface of anal fistula, patients with diabetes can have an increased probability of wound infection, which makes it hard to heal. There is an extensive clinical experience for wound healing in traditional Chinese medicine (TCM). The Jiedu Shengji decoction (JSD) is a widely used external washing decoction in clinical practice. However, the current evidence on it is still insufficient. Therefore, we report this carefully designed clinical trial to assess the efficacy and safety of JSD in the treatment of postoperative wounds in diabetic patients with anal fistula.Methods and analysis: This study was designed to be a randomized, double-blind, placebo-controlled, multi-center clinical trial. There were 60 eligible participants who were randomized at a 1:1 ratio to the intervention and placebo groups. Both groups received the same standard treatment. The intervention group was given external washing decoction of TCM (JSD), while the placebo group was given the placebo made of excipients and flavoring agents. The main outcome measures include wound healing, distribution of wound pathogens, levels of inflammatory mediators, and blood glucose. The secondary outcome measures included lipids, the quality of the life evaluation scale (Short-Form Health Survey 36). Assessments were performed before the start of the study, at 1st, 2nd, 3rd, and 4th weeks after the intervention, and at 8th, 12th, and 16th follow-up weeks.Discussion: The clinical study we proposed will be the first randomized, double-blind, placebo-controlled, multi-center clinical trial study to assess the efficacy and safety of TCM external washing (JSD) in the treatment of postoperative wounds in diabetic patients with anal fistula.Ethics and dissemination: The Medical Ethics Committee of Hospital of Chengdu University of Traditional Chinese Medicine has reviewed this study protocol and gave its approval and consent on 17 March, 2022 (Ethical Review Number: 2022KL-018).

The use of upper limb rehabilitation robots to assist the affected limbs for active rehabilitation training is an inevitable trend in the field of rehabilitation medicine. In particular, the active motion intention-based control of the upper limb rehabilitation robots to assist subjects in rehabilitation training is a hot research topic in human-computer interaction control. Therefore, improving the accuracy of active motion intention recognition is the premise of the human-machine interaction controller design. Furthermore, there are external disturbances (bounded/unbounded disturbances) during rehabilitation training, which seriously threaten the safety of subjects. Thereby, eliminating external disturbances (especially unbounded disturbances) is the difficulty and key to the human-machine interaction control of the upper limb rehabilitation robots. In response to these problems, based on the surface electromyogram signal of the human upper limb, this paper proposes a fuzzy neural network active motion intention recognition method to explore the internal connection between the surface electromyogram signal of the human upper limb and active motion intention, and improve the real-time and accuracy of recognition. Based on this, two types of human-machine interaction controllers, which can be called as zeroing neural network controller and noise-suppressing zeroing neural network controller are designed to establish a safe and comfortable training environment to avoid secondary damage to the affected limb. Numerical experiments verify the feasibility and effectiveness of the proposed theories and methods.

BackgroundMicroplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational cross-sectional study focusing on the effects of microplastics on the nasal and gut microbiota in a highly exposed population.MethodsWe recruited 20 subjects from a Plastic Factory (microplastics high-exposure area) and the other 20 from Huanhuaxi Park (microplastics low-exposure area) in Chengdu, China. We performed the microplastic analysis of soil, air, and intestinal secretions by laser infrared imaging, and microbiological analysis of nasal and intestinal secretions by 16S rDNA sequencing.ResultsThe result shows that the detected points of microplastics in the environment of the high-exposure area were significantly more than in the low-exposure area. Polyurethane was the main microplastic component detected. The microplastic content of intestinal secretions in the high-exposure group was significantly higher than in the low-exposure group. Specifically, the contents of polyurethane, silicone resin, ethylene-vinyl acetate copolymer, and polyethylene in the high-exposure group were significantly higher than in the low-exposure group. Moreover, high exposure may increase the abundance of nasal microbiotas, which are positively associated with respiratory tract diseases, such as Klebsiella and Helicobacter, and reduce the abundance of those beneficial ones, such as Bacteroides. Simultaneously, it may increase the abundance of intestinal microbiotas, which are positively associated with digestive tract diseases, such as Bifidobacterium, Streptococcus, and Sphingomonas, and reduce the abundance of intestinal microbiotas, which are beneficial for health, such as Ruminococcus Torquesgroup, Dorea, Fusobacterium, and Coprococcus. A combined analysis revealed that high exposure to microplastics may not only lead to alterations in dominant intestinal and nasal microbiotas but also change the symbiotic relationship between intestinal and nasal microbiotas.ConclusionThe results innovatively revealed how microplastics can affect the intestinal and nasal microecosystems.Clinical trial registrationChiCTR2100049480 on August 2, 2021.

BackgroundCurrently, breast cancer (BC) is ranked among the top malignant tumors in the world, and has attracted widespread attention. Compared with the traditional analysis on biological determinants of BC, this study focused on macro factors, including light at night (LAN), PM2.5, per capita consumption expenditure, economic density, population density, and number of medical beds, to provide targets for the government to implement BC interventions.MethodsA total of 182 prefecture-level cities in China from 2013 to 2016 were selected as the sample of the study. The geographically and temporally weighted regression (GTWR) model was adopted to describe the spatiotemporal correlation between the scale of BC and macro factors.ResultsThe results showed that the GTWR model can better reveal the spatiotemporal variation. In the temporal dimension, the fluctuations of the regression coefficients of each variable were significant. In the spatial dimension, the positive impacts of LAN, per capita consumption expenditure, population density and number of medical beds gradually increased from west to east, and the positive coefficient of PM2.5 gradually increased from north to south. The negative impact of economic density gradually increased from west to east.ConclusionThe fact that the degree of effect of each variable fluctuates over time reminds the government to pay continuous attention to BC prevention. The spatial heterogeneity features also urge the government to focus on different macro indicators in eastern and western China or southern and northern China. In other words, our research helps drive the government to center on key regions and take targeted measures to curb the rapid growth of BC.

The optimal preventive maintenance timing of traditional asphalt pavement is based on the maximum benefit-cost ratio. For cost evaluation indicators, mainly agency cost and user cost, use life cycle cost analysis (LCCA) to determine. The environmental impact of pavement preventive maintenance activities is often overlooked. For the benefit evaluation index, only the new area under the performance curve is used to express the maintenance benefit, and the benefit evaluation index is single. This study proposes an integrated approach combining life cycle assessment (LCA) and LCCA to model preventive maintenance timing decisions considering economic, social, and environmental factors. In this paper, LCA is used to quantitatively analyze the energy consumption and emissions in the pavement operation and maintenance process, and the environmental costs are also included in the accounting scope of the costs. The costs that constitute pavement use are analyzed from three aspects: the agency cost, the user cost, and the environmental cost. At the same time, in the process of constructing the cost model, the costs caused by the maintenance construction process to users and the environment are also taken into consideration. Aiming at the benefit index and comprehensively considering the economic benefits, social benefits, and environmental benefits brought by maintenance, a comprehensive evaluation model of maintenance benefits was constructed based on the analytic hierarchy process (AHP). On the basis of accurately calculating the cost and benefit of maintenance in the life cycle, the model of the optimal preventive maintenance timing of asphalt pavement is constructed so as to calculate the optimal timing of preventive maintenance and provide certain information for the formulation of expressway pavement preventive maintenance programs. For reference. Taking a highway project in China as an example to verify the applicability of the model

As an infrastructure project, the cost and benefits of road maintenance should be measured through social costs. In order to fully consider user interests and make road maintenance decisions more reasonable, two types of user costs that may affect road maintenance benefits have been quantified through analysis of existing literature. At the same time, environmental issues have gradually become the focus of various industries, and in optimizing road maintenance decisions, the impact of environmental issues on decision making should also be considered. This article first analyzes and quantifies the user costs that affect the effectiveness of road maintenance. Secondly, based on the concept of sustainable development of roads, the optimization of road maintenance decisions is divided into two steps: the first step is to determine the minimum maintenance budget funds, and the second step is to determine the optimal plan. The specific optimization method is to use the 0-1 mathematical programming method to establish a network-level pavement maintenance decision optimization model based on a quantitative model. The most reasonable maintenance optimization plan is determined from four aspects: maintenance funds, maintenance performance improvement value, user benefit improvement, and reducing environmental impact. Finally, a provincial road network for a case study is selected. The applicability of the new model is verified through a case study. This study can help decision makers deal with asphalt pavement maintenance arrangements at the network level with four decision objectives: maintenance funds, pavement performance, road users, and environmental impacts.

Abstract Background To explore the psychological status and vulnerability characteristics of medical staff with the progress of the epidemic. Methods This study investigated the prevalence of mental problems of 2748 medical staff in four stages. The PHQ-9 (Patient Health Questionnaire), GAD-7 (Generalized Anxiety Disorder questionnaire), SSS (Somatization Symptom Checklist), Pittsburgh sleep quality index, and PCL-C (Self-rating scale for post-traumatic stress disorder) were used for the psychological evaluation, and univariate logistic standardised analysis, and multivariate logistic regression for data analysis. Results The prevalence of mental problems showed a statistically significant difference. In Stage 1, mild anxiety and mild depression reached the highest value of 41.4 and 40.72% respectively. Between 4 and 17 March that of mild depression rose from 16.07 to 26.7%, and between 17 and 26 March the prevalence of mild anxiety increased from 17.28 to 20.02%. Female, unmarried, and working in Wuhan are the risk factors of mental health of medical staff (P

Freeze‒thaw (FT) erosion has gradually become more severe due to climate warming, and concerns about FT erosion in ecologically fragile areas (e.g., high-altitude and high-latitude areas) continues to grow. Tibet, located at the Third Pole of Earth, is also in a substantial part underlain with seasonally frozen soil and subject to FT erosion. Evaluating the sensitivity and influential factors of FT erosion in Tibet is warranted to manage the ecological environment and human production activities. In this study, we investigated the sensitivity and spatial distribution characteristics of FT erosion in Tibet based on advanced remote sensing and geographic information system (GIS) technologies. To further explore the influence of each factor on FT erosion, we analyzed the sensitivity of FT erosion under each factor condition. Our results showed that the annual temperature range is the most influential factor on FT erosion among temperature, precipitation, topography and vegetation. In addition, we introduced the coefficient of variation (CV) to represent the stability of temperature and then used CMIP5 simulation data to estimate the susceptibility of FT erosion in Tibet over the next 30 years. The CVs in central and western Tibet were higher than those in other areas and thus need more attention to FT erosion in central and western Tibet in the future.

BackgroundThere are huge differences in female breast cancer mortality between urban and rural China. In order to better prevent breast cancer equally in urban and rural areas, it is critical to trace the root causes of past inequities and predict how future differences will change. Moreover, carcinogenic factors from micro-individual to macro-environment also need to be analyzed in detail. However, there is no systematic research covering these two aspects in the current literature.MethodsBreast cancer mortality data in urban and rural China from 1994 to 2019 are collected, which from China Health Statistical Yearbook. The Age-Period-Cohort model is used to examine the effects of different age groups, periods, and birth cohorts on breast cancer mortality. Nordpred project is used to predict breast cancer mortality from 2020 to 2039.ResultsThe age effect gradually increases and changes from negative to positive at the age of 40–44. The period effect fluctuates very little and shows the largest difference between urban and rural areas in 2019. The birth cohort effect gradually decreases with urban-rural effects alternating between strong and weak. In the predicted results, the urban-rural mortality gap becomes first narrow and then wide and shows a trend of younger death.ConclusionsFrom the perspective of a temporal system, the changing trend of breast cancer mortality is highly consistent with the history of social and economic structural changes in China. From the perspective of the theory of social determinants of health, individuals, families, institutions and governments need to participate in the prevention of breast cancer.

In order to reveal the response characteristics of total dissolved solids (TDS) increase to groundwater level decline and the main chemical components that drive TDS to increase in the core area of the groundwater level funnel in the Hufu piedmont plain, geological statistical analysis, time series variation analysis and GIS spatial feature analysis technology are applied to analyze the variation characteristics of groundwater level depth, TDS and chemical compositions in the study area in the past 50 years (1972-2017). The results show that (1) the increase of TDS is characterized by stages along with the decrease of groundwater levels. In the initial stage of the funnel formation (1972-1980), the annual decrease of groundwater levels was the largest, and the annual increase of groundwater TDS was also the largest. In the middle period (1981-2000), the average annual decrease of groundwater level was the lowest, and the average annual increase of groundwater TDS was also the lowest. At the end of the period (2001-2017), the average annual decline of groundwater level was in the middle, and the average annual increase of groundwater TDS was also in the middle. (2) The influence of groundwater level on the increasing TDS presents a decreasing effect with the increase of the depth of groundwater level. For each increase of groundwater level of 1.0 m, the average growth rate of groundwater TDS increased by 21.96 mg/L at the initial stage of the funnel formation (the groundwater level buried depth ranged from 9.10 m to 23.20 m), the average growth rate of groundwater TDS increased by 13.54 mg/L at the middle stage (the groundwater level buried depth ranged from 13.40 m to 42.28 m), and the average growth rate of groundwater TDS increased by 12.32 mg/L at the end stage (the groundwater level buried depth ranged from 21.41 m to 50.29 m). (3) The increase of concentrations of Na+ and \begin{document}${\rm{SO}}_4^{2-} $\end{document} in groundwater is the main reason for the increase of TDS in the funnel core area. From the initial stage to the final stage of the funnel formation, with the increasing depth of groundwater level and TDS, the ratio of the increment of Na+ and \begin{document}${\rm{SO}}_4^{2-} $\end{document} in groundwater to the increment of TDS in each stage shows an increasing characteristic. However, the total ratio of the increment of Ca2+, Mg2+, \begin{document}${\rm{HCO}}_3^- $\end{document} and Cl− contents in the final stage to the increment of TDS is still 65.88%, which still plays a crucial role in the increasing of groundwater TDS in the funnel core area.

Abstract Aberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

Abstract Background The vulnerability of cardiovascular disease (CVD) patients’ health abilities, combined with the severity of the disease and the overlapping risk factors, leads such people to bear the economic burden of the disease due to the medical services. We estimated the economic burden of CVD and identified the weak link in the design of the medical insurance. Methods Data from 5610 middle-aged and elderly with CVD were drawn from the 2015 wave of “China Health and Retirement Longitudinal Study” (CHARLS). The recommended method of the “World Health Organization” (WHO) was adopted to calculate “catastrophic health expenditure” (CHE), “impoverishment by medical expenses” (IME), and applied the treatment-effect model to analyze the determinants of CHE. Results The incidence of CHE was 19.9% for the elderly families with CVD members, which was 3.6% higher than for uninsured families (16.3%). Families with CVD combined with > 3 other chronic diseases (38.88%) were the riskiest factor for the high CHE in the new rural cooperative medical system (NCMS). Moreover, families with members > 75 years old (33.33%), having two chronic disease (30.74%), and families having disabled members (33.33%), hospitalization members (32.41%) were identified as the high risky determinants for the high CHE in NCMS. Conclusions Elderly with physical vulnerabilities were more prone to CHE. The medical insurance only reduced barriers to accessing health resources for elderly with CVD; however it lacked the policy inclination for high-utilization populations, and had poorly accurate identification of the vulnerable characteristics of CVD, which in turn affects the economic protection ability of the medical insurance. The dispersion between the multiple medical security schemes leads to the existence of blind spots in the economic risk protection of individuals and families.