ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective To observe the effects of Angelicae Sinensis Radix-Paeoniae Radix alba combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on liver inflammation and hepatocytes regeneration in non-alcoholic steatohepatitis(NASH)associated cirrhosis;To discuss its possible mechanism.Methods West diet combined with carbon tetrachloride was used to prepare the NASH related cirrhosis model.The mice were randomly divided into control group,model group,Angelicae Sinensis Radix-Paeoniae Radix alba group,BM-MSCs group,and Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,with 12 mice in each group.After successful modeling,corresponding interventions were given according to grouping for 4 consecutive weeks.HE staining was used to observe the morphology of liver tissue;the contents of serum ALT,AST,TBil,TG,ALB,AFP,as well as the contents of IL-1β,TNF-α and HGF in liver tissue were detected;RT-qPCR was used to detect TLR9,MyD88,TRAF6 and NF-κBp65 mRNA expression in liver cells;primary liver cells were separated,CpG ODN 2216 stimulation was induced in vitro,cells supernatant was extracted,and IL-1β and TNF-α content were detected.Results Compared with the control group,inflammatory cell infiltrated in liver tissue of model group mice,accompanied by hepatocyte necrosis and collagen deposition,forming pseudo lobules;the contents of serum ALT,AST,TBil and TG increased,the content of ALB decreased,the content of HGF in liver tissue decreased,the contents of IL-1β and TNF-α increased,with statistical significance(P<0.05);the mRNA expressions of TLR9,MyD88,TRAF6 and NF-κBp65 in liver cells increased(P<0.05),and the contents of IL-1β and TNF-α in cells supernatant increased after CpG ODN 2216 induction(P<0.05).Compared with the model group,the inflammatory infiltration in liver tissue and necrosis of liver cells were reduced and the degree of liver fibrosis was alleviated in the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,the liver tissue damage in Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group were slightly improved;except for the TG content in BM-MSCs group,all detection indicators showed significant improvement in each intervention group(P<0.05).Compared with the Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group,the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group showed statistical significance in related detection indicators(P<0.05),and demonstrated a synergistic effect.Conclusion Angelicae Sinensis Radix-Paeoniae Radix alba combined with BM-MSCs transplantation could effectively improve the liver function and promote liver cell regeneration.The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expressions and function,the inhibition of inflammatory cytokines secretions,and the improvement of liver inflammatory microenviroment.

BACKGROUND: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue. METHODS: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M–CS) for the treatment of fullthickness skin wounds in mice. RESULTS: Experiments confirmed that there is cell–cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell–cell talk also upregulates the gene expression of proangiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components. CONCLUSIONS Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Background The safety of drinking water is closely related to people's health. In recent years, relevant studies have identified some health related problems with drinking water in Inner Mongolia Autonomous Region. The complex and diverse natural environment embraced by the vast jurisdiction of the region may lead to uneven drinking water quality across the region. Objective To evaluate eight chemicals including arsenic, cadmium, chromium (hexavalent), lead, mercury, fluoride, trichloromethane, and carbon tetrachloride in urban drinking water in Inner Mongolia Autonomous Region in 2021, and to provide reference for optimizing urban water supply system and ideas for further developing strategies to promote population health. Methods A total of 1228 monitoring sites were set up in urban areas of Inner Mongolia, and water samples were collected once in dry season (May) and once in wet season (August−September). Eight chemicals of interest in drinking water were detected according to the Standard examination methods for drinking water, and assessed for health risks using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA) and following the Technical guide for environmental health risk assessment of chemical exposure. Mann-Whitney U test was used to compare the concentrations of eight chemicals in urban drinking water by water seasons and water sample types. Results In 2021, a total of 2381 samples of urban drinking water were tested in the Inner Mongolia Autonomous Region, including 1195 samples in wet season and 1186 samples in dry season; 389 samples of finished water and 1992 samples of tap water. The positive rates of arsenic and fluoride were 26.25% and 96.77%, respectively. The positive rates of cadmium, chromium (hexavalent), lead, mercury, trichloromethane, and carbon tetrachloride were 6.22%, 16.63%, 6.09%, 16.67%, 18.98%, and 8.36%, respectively. The exceeding standard rate of fluoride was 4.87%. Trichloromethane and carbon tetrachloride were qualified in all samples. There were statistical differences in the concentrations of arsenic, cadmium, chromium (hexavalent), lead, and carbon tetrachloride in urban drinking water between water seasons (Z=−3.847, P<0.05; Z=2.464, P=0.014; Z=−3.129, P=0.002; Z=4.341, P<0.05; Z=4.342, P<0.05). Only fluoride concentration was found statistically different among different water sample types (Z=−2.287, P=0.022). The non-carcinogenic risks of ingestion and dermal exposure to each chemical in drinking water by water seasons and water sample types were all less than 1, but the P₉₅ total non-carcinogenic risks of oral exposure were greater than 1. The P₉₅ carcinogenic risks of oral exposure to some chemicals in drinking water by water seasons and water sample types were>10⁻⁴, which suggested carcinogenic risks, while the carcinogenic risks of dermal explore to chemicals were all less than 10⁻⁶. Conclusion In 2021, urban drinking water in Inner Mongolia Autonomous Region is generally safe, but arsenic, cadmium, chromium (hexavalent), lead, mercury, and fluoride still exceed the national limits, posing certain health risks.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61;95% confidence interval [95% CI], −2.44 to −0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

Objective: To clarify the importance and practical significance of the standardized rate in primary healthcare work by comparing the differences in the prevalence of myopia in districts in Beijing before and after standardization. Methods: This study recruited a total of 41 029 students from 107 primary and secondary schools and 35 kindergartens from the 16 districts of Beijing municipality. All participants underwent distance vision and refractive testing. The presence of myopia was defined as naked eye vision of <5.0 and non-ciliary muscle paralysis under computer optometry with a spherical equivalent objective refractive error of <-0.50 diopters (<-0.50 D). The student composition outlined in the 2018-2019 Beijing Education Development Statistics Summary was used as a standard group to standardize the prevalence of myopia in students from various districts of Beijing. The difference in the pre-and post-standardization rates was used to compare the change in myopia in each district before and after standardization. Results: In 2018, the prevalence of myopia in students from Beijing was 57.3%. Stratified by school period, the prevalence of myopia in preschool, primary school, junior high school, ordinary high school, and vocational high school students was 12.1%, 38.4%, 77.2%, 88.3%, and 73.1%, respectively. Although the prevalence of myopia in Daxing District was the highest both before and after standardization, the difference in the prevalence rate was 13.8 percentage points. The prevalence of myopia in Miyun District was the lowest before standardization. However, after standardization, the prevalence of myopia was lowest in Huairou District. Conclusion The prevalence of myopia among Beijing students is generally high. Before and after standardization, the prevalence of myopia in different districts was quite different. The results show that, in practice, the standardized prevalence can reveal the true epidemiological characteristics of specific disease.

Objective: To understand the current situation of tobacco use in primary and secondary school staff members in Beijing in 2019, and its association with adolescent tobacco use and exposure, in order to promote the construction of smoke-free schools. Methods: During April to June in 2019，PPS sampling was used to select primary schools, secondary schools and vocational high school. Each selected school randomly investigates 20 faculty members, totalling 2 737. The monitoring contents mainly include the current tobacco use, knowledge and attitude towards health risk of smoking among the school staff. Results: The faculty did not receive the training of adolescent tobacco control (OR=0.20,95%CI=0.14-0.28) were only 20% likely to teach tobacco hazard knowledge compared to the trained staff, and refusal to use tobacco control instruction manual (OR=0.21,95%CI=0.14-0.32) was negatively associated with teaching tobacco control with students. Staff members having given lectures on tobacco refusal were more inclined to uphold "any people can t smoke anywhere on campus "(98.53%), and the interpretation of the rules tends to be more clear. Staff who has been employed for 20-30 years (OR=3.35,95%CI=2.22-5.05) were the most probably to preach tobacco control among students(P＜0.05). Conclusion Staff caring about health and participate actively in health training were more willing to spread health knowledge. More attention should be paid to the cultivation of health literacy of school staff, and proactively guide faculty unwilling to instruct students in health hazard of smoking to gradually realize the importance of adolescent tobacco control.

Objective: To understand current situation of e cigarette use and associated factors in primary and secondary school students in Beijing, in order to promote the construction of smoke free schools. Methods: During April to June in 2019, PPS sampling was used to select primary schools, secondary schools and trade schools. In each selected school, randomly sampling method was conducted until the sample size was reached. There were 18 312 students included in the analysis. Surveillance information mainly included the current situation of electronic cigarette use and associated factors. Results: Among primary and secondary school students who have known about e cigarettes, female students were less likely to use e cigarettes than male students ( OR = 0.47 , 95% CI =0.42- 0.54 ). After entering the second year of junior high school, the possibility of using e cigarettes increased. Smoke free home was associated less e cigarettes usage ( OR =0.78, 95% CI =0.69-0.88). Primary and secondary school students with average daily allowance of 30~<150 yuan and no less than 150 yuan were 1.43 (95% CI =1.22-1.67) times and 2.24 (95% CI =1.79-2.79) times more likely to use e cigarettes than those with 0-10 yuan allowance, respectively. The probability of using e cigarettes among primary and secondary school students who have not tried using cigarettes was only 16.4% compared with those who have tried cigarettes ( OR =0.16, 95% CI =0.14-0.19). Conclusion It is necessary to curb the prevalence of e cigarettes among primary and secondary school students. Actions need to be taken urgently to fill in the gaps or correct the mistakes in children and adolescents cognition of e cigarettes, and to adopt more innovative methods to scientifically guide children and adolescents to stay away from e cigarettes.

Objective:To explore the learning guidance model and its influencing factors of undergraduates in medical schools.Methods:Based on the developmental learning guidance theory, 1 117 undergraduates from two undergraduate medical universities were selected as the research objects, through questionnaire surveys to collect their knowledge learning, curriculum learning and other core variables, and balanced guidance, compound guidance and other outcome variables, using Smart PLS 3.0 to test the validity of the samples.Results:There were statistical significance in the path relationship affecting the core variables and the outcome variables of the learning guidance model, P<0.05, indicating that the influencing factors of the learning guidance model had a significantly positive effect on the learning guidance model construction. Conclusion:Constructing a "balanced-compound-special" learning guidance model suitable for undergraduates' learning activities in medical universities provides a reference for the application and promotion of learning guidance model in medical undergraduate stage.