Objective: To investigate the prevalence of undernutrition and its associated factors among left behind and non left behind primary and secondary school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) areas of central and western China, so as to provide evidence for improving the nutritional status of children and adolescents. Methods: A survey was conducted among 123 782 students selected by random cluster sampling method in grades 3-9 from NIPRCES in central (Hebei, Shanxi, Heilongjiang, Jilin, Anhui, Jiangxi, Henan, Hunan, Hubei, and Hainan) and western (Gansu, Guangxi, Inner Mongolia, Ningxia, Tibet, Shaanxi, Guizhou, Sichuan, Xinjiang, the Xinjiang Production and Construction Corps, Yunnan, Qinghai, and Chongqing) China in 2023. Anthropometric measurements and questionnaires were used to assess nutritional and dietary status. The prevalence of undernutrition was compared between left behind and non left behind students by Chi square test, and associated factors were analyzed by three level Logistic mixed effects model. Results: The prevalence of undernutrition was 8.5% (4 326) in left behind students and 8.1% (5 905) in non left behind students. Three level Logistic mixed effect model analysis showed that whether left behind or non left behind, the undernutrition rates of primary and secondary students in western regions were higher than those of students in central regions [ OR (95% CI )=1.72(1.57-1.87),2.25(2.07- 2.43 )]; the undernutrition risk was lower for those whose fathers had a cultural level of high school or above [ OR (95% CI )=0.69(0.62-0.77),0.90(0.82-0.98)] or junior high school [ OR (95% CI )=0.72(0.66-0.79),0.92(0.85-0.99)] compared to those with primary school or below; picky eating or selective eating increased the risk of undernutrition [ OR (95% CI )=2.36(2.07-2.68),2.28(2.04-2.55)], and primary and secondary school students without nutritional content in health education classes had higher rates of undernutrition [ OR (95% CI )=1.12(1.03-1.23),1.09(1.01-1.17)](all P <0.05). Conclusion The prevalence of undernutrition is slightly higher in left behind primary and secondary students than in non left behind primary and secondary students in central and western NIPRCES areas, with variations across different characteristics.

Objective: To analyze the trends of the frequency of meat, egg, and milk consumption among rural primary and junior high school students in central and western China covered by the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) from 2015 to 2023, so as to provide basis for formulating more targeted nutrition intervention policies and health education strategies. Methods: Using data from six rounds of monitoring and evaluation (2015-2021 and 2023), the study included 323 870 students from grade 3 to 9 across 22 provinces (autonomous regions and municipalities) in central and western China. The consumption frequencies of meat, egg, and milk over the past week were collected via questionnaires. The Cochran-Armitage trend test was used to analyze temporal trends, and multivariable Logistic regression models were employed to analyze factors associated with the frequency of meat, egg and milk consumption and to test for interaction effects between the year and gender, region, and grade level. Results: From 2015 to 2023, the proportion of students consuming meat, egg, and milk ≥1 time/day increased from 23.20 %, 10.71%, and 0.74% to 35.53%, 22.09%, and 26.63%, respectively. Trend tests indicated a significant upward trend for the daily intake of all three food categories for meat, egg and milk over the years ( Z =67.18, 64.90, 93.14, all P <0.01). Multivariable Logistic regression analysis showed that the daily meat intake was lower in the central region than in the western region ( OR=0.77, 95%CI =0.76-0.78), whereas the daily intake of eggs ( OR=1.19, 95%CI =1.17-1.22) and milk ( OR= 1.27 , 95%CI =1.24-1.29) was higher in the central region (all P <0.05). Compared with grade 3-4 students, junior high school students had lower daily intake of meat, eggs, and milk≥1 time/day ( OR =0.95, 0.77, 0.77, all P <0.05), with a declining trend as grade increased. Girls also had lower daily intake of meat, eggs, and milk ≥1 time/day than boys ( OR =0.95，0.93，0.91, all P < 0.05). Significant interactions were observed between year and region, as well as between year and grade (all P <0.05). Conclusion From 2015 to 2023, the NIPRCES improved the intake level of among rural students, but the situation of relatively insufficient intake of egg and milk among females, junior high school students and those in the western region still exists.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

BACKGROUND:Osteoarthritis is a common degenerative joint disease,and the etiology and development of its pathogenesis are still unclear.Timely diagnosis and treatment of early osteoarthritis are crucial,and there is currently no definite and effective method.Extracellular vesicles come from a wide range of sources,including non-coding RNAs such as small RNAs,circular RNAs,and long chain non-coding RNAs.Extracellular vesicles non-coding RNAs can be directly delivered from primitive cells to neighboring or remote cells,regulating cell activity through intercellular communication and playing an important regulatory role in reshaping the bone and joint microenvironment.OBJECTIVE:To summarize the intervention effects of exosome-derived non-coding RNAs on the joint microenvironment of osteoarthritis and the progress made in clinical application,and to clarify the potential of exosome-derived non-coding RNAs in the diagnosis and treatment of osteoarthritis.METHODS:Search terms "exosomes,non-coding RNA,osteoarthritis,application,signal pathway,synovial fluid,cartilage cells,cartilage matrix,subchondral,mechanism" were used for the search on PubMed database.Finally,66 related articles were included for review analysis.RESULTS AND CONCLUSION:(1) Exosome-derived non-coding RNAs play an important regulatory role in the joint microenvironment during the pathogenesis of osteoarthritis,mainly reflected in:exosome non-coding RNAs regulating the inflammatory response in the joint,degeneration of chondrocytes and cartilage matrix,subchondral bone remodeling,and intercellular communication.(2) The non-coding RNAs in exosomes can serve as biomarkers for osteoarthritis,aiding in the early diagnosis and monitoring of disease progression and prognosis.(3) Exosome non-coding RNAs serve as therapeutic targets for osteoarthritis.Exosomes carry miRNAs to the articular chondrocytes and cartilage matrix to play a regulatory role.(4) Exosomes non-coding RNAs can improve the effect of cartilage tissue engineering by regulating gene expression and promoting intercellular communication to repair or regenerate damaged cartilage.(5) In future research,researchers should continue to explore the intervention mechanism of non-coding RNAs derived from exosomes on osteoarthritis,and apply them to clinical practice in combination with the latest research outcomes in cartilage tissue engineering,which will effectively help solve the pain of osteoarthritis patients.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

OBJECTIVE To establish skin contamination models with sulfur mustard analogue 1-chloro-2-ethylsulfanyl ethane(CEES),and evaluate the therapeutic efficacy of reactive skin decontamination lotion kit(RSDL).METHODS ①Kunming,BALB/c,BALB/c-nu,and C57BL/6N were contaminted with CEES 75 μL·kg-1 using exposed method and covered method for 10 min on the dorsal skin.Wound healing times and areas were assessed to determine the stock of mice and exposure method.② BALB/c mice were exposed to a gradient of CEES at the doses of 75,150,250,350 and 500 μL·kg-1(10 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were used to determine the optimal dose.③ BALB/c mice were exposed to CEES 150 μL·kg-1 for varying durations(5,10 and 20 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were analyzed to determine the optimal exposure time.④ BALB/c mice were divided into four groups:control(exposed with the covered method at 150 μL·kg-1,10 min),treatment(20 μL RSDL treatment after exposure,as the control group),5 min treatment(20 μL RSDL treatment after 5 min of exposure,followed by 5 min of coverage)and immediate-treatment(exposed with the exposed method at 150 μL·kg-1,immediately treated with 20 μL RSDL,followed by 10 min of coverage).The therapeutic efficacy was evaluated based on the wound area,subcutaneous microvesicle count,epidermal thick-ness,and inflammatory cytokine(IL-6 and TNF-α)expressions.RESULTS ① The covered method caused more severe and prolonged wounds than the exposed method.BALB/c mice exhibited a high sensitivity to CEES with delayed wound healing and were therefore selected as the model animal.② Survival rates in BALB/c mice dropped below 50%at doses of 250,350 and 500 μL·kg-1,whereas an 83.3%survival rate was observed at 150 μL·kg-1.③ The mice exposed to CEES(150 μL·kg-1,20 min)died within 3 days.The wound area was consistently smaller in the 5 min covered group than in the 10 min covered group.④CEES-induced skin injury led to epidermal nuclear pyknosis,follicular disrup-tion,inflammatory infiltration,and microvesicle formation in both treatment and poisoned control groups.As more immediate treatment,the wound area significantly decreased.While the IL-6 expres-sion showed no significant intergroup difference,the TNF-α expression was significantly higher in the treatment group.CONCLUSION A CEES-induced skin contamination model has been established in BALB/c mice using the covered method(150 μL·kg-1,10 min covered).However,RSDL should be ad-ministered in 10 min post-contamination.

Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

BACKGROUND:Osteoarthritis is a common degenerative joint disease,and the etiology and development of its pathogenesis are still unclear.Timely diagnosis and treatment of early osteoarthritis are crucial,and there is currently no definite and effective method.Extracellular vesicles come from a wide range of sources,including non-coding RNAs such as small RNAs,circular RNAs,and long chain non-coding RNAs.Extracellular vesicles non-coding RNAs can be directly delivered from primitive cells to neighboring or remote cells,regulating cell activity through intercellular communication and playing an important regulatory role in reshaping the bone and joint microenvironment.OBJECTIVE:To summarize the intervention effects of exosome-derived non-coding RNAs on the joint microenvironment of osteoarthritis and the progress made in clinical application,and to clarify the potential of exosome-derived non-coding RNAs in the diagnosis and treatment of osteoarthritis.METHODS:Search terms "exosomes,non-coding RNA,osteoarthritis,application,signal pathway,synovial fluid,cartilage cells,cartilage matrix,subchondral,mechanism" were used for the search on PubMed database.Finally,66 related articles were included for review analysis.RESULTS AND CONCLUSION:(1) Exosome-derived non-coding RNAs play an important regulatory role in the joint microenvironment during the pathogenesis of osteoarthritis,mainly reflected in:exosome non-coding RNAs regulating the inflammatory response in the joint,degeneration of chondrocytes and cartilage matrix,subchondral bone remodeling,and intercellular communication.(2) The non-coding RNAs in exosomes can serve as biomarkers for osteoarthritis,aiding in the early diagnosis and monitoring of disease progression and prognosis.(3) Exosome non-coding RNAs serve as therapeutic targets for osteoarthritis.Exosomes carry miRNAs to the articular chondrocytes and cartilage matrix to play a regulatory role.(4) Exosomes non-coding RNAs can improve the effect of cartilage tissue engineering by regulating gene expression and promoting intercellular communication to repair or regenerate damaged cartilage.(5) In future research,researchers should continue to explore the intervention mechanism of non-coding RNAs derived from exosomes on osteoarthritis,and apply them to clinical practice in combination with the latest research outcomes in cartilage tissue engineering,which will effectively help solve the pain of osteoarthritis patients.