Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Objective:To study the current prevalence and temporal patterns of Keshan disease in Gansu Province, thereby establishing a scientific foundation for development of targeted prevention and control strategies.Methods:From March 2019 to October 2021, monitoring of Keshan disease was conducted in all affected townships (towns) across 28 counties (districts, cities) in Gansu Province. Demographic data were collected from affected villages, and suspected chronic Keshan disease cases were identified through village clinics, township health centers, county hospitals, and other medical institutions. These suspected cases were diagnostically verified according to the "Diagnosis of Keshan Disease" (WS/T 210-2011). Current chronic Keshan disease cases underwent re-examination and follow-up monitoring.Results:There were a total of 254 endemic townships (towns) and 2 611 endemic villages across the province, with a permanent resident population of 3.667 1 million in the affected areas. New cases of chronic Keshan disease continued to emerge throughout the study period, totaling 6 cases. From 2020 to 2021, among the total number of chronic Keshan disease cases, 88.92% (923/1 038) remained stable in condition, while mortality cases accounted for 9.54% (99/1 038). Over the past three years, there were 886 males and 687 females with current chronic Keshan disease, mainly aged between 50 and 60 years old, accounting for 38.78% (610/1 573).Conclusions:While Keshan disease in Gansu Province maintains a sustained level of elimination, new chronic cases continue to emerge. It is essential to enhance disease surveillance efforts, and effectively consolidate the achievements in Keshan disease prevention and control measures.

Objective To establish an animal model of hand,foot,and mouth disease(HFMD)in Syrian hamsters coinfected with coxsackievirus A6(CVA6)and coxsackievirus B1(CVB1).Methods 42 Syrian hamsters were divided into a CVA6 infection group,CVB1 infection group,CVA6 and CVB1 coinfection group and control group.A HFMD model was established by nasal instillation of virus solution and phosphate-buffered saline.Clinical and physiological indicators and detoxification status were monitored and recorded for 15 d,and animals were selected on day 7(D7)after infection for histopathology and viral antigen and nucleic acid testing.Results Hamsters in the single-infection and coinfection groups showed clinical symptoms similar to human HFMD.White blood cell,neutrophil,and lymphocyte result were characteristic of viral infection.Both viral nucleic acids were detected in throat swabs,feces,blood,and tissues and both viruses were isolated from fecal samples.Pathological damage and positive co-localization of CVA6 and CVB1 viral antigen proteins and nucleic acids were found in brain and other tissues.Conclusions Nasal instillation of a CVA6 and CVB1 mixture can successfully coinfect Syrian hamsters,replicate herpes infection similar to human HFMD,and cause pathological viral myocarditis and encephalitis damage.The result showed that the coinfection group was more seriously affected than the single-infection group,with worse clinical symptoms,increased viral replication,and obvious tissue pathological damage.This study provides a reference for further basic and clinical research into human enterovirus coinfection.

Objective:To study the current prevalence and temporal patterns of Keshan disease in Gansu Province, thereby establishing a scientific foundation for development of targeted prevention and control strategies.Methods:From March 2019 to October 2021, monitoring of Keshan disease was conducted in all affected townships (towns) across 28 counties (districts, cities) in Gansu Province. Demographic data were collected from affected villages, and suspected chronic Keshan disease cases were identified through village clinics, township health centers, county hospitals, and other medical institutions. These suspected cases were diagnostically verified according to the "Diagnosis of Keshan Disease" (WS/T 210-2011). Current chronic Keshan disease cases underwent re-examination and follow-up monitoring.Results:There were a total of 254 endemic townships (towns) and 2 611 endemic villages across the province, with a permanent resident population of 3.667 1 million in the affected areas. New cases of chronic Keshan disease continued to emerge throughout the study period, totaling 6 cases. From 2020 to 2021, among the total number of chronic Keshan disease cases, 88.92% (923/1 038) remained stable in condition, while mortality cases accounted for 9.54% (99/1 038). Over the past three years, there were 886 males and 687 females with current chronic Keshan disease, mainly aged between 50 and 60 years old, accounting for 38.78% (610/1 573).Conclusions:While Keshan disease in Gansu Province maintains a sustained level of elimination, new chronic cases continue to emerge. It is essential to enhance disease surveillance efforts, and effectively consolidate the achievements in Keshan disease prevention and control measures.

Purpose To study the mechanism of invasion and metastasis of hepatocellular carcinoma(HCC)based on LINC02036 expression.Methods A total of 60 pairs of the HCC tissues along matched adjacent non-tumor tissues were col-lected.The differential expression of lncRNA was confirmed by RNA sequencing.LINC02036 knockdown and overexpressing Huh7 cells were constructed in vitro,and the proliferation and invasion ability of the cells were detected by CCK-8,colony for-mation test,and Transwell method,respectively.The epithelial-mesenchymal transition(EMT)marker protein was detected by Western blot.In addition,the interaction between LINC02036 and TGF-β1 was identified by RNA pull down and mass spec-trometry(MS),which was further validated by RNA immuno-precipitation(RIP).Results It was confirmed by RNA se-quencing that LINC02036 was differentially expressed in adja-cent normal tissues and HCC tissues.High expression of LINC02036 was significantly correlated with the largest tumor size(P=0.025),advanced TNM staging(P=0.028),and micro vascular invasion(P＜0.001).In vitro experiments,overexpression of LINC02036 obviously elevated cell viability,metastasis,invasion and EMT(P＜0.05),while knockout of LINC02036 showed the opposite effects(P＜0.05).TGF-β1 was identified as a potential interactive protein and pulled down by LINC02036 in HCC cell lysates.We verified the interaction between LINC02036 and TGF-β1 by RIP assay.Moreover,acti-nomycin D assay showed that overexpression of TGF-β1 en-hanced the RNA stability of LINC02036(P＜0.05).Conclu-sion LINC02036 plays a carcinogenic effect in HCC,promotes tumor proliferation and microvascular invasion,and the related mechanism may involve the enhancement of its RNA stability by TGF-β1.

Objective:To study the correlation between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and echocardiographic parameters in patients with chronic Keshan disease, providing reference for diagnosis and prognosis evaluation of chronic Keshan disease.Methods:Ninety-nine patients with chronic Keshan disease who received standardized treatment at Jingchuan County People's Hospital in Pingliang City, Gansu Province from January to December 2020 were selected. Among them, 16 patients were classified as cardiac function grade Ⅱ according to New York Heart Association (NYHA), 69 as grade Ⅲ and 14 as grade Ⅳ. The patients underwent echocardiography and their serum NT-proBNP level was measured using fluorescence immunochromatography. The differences in serum NT-proBNP levels among patients with different cardiac function grades were compared, and the correlation between cardiac function grades, serum NT-proBNP level and echocardiographic parameters was analyzed.Results:The serum NT-proBNP levels in patients with cardiac function grades Ⅱ, Ⅲ, and Ⅳ were (1 107.26 ± 268.03), (2 125.98 ± 293.02), and (8 268.59 ± 2 659.50) pg/ml, respectively. The differences among the three groups were statistically significant ( F = 13.94, P < 0.001). The serum NT-proBNP level was positively correlated with cardiac function grades ( r = 0.44, P < 0.001), left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial diameter ( r = 0.45, 0.52, 0.38, P < 0.001), and negatively correlated with fractional shortening and left ventricular ejection fraction ( r = - 0.39, - 0.46, P < 0.001). Conclusions:The serum NT-proBNP level in patients with chronic Keshan disease with different cardiac function grades is different, and is positively correlated with echocardiographic parameters reflecting the degree of cardiac structural and functional impairment. The NT-proBNP level may become an early diagnostic, grading, and prognostic indicator for chronic Keshan disease.

Background Non-suicidal self-injury(NSSI)behavior has become a major public health concern and can have significant implications for the physical and mental health of adolescents.Peer victimization is a risk factor for adolesents to have NSSI behavior,so exploring the relationship and underlying mechanism between peer victimization and NSSI functions will provide a promising strategy for the prevention and intervention of NSSI behavior.Objective To investigate the relationship between peer victimization and NSSI functions in adolescents with unipolar and bipolar depression,so as to provide references for the intervention of NSSI behavior in adolescent patients with unipolar and bipolar depression.Methods Using multi-stage stratified sampling,940 adolescents with unipolar and bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria for bipolar depressive episodes or depressive disorders were selected from 14 psychiatric hospitals in China.All participations were assessed using Chinese version of the Functional Assessment of Self-Mutilation(C-FASM),Multidimensional Peer-Victimization Scale(MPVS),UCLA Loneliness Scale(UCLA-LS)and Patient Health Questionnaire-9 item(PHQ-9).Pearson correlation coefficient was to assess the correlation among above scales,and the model fit and path coefficients for mediation were analyzed with model 4 in Process 4.0 for SPSS.Results A total of 698(74.26%)adolescents with unipolar and bipolar depression completed the questionnaire survey.NSSI behavior was detected in 374 patients(53.58%).Among adolescents with unipolar and bipolar depression and NSSI behavior,MPVS total score was positively correlated with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.104,0.130,0.266,P<0.05 or 0.01),UCLA-LS score also yielded a positive correlation with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.321,0.112,0.246,P<0.05 or 0.01),and UCLA-LS score was positively correlated with MPVS total score(r=0.241,P<0.01).Loneliness demonstrated a complete mediating role in the relationship between peer victimization and emotion regulation function,with an indirect effect value of 0.033(95%CI:0.019～0.050)and an effect size of 73.33%.A partial mediating effect of loneliness was also observed for the relationship between peer victimization and social avoidance function,with an indirect effect value of 0.016(95%CI:0.007～0.025)and an effect size of 17.98%.Conclusion Loneliness may act as a mediator in the relationship between the peer victimization and the NISS emotion regulation and social avoidance functions in adolescents with unipolar and bipolar depression and NSSI behaviors.

Objective:To evaluate the application of the standard of "Delimitation and Classification of Keshan Disease Areas" (GB 17020-2010, Standard for short), learn about the applicability of its technical indicators and requirements, and provide a basis for revision of the Standard.Methods:In March 2022, provinces with severe epidemic areas of Keshan disease or new cases reported in recent years were selected, including Gansu Province, Inner Mongolia Autonomous Region, Shandong Province, Shaanxi Province, Yunnan Province, Shanxi Province, Liaoning Province, and Chongqing City. Multi-stage stratified sampling method and questionnaire survey were adopted to collect information on the application of Standard by relevant health institutions.Results:A total of 448 questionnaires were collected, including 445 valid. The survey results showed that 87.64% (390/445) of the respondents were aware of the Standard, and 64.72% (288/445) had received training on the Standard. Eighty-two point two per cent (365/445) of the respondents believed that the Standard was simple and easy to operate, 83.82% (373/445) believed that the determination of the diseased townships was scientific and reasonable, and could be effectively implemented, and 83.60% (372/445) believed that the determination of historical epidemic areas was applicable to the current situation of Keshan disease; 38.88% (173/445), 38.20% (170/445), and 37.98% (169/445) of the respondents believed that the classification indicators for classifying epidemic areas (severe, moderate, and mild epidemic areas) were not applicable to the current situation of the disease in the local or provinces with Keshan disease, respectively. Among the indicators for epidemic areas classification, 30.79% (137/445), 29.21% (130/445), and 28.54% (127/445) of the respondents thought that the annual prevalence, the annual number of new cases and the annual incidence were most suitable for classification of Keshan disease areas.Conclusions:The Standard has been applied well in practice. However, based on the current situation of Keshan disease, it is suggested to redefine the standard for the severity of the disease and the classification of historical epidemic areas.

Purpose To study the mechanism of invasion and metastasis of hepatocellular carcinoma(HCC)based on LINC02036 expression.Methods A total of 60 pairs of the HCC tissues along matched adjacent non-tumor tissues were col-lected.The differential expression of lncRNA was confirmed by RNA sequencing.LINC02036 knockdown and overexpressing Huh7 cells were constructed in vitro,and the proliferation and invasion ability of the cells were detected by CCK-8,colony for-mation test,and Transwell method,respectively.The epithelial-mesenchymal transition(EMT)marker protein was detected by Western blot.In addition,the interaction between LINC02036 and TGF-β1 was identified by RNA pull down and mass spec-trometry(MS),which was further validated by RNA immuno-precipitation(RIP).Results It was confirmed by RNA se-quencing that LINC02036 was differentially expressed in adja-cent normal tissues and HCC tissues.High expression of LINC02036 was significantly correlated with the largest tumor size(P=0.025),advanced TNM staging(P=0.028),and micro vascular invasion(P＜0.001).In vitro experiments,overexpression of LINC02036 obviously elevated cell viability,metastasis,invasion and EMT(P＜0.05),while knockout of LINC02036 showed the opposite effects(P＜0.05).TGF-β1 was identified as a potential interactive protein and pulled down by LINC02036 in HCC cell lysates.We verified the interaction between LINC02036 and TGF-β1 by RIP assay.Moreover,acti-nomycin D assay showed that overexpression of TGF-β1 en-hanced the RNA stability of LINC02036(P＜0.05).Conclu-sion LINC02036 plays a carcinogenic effect in HCC,promotes tumor proliferation and microvascular invasion,and the related mechanism may involve the enhancement of its RNA stability by TGF-β1.