ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: To study the epidemiological characteristics of respiratory syncytial virus (RSV) infection in hospitalized children with community-acquired pneumonia (CAP) in Hebei Province. METHODS: Hospitalized children with CAP who tested positive for RSV and were admitted to Hebei Children's Hospital from various cities and counties across Hebei Province between January 2019 and December 2023 were included in the study. Clinical data were collected and analyzed to assess epidemiological characteristics. RESULTS: The clinical data of 43 978 children with CAP were collected, with an overall RSV detection rate of 25.98%. The detection rate was higher during the implementation of non-pharmaceutical interventions (NPIs) (30.60%) than in the non-NPIs period. Winter and spring were the primary epidemic seasons for RSV each year except in 2022. The detection rate in males (26.62%) was higher than in females (25.06%) (P<0.001). The highest detection rate (59.18%) was found in infants aged 29 days to <1 year. Single RSV infection was more common, with rhinovirus being the most frequent co-infection. CONCLUSIONS The overall RSV detection rate in Hebei Province is influenced by NPIs, being higher during their implementation. RSV predominantly circulates in winter and spring. The detection rate of RSV is higher in males and infants. RSV infection is primarily single, most often co-occurring with rhinovirus.
Humans ; Respiratory Syncytial Virus Infections/epidemiology* ; Female ; Male ; Infant ; Child, Preschool ; Seasons ; China/epidemiology* ; Infant, Newborn ; Community-Acquired Infections/epidemiology* ; Child

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Objective:To construct a method for hepatitis B virus (HBV) DNA detection based on recombinase-mediated isothermal amplification (RAA)-clustered regularly interspaced short palindromic repeats and their associated protein 13a (CRISPR-Cas13a).Methods:Through the alignment and screening of HBV DNA sequences, a positive plasmid was constructed, and recombinase-aided amplification (RAA) primers and CRISPR RNA (crRNA) were designed. A method for detecting HBV DNA based on the RAA-CRISPR-Cas13a system was developed, and the specificity and sensitivity were evaluated. Utilizing the CRISPR-Cas13a system, 70 clinical samples from HBV DNA-positive patients with various viral loads collected at Beijing You′an Hospital from 2019 to 2021 were analyzed. The detection results were further compared with those results using real-time quantitative polymerase chain reaction (qPCR).Results:The optimal RAA amplification primers and crRNA were first screened using the RAA-CRISPR-Cas13a method, with the sensitivities for detecting HBV DNA standards and for clinical samples at 1 IU/ml and<10 IU/ml, respectively, demonstrating specificity for HBV DNA detection. Compared with qPCR (the gold standard), the detection consistency between the two methods was 100% (70/70).Conclusion:This study established a method for detecting HBV DNA by integrating recombinase-aided amplification (RAA) technology with CRISPR/Cas13a technology.

Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.