ObjectiveTo investigate the association of serum exosomal microRNAs （miRNAs） with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B （CHB）. MethodsPeripheral serum samples were collected from six healthy adults and six patients with CHB， and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis， and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine， a rat model of liver fibrosis induced by carbon tetrachloride， and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； an analysis of variance was used for comparison between multiple groups， and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. ResultsAbnormal expression of serum exosomal miR-122-5p was observed in patients with CHB， and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis， compared with the control group， the model group had a significant reduction in the expression level of miR-122-5p in the liver （P=0.048 and 0.014）， and compared with the patients with mild liver injury， the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue （P<0.05）. Among the 84 CHB patients， the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury （P<0.001 and P=0.003）. The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis （odds ratio ［OR］=0.001， 95% confidence interval ［CI］： 0.000‍ ‍—‍ ‍0.037， P=0.005） and liver fibrosis degree （OR=0.568， 95%CI： 0.331‍ ‍—‍ ‍0.856， P=0.019）. In addition， compared with the patients with low expression of miR-122-5p， the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy （64.3% vs 38.1%， P=0.029）. ConclusionSerum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis， and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis， promote the progression of fibrosis， and affect the histological outcome of CHB patients after antiviral therapy.

Objective To retrospectively analyze the epidemiological trend of children with lower gastrointestinal bleeding in recent 10 years,and investigate the change of their disease burden,so as to provide a theoretical basis for the accurate prevention and control of children's lower gastrointestinal bleeding. Methods A total of 671 children with "lower gastrointestinal bleeding" who were diagnosed in our hospital from 2012 to 2021 were collected as research subjects. To analyze the microscopic examination rate and common etiology of lower gastrointestinal bleeding in children in the past 10 years,as well as the epidemiological characteristics of different age groups, different regions and different basic diseases; Calculate and compare the rate of disability life lost (YLD), early death life lost (YLL) and disability adjusted life year (DALY) of children with lower gastrointestinal bleeding within 10 years, and calculate the annual change percentage (AAPC) to analyze the change trend of disease burden. Results The microscopic examination rate of children with lower gastrointestinal bleeding showed a trend of increasing in the past 10 years (P<0.001). Among them, the most common causes are Crohn's disease, ulcerative colitis and chronic colitis. The proportion of children with lower gastrointestinal bleeding was higher in boys, >18 years old, hypertension and gastroenteritis. The DALY rate, YLL rate and YLD rate caused by lower gastrointestinal bleeding in the past 10 years showed an upward trend (P<0.05). Conclusion The microscopic examination rate of lower gastrointestinal bleeding in children was graduallyincreasing,and the prevalence rate of basic diseases such as boys,hypertension and gastroenteritis was increasing;in addition,the disease burden caused by children's lower gastrointestinal bleeding was also increasing year by year and should be protected.

ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective:To describe functional disability rate of anxiety disorders in Chinese community adults and explore related risk factors of functional disability.Methods:To conduct in-depth data analysis on China Mental Health Survey(CMHS).The diagnostic tool for anxiety disorders was the Composite International Diagnostic Inter-view-3.0,according to the Diagnostic and Statistical Manual for Mental Disorders,Fourth Edition(DSM-Ⅳ).The World Health Organization Disability Assessment Schedule,2nd edition,was the functional disability assessment standard for anxiety disorders.Weighted 12-month functional disability rate of DSM-Ⅳ anxiety disorder with co-morbidities and only anxiety disorder in population and those in patients,as well as days of partial disability were calculated.The effects of anxiety disorders comorbid other mental disorders and physical diseases and demographic factors on the severity and occurrence of functional disability were analyzed by multiple linear regression and logis-tic regression.Results:The functional disability rate of anxiety disorder with comorbidities in population was 1.7％,and 42.2％in patients,in which constituent rate of grade-four disability was the highest as 84.1％.The functional disability rate of only anxiety disorder in population was 0.3％,and 17.8％in patients.The medians of days of partial disability days in the past 30 days were from 0 to 14.42.Multiple linear regression showed a positive association between comorbid anxiety disorder with other mental disorders and physical diseases(β=0.24),comor-bid other mental disorders and physical diseases(β=0.21),physical diseases(β=0.18),comorbid anxiety disor-der and physical diseases(β=0.15),comorbid anxiety disorder with other mental disorders(β=0.08),other men-tal disorders(β=0.07),only anxiety disorder(β=0.06),lower education level(β=0.12),lower economic status(β=0.08),older age(β=0.06),non-marital status(β=0.06),male(β=0.02)and the severity of functional dis-ability.Logistic regression showed that comorbid anxiety with other mental disorders and physical diseases(OR=64.07),comorbid anxiety disorders with other mental disorders(OR=36.75),comorbid other mental disorders with physical diseases(OR=20.60),comorbid anxiety with physical diseases(OR=18.88),anxiety disorder(OR=9.20),other mental disorders(OR=6.65),physical diseases(OR=4.00),65 years old and over(OR=4.40),50 to 64 years old(OR=2.33),low economic status(OR=2.10),illiterate and below primary school educational level(OR=1.89),middle economic status(OR=1.70),elementary school educational level(OR=1.59),non-marital status(OR=1.47),male(OR=1.16)were the risk factors of the occurrence of functional disability.Conclusion:Comorbidity of anxiety disorders and other mental disorders,and physical diseases increases severity and occurrence of functional disability.Comorbidity,male,gender,older age,lower economic and educa-tional level and non-marital are risk factors of anxiety disorder functional disability.

Objective:To evaluate the efficacy of modified femoral neck osteotomy(mFNO)in the surgical treatment of patients with ankylosing spondylitis(AS)and severe spinal kyphosis combined with hip flexion contracture.Methods:A retrospective analysis was conducted on 61 AS patients(103 hips)with spinal kyphosis and hip flexion contracture who underwent pedicle subtraction osteotomy(PSO)and total hip arthroplasty(THA)from January 1,2019 to November 15,2023.Data on mFNO operation time,blood loss,preoperative and postoperative values of the angle of the trunk and lower limb(ATL),hip passive range of motion(ROM),visual analogue scale(VAS),and incidence of in-hospital compli-cations were recorded.Statistical analysis was performed using paired-samples t test.P＜0.05 was con-sidered statistically significant.Results:The study ultimately included 10 cases,9 males and 1 female,with an average age of(41.30±9.03)years.These patients underwent surgery for a total of 52 times,including 19 hips both receiving mFNO and THA,and 14 times PSO.The average operation time for nine bilateral mFNO was(133.11±34.81)min,with blood loss of(433.33±187.10)mL.A unilateral mFNO took 60 min with 200 mL of blood loss.The preoperative ATL of 19 hips was 40.37°±13.66°,and the postoperative ATL value was 88.47°±12.46°(P＜0.05).The preoperative VAS score was 0,while the postoperative VAS score was 5.95±1.51(P＜0.05).The preoperative hip extension ROM was 37.37°±18.13°,while the postoperative hip extension ROM was-4.95°±21.24°(P＜0.05).Hip flexion ROM improved from 37.37°±18.13° to 50.79°±20.36° after FNO(P＜0.05).There were three cases of in-hospital complications(3/52,5.67％):One case of postoperative atelectasis fol-lowing PSO(1/52,1.92％),one greater trochanter fracture identified during THA(1/52,1.92％),and one early dislocation post-THA(1/52,1.92％).Conclusion:mFNO significantly improves the ATL in AS patients with severe spinal kyphosis combined with hip flexion contracture,facilitating PSO and THA surgeries.

Objective:To investigate the current situation of key endemic disease prevention and control in Shanxi Province, and provide a scientific basis for further strengthening the implementation of prevention and control measures.Methods:In 2021, monitoring of key endemic disease prevention and control projects in Shanxi Province was carried out in accordance with the current national monitoring plans for iodine deficiency disorders and water source high iodine areas, for endemic fluorosis, endemic arsenic poisoning, Kashin-Beck disease, and Keshan disease. The effect of prevention and control measures was evaluated in accordance with the "Evaluation Measures for Key Endemic Disease Control and Elimination (2019 Edition)". Patient management services and treatment subsidy projects were carried out in accordance with the "Management Service Standards for Endemic Disease Patients" and the "Management Measures for Treatment of Endemic Disease Patients".Results:All 117 counties (cities, districts, hereinafter referred to as counties) in Shanxi Province had reached the national elimination standards for iodine deficiency disorders, and the overall iodine nutrition of the population was generally suitable. However, the consumption rate of qualified iodine salt in 8 counties was ≤90%, and the iodine nutrition of pregnant women in 13 counties was insufficient. The water improvement rate in 295 villages in 12 counties across the province with high water iodine level was 80.68% (238/295), and the proportion of villages with qualified water iodine after water improvement was 38.31% (113/295). The prevention and control measures of 93.55% (58/62) of the counties in the province with endemic fluorosis caused through drinking water reached the national control standards. Totally 20 counties ravaged by coal-burning borne endemic fluorosis, 16 counties ravaged by drinking water borne endemic arsenicosis (high arsenic areas), 35 counties ravaged by Kashin-Beck disease, and 11 counties ravaged by Keshan disease met the national elimination standards. In 2021, 11 197 patients with endemic diseases were followed up and managed in Shanxi Province, and drug treatment programs were carried out on 3 413 patients with skeletal fluorosis, 2 088 patients with Kashin-Beck disease, and 10 patients with chronic Keshan disease.Conclusions:The overall prevention and control of key endemic diseases in Shanxi Province remains under control or elimination. However, the water improvement in some drinking water borne endemic fluorosis areas still needs to be further strengthened. Measures for water improvement and supply of non-iodized salt in water source high iodine areas still need to be coordinated and promoted. Key endemic disease patients in Shanxi Province have basically achieved standardized management.

Objective To investigate the expression of disulfidptosis-related genes in hepatocellular carcinoma(HCC)and the prognostic value of disulfidptosis in HCC,to construct a prognostic model,and to analyze its impact on the biological processes of HCC and sorafenib resistance.Methods The TCGA-LIHC database was used to collect the mRNA expression profiles and corresponding clinical data of HCC patients,and the LASSO-Cox regression algorithm was used to construct a four-gene predictive model for prognosis in the TCGA cohort.The external datasets ICGC and GSE14520 were used to validate the prognostic efficacy of the model,and the Cancer Drug Sensitivity Genomics(GDSC)data were used to investigate the value of the disulfidptosis model in predicting sorafenib treatment response,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were used to investigate the biological functions of disulfidptosis-related genes.The independent-samples t test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The Kaplan-Meier curve and the log-rank test were used to evaluate the difference in prognosis,and univariate and multivariate Cox regression analyses were used to investigate whether risk score was an independent influencing factor for patient prognosis.Results The univariate Cox regression analysis in the TCGA cohort showed that seven known disulfidptosis-related genes were significantly associated with overall survival(OS)in HCC(all P<0.05).The LASSO-Cox regression analysis was used to construct a prognostic model based on disulfidptosis-related genes(DRG),and the risk score RS-DRG was calculated as RS-DRG=(0.061 6)×GYS1 expression level+(0.152 8)×LRPPRC expression level+(0.268 3)×RPN1 expression level+(0.183 5)×SLC7A11 expression level.The log-rank test showed that the patients with a high risk score based on the disulfidptosis model had a significantly lower OS than those with a low risk score(P<0.001).Based on the results of the multivariate Cox regression analysis,risk score was an independent predictive factor for OS in both TCGA and ICGC cohorts(TCGA:hazard ratio[HR]=1.869,P=0.002;ICGC:HR=3.469,P=0.004).The Spearman correlation analysis showed that RS-DRG was significantly positively correlated with the infiltration level of various immune cells(including B lymphocytes,CD4+T lymphocytes,neutrophils,macrophages,and dendritic cells)in tumor microenvironment(all P<0.05).The patients in the high-risk score group had a significantly lower IC50 value of sorafenib and were more sensitive to sorafenib(P<0.001).The KEGG/GO enrichment analysis showed that the differentially expressed disulfidptosis-related genes were significantly enriched in various mitosis-related molecular functions.Conclusion This study constructed a novel prognostic model based on disulfidptosis-related genes,which has a potential clinical value in predicting the prognosis of HCC,and targeting disulfidptosis-related genes may provide a promising approach for HCC treatment.

Liver fibrosis is the inevitable course for the progression of chronic hepatitis B to liver cirrhosis and is also the most important risk factor for hepatocarcinogenesis, and therefore, blocking and reversing liver fibrosis is an important strategy to effectively reduce the development of chronic hepatitis B cirrhosis and liver cancer. There are currently no effective drugs and measures for the treatment of liver fibrosis in Western medicine, and traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis; however, due to a lack of strict and standardized clinical research, there is still no high-quality evidence for support from the aspect of evidence-based medicine (EBM). With subsidies from National Science and Technology Major Project in the 12th and 13th five-year plans, the authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial on compound Biejia Ruangan tablets combined with entecavir in blocking and reversing chronic hepatitis B liver fibrosis. With liver biopsy as the gold standard, 1000 patients were enrolled to confirm the efficacy of compound Biejia Ruangan tablets combined with entecavir in blocking and reversing liver fibrosis and cirrhosis, and this study has become the first clinical trial investigating the anti-liver fibrosis effect of TCM supported by high-quality EBM evidence, bringing great hope to patients with chronic liver diseases and helping TCM move towards the world. This article introduces these research findings and reviews the current status and challenges of TCM in blocking and reversing liver fibrosis.

Objective To investigate the role of P-I-R classification and Laennec grading in evaluating histological changes in patients with hepatitis B cirrhosis after receiving antiviral therapy, as well as the association of these two evaluation systems with clinical prognosis. Methods A total of 218 patients from 14 centers were consecutively screened from October 2013 to October 2014, and these patients were diagnosed with liver cirrhosis based on pathology (Ishak score ≥5), received antiviral therapy for 72 weeks, completed two liver biopsies, and met the P-I-R classification criteria. The 218 patients were divided into non-hepatocellular carcinoma (HCC) group with 186 patients and HCC group with 32 patients. The chi-square test and the Fisher's exact test were used for comparison of categorical data between groups. For the comparison of HCC after antiviral therapy, the non-parametric Mann-Whitney U test was used for continuous variables, and for the comparison of P-I-R classification and Laennec grading, the non-parametric Kruskal-Wallis H test was used for continuous variables. Univariate and multivariate Cox regression analyses were used to calculate hazard ratio ( HR ) and 95% confidence interval ( CI ), and the Kaplan-Meier method was used to calculate the cumulative incidence rate of HCC. Results After 72 weeks of antiviral therapy, there was a significant difference in P-I-R classification between the non-HCC group and the HCC group ( P < 0.001). There were significant differences in the distribution of Laennec grading and P-I-R classification before and after antiviral therapy ( P < 0.001). After antiviral therapy, the 218 patients were divided into 4A group with 33 patients, 4B group with 71 patients, and 4C group with 114 patients according to Laennec grading, and there were significant differences between these three groups in platelet count (PLT) ( H =36.429, P < 0.001), liver stiffness measurement (LSM) ( H =13.983, P =0.004), Ishak score ( χ 2 =23.060, P < 0.001), and HAI score ( P < 0.001). After antiviral therapy, the 218 patients were divided into R group with 70 patients, I group with 52 patients, and P group with 96 patients according to P-I-R classification, and there were significant differences between these three groups in PLT ( H =7.193, P =0.028), LSM ( H =6.238, P =0.045), Ishak score ( χ 2 =7.986, P < 0.001), HAI score ( P =0.002), and HCC ( P < 0.001). There was a significant difference in the incidence rate of HCC between the P and R groups based on P-I-R classification ( HR =24.21, 95% CI : 0.46-177.99, P =0.002). After adjustment for other confounding factors, P-I-R classification was an independent predictive factor for HCC ( HR =12.69, 95% CI : 4.63-34.80, P =0.002). Conclusion Both P-I-R classification and Laennec grading can reflect the features and changes of fibrosis before and after antiviral therapy, and P-I-R classification is more sensitive to fibrosis changes after antiviral therapy. P-I-R classification (after treatment) can be used to assess the risk of HCC in patients after antiviral therapy.