ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

Objective To study the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway. Methods Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group (400 mg/kg), low, medium and high dose groups of Lishukang capsule (400、 600、 800 mg/kg), with 10 mice in each group. The normal control group was fed at the local altitude (1 500 m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500 m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given normal saline once a day, and 1 hour after the last administration, the eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice. Results Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased （P<0.01）. Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased（P<0.01）. Conclusion High altitude hypoxia can lead to oxidative stress injury in mice and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment in mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective:To explore the potential profiles of health literacy in patients with chronic atrophic gastritis (CAG) and analyze their influencing factors.Methods:A cross-sectional study was conducted to select CAG patients admitted to Nanjing Hospital of Traditional Chinese Medicine or attending outpatient clinics from January 2023 to June 2024 by convenience sampling method, and all patients participated in this study two months after treatment. The General Information Questionnaire, the General Self-Efficacy Scale, and the All-around Health Literacy Measurement Scale (AAHLS) were used to conduct the questionnaire survey. The three dimensions of AAHLS were used as exogenous indicators for potential profile analysis, to compare the differences in general information and self-efficacy of patients with different potential profiles, and to analyze the influencing factors of different potential profiles of health literacy in CAG patients by multi classification Logistic regression.Results:The recovery rate of valid questionnaires was 97.71%(256/262). Among the 256 patients, there were 164 males and 92 females, with 86 patients aged 18-44 years old, 110 patients aged 45-59 years old, and 60 patients aged ≥ 60 years old. The health literacy of CAG patients was categorized into 3 potential profiles, including the high health literacy-appraisal and application competence group (14.84%, 38/256), the medium health literacy-appraisal and application competence group (32.81%, 84/256), and the low health literacy-appraisal and application competence group (52.34%, 134/256). The results of multi classification Logistic regression analysis showed that when the low health literacy-appraisal and application competence group was used as a reference, aged 18-44 years old ( OR=8.954, 95% CI 2.049-39.127), poor self-efficacy ( OR=0.089, 95% CI 0.027-0.293), duration of disease <5 years ( OR=0.049, 95% CI 0.014-0.169), per capita monthly household income<3 000 yuan ( OR=0.072, 95% CI 0.018-0.299), and primary school education or below ( OR=0.016, 95% CI 0.003-0.088) were independent influences in the the high health literacy-appraisal and application competence group (all P<0.05); poorer self-efficacy ( OR=0.458, 95% CI 0.251-0.834) and per capita monthly household income<3 000 yuan ( OR=0.212, 95% CI 0.100-0.453) were independent influences in the medium health literacy-appraisal and application competence group (both P<0.05). Conclusions:The health literacy of CAG patients is obviously heterogeneous, and healthcare professionals in clinical work should adopt targeted assessment and intervention according to the different characteristics of each category in order to improve the health literacy of CAG patients.

Objective To analyze the status and its influencing factors of high-frequency hearing loss (HFHL) among occupational noise-exposed workers. Methods A total of 6 764 noise-exposed workers who participated in occupational medical examinations during their employment were selected as the study subjects using the judgmental sampling method. Their pure-tone audiometry results were analyzed. Results The detection rate of HFHL among the study subjects was 10.3%. Binary logistic regression analysis result revealed that males had a higher risk of HFHL than females (P<0.05). The HFHL risk of workers increased with age (all P<0.01). Workers with longer noise exposure durations had a higher risk of HFHL (all P<0.01). Smokers had a higher detection rate of HFHL than non-smokers (P<0.01). Workers in the mining industry, electricity/heat/gas and water production and supply industry, and other industries had a higher HFHL detection rate compared with manufacturing workers (all P<0.05). Medium-sized enterprise workers had a lower HFHL detection rate compared with micro-sized enterprise workers (P<0.05), while workers in private enterprises had a higher HFHL detection rate compared with those in state-owned enterprises (P<0.05). Workers who exposed to noise combined with dust, lead, high temperature, or multiple factors had a higher HFHL risk than those only exposed to noise (all P<0.05). Conclusion Gender, age, noise exposure duration, smoking, industry, and exposure to noise combined with other occupational hazard factors are all influencing factors for HFHL among noise-exposed workers. Targeted occupational health education on noise hazard prevention and occupational medical surveillance should be strengthened for key populations in priority industries, including male workers, older employees, individuals with prolonged noise exposure, smokers, and those concurrently exposed to noise and one of the following: dust, lead, high temperatures, or multiple occupational factors.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective:To analyze by bioinformatics the association between the expression of membrane-associated tyrosine/threonine protein kinase 1(PKMYT1)in glioma with its prognostic value,biological function,drug sensitivity,gene mutation,and immune infiltration.Methods:The differential expression of PKMYT1 was analyzed based on the Chinese Glioma Genome Atlas database(CGGA)and the Cancer Genome Atlas database(TCGA).Pathways likely to be enriched for PKMYT1 were predicted by gene ontology analysis(GO)and gene set enrichment analysis(GSEA).PKMYT1 was subjected to Pearson correlation and gene set variation analysis(GSVA)with cell cycle-related genes and gene sets.The survival prognosis,gene mutation,drug sensitivity and immune infiltration were further analyzed for PKMYT1 high and low expression groups of glioma patients.Results:PKMYT1 was significantly highly expressed in WHO high-grade glioma(P<0.000 1),IDH wild-type glioma(P<0.05),and glioblastoma(P<0.000 1).Overall survival(OS)of patients in the PKMYT1 low expression group was significantly higher than that of the high expression group(P<0.05).Cox regression analysis showed that PKMYT1 expression level was an independent prognostic factor for OS(P<0.05).GO and GSEA analyses showed that the gene sets co-expressed with PKMYT1 were mainly enriched in signaling pathways such as cell cycle,DNA replication and DNA damage repair.Pearson correlation and GSVA analyses showed that the expression of PKMYT1 was significantly and positively correlated with the cell cycle-related genes,gene sets and cell cycle checkpoint genes(P<0.01).Drug sensitivity analysis revealed that patients in the PKMYT1 high expression group had high sensitivity osimertinib,dabrafenib,carmustine and cediranib(P<0.05).Mutation analysis revealed that the IDH1 gene had a higher mutation frequency in the PKMYT1 low expression group.The results of immune infiltration analysis showed that PKMYT1 expression was significantly positively correlated with glioma stroma score(r=0.13,P<0.001),immune score(r=0.11,P<0.01)and ESTIMATE score(r=0.13,P<0.001);and was significantly positively correlated with immune cell infiltration level of regulatory T(Treg)cells and M2-type macrophages(P<0.05).Conclusion:Patients with high PKMYT1 expression have a poorer prognosis,and the mechanism may be related to tumor immune infiltration and cell cycle regulation.PKMYT1 is expected to be a potential target for the diagnosis and treatment of glioma.

Objective:To explore the potential profiles of health literacy in patients with chronic atrophic gastritis (CAG) and analyze their influencing factors.Methods:A cross-sectional study was conducted to select CAG patients admitted to Nanjing Hospital of Traditional Chinese Medicine or attending outpatient clinics from January 2023 to June 2024 by convenience sampling method, and all patients participated in this study two months after treatment. The General Information Questionnaire, the General Self-Efficacy Scale, and the All-around Health Literacy Measurement Scale (AAHLS) were used to conduct the questionnaire survey. The three dimensions of AAHLS were used as exogenous indicators for potential profile analysis, to compare the differences in general information and self-efficacy of patients with different potential profiles, and to analyze the influencing factors of different potential profiles of health literacy in CAG patients by multi classification Logistic regression.Results:The recovery rate of valid questionnaires was 97.71%(256/262). Among the 256 patients, there were 164 males and 92 females, with 86 patients aged 18-44 years old, 110 patients aged 45-59 years old, and 60 patients aged ≥ 60 years old. The health literacy of CAG patients was categorized into 3 potential profiles, including the high health literacy-appraisal and application competence group (14.84%, 38/256), the medium health literacy-appraisal and application competence group (32.81%, 84/256), and the low health literacy-appraisal and application competence group (52.34%, 134/256). The results of multi classification Logistic regression analysis showed that when the low health literacy-appraisal and application competence group was used as a reference, aged 18-44 years old ( OR=8.954, 95% CI 2.049-39.127), poor self-efficacy ( OR=0.089, 95% CI 0.027-0.293), duration of disease <5 years ( OR=0.049, 95% CI 0.014-0.169), per capita monthly household income<3 000 yuan ( OR=0.072, 95% CI 0.018-0.299), and primary school education or below ( OR=0.016, 95% CI 0.003-0.088) were independent influences in the the high health literacy-appraisal and application competence group (all P<0.05); poorer self-efficacy ( OR=0.458, 95% CI 0.251-0.834) and per capita monthly household income<3 000 yuan ( OR=0.212, 95% CI 0.100-0.453) were independent influences in the medium health literacy-appraisal and application competence group (both P<0.05). Conclusions:The health literacy of CAG patients is obviously heterogeneous, and healthcare professionals in clinical work should adopt targeted assessment and intervention according to the different characteristics of each category in order to improve the health literacy of CAG patients.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.