Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg^-1）， and high-（10 g·kg^-1）， medium-（5 g·kg^-1）， low-dose （2.5 g·kg^-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.

Objective:To study the long-term prognostic outcomes of antiviral therapy in patients with chronic hepatitis B (CHB) accompanied with normal alanine aminotransferase (ALT), mild or slight inflammation, and/or liver fibrosis.Methods:A retrospective study method was used. Patients with CHB who underwent liver biopsy at Zhenjiang Third People's Hospital, affiliated with Jiangsu University, from January 2005 to July 2022 were included. Baseline data, clinical data, and clinical outcome events at the end of follow-up were collected. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the risk of clinical events.Results:A total of 149 CHB cases with normal ALT with mild or slight inflammation or fibrosis were included. Eighty-six cases were treated with antiviral therapy, while 63 were not. The median follow-up time was 82.00 (45.50,153.00) months. In the follow-up endpoint events, four cases (4.65%, 4/86) in the antiviral group had liver cirrhosis, while none had progressed to hepatocellular carcinoma. Five cases (7.94%, 5/63) in the non-antiviral group had liver cirrhosis, and two cases (3.17%, 2/63) had hepatocellular carcinoma. Kaplan-Meier survival analysis showed that the cumulative risk of clinical events did not significantly increase in the non-antiviral group ( P>0.05). The presence of liver fibrosis with high-normal ALT levels at baseline were associated with an increased risk of clinical events ( P<0.05). Cox analysis showed that baseline age, high ALT level, and presence of liver fibrosis were independent risk factors for clinical events. The two groups differed significantly in terms of the proportion of HBVDNA below the detection value and ALT normalization rate at the endpoint ( P<0.05). However, there was no significant difference in the HBsAg negative conversion rate between the two groups at the end ( P>0.05). Conclusion:The occurrence risk of long-term liver adverse events was not significantly improved by antiviral treatment in patients with chronic hepatitis B accompanied by normal ALT levels, mild or slight inflammation, and/or liver fibrosis. However, clinical outcomes were associated with baseline age, higher ALT levels, and liver fibrosis, suggesting that these factors are independent risk factors for the occurrence of clinical events.

ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. 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. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ²=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ²=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

Objective:To study the long-term prognostic outcomes of antiviral therapy in patients with chronic hepatitis B (CHB) accompanied with normal alanine aminotransferase (ALT), mild or slight inflammation, and/or liver fibrosis.Methods:A retrospective study method was used. Patients with CHB who underwent liver biopsy at Zhenjiang Third People's Hospital, affiliated with Jiangsu University, from January 2005 to July 2022 were included. Baseline data, clinical data, and clinical outcome events at the end of follow-up were collected. Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the risk of clinical events.Results:A total of 149 CHB cases with normal ALT with mild or slight inflammation or fibrosis were included. Eighty-six cases were treated with antiviral therapy, while 63 were not. The median follow-up time was 82.00 (45.50,153.00) months. In the follow-up endpoint events, four cases (4.65%, 4/86) in the antiviral group had liver cirrhosis, while none had progressed to hepatocellular carcinoma. Five cases (7.94%, 5/63) in the non-antiviral group had liver cirrhosis, and two cases (3.17%, 2/63) had hepatocellular carcinoma. Kaplan-Meier survival analysis showed that the cumulative risk of clinical events did not significantly increase in the non-antiviral group ( P>0.05). The presence of liver fibrosis with high-normal ALT levels at baseline were associated with an increased risk of clinical events ( P<0.05). Cox analysis showed that baseline age, high ALT level, and presence of liver fibrosis were independent risk factors for clinical events. The two groups differed significantly in terms of the proportion of HBVDNA below the detection value and ALT normalization rate at the endpoint ( P<0.05). However, there was no significant difference in the HBsAg negative conversion rate between the two groups at the end ( P>0.05). Conclusion:The occurrence risk of long-term liver adverse events was not significantly improved by antiviral treatment in patients with chronic hepatitis B accompanied by normal ALT levels, mild or slight inflammation, and/or liver fibrosis. However, clinical outcomes were associated with baseline age, higher ALT levels, and liver fibrosis, suggesting that these factors are independent risk factors for the occurrence of clinical events.

Atherosclerosis (AS) is a chronic and progressive arterial disease. It is an important cause of the occurrence and development of cardiovascular and cerebrovascular diseases. With the development of Traditional Chinese Medicine (TCM), TCM has many advantages in the therapy of AS, with less adverse reactions. Studies have shown that TCM can resist AS, and the mechanism mainly belongs to regulating lipid metabolism, anti-lipid peroxidation, anti-inflammation, anticoagulation, and protecting the structure and function of vascular endothelial cells. The mechanism of TCM for AS is warranted to be studied systematically, and the chemical components need to be further clarified.

Objective To survey the factors associated with deep venous thrombosis after artificial liver treatment in patients with liver failure. Methods A retrospective survey was used in our hospital from January 2014 to December 2016 consecutive liver failure patients by artificial liver treatment, collected patient data, including general demographic information, medical history. Results Medical history data were collected from 189 compliance cases, including deep venous thrombosis group (11 cases),no deep venous thrombosis group(178 cases),and 5.82%(11/189)of deep vein thrombosis.There were significant differences in age(χ2=7.17, P=0.027), catheterization(χ2=4.99, P=0.025), number of successful venipuncture(χ2=10.856, P=0.004),artificial liver frequency(χ2=67.481, P<0.01), activity status(χ2=9.607, P=0.022), D-dimer(t=12.318, P<0.01), infection(χ2=17.231, P=0.001)and other factors in thrombosis group and thrombus group(P<0.05).Logistic regression showed that age(OR=1.643, P=0.01),activity status(OR=1.643,P=0.01),number of successful venipuncture(OR=6.049,P<0.01),D-dimer(OR=2.532, P=0.005)and infection(OR=2.463, P=0.008)were independent risk factors for thrombosis. Conclusions Deep vein thrombosis after artificial liver injury in liver failure is not uncommon, and the prevention of deep vein thrombosis after artificial liver surgery is strengthened, especially for elderly, absolute bed, venous puncture injury patients, elevated D-dimer and infected patients.

ObjectiveTo survey the effects of nucleos(t)-ide analogues on the drug compliance of patients with e-antigen negative chronic hepatitis B patients and its influencing factors.MethodsA retrospective survey was used to investigate consecutive patients who were hospitalized in our hospital from January 2008 to December 2009. Telephone interviews,medical inquiries,questionnaires and follow-ups were used to collect patients′ general information,which included general demographic information,medical history,and hepatitis B knowledge questionnaire.Results Follow-up data were collected from 327 compliance cases,which included 149 cases of good compliance and 178 cases of poor compliance. The compliance ratio was 45.57%. There were significant differences between good compliance group and poor compliance group in education background, economic status,insurance type,and the knowledge about hepatitis B (P<0.05). Binary Logistic regression analysis showed that high-income level,good knowledge about hepatitis B were the independent risk factors of high compliance (P<0.001).Conclusions The drug compliance of patients who use nucleos(t)-ide analogues to treat e-antigen negative chronic hepatitis B is poor,and we should strengthen the health education to improve the drug compliance of using nucleos(t)-ide analogues.