Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients.

Reasonable and standardised placebo setting for acupoint application pastes is a key factor for clinical trials to verify the safety and effectiveness of acupoint application. By sorting out the current design status of placebo in the allocation concealment and blind design， paste components， paste location， paste duration in the current clinical trials of acupoint application pastes， it is proposed that there are problems such as low application rate of blinding and non-standardised reporting， insufficient standardisation of placebo settings and lack of systematic research， and lack of uniform standards of the placebo evaluation method. Based on the action mechanism of acupoint application， the idea of setting placebo for acupoint application paste is proposed in terms of replacing the application material， controlling the physicochemical effect produced by transdermal absorption of drugs， and setting the permeability of placebo， in order to enrich the methodological content of the placebo setting for acupoint application， and providing more scientific and reliable clinical evidence of acupoint application.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Objective:To establish a risk scoring system for moderate to severe spermatogenic dysfunction based on scrotal ultrasound parameters and machine learning, and to explore its value.Methods:A retrospective cohort analysis was conducted on 112 patients diagnosed with azoospermia, moderate to severe oligospermia, and asthenospermia in the Department of Reproductive Medicine at Binzhou Medical University Affiliated Hospital from June 2021 to December 2022. Scrotal ultrasound parameters of these patients were compared with those of 116 normal male patients who visited the same hospital during the same period for reproductive assistance. Models were constructed using Random Forest, Support Vector Machine, logistic Regression, K-nearest neighbor algorithm, and XGBoost. A risk scoring system was established based on the average SHapley Additive exPlanation values of each model. The predictive performance of the model was evaluated using the receiver operating characteristic curve, and the clinical application value of the model was evaluated using the decision curve analysis.Results:The scoring system included bilateral testicular total volume, whether the testicular echo was uniform, the inner diameter of the right spermatic vein, and the reflux time of varicocele. The area under the curve (AUC) of the risk scoring system for the training set was 0.757, and the AUC for the test set was 0.718. The decision curve showed that this scoring system had a high clinical value.Conclusion:A risk scoring system based on scrotal ultrasound parameters and machine learning can effectively predict moderate to severe spermatogenic dysfunction, which is of positive significance for early detection of such patients.

Objective:To establish a risk scoring system for moderate to severe spermatogenic dysfunction based on scrotal ultrasound parameters and machine learning, and to explore its value.Methods:A retrospective cohort analysis was conducted on 112 patients diagnosed with azoospermia, moderate to severe oligospermia, and asthenospermia in the Department of Reproductive Medicine at Binzhou Medical University Affiliated Hospital from June 2021 to December 2022. Scrotal ultrasound parameters of these patients were compared with those of 116 normal male patients who visited the same hospital during the same period for reproductive assistance. Models were constructed using Random Forest, Support Vector Machine, logistic Regression, K-nearest neighbor algorithm, and XGBoost. A risk scoring system was established based on the average SHapley Additive exPlanation values of each model. The predictive performance of the model was evaluated using the receiver operating characteristic curve, and the clinical application value of the model was evaluated using the decision curve analysis.Results:The scoring system included bilateral testicular total volume, whether the testicular echo was uniform, the inner diameter of the right spermatic vein, and the reflux time of varicocele. The area under the curve (AUC) of the risk scoring system for the training set was 0.757, and the AUC for the test set was 0.718. The decision curve showed that this scoring system had a high clinical value.Conclusion:A risk scoring system based on scrotal ultrasound parameters and machine learning can effectively predict moderate to severe spermatogenic dysfunction, which is of positive significance for early detection of such patients.