Objective:To explore the effects of Yishen Tonglong Granules (YSTLG) on cell proliferation and apoptosis in a nude mouse model of androgen independent prostate cancer subcutaneous transplantation based on non classical Wnt signaling pathway.Methods:The tumor-bearing nude mouse model was established using the human prostate cancer bone metastatic cell line PC-3. After successful modeling, the mice were equally divided into six groups using the random number table method: model group, Western medicine group, Chinese materia medica low-, medium-, and high-dosage groups, and Chinese materia medica-Western medicine combination group. Corresponding drug interventions were administered to each group. Following 28 consecutive days of drug administration, the nude mice were euthanized. Tumor tissues were harvested for pathological observation via HE staining. Cell proliferation was assessed by immunohistochemistry; apoptosis was detected using TUNEL assay; the expressions of non-canonical Wnt signaling pathway-related proteins (Wnt5a, Rac1, RhoA, NFATc1) were analyzed through Western blot and immunohistochemical methods.Results:THE staining results demonstrated that YSTLG could effectively ameliorate pathological alterations in tumor tissues. Compared with the model group, the Chinese materia medica low-, medium-, and high-dosage groups, as well as the Chinese materia medica-Western medicine combination group, exhibited reduced proliferation indices ( P<0.01), elevated apoptosis indices ( P<0.01), down-regulated protein expressions of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01), and decreased optical density values of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01). These effects displayed a dosage-dependent trend. The Chinese materia medica-Western medicine combination group achieved the most pronounced therapeutic outcomes. Conclusions:YSTLG may exert inhibitory effects on the proliferation of androgen-independent prostate cancer cells and promote apoptosis, possibly through suppression of the non-canonical Wnt signaling pathway. Furthermore, its combination with Wnt signaling inhibitors may exhibit synergistic therapeutic effects.

Objective:To investigate the clinical effect of lingual mucosal augmentation urethroplasty with non-transecting urethral cavernous anastomosis in the treatment of traumatic urethral stricture.Methods:The clinical data of 39 patients with traumatic urethral stricture admitted to our clinical center from March 2023 to December 2023 were retrospectively analyzed. Their mean age was (49.7±2.0)years. The cause of urethral injury was pelvic fracture in 32 cases, riding injury in 5 cases, and iatrogenic injury in 2 cases. Suprapubic vesicostomy tube was indwelled before operation in 39 cases. There was 1 case with hypospadias and 1 case with urethral false passage. 9 patients had urethral dilatation before surgery, 5 had internal urethrotomy operation, 5 had urethroplasty, and 22 had no history of urethral surgery. The International Erectile Function Index (IIEF-5)score of 39 cases last 1 month before surgery was collected and classified.In which, the IIEF-5 score of 19 cases with no or mild erectile dysfunction was median 20 (18, 23)points, the MSHQ-Ejd score was median 16 (11, 19)points, and the number of effective erections was median 4(3, 5)times on the NPT. And in which, the IIEF-5 score of 20 cases with moderate to severe erectile dysfunction was median 10 (3, 14)points, the MSHQ-Ejd score was median 3(1, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT. All 39 cases underwent non-transecting anastomotic lingual mucosal augmentation urethroplasty. The central tendon of the perineum and the ventral side of the bulbar urethra were preserved through perineal approach. The dorsal side of the urethra was mobilized and through the dorsal side of the urethra, the scar of the urethra was enucleated along the mucosa of the urethra. Then the ventral mucosa of the urethra was anastomosed end to end and the dorsal urethra was repaired by lingual mucosa transplantation. The Clavien-Dindo complication grading system was performed. The catheter was removed 4 weeks after operation, and urine flow rate was recorded 1 month after extubation. IIEF-5 score, MSHQ-Ejd score and NPT were recorded 6 months after operation.Results:The mean operation time of 39 cases was (118.0±18.3)min. 39 cases were followed up for median 8.0(6.0, 10.0)months. The Q max ≥15 ml/s in 24 cases. The Q max <15ml/s in 13 cases, of which, the Q max ≥15 ml/s after 1 internal urethrotomy operation in 10 cases and Q max≥15 ml/s after 2 internal urethrotomy operations in 3 cases. 2 cases were still failed to urinate and Q max≥15 ml/s after end-to-end urethral anastomosis. All 39 cases’ Clavien-Dindo complications were graded Ⅰ.Of the 19 cases with no or mild erectile dysfunction, the IIEF-5 score was median 20(17, 23)points, the MSHQ-Ejd score was median 16(11, 19)points, and the number of effective erections was median 4(3, 4)times on the NPT postoperatively, all were not significantly different from those before operation ( P> 0.05). Of the 20 cases with moderate and severe erectile dysfunction, the IIEF-5 score was median 9(4, 13)points, the MSHQ-Ejd score was median 4(2, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT postoperatively, and all were not significantly different from those before operation ( P>0.05). Conclusions:Non-transecting anastomotic lingual mucosal augmentation urethroplasty is a reliable surgical method with few complications for traumatic urethral stricture. Moreover, the operation has little effect on the sexual function of patients.

OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system.METHODS A survey was conducted on 38 new institutions(obtained qualifications during the implementation of the filing system)and old institutions(obtained qualifications during the implementation of the recognition system)that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province.The survey focused on the basic information of the institutions,the number of registered principal investigator(PI),institutional hardware and information construction,personnel allocation and training,and drug registration clinical trials undertaken by the institutions.RESULTS Of 38 institutions surveyed,there were 22 general hospitals and 16 specialized hospitals;there were 24 old institutions and 14 new institutions.Whether in general hospitals or specialized hospitals,the old institutions were better than the new institutions in the number of approved beds,the number of outpatients,the number of inpatients,the number of specialties,and the number of PI;both old and new institutions had separate offices;all new institutions were set up with GCP pharmacy.The adoption of clinical trial management system in new institutions is significantly less than in old institutions.In the general hospital,both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions,while the opposite was true at the level of specialized hospitals.In terms of centralized training on GCP,new institutions were all better than the old ones.Whether in general hospitals or specialized hospitals,the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones.CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals,and the number of clinical trials undertaken by new institutions is also less than old institutions.

Objective:To investigate the clinical effect of lingual mucosal augmentation urethroplasty with non-transecting urethral cavernous anastomosis in the treatment of traumatic urethral stricture.Methods:The clinical data of 39 patients with traumatic urethral stricture admitted to our clinical center from March 2023 to December 2023 were retrospectively analyzed. Their mean age was (49.7±2.0)years. The cause of urethral injury was pelvic fracture in 32 cases, riding injury in 5 cases, and iatrogenic injury in 2 cases. Suprapubic vesicostomy tube was indwelled before operation in 39 cases. There was 1 case with hypospadias and 1 case with urethral false passage. 9 patients had urethral dilatation before surgery, 5 had internal urethrotomy operation, 5 had urethroplasty, and 22 had no history of urethral surgery. The International Erectile Function Index (IIEF-5)score of 39 cases last 1 month before surgery was collected and classified.In which, the IIEF-5 score of 19 cases with no or mild erectile dysfunction was median 20 (18, 23)points, the MSHQ-Ejd score was median 16 (11, 19)points, and the number of effective erections was median 4(3, 5)times on the NPT. And in which, the IIEF-5 score of 20 cases with moderate to severe erectile dysfunction was median 10 (3, 14)points, the MSHQ-Ejd score was median 3(1, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT. All 39 cases underwent non-transecting anastomotic lingual mucosal augmentation urethroplasty. The central tendon of the perineum and the ventral side of the bulbar urethra were preserved through perineal approach. The dorsal side of the urethra was mobilized and through the dorsal side of the urethra, the scar of the urethra was enucleated along the mucosa of the urethra. Then the ventral mucosa of the urethra was anastomosed end to end and the dorsal urethra was repaired by lingual mucosa transplantation. The Clavien-Dindo complication grading system was performed. The catheter was removed 4 weeks after operation, and urine flow rate was recorded 1 month after extubation. IIEF-5 score, MSHQ-Ejd score and NPT were recorded 6 months after operation.Results:The mean operation time of 39 cases was (118.0±18.3)min. 39 cases were followed up for median 8.0(6.0, 10.0)months. The Q max ≥15 ml/s in 24 cases. The Q max <15ml/s in 13 cases, of which, the Q max ≥15 ml/s after 1 internal urethrotomy operation in 10 cases and Q max≥15 ml/s after 2 internal urethrotomy operations in 3 cases. 2 cases were still failed to urinate and Q max≥15 ml/s after end-to-end urethral anastomosis. All 39 cases’ Clavien-Dindo complications were graded Ⅰ.Of the 19 cases with no or mild erectile dysfunction, the IIEF-5 score was median 20(17, 23)points, the MSHQ-Ejd score was median 16(11, 19)points, and the number of effective erections was median 4(3, 4)times on the NPT postoperatively, all were not significantly different from those before operation ( P> 0.05). Of the 20 cases with moderate and severe erectile dysfunction, the IIEF-5 score was median 9(4, 13)points, the MSHQ-Ejd score was median 4(2, 7)points, and the number of effective erections was median 1(0, 2)times on the NPT postoperatively, and all were not significantly different from those before operation ( P>0.05). Conclusions:Non-transecting anastomotic lingual mucosal augmentation urethroplasty is a reliable surgical method with few complications for traumatic urethral stricture. Moreover, the operation has little effect on the sexual function of patients.

Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82％,75.00％,and 59.09％in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate amino-transferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registration:ClinicalTrials.gov NCT03920618.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective To investigate the changing trend of platelet count (PLT) and related influencing factors in patients with hepatitis B virus-related chronic-on-acute liver failure (HBV-ACLF) after artificial liver support system (ALSS) therapy. Methods A total of 152 patients with HBV-ACLF who were hospitalized and treated in The Third Affiliated Hospital of Sun Yat-Sen University from January 2018 to November 2021 were included in the study, among whom 102 patients received plasma exchange (PE) and 50 patients received double plasma molecular absorption system combined with low-dose PE, and their clinical data and laboratory marker were measured. The independent samples t -test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and the chi-square test was used for the comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the risk factors for PLT > 50×10 9 /L after ALSS therapy; the receiver operating characteristic (ROC) curve was used to investigate the value of baseline PLT in predicting PLT > 50×10 9 /L after ALSS therapy. Results The patients were mostly middle-aged male adults; among the 152 patients, 70 (46.1%) had liver cirrhosis on admission, 114 (75.0%) received three sessions of ALSS therapy, and 88% had a baseline PLT count of > 50×10 9 /L. There was a significant reduction in PLT from baseline to after ALSS therapy (79.5±47.7 vs 112.5±64.1, t =4.965, P < 0.001), and at 1 week after treatment, PLT increased to the baseline level (97.2±50.7 vs 112.5±64.1, t =1.787, P =0.075). As for the change in PLT from baseline to 1 week after ALSS therapy, the liver cirrhosis group had a significantly greater reduction in PLT than the non-liver cirrhosis group ( U =1986.5, P =0.026), while there was no significant difference between different procedures of ALSS therapy and different sessions of treatment (3-5 sessions) (all P > 0.05). The multivariate logistic regression analysis showed that cirrhosis (odds ratio [ OR ]=3.097, 95% confidence interval [ CI ]: 1.255-7.645, P =0.014) and PLT > 50×10 9 /L at baseline ( OR =0.019, 95% CI : 0.002-0.154, P < 0.001) were independent risk factors for PLT > 50×10 9 /L after ALSS therapy. The ROC curve analysis of baseline PLT showed that PLT > 80.5×10 9 /L at baseline was the optimal cut-off value affecting PLT > 50×10 9 /L after treatment, with an area under the ROC curve of 0.818. Conclusion The influence of ALSS therapy on PLT is temporary, but cirrhotic patients have a weaker PLT generation ability than non-cirrhotic patients. PLT > 80.5×10 9 /L at baseline is the optimal cut-off value to reduce the risk of bleeding after ALSS therapy.

Objective:To report the clinical and genetic characteristics of a family of creatine transporter deficiency (CRTR-D) caused by SLC6A8 gene mutation.Methods:A patient, who came from Department of Neurology, Shanxi Children′s Hospital in September 2018, with epilepsy and unexplained general developmental retardation, was clinically examined. The medical history of his family was also collected. Genetic detection was performed to analyze their genetic causes.Results:The proband, a three years and three months old boy, was walking unsteadily, unable to speak and having frequent seizures, with increased urine creatine/creatinine ratio and decreased peak of cerebral creatine indicated by magnetic resonance spectrum. The proband′s uncle had the similar symptoms with him. The mother of the proband only showed some learning difficulties, while the father, sister and grandparents of the proband had no symptoms. The proband was found to have TTC deletion mutation of SLC6A8 gene (NM_005629), c. 1222_1224del (p.Phe408del), suggestting the diagnosis of X-linked CRTR-D. The proband′s mother and grandmother had heterozygous mutations. The proband′s uncle carried the same hemizygous mutation, which was not detected in the proband′s father, sister or grandfather.Conclusion:In this family of CRTR-D caused by SLC6A8 gene mutation, two female carriers with the same mutation presented different clinical features, suggesting phenotypic variation, which has a great significance in studying the correlation between genotype and phenotype.

Objective: To study the clinical efficacy of Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection in treatment of cerebral thrombosis. Methods: According to the random number table method, 91 cerebral thrombosis patients who met the inclusion criteria were divided into the control group (45 cases) and the study group (46 cases). The control group was treated with ozagrel sodium injection on the basis of routine treatment, while the study group was treated with Qixie-Huoxue-Tongluo decoction on the basis of the control group. The two groups were treated for 7 days. The National Institute of Health Stroke Scale (NIHSS)was used to assess the degree of neurological impairment, the Activity of Daily Living (ADL) was used to assess the quality of life; and the levels of MDA, SOD, NO, neuron-specific enolase (NSE) and neuronal protein (S-100β)were detected by ELISA.The clinical efficacy was evaluated. Results: The total effective rate was 93.5% (43/46) in the study group and 71.1% (32/45) in the control group, there was significant difference between the two groups (χ²=7.853, P=0.005). After treatment, the NIHSS score in the study group was significantly lower than that in the control group (16.1 ± 5.0 vs. 20.3 ± 5.3; t=3.889, P<0.01), and the ADL score in the study group (51.9 ± 9.3 vs. 45.3 ± 8.6, t=3.461) was significantly higher than that in the control group (P<0.01); the serum level of MDA (3.10 ± 0.48 mmol/L vs. 4.25 ± 0.76 mmol/L, t=11.427) and NO (41.14 ± 6.74 U/L vs. 62.20 ± 8.43 U/L, t=10.028) in the study group were significantly lower than those in the control group (P<0.01), the SOD (204.36 ± 21.29 vs. 163.39 ± 17.45, t=13.177) level in the study group was significantly higher than that of the control group (P<0.01); the serum NSE (4.85 ± 1.03 μg/L vs. 7.93 ± 1.14 μg/L, t=13.529) and S-100β protein (0.18 ± 0.03 μg/L vs. 1.02 ± 0.15 μg/L, t=37.232) levels in the study group were significantly lower than those in the control group (P<0.01). Conclusions Qixie-Huoxue-Tongluo decoction combined with ozagrel sodium injection can improve the degree of neurological impairment in patients with cerebral thrombosis, improve the quality of life clinical efficacy. And the mechanism may be related to inhibition of lipid peroxidation, anti-free radicals and so on.