Regression-based Chinese norms of number connection test A and digit symbol test for diagnosing minimal hepatic encephalopathy.

Number connection test A (NCT-A) and digit symbol test (DST), the preferential neuropsychological tests to detect minimal hepatic encephalopathy (MHE) in China, haven't been standardized in Chinese population. We aimed to establish the norms based on a multi-center cross-sectional study and to detect MHE in cirrhotic patients. NCT-A and DST were administered to 648 healthy controls and 1665 cirrhotic patients. The regression-based procedure was applied to develop demographically adjusted norms for NCT-A and DST based on healthy controls. Age, gender, education, and age by education interaction were all predictors of DST, while age, gender, and education by gender interaction were predictors of log10 NCT-A. The predictive equations for expected scores of NCT-A and DST were established, and Z-scores were calculated. The norm for NCT-A was set as Z ≤ 1.64, while the norm for DST was set as Z ≥ - 1.64. Cirrhotic patients with concurrent abnormal NCT-A and DST results were diagnosed with MHE. The prevalence of MHE was 8.89% in cirrhotic patients, and only worse Child-Pugh classification (P = 0.002, OR = 2.389) was demonstrated to be the risk factor for MHE. The regression-based normative data of NCT-A and DST have been developed to detect MHE in China. A significant proportion of Chinese cirrhotic patients suffered from MHE, especially those with worse Child-Pugh classification.

Scoparone inhibits the development of hepatocellular carcinoma by modulating the p38 MAPK/Akt/NF-κB signaling in nonalcoholic fatty liver disease mice.

BACKGROUND AND STUDY AIM: The mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms. MATERIALS AND METHODS: A model of NAFLD-HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT-PCR were performed to analyze protein expression and measure mRNA expression levels, respectively. RESULTS: Scoparone could ameliorate the pathological alterations observed in NAFLD-HCC mouse model. IHC analysis indicated an upregulation of NF-κB p65 expression in both NAFLD and NAFLD-HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF-κB target genes, including TNF-α, MCP-1, iNOS, COX-2, NF-κB, and MMP-9, which were originally elevated in the NAFLD-HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD-HCC model. CONCLUSION: These findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD-associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF-κB signaling cascade.

Predicting Positive Repeat Prostate Biopsy Outcomes: Comparison of Machine Learning Approaches to Identify Key Parameters and Optimal Algorithms.

BACKGROUND: Innovative strategies are necessary to enhance prostate cancer diagnosis whilst reducing unnecessary and invasive repeat biopsies. This study aimed to determine the significant parameters affecting repeat prostate biopsy outcomes and develop an optimal machine learning algorithm for predicting positive repeat prostate biopsy results. METHODS: We analysed data from 174 men who underwent repeated prostate biopsies between January 2008 and December 2022. Systematic multiple-core, ultrasound-targeted prostate biopsies were performed, each two samples from prostatic transitional zone and peripheral zone were obtained bilaterally. Clinical characteristics were collected, including patients' age, initial prostate volume, prostate-specific antigen (PSA) level, free PSA (fPSA)/PSA ratio, biopsy core numbers, pathological result; The time interval between first and latest prostate biopsy; Latest PSA level, fPSA/PSA ratio, biopsy core numbers; And final pathological diagnosis. Six feature selection methods, namely, variable ranking, correlation matrix, random forest regression, recursive feature elimination, cross-validation and forward selection, were employed to identify key influencing factors for repeat biopsy outcomes. Subsequently, the performance of seven machine learning algorithms, namely, multivariable logistic regression (LR), K-nearest neighbour search (KNN), support vector classification (SVC), decision tree (DT), random forest classifier (RF), naïve Bayes classifier (NBC) and gradient booster tree (GB), was assessed based on accuracy, misclassification, recall, specificity, precision and receiver operating characteristic (ROC) area under the curve (AUC). About 70% of patients were used as the training dataset, meanwhile remaining 30% as validation dataset. RESULTS: 52 were ultimately diagnosed with prostate cancer following the final pathological examination. The remaining 122 patients were negative. Amongst six feature selection methods, the variable ranking emerged as the most effective method for identifying the essential factors influencing repeat biopsy results. Amongst the machine learning algorithms, SVC demonstrated superior accuracy (0.7365), low recall rate (0.2500) and low misclassification rate (0.2093) for both patients with cancer and healthy individuals. Meanwhile, the ROC curve of SVC showed a relatively high AUC (0.6871). CONCLUSIONS: We developed an SVC-based machine learning algorithm for predicting positive repeat prostate biopsy results. Our analysis revealed that initial and latest prostate volumes, initial and latest PSA levels, latest fPSA/PSA ratio and age are significant factors for this model.

Predicting Positive Repeat Prostate Biopsy Outcomes: Comparison of Machine Learning Approaches to Identify Key Parameters and Optimal Algorithms

Background: Innovative strategies are necessary to enhance prostate cancer diagnosis whilst reducing unnecessary and invasive repeat biopsies. This study aimed to determine the significant parameters affecting repeat prostate biopsy outcomes and develop an optimal machine learning algorithm for predicting positive repeat prostate biopsy results. Methods: We analysed data from 174 men who underwent repeated prostate biopsies between January 2008 and December 2022. Systematic multiple-core, ultrasound-targeted prostate biopsies were performed, each two samples from prostatic transitional zone and peripheral zone were obtained bilaterally. Clinical characteristics were collected, including patients’ age, initial prostate volume, prostate-specific antigen (PSA) level, free PSA (fPSA)/PSA ratio, biopsy core numbers, pathological result; The time interval between first and latest prostate biopsy; Latest PSA level, fPSA/PSA ratio, biopsy core numbers; And final pathological diagnosis. Six feature selection methods, namely, variable ranking, correlation matrix, random forest regression, recursive feature elimination, cross-validation and forward selection, were employed to identify key influencing factors for repeat biopsy outcomes. Subsequently, the performance of seven machine learning algorithms, namely, multivariable logistic regression (LR), K-nearest neighbour search (KNN), support vector classification (SVC), decision tree (DT), random forest classifier (RF), naïve Bayes classifier (NBC) and gradient booster tree (GB), was assessed based on accuracy, misclassification, recall, specificity, precision and receiver operating characteristic (ROC) area under the curve (AUC). About 70% of patients were used as the training dataset, meanwhile remaining 30% as validation dataset. Results: 52 were ultimately diagnosed with prostate cancer following the final pathological examination. The remaining 122 patients were negative (AU)

The relationship between vitamin D deficiency and diabetic foot ulcer: A meta-analysis.

A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/ß-Catenin Axis.

Objective: Liver cancer seriously threatens the health of people. Meanwhile, it has been reported that bufalin could act as an inhibitor in liver cancer. In addition, alisol B 23-acetate is a natural product derived from Alisma plantago-aquatica Linn which has an antitumor effect. In this study, we aimed to explore whether alisol B 23-acetate could increase the antitumor effect of bufalin on liver cancer. Methods: In order to detect the effect of alisol B 23-acetate in combination with bufalin on liver cancer, human liver cancer SMMC-7721 and MHCC97 cells were used as subjects. Bufalin and alisol B 23-acetate were performed on cells. Cell viability was tested by MTT assay. In addition, flow cytometry was performed to assess the cell apoptosis. Autophagy-related protein levels were tested by western blotting. Results: The data revealed that bufalin significantly decreased the viability of liver cancer cells, and the inhibitory effect was further increased by alisol B 23-acetate. In addition, alisol B 23-acetate notably enhanced the apoptotic effect of bufalin on liver cancer cells through mediation of Mcl-1, Bax, Bcl-2, and cleaved caspase-3. Meanwhile, alisol B 23-acetate in combination with bufalin induced the autophagy in liver cancer cells through mediation of Beclin-1 and p62. Furthermore, alisol B 23-acetate in combination with bufalin significantly downregulated the level of GSK-3ß and increased the expression of ß-catenin in liver cancer cells. Conclusion: In summary, these findings provide the first evidence that alisol B 23-acetate improves the anticancer activity of bufalin on liver cancer through activation of the Wnt/ß-catenin axis, and these outcomes might shed new lights on exploring the new methods against liver cancer.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

Alleviation of non-alcoholic fatty liver disease by Huazhi Fugan Granules is associated with suppression of TLR4/NF-kB signaling pathway / El alivio de la enfermedad de hígado graso no alcohólico con gránulos de Huazhi Fugan está asociado con la supresión de la vía de señalización de TLR4/NF-kB

Introduction: In parallel with the improvement of living standard, Non-alcoholic fatty liver disease (NAFLD) becomes the most common liver disease around the world. Huazhi Fugan Granules (HZFGG) is a formula which is used to treating of fatty liver, Based on the data we studied, HZFGG may have potential as a therapeutic formula for the alleviation of NAFLD. Objectives: The aim of our study was to identifying the improvement of HZFGG on NAFLD and exploring the potential mechanisms. Methods: MCD diet fed C57BL/6 mice once a day for 4 weeks to induce NAFLD model, HZFGG (10, 15, 20g/kg) orally administered simultaneously. The serum levels of TC, TG, ALT, AST were detected. H&E and Oil Red O staining were used to observed the liver sections. TNF-α, IL-1β and Gpx were also detected. The expression levels of TLR4, MyD88, p-NF-κB, NF-κB, p-IκBa were measured by western blotting assay. The apoptosis of the liver tissues were detected by TUNEL assay. Results: HZFGG decreased the serum levels of TC, TG, ALT, AST in MCD-diet mice. HZFGG alleviated inflammation by decreasing the levels of TNF-α and IL-1β and ameliorated oxidative stress through increased the level of Gpx. HZFGG Attenuates MCD-induced liver steatosis and injury in mice. Hepatocyte apoptosis was decreased after HZFGG treatment. Furthermore, HZFGG also suppressed the expression levels of TLR4 and MyD88, subsequently, inhibited the phosphorylation of NF-κB and IκBa. Conclusion: HZFGG can improved MCD induced hepatic injury through inhibited TLR4/NF-κB signaling pathway in NAFLD model.(AU)

Introducción: En paralelo con la mejora de la calidad de vida, la enfermedad de hígado graso no alcohólico (EHGNA) se ha convertido en la enfermedad hepática más común a nivel mundial. Los gránulos de Huazhi Fugan (HZFGG) son una fórmula utilizada para tratar el hígado graso. Basándonos en los datos que estudiamos, HZFGG puede tener potencial de fórmula terapéutica para el alivio de EHGNA. Objetivos: El objetivo de este estudio fue identificar la mejora de EHGNA con el uso de HZFGG y explorar los mecanismos potenciales. Métodos: Se alimentó con dieta deficiente en metionina y colina (MCD) a ratones C57BL/6 una vez al día durante cuatro semanas, para inducir el modelo EHGNA, administrándose simultáneamente HZFGG oral (10, 15, 20 g/kg). Se detectaron los niveles séricos de TC, TG, ALT y AST. Se utilizaron tinciones de hematoxilina-eosina y rojo aceite para observar las secciones hepáticas. También se detectaron TNF-α, IL-1β y Gpx. Se midieron los niveles de expresión de TLR4, MyD88, p-NF-κB, NF-κB y p-IκBa, mediante la técnica de Western blot. Se detectó la apoptosis de los tejidos hepáticos utilizando la técnica TUNEL. Resultados: HZFGG redujo los niveles séricos de TC, TG, ALT, AST en los ratones con dieta MCD. HZFGG alivió la inflamación reduciendo los niveles de TNF-α e IL-1β, y mejoró el estrés oxidativo a través del incremento del nivel de Gpx. HZFGG atenúa la esteatosis y lesión hepáticas inducidas por MCD. La apoptosis hepatocítica se redujo tras el tratamiento con HZFGG. Además, HZFGG suprimió también los niveles de expresión de TLR4 y MyD88, y posteriormente inhibió la fosforilación de NF-κB e IκBa. Conclusión: HZFGG puede mejorar la lesión hepática inducida por MCD, mediante la inhibición de la vía de señalización de TLR4/NF-κB en un modelo de EHGNA.(AU)

Alleviation of non-alcoholic fatty liver disease by Huazhi Fugan Granules is associated with suppression of TLR4/NF-κB signaling pathway.

INTRODUCTION: In parallel with the improvement of living standard, Non-alcoholic fatty liver disease (NAFLD) becomes the most common liver disease around the world. Huazhi Fugan Granules (HZFGG) is a formula which is used to treating of fatty liver, Based on the data we studied, HZFGG may have potential as a therapeutic formula for the alleviation of NAFLD. OBJECTIVES: The aim of our study was to identifying the improvement of HZFGG on NAFLD and exploring the potential mechanisms. METHODS: MCD diet fed C57BL/6 mice once a day for 4 weeks to induce NAFLD model, HZFGG (10, 15, 20g/kg) orally administered simultaneously. The serum levels of TC, TG, ALT, AST were detected. H&E and Oil Red O staining were used to observed the liver sections. TNF-α, IL-1ß and Gpx were also detected. The expression levels of TLR4, MyD88, p-NF-κB, NF-κB, p-IκBa were measured by western blotting assay. The apoptosis of the liver tissues were detected by TUNEL assay. RESULTS: HZFGG decreased the serum levels of TC, TG, ALT, AST in MCD-diet mice. HZFGG alleviated inflammation by decreasing the levels of TNF-α and IL-1ß and ameliorated oxidative stress through increased the level of Gpx. HZFGG Attenuates MCD-induced liver steatosis and injury in mice. Hepatocyte apoptosis was decreased after HZFGG treatment. Furthermore, HZFGG also suppressed the expression levels of TLR4 and MyD88, subsequently, inhibited the phosphorylation of NF-κB and IκBa. CONCLUSION: HZFGG can improved MCD induced hepatic injury through inhibited TLR4/NF-κB signaling pathway in NAFLD model.

Entecavir combining Chinese herbal medicine for HBeAg-positive chronic hepatitis B patients: a randomized, controlled trial.

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. METHODS: 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. RESULTS: The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. CONCLUSION: Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. CLINICAL TRIAL NUMBER: ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

Preliminary Experience of Nontransecting Urethroplasty for Pelvic Fracture-related Urethral Injury.

OBJECTIVE: To evaluate the urinary outcomes and preservation of erectile function in patients with pelvic fracture-related urethral injury (PFUI) after nontransecting spongiosum anastomotic urethroplasty (NTSAU). MATERIALS AND METHODS: Fifty-nine male patients with PFUI following traumatic pelvic fracture underwent NTSAU. Inclusion criteria were age 18-60 years, posterior urethral stenosis <2.5 cm without previous urethroplasty, and intact erectile function. Exclusion criteria were history of open urethroplasty, long-segment posterior urethral stenosis (>2.5 cm), preoperative impotency, or age over 60 years. Pre- and postoperative outcome analyses were performed with a paired t test and chi-square test. RESULTS: Between January 2011 and August 2015, 59 patients with a mean age of 38.5 years (range, 21-59 years) and a mean stricture length of 2.0 cm (range, 1-2.5 cm) underwent simple NTSAU (group 1, n = 41) or NTSAU with inferior pubectomy (group 2, n = 18). Patients were followed for a mean 25 months (range, 12-60 months). The primary success rate was 96.6% (57 of 59), and stricture recurrence occurred in 2 (3.4%) patients. The secondary outcomes revealed no significant changes in number of events, tip rigidity, or duration of best episode between pre- and postoperative nocturnal penile tumescence test (on RigiScan) in group 1, but a slight decrease in group 2 (P <.05). The limitation was the small sample size and heterogeneous population. CONCLUSION: NTSAU is a safe, feasible, minimally invasive procedure for PFUI, optimizing erectile preservation.

The association of DENND1A gene polymorphisms and polycystic ovary syndrome risk: a systematic review and meta-analysis.

PURPOSE: Polycystic ovary syndrome is heterogeneity disease, and the association with DEEND1A gene has been discussed incompatibly for a long time. We conducted a meta-analysis to evaluate the rs10818854, rs2479106, and rs10986105 polymorphism in DENND1A gene with PCOS susceptibility. METHODS: Meta-analysis was performed for common allele versus rare allele using random effect model on published papers from January 1, 1980 to October 1, 2015. Subgroup analysis, sensitivity analysis and publication bias were also carried out ultimately. The combined odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the strength of the association. RESULTS: The results showed that rs10818854 (OR = 1.36, 95 % CI 1.12-1.61) and rs10986105 (OR = 1.39, 95 % CI 1.20-1.58) polymorphism increased the risk of PCOS probably. A significant association was also found between rs2479106 mutation and Asian PCOS patients but not Europeans (OR = 1.32, 95 % CI 1.25-1.39; OR = 1.01, 95 % CI 0.97-1.05, respectively). CONCLUSIONS: In conclusion, the DENND1A gene variant is likely to have influence on PCOS risk. Further studies are warranted to assess these associations in greater detail, especially in different populations and different subtype of PCOS patients.

Long non-coding RNA-H19 antagonism protects against renal fibrosis.

Although long non-coding RNAs (lncRNAs) are important players in the initiation and progression of many pathological processes, the role of lncRNAs in renal fibrosis still remains unclear. We showed that lncRNA-H19 expression was significantly up-regulated in TGF-ß2-induced HK-2 cell fibrosis and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo. H19 knockdown significantly attenuated renal fibrosis in vitro and in vivo. LncRNA-H19, miR-17, and fibronectin constituted to a regulatory network involved in renal fibrosis. We also detected up-regulated H19 expression and down-regulated miR-17 expression in the early and advanced animal models of renal fibrosis. This study indicates that H19 up-regulation contributes to renal fibrosis. H19 inhibition might represent a novel anti-fibrotic treatment in renal diseases.

Seeding cell approach for tissue-engineered urethral reconstruction in animal study: A systematic review and meta-analysis.

We systematically reviewed published preclinical studies to evaluate the effectiveness of cell-seeded tissue engineering approach for urethral reconstruction in an animal model. The outcomes were summarized by success factors in the animal experiments, which evaluate the possibility and feasibility of a clinical application in the future. Preclinical studies of tissue engineering approaches for urethral reconstruction were identified through a systematic search in PubMed, Embase, and Biosis Previews (web of science SP) databases for studies published from 1 January 1980 to 23 November 2014. Primary studies were included if urethral reconstruction was performed using a tissue-engineered biomaterial in any animal species (with the experiment group being a cell-seeded scaffold and the control group being a cell-free scaffold) with histology and urethrography as the outcome measure. A total of 15 preclinical studies were included in our meta-analysis. The histology and urethrography outcome between the experimental and control groups were considered to be the most clinically relevant. Through this systematic approach, our outcomes suggested that applying the cell-seeded biomaterial in creating a neo-urethra was stable and effective. And multi-type cells including epithelial cells as well as smooth muscle cells or fibroblasts seemed to be a better strategy. Stem cells, especially after epithelial differentiation, could be a promising choice for future researches.

Single-Staged Improved Tubularized Preputial/Penile Skin Flap Urethroplasty for Obliterated Anterior Urethral Stricture: Long-Term Results.

INTRODUCTION: To present an improved tubularized flap (ITF) technique and report the outcome of single-stage urethroplasty using preputial/penile skin flaps (PSFs) for the treatment of obliterative anterior urethral strictures (AUSs). MATERIALS AND METHODS: From January 2000 to June 2012, 42 cases of obliterative AUS (3-14 cm, mean 6.38 cm) with urethral plate unsalvageable were treated using PSF-ITF urethroplasty including longitudinal skin flap, circular island flap, L-flap, Q-flap. Patients were divided into 3 groups: pendulous urethral stricture (Group A), bulbar urethral stricture (Group B) and panurethral strictures (Group C). Patients were followed up by uroflowmetry, urethrography and ureteroscope when necessary. RESULTS: The mean follow-up in these patients was 65 months (range 36 months-15 years). The primary success rates at 3-year follow-up were 75, 75 and 60% for Groups A, B and C, respectively. The overall success rates were 85, 83 and 70% with the remedial measure of a single visual internal urethrotomy at 3-year follow-up. A total 60% of the patients in the study completed more than 5 years of follow-up with no additional recurrence. CONCLUSIONS: Improved tubularized preputial/PSF urethroplasty with relatively high overall satisfaction is a novel technique for treatment of AUS when there is inadequate urethral plate or obliterative defects.

[Efficacy observation on navel-warming therapy combined with western medication for yang-deficiency tympanites].

OBJECTIVE: To observe the effects of navel-warming therapy on clinical efficacy in patients with yang-deficiency tympanites based on regular treatment of western medication. METHODS: One hundred and twenty cases of yang-deficiency tympanites were randomly divided into a navel-warming therapy group and a western medication group, sixty cases in each one. The regular treatment of western medicine was applied in the western medication group, including oral administration of antiviral drug and diuretics as well as intravenous drip of hepatic protector. Based on western medicine treatment, the navel-warming therapy was applied in the navel-warming group. A medical cake was laid on Shenque (CV 8), and then a medical cylinder was placed above the medical cake and ignited. The treatment was given once daily. One month was considered as a treatment session in both groups and totally one session was required. The TCM symptom score, B-ultrasound ascites and temporary use of diuretics before and after treatment were observed in both groups; also the efficacy was evaluated. RESULTS: The total effective rate was 81.7% (49/60) in the navel-warming therapy group, which was superior to 56.7% (34/60) in the western medication group (P < 0.05). After the treatment, the TCM symptom score and ascites were improved in both groups (all P < 0.05), which was more significant in the navel-warming therapy group (all P < 0.05). The temporary use of diuretics was statistically different between the two groups (P < 0.05), indicating the navel-warming therapy group could obviously reduce or stop the use of diuretics. CONCLUSION: Based on regular treatment of western medication, the navel-warming therapy could significantly improve therapeutic efficacy, effectively relieve clinical symptoms and ease ascites.