OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.

METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.

RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.

CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the clinical results of the treatment of severe infantile hemangioma with high-dose propranolol in Chinese.

METHODS56 cases with severe infantile hemangioma were treated with propranolol. Clinical evaluation, electrocardiography, and experimental examination of liver function and heart function were performed before treatment. The daily dose of propranolol was increased from 1 mg/kg at the first day to 1.5 mg/kg at the second day, and to 2 mg/kg at the third day. The propranolol was given twice a day. The treatment was lasted for six months. The patients were visited every month.

RESULTSThe lesion color was changed after 2-4 days of treatment in all the cases. All the lesions were dramatically improved after one month of treatment. The ulceration were healed, except one case. Until now, complete regression was achieved in 10 cases and marked improvement in 46 cases. Side effects were happened in 3 cases, including one case of abnormal liver function, one case of CK-MB increase and one case of continuous increase of CK-MB, LDH, ALT, GGT.

CONCLUSIONSHigh-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period. It might he used as the first-line treatment for infantile hemangioma.

China ; Female ; Hemangioma ; drug therapy ; Humans ; Infant ; Male ; Propranolol ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients.

METHODSTwenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains.

RESULTSThe cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy.

CONCLUSIONIncreased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Drug Resistance, Viral ; Evolution, Molecular ; Female ; Hepatitis B virus ; classification ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; Male ; Middle Aged ; Organophosphonates ; therapeutic use

OBJECTIVERecent study demonstrated that hypoxia could regulate the proliferation and differentiation of neural stem cells in vitro. In the present study, effects of low glucose and/or hypoxia on the proliferation and metabolism of neural stem cells were investigated in vitro.

METHODSThe neural stem cells were isolated from the rat embryonic mesencephalon (E13.5), and exposed to different oxygen concentrations (low oxygen: 3% O2 or normoxia: 20% O2) and different glucose concentrations (high glucose concentration: 4.5 g/L and low glucose concentration: 1.4 g/L) for 3 days. The proliferation of neural stem cells were examined by CCK-8 assay. Furthermore, the content of glucose, lactate, and pyruvic acid in the medium were measured after cultured in different condition for 1, 3, 5 days.

RESULTSLow oxygen and low glucose could increase the proliferation of neural stem cells respectively; in addition, the number of neurospheres under both low oxygen and glucose was the most among the four groups. The content of glucose and pyruvic acid in the medium from low oxygen or low glucose condition decreased, while the lactate concentration increased compared with the control group.

CONCLUSIONThe results indicate the neural stem cells prefer grow under the low glucose and low oxygen condition, and that is mainly under going glycolysis to maintain its self-renew ability. This study may provide us a useful clue for application of neural stem cells transplantation.

Animals ; Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Female ; Glucose ; metabolism ; Glycolysis ; Neural Stem Cells ; cytology ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Purpose: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. Methods: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. Results: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. Conclusions In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Background/Aims: Steatotic liver disease (SLD) is a common manifestation in chronic hepatitis C (CHC). Metabolic alterations in CHC are associated with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to elucidate whether hepatitis C virus (HCV) eradication mitigates MASLD occurrence or resolution. Methods: We enrolled 5,840 CHC patients whose HCV was eradicated by direct-acting antivirals in a nationwide HCV registry. MASLD and the associated cardiometabolic risk factors (CMRFs) were evaluated at baseline and 6 months after HCV cure. Results: There were 2,147 (36.8%) patients with SLD, and 1,986 (34.0%) of them met the MASLD criteria before treatment. After treatment, HbA1c (6.0% vs. 5.9%, p<0.001) and BMI (24.8 kg/m2 vs. 24.7 kg/m2, p<0.001) decreased, whereas HDL-C (49.1 mg/dL vs. 51.9 mg/dL, p<0.001) and triglycerides (102.8 mg/dL vs. 111.9 mg/dL, p<0.001) increased significantly. The proportion of patients with SLD was 37.5% after HCV eradication, which did not change significantly compared with the pretreatment status. The percentage of the patients who had post-treatment MASLD was 34.8%, which did not differ significantly from the pretreatment status (p=0.17). Body mass index (BMI) (odds ratio [OR] 0.89; 95% confidence intervals [CI] 0.85–0.92; p<0.001) was the only factor associated with MASLD resolution. In contrast, unfavorable CMRFs, including BMI (OR 1.10; 95% CI 1.06–1.14; p<0.001) and HbA1c (OR 1.19; 95% CI 1.04–1.35; p=0.01), were independently associated with MASLD development after HCV cure. Conclusions HCV eradication mitigates MASLD in CHC patients. CMRF surveillance is mandatory for CHC patients with metabolic alterations, which are altered after HCV eradication and predict the evolution of MASLD.

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.