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Objective: To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).Design: A multicenter randomized double-blinded placebo-controlled trial.Setting: Reproductive and developmental network sites.Patient(s): Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups.Interventions(s): Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant.Main Outcomes Measure(s): Cumulative live births.Results: The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group.Conclusion(s): Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole.Clinical Trial Registration Number: ChiCTR-TRC-09000376 (http://apps.who.int/trialsearch/). [ABSTRACT FROM AUTHOR]

Background: Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer.Purpose: We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines.Materials and Methods: Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur-sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times.Results: Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6±2.91 nmol/[mg·min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3±7.02nmol/[mg·min]).Conclusions: Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment. [ABSTRACT FROM AUTHOR]