Efficacy and safety of sertraline for the treatment of premature ejaculation: Systematic review and meta-analysis.

BACKGROUD: Evidence on the efficacy and safety of sertraline in patients with premature ejaculation (PE) was inconsistent. The objective of this article is to evaluate the efficacy and safety of sertraline for the treatment of PE. METHODS: We searched Medline (OVID), Embase, the Cochrane Library, and 2 Chinese databases for randomized controlled trials (RCTs) and randomized crossover trials (RTs) that evaluated the efficacy and safety of sertraline in patients with PE. A meta-analysis was performed to calculate their pooled estimates with 95% confidence interval. RESULTS: Of the 645 records obtained, we included 12 RCTs and 2 RTs (n = 977). Meta-analysis showed that sertraline prolonged intravaginal ejaculation latency time (IELT) in PE patients ((standard mean difference (SMD) = 2.14, 95% CI 1.20 to 3.08). Subgroup analyses indicated a prolonged IELT for different treatment courses: 4 weeks (SMD = 2.66, 1.06 to 4.26), 6 weeks (SMD = 0.95, 0.31 to 1.58), and 8 weeks (SMD = 1.81, 0.78 to 2.85). The sexual satisfaction rates of patients (SMD = 2.20, 1.57 to 2.84) and spouses (SMD = 2.27, 1.44 to 3.09) were also improved. We observed a significant increased risk of gastrointestinal upset (risk ratio = 2.71, 1.39 to 5.28) in the sertraline group. CONCLUSION: Sertraline can prolong IELT of PE patients, improve sexual satisfaction rates of patients and spouses, but increase risk of gastrointestinal upset.

SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43.

Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma cells significantly contribute to the progression of multiple myeloma (MM). However, little is known about the molecular mechanisms that regulate these interactions. Connexin-43 (Cx-43) has been implicated in the interplay between BMSCs and MM cells. In this study, we hypothesized that the steroid receptor co-activator-3 (SRC3) expressed in BMSCs regulates the expression of Cx-43 to promote the proliferation and migration of myeloma cells. To address this, we co-cultured a human multiple myeloma cell line, RPMI-8226 transfected with either control BMSCs or sh-SRC3-BMSCs. We found that knocking down SRC3 expression in BMSCs inhibited the proliferation and migration of RPMI-8226 cells. In addition, we found that co-culturing RPMI 8266 cells with BMSCs increased Cx43 expression, while knocking down SRC3 expression in BMSCs decreased Cx43 expression. Moreover, our work revealed that SRC3 in BMSCs regulates Cx43 expression via the mitogen-activated protein kinase (MAPK) pathway. To validate this result in vivo, we knocked down SRC3 expression in BMSCs in nude mice and found that tumor growth and cell apoptosis were significantly decreased. In addition, mice treated with either RPMI 8266 cells overexpressing Cx43 or with a P38 MAPK inhibitor (SB202190) exhibited increased intratumoral leukocyte populations and promoted cell apoptosis in tumor tissue. Our findings demonstrate how SRC3 and Cx43 regulation between BMSCs and myeloma cells mediate cell growth and disease progression, with potential implications for prognosis and therapeutic interventions.