Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis.

OBJECTIVES: Pregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of different IVF/ICSI protocols on pregnancy outcomes. DESIGN: Meta-analysis. DATA SOURCES: PubMed, Web of Science and Cochrane library were searched up to October 2023. ELIGIBILITY CRITERIA: Comparative studies on IVF/ICSI outcomes in the adenomyosis population were eligible. Studies on preimplantation genetic testing, reviews, case reports and animal experiments were excluded. DATA EXTRACTION AND SYNTHESIS: Valid information was extracted by two independent authors according to a standard data format. All analyses were conducted using Review Manager (RevMan, V.5.3). RESULTS: Compared with the non-adenomyosis population, adenomyosis was responsible for a 26% reduction in clinical pregnancy rate (CPR; 42.47% vs 55.89%, OR: 0.74, 95% CI: 0.66 to 0.82, p<0.00001), a 35% reduction in live birth rate (LBR; 30.72% vs 47.77%, OR: 0.65, 95% CI: 0.58 to 0.73, p<0.00001) and a 1.9-fold increase in miscarriage rate (MR; 27.82% vs 13.9%, OR: 1.90, 95% CI: 1.56 to 2.31, p<0.00001). Subgroup analysis suggested that, in fresh embryo transfer (ET) cycles, the CPR (34.4% vs 58.25%) in the long/short/antagonist protocol group was poorer than that in the ultralong protocol group. In frozen ET (FET) cycles, there were no statistical differences in CPR ((GnRHa+FET) AM(adenomyosis) vs non-AM: 51.32% vs 43.48%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 50.25% vs 60.10%, p=0.82), MR ((GnRHa+FET) AM vs non-AM:12.82% vs 12.50%, p=0.97; (non-GnRHa+FET) AM vs non-AM: 30.5% vs 15.54%, p=0.15) and LBR ((GnRHa+FET) AM vs non-AM:44.74% vs 36.96%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 34.42% vs 50.25%, p=0.28). The MR in the adenomyosis group was high in the fresh ET and FET cycles. CONCLUSIONS: FET might be a better choice for women with adenomyosis, especially those pretreated with GnRHa. In fresh ET cycles, pregnancy outcomes of the long/short/antagonist protocols were poorer than those of the ultralong protocol. TRIAL REGISTRATION NUMBER: CRD42022340743.

Prognostic value of flotillins (flotillin-1 and flotillin-2) in human cancers: A meta-analysis.

Increasing evidence indicates that flotillins which associate with cell infiltration and metastasis are overexpressed in multiple tumors. The prognostic role of flotillins remains controversial. We conducted a comprehensive meta-analysis of published research to investigate the prognostic value of flotillins in patients with cancer. Pooled HRs (hazard ratio) with 95% CIs (confidence interval) were collected to estimate the prognostic value. Twenty-seven studies with 4803 cancer patients were finally identified. The results indicated that: (1) elevated flotillins predicted poorer OS (overall survival) (HR = 2.17, 95% CI 1.87 to 2.52; HR = 1.61, 95% CI 1.44 to 1.81) and DFS (disease-free survival) (HR = 2.41, 95% CI 1.83 to 3.18; HR = 3.01, 95% CI 2.12 to 4.27) in patients with cancer; (2) Subgroup analysis showed that the prognostic value of flotillin-1 on OS and DFS in the investigated tumors were not altered by tumor type (such as digestive system cancers, renal cell cancer, lung cancer, or others), country (China or Canada), cutoff value, detection method, analysis type or paper quality and flotillin-2 overexpression indicates poor OS in human cancers except for nasopharyngeal carcinoma. Flotillins are promising as new biomarkers to predict poor prognosis of patients with tumors. This conclusion needs more clinical studies with different types of cancer to be proven.

TRPC1/3/6 inhibition attenuates the TGF-ß1-induced epithelial-mesenchymal transition in gastric cancer via the Ras/Raf1/ERK signaling pathway.

Gastric cancer (GC) is one of the most common malignancies worldwide. TGF-ß1 induces the epithelial-mesenchymal transition (EMT) in GC, mainly through Smad-dependent pathways. Nevertheless, few studies have focused on the activation of non-canonical transduction pathways. TRPC, Ca2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF-ß1-induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT-related proteins in SGC-7901 cells incubated with or without TGF-ß1. The expression of TRPC1/3/6 and EMT-related molecules, including E-cadherin, vimentin, and α-SMA, was detected by qRT-PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC-7901 cells. Following TGF-ß1 stimulation, the expression of vimentin, α-SMA, and TRPC1/3/6 increased and E-cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2-APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF-ß1-induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.