Salvia miltiorrhiza-Containing Chinese Herbal Medicine Combined With GnRH Agonist for Postoperative Treatment of Endometriosis: A Systematic Review and meta-Analysis.

Background: Endometriosis is an estrogen-dependent gynecological inflammatory condition that may lead to infertility and recurrent pelvic pain. The purpose of this research was to determine the efficacy and safety of Salvia miltiorrhiza-containing Chinese herbal medicine (CHM) combined with gonadotropin-releasing hormone agonist (GnRH-a) for postoperative endometriosis management. Methods:Eight databases were systematically searched before October 2021, including PubMed, Embase, Cochrane Library, Scopus, Web of Sceince, CNKI, VIP, and Wanfang. Finally, all randomized controlled studies comparing Salvia miltiorrhiza-containing CHM paired with GnRH-a to GnRH-a alone for postoperative endometriosis management were included. Results: A total of 10 trials involving 836 patients were reported and analyzed. Compared with the control group, the Salvia miltiorrhiza-containing CHM combined with GnRH-a group showed significant superiority in decreasing endometriosis recurrence (risk ratio [RR] = 0.26; 95% confidence intervals [CI]: 0.16-0.41) and increasing the pregnancy rate ([RR] = 1.96; 95% CI: 1.58-2.44). Similarly, the effect of the Salvia miltiorrhiza-containing CHM combined with GnRH-a on CA-125 serum levels was positive (standardized mean difference [SMD] = -0.79; 95% CI: -1.11 to -0.47). Furthermore, this group showed a significant reduction in adverse effects. Conclusion: The results indicate that Salvia miltiorrhiza-containing CHM may be a viable choice for postoperative endometriosis therapy, with the potential to enhance pregnancy while decreasing recurrence and adverse effects.

Matching the Optimal Operating Mode of Polydimethylsiloxane Check Valves by Tuning the Resonant Frequency of the Resonator in a Piezoelectric Pump for Improved Output Performance.

This paper proposes to improve the output performance of a piezoelectric pump by matching the resonant frequency of the resonator to the optimal operating mode of bridge-type polydimethylsiloxane (PDMS) check valves. Simulation analyses reveal that the side-curling mode of the PDMS valve is conducive to liquid flow and exhibits a faster frequency response compared with the first bending mode. The first bending resonant frequency of a beam-type piezoelectric resonator was tuned close to the side-curling mode of the PDMS valve by adjusting the weight of two mass blocks installed on both ends of the resonator, so that both the resonator and the valve could work at their best conditions. Experiments were conducted on a detachable prototype piezoelectric pump using PDMS valves with three different lengths. The results confirm that the peak flowrate at the resonant point of the pump reaches its maximum when the resonant frequencies between the resonator and the valve are matched. Maximum peak flowrates of 88 mL/min, 72 mL/min and 70 mL/min were achieved at 722 Hz, 761 Hz and 789 Hz, respectively, for diaphragm pumps using five-, four- and three-inlet-hole PDMS valves, under a driving voltage of 300 Vpp.

Hyperandrogenism and insulin resistance contribute to hepatic steatosis and inflammation in female rat liver.

Women with polycystic ovary syndrome (PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). While insulin resistance is a common trait for both PCOS and NAFLD, hyperandrogenism is also considered to be a key factor contributing to PCOS, and the molecular mechanisms behind the interactions between insulin resistance and hyperandrogenism in the female liver remain largely unexplored. Using chronic treatment with insulin and/or human chorionic gonadotropin (hCG), we showed that all female rats with different treatments induced imbalance between de novo lipogenesis and mitochondrial ß-oxidation via the Pparα/ß-Srebp1/2-Acc1 axis, resulting in varying degrees of hepatic steatosis. Given the fact that hepatic lipid metabolism and inflammation are tightly linked processes, we found that hCG-induced hyperandrogenic rats had strongly aggravated hepatic inflammation. Further mechanistic investigations revealed that dysregulation of the IRS-PI3K-Akt signaling axis that integrated aberrant inflammatory, apoptotic and autophagic responses in the liver was strongly associated with hyperandrogenism itself or combined with insulin resistance. Additionally, we found that hCG-treated and insulin+hCG-induced rats developed visceral adipose tissue inflammation characterized by the presence of "crown like" structure and increased inflammatory gene expression. Because a more pronounced hepatic steatosis, inflammatory responses, and hepatocyte cell damage were observed in insulin+hCG-induced PCOS-like rats, our finding suggest that NAFLD seen in PCOS patients is dependent of hyperandrogenism and insulin resistance.

Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome.

Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial-stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K-Akt-NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.

Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus.

Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3ß (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients.