mtDNA regulates cGAS-STING signaling pathway in adenomyosis.

In various hyperproliferative disorders, damaged mitochondria can release mitochondrial DNA (mtDNA) into the cytoplasm, activating the cGAS-STING signaling pathway and subsequent immune imbalances. Our previous research has demonstrated that hypoxia plays a role in the development of adenomyosis (AM) by inducing mitochondrial dysfunction. However, the precise involvement of the cGAS-STING signaling pathway and mtDNA in AM remains unclear. Therefore, this study aims to investigate the relationship between mtDNA secretion, changes in the cGAS-STING signaling pathway, and the abnormal cellular proliferation observed in AM. We found the cGAS, STING, TBK1, p-TBK1, IRF3, and p-IRF3 proteins levels were significantly elevated in the tissues of patients with AM compared to the control group. Additionally, there was an increase in the expression of the pro-inflammatory cytokines IL-6 and IFN-α in the AM tissues. Hypoxia-induced an increase in the proliferation and migration abilities of endometrial stromal cells (ESCs), accompanied by the activation of the cGAS-STING signaling pathway and elevated levels of IFN-α. Furthermore, hypoxia promoted the leakage of mtDNA into the cytoplasm in AM ESCs, and the deletion of mtDNA reduced the activation of the cGAS-STING pathway. Moreover, knockdown of the STING gene inhibited the expression of TBK1, p-TBK1, IRF3, and p-IRF3 and suppressed the secretion of the inflammatory cytokines IL-6 and IFN-α. Furthermore, the migration and invasion abilities of AM ESCs were significantly diminished after STING knockdown. These findings provide valuable insights into the role of mtDNA release and the cGAS-STING signaling pathway in the pathogenesis of AM.

Assessing the role of robotic surgery versus laparoscopic surgery in patients with a diagnosis of endometriosis: A meta-analysis.

BACKGROUND: Surgical management of endometriosis can be carried out with the traditional standard laparoscopic technique or the robotic surgery technique; however, it is not clear if there is a significant difference between techniques. This meta-analysis aims to evaluate and compare the impact of robotic and standard laparoscopic techniques in endometriosis regarding the clinical outcome. METHODS: Studies comparing robotic surgery to laparoscopic surgery for endometriosis were among the studies from various languages that met the inclusion criteria. Using dichotomous and continuous random-effect models, the results of these investigations (surgery time, hospitalization time, blood loss, complications, and conversion rate) were examined, and the mean difference with 95% confidence intervals was computed. RESULTS: Eight studies from 2013 to 2022 were selected for the current analysis including 1741 patients with endometriosis. The studied data revealed a statistically significant (P = .01) lower operation time related to laparoscopic surgery compared with the robotic technique. In addition, the hospitalization time of laparoscopic surgery is significantly (P = .03) lower than that of robotic surgery. On the other hand, blood loss, rehospitalization, postoperative and intraoperative complications, and conversion rates were not significantly different between both techniques. Heterogeneity values were variable according to the analysis factor, from 0% to 91%. CONCLUSION: Both robotic and standard laparoscopic techniques have similar outcomes regarding blood loss, rehospitalization, conversion rate, and rate of complication. However, the substantial difference between techniques was in favor of standard laparoscopic surgery regarding operation and hospitalization time.

Exosomes: potential diagnostic markers and drug carriers for adenomyosis.

Adenomyosis is a common benign gynecological disorder and an important factor leading to infertility in fertile women. Adenomyosis can cause deep lesions and is persistent and refractory in nature due to its tumor-like biological characteristics, such as the ability to implant, adhere, and invade. The pathogenesis of adenomyosis is currently unclear. Therefore, new therapeutic approaches are urgently required. Exosomes are nanoscale vesicles secreted by cells that carry proteins, genetic materials and other biologically active components. Exosomes play an important role in maintaining tissue homeostasis and regulating immune responses and metabolism. A growing body of work has shown that exosomes and their contents are key to the development and progression of adenomyosis. This review discusses the current research progress, future prospects and challenges in this emerging therapeutic tool by providing an overview of the changes in the adenomyosis uterine microenvironment and the biogenesis and functions of exosomes, with particular emphasis on the role of exosomes and their contents in the regulation of cell migration, proliferation, fibrosis formation, neovascularization, and inflammatory responses in adenomyosis.

Comparative Efficacy and Safety of Chinese Patent Medicines for Cervical High-risk Human Papillomavirus Infection: A Bayesian Network Meta-analysis.

Background: Many Chinese patent medicines have been reported to show anti-tumor cell effects on cervical cancer. To estimate the comparative effectiveness and safety of Chinese patent medicines for cervical high-risk human papillomavirus (HR-HPV) infection. Methods: Randomized controlled trials (RCTs) of Chinese patent medicines for HR-HPV infection were searched in eight databases until 31 August 2022, and two review authors independently extracted data and assessed the risk of bias. Outcomes concerning efficacy were evaluated as odds ratio (OR) and 95% credible intervals (CrI) utilizing R 4.1.2 and Stata 16.1. The protocol was registered on the International Prospective Register of Systematic Reviews (CRD42022351120). Results: We ultimately identified 60 RCTs that involved 5,951 participants and 8 interventions. Chinese patent medicines combined with recombinant human interferon (rhIFN) have better treatment effects than rhIFN alone. The results showed that Baofukang suppository (BFK) combined with rhIFN is greater for the rate of HR-HPV clearance follow-up at 6 months (SUCRA = 78.16%). Kushen gel (KS) combined with rhIFN ranked first for the rate of HR-HPV clearance after treatment (SUCRA = 90.77%). Furthermore, KS + rhIFN is most likely to be the best intervention for improving the clinical effectiveness rate (SUCRA = 87.39%). Adverse reactions were not statistically significant in BFK + rhIFN versus BFK, BFK + rhIFN versus rhIFN, and BFK versus rhIFN. Conclusion: The combination of Chinese patent medicines with rhIFN may demonstrate a higher efficacy than rhIFN alone in clearing the virus and improving cervical symptoms. Weighing with the clinical comprehensive efficacy, BFK + rhIFN and KS + rhIFN maybe the optimal treatments for cervical HR-HPV infection. However, more high-quality randomized controlled trials are needed in the future to further confirm the efficacy and safety of proprietary Chinese medicines for cervical HR-HPV infection.

The associations between TMAO-related metabolites and blood lipids and the potential impact of rosuvastatin therapy.

BACKGROUND: Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites. METHODS: A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites. RESULTS: A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = - 0.405 and - 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and - 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05). CONCLUSIONS: This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic.

Acupuncture for glucose and lipid metabolic disorders of polycystic ovarian syndrome: A systematic review protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecological disease that is often accompanied by some metabolic abnormality such as insulin resistance and dyslipidemia. As a non-pharmacological therapy, acupuncture is widely used for the treatment of PCOS, but the effectiveness for insulin resistance and lipid metabolic disorder remains controversial. OBJECTIVES: To assess the effectiveness and safety of acupuncture for insulin resistance and lipid metabolic disorder of women with PCOS. SEARCH METHODS: Eight databases will be searched from inception to June 2021, three clinical trial registration platforms will be searched for relevant trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) of acupuncture therapy for insulin resistance and lipid metabolic of PCOS will be included. DATA COLLECTION AND ANALYSIS: Study screening, data collection, and analysis will be performed by two or more reviewers independently. We will calculate mean difference (MD), standard mean difference (SMD) with 95% confidence intervals (CIs). Data synthesis will be performed with RevMan V.5.3 software and with Stata V.15.0 software when necessary. PROSPERO REGISTRATION NUMBER: CRD42020177846.

Adjuvant therapy of Chinese herbal medicine for the treatment of adenomyosis: A protocol for systematic review.

BACKGROUND: Adenomyosis is benign gynecologic condition with complex etiologies. Common symptoms associated with adenomyosis (AM) include menorrhagia, dysmenorrhea, chronic pelvic pain, metrorrhagia, and dyspareunia. Although Chinese herbal medicine (CHM) has often been utilized for managing AM in clinical practice in China, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a systematic review to assess the effectiveness and safety of CHM combined with Levonorgestrel-releasing intrauterine system for AM. METHODS: The following 7 databases will be searched from the publishment to December 2019: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Digital Periodicals (WAN FANG), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP). The primary outcomes will be relief in pain and uterine bleeding. The secondary outcomes include the adverse effects, CA125 variation in peripheral blood, reduction in uterine volume, and endometrial thickness. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis will be conducted. We will use risk ratio with 95% confidence interval for dichotomous data and the mean difference for continuous data. RESULTS: This study will provide the latest analysis of the currently available evidence for the efficacy of the adjuvant therapy of CHM for the treatment of AM. REGISTRATION NUMBER: OSF (DOI 10.17605/OSF.IO/A2GHY) ETHICS AND DISSEMINATION:: No ethical issues are required. The findings will be published in a peer-reviewed scientific journal.

Acupuncture for patients with premature ovarian insufficiency: A systematic review protocol.

BACKGROUND: Premature ovarian insufficiency (POI) is a difficult-to-treat gynecological disorder with complex etiologies. Although acupuncture has gained increased popularity for the management of POI, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of acupuncture for patients with POI. METHODS: The following 10 databases will be searched from the publishment to July 2019: PubMed, Embase, the Web of Science, the Cochrane Central Register of Controlled Trials, 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Digital Periodicals, Chinese Biomedical Literature Database, Chinese Scientific Journal Database database), 1 Korean medical database (KoreaMed), 1 Japanese medical database (National Institute of Informatics). The primary outcomes will be the resumption of menstruation and the serum FSH levels, and the secondary outcomes include the serum Estradiol levels, anti-Mullerian hormone levels, antral follicle count, follicular growth, endometrial thickness, and adverse events. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis or a subgroup analysis will be conducted. Risk ratio for dichotomous data and mean differences or standardized mean differences for continuous data will be calculated with 95% confidence intervals using a random effects model or a fixed effects model. RESULTS: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture in treating POI. PROSPERO REGISTRATION NUMBER: CRD42019125996.

Detoxification therapy of traditional Chinese medicine for genital tract high-risk human papillomavirus infection: A systematic review and meta-analysis.

BACKGROUND: Persistence of high-risk human papillomavirus (hr-HPV) infections is the most critical risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). Treatment of persistent oncogenic HPV-positive women after 12-24 months follow-up is still controversy. Detoxification therapy of Chinese medicine (DTCM) has been conducted recently. However, the conclusions are still unclear. We planned to conduct a systematic review and meta-analysis to explore DTCM in the treatment of persistent hr-HPV infections. METHODS: Nine electronic databases were systematically searched from their inception to 30 September 2018. Randomized controlled trials comparing DTCM with follow-up or placebo were included. Risk of bias was assessed by the Cochrane 'Risk of Bias' tool. Review Manager 5.3 was used for statistical analyses. Relative ratios (RR) and 95% confidence intervals were used for dichotomous data, and the mean difference (MD) was used for continuous data. We assessed the quality of trials by the GRADE. RESULTS: Seventeen RCTs from 2011 to 2018 with 1906 participants were included. The evidence showed that DTCM had a pooled efficacy difference in favor of increasing the HPV clearance rate compared to placebo groups (RR = 2.62, 95% CI 1.28 to 5.33, very low quality) and follow-up groups (RR = 1.88, 95% CI 1.60 to 2.22, low quality). The median HPV persistence tended to decline from 50% within six months to 41.5% at 12 months, and 31.5% at 24 months. A significantly increased regression rate of CIN was found in the DTCM compared with placebo groups (RR = 3.61, 95% CI 1.21 to 10.83, very low quality) and follow-up groups (RR = 1.79, 95% CI 1.31 to 2.45, very low quality). Additionally, we found DTCM have an impact on TNF-α (MD = 2.99, 95% CI 1.90 to 4.07; very low quality), IFN-α (MD = 3.47, 95% CI 2.42 to 4.52; very low quality), CD4+/CD8+ cells (MD = 0.21, 95% CI 0.05 to 0.37; very low quality) compared with follow up groups in some trials with small sample sizes. The major adverse events were genital mucosal irritation symptoms (10%, 5/50). CONCLUSIONS: DTCM have favorable outcomes on improving the HPV clearance rate, increasing the regression rate of CIN, and impacting the proportion of some immune cells and cytokine levels. However, most of the evidence was of low quality. Any future high-quality trials and a more extended follow-up period of 24 months or more should be performed.

Rhein ameliorates adenomyosis by inhibiting NF-κB and ß-Catenin signaling pathway.

In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and ß-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of ß-catenin during canonical Wnt signaling, we found that the degradation complex of ß-catenin was improved by rhein. In addition, ß-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial-mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on ß-catenin in stromal cells. Stimulation of IL-1ß significantly increased the nuclear translocation of ß-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/ß-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of ß-catenin -associated diseases.

[Effect of Neiyi Kangfu suppository on expressions of cytochrome C and survivin in ectopic and eutopic endometrium in rats with endometriosis].

OBJECTIVE: To explore the different effects of rectal application of Neiyi Kangfu Suppository (NYKFS) on the expressions of cytochrome C (Cyt C) and Survivin in ectopic and eutopic endometrium in endometriosis (EMT) model rats. METHODS: EMT rats were randomly divided into 6 groups, the high- and low-dose NYKFS groups, the Danazol Capsule (DN) group, the Dan'e Fukang Soft Extract (DFE) group, the model group and the blank group. The expressions of Cyt C and Survivin were measured using immunohistochemical SP staining method. RESULTS: (1) After treatment, the IOD value of Cyt C in ectopic endometrium significantly increased in the high-dose and low-dose NYKFS groups respectively to 6.08 +/- 0.35 and 6.23 +/- 0.35, which was significantly higher than that in the model group (5.07 +/- 0.70) and DFE group (5.98 +/- 1.02) respectively (P < 0.05, P < 0.01); while those of Survivin in ectopic endometrium was significantly decreased to 5.73 +/- 0.93 and 5.62 +/- 0.93 and was significantly lower than that in the model group (6.01 +/- 1.16, P < 0.05 or P < 0.01). (2) The lowered eutopic endometrial level of Cyt C in EMT rats after treatment was significantly higher in the two NYKFS groups than that in the model group (P < 0.05); while that of eutopic endometrial Survivin was insignificantly different between the NYKFS groups and the model group or the blank group (P > 0.05). CONCLUSION: NYKFS plays its role in inducing apoptosis by increasing the expression of Cyt C and decreasing the expression of Survivin in ectopic endometrium, but it up-regulates expression of Cyt C, has no obvious effect on Survivin expression in eutopic endometrium.