Backgrounds: A large number of studies have investigated the effect of early menopause on osteoporosis outcomes and the relationship between the content of bone mineral density (BMD) and primary ovarian insufficiency (POI). Methods: To provide a systematic literature review and meta-analysis on BMD content among women with POI. Search strategy: We performed a systematic literature search in the databases PubMed, Embase, Cochrane Library and Web of Science databases from inception through 1 April 2022 . Selection criteria: Studies including women with POI and controls were eligible. Data collection and analysis: Two reviewers independently evaluated study eligibility. We used DerSimonian-Laird random effects model for meta-analysis. Main results: A total of 10 studies featuring 578 women with POI and 480 controls were selected. The meta-analysis showed that the BMD content of femur neck(SMD:-0.76; 95% CI: -1.20 to -0.31; P=0.0008), the BMD content of nondominating forearm (SMD:-0.67; 95% CI: -1.15 to -0.18; P=0.007) were significantly decreased in women with POI. There was no significant change in the BMD content of lumbar spine (SMD: -0.32; 95% CI: -0.74 to 0.10; P=0.14), the total hip (SMD: -0.08; 95% CI: -0.79 to 0.63; P=0.82), as well as the hip neck (SMD: -0.15; 95% CI: -0.85 to 0.56; P=0.68). Conclusions: Scientific evidence suggests that the BMD content altered in patients with primary ovarian insufficiency compared with healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of fracture morbidity and mortality associated with osteopenia in patients with POI.

Objective Many studies have investigated the impact of precocious puberty on cardiovascular disease (CVD) outcomes and the association between lipid profile levels and precocious puberty. However, the results have been inconsistent. The aim of this meta-analysis was to evaluate whether triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL)and low density lipoprotein (LDL) levels were altered in girls with precocious puberty compared with healthy controls. Methods References published before June 2022 in the EMBASE, Cochrane Library, PubMed and Web of Science databases were searched to identify eligible studies. A DerSimonian-Laird random-effects model was used to evaluate the overall standard mean difference (SMD) between precocious puberty and healthy controls. Subgroup analyses and sensitivity analyses were preformed, and publication bias was assessed. Results A total of 14 studies featuring 1023 girls with precocious puberty and 806 healthy girls were selected for analysis. The meta-analysis showed that TG (SMD: 0.28; 95% CI: 0.01 to 0.55; P = 0.04), TC (SMD: 0.30; 95% CI: 0.01 to 0.59; P = 0.04), LDL (SMD: 0.45; 95% CI: 0.07 to 0.84; P = 0.02)levels were significantly elevated in girls with precocious puberty. HDL levels did not change significantly (SMD: -0.06; 95% CI: -0.12 to 0.61; P = 0.62). Subgroup analyses revealed that the heterogeneity in the association between lipid profile and precocious puberty in this meta-analysis may arise from disease type, region, sample size, chronological age, body mass index difference and drug usage. Conclusion Lipid profile levels altered in girls with precocious puberty compared with healthy controls. In order to minimize the risk of CVD morbidity and mortality, early interventions were needed to prevent obesity in children and adolescents, especially those with precocious puberty.

SCOPE:Endometrial receptivity plays a vital role in embryonic implantation. Yueliang Yin is a marketed solid drink in China, also known as Bushen Cuyun Recipe (BCR), that is, assumed to have a therapeutic effect on infertility by improving endometrial receptivity. This study investigates the effects and mechanisms of BCR in protecting the endometrium. METHODS AND RESULTS:Mice with mifepristone-induced embryo implantation failure that exhibited a decreased implantation sites number, thinner endometrium, reduced endometrial glands number, and poor pinopode expression levels are treated with BCR, and these mentioned conditions significantly improves afterward. Molecular docking shows that the main active components kaempferol, quercetin, and hesperetin of BCR stably bound to gasdermin D (GSDMD). Experimental results demonstrate that levels of GSDMD, cleaved caspase-1 and leucine-rich repeat, and pyrin domain-containing 3 and IL-1β levels in model mice are significantly decreased and expressions of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB) expression levels are significantly elevated after BCR treatments, and that the DNA damage is significantly reversed in BCR-treated mice. CONCLUSIONS:BCR is potent and effective in ameliorating endometrial receptivity. The potential mechanisms of BCR on endometrial receptivity may mediate by activating BDNF/TrkB pathway activation and protecting endometrial cells' protection against pyroptosis.

BACKGROUNDS:Existing studies have investigated the relationship between the levels of serum inhibin B (INHB), anti-müllerian hormone (AMH) and precocious puberty in girls, but the results are inconsistent.OBJECTIVE:The aim of this meta-analysis was to assess whether the INHB and AMH levels changed in girls with precocious puberty relative to healthy controls.METHODS:PubMed, Embase, Cochrane Library and Web of Science were searched through June 2022. We included observational clinical studies reporting the serum levels INHB and AMH in girls with precocious puberty. Conference articles and observational study abstracts were included if they contained enough information regarding study design and outcome data. Case series and reports were excluded. An overall standard mean difference (SMD) between precocious puberty and healthy controls was estimated using a DerSimonian-Laird random-effects model.RESULTS:A total of 11 studies featuring 552 girls with precocious puberty and 405 healthy girls were selected for analysis. The meta-analysis showed that the INHB level of precocious puberty [including central precocious puberty (CPP) and premature the larche (PT)] were significantly increased. While there was no significant association between precocious puberty [including CPP, PT, premature pubarche (PP) and premature adrenarche (PA)] and the level of serum AMH.CONCLUSION:Scientific evidence suggested that the INHB level, but not the AMH level, altered in girls with precocious puberty compared with healthy controls. Through our results we think that INHB level might be a marker for the auxiliary diagnosis of precocious puberty (especially CPP and PT). Therefore, it is important to evaluate and thoroughly investigate the clinical indicators (e.g., INHB) in order to ensure early diagnosis and medical intervention, and the risk of physical, psychological and social disorders in immature girls with precocious puberty is minimized.

Objective: To explore the effect and mechanism of action of the Wenjing Zhitong recipe（WZR） in primary dysmenorrhea（PD） treatment.Methods: Uterine contractions were induced by estradiol benzoate and oxytocin in a PD model and WZR was administrated. The rate of change in uterine contractility and the writhing test were used to evaluate the effects of WZR. The serum levels of prostaglandin F 2a (PGF 2a ) and prostaglandin E 2 （PGE 2 ）, and the activity of cyclooxygenase-2（COX2） were detected by enzyme-linked immunosorbent assay（ELISA）. The changes in phosphor-phospholipase C（pPLC/PLC）, phosphor-protein kinase C（pPKC/PKC）, and connexin 43（CX43） expression were detected using immunohistochemistry and western blot.Results: WZR significantly reduced the rate of change in uterine contractility and writhing times in the PD model. WZR treatment inhibited the enzymatic activity of COX2 and reduced the levels of PGF 2a ,PGF 2a /PGE2and COX2 in the PD model. WZR also significantly reduced the expression of pPLC/PLC, pPKC/PKC and CX43. Targeting the inhibition of COX2 activity, caffeic acid and 1-acetyl-β-carboline were validated as the active ingredients in WZR responsible for reducing uterine contractions.Conclusion: WZR attenuated PD by inhibiting COX2 activity, downregulating PGF 2a /PGE 2 expression, and inhibiting the PKC signaling pathway.

中医药诊治妇科疾病具有独特的优势,"洛阳象庄秦氏妇科"代表性传承人秦月好在治疗妇科疾病方面积累了丰富的临证经验,形成了独到的学术见解.独创"荡胞六法"治疗妇科疾病之实证,对妇科虚证重视补肾;创建辨证-辨病-辨期多元化诊疗模式;提出妇科特有的中西医结合周期疗法;重视中医外治法;善用经方、习用药对、巧用虫药;并且强调中医妇科临床治疗优势在于止血、止痛、促孕.本文系统阐释秦月好治疗妇科疾病的学术思想及临证经验,以期为名老中医经验传承和中医药防治妇科疾病提供有益借鉴.

Backgrounds A large number of studies have investigated the effect of early menopause on cardiovascular disease (CVD) outcomes and the relationship between the levels of lipid profile and primary ovarian insufficiency (POI). However, the results are inconsistent. The aim of this meta-analysis was to assess whether the levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) changed in women with POI relative to healthy controls. Methods To identify eligible studies, references published prior to December 2021 were searched in the PubMed, Embase, Cochrane Library and Web of Science databases. DerSimonian-Laird random-effects model was used to estimate the overall standard mean difference (SMD) between POI and healthy control subjects. Subgroup analysis and sensitivity analysis were preformed, and publication bias was assessed. Results A total of 12 studies featuring 846 women with primary ovarian insufficiency and 959 healthy women were selected for analysis. The meta-analysis showed that the levels of TC (SMD: 0.60; 95% CI: 0.32 to 0.89; P<0.0001), TG (SMD: 0.36; 95% CI: 0.12 to 0.60; P=0.003), LDL (SMD: 0.46; 95% CI: 0.16 to 0.76; P=0.003) were significantly increased in women with POI. There was no significant change in the level of HDL (SMD: 0.25; 95% CI: -0.12 to 0.61; P=0.19). Subgroup analysis showed that the heterogeneity in this meta-analysis of the correlation between lipid profile and POI might come from by region, sample size, number of cases, mean body mass index (BMI) value of cases and mean age of cases. Conclusions Scientific evidence suggests that the lipid profile levels were altered in patients with primary ovarian insufficiency compared to healthy controls. Therefore, we recommend that early medical intervention (e.g., hormone replacement therapy) to minimize the risk of CVD morbidity and mortality associated with dyslipidemia in patients with POI. Systematic Review Registration PROSPERO, identifier CRD42021297088

肾-天癸-冲任-胞宫生殖轴调控女子的经、带、胎、产.子宫内膜容受性指子宫内膜在"着床窗口期"内允许胚胎着床的能力,是子宫内膜对胚胎的接受能力的体现,因辅助生殖技术的应用而备受学术界重视.中医药改善子宫内膜容受性具有独特优势,尤其是中医理论在其中发挥了重要的指导作用,肾藏精、主生殖,天癸为肾气发挥生理作用的物质基础,冲任二脉亦包涵了生殖功能,胞宫为胎儿孕育的场所.子宫内膜容受性作为胞宫实现生理功能的一部分,受肾-天癸-冲任-胞宫生殖轴的调节.肾气、天癸、冲任、胞宫的各自的生理功能以及相互作用的功能正常,子宫内膜才能发挥容受胚胎的生殖功能.本文通过查阅、梳理文献,就肾-天癸-冲任-胞宫生殖轴与子宫内膜容受性的关系进行初步探究,以期为子宫内膜容受性低下的辨治提供理论依据.

原发性痛经是指无生殖器官器质性病变的妇女在经期或行经前后,出现周期性小腹疼痛,严重者可影响工作及生活质量.秦月好主任医师采用辨证-辨病-辨体-辨期相结合的多元化的诊疗模式对原发性痛经进行治疗,同时重视"荡胞"法的运用.秦师认为该病的核心病机为"寒凝气滞血瘀",提出以"逐瘀荡胞""行气荡胞""温经荡胞"三法治疗,效果显著.且秦师擅于使用升降散来调理气机升降紊乱,治疗邪气壅滞之痛证,习用延胡索与乌药、五灵脂与蒲黄等药对、巧用僵蚕、蝉蜕等虫药以增加疗效.

Backgrounds Diminished ovarian reserve (DOR) contributes significantly to female infertility. Bushen Cuyun Recipe (BCR, Tradename Yueliang Yin), a product marketed in China, has shown effects in the treatment of female infertility in clinical practices of traditional Chinese medicine (TCM). In this study, we aimed to investigate the chemical compositions of BCR and its efficacy based on scientific evidence and pharmacological mechanisms in DOR treatments. Methods The chemical compositions of BCR were determined by the UHPLC-LTQ-Orbitrap MS method. DOR was induced in a rat model by intraperitoneal injection of cyclophosphamide (CTX) 90 mg/kg once. After the CTX treatment for 14 days, rats were intragastrically administrated deionized water, dehydroepiandrosterone (DHEA), or BCR in low, middle, and high doses for 30 days. Ovarian index, ovarian morphology, follicle number, and anti-Müllerian hormone (AMH) in serum were determined to assess the effects of BCR. To investigate possible action mechanisms, network pharmacological analysis was used to predict possible pathways in the effects of BCR on female infertility. In experimental studies, the contents of hormones in the hypothalamic-pituitary-ovarian axis (HPOA, including estradiol (E2), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH)) and pyroptosis-related proteins, including gasdermin D (GSDMD), caspase-1, and interleukin-18 (IL-18), in ovarian were detected by ELISA, immunofluorescence and Western blot. Results Chemical studies revealed a total 84 components in BCR, which included 43 flavonoids, 13 triterpenoids, 11 phenolic acids, 8 alkaloids, 1 coumarin, 1 anthraquinone, and 7 other components. After treatments with BCR, the ovarian morphology, ovarian index, estrous cycle, growing follicles and corpus luteum from last ovulation, and serum AMH in DOR rats were significantly improved. Network pharmacological analysis suggested that the NOD-like receptor signaling pathway ranked No. 1 among the mechanisms by which BCR affects female infertility. Experimental results demonstrated that the content of serum FSH in DOR rats was significantly decreased and the contents of serum GnRH and E2 were significantly elevated after BCR treatment and that the elevated level of GSDMD, caspase-1, and IL-18 was significantly reversed in BCR-treated rats. Conclusions The chemical compositions of BCR were first identified in the present study. BCR was demonstrated to show protective effects on DOR. The possible mechanisms of BCR on DOR might be mediated by regulating gonadal hormones of the HPOA and protecting granulosa cells in ovary against pyroptosis.

三焦膜系是连接上下、沟通内外的膜层,肾-天癸-冲任-胞宫生殖轴调控女子的月经和胎孕.子宫内膜容受性是子宫内膜对胚胎的接受能力,因辅助生殖技术的应用而备受学术界重视.中医药改善子宫内膜容受性具有独特优势,中医理论在其中发挥了重要的指导作用.文章通过查阅、梳理文献,就三焦膜系、肾-天癸-冲任-胞宫生殖轴与子宫内膜容受性的关系进行初步探究,试揭示子宫内膜容受性的中医理论基础,以期为子宫内膜容受性低下的辨治提供理论依据.

Objective:Bushen Chengyun granule（BCG） is an empirical treatment for female infertility（FI） caused by low endometrial receptivity（LER） involving a poorly understood mechanism.In this study,network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER.Methods:The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature.Disease targets were obtained from the following databases:Comparative Toxicogenomics Database,Human Phenotype Ontology,and Therapeutic Target Database.Treatments for LER using BCG have used target matching（BCG-LER target）.Then,the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses.Furthermore,triptorelin acetate for injection+menotrophin+chorionic gonadotro pin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation.Results:Overall,156 bioactive chemical components and 1092 targets of BCG were identified.The results indicated that 482 biological processes（FDR ＜0.01） and 15 pathways（FDR ＜0.01） related to BCG participated in the complex treatment effects and were associated with the endocrine system,inflammatory responses,metabolism,apoptosis,ovulatory performance,and angiogenesis.Moreover,16 hub nodes of BCG including estrogen receptor（ESR1）,estrogen receptor beta（ESR2）,progesterone receptor,et al,were recognized as potential treatment targets and might help clarify the underlying therapeutic mechanisms of BCG for female infertility.BCG significantly increased the protein expressions of estrogen receptors and progesterone receptors.Conclusions:These findings reveal the potential therapeutic mechanism of BCG for female infertility involves low endometrial receptivity,which should be evaluated further.

Background: Asthma is a common chronic disease with heavy burden. The number of asthma patients may continue to grow in the next 10 years. Existing conventional treatments have problems in which a small number of patients do not respond, often accompanied by side effects, or are too expensive. Probiotics, prebiotics, and synbiotics have been widely used in allergic and inflammatory diseases including asthma. However, their effectiveness and safety are still obscure and deserve further investigation. Objective: To assess the effect and safety of probiotics, prebiotics, and synbiotics in treating asthma. Methods: We will summarize and meta-analyze randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics for the treatment of asthma. RCTs comparing probiotics, prebiotics, and synbiotics with blank control, placebo, or conventional therapies will be included. RCTs comparing probiotics, prebiotics, and synbiotics plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Data. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. Grading of recommendations assessment, development, and evaluation pro GDT web solution will be used for evidence evaluation. Results: This review will evaluate the effects of probiotics, prebiotics, and synbiotics on symptoms, lung function, asthma exacerbations, quality of life, and safety in patients with asthma. Conclusions: This review will provide clear evidence to assess the effectiveness and safety of probiotics, prebiotics, and synbiotics for asthma. OSF registration number: DOI 10.17605/OSF.IO/V7DM9.

Abstract Background: Asthma is a common chronic disease with heavy burden. The number of asthma patients may continue to grow in the next 10 years. Existing conventional treatments have problems in which a small number of patients do not respond, often accompanied by side effects, or are too expensive. Probiotics, prebiotics, and synbiotics have been widely used in allergic and inflammatory diseases including asthma. However, their effectiveness and safety are still obscure and deserve further investigation. Objective: To assess the effect and safety of probiotics, prebiotics, and synbiotics in treating asthma. Methods: We will summarize and meta-analyze randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics for the treatment of asthma. RCTs comparing probiotics, prebiotics, and synbiotics with blank control, placebo, or conventional therapies will be included. RCTs comparing probiotics, prebiotics, and synbiotics plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Data. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. Grading of recommendations assessment, development, and evaluation pro GDT web solution will be used for evidence evaluation. Results: This review will evaluate the effects of probiotics, prebiotics, and synbiotics on symptoms, lung function, asthma exacerbations, quality of life, and safety in patients with asthma. Conclusions: This review will provide clear evidence to assess the effectiveness and safety of probiotics, prebiotics, and synbiotics for asthma. OSF registration number: DOI 10.17605/OSF.IO/V7DM9.

BACKGROUND:Low endometrial receptivity is associated with infertility in women through multiple and complex mechanisms. Existing treatments are not always effective. Symptomatic drugs such as estradiol valerate and/or aspirin do not completely solve the problem. Traditional Chinese herbs have been widely used in infertility and uterine disease including low endometrial receptivity. However, their effectiveness and safety are still obscure and deserve further investigation. OBJECTIVE:To assess the effect and safety of traditional Chinese herbs in treating low endometrial receptivity. METHODS:We will summarize and meta-analyze randomized controlled trials (RCTs) of traditional Chinese herbs for the treatment of low endometrial receptivity. RCTs comparing traditional Chinese herbs with blank control, placebo, or conventional therapies will be included. RCTs comparing traditional Chinese herbs plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WANFANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. GRADE pro GDT web solution will be used for evidence evaluation. RESULTS:This review will evaluate the effects of traditional Chinese herbs on estradiol, progesterone, thickness, volume, and perfusion index(PI) of the endometrium, pregnancy rate, and symptoms. CONCLUSIONS:This review will provide clear evidence to assess the effectiveness and safety of traditional Chinese herbs for low endometrial receptivity. OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/M85VT.