Modified Hongteng Baijiang decoction enema improves sequelae of pelvic inflammatory disease by regulating the LIF/JAK2/STAT3 pathway and gut microbiota.

OBJECTIVE: The sequelae of pelvic inflammatory disease (SPID) are major causes of secondary infertility. Modified Hongteng Baijiang decoction (MHTBD) has produced positive results in the treatment of patients with chronic pelvic inflammatory disease; however, its role in SPID remains elusive. Therefore, this study clarified the role of MHTBD in SPID pathogenesis. METHODS: The main components in MHTBD were analyzed by using liquid chromatography‒mass spectrometry (LC/MS). An SPID rat model was established, and the rats were treated with different doses of MHTBD (0.504 g of raw drug/kg, 1.008 g of raw drug/kg, and 2.016 g of raw drug/kg). Endometrial pinopodes were observed via scanning electron microscopy, endometrial thickness and inflammatory cell infiltration were assessed via HE staining, and the expression of estrogen receptor (ER), progesterone receptor (PR), integrin ß3 (ITGB3), and CD31 in the endometrium was detected by using immunohistochemistry. Western blot analysis was used to detect the protein expression of LIF, JAK2, p-JAK2, STAT3, and p-STAT3 in the endometrium. Moreover, the changes in the gut microbiota were analyzed via 16S rRNA sequencing. RESULTS: MHTBD improved endometrial receptivity, attenuated endometrial pathologic damage, reduced inflammatory cell infiltration, decreased ER and PR expression in the endometrium, and promoted the expression of LIF, p-JAK2, and p-STAT3 in the endometrium (p < .05) in SPID rats. Additionally, MHTBD treatment affected the composition of the gut microbiota in SPID rats. Furthermore, MHTBD attenuated endometrial receptivity and pathological damage in SPID rats by promoting the LIF/JAK2/STAT3 pathway. CONCLUSION: MHTBD attenuates SPID in rats by promoting the LIF/JAK2/STAT3 pathway and improving the composition of the gut microbiota. MHTBD may be a valuable drug for SPID therapy.

The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Exploring the therapeutic effect of Pen Yan Kang Fu Decoction on SPID rats based on LIF/JAK2/STAT3 signaling pathway.

Tubal inflammation, endometritis, and uterine adhesions due to post-pelvic inflammatory disease (SPID) are important causes of infertility. Chronic endometritis (CE) belongs to SPID, which seriously affects women's reproductive health, quality of life, and family harmony, and is a hot and difficult problem in clinical research. The efficacy of Pen Yan Kang Fu Decoction (PYKFD) has been verified in long-term clinical practice for chronic endometritis infertility caused by the SPID. Numerous studies have confirmed that the LIF/JAK2/STAT3 signaling pathway is important in embryo implantation and development, and endometritis infertility is close to LIF/JAK2/STAT3. In vivo results showed that PYKFD increased endometrial receptivity, repaired uterine tissue damage, and regulates the expression of endometrial receptivity-related factors ER (estrogen receptor), PR (progesterone receptor), CD31, and integrin αvß3, and induced the transduction of LIF/JAK2/STAT3 signaling pathway. PYKFD can also regulate the expression of IL-6. The results of in vitro experiments showed that PYKFD regulates the behavior of rat endometrial epithelial cells (REECs) involving LIF. In conclusion, PYKFD can improve endometrial receptivity and promote endometrial repair by LIF/JAK2/STAT3 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03981-0.

Analysis of related factors influencing postoperative recurrence of adenomyosis treated with HIFU.

OBJECTIVE: To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors. METHODS: Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients' age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia. RESULTS: Among the 308 patients, 238 (77%) were followed up from 6 to 36 months, with an average follow-up time of 15.24 ± 9.97 months. The other 70 (23%) were lost to follow-up. At 6-month after surgery, efficacy rates of dysmenorrhea and menorrhagia management were 86.7% and 89.3%, respectively. Postoperative recurrence rates were 4.8% (1-12 months), 9.0% (12-24 months), and 17.0% (24-36 months) for dysmenorrhea; and 6.3% (1-12 months), 2.4% (12-24 months), and 12.2% (24-36 months) for menorrhagia. Multivariate logistic regression analyses showed that parity (P = 0.043, OR = 1.773, 95% CI 1.018-3.087), uterine size (P = 0.019, OR = 1.004, 95% CI 1.001-1.007), combined treatment of TCM (P = 0.047, OR = 1.846, 95% CI 1.008-3.381), diffuse lesion type (P = 0.013, OR = 0.464, 95% CI 0.254-0.848) and ablation rate (P = 0.015, OR = 0.481, 95%CI 0.267-0.868) were prognostic factors (P < 0.05). Age, course of disease, gravidity, duration of HIFU, duration of irradiation, treatment intensity, preoperative dysmenorrhea score, time of follow-up, western medicine adjuvant therapy, lesion location, and preoperative menstrual volume had no effect on prognosis (P > 0.05). CONCLUSION: HIFU can effectively relieve dysmenorrhea and reduce menstrual volume in patients with adenomyosis. Parity, uterine size, lesion type (diffuse), and ablation rate are risk factors for symptom recurrence after HIFU, while the combination of TCM therapy is a protective factor for relapse. We, therefore, recommend TCM in the adjuvant setting after HIFU according to patient condition.

The Impact and Correlation of Anxiety and Depression on Pressure Pain Threshold of Acupoints in Patients with Chronic Pelvic Inflammatory Disease.

Background: Chronic pelvic inflammatory disease (CPID) is a clinically common gynecological disease. Patients experience chronic pelvic pain and often accompany with emotional dysfunction. However, the impact and correlation of anxiety and depression on pain sensitization is not completely known. Objective: To explore the differences and correlations among anxiety, depression, and pressure pain threshold (PPT) of acupoints in patients with CPID. Methods: One hundred and forty-seven patients with CPID were recruited. The Visual Analog Scale (VAS) and short-form McGill Pain Questionnaire (SF-MPQ) were used to assess pain. Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to evaluate the emotional state of patients. The PPT of acupoints was collected using an electronic Von Frey by two licensed acupuncturists. Results: The CPID patients were divided into anxiety-depression group (group A) or nonanxiety-depression group (group B), according to the SAS and SDS scores. Finally, there were 73 patients in group A and 74 patients in group B. Group A had significantly higher SAS, SDS, VAS, and SF-MPQ scores than group B (P < 0.05). In addition, significant differences were observed in the PPTs of ST28 (R), ST29 (R), SP10 (R), SP9 (R), SP9 (L), ST36 (R), and LR3 (L) between the two groups (P < 0.05). No considerable differences in PPTs at the other acupoints were observed between the two groups. SAS scores showed a positive correlation with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L). No remarkable correlation was observed between the SDS scores and PPTs. Conclusion: Anxiety and depression can affect the PPT of some acupoints in CPID patients, which may provide a reference for acupoint selection for acupuncture treatment of CPID with emotional disorders. This trial is registered with ChiCTR2100052632.

Alterations of gut microbiota biodiversity and relative abundance in women with PCOS: A systematic review and meta-analysis.

BACKGROUND: Numerous studies have implicated that the gut microbiota is associated with polycystic ovary syndrome (PCOS). However, a comprehensive data-based summary shown that the effects of the PCOS on the gut microbiota is minimal. We aim to assess the alterations of gut microbiota in women with PCOS. METHODS: An electronic search of PubMed, Web of Science, Embase, Cochrane Library and Ovid was conducted for eligible studies published from inception to 28 March 2023, without any language or regional restrictions. We used Newcastle-Ottawa Quality Assessment Scale (NOS) to complete the assessment of the risk of bias and Stata 15.1 software to performed meta-analysis. RESULTS: There were 19 human observational studies in total with 617 women with PCOS and 439 healthy individuals were identified. Compared to the control group, the Chao index (WMD -28.88, 95% CI -45.78 to -11.98, I2 = 100%), Shannon index (WMD -0.11, 95% CI -0.18 to 0.00, I2 = 92.2%); and observed operational taxonomic units (OTUs) counts (WMD - 23.48, 95% CI -34.44 to -12. 53, I2 = 99.6%) were significantly lower in women with PCOS. The relative abundance of Bacteroidaceae was significantly higher (WMD 0.12, 95% CI 0.02 to 0.22, I2 = 9.2%), however there were no statistical differences in Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Alcaligenaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Lachnospiraceae, Prevotellaceae, Ruminococcaceae, Veillonellaceae, Bacteroides, Bifidobacterium, Blautia, Dialister, Escherichia-Shigella, Faecalibacterium, Lachnoclostridium, Lachnospira, Megamonas, Phascolarctobacterium, Prevotella, Roseburia, and Subdoligranulum. CONCLUSION: We demonstrated the alpha diversity of gut microbiota and the relative abundance of Bacteroidaceae in women with PCOS are altered. The results indicates that dysbiosis may be a potential pathogenetic factor in PCOS and provided reliable information to investigate the role of gut microbiota in the development and progression of PCOS.

Challenges of hesitancy in human papillomavirus vaccination: Bibliometric and visual analysis.

BACKGROUND: Human papillomavirus (HPV) vaccine has immense research value in the prevention of related tumours. A huge body of work has been published in this field, which may pose difficulties for researchers aiming to investigate all the available information. However, bibliometrics can provide deep insights into this research field. OBJECTIVE: We aimed to study HPV vaccine development, visually analyse the development status, trends, research hotspots, and frontiers of this field, and provide a reference for research on it. METHODS: Articles were acquired from the Web of Science Core Collection. VOS viewer and CiteSpace software were used to analyse publication growth, country/region, institution, journal distribution, author, reference, and keywords, and collected burst keyword words to display research hotspots. RESULTS: A total of 4831 references were obtained, and the annual number of publications increased fluctuating over the past decade. The United States of America ranked at the top in terms of percentage of articles. The institution with the highest number of research publications in this field was the Centers for Disease Control and Prevention. The most productive and frequently cited authors was Lauri E Markowitz. The journal with the most publications in this field was Vaccine, and the most influential journal was Paediatrics. The most frequently cited reference was 'A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women'. Burst detection analysis of top keywords showed that 'national immunisation survey', 'social media', and 'hesitancy' are the current research frontiers in this field. CONCLUSION: This study provides useful information for acquiring knowledge on HPV vaccine. Research on solving the hesitation of HPV vaccination will become an academic trend in this field, which can offer guidance for more extensive and in-depth studies in the future.

Intestinal flora: A new target for traditional Chinese medicine to improve lipid metabolism disorders.

Lipid metabolism disorders (LMD) can cause a series of metabolic diseases, including hyperlipidemia, obesity, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS). Its development is caused by more pathogenic factors, among which intestinal flora dysbiosis is considered to be an important pathogenic mechanism of LMD. In recent years, the research on intestinal flora has made great progress, opening up new perspectives on the occurrence and therapeutic effects of diseases. With its complex composition and wide range of targets, traditional Chinese medicine (TCM) is widely used to prevent and treat LMD. This review takes intestinal flora as a target, elaborates on the scientific connotation of TCM in the treatment of LMD, updates the therapeutic thinking of LMD, and provides a reference for clinical diagnosis and treatment.

Forty years of development of salpingitis animal modeling.

This review summarizes and examines research in the area of salpingitis animal modeling in the last 40 years, focusing primarily on Chlamydia trachomatis animal models, which are the most numerous in the literature. Early animal models are examined, followed by a discussion of study parameters and their impact on modeling success, subsequent considerations of fertility measures in modeling, explorations of treatment options, and finally exploring recent directions with a brief discussion of models using other bacterial pathogens.

The impact of herbal medicine in regulating intestinal flora on female reproductive disorders.

As an important part of the human intestinal microecology, the intestinal flora is involved in a number of physiological functions of the host. Several studies have shown that imbalance of intestinal flora and its regulation of the intestinal barrier, intestinal immune response, and intestinal flora metabolites (short-chain fatty acids and bile acids) can affect the development and regression of female reproductive disorders. Herbal medicine has unique advantages in the treatment of female reproductive disorders such as polycystic ovary syndrome, endometriosis and premature ovarian insufficiency, although its mechanism of action is still unclear. Therefore, based on the role of intestinal flora in the occurrence and development of female reproduction-related diseases, the progress of research on the diversity, structure and composition of intestinal flora and its metabolites regulated by botanical drugs, Chinese herbal formulas and active ingredients of Chinese herbal medicines is reviewed, with a view to providing reference for the research on the mechanism of action of Chinese herbal medicines in the treatment of female reproductive disorders and further development of new herbal medicines.

Shipi Shugan Decoction Protected against Sequela of Pelvic Inflammatory Disease via Inhibiting SIRT1/NLRP3 Signaling Pathway in Pelvic Inflammatory Disease Rats.

Sequela of pelvic inflammatory disease (SPID) is a common and frequently occurring disease clinically. Traditional Chinese medicine (TCM) provided unique advantages in the treatment of SPID. In this study, we aimed to investigate the protective mechanism of Shipi Shugan Decoction (SSD), a Chinese herbal formula, on SPID using a SPID rat model. Mixed bacterial infection and mechanical injury were used for modeling. The chemical composition of SSD was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA) and western blot techniques. We found that SSD dose-dependently inhibited the content of IL-18, IL-1ß, TNF-α, and IL-6 in serum samples of SPID rats. The results from the hematoxylin and eosin (H&E) stain showed that SSD improved pathological injury of the uterus and fallopian tubes induced by a pathogen. In addition, SSD dose-dependently inhibited mitochondrial dysfunction and oxidative stress of SPID rats. The expression of SIRT1 was promoted, and NLRP3 inflammasome was deactivated by SSD gavage compared with the SPID group. Specifically, SIRT1 inhibitor EX-527 cotreatment significantly reversed the improvement effect of SSD on pelvic inflammatory disease in rats. Taken together, the results of this study suggest that Shipi Shugan Decoction may be an effective TCM for the treatment of SPID.

A systematic review and meta-analysis of the association between Hashimoto's thyroiditis and ovarian reserve.

OBJECTIVE: Currently, whether Hashimoto's thyroiditis decreases ovarian reserve is not clearly known, given the conflicting findings from previous studies. This study was conducted to systematically review and summarize the association of Hashimoto's thyroiditis (HT) with ovarian reserve. METHODS: Studies investigating ovarian reserve in women with HT and the incidence of HT in women with premature ovarian aging (POA) were searched in major electronic databases. Pre-specified subgroup analyses were performed in terms of agedistribution and thyroidfunction. RESULT (S): A total of 935 studies were retrieved from which 30 were included in the meta-analysis and 5 were finallyselectedfor detailed review. Overall, no statistically significant difference in ovarian reserve parameters (AMH, AFC, FSH, E2) between females with HT and the controls. In subgroup meta-analyses, reproductive aged women with HT had a statistically significant reduction in AMH (SMD -0.35; 95% CI: -0.51, -0.19; P＜0.0001; I2 = 52%), AFC (MD -0.43; 95% CI: -0.56, -0.30; P＜0.00001; I2 = 62%), and increase in basal FSH (SMD 0.1; 95% CI: 0.01, 0.19; I2 = 19%; P = 0.04) compared with age matched controls. Furthermore, POA inreproductive aged women wasassociatedwith higher frequency ofpositiveTPOAb (OR 2.26, 95% CI: 1.31-3.92, p = 0.004) but not positive TgAb(OR 3.17, 95% CI: 0.89-11.38, p = 0.08). CONCLUSION(S): These bidirectional associations suggested that reproductive aged women with HT have a significantly higher risk of diminished ovarian reserve.

Motherwort injection in preventing post-abortion hemorrhage after induced abortion: A multi-center, prospective, randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of motherwort injection (MI, Yi mu cao) in preventing post-abortion hemorrhage and promoting uterine retraction after induced abortion surgery. METHODS: In this multi-center randomized controlled trial undertaken between September 2014 and August 2016, 408 child-bearing age women who underwent induced abortion surgery and randomly assigned to two groups: MI group who received intramuscular MI treatment (n = 207) and no-treatment group (n = 201). The volume of vaginal bleeding and its duration were used as primary end points; and uterine size and dimension were measured as secondary end points. Blood coagulation indices, routine blood and adverse events were recorded to evaluate the safety. RESULTS: The efficacy analysis was based on 366 patients. No significant difference were found in baseline characteristics between the two groups (P > 0.05). The amount of vaginal bleeding and duration of bleeding were significantly reduced in MI group compared with on-treatment group in Full Analysis Set (FAS) and Per Protocol Set (PPS) populations (P < 0.001). The volume and perimeter of the uterine dimensions in MI group were smaller than no-treatment group (P < 0.001). No significant abnormal vital signs were observed. Only 1 case of mild, transient erythema was found in MI group. CONCLUSIONS: MI could reduce post-abortion hemorrhage and improve uterine retraction in women undergoing surgical induced abortion, without serious adverse events. It was a safe and effective treatment in preventing post-abortion hemorrhage after induced abortion.