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.

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.

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.

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.