Treatment ideas of acupuncture and moxibustion for adenomyosis based on "etiology, location, nature and development of disease". / 基于"ç— å› ã€ç— ä½ã€ç— æ€§ã€ç— åŠ¿"æµ æžå­å®«è ºè‚Œç—‡çš„é’ˆç¸æ²»ç–—æ€è·¯.

Focusing on the syndrome/pattern differentiation to determine treatment, the approaches to the diagnosis and treatment of acupuncture and moxibustion for adenomyosis are explored by identifying the etiology, location, nature and development of disease. The syndromes/patterns of adenomyosis are differentiated in view of both zangfu and meridian theories. The treatment is delivered complying with the menstrual cycle and the basic rule of treatment, "treating the symptoms in the acute stage, while the root causes in the recovery stage". During menstrual period, stopping pain and eliminating stasis are dominant; while during the other days of menstrual cycle, regulating zangfu dysfunction (excess or deficiency) is emphasized. In general, the functions of the thoroughfare vessel and the conception vessel should be specially considered and adjusted, and the principles of treatment include strengthening the spleen, regulating the kidney and soothing the liver. Acupoints are selected mainly from the spleen meridian of foot-taiyin, the kidney meridian of foot-shaoyin and the conception vessel. Ciliao (BL 32), Shiqizhui (EX-B 8), Zigong (EX-CA 1), Diji (SP 8) and four-gate points (bilateral Hegu [LI 4] and Taichong [LR 3]) are used in menstrual period; Zusanli (ST 36), Sanyinjiao (SP 6) and Taixi (KI 3) in postmenstrual phase; Guanyuan (CV 4), Luanchao (Ovary, Extra) and Qihai (CV 6) in intermenstrual phase; while, Guanyuan (CV 4), Qihai (CV 6) and Shenque (CV 8), combined with Gongsun (SP 4), Neiguan (PC 6) and Jianshi (PC 5) in premenstrual phase. According to the dynamic development of patient's conditions, the reinforcing or reducing techniques of acupuncture and moxibustion are feasibly applied in treatment of adenomyosis.

Paris polyphylla ethanol extract and polyphyllin I ameliorate adenomyosis by inhibiting epithelial-mesenchymal transition.

BACKGROUND: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. PURPOSE: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. METHODS: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. RESULTS: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFß1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFß1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFß1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. CONCLUSIONS: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFß1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.

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.

Pulmonary embolism after diagnostic curettage in patient with adenomyosis and hysteromyoma: A case report and brief review of literature.

RATIONALE: Pulmonary embolism (PE) is a common cause of cardiovascular death whose major acquired risk factors include postoperative states, pregnancy, malignancy, and age. We report a case of PE that occurred after diagnostic curettage for abnormal uterine bleeding, with a medical history of adenomyosis and hysteromyoma. PATIENT CONCERNS AND DIAGNOSES: A 31-year-old Han Chinese female was referred to our hospital with menstrual disorders, increased menstrual flow, and severe anemia. After admission, the patient was treated with a blood transfusion, iron supplementation, and erythropoietin, and diagnostic curettage was performed the following day. On the first postoperative day, the patient developed pulmonary embolism with dyspnea and fever diagnosed by CT pulmonary angiography and significantly elevated D-dimer. INTERVENTIONS AND OUTCOMES: Molecular weight heparin was administered for PE for 2 weeks, dyspnea was relieved significantly after 2 days of treatment and the uterine bleeding did not increase; and gonadotropin-releasing hormone agonists were administered for adenomyosis after 1 week of anticoagulant therapy to reduce bleeding. We followed up for 6 months, and the patient had no recurrence of thrombosis and uterine bleeding had improved. CONCLUSION: We speculate that the occurrence of pulmonary embolism was closely related to adenomyosis, hysteromyoma, and curettage in this patient. Treating the presence of both menstrual bleeding and thromboembolism is challenging, and careful management is necessary to avoid therapeutic contradictions.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk.

OBJECTIVE: To investigate cannabis smoking and tobacco cigarette smoking in relation to adenomyosis risk. DESIGN: We used data from a case-control study of adenomyosis conducted among enrollees ages 18-59 years of an integrated health care system in Washington State. The case-control study used 2 control groups given the challenge of selecting noncases when cases are diagnosed by hysterectomy. SUBJECTS: Cases (n = 386) were enrollees with incident, pathology-confirmed adenomyosis diagnosed between April 1, 2001, and March 31, 2006. The 2 control groups comprised hysterectomy controls (n = 233) with pathology-confirmed absence of adenomyosis and population controls (n = 323) with an intact uterus selected randomly from the health care system population and frequency matched to cases on age. EXPOSURE: Detailed data on cannabis and tobacco cigarette smoking history were ascertained through in-person structured interviews, allowing estimation of joint-years of cannabis smoking and pack-years of tobacco cigarette smoking. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between cannabis smoking, tobacco cigarette smoking, and adenomyosis were estimated using multivariable unconditional logistic regression. Analyses were adjusted for age, reference year, menarche age, education, and pack-years of cigarette smoking (or joint-years of cannabis smoking). RESULTS: No association was observed between cannabis smoking history and adenomyosis risk. However, we did observe the suggestion of an association between ever tobacco cigarette smoking and adenomyosis risk, comparing cases to hysterectomy controls (OR, 1.3; 95% CI, 0.9-1.9) and population controls (OR, 1.2; 95% CI, 0.8-1.8). Our data suggested a 50% increased odds of adenomyosis with >15 pack-years of smoking (vs. never smoking), comparing cases to hysterectomy controls (OR, 1.5; 95% CI, 0.9-2.6; Ptrend=.135). The suggestion of a 40% increased adenomyosis odds was observed with smoking >5-15 pack-years (vs. never smoking), comparing cases to population controls (OR, 1.4; 95% CI, 0.8-2.4; Ptrend=0.136). CONCLUSION: In the first study of cannabis smoking and adenomyosis risk, no association was observed. However, our data suggested an increased odds of adenomyosis with history of tobacco cigarette smoking. Further research is warranted to replicate our results given the substantial morbidity with adenomyosis and frequency of cigarette smoking and recreational and medical cannabis use.

Breastfeeding history and adenomyosis risk using a novel case-control study design.

OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and risk of adenomyosis. DESIGN: We used data from a case-control study designed with 2 control groups to address the challenge of selecting noncases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among premenopausal and postmenopausal enrollees aged 18-59 years in a large, integrated health care system in western Washington state. PATIENT(S): Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed during 2001-2006 (n = 386). The 2 control groups were as follows: (1) randomly selected age-matched enrollees with intact uteri ("population controls," n = 323) and (2) hysterectomy controls (n = 233). INTERVENTION(S): Data on breastfeeding history were collected by in-person interviews. For each reported live birth, participants were asked whether they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation. MAIN OUTCOME MEASURE(S): Among participants with at least 1 live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CIs) for the associations between the following: (1) ever breastfeeding, (2) ever breastfeeding for ≥8 weeks, (3) lifetime breastfeeding, and (4) lifetime exclusive breastfeeding and risk of adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity. RESULT(S): In analyses comparing cases with population controls, we observed a 40% decreased odds of adenomyosis with a history of ever breastfeeding (adjusted odds ratio, 0.6; 95% CI, 0.3-1.0) and breastfeeding for ≥8 weeks (adjusted odds ratio, 0.6; 95% CI, 0.4-0.8). The strongest associations, 60%-70% decreased odds of adenomyosis, were observed with ≥12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio, 0.4; 95% CI, 0.2-0.6) and 9 to <12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio, 0.3; 95% CI, 0.2-0.6), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude. CONCLUSION(S): Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a previous study lends support that breastfeeding may modify risk of adenomyosis.

Efficacy and safety of acupuncture for adenomyosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Adenomyosis (AM) is a disease in which the endometrium (including glands and stroma) invades the myometrium and grows. The main clinical symptoms include menorrhagia, dysmenorrhea, chronic pelvic pain, metrorrhagia, and dyspareunia, which will seriously affect the physical and mental health of patients, and most of which occur in women of childbearing age. Acupuncture, as a special external treatment of Traditional Chinese medicine, has shown good effects in the treatment of adenomyosis. At present, there is a lack of systematic review on acupuncture in the treatment of adenomyosis. We conduct this study to evaluate the efficacy and safety of acupuncture in the treatment of adenomyosis. METHODS: We will search Chinese and English databases: Medline, Pubmed, EMBASE, Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Scientific and Journal Database, Wan Fang database (Wanfang), Chinese Biomedical Literature Database (CBM) to identify articles of randomized clinical trials of acupuncture for adenomyosis. All above electronic databases will be searched from inception to September 30, 2021. RevMan 5.3 software will be used to conduct this systematic review. No language and publication status restrictions will be applied. RESULTS: The study will prove the efficacy and safety of acupuncture for adenomyosis. CONCLUSION: We plan to submit this systematic review to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42021277136.

Laparoscopic Uterine Artery Occlusion Combined with Uterine-sparing Pelvic Plexus Block and Partial Adenomyomectomy for Adenomyosis: A Video Case Report.

OBJECTIVE: Adenomyosis usually causes dysmenorrhea and anemia. Clinically, it is difficult to be treated with medicine or by traditional surgery, however, hysterectomy is always performed for radical treatment. In this article, we introduce a new method that could control the dysmenorrhea and the anemia through laparoscopic uterine artery occlusion (LUAO) combined with uterine-sparing pelvic plexus block and partial adenomyomectomy for uterus preservation. DESIGN: Surgical video article. Local institutional review board approval for the video reproduction was obtained. SETTING: A 42-year-old patient, who had a history of a previous cesarean delivery, was admitted to our department with complaints of progressive dysmenorrhea for more than 5 years and aggravated with anemia for 1 year. The patient had failed treatment with traditional Chinese medicine and gonadotropin-releasing hormone and had to take painkillers for nearly half a year. The patient had no desire for another pregnancy. After careful consideration, the patient strongly rejected hysterectomy and demanded the preservation of the uterus, insisting on the integrity of the organs. A gynecologic examination showed that the uterus was hard and enlarged similar to one that is more than 8 gestational weeks, without tender nodules in the rectouterine pouch. The visual analog scale pain score was 7, and her hemoglobin was 93 g/L (after correction). The preoperative magnetic resonance imaging implied that there was 1 lesion in the posterior wall and the maximum diameter of the lesion was 7.8 cm. INTERVENTIONS: We performed laparoscopic partial adenomyomectomy combined with occlusion of uterine artery to limit the amount of intraoperative bleeding, dissected the uterine branch of pelvic plexus nerve, and performed electrocoagulation blocking to relieve the dysmenorrhea. The specific operation procedures are as follows (Video): Firstly, we opened the peritoneum through Cheng's triangle, which contained the external iliac blood vessels, the round ligament, and the infundibulopelvic ligament (Fig. 1). Secondly, we separated the lateral rectal space and exposed the ureter, the internal iliac artery, the uterine artery, and the deep uterine vein. Thirdly, we found that the pelvic plexus was located on the outside of the sacral ligament and was approximately 2 to 3 cm below the ureter, going against the sacral ligament and passing through below the deep uterine vein (Supplemental Video 1). Fourthly, we separated the 4 layers of the paracervix [1]. The first layer included the internal iliac artery and the uterine artery. The second layer was the ureter. The third layer was the deep uterine vein. The last layer was the pelvic plexus, which involved the forward-going bladder branch, the inward-going uterine branch, and the downward-going rectal branch (Supplemental Video 2). These anatomic structures are similar to the complex architecture of an overpass called the Cheng's Cross [2] (Fig. 2). In this operation, only the uterine artery and the uterine branch would be blocked. Finally, we performed the partial adenomyomectomy. The endometrium, the myometrial tissues, and the serosa were repaired in some layers with continuous suture, depending on the depth of incision. The operation time was 92 minutes, and the intraoperative hemorrhage was approximately 50 mL. The patient was able to get out of bed on the first day after the operation and urinate after removing the catheter. On the second day after the surgery, the patient had exhaustion and defecation. From the third day after the surgery, gonadotropin-releasing hormone (Goserelin Acetate Sustained-Release Depot,3.6mg each, subcutaneous injection, name of the enterprise: AstraZeneca UK Limited) was used every 4 weeks, with a total of 3 times. Menstruation began on the 67th day after withdrawal of the drug. The results of postoperative condition of the patient followed up at 6 months after surgery were collected as follows: dysmenorrhea was significantly relieved (visual analog scale score was 2), hemoglobin was 123 g/L, and uterine volume was reduced to 43% of preoperative volume. The comparison of the patient's preoperative and postoperative magnetic resonance imaging showed that the uterus was approximately the same size as that of a woman of the same age, and the incision healed well (Fig. 3). CONCLUSION: Adenomyosis is a common gynecologic disease, mainly occurring in women of childbearing age. Adenomyosis is defined as endometrial glands and stroma that invade the myometrium and is surrounded by chronical inflammation in the endometrium [3]. Secondary dysmenorrhea and menorrhagia are the most common chief complaints in patients with adenomyosis, among which dysmenorrhea is the most unbearable symptom [2]. In the past, we had always treated adenomyosis by hysterectomy [4]. With the continuous pursuit of quality of life, it is difficult to meet clinical needs through drugs and traditional surgical methods. Uterine sparing surgery is a current trend in the treatment of adenomyosis, which enables women to maintain fertility and avoid the effects of hysterectomy on sexual function and mental discomfort. Dysmenorrhea can be divided into peripheral dysmenorrhea and central dysmenorrhea. According to our previous studies on dysmenorrhea, the uterine branch nerve has a controlling effect on dysmenorrhea [2]. The purpose of pelvic plexus uterine branch ablation is to further relieve dysmenorrhea by blocking nerve conduction pathways. Therefore, we selectively blocked the uterine branch nerve to alleviate the dysmenorrhea of adenomyosis. The uterine artery controls 90% of uterine blood flow. According to our team research, LUAO is an effective method to treat symptomatic uterine myomas and adenomyosis. We investigated the morphologic change and apoptosis occurring in myomal and adjacent myometrial tissues after LUAO. We concluded that apoptosis through mitochondrial pathways may lead to reduction of the volume of myoma and myometrium and eventually relief of symptoms [5,6]. We speculated "single organ shock uterine" to explain uterine artery occlusion (UAO) mechanism, which was different from uterine artery embolization. The single organ shock theory of UAO can still inhibit the growth of myomas effectively. It is difficult to completely remove adenomyosis lesions during surgery, especially for diffuse adenomyosis. Therefore, in our team, we performed UAO combined with resection of focal lesions in key areas for patients with diffuse adenomyosis, instead of pursuing radical resection [7,8]. The purpose of UAO is to reduce the amount of bleeding during surgery and further atrophy of residual and scattered adenomyosis lesions in utero [5,6]. The intraoperative blocking of the uterine artery can reduce intraoperative bleeding and operation time, improve operation quality, and decrease recurrence rate. In our team, this technique has been used in clinic for more than 10 years. Our previous studies have shown that LUAO combined with pelvic plexus uterine branch nerve block and resection of most of the adenomyosis has achieved satisfactory clinical efficacy as a treatment for adenomyosis [2,3]. With this procedure, we can help patients with adenomyosis retain their uterus and relieve the anxiety caused by hysterectomy. In conclusion, UAO and uterine branch ablation in uterine sparing laparoscopic treatment is a safe and effective method, which may be considered as a good choice for symptomatic adenomyosis.

Long-term durability of uterine artery embolisation for treatment of symptomatic adenomyosis.

BACKGROUND: Failing conservative therapies, uterine artery embolisation (UAE) has been proposed as a uterine-sparing option for treatment of symptomatic adenomyosis. UAE appears effective at short-term; however long-term durability is less well established. AIMS: To evaluate the long-term clinical efficacy of UAE for treatment of adenomyosis. MATERIALS AND METHODS: One hundred and four women with initial clinical success following UAE for adenomyosis (results previously published) were further followed with a two-part online survey. Part one inquired about menopause, symptom recurrence, need for further intervention and overall satisfaction. Part two comprised the Uterine Fibroid Symptom and health-related Quality of Life (UFS-QOL) questionnaire. Maintenance of clinical success was defined as remaining 'happy' or 'very happy' with overall outcome, no recurrence of symptoms, or need for further intervention. RESULTS: Of those women with initial success, 91/104 (88%) participated in this long-term study at mean 52 months following UAE. Maintenance of clinical success was demonstrated in 82/91 (90%) women. For the remaining 9/91 (10%) women, mean time to failure was 31 months. There were 53/91 (58%) women who reached menopause at mean age of 51.5 years, occurring at mean 30 months post-UAE. UFS-QOL demonstrated significant decrease in symptom severity from 58.9 to 20.0 (P < 0.001); and significant increase in QOL from 40.3 to 86.3 (P < 0.001). CONCLUSIONS: Long-term durability of UAE for treatment of adenomyosis was demonstrated, with cumulative success rate of 80% at mean 52 months. UAE did not appear to bring forward menopause. UAE should be considered as an alternative to hysterectomy to treat adenomyosis.

[Study on mechanism of Rhei Radix et Rhizoma-Persicae Semen in treatment of adenomyosis based on network pharmacology].

The aim of this paper was to screen the active targets of Rhei Radix et Rhizoma and Persicae Semen in the treatment of adenomyosis(AM) by means of network pharmacology, and to investigate their mechanism of action. The effective components of Rhei Radix et Rhizoma and Persicae Semen were screened out by using traditional Chinese medicine systematic pharmacological(TCMSP) database, with oral bioavilability(OB) ≥30% and drug-like(DL) ≥0.18 selected as the thresholds. A network was built between the main components and their corresponding targets. Ninety-five human genes corresponding to the medicine targets were obtained from Uniprot database; 220 genes corresponding to AM were obtained from GeneCards database. A total of 21 intersection genes were screened from disease genes and medicine genes, and the protein-protein interaction network interaction(PPI)analysis was conducted by using STRING tool. Disease-target PPI network was drawn by using Cytoscape software, and component-target-disease network was constructed. Twenty-five nodes and 74 connections were found, and then core networks and targets were screened for Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The animal model of AM was established by feeding tamoxifen citrate mixed droplets to primary mice for verification of the mechanism. Twenty-three signaling pathways were involved in KEGG pathway enrichment. It was found that the therapeutic mechanism of Rhei Radix et Rhizoma and Persicae Semen on AM may involve multiple targets such as inflammation and immunity, proliferation and apoptosis, endocrine and oxidative stress. Among them, the P53 signaling pathway and the apoptotic signaling pathway which mediated the expression of P53 and BAX may be the important ones. Animal experiments proved that the effective components of Rhei Radix et Rhizoma and Persicae Semen can interfere with the P53 signaling pathway and the apoptotic signaling pathway at the junction of endometrial muscle layer, increase the expression of P53 and BAX in muscle layer cells, and promote the apoptosis of cells with abnormal proliferation ability.

500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis.

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.

[Acupuncture for secondary dysmenorrhea of adenomyosis: a prospective case-series study].

OBJECTIVE: To observe the clinical effect of acupuncture by stages on secondary dysmenorrhea of adenomyosis through prospective case-series study. METHODS: A total of 36 cases of adenomyosis patients with moderate-to-severe dysmenorrhea were treated with acupuncture by stages. The acupoints of Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32) and Shiqizhui (EX-B 8) were selected and acupuncture was given once a day during menstrual period; the acupoints of Guanyuan (CV 4), Zigong (EX-CA1), Sanyinjiao (SP 6) and Zusanli (ST 36) ect. were selected and acupuncture was given twice per week during non-menstrual period. All the treatment was given for three menstrual cycles. The visual analogue scale (VAS), Cox menstrual symptom scale (CMSS), Endometriosis Health Profile-5 (EHP-5) scores and the menstrual blood volume of pictorial blood loss assessment chart (PBAC) were observed before treatment and at the 1st, 2nd and 3rd menstrual cycle into treatment. Before treatment and at the 3rd menstrual cycle into treatment, the volume of uterus was measured by transvaginal ultrasound and the correlation among the quality of life, the severity of pain and symptoms was analyzed. RESULTS: The VAS, CMSS and EHP-5 scores at the 1st, 2nd and 3rd menstrual cycle into treatment were lower than those before treatment (P<0.01, P<0.05), and the PBAC scores were reduced but without statistical different (P>0.05). Compared before treatment, at the 1st, 2nd and 3rd menstrual cycle into treatment, the PBAC scores were reduced in patients with PBAC>100 points (P<0.01). Compared between 2nd and 1st menstrual cycle into treatment, between 3rd and 2nd menstrual cycle into treatment, the VAS, CMSS scores were all decreased (P<0.01, P<0.05). There was a significant positive correlation between the severity score of CMSS and EHP-5 at the corresponding time points of the 1st, 2nd and 3rd menstrual cycle into treatment (P<0.01). CONCLUSION: The acupuncture by stages has significant analgesic effect in patients with secondary dysmenorrhea of adenomyosis, and has the advantages of relieving the menstruation-related symptoms, regulating menstrual blood volume and improving the quality of life.

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.

Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment.

BACKGROUND: Sanjie Zhentong capsule (SZC) offers excellent effect in treating adenomyosis (AM), which is a common and difficult gynecological disease in the clinic. However, the systematic analysis of its mechanism has not been carried out yet and further studies are needed to reveal the role of SZC. METHODS: A systematic network pharmacology analysis was conducted by integrating construction of SZC compound database and AM target database, prediction of potential active compounds and targets by molecular docking combined with compound-target prediction graph (CTPG), protein-protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the anti-inflammation experiments in vitro were performed by investigating SZC and the representative compounds regulating nitric oxide (NO), interleukin-6 (IL-6), and interleukin-10 (IL-10). RESULTS: Our findings show that SZC mainly treated AM by stimulating 28 core targets through 30 key potential active compounds, and affecting 4 crucial pathways. The treatment was associated with inflammation reaction, hormone regulation, cell adhesion, proliferation, and angiogenesis. Additionally, SZC achieved the anti-inflammatory activity by the cooperation of the compounds through inhibiting NO and IL-6, both promoting and inhibiting IL-10. CONCLUSION: This study investigated the anti-inflammatory activity of SZC based on a systematic analysis of SZC remedying AM, which was revealed to be one of the essential mechanisms. These findings will provide valuable guidance for further research of the SZC treatment of AM, and help improve the comprehension of SZC pharmacological basis as well as AM pathogenesis.

[Feasibility and safety of MRgFUS ablation for uterine fibroids and adenomyosis: a preliminary study].

Objective: To investigate the feasibility and safety of magnetic resonance guided focused ultrasound surgery (MRgFUS) ablation treatment for uterine fibroids and adenomyosis. Methods: From February 2017 to July 2018, a total of 61 women in Foshan Hospital of Traditional Chinese Medicine with uterine fibroids or adenomyosis (36 cases of fibroids and 25 cases of adenomyosis) were included for treatment of MRgFUS, mean age was 27-48 (39±5) years. The treatment status, treatment effect and complications were recorded, and the differences between myoma and adenomyosis were compared. Results: Thirty-two (88.9%) patients of fibroid group and twenty-one (84.0%) patients of adenomyosis group were completed MRgFUS treatment respectively (P>0.05). The spot energy of adenomyosis group was 1 039-5 698(2 852±991) J, which was higher than 600-6 466(2 485±1 137) J of fibroid group (P<0.01). There was no significant statistical difference in mean temperature of spot and ablation time between the two groups (P>0.05).The non-perfusion volume ratio (NPVR) of the fibroid and adenomyosis group was 54%-99%(84%±15%) and 60%-98%(82%±12%) and there was no significant statistical difference (P>0.05), but the ablation efficiencies of adenomyosis group was less than fibroid group (0.8-4.3(2.1±0.9) cm(3)/min vs 1.3-7.8(3.6±1.5)cm(3)/min, P<0.01).The incidence of complications of adenomyosis group was 47.6%(10/21), it was higher than fibroid group 18.8%(6/32) (P<0.05). Conclusions: MRgFUS is a non-invasive, safe and effective treatment for both uterine fibroids and adenomyosis. Compared with uterine fibroids, MRgFUS treatment of adenomyosis has some disadvantages such as higher energy, lower ablation efficiency and more adverse reactions, and further optimization is needed.

Berberine inhibits growth and inflammatory invasive phenotypes of ectopic stromal cells: Imply the possible treatment of adenomyosis.

Adenomyosis is a common chronic gynecological disorder with some tumor-like properties, including aberrant proliferation, invasion and migration. Berberine (BBR) is an isoquinoline derivative alkaloid with diverse pharmacological activities for the treatment of a wide variety of diseases. However, the effect of BBR on adenomyosis has not been understood. This study was to evaluate the potential therapeutic effect of BBR on ectopic endometrial stromal cells (EESCs) isolated from patients with adenomyosis. Our data showed that BBR significantly inhibited the proliferation and viability of eutopic endometrial stromal cells (EuESCs) and EESCs, while slightly affected the growth of normal endometrial stromal cells (NESCs). BBR markedly exhibited a growth inhibitory effect on EESCs by triggering apoptosis and cell cycle arrest, and alleviating the expression of inflammatory invasive phenotypes (IL-6, IL-8, TGF-ß, EGF, VEGF, and MMP2). The alleviation of inflammatory invasive phenotypes partly involved nuclear translocation of NFκB/p65 and stat3 activation. Taken together, BBR markedly inhibits the growth of EESCs and might be a promising new strategy for the treatment of adenomyosis.

[Discussion on the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis].

To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment for secondary dysmenorrhea of adenomyosis on the basis of disease location and pathogenesis. In clinic, we take the "principle, method, prescription, acupoint and technic" as the outline, paying attention to identify disease location and establishing the method of "promoting blood to remove stasis, regulating thoroughfare vessel and conception vessel" on the basis of the pathogenesis of "stasis obstructing uterus, disharmony of thoroughfare vessel and conception vessel". The prescription combines "dredging" with "conditioning", and the emphasis should be different in different periods. In menstrual period, we put emphasis on activating the circulation of qi and blood as well as clearing meridians to relieve pain and choose the acupoints on the spleen meridian of foot-taiyin and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate the qi and blood of thoroughfare vessel and conception vessel, and the function of viscera. The acupoints for the disease root are mainly at spleen meridian of foot-taiyin and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36). And the reinforcing and reducing technic are applied accordingly.