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Liquiritin ameliorates metabolic and endocrine alterations in a mouse model of polycystic ovary syndrome

Reproductive and Developmental Medicine 2022年第2期6卷 104-112页

作者： Zhi Li Yan Liu Hai-Ou Liu Zhi-Yong Wu cong-jian xu Fei-Fei Zhang Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China Department of Obstetrics and Gynecology Shanghai Medical CollegeFudan UniversityShanghai 200032China

Objective::Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties;however, limited information is available regarding its therapeutic potential in PCOS.Methods::Female C57BL/6 mice were randomly assigned into four groups ( n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed. Results::Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone ( P < 0.001) and dehydroepiandrosterone sulfate ( P < 0.05) in the PCOS group. Histomorphological inspection of ovaries from the liquiritin group revealed fewer cystic dilated follicles than in the PCOS group. Moreover, liquiritinsignificantly ( P < 0.01) decreased Cyp17a1, Cyp19a1, Fshr, Hsd3b2, Runx2, and Ccn2 mRNA expression compared to letrozole-induced PCOS. Conclusion::Liquiritin may be safe and helpful in ameliorating PCOS-associated hyperandrogenemia and hyperglycemia. However, clinical trials investigating different liquiritin dosages are needed to confirm these findings.

关键词： Liquiritin Metabolic phenotypes Polycystic ovary syndrome Reproductive phenotypes

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How fertility preservation guidelines have progressed worldwide:Potential implications and inspiration

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Reproductive and Developmental Medicine 2022年第1期6卷 34-41页

作者： Min-Xin Chen Ying Zhang Qing-Qing Cai Shuo Zhang Ran xu Hua Chen Yu Kang Yue Wu Ri-Cheng Chian cong-jian xu President Office Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Fertility Preservation Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Department of Genetics Shanghai JIAI Genetics and IVF InstituteShanghai 200011China Department of International Law China Foreign Affairs UniversityBeijing 100032China Department of Infertility Shanghai JIAI Genetics and IVF InstituteShanghai 200011China Clinical Research Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Center for Reproductive Medicine Shanghai 10th People's Hospital of Tongji UniversityShanghai 200072China

To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China BioMedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

关键词： Fertility preservation Cancer patient Aging Guidance

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Current Status and Recent Advances in Preimplantation Genetic Testing for Structural Rearrangements

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Reproductive and Developmental Medicine 2020年第1期4卷 1-6页

作者： Shuo Zhang Cai-Xia Lei Xiao-Xi Sun cong-jian xu Department of Genetics Shanghai Ji Ai Genetics and IVF InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Preimplantation genetic testing(PGT)is an early form of prenatal genetic diagnosis,which can identify the abnormal embryos cultured in vitro,allow only transfer of genetically normal embryos,and improve the pregnancy rate.In recent years,the rapid development of microarrays and next-generation sequencing(NGS)technologies has remarkably accelerated the clinical application of PGT.In particular,a variety of detection methods have emerged and achieved significant progress in PGT for structural rearrangements(PGT-SR).The detection-related abilities of these methods range from the detection of limited chromosome aneuploidy to comprehensive chromosome screening of the whole genome to differentiation of embryos with normal or balanced translocation/inversion karyotypes.In this study,we reviewed PGT-SR-related detection techniques to provide a better reference for clinical application and research.We have also discussed the potential development of novel techniques in the future.

关键词： Chromosome Aneuploidy Inversion Karyotype Preimplantation Genetic Testing Structural Chromosomal Rearrangement Structural Rearrangement Translocation Karyotype

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Dysbiosis of Gut Microbiota Contributes to Chronic Stress in Endometriosis Patients via Activating Inflammatory Pathway

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Reproductive and Developmental Medicine 2017年第4期1卷 221-227,I0001页

作者： Jing xu Ke Li Lin Zhang Qi-Yu Liu Yun-Ke Huang Yu Kang cong-jian xu Department of Obstetrics and Gynecology Shanghai Medical SchoolFudan UniversityShanghai 200032China Department of Integrated Traditional Chinese and Western Medicine Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China

Background:Gut microbiota can interact with the central nervous system through the gut-brain axis,thus affecting the host’s chronic stress level,such as anxiety and depression.Current researches show that patients with endometriosis often have a high level of chronic stress,which will in turn aggravate endometriosis by activating theβ-adrenergic signaling pathway.Therefore,we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients,which may provide new insights on how to improve treatment.Methods:We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients’fecal specimens and tissue specimens.Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method,and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues.Results:We found that in patients with endometriosis,the dysbiosis of gut microbiota was associated with their stress levels.Furthermore,the levels of Paraprevotella,Odoribacter,Veillonella,and Ruminococcus were significantly reduced in chronic stressed endometriosis patients,suggestive of a disease-specific change of gut microbiota at the genus level.Compared to the healthy women,the expression levels of inflammatory cytokines,nuclear factor-κB p65,and cyclooxygenase-2 increased in the chronic stressed endometriosis patients,indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut-brain axis.Conclusions:We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level.These changes may also provide new insights for psychological intervention,thus reducing the stress level and improving the prognosis of endometriosis patients.

关键词： Chronic Stress Endometriosis Gut Microbiota Gut-brain Axis

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A Defective CXCL16/CXCR6 Axis Increases the Risk of Pregnancy Loss via the Abnormal Crosstalk between Decidual γδ T Cells and Trophoblasts

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Reproductive and Developmental Medicine 2021年第3期5卷 129-139页

作者： Deng-xuan Fan Ming-Qing Li Wen-Jie Zhou Hong-Lan Huang Hui-Li Yang cong-jian xu Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Department of Obstetrics and Gynecology of Shanghai Medical School Fudan UniversityShanghai200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Fudan UniversityShanghai200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute of Planned Parenthood Research) Hospital of Obstetrics and GynecologyFudan UniversityShanghai200080China Department of Obstetrics and Gynecology Reproductive Medical CenterRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely illustrated.This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow cytometry.The expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay.Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells.Expression of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry.Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay.Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal pregnancies.The expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased.Expression of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT cells.Both the expression of CXCR6 in the decidualγδT cells and proliferation of the decidualγδT cells were promot

关键词： CXCL16 CXCR6 DecidualγδT Cells Maternal-fetal Interface Recurrent Spontaneous Abortion Trophoblasts

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Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第10期12卷 787-795页

作者： Jun HU Li-rong ZHU Zhi-qing LIANG Yuan-guang MENG Hong-yan GUO Peng-peng QU Cai-ling MA cong-jian xu Bi-bo YUAN Department of Gynecology Peking University First Hospital Beijing 100034 China Department of Gynecology Southwest Hospital of Third Military Medical University Chongqing 400038 China Department of Gynecology Chinese PLA General Hospital ＆ Chinese PLA Postgraduate Medical School Beijing 100853 China Department of Gynecology Peking University Third Hospital Beijing 100191 China Tianjin Central Obstetrics and Gynecological Hospital Tianjin 300052 China Department of Gynecology Xinjiang Medical University First Teaching Hospital Urumqi 830054 China Shanghai Red House Hospital of Obstetrics and Gynecology Shanghai 200011 China Department of Gynecology Tianjin Medical University General Hospital Tianjin 300052 China

Objective:To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC).Methods:A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions.Results:Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months.As histologic grade increased,overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined.Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS.Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group.Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups.Conclusions:Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients.The surgical procedure and surgical route might not significantly influence the prognosis.Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

关键词：上皮的卵巢的癌富饶圆材治疗全面幸存没有疾病的幸存怀孕

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Spectrum of Diseases in Female Children and Adolescents Admitted to the Obstetrics and Gynecology Hospital, Shanghai, between 2003 and 2017

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Reproductive and Developmental Medicine 2019年第1期3卷 54-59页

作者： Hai-Xia Huang Ming-Xing Zhang Hong-Wei Zhang Meng Zhang Yi Yu Yu Kang Gui-Ling Li cong-jian xu Department of Gynecology Obstetrics and GynecologyHospital of Fudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China

Objective:To investigate the spectrum of diseases in female children and adolescents hospitalized for obstetric and gynecological conditions.Methods:This retrospective study included patients(age≤19 years)admitted to the Obstetrics and Gynecology Hospital of Fudan University,Shanghai,between January 2003 and December 2017.Their medical records-age,principal diagnosis,and treatment-were reviewed and analyzed.Diagnoses were divided into eight disease classifications.Comparison between groups was analyzed with Student’s t-test.Results:This study enrolled 4,628 inpatients.The number of inpatients increased each year,especially in the groups of gynecologic tumors,pregnancy-related conditions,and disorders of the breast.The mean age was 16.33±2.42 years(range:2-19 years).Of all the inpatients,41.9%(n=1,939)were hospitalized for gynecologic tumors,and 85.5%(n=1,657)of the tumors were benign.Altogether,ovarian cysts(28.66%,n=1,325)were the most common disease observed in this group.In addition,32.9%(n=1,524)of the inpatients were hospitalized for pregnancy,childbirth,and puerperium;within this group,21.9%(n=1,014)were hospitalized for artificial abortions.Conclusions:The efforts of all stakeholders toward the implementation of government policies to promote sexual and reproductive health among children and adolescents in China have been effective.

关键词： Children and Adolescents Disease Attributes Hospitalized Reproductive Health Education

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Baicalein Ameliorates Chronic Stress-Mediated Ovarian Dysfunction by Upregulating the Expression of Gamma-Aminobutyric Acid B2 Receptor

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Reproductive and Developmental Medicine 2018年第1期2卷 21-29页

作者： Ke Li Jing Li Jing xu Ling Zhang Qi-Yu Liu Yun-Ke Huang Zhi-Gang Zhang Yu Kang cong-jian xu Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China

Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in th

关键词： Baicalein Chronic Stress Gamma‑Aminobutyric Acid B2 Receptor Ovarian Dysfunction

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Insights into Stem Cell Therapy for Premature Ovarian Insufficiency

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Reproductive and Developmental Medicine 2021年第4期5卷 237-246页

作者： Zhen-Le Pei Zhe-Yi Wang Wen-Han Lu Fei-Fei Zhang Xin Li Xiao-Yu Tong Yi Feng cong-jian xu Department of Gynecology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesObstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Integrative Medicine and Neurobiology Institute of Integrative Medicine of Fudan UniversityInstitute of Brain ScienceSchool of Basic Medical SciencesFudan UniversityShanghai 200032China

Hormone therapy,assisted reproductive technology,and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency(POI),with limited success.It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell(SC)therapy for patients with POI.We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms,including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines.Next,we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging.Finally,we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI.In summary,SCs and SC-derived exosomes,induced pluripotent SCs,engineered SCs,and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI.Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.

关键词： Premature ovarian failure Premature ovarian insufficiency Regenerative medicine Stem cell Tissue engineering

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Efficacy and Safety of SanJieZhenTong Capsules,a Traditional Chinese Patent Medicine,on Long-term Management of Endometriosis:A Randomized Controlled Trial

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Reproductive and Developmental Medicine 2021年第1期5卷 15-22页

作者： Jing-Yao Ruan Yun-Xi Zheng Qi Tian Jun-Ya Ke Li Wang Yan Du Zhi-Ling Zhu Xiao-Fang Yi cong-jian xu Department of Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Department of Obstetrics and Gynecology Shanghai Medical SchoolFudan UniversityShanghai 200011China Department of Gynecology Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011China Department of Integrated Traditional and Western Medicine Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Department of Integrated Traditional and Western Medicine Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011China Office of Clinical Epidemiology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Objective:To compare the efficacy of the traditional Chinese medicine SanJieZhenTong(SJZT)capsules versus gonadotropin-releasing hormone analogs(GnRHa)or oral contraceptives(OCs)in the postoperative treatment of moderate-to-severe endometriosis.Methods:In this prospective clinical trial,women with stage III-IV endometriosis according to the revised American Fertility Society scoring system received three doses of GnRHa immediately after laparoscopic conservative surgery,followed by random assignment to receive treatment with SJZT,GnRHa,or OCs for another 6 months.The primary endpoint was 2-year recurrence,and the secondary endpoints were adverse events,changes in physical function,and quality of life(QoL).Recurrence was assessed using Kaplan-Meier curves and log-rank tests.Generalized estimating equations were used to determine the parameters of the secondary endpoints.Results:A total of 66 women were randomly assigned to the SJZT(n=21),GnRHa(n=21),and OCs(n=24)groups.At a median follow-up of 22 months,no difference in recurrence was found(P=0.72),with one(4.8%),two(9.5%),and one(4.2%)incidence in the SJZT,GnRHa,and OCs groups,respectively.Expectedly,the incidence of side effects such as hot flush,insomnia,and arthralgia in the SJZT and OCs groups was significantly lower than that in the GnRHa group(P=0.00).In addition,the female sexual function index was significantly improved in the SJZT group,with a higher value than that in the GnRHa(odds ratio[OR]=5.25,95%confidence interval[CI]:2.09-13.14,P=0.00)and OCs(OR=3.94,95%CI:1.58-9.83,P=0.00)groups.Conclusions:SJZT showed more effective pain relief and QoL improvement in patients with moderate-to-severe endometriosis than GnRHa or OCs did.Fewer adverse events than those observed with other agents indicate that this alternative medicine,SJZT,could be a novel option for the long-term management of endometriosis.

关键词： Alternative Medicine Endometriosis Long-term Management SanJieZhenTong Capsules

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