Analysis on constructing a risk prediction model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery based on decision tree method / 中华内分泌外科杂志

Objective:The decision tree Chi-square automatic interactive detection (CHAID) algorithm and binary Logistic regression analysis were used to construct the risk prediction model of premature ovarian failure (POF) in patients with uterine fibroids complicated with hypertension after surgery, and the results of the risk prediction model were compared and analyzed.Methods:Patients with uterine fibroids complicated with hypertension admitted to Taizhou Hospital of Zhejiang Province from Jan. 2019 to Sep. 2022 were retrospectively analyzed as the research objects. CHAID algorithm and Logistic regression analysis were used to establish risk prediction models, respectively. The area under the curve (AUC) of receiver operating characteristic curve (ROC) was used to compare and evaluate the prediction effects of the two models.Results:A total of 860 patients were collected, including 56 patients with premature ovarian function failure after operation, and the incidence of premature ovarian function failure was 6.51%. CHAID method and Logistic regression analysis showed that uterine myoma surgery, hypertension, smoking or passive smoking, family history of premature ovarian failure, sleep status, physical exercise and history of induced curettage were important influencing factors of premature ovarian failure. The accuracy of risk prediction of decision tree model was 88.2%, and the fitting effect of the model was good. The Logistic regression model Hosmer-Leme-show goodness of fit test showed that the model fit was good. The AUC of Logistic regression model was 0.893 (95% CI: 0.862-0.899), and the AUC of decision tree model was 0.882 (95% CI: 0.856-0.899). The predictive value of the two models was moderate, and there was no significant difference between them ( Z=0.254, P>0.05) . Conclusions:The combination of decision tree and Logistic regression model can find the influencing factors of premature ovarian function failure in patients with uterine fibroids complicated with hypertension after operation from different levels, and the relationship between the factors can be more fully understood. The establishment of a risk model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery can provide a reference for postoperative intervention in patients with uterine fibroids complicated with hypertension, and more effectively help patients actively prevent and slow down the occurrence and development of POF.

Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics / 中国中药杂志

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

Research progress in dialectical treatment of premature ovarian failure by Zhejiang TCM gynecology schools / 中国基层医药

In traditional Chinese medicine, premature ovarian failure is attributed to the menstrual diseases such as amenorrhea, infertility, premenopausal and postmenopausal syndromes. The Zhejiang TCM gynecology schools are good at dialectical treatment of the above menstrual diseases similar to premature ovarian failure, especially Gynecology of Xiaoshan Zhulin Temple, Gynecology of Haining Chen Mushan, Gynecology of Ningbo Song's Family and Gynecology of Hangzhou He's Family. This paper summarizes the characteristics and experience of the four Zhejiang TCM gynecology schools in the dialectical treatment of premature ovarian failure, which can be used for reference.

Mechanism of Jiawei Bazhen Yimu Capsule in Treatment of Premature Ovarian Failure Based on Estrogen Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Jiawei Bazhen Yimu capsule on serum sex hormones， sexual organs and estrogen signaling pathway in female rats with premature ovarian failure. MethodThe key target proteins of Jiawei Bazhen Yimu capsule in the treatment of premature ovarian failure were screened out by network pharmacology analysis. Female healthy SD rats were selected, and the rat model of premature ovarian failure was established by ovariectomy. Fifty ovariectomized rats were randomly divided into a model group, an estradiol (E2) valerate group, and Jiawei Bazhen Yimu capsule low, medium, and high-dose groups. Another 10 healthy female rats were set as a sham operation group. The sham operation group and the model group were given distilled water by gavage, and other administration groups were given corresponding doses of drugs by gavage. After 21 d, the serum hormone levels of female rats were measured, including E2, progesterone (P), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Immunofluorescence staining (IF) was used to detect the protein expression levels of estrogen receptor 1 (ESR1), estrogen metabolism P4503A4 enzyme (CYP3A4), and P45019A1 enzyme (CYP19A1) in the uterine tissues of female rats. ResultAs compared with the model group, the serum E2 and P levels of female rats in the Jiawei Bazhen Yimu capsule low, medium, and high-dose groups were significantly increased. Jiawei Bazhen Yimu capsule improved the endometrial status of female rats and increased positive expression of ESR1, CYP3A4, and CYP19A1 in the uterine tissues of female rats (P<0.05). ConclusionThe mechanism of Jiawei Bazhenyimu capsule in the treatment of premature ovarian failure may be related to its hormone-like effect and activation of the estrogen signaling pathway.

Effect of Siwutang on Diminished Ovarian Reserve in Rats Based on 16S rRNA Sequencing of Intestinal Flora / 中国实验方剂学杂志

ObjectiveTo study the effect of Siwutang （SWT） on intestinal flora in rats with diminished ovarian reserve （DOR） induced by Tripterygium wilfordii polyglycoside （TWP） based on 16S rRNA sequencing. MethodTwenty 8-week-old female SD rats were randomly assigned into four groups： blank group， model group， SWT high-dose group， and SWT low-dose group. Except the blank group， the other three groups were underwent intragastric administration of TWP tablets at a dose of 50 mg·kg-1 for 14 days. On day 15， the high-dose group was administrated at 3 times of the human dosage （40 g/person/day）， the low-dose group at 1.5 times of the human dosage， and the model group and the blank group with the same volume of normal saline for 18 days. Then， feces were collected for 16S rRNA sequencing. One hour after administration， blood was sampled from abdominal aorta after anesthesia for the measurement of hormone levels by radioimmunoassay， and ovaries were sampled， embedded， sliced， and stained with haematoxylin-eosin （HE） for pathological observation. ResultThe model group had higher level of luteinizing hormone （LH， P<0.05） and lower level of estradiol （E2， P<0.05） than the blank group. The SWT high-dose group and low-dose group had lower LH levels （P<0.05） and higher E2 levels than the model group （P<0.05）. SWT reversed the elevation in follicle-stimulating hormone （FSH） and LH levels and the decline in E2 and progesterone （P） levels caused by TWP to some extent. There were a large number of follicles at different developmental stages in the blank group， while atretic follicles increased significantly in the model group. A large number of mature follicles， secondary follicles， and primary follicles were observed in the high-dose SWT group， and primordial follicles， secondary follicles， and increased corpus luteum in the low-dose SWT group. Compared with that in the blank group and the administration group， the abundance of Verrucomicrobia and Epsilonbacteraeota in the model group significantly reduced. Compared with the blank group， the model group had different intestinal flora in phylum， class， order， family， and genus levels. Specifically， the model group had increased proportions of Firmicutes and Bacteroidetes. After TWP modeling， the abundance of Lachnospiraceae decreased significantly while that of Ruminococcaceae UCG-005 increased significantly. SWT groups， blank group， and model group can be clearly distinguished， and SWT groups had a tendency to approach the blank group. ConclusionSWT may improve the ovarian function of rats with TWP-induced DOR by regulating intestinal flora diversity.

Protection of Zuoguiwan Against Apoptosis of Follicles in Rats Injured by 60Co-γ Rays： Based on PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Zuoguiwan against 60Co-γ ray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodSixty sexually mature female SD rats were irradiated with 60Co-γ rays （6.0 Gy， LD40） for 24 h at one time. Then they were randomized into model group， Bujiale group （0.18 g·kg-1·d-1）， Bujiale （0.09 g·kg-1·d-1） + high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， medium-dose Zuoguiwan group （9.45 g·kg-1·d-1）， and low-dose Zuoguiwan group （4.725 g·kg-1·d-1）. The administration （once a day） lasted 21 days. Serum indexes ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）］ of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and morphological changes of ovarian tissues were observed based on hematoxylin and eosin （HE） staining. The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） and the protein expression of phosphorylated （p）-PI3K， p-Akt， p-mTOR， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in ovarian tissues by Western blot. ResultCompared with normal group， model group demonstrated increase in serum FSH （P<0.01）， decrease in E2 （P<0.05）， and reduction of follicles and luteum in early ovary （P<0.01）. Moreover， the elevation of apoptosis rate of granulosa cells （P<0.01）， down-regulation of p-PI3K， p-Akt， p-mTOR， and Bcl-2 in ovarian tissue， and increase in expression of Bax were also observed in the model group as compared with the normal group （P<0.01）. In comparison with the model group， the administration groups showed rise of the number of early ovarian follicles， decrease in the apoptosis rate of granulosa cells， increase in the expression of p-PI3K， p-Akt， p-mTOR， and Bcl-2， and down-regulation of Bax， particularly the Bujiale + high-dose Zuoguiwan group（P<0.05，P<0.01）. ConclusionZuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue， increasing Bcl-2， and inhibiting the expression of Bax.

Protection of Zuoguiwan Against Apoptosis of Follicles in Rats Injured by 60Co-γ Rays： Based on PI3K/Akt/mTOR Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Zuoguiwan against 60Co-γ ray-induced premature aging of rats based on the phosphatidylinositol-3-kinases/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway. MethodSixty sexually mature female SD rats were irradiated with 60Co-γ rays （6.0 Gy， LD40） for 24 h at one time. Then they were randomized into model group， Bujiale group （0.18 g·kg-1·d-1）， Bujiale （0.09 g·kg-1·d-1） + high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， high-dose Zuoguiwan group （23.625 g·kg-1·d-1）， medium-dose Zuoguiwan group （9.45 g·kg-1·d-1）， and low-dose Zuoguiwan group （4.725 g·kg-1·d-1）. The administration （once a day） lasted 21 days. Serum indexes ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E2）］ of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and morphological changes of ovarian tissues were observed based on hematoxylin and eosin （HE） staining. The apoptosis rate of granulosa cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） and the protein expression of phosphorylated （p）-PI3K， p-Akt， p-mTOR， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in ovarian tissues by Western blot. ResultCompared with normal group， model group demonstrated increase in serum FSH （P<0.01）， decrease in E2 （P<0.05）， and reduction of follicles and luteum in early ovary （P<0.01）. Moreover， the elevation of apoptosis rate of granulosa cells （P<0.01）， down-regulation of p-PI3K， p-Akt， p-mTOR， and Bcl-2 in ovarian tissue， and increase in expression of Bax were also observed in the model group as compared with the normal group （P<0.01）. In comparison with the model group， the administration groups showed rise of the number of early ovarian follicles， decrease in the apoptosis rate of granulosa cells， increase in the expression of p-PI3K， p-Akt， p-mTOR， and Bcl-2， and down-regulation of Bax， particularly the Bujiale + high-dose Zuoguiwan group（P<0.05，P<0.01）. ConclusionZuoguiwan protects radiation-damaged ovary by activating the expression of PI3K/Akt/mTOR protein in ovarian tissue， increasing Bcl-2， and inhibiting the expression of Bax.

Síndrome X frágil y otras patologías asociadas al gen FMR1 / Fragile X Syndrome and Other Pathologies Associated with the FMR1 Gene / Síndrome do X frágil e outras patologias associadas ao gene FMR1

Resumen: el síndrome X frágil es la causa más frecuente de retraso psicomotor vinculado al cromosoma X en niños, con una prevalencia de 1 : 5.000 en hombres y 1 : 4.000 - 8.000 en mujeres. Además, es la causa hereditaria más asociada al síndrome del espectro autista. Esta patología posee como base etiológica la expansión del triplete CGG en el extremo distal del gen FMR1, lo que causa su silenciamiento. Los pacientes afectados con este síndrome suelen padecer de problemas conductuales, neurológicos, cardíacos y ortopédicos. Este síndrome también se relaciona con la insuficiencia ovárica primaria asociada al X frágil, y el síndrome de temblor y ataxia asociado al X frágil que afectan a la madre y al abuelo materno, y que, por su reciente descripción, podrían ser desconocidos por el personal sanitario, lo que retrasa su diagnóstico y tratamiento. El objetivo de este artículo es analizar estas enfermedades, con el fin de describir el conocimiento actual sobre su etiología, las manifestaciones clínicas, el diagnóstico y el tratamiento. Esto se realizó mediante la recopilación de artículos en Pubmed, con algunas contribuciones de las bases de datos Scielo, Redalyc, Europe PMC, Science Direct, Google Académico y Genetics Home Reference. Entre las conclusiones principales se destaca que los fenotipos asociados a la premutación del gen FMR1 contemplan mecanismos fisiopatológicos diferentes al síndrome X frágil, a pesar de estar íntimamente relacionados.

Abstract: fragile X syndrome is the most common cause of X-linked psychomotor retardation in children, with a prevalence of 1 : 5.000 in males and 1 : 4.000 -8.000 in females. It is also the hereditary cause most associated with autism spectrum syndrome. The etiological basis of this pathology is the expansion of the CGG triplet at the distal end of the FMR1 gene, which causes its silencing. Patients affected with this syndrome usually suffer from behavioral, neurological, cardiac and orthopedic problems. This syndrome is also related to Fragile X-associated primary ovarian insufficiency, and Fragile X-associated tremor and ataxia syndrome affecting the mother and maternal grandfather, which, because of their recent description, may be unknown to health care providers, delaying their diagnosis and treatment. The objective of this article is to analyze these diseases, in order to describe the current knowledge about their etiology, clinical manifestations, diagnosis and treatment. This was done by collecting articles in Pubmed, with some contributions from Scielo, Redalyc, Europe PMC, Science Direct, Google Scholar and Genetics Home Reference databases. Among the main conclusions, it is highlighted that the phenotypes associated with FMR1 gene premutation involve different pathophysiological mechanisms to Fragile X syndrome, despite being closely related.

Resumo: a síndrome do X frágil é a causa mais comum de retardo psicomotor ligado ao cromossomo X em crianças, com prevalência de 1 : 5.000 em homens e 1 : 4.000 a 8.000 em mulheres. Além disso, é a causa mais hereditária associada à síndrome do espectro do autismo. Essa patologia tem como base etiológica a expansão do trigêmeo CGG na extremidade distal do gene FMR1, o que causa seu silenciamento. Pacientes com essa síndrome geralmente sofrem de problemas comportamentais, neurológicos, cardíacos e ortopédicos. Essa síndrome também está relacionada à insuficiência ovariana primária associada ao X frágil, à síndrome do tremor e à ataxia associada ao X frágil, que acometem a mãe e o avô materno, e que, devido à sua descrição recente, poderiam ser desconhecidas pelos profissionais de saúde, o que atrasa seu diagnóstico e tratamento. O objetivo deste artigo é analisar essas doenças, a fim de descrever o conhecimento atual sobre sua etiologia, manifestações clínicas, diagnóstico e tratamento. Isso foi feito através da recopilação de artigos no Pubmed, com algumas contribuições das bases de dados Scielo, Redalyc, Europe PMC, Science Direct, Google Academic e Genetics Home Reference. Dentre as principais conclusões, destaca-se que os fenotipos associados à premutação do gene FMR1 incluem outros mecanismos fisiopatológicos além da síndrome do X frágil, apesar de eles estarem intimamente relacionados.

Insuficiencia ovárica primaria en adolescentes: revisión de la literatura a propósito de un caso clínico / Primary ovarian insufficiency in adolescents: review of the literature regarding a clinical case

El objetivo de este manuscrito es realizar una revisión y actualización de la literatura de la insuficiencia ovárica primaria (IOP) en población adolescente, a partir del diagnóstico, manejo y seguimiento de un caso clínico. La insuficiencia ovárica primaria se define como la menopausia en una mujer antes de los 40 años, acompañada de amenorrea, hipogonadismo hipergonadotrópico e infertilidad. Su prevalencia varía entre 1 a 2%, y en mujeres menores de 20 años su prevalencia es un caso de cada 10,000. Aunque se sabe que muchas afecciones pueden llevar a una IOP, la más común es la causa idiopática. La presentación clínica es diversa, y varios trastornos diferentes pueden también, llevar a esta condición. CASO CLÍNICO: Se presenta el caso de una adolescente de 17 años, previamente sana, con historia de amenorrea secundaria, no embarazada, con examen físico general y ginecológico normal. Se solicita estudio analítico complementario resultando con niveles de hormona folículo estimulante (FHS), estradiol (E2) y hormona antimülleriana (AMH) compatibles con una insuficiencia ovárica como la observada en la posmenopausia. Se inicia terapia hormonal (TH) clásica con estradiol y progesterona, siendo posteriormente reemplazada por anticoncepción hormonal combinada (AHC) oral, coincidente con el inicio de vida sexual, con respuesta favorable y sangrados regulares. La IOP tiene graves consecuencias para la salud incluyendo trastornos psicológicos como angustia, síntomas depresivos o depresión, infertilidad, osteoporosis, trastornos autoinmunes, cardiopatía isquémica, y un mayor riesgo de mortalidad. La enfermedad de Hashimoto es el trastorno autoinmune más frecuente asociado a la IOP. Su tratamiento y diagnóstico deben establecerse de forma precoz para evitar consecuencias a largo plazo. La terapia con estrógenos es la base del tratamiento para eliminar los síntomas de la deficiencia de estrógenos, además de evitar las consecuencias futuras del hipogonadismo no tratado. También el manejo debe incluir los siguientes dominios: fertilidad y anticoncepción, salud ósea, problemas cardiovasculares, función psicosexual, psicológica y neurológica, informando a los familiares y a la paciente sobre la dimensión real de la IOP y la necesidad de tratamiento multidisciplinario en muchos casos. CONCLUSIÓN: El caso presentado, pese a ser infrecuente, permite abordar de manera sistematizada el diagnostico de IOP y evaluar alternativas de manejo plausibles para evitar graves consecuencias en la salud, así como conocer respuesta clínica y de satisfacción de la adolescente.

The objective of this manuscript is to review and update the literature on primary ovarian insufficiency (POI) in an adolescent population, based on the diagnosis, management and follow-up of a clinical case. Primary ovarian insufficiency is defined as menopause in a woman before the age of 40, accompanied by amenorrhea, hypergonadotropic hypogonadism, and infertility. Its prevalence varies between 1 to 2%, and in women under 20 years of age its prevalence is one case in every 10,000. Although it is known that many conditions can lead to POI, the most common is the idiopathic cause. The clinical presentation is diverse, and several different disorders can also lead to this condition. CLINICAL CASE: The case of a 17-year-old adolescent, previously healthy, with a history of secondary amenorrhea, not pregnant, with a normal general physical and gynecological examination is presented. A complementary analytical study is requested, resulting in levels of follicle stimulating hormone (FHS), estradiol (E2) and anti-müllerian hormone (AMH) compatible with ovarian insufficiency such as that observed in postmenopause. Classic hormonal therapy (HT) with estradiol and progesterone was started, later being replaced by combined hormonal contraception (CHC), coinciding with the beginning of sexual life, with a favorable response and regular bleeding. POI has serious health consequences including psychological disorders such as distress, depressive symptoms or depression, infertility, osteoporosis, autoimmune disorders, ischemic heart disease, and an increased risk of mortality. Hashimoto's disease is the most common autoimmune disorder associated with POI. Its treatment and diagnosis must be established early to avoid long-term consequences. Estrogen therapy is the mainstay of treatment to eliminate the symptoms of estrogen deficiency, in addition to avoiding the future consequences of untreated hypogonadism. Management should also include the following domains: fertility and contraception, bone health, cardiovascular problems, psychosexual, psychological and neurological function, informing family members and the patient about the real dimension of POI and the need for multidisciplinary treatment in many cases. CONCLUSION: The case, although infrequent, allows a systematic approach to the diagnosis of POI and evaluate plausible management alternatives to avoid serious health consequences, as well as to know the clinical response and satisfaction of the adolescent.

Research progress of methods to promote the survival of cryopreserved ovarian tissue auto-transplantation / 器官移植

With the technology development of cancer treatment, the survival rate of patients with cancer has been significantly improved. However, chemotherapy and radiation therapy may lead to premature ovarian failure and infertility in young women with cancer. Cryopreserved ovarian tissue auto-transplantation is an effective method to preserve fertility of such female patients. At present, the biggest challenge of this technique is mass loss of follicles after transplantation. In this article, the influencing factors and improvement methods of survival of cryopreserved ovarian tissue auto-transplantation were reviewed.

Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway / 中国天然药物

Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg

Time for preparing a mouse model of autoimmune premature ovarian failure / 中国组织工程研究

BACKGROUND: Studies have confirmed that anti-zona zona antibodies can accelerate the destruction and depletion of oocytes, thereby causing premature ovarian failure. OBJECTIVE: To investigate the time of establishing autoimmune premature ovarian failure model in BALB/c mice induced by zona pellucida 3 peptides. METHODS: Thirty healthy female BALB/c mice (7-8 weeks) were randomly divided into immune experimental group (20 mice) and the control group (10 mice). In the experimental group, the mice were given immunization injection starting at 0 week, 0.15 mL of immune reagent injected into the soles at both sides and the lower abdomen. The vaginal exfoliated cell smears were observed every morning to observe the changes in the estrous cycle of the mice. After 2 weeks of injection, 0.15 mL of immune enhancement agent was injected subcutaneously into the same site. On the first day of weeks 4 and 6, the immune agent or immune enhancement agent was injected alternatively. Blood samples were collected before each injection and the serum sex hormone level was measured by enzyme-linked immunosorbent assay. Finally, ovarian tissue and uterus morphology were observed. RESULTS AND CONCLUSION: There was no difference in serum follicle stimulating hormone and estrogen levels between the first immunization injection and 2 weeks after the injection. The serum estrogen level in the experimental group was significantly lower than that in the control group at 4 weeks after injection. The serum estrogen level of the experimental group was significantly lower than that of the control group at 6 weeks after injection (P < 0.05), and meanwhile the serum follicle stimulating hormone level was significantly higher than that of the control group (P < 0.01). The degree of ovarian interstitial fibrosis in the experimental group was more obvious than that in the control group. The ovarian volume decreased and the uterus atrophied in the experimental group. The number of primitive follicles, primary follicles and secondary follicles in mice was significantly lower in the experimental group than the control group, and the number of atresia follicles was significantly higher than the control group (P < 0.05). Therefore, 75 μg of zona pellucida 3 peptides can be used to establish an autoimmune premature ovarian failure disease model in BALB/c mice, and a good modelling effect can be achieved at 6 weeks after immunization.

Study on the Mechanism of Couplet Medicine of Cuscutae Semen-Lycii Fructus in the Treatment of Premature Ovarian Failure Based on Network Pharmacology / 中国药房

OBJECTIVE：To investi gate the potential mechanism of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure. METHODS ：Main active components and related targets of couplet medicine of Cuscutae Semen-Lycii Fructus in the treatment of premature ovarian failure were obtained from TCMSP ，GeneCards and OMIM database. The intersection genes between them were screened using Venn online tool. Cytoscape 3.7.0 software was adopted to establish the active ingredients-target network and the PPI network. GO and KEGG pathway enrichment analysis on intersection genes were carried out by DAVID database. Finally ，an active component-target-key pathway network was constructed. RESULTS ：Totally 42 active components ，231 and 1 913 targets for active components and disease were obtained from couplet medicine of Cuscutae Semen-Lycii Fructus. The components with high node degree included quercetin ，kaempferol，β-sitosterol，isorhamnetin，glycitein， stigmasterol and sesamin ，etc. There were 149 intersection genes between the active component targets and premature ovarian failure targets. PPI network contained 149 nodes and 2 970 edges，with an average node degree of 39.9 and an average medium of 0.005 4. The results of GO analysis showed that molecule function of the above-mentioned genes mainly involved protein binding ， enzyme binding ，etc. Biological process mainly included that positive regulatio n of transcription from RNA polymerase Ⅱ promoter，positive regulation of transcription DNA-templated ， Cell components mainly included nucleus ，cytoplasm，etc. Signaling pathway mainly involved cancer signaling pathway ， hepatitis B signling pathway ，PI3K/AKT signaling pathway ， MAPK signaling pathway ， etc. The results of active 617693370@qq.com component-target-key pathway network showed that active components of Cuscutae Semen and Lycii Fructus were flavonoids and alcohols ；key target included AKT 1，TP53， VEGFA，IL6，TNF，etc. Signaling pathway mainly involved cancer signaling pathway ，hepatitis B signaling pathway ，PI3K/AKT signaling pathway ，MAPK signaling pathway ，etc. CONCLUSIONS ：Through PI 3K/AKT signaling pathway and MAPK signaling pathway，the active components of couplet medicine of Cuscutae Semen-Lycii Fructus may act on AKT 1，TP53 and other targets ， and then play a therapeutic role on premature ovarian failure. The Potential active components stigmasterol ，sesamin and potential targets IL 6，TNF were found.

Effect of ginsenoside Rg_1 in delaying premature ovarian failure induced by D-gal in mice through PI3K/Akt/mTOR autophagy pathway / 中国中药杂志

The aim of this paper was to study the role of phosphoinositide 3-kinase(PI3 K), protein kinase B(Akt) and mamma-lian target of rapamycin(mTOR) in the inhibition of premature ovarian failure induced by D-galactose(D-gal) in mice model by ginsenoside Rg_1(Rg_1). Fifty-four female SPF BALB/c mice were randomly divided into PBS group, D-gal group, and Rg_1 group. In the D-gal group, D-galactose(200 mg·kg~(-1)·d~(-1)) was injected subcutaneously into the neck and back for 42 days. In the PBS group, an equal amount of phosphate buffered saline(PBS) was injected into the neck and back for 42 days. In addition to the therapy of D-gal group, Rg_1 group was given Rg_1(20 mg·kg~(-1)·d~(-1)) through intraperitoneal injection since the 15 th day for 28 days, at the same time, the D-gal group and the PBS group were also given an equal amount of PBS through intraperitoneal injection since the 15 th day for 28 days. After the treatment, the estrous cycle changes of the mice were detected, and the ovarian SA-β-Gal staining was used to detect the changes of ovarian aging. Western blot was used to detect the changes in protein expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). Fluorescence quantitative PCR was used to detect the changes in mRNA expressions of PI3 K, Akt, mTOR, S6 k, LC3-Ⅱ and P16~(INK4 a). According to the findings, compared with the PBS group, the D-gal group began to show estrous cycle disorder in the 3 rd week,the ovarian SA-β-Gal staining positive granulosa cells increased in the D-gal group, the expression of senescence marker P16~(INK4 a) increased, while the expression of autophagy signaling molecule LC3-Ⅱ decreased. After treatment with Rg_1, the positive rate of ovarian SA-β-Gal staining in Rg_1 group decreased, the expression level of autophagy signaling molecule LC3-Ⅱ in Rg_1 group was higher than that in D-gal group, while the expression level of senescence marker P16~(INK4 a) was lower than that in D-gal group. Compared with the PBS group, the protein and mRNA expressions of PI3 K, Akt, mTOR and S6 k in the D-gal group were up-regulated, the protein expressions of Akt, mTOR and S6 k in the Rg_1 group were up-regulated, and the mRNA expressions of PI3 K and mTOR were up-regulated. After treatment with Rg_1, the protein expressions of PI3 K, Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group, while the mRNA expressions of Akt, mTOR and S6 k in the Rg_1 group were lower than those in the D-gal group. The finding ssuggested that Rg_1 has the effect in delaying ovarian premature failure in D-gal-induced mouse models, and PI3 K/Akt/mTOR autophagy signaling pathways play an important role.

Study of incidence of premature ovarian failure in patient attending outpatient department for infertility in a tertiary care centre

Background: To assess the incidence of premature ovarian failure in cases attending infertility outpatient Department of Obstetrics and Gynecology in a tertiary care centre. A total of 350 patients attending infertility opd were screened over period of 150 days from which authors observed premature menopause in 10 cases accounting for an incidence of 2.8%. POF affects approximately one in 10,000 women by age 20; one in 1,000 women by age 30; one in 100 women by age 40.  Premature ovarian failure is a common cause of infertility in women.Methods: Patient attending outpatient Department of Obstetrics and Gynecology with age less than 40 years and infertility, symptoms of menopause were enrolled for the study for duration of 150 days.Results: Present study authors found a total of 2.8% of patient presenting in our outpatient department for infertility had Premature ovarian failure.80% of them were symptomatic suffering with symptoms of hormonal deficiencies .100% of patient with infertility diagnosed as premature ovarian failure had low AMH and High FSH and LH levels indicating poor prognosis.Conclusions: Patient presenting with infertility and amenorrhoea can be cases of premature menopause. Here it is essential to investigate and treat the patient. Infertility might be one of the early presenting symptoms if not the first one. These patients if treated and diagnosed early can have a better living. Considering the wide spectrum of functional derangements in patient with early menopause and benefits of early hormone replacements these patients should be diagnosed and treated early.

Premature ovarian failure incidence, risk factors and its relation to BMI and infertility

Background: Premature ovarian failure (POF) is cessation in the normal functioning of the ovaries in women younger than age 40 years. It is estimated to affect1% of women younger than 40 years and 0.1% of those under 30 years. Premature ovarian failure is a common cause of infertility in women.Methods: Patient attending outpatient Department of Obstetrics and Gynecology with age less than 40 years and complaint of menstrual disturbances, symptoms of menopause were enrolled for the study for duration of 1year. This study is planned to calculate the incidence, risk factors, relation to BMI and infertility in patients attending outpatient department at Geetanjali medical college and hospital, Udaipur for all enrolled patient coming with complaints of menstrual disturbances. FSH levels were send for all the patients and those with FSH level more than 20 at day 2/3 for menstruating women and random FSH level for amenorrhea patient more than 20 were classified in to study group and all those women with FSH less than 20 are taken as control group.Results: Present study strongly suggests that simple laboratory test FSH and symptoms of missed and irregularity of menstrual cycle help in early and prompt diagnosis of premature ovarian failure. And early diagnosis helps in avoiding unnecessary medications and helps in improving long term morbidity.Conclusions: Disturbances in menstrual cycle like amenorrhea and infrequent cycles are the symptoms which are associated with premature ovarian failure after ruling out pregnancy and other hormonal and structural causes.

Reality of premature ovarian failure in Argentina

SUMMARY Premature Ovarian Insufficiency is defined as a decline in ovarian function that is accompanied by two biochemical determinations of Follicle Stimulating Hormone in hypergonadotropic values, in addition to low levels of circulating estrogens in women under 40 years old. Although some of its possible etiologies are recognized and diagnosed, most of the time, its cause remains unknown. It is a pathology with medical, psychological, and reproductive implications. Patients may experience climacteric symptoms, infertility, and emotional distress. In the medium and long term, cardiovascular and bone health can be affected, and some degree of cognitive deterioration can be evidenced. The therapeutic approach needs to be comprehensive for the patient and multidisciplinary. SAEGRE created in Argentina an interhospital network dedicated to gathering relevant statistical information regarding this and other pathologies in order to provide better assistance for these patients.

RESUMO Insuficiência ovariana primária é definida como um declínio da função ovariana acompanhado por dois determinantes bioquímicos do Hormônio Folículo Estimulante em valores hipergonadotróficos, além de baixos níveis de estrogênios circulantes em mulheres com menos de 40 anos de idade. Embora algumas das suas possíveis etiologias serem reconhecidas e diagnosticadas, na maioria das vezes sua causa permanece desconhecida. Trata-se de patologia com a implicações médicas, psicológicas e reprodutivas. Os pacientes podem vivenciar sintomas climatéricos, infertilidade e problemas emocionais. A médio e longo prazo, a saúde cardiovascular e óssea pode ser afetada, e algum grau de deterioração cognitiva pode ser observado. A abordagem terapêutica precisa ser abrangente para o paciente e multidisciplinar. A SAEGRE criou na Argentina uma rede interospitalar dedicada a reunir informações estatísticas relevantes sobre esta e outras patologias, a fim de proporcionar uma melhor assistência para esses pacientes.

Criteria, diagnosis and treatment of decreased ovarian function: Recent progress / 第二军医大学学报

Fallopian tube factors and decreased ovarian function are the main causes of female infertility. Decreased ovarian function includes premature ovarian failure, diminished ovarian reserve, premature ovarian insufficiency and poor ovarian response. The main feature of ovarian function decline is the decrease in the number and/or the low quality of ova, manifested as ovulation disorders, infertility and reproductive endocrine disorders. This article summarizes the progress in different evaluation criteria and treatment of decreased ovarian function, hoping to provide reference for future diagnosis and treatment.

Repair effect of bone marrow mesenchymal stem cells over-expressing miR-21 on chemotherapeutic premature ovarian failure / 解放军医学杂志

[Abstract] Objective To explore the repair effects of bone marrow mesenchymal stem cells (BMSCs) over-expressing miR-21 on chemotherapeutic premature ovarian failure (POF) in rats. Methods The expression vector of lentivirus-mediated miR-21 (LV-miR-21) was constructed, and BMSCs were transfected with LV-miR-21 to construct miR-21-BMSCs. A hundred rats were divided into 5 groups (20 each): normal group, model group, miR-21 group, BMSCs group and miR-21-BMSCs group. The chemotherapeutic POF model was established by intraperitoneal injection of cyclophosphamide (CTX) in rats of the latter 4 groups. Then LV-miR-21, BMSCs and miR-21-BMSCs were injected respectively into the bilateral ovaries of the rats in the latter 3 groups, and physiological saline was injected into the rats of normal group and model group. At 15, 30, 45 and 60 days after injection, the estrus cycle, estradiol (E2) and follicle stimulating hormone (FSH) level, ovarian weight, follicle count at all levels, and apoptotic rate of granulosa cells in each group were detected. Results After injection of CTX, the estrus cycle of rats remained regular in normal group, and fell into disorder in the other four groups, of which the number of rats with recovered estrus cycle in the miR-21-BMSCs group was more than the other three groups; The ovarian weight and follicle count at all levels were significantly higher in miR-21-BMSCs group than in model group, miR-21 group and BMSCs group 30, 45 and 60 days after CTX injection (P<0.05); The basal levels of E2 and FSH showed no significant difference in each group during the experiment, while the E2 concentration decreased and FSH concentration increased in all the groups except the normal group. The hormone levels of E2 and FSH in miR-21-BMSCs group (F30d=43.10 and F30d=14.71) were significantly different when compared to those in miR-21 group and BMSCs group (F45d=43.57 and F45d=13.16, P<0.05; and F60d=44.98 and F60d=15.20, P<0.05); The apoptotic rate of ovarian granular cells in miR-21-BMSCs group was significantly lower (F60d=21.20) than that in model group, miR-21 group and BMSCs group (F15d=27.20, F30d=23.60 and F45d=21.80, P<0.05). Conclusion miR-21 may enhance the therapeutic effect of BMMSCs on chemotherapeutic premature ovarian failure, and significantly improve the ovarian structure and function.