Abstract:Premature ovarian insufficiency(POI)is a major disorder characterized by the decline of ovarian reserve function in reproductive-aged women.Its pathogenesis involves multiple factors,including immune dysregulation,genetic predisposition,infectious agents,and iatrogenic interventions.Aberrant cellular immunity is recognized as one of the critical etiological drivers of POI.As a key subset of lymphocytes in cellular immune responses,the helper T cells(Th cells)play a pivotal role in regulating ovarian endocrine function and folliculogenesis through the mechanisms of differentiation and immune regulation.Among Th cell subsets,Th17 cells and their signature cytokine,interleukin-17A(IL-17A),have emerged as the central players in the immunological pathogenesis of POI.Th17 cells secrete the pro-inflammatory cytokine IL-17A,which directly induces local ovarian inflammation and disrupts tissue architecture.Additionally,they also impair the follicular microenvironment,thereby compromising the granulosa cell function and leading to the reduction in ovarian reserve.Furthermore,Th17 cells disrupt immune homeostasis,thereby promoting the autoimmune injury that ultimately results in ovarian insufficiency.This target may become a potential novel immunotherapy strategy for POI.

Abstract:Gong-han infertility,as a classical pathogenesis of infertility in traditional Chinese medicine(TCM),fundamentally results from the deficiency of yang qi in the body,leading to loss of warmth in the uterus.Its etiology originates from the endogenous cold pathogenic factors(innate yang deficiency,excessive sexual activity and multiple childbirths consuming kidney yang)and the exogenous cold pathogenic factors(indulgence in cold food/drinks,prolonged living in damp environments).The modern biological mechanisms are manifested as follows:kidney yang deficiency causes hypothalamic-pituitary-gonadal axis dysfunction;the astringent property of cold activates the endothelin system,leading to the decreased ovarian microcirculatory perfusion and the reduced endometrial receptivity;mitochondrial dysfunction and the decreased ATP production result in delayed energy metabolism;cold qi generating turbidity accompanied by the activation of inflammatory factors induces the accumulation of pathological products like endometrial hyperplasia and polyps.The treatment focuses on"warming yang as the foundation and resolving turbidity to generate newness",while simultaneously strengthening the spleen to cultivate earth and regulating qi to smooth mechanism,so as to restore the reproductive function of the uterus.This provides a theoretical basis and clinical reference for the integrated traditional Chinese and Western medicine diagnosis and treatment of"Gong-han infertility".Based on the TCM thought of"Heaven-human correspondence"and metaphorical cognition,this paper systematically elaborates the theoretical connotation,etiology,pathogenesis,modern biological mechanisms,and treatment strategies of"Gong-han infertility".

Abstract:A case of retroperitoneal solitary fibrous tumor(SFT)in our hospital was reported.The first treatment,10-year follow-up and diagnosis and treatment after recurrence were summarized.In 2015,the first surgery was performed to completely remove the tumor located in the left anterior sacrum of retroperitoneum under laparoscopy.Pathology showed SFT with the rich focal cells.There were no symptoms after the first surgery,and the patient was not followed up regularly.Recurrence was first detected in 2022:physical examination and a series of imaging examinations revealed pelvic pararectal nodules,which gradually increased in the number and volume.In 2023,the reexamination revealed that nodules continued to increase.In November 2024,the operation of laparoscopic left deep retroperitoneal tumor resection plus tumor resection near internal iliac artery plus pelvic adhesiolysis was performed.Pathology showed SFT,and the increased cell density and slightly increased mitotic figures(＜4 per 10 high-power fields).After six months of the second surgery,the patient did not undergo reexamination due to the continuous urinary retention rehabilitation therapy.Retroperitoneal SFT is very rare,which is belonged to low-grade malignant tumor.SET has recurrence risk,suggesting the necessity of lifelong follow-up.The tumor of this patient is located in the deep part of retroperitoneal pelvic floor,adjacent to pelvic floor nerves and blood vessels.Multi-disciplinary team(MDT)should be recommended for the preoperative diagnosis and treatment.Intraoperative multidisciplinary surgery can significantly improve the safety and success rate of surgery.

Abstract:Objective:To investigate the status of appropriate medication at the different stages of in vitro fertilization(IVF)in infertility patients undergoing IVF treatment,and its effects on clinical pregnancy.Methods:From June 2024 to December 2024,a total of 369 female patients with IVF were selected from Reproductive Medicine Center of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine.The patient were investigated by general information questionnaire,medication accuracy and medication guidance satisfaction questionnaire,self-efficacy for appropriate medication use scale(SEAMS),perceived social support scale(PSSS)at the different stages of IVF treatment.The influencing factors of the final pregnancy outcome were screened by multivariate Logistic regression analysis.Results:About 48.78％(180/369)to 55.28％(204/369)of the patients didn't have high medication adherence at the different stages of IVF,with the'uncertain factors'dimension having the lowest score rate.The SEAMS scores,medication guidance satisfaction scores,and PSSS scores at different stages were positively correlated with each other(P＜0.001).Logistic regression analysis found that,age ≤30 years old(OR=0.35,95％CI:0.19-0.66,P=0.001),age 31-35 years old(OR=0.37,95％CI:0.20-0.66,P=0.001),medium score of SEAMS during transplantation cycle(OR=0.29,95％CI:0.13-0.61,P=0.001),and ≥ 3 types of daily medication delivery routes in luteal support period(OR=0.53,95％CI:0.29-0.98,P=0.048),and the high satisfaction score of medication guidance during luteal support period(OR=0.72,95％CI:0.60-0.88,P=0.001)were the protective factors for successful clinical pregnancy.Conclusions:Paying attention to the age of IVF patients,the types of medication delivery routes and conditions of medication during the transplantation stage,taking corresponding measures to guide medication,and improving their satisfaction,can improve the success rate of clinical pregnancy in IVF patients.

Abstract:Ring chromosome 4 is a rare chromosomal structural abnormality with significant clinical heterogeneity.We report a case of an adult male patient with multiple malformations including microcephaly,micrognathia,hooked nose,short stature,congenital heart defects,and azoospermia.The patient was scheduled for surgery due to a bladder malignancy,and requested fertility preservation before the operation.However,multiple semen analyses indicated azoospermia,and a percutaneous testicular sperm aspiration showed no sperm in both testes.Pathological examination revealed approximately 40 seminiferous tubules with a small number of spermatocytes and a few sperm,and a Johnsen score of 8.Chromosome karyotype analysis showed mos 46,XY,r(4)(?p16.3?q35)[94]/46,XY[6].It was suggested that the patient undergo microdissection testicular sperm extraction and sperm cryopreservation during the bladder tumor resection.However,due to malignant tumor and other factors,the patient ultimately decided to forgo fertility preservation and only underwent radical tumor surgery.The patient typically presents with multiple system dysfunctions such as growth retardation and abnormal fertility.It is necessary to complete the chromosomal G-banding karyotype analysis and related molecular-level examinations as soon as possible.After diagnosis,genetic counseling should be actively carried out,and assisted reproductive technology should be utilized in a timely manner to better achieve eugenics and good childbearing.

Abstract:Sperm morphology is a key indicator for assessing male fertility.The abnormality of sperm morphology is closely associated with the reduced sperm motility,lower fertilization rate and male infertility.Long-term or excessive consumption of high fat diet can lead to obesity,metabolic disorders and hormonal imbalances,which is significantly correlated with abnormal sperm morphology.The potential mechanisms by which high-fat diet induces sperm morphological abnormality involve the multiple disruptions in the hypothalamic-pituitary-gonadal axis,aberrant sperm membrane lipid metabolism,cytoskeletal dynamic imbalance,oxidative stress,testicular microenvironment inflammation,and epigenetic modifications.Interventions such as adopting a Mediterranean diet pattern or supplementing with antioxidants(e.g.,vitamin C,coenzyme Q10)may ameliorate the high fat diet-induced abnormalities in sperm morphology and function.We review the recent advances in the potential mechanism of how high fat diet-induced sperm morphological abnormalities,providing clinically strategies based on dietary modification and antioxidant intervention.

Abstract:Alstrom syndrome is an autosomal recessive disorder with multisystem involvement caused by the mutations in ALMS1 gene.The pathogenesis of the disease is not fully understood,the effective treatment is also lacking,and the prognosis is poor.The young age of onset,wide range of clinical symptoms and varying severity of the disease make it difficult to diagnose and treat.We report a female case of Alstrom syndrome diagnosed by whole exome sequencing(WES).The patient presented with congestive heart failure,congenital cardiomyopathy,atrial septal defect,growth retardation and recurrent pneumonia.She was given symptomatic treatments including infection control,cardiotonic,diuretic,and calcium supplementation,but the final prognosis was poor.The ALMS1 compound heterozygous variant c.11647_c.11648delAT(p.M3883fs*9)/c.2888_c.2897del GTGTTTTCTA(p.S963fs*15)was found to be a rare variant.The discovery of this compound heterozygous variant provided a new reference for the genetic study of Alstrom syndrome.

Abstract:We report a case of a child with haemophilia A complicated by compound heterozygous variants in the CYP21A2 gene.Routine tests upon the child's admission indicated the abnormal coagulation function.Whole exome sequencing(WES)analysis revealed that the child had the compound heterozygous variants c.292+1G＞A and c.-113G＞A in the CYP21A2 gene.Verified by Sanger sequencing,the c.-113G＞A site variant was inherited from the mother,and this site was rated as a likely pathogenic variant.The c.292+1G＞A site variant was inherited from the father,and this site was rated as a pathogenic variant.Since WES did not detect the variants highly correlated with the child's current clinical phenotype,and the clinical phenotype highly suggested haemophilia,long-range polymerase chain reaction(LR-PCR)was simultaneously carried out.The results of LR-PCR indicated an inversion of intron 22 in F8 gene.The child's mother was a carrier,while the father had a normal genetic profile.After admission,the child received symptomatic treatment and supplementation with exogenous factor Ⅷ,and then was discharged in an improved condition.During the follow-up,the child has been regularly receiving exogenous supplementation of factor Ⅷ,and the condition remains stable with no other abnormalities.The genetic diagnosis of the child was clarified through the combined use of WES and LR-PCR,which provided us a basis for genetic counseling of family members,future prenatal diagnosis and the subsequent management.

Abstract:Endometriosis(EMs)is a common gynecological disease among women of childbearing age.It is characterized by a complex pathogenesis,gradual aggravation,a tendency to prolong the disease and be difficult to cure.It can significantly reduce the quality of life and fertility.The monomer of traditional Chinese medicine(TCM)is a single chemical component with a clear chemical structure and pharmacological activity,which is extracted and purified from TCM.Recent studies have shown that TCM monomers such as aldehydes,phenols,alkaloids,terpenoids,flavonoids and polysaccharides can effectively intervene in the pathological process of EMs through multiple pathways.The mechanisms of action include reducing inflammatory responses,inhibiting angiogenesis,regulating hormone levels,alleviating pain sensitization,promoting apoptosis and antioxidation,etc.Compared with traditional surgery and hormone therapy,TCM monomers have many advantages such as multiple targets and fewer side effects,and have increasingly become a research hotspot.Based on this,this article sorts out and summarizes the research literature at home and abroad on the use of TCM monomers in the treatment of EMs,with the aim of providing a certain basis for the new drug development and clinical application of EMs.

Abstract:Ovarian cancer,cervical cancer and endometrial cancer are the three common malignant tumors in gynecology,and exploring safer and more efficient treatments to improve the long-term survival rate and life quality of patients has become a hot topic in the current research.Resveratrol(RES),a natural polyphenolic compound,exists in a variety of plants.In recent years,a large number of studies have shown that RES has a certain value in the treatment of malignant tumors.The mechanism of RES anti-tumor role is very complex,including anti-inflammatory,immunomodulation,inhibition of tumor proliferation and metastasis,promotion of autophagy and apoptosis,and inhibition of angiogenesis.In this paper,we review the role and mechanism of RES in the three major gynecologic malignant tumors,in order to provide a scientific basis for the development of RES clinical application in the treatment of gynecologic malignant tumors.

Abstract:The family of heterogeneous nuclear ribonucleoprotein(hnRNP)includes more than twenty kinds of RNA-binding proteins that play an important role in many life processes.Besides RNA binding,hnRNP mainly involved in regulating key biological processes such as N6-methyladenosine(m6A)modification and DNA damage repair.Many studies have shown that many members of hnRNP family,including HNRNPA2B1,HNRNPC,HNRNPH1 and HNRNPK,play an important role in the development of oocytes,and that the loss of hnRNP function can lead to the abnormal development of oocytes and infertility.However,the in-depth mechanism reaserch of hnRNP regulating oocyte development is insufficient.Reviewing the biological function of hnRNP in regulating oocyte development can provide reference for future research in reproductive field.

Abstract:The technology of enucleated oocyte donation(EOD),also known as mitochondria donation,aims to transfer the nuclear genetic material of the patient's oocytes or fertilized eggs into the cytoplasm of healthy enucleated donor oocytes,in order to block the inheritance of mitochondrial DNA(mtDNA)mutations to offspring or solve the problem of embryonic development arrest caused by cytoplasmic factors.EOD technology mainly includes pronuclear transfer(PNT),polar body transfer(PBT),and spindle-chromosome complex transfer(ST).Both PNT and ST have successfully helped female carriers of mtDNA mutations and women with repeated in vitro fertilization-embryo transfer failures to achieve clinical pregnancy.However,some offspring still carry a small amount of mtDNA mutations,and even have an increased proportion of residual mtDNA mutations.The first polar body transfer(PB1T)has also been used to obtain the mutant free reconstructed blastocysts in women with mtDNA mutations.EOD technology still faces multiple challenges:there is a risk of fertilized egg damage in medicine,ethical controversies focus on the status of donors in the three parent structure and their impact on offspring,safety concerns involve compatibility issues between mitochondria and cell nuclei,and genetic risks of mutated mtDNA.Regulatory authorities need to prevent clinical abuse and the lack of informed consent.

Abstract:Ovarian fibroma is a common benign sex cord stromal tumor,accompanied by pleural effusion and ascites,which regress to Meigs syndrome after resection.The incidence of Meigs syndrome is relatively low,and the ovarian fibroma with the elevated carbohydrate antigen 125(CA125)is easily misdiagnosed as malignant tumor.We report a case of 18-year-old female patient with ovarian fibroma who was admitted to an external hospital due to abdominal distension and lower abdominal distension.Imaging showed a huge cystic solid mass in the pelvic cavity(11.3 cm × 10.6 cm × 7.9 cm),a large amount of pelvic and abdominal fluid accumulation,and a significant increase in serum CA125(1 168.00 U/mL).The patient underwent adnexectomy on the affected side at the First Hospital of Lanzhou University.Multiple adhesive lesions were observed during the surgery,and the postoperative pathological diagnosis was ovarian fibroma.After tumor resection,the patient experienced chest tightness and shortness of breath,and CT showed bilateral pleural effusion.One month after surgery,the pleural and ascites completely subsided,and the level of CA125 returned to normal.Follow up for 2 year after surgery,the patient showed no recurrence or metastasis.Therefore,in clinical practice,pelvic masses with the elevated CA125 and Meigs syndrome may be misdiagnosed as ovarian cancer.This case emphasizes the possibility of ovarian fibroids/follicular membrane fibroids in the differential diagnosis of ovarian tumors with elevated CA125.Surgical resection is the preferred treatment method,and the postoperative prognosis is good.

Abstract:The aberrant expression of adipokines may contribute to the onset and progression of polycystic ovary syndrome(PCOS),with its mechanism involving the regulation of multiple signaling pathways including Wnt/β-catenin,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),c-Jun N-terminal kinase(JNK)/mitogen-activated protein kinase(MAPK),Janus kinase(JAK)/signal transducer and activator of transcription(STAT),nuclear factor-κB(NF-κB)and their downstream signaling molecules.Research indicates that various therapeutic modalities,such as exogenous adipokines,specific adipokine antagonists,conventional hypoglycemic agents and dietary interventions,can ameliorate PCOS-related ovarian pathology,modulate insulin signal transduction and the expression of genes associated with hormone synthesis,suppress oxidative stress and inflammatory reactions,enhance endometrial receptivity,and facilitate embryo implantation and development by rectifying the expression of adipokines and their receptors.In turn,these interventions alleviate PCOS-related endocrine and metabolic disturbances,immune abnormalities,and reproductive dysfunctions.Adipokines may be as a potential target for the PCOS treatment.Nevertheless,owing to the intricate crosstalk between adipokines and the substantial heterogeneity among PCOS patients,current research primarily centers on animal studies.Based on these animal studies,additional clinical trials should be well designed to develope the innovative regimens of PCOS treatment based on adipokine regulation.

Abstract:Ovarian cancer(OC)is one of the common malignant tumors in women.Most of patients are diagnosed at the advanced stage due to its insidious onset,resulting in poor clinical treatment outcomes.Currently,the treatment of OC mainly relies on chemotherapy and surgery,but the chemotherapy resistance and adverse reactions remain the clinical challenge.Studies have shown that the abnormal expressions of multiple signaling pathways are related to the pathogenesis of OC,such as the abnormal activation of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.The active components of traditional Chinese medicine can regulate the PI3K/Akt signaling pathway to inhibit the proliferation,invasion,migration and angiogenesis of OC cells,to promote the apoptosis of OC cells,and to improve the chemosensitivity of OC cells.This review summarizes the role of the PI3K/Akt signaling pathway in OC and the research progress on the mechanism of the active components of traditional Chinese medicine in regulating the PI3K/Akt signaling pathway,with the aim of providing a reference for the clinical application of traditional Chinese medicine in the treatment or adjutant therapy of OC.

Abstract:Objective:To summarize the experience of molecular genetic analysis of two patients with Gitelman syndrome.Methods:Two patients admitted to our hospital due to recurrent hypokalemia were highly suspected as Gitelman syndrome in clinical.Peripheral venous blood samples were collected from the patients and their parents.Genomic DNA was extracted and analyzed by whole exome sequencing(WES).Results:The trio-WES analysis showed that two patients had the compound heterozygous variations in the SLC12A3 gene.The variation sites were c.965-1_976delinsACCGAAAATTTT and c.1964G＞A in one patient,and c.486_491delinsAC and c.2178+1G＞T in another patient.Both parents were carriers of the mutant sites with normal phenotypes.The results of Sanger sequencing were consistent with those of trio-WES.Conclusions:The compound heterozygous pathogenic variations in the SLC12A3 gene may be the genetic cause of these two patients,which expands the spectrum of pathogenic variations of this gene.For those patient suspected as Gitelman syndrome,the genetic testing of the patient and parents should be completed,so as to make a clear diagnosis,provide more comprehensive genetic counseling and more accurate prenatal diagnosis for subsequent pregnancies.

Abstract:Per-and polyfluoroalkyl substances(PFAS)exist in life area and consumer products,and enter the human body through breathing,diet,skin contact and other ways.PFASs cause the adverse consequence to female reproductive health.Studies have shown that PFAS can affect ovarian function by interfering with the endocrine axis,damaging mitochondria,inducing oxidative stress,disrupting gap junction communication,and regulating epigenetics,and resulting in reproductive toxicity,which is also related to many diseases of female reproductive system such as polycystic ovary syndrome,premature ovarian insufficiency,diminished ovarian reserve and endometriosis.In infertile people treated with assisted reproductive technology(ART),it was also found that the level of PFAS was negatively correlated with oocyte yield,the number of two pronuclei,and embryo quality,adversely affecting ART outcomes.We review the impact of PFAS on female reproductive health and ART outcomes,in order to provide a new evidence for the subsequent research.

Abstract:The pathogenesis of endometriosis(EMs),as a common and difficult gynecological disease,is not very clear.The possible mechanisms include chronic inflammation,neovascularization,estrogen dependence,weakened progesterone response,epithelial-mesenchymal transition and fibrosis,etc.Galectin-3 is the only member of the Galectinin family with a chimeric structure.It participates in mutiple biological processes such as cell adhesion,migration,invasion,angiogenesis and fibrosis,which is closely related to the occurrence of cancer and inflammatory diseases.The correlation between Galectin-3 and EMs has received the extensive attention in recent years.The latest studies have shown that the overexpression of Galectin-3 can affect the occurrence and development of EMs by promoting the survival of inflammatory cells,epithelial-mesenchymal transition,fibrosis,and participating in the regulation of sex hormones.This article summarizes the functions of Galectin-3 and its correlation with the pathophysiology of EMs,with the aim of providing new ideas for the clinical diagnosis and treatment of EMs.

Abstract:Objective:To investigate the mechanism of Yishen Quzhuo Formula in treating polycystic ovary syndrome with insulin resistance(PCOS-IR)through the network pharmacology and experimental validation.Methods:Active components and targets of Yishen Quzhuo Formula were retrieved from databases such as Traditional Chinese Medicine Systems Pharmacology(TCMSP).The targets of PCOS-IR-related disease were screened using GeneCards,OMIM,and DrugBank databases.A drug-component-target network was then constructed.Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)function,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using STRING and DAVID.Molecular docking was conducted with AutodockTools 1.5.7 software.A PCOS-IR rat model was established using the high-fat diet combined with letrozole.Serum hormone levels and glucose metabolism indices were evaluated.The expression of key targets was validated via Western blotting and quantitative polymerase chain reaction(qPCR).Results:A total of 136 potential active components of Yishen Quzhuo Formula and 406 PCOS-IR-related targets were identified.Five core components,including kaempferol,quercetin,and β-sitosterol,were selected.The top 10 key targets,such as interleukin-6(IL-6),signal transducer and activator of transcription 3(STAT3),protein kinase B1(AKT1),heat shock protein 90(HSP90),and tumor protein 53(TP53),were ranked by the degree values in the core network,enriched in the pathways like advanced glycation end product-receptor for advanced glycation end product(AGE-RAGE)and phosphoinositide 3-kinase(PI3K)-AKT.Animal experiments showed that Yishen Quzhuo Formula significantly reduced the levels of serum luteinizing hormone(LH),testosterone,fasting insulin(FINS),and homeostasis model assessment of insulin resistance(HOMA-IR)in PCOS-IR rats(all P＜0.05),and downregulated the expressions of STAT3,epidermal growth factor receptor(EGFR)and HSP90 in the ovarian tissues of PCOS-IR rats,while upregulated the expressions of AKT1 and TP53(all P＜0.05).Conclusions:Yishen Quzhuo Formula ameliorates the endocrine abnormalities and glucose metabolism disorders of PCOS-IR through multi-component,multi-target and multi-pathway mechanisms.

Abstract:Preeclampsia(PE)is a common complication during pregnancy.The pathogenesis of PE is closely related to immune imbalance,inflammatory responses,and placental dysfunction.The triggering receptors expressed on myeloid cells-1(TREM-1)is an important pro-inflammatory receptor,widely expressed in neutrophils and mononuclear macrophages.TREM-1 plays a role in amplifying inflammatory responses in various inflammatory diseases.Studies have found that TREM-1 expression is significantly elevated in the peripheral blood and placental tissues of PE patients.It can activate nuclear factor-κB(NF-κB)and promote the release of cytokines through the multiple signaling pathways such as DNAX-associated protein 12(DAP 12),Toll-like receptor 4(TLR4),and nucleotide-binding oligomerization domain receptors(NLRs),thereby exacerbating inflammatory damage and endothelial dysfunction.TREM-1 may also serve as a potential biomarker for the early assessment of PE risk and severity.This review focuses on the structure of TREM-1,its signaling pathways and possible mechanisms in the development of PE,aiming to provide a theoretical basis for the early diagnosis and targeted intervention of PE.