Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance...Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.展开更多
The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Re...The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.595–603.展开更多
Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protei...Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.展开更多
Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stim...Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.展开更多
BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs inc...BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs include abdominal pain,an abdominal mass,menstrual abnormalities,and infertility.Infrequently,patients will experience androgen-related manifestations of masculinization,such as increased hair,acne,or a low voice.Diagnosis must be confirmed by immunohistochemical analysis of the tissue as clinical symptoms and imaging studies are unreliable.CASE SUMMARY A 14-year-old female presented with amenorrhea.After a thorough medical examination,endocrine and tumor markers analysis,and imaging,a pelvic mass was discovered.The patient also exhibited endocrine dysfunction but was not positive for any tumor markers.The patient underwent surgery to remove the ovarian tumor.Immunohistochemical analysis of the resected specimen indicated an OSST.During the postoperative follow-up,the patient had attained menarche.CONCLUSION This case’s clinical manifestation of endocrine dysfunction due to OSST provides new insights that will assist clinicians in the diagnosis and treatment of this common tumor.展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Background: The use of assisted reproductive technique (ART) is becoming more common in infertility. During ART most patients undergo ovarian stimulation. In this study we study the correlation between ovarian reserve...Background: The use of assisted reproductive technique (ART) is becoming more common in infertility. During ART most patients undergo ovarian stimulation. In this study we study the correlation between ovarian reserve markers: Anti-Mullerian hormone (AMH) and antral follicle count (AFC), and the response to ovarian stimulation at in vitro fertilization (IVF) centres in Douala Cameroon. Methods: This was a hospital based cross-sectional sectional analytic study carried out over a period of 3 years, 4 months at Clinique de l’Aéroport, Clinique Odyssée and Clinique Urogyn. Inclusion criteria were: Female partners of infertile couples undergoing ovarian stimulation for an in vitro fertilization cycle, patients who had both ovaries and had done either AMH, AFC or both before ovarian stimulation. Patients were divided into three groups based on the number of oocytes retrieved: low ovarian response for ≤3 oocytes, normal ovarian response for 4 - 15 oocytes and high ovarian response for >15 oocytes. Data obtained was analyzed by SPSS version 25.0. Results: The ages of participants ranged from 20 - 4 7 years, with a mean age of 34.11 ± 5.11 years. Most of them had secondary infertility (57.9%). The GnRH antagonist protocol was mainly used, and ovulation was triggered using HCG predominantly. On Multivariate analysis, age and history of PCOS were significantly associated with ovarian response in the low and high ovarian response groups, respectively. Conclusion: AMH has a better predictive value than AFC, however, it is less sensitive but more specific than AFC.展开更多
Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian resto...Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.展开更多
BACKGROUND Ovarian carcinoma has the highest mortality rate among all gynecological cancers.Several reproductive and hormonal risk factors,including early menarche,late menopause,limited use of oral contraceptives,and...BACKGROUND Ovarian carcinoma has the highest mortality rate among all gynecological cancers.Several reproductive and hormonal risk factors,including early menarche,late menopause,limited use of oral contraceptives,and a low pregnancy rate,have been identified as contributors to the increased susceptibility to ovarian cancer.Advancements in cancer therapy over the past century,including the emergence of precision oncology,underscore the importance of early detection and tailored interventions,factors particularly critical in ovarian cancer,where late-stage diagnosis remains a persistent barrier to survival.This challenge is compounded by the lack of a universally endorsed screening program,resulting in late-stage identification and widespread metastasis.AIM To evaluate demographic differences in ovarian cancer-related mortality from 1999 to 2020 among adult females aged≥25 years within the United States.METHODS Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was used to collect de-identified death certificate data for malignant neoplasm of the ovaries related deaths in female adults aged 25 years and older from the year 1999 to 2020.Crude mortality rates and age-adjusted mortality rates(AAMRs)per 100000 people were calculated.Join point regression program was used to assess annual percent changes in mortality trends,with statistical significance set at P value<0.05.RESULTS Between 1999 and 2020,337619 deaths due to ovarian cancer occurred among United States females aged 25 to>85.The AAMR decreased from 14.62 in 1999 to 10.15 in 2020,with significant declines across various demographics.The AAMRs were highest among non-Hispanic White women,i.e.,13.53.Based on region,they were the highest in the Northeast(13.06)and Midwest(12.94).The steepest decline was observed in metropolitan areas as compared to nonmetropolitan ones.The study highlights significant progress in reducing ovarian cancer mortality across age,race/ethnicity,and geographic regions during this period.CONCLUSION The mortality trends for ovarian carcinoma patients showed an overall decrease,with the highest mortality rates observed among older individuals(65 to>85 years)and non-Hispanic Whites.These disparities underscore the need for equitable healthcare access and targeted policy interventions.展开更多
PURPOSE:To investigate the differences in gut microbial characteristics between two traditional Chinese syndromes of premature ovarian insufficiency(POI).METHODS:Forty women with POI were recruited from the Department...PURPOSE:To investigate the differences in gut microbial characteristics between two traditional Chinese syndromes of premature ovarian insufficiency(POI).METHODS:Forty women with POI were recruited from the Department of Traditional Chinese Medicine at Shenzhen Maternity and Child Healthcare Hospital between June and December 2020.Women with POI were divided into the kidney deficiency and blood stasis syndrome(SDBS)and Qi and blood deficiency syndrome(QBDS)groups.Gut microbial community profiles were analyzed by 16S rRNA gene sequencing using an Illumina Mi Seq system.A retrospective study comparing hormone levels and gut microbiota information was performed between the SDBS and QBDS groups.RESULTS:Compared with the QBDS group,the serum levels of estradiol(E2)and anti-Müllerian hormone(AMH)were significantly decreased in the SDBS group.The quantities of Adlercreutzia,Eggerthella,Klebsiella,and Paraprevotella significantly increased in the SDBS group,whereas Lactobacillus decreased significantly.Moreover,alterations in the microbiome in the SDBS and QBDS groups were closely related to the levels of E2 and AMH.The area under the receiver operating characteristic curve for the classification of the two syndromes by the gut microbiome was 0.71.CONCLUSIONS:There were significant differences in the dominant microbiota between the SDBS and QBDS groups,and the change in Proteobacteria in the QBDS group was more significant.The characteristics of gut microbiota help us differentiate between the SDBS and QBDS groups,which may provide a basis for the objectification of TCM syndrome types.展开更多
Objectives:Monitoring of Cancer Antigen 125(CA125)during ovarian cancer(OC)maintenance treatment with poly(ADP-ribose)polymerase inhibitors(PARPis)may be insufficient when using Gynecologic Cancer Intergroup(GCIG)bioc...Objectives:Monitoring of Cancer Antigen 125(CA125)during ovarian cancer(OC)maintenance treatment with poly(ADP-ribose)polymerase inhibitors(PARPis)may be insufficient when using Gynecologic Cancer Intergroup(GCIG)biochemical progression criteria.This study aimed to evaluate the usefulness of CA125 monitoring in detecting OC recurrence during PARPis maintenance treatment.Methods:This multicenter retrospective cohort study included patients with primary OC who achieved complete or partial response after first-line platinum-based chemotherapy followed by PARPis maintenance treatment.Progressionwas defined using Response EvaluationCriteria in Solid Tumors(RECIST)and GCIG biochemical criteria.New biochemical progression definitions,based on CA125 nadir determined using receiver operating characteristic(ROC)curve analysis,were proposed.Concordance between radiological and biochemical progression was assessed.Results:Of 142 patients,progression was detected in 54(38.03%)and 29(20.42%)using RECIST and GCIG criteria,respectively.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of the GCIG criteria were 53.70%[95%confidence interval(CI):39.61%–67.38%],100.00%[95%CI:95.91%–100.00%],100.00%[95%CI:88.10%–100.00%]and 77.88%[95%CI:72.54%–82.43%],respectively.A cut-off of 1.59×nadir achieved 88.90%sensitivity and 87.20%specificity[Area Under Curve(AUC):91.10%,95%CI:84.70%–97.40%]with a false positive rate(FPR)of 12.67%.Defining biochemical progression as an increase in CA125 of≥3×nadir achieved sensitivity,specificity,PPV,NPV,and FPR of 79.63%[95%CI:66.47%–89.37%],98.86%[95%CI:93.83%–99.97%],97.73%[95%CI:85.91%–99.67%],88.78%[95%CI:82.35%–93.06%],and 1.14%,respectively.Diagnostic accuracy was higher using the≥3×nadir criterion compared with GCIG definition(91.55%vs.82.39%).Conclusion:GCIG biochemical progression criteria during PARPis maintenance treatment after first-line chemotherapymissed 46.3%of progressing patients.Anewcriterion—CA125≥3×nadir—improves sensitivity and NPV,while maintaining high specificity,offering a simple and practical approach for clinical implementation.展开更多
BACKGROUND Ovarian hyperstimulation syndrome(OHSS)is a life-threatening complication that can occur in the luteal phase or early pregnancy after controlled ovarian stimulation.This case report highlights a unique mani...BACKGROUND Ovarian hyperstimulation syndrome(OHSS)is a life-threatening complication that can occur in the luteal phase or early pregnancy after controlled ovarian stimulation.This case report highlights a unique manifestation of OHSS involving pleural effusion(PE)in a patient without identifiable risk factors.CASE SUMMARY A 39-year-old woman who underwent controlled ovarian hyperstimulation for an in vitro fertilization(IVF)cycle experienced dyspnea on the eleventh day of post oocyte retrieval.The diagnosis was severe OHSS with a unique manifestation of PE without ascites.Clinical management involved fluid balance and treatment with albumin,furosemide,thromboembolic prophylaxis,and thoracentesis.A continued drainage of the pleural cavity was performed.The patient had a favo-rable outcome,and a dichorionic diamniotic gestation passed without incident.CONCLUSION OHSS and its potential complications can include respiratory distress and PE,as well as thromboembolic disorders.展开更多
BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnose...BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.展开更多
Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have diffe...Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have different degrees of adverse reactions, which will cause damage to the patient’s body once they occur. This paper retrospectively analyzed the clinical data of patients with severe allergic reactions such as fecal incontinence and numbness of hands and feet caused by the use of paclitaxel liposome during postoperative chemotherapy in a case of ovarian cancer admitted to our hospital. The causes and corresponding treatment measures were analyzed, in order to provide the reference for medical staff to take effective countermeasures in advance in the future.展开更多
c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal tr...c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal transduction pathway, which is closely related to the occurrence and development of gynecological tumors, especially ovarian cancer. This article reviews the mechanisms of platinum resistance in ovarian cancer and the research progress of c-Kit in ovarian cancer.展开更多
BACKGROUND Ovarian vein thrombosis(OVT)is a rare condition that most commonly affects postpartum women.It is particularly prevalent in the first 10 days postpartum,a period when women are more prone to developing this...BACKGROUND Ovarian vein thrombosis(OVT)is a rare condition that most commonly affects postpartum women.It is particularly prevalent in the first 10 days postpartum,a period when women are more prone to developing this condition.The right ovarian vein is often affected due to its tortuous nature and less competent valves.OVT presents similarly to acute abdominal conditions,such as acute appendicitis,especially when the right ovarian vein is involved.Given the overlap in clinical presentation,diagnosis requires high-quality imaging techniques and a high degree of suspicion.CASE SUMMARY Herein,we report a rare case of OVT in a young postpartum female who presented to the emergency department with signs and symptoms of acute abdomen.The patient had a history of pulmonary tuberculosis treatment.A provisional diagnosis of a perforated appendix was made,and a lower midline exploratory laparotomy was planned.During surgery,the appendix and inte-stines appeared normal,but a distended and thrombosed right ovarian vein was found.The affected ovarian vein was excised,and the patient was placed on anti-coagulants postoperatively.The recovery was unremarkable,and anticoagulants were continued for six months.CONCLUSION OVT is most commonly seen in the early postpartum period,especially within the first 10 days.Due to its anatomical characteristics,the right ovarian vein is more commonly involved.The clinical presentation of OVT can closely mimic acute abdomen or acute appendicitis,making diagnosis challenging.Accurate diagnosis requires a high index of suspicion and advanced imaging techniques to differentiate OVT from other conditions with similar presentations.展开更多
Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subuni...Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.展开更多
Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this stu...Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this study,Cell Counting Kit 8(CCK8)assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D.Migration and invasion experiments confirmed its inhibitory effects on OVHM cells,while flow cytometry analysis demonstrated Emd-D-induced apoptosis.Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4.This was corroborated by alterations in intracellular lactate and pyruvate levels,as well as glucose transporter 1(GLUT1)and hexokinase 2(HK2)expression.PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis.In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment,accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors.In conclusion,our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis.These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.展开更多
Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple o...Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.展开更多
基金supported by the Academic Leader Training Programof Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13)Shanghai Municipal Health Commission(Grant No.202340094).
文摘Objectives:Ribosomal protein S6 kinase A2(RPS6KA2)has been identified as a potential prognostic biomarker in several cancers,including breast cancer,glioblastoma,and prostate cancer.However,its functional significance in ovarian cancer is not well characterized.This study was designed to explore the therapeutic relevance of modulating RPS6KA2 in the context of ovarian cancer,particularly in relation to cisplatin resistance.Methods:The expression levels of RPS6KA2 and key regulators involved in autophagy and ferroptosis were assessed using quantitative reverse transcription-PCR,immunofluorescence staining,immunohistochemistry,and western blotting.Prognostic associations were conducted using the Kaplan-Meier Plotter database.Autophagy flux assays and visualization of autophagosomes were performed to assess autophagy activity.Ferroptosis-related parameters,including intracellular iron content,glutathione(GSH)levels,reactive oxygen species(ROS)generation,and mitochondrial membrane potential,were measured to determine ferroptotic changes.In vivo experiments were carried out to determine the antitumor efficacy of RPS6KA2 modulation in combination with pathway-specific agents.Results:Using ovarian cancer cell lines and clinical tissue samples,we demonstrated that RPS6KA2 expression was significantly downregulated in cisplatin-resistant cells and tissues compared to their sensitive counterparts.Low RPS6KA2 expression correlated with unfavorable patient outcomes and enhanced chemoresistance.Mechanistically,RPS6KA2 inhibited autophagy by modulating the phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin(PI3K-AKT-mTOR)signaling pathway,which in turn increased sensitivity to cisplatin.Additionally,RPS6KA2 facilitated ferroptosis,contributing to its tumor-suppressive function.miR-512-3p was identified as a negative regulator of RPS6KA2,driving cisplatin resistance through suppression of RPS6KA2 expression.In vivo validation confirmed that combining RPS6KA2 targeting with autophagy inhibitors or ferroptosis inducers significantly enhanced cisplatin sensitivity in ovarian cancer models.Conclusion:These results collectively indicate that targeting the miR-512-3p/RPS6KA2 regulatory axis may offer a novel and effective strategy for overcoming cisplatin resistance in ovarian cancer.
文摘The published article titled“Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.595–603.
文摘Objectives:High-grade serous ovarian cancer(HGSOC),the most common subtype of epithelial ovarian cancer(EOC),exhibits a mesenchymal phenotype characterized by fibrotic stroma and poor prognosis.Human epididymis protein 4(HE4),a key diagnostic biomarker for ovarian cancer,is involved in fibrotic processes in several non-malignant diseases.Given the clinical significance of stromal fibrosis in HGSOC and the potential link between HE4 and fibrosis,this study aimed to investigate the role of HE4 in the formation of stromal fibrosis in HGSOC.Methods:A total of 126 patients with gynecological conditions were included and divided into normal,benign,and EOC groups.Tissue stiffness was quantitatively measured and analyzed for its correlation with clinicopathological features.We further investigated the correlation between tumor stiffness and the expression levels of HE4 and fibroblast activation markers(α-smooth muscle actin(α-SMA)and fibroblast activation protein(FAP))in tumor tissues from 22 HGSOC patients.In vitro,primary fibroblasts were treated with recombinant HE4(rHE4)or conditioned media from HE4-knockdown ovarian cancer cells to assess fibroblasts activation and matrix contractility(Collagen gel contraction assays).In vivo,a subcutaneous xenograft model using HE4-knockdown cells was established to evaluate the effects of HE4 suppression on tumor growth and extensive extracellular matrix(ECM)remodeling.Results:Ovarian cancer tissues showed significantly increased stiffness compared to benign/normal groups,showing positive correlation with serum HE4 levels.High-stiffness HGSOC tumors exhibited upregulated expression of HE4,α-SMA,FAP,and collagen I.rHE4 stimulated fibroblast activation and enhanced matrix contractility,whereas HE4 knockdown in cancer cells abrogated these pro-fibrotic effects.In vivo,HE4-silenced xenografts displayed restricted tumor growth accompanied by reduced stromal expression ofα-SMA,FAP,and collagen I.Conclusion:Our findings suggest that HE4 may facilitate ECM remodeling in HGSOC through promoting fibroblast activation and increasing collagen deposition.
基金supported by the National Key Research&Developmental Program of China(2022YFC2703800,2022YFC2703000)the National Natural Science Foundation of China(82125014,82371646,32070847)+1 种基金Basic Science Center Program of NSFC(31988101)the Natural Science Foundation of Shandong Province(ZR202105250005,ZR2022YQ69,tsqn202211371).
文摘Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.
文摘BACKGROUND Ovarian sclerosing stromal tumors(OSSTs)are found most commonly in females at 20-30 years of age.They can also occur at any point during pre-puberty,puberty,or menopause.Clinical manifestations of OSSTs include abdominal pain,an abdominal mass,menstrual abnormalities,and infertility.Infrequently,patients will experience androgen-related manifestations of masculinization,such as increased hair,acne,or a low voice.Diagnosis must be confirmed by immunohistochemical analysis of the tissue as clinical symptoms and imaging studies are unreliable.CASE SUMMARY A 14-year-old female presented with amenorrhea.After a thorough medical examination,endocrine and tumor markers analysis,and imaging,a pelvic mass was discovered.The patient also exhibited endocrine dysfunction but was not positive for any tumor markers.The patient underwent surgery to remove the ovarian tumor.Immunohistochemical analysis of the resected specimen indicated an OSST.During the postoperative follow-up,the patient had attained menarche.CONCLUSION This case’s clinical manifestation of endocrine dysfunction due to OSST provides new insights that will assist clinicians in the diagnosis and treatment of this common tumor.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
文摘Background: The use of assisted reproductive technique (ART) is becoming more common in infertility. During ART most patients undergo ovarian stimulation. In this study we study the correlation between ovarian reserve markers: Anti-Mullerian hormone (AMH) and antral follicle count (AFC), and the response to ovarian stimulation at in vitro fertilization (IVF) centres in Douala Cameroon. Methods: This was a hospital based cross-sectional sectional analytic study carried out over a period of 3 years, 4 months at Clinique de l’Aéroport, Clinique Odyssée and Clinique Urogyn. Inclusion criteria were: Female partners of infertile couples undergoing ovarian stimulation for an in vitro fertilization cycle, patients who had both ovaries and had done either AMH, AFC or both before ovarian stimulation. Patients were divided into three groups based on the number of oocytes retrieved: low ovarian response for ≤3 oocytes, normal ovarian response for 4 - 15 oocytes and high ovarian response for >15 oocytes. Data obtained was analyzed by SPSS version 25.0. Results: The ages of participants ranged from 20 - 4 7 years, with a mean age of 34.11 ± 5.11 years. Most of them had secondary infertility (57.9%). The GnRH antagonist protocol was mainly used, and ovulation was triggered using HCG predominantly. On Multivariate analysis, age and history of PCOS were significantly associated with ovarian response in the low and high ovarian response groups, respectively. Conclusion: AMH has a better predictive value than AFC, however, it is less sensitive but more specific than AFC.
基金supported by the National Natural Science Foundation of China(82271671)Nanjing Drum Tower Hospital Academic Innovation Peak Fund(2024-DF-02)+4 种基金Clinical Trials from Nanjing Drum Tower Hospital(2023-LCYJ-MS-05)Nanjing International Science and Technology Cooperation Program(202201027)to L.D.Research Project of State Key Laboratory of Reproductive Medicine and Offspring Health(SKLRM-2022D2)Changzhou Medical Center of Nanjing Medical University(CMCM202203)Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-02)to H.S.
文摘Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.
文摘BACKGROUND Ovarian carcinoma has the highest mortality rate among all gynecological cancers.Several reproductive and hormonal risk factors,including early menarche,late menopause,limited use of oral contraceptives,and a low pregnancy rate,have been identified as contributors to the increased susceptibility to ovarian cancer.Advancements in cancer therapy over the past century,including the emergence of precision oncology,underscore the importance of early detection and tailored interventions,factors particularly critical in ovarian cancer,where late-stage diagnosis remains a persistent barrier to survival.This challenge is compounded by the lack of a universally endorsed screening program,resulting in late-stage identification and widespread metastasis.AIM To evaluate demographic differences in ovarian cancer-related mortality from 1999 to 2020 among adult females aged≥25 years within the United States.METHODS Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database was used to collect de-identified death certificate data for malignant neoplasm of the ovaries related deaths in female adults aged 25 years and older from the year 1999 to 2020.Crude mortality rates and age-adjusted mortality rates(AAMRs)per 100000 people were calculated.Join point regression program was used to assess annual percent changes in mortality trends,with statistical significance set at P value<0.05.RESULTS Between 1999 and 2020,337619 deaths due to ovarian cancer occurred among United States females aged 25 to>85.The AAMR decreased from 14.62 in 1999 to 10.15 in 2020,with significant declines across various demographics.The AAMRs were highest among non-Hispanic White women,i.e.,13.53.Based on region,they were the highest in the Northeast(13.06)and Midwest(12.94).The steepest decline was observed in metropolitan areas as compared to nonmetropolitan ones.The study highlights significant progress in reducing ovarian cancer mortality across age,race/ethnicity,and geographic regions during this period.CONCLUSION The mortality trends for ovarian carcinoma patients showed an overall decrease,with the highest mortality rates observed among older individuals(65 to>85 years)and non-Hispanic Whites.These disparities underscore the need for equitable healthcare access and targeted policy interventions.
基金Sanming Project of Medicine in Shenzhen:the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Luo Songping National Famous Chinese Medicine Practitioner Female Reproductive Disorders Prevention and Treatment Team(SZZYSM202311010)Guangdong Provincial Administration of Traditional Chinese Medicine:Investigation of the Mechanism of Regulating Ren-Tong-Du Acupuncture on Ovarian Granulosa Cells in Polycystic Ovary Syndrome based on Activin A/Smads Signalling Pathway(No.20181229)+1 种基金Guangdong Provincial Administration of Traditional Chinese Medicine:Evaluation of the Efficacy of Menstrual Regulation and Pregnancy Promotion by Acupuncture in the Treatment of Premature Ovarian Insufficiency(No.20201294)Shenzhen Science and Innovation Commission:Investigating the Mechanism of Action of Acupuncture in Regulating the Gut Microbiome to Inhibit Apoptosis of Ovarian Granulosa Cells in Premature Ovarian Insufficiency Mice based on the Rictor/Torepamycin Target Protein C2 Pathway(No.JCYJ20210324130001004)。
文摘PURPOSE:To investigate the differences in gut microbial characteristics between two traditional Chinese syndromes of premature ovarian insufficiency(POI).METHODS:Forty women with POI were recruited from the Department of Traditional Chinese Medicine at Shenzhen Maternity and Child Healthcare Hospital between June and December 2020.Women with POI were divided into the kidney deficiency and blood stasis syndrome(SDBS)and Qi and blood deficiency syndrome(QBDS)groups.Gut microbial community profiles were analyzed by 16S rRNA gene sequencing using an Illumina Mi Seq system.A retrospective study comparing hormone levels and gut microbiota information was performed between the SDBS and QBDS groups.RESULTS:Compared with the QBDS group,the serum levels of estradiol(E2)and anti-Müllerian hormone(AMH)were significantly decreased in the SDBS group.The quantities of Adlercreutzia,Eggerthella,Klebsiella,and Paraprevotella significantly increased in the SDBS group,whereas Lactobacillus decreased significantly.Moreover,alterations in the microbiome in the SDBS and QBDS groups were closely related to the levels of E2 and AMH.The area under the receiver operating characteristic curve for the classification of the two syndromes by the gut microbiome was 0.71.CONCLUSIONS:There were significant differences in the dominant microbiota between the SDBS and QBDS groups,and the change in Proteobacteria in the QBDS group was more significant.The characteristics of gut microbiota help us differentiate between the SDBS and QBDS groups,which may provide a basis for the objectification of TCM syndrome types.
文摘Objectives:Monitoring of Cancer Antigen 125(CA125)during ovarian cancer(OC)maintenance treatment with poly(ADP-ribose)polymerase inhibitors(PARPis)may be insufficient when using Gynecologic Cancer Intergroup(GCIG)biochemical progression criteria.This study aimed to evaluate the usefulness of CA125 monitoring in detecting OC recurrence during PARPis maintenance treatment.Methods:This multicenter retrospective cohort study included patients with primary OC who achieved complete or partial response after first-line platinum-based chemotherapy followed by PARPis maintenance treatment.Progressionwas defined using Response EvaluationCriteria in Solid Tumors(RECIST)and GCIG biochemical criteria.New biochemical progression definitions,based on CA125 nadir determined using receiver operating characteristic(ROC)curve analysis,were proposed.Concordance between radiological and biochemical progression was assessed.Results:Of 142 patients,progression was detected in 54(38.03%)and 29(20.42%)using RECIST and GCIG criteria,respectively.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of the GCIG criteria were 53.70%[95%confidence interval(CI):39.61%–67.38%],100.00%[95%CI:95.91%–100.00%],100.00%[95%CI:88.10%–100.00%]and 77.88%[95%CI:72.54%–82.43%],respectively.A cut-off of 1.59×nadir achieved 88.90%sensitivity and 87.20%specificity[Area Under Curve(AUC):91.10%,95%CI:84.70%–97.40%]with a false positive rate(FPR)of 12.67%.Defining biochemical progression as an increase in CA125 of≥3×nadir achieved sensitivity,specificity,PPV,NPV,and FPR of 79.63%[95%CI:66.47%–89.37%],98.86%[95%CI:93.83%–99.97%],97.73%[95%CI:85.91%–99.67%],88.78%[95%CI:82.35%–93.06%],and 1.14%,respectively.Diagnostic accuracy was higher using the≥3×nadir criterion compared with GCIG definition(91.55%vs.82.39%).Conclusion:GCIG biochemical progression criteria during PARPis maintenance treatment after first-line chemotherapymissed 46.3%of progressing patients.Anewcriterion—CA125≥3×nadir—improves sensitivity and NPV,while maintaining high specificity,offering a simple and practical approach for clinical implementation.
文摘BACKGROUND Ovarian hyperstimulation syndrome(OHSS)is a life-threatening complication that can occur in the luteal phase or early pregnancy after controlled ovarian stimulation.This case report highlights a unique manifestation of OHSS involving pleural effusion(PE)in a patient without identifiable risk factors.CASE SUMMARY A 39-year-old woman who underwent controlled ovarian hyperstimulation for an in vitro fertilization(IVF)cycle experienced dyspnea on the eleventh day of post oocyte retrieval.The diagnosis was severe OHSS with a unique manifestation of PE without ascites.Clinical management involved fluid balance and treatment with albumin,furosemide,thromboembolic prophylaxis,and thoracentesis.A continued drainage of the pleural cavity was performed.The patient had a favo-rable outcome,and a dichorionic diamniotic gestation passed without incident.CONCLUSION OHSS and its potential complications can include respiratory distress and PE,as well as thromboembolic disorders.
基金Supported by National Key Technology Research and Developmental Program of China,No.2022YFC2704400 and No.2022YFC2704405.
文摘BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
文摘Paclitaxel is one of the commonly used drugs in postoperative chemotherapy for ovarian cancer patients. However, affected by drug dosage and individual differences in the course of medication, patients will have different degrees of adverse reactions, which will cause damage to the patient’s body once they occur. This paper retrospectively analyzed the clinical data of patients with severe allergic reactions such as fecal incontinence and numbness of hands and feet caused by the use of paclitaxel liposome during postoperative chemotherapy in a case of ovarian cancer admitted to our hospital. The causes and corresponding treatment measures were analyzed, in order to provide the reference for medical staff to take effective countermeasures in advance in the future.
文摘c-Kit (CD117) is a type IIIa receptor tyrosine kinase (RTK) that plays a key role in regulating the normal physiological processes of cells. In addition, the activation of c-Kit activates the tyrosine kinase signal transduction pathway, which is closely related to the occurrence and development of gynecological tumors, especially ovarian cancer. This article reviews the mechanisms of platinum resistance in ovarian cancer and the research progress of c-Kit in ovarian cancer.
文摘BACKGROUND Ovarian vein thrombosis(OVT)is a rare condition that most commonly affects postpartum women.It is particularly prevalent in the first 10 days postpartum,a period when women are more prone to developing this condition.The right ovarian vein is often affected due to its tortuous nature and less competent valves.OVT presents similarly to acute abdominal conditions,such as acute appendicitis,especially when the right ovarian vein is involved.Given the overlap in clinical presentation,diagnosis requires high-quality imaging techniques and a high degree of suspicion.CASE SUMMARY Herein,we report a rare case of OVT in a young postpartum female who presented to the emergency department with signs and symptoms of acute abdomen.The patient had a history of pulmonary tuberculosis treatment.A provisional diagnosis of a perforated appendix was made,and a lower midline exploratory laparotomy was planned.During surgery,the appendix and inte-stines appeared normal,but a distended and thrombosed right ovarian vein was found.The affected ovarian vein was excised,and the patient was placed on anti-coagulants postoperatively.The recovery was unremarkable,and anticoagulants were continued for six months.CONCLUSION OVT is most commonly seen in the early postpartum period,especially within the first 10 days.Due to its anatomical characteristics,the right ovarian vein is more commonly involved.The clinical presentation of OVT can closely mimic acute abdomen or acute appendicitis,making diagnosis challenging.Accurate diagnosis requires a high index of suspicion and advanced imaging techniques to differentiate OVT from other conditions with similar presentations.
基金supported by the National Natural Science Foundation,China(32230108 to Z.Y.)National Key Research and Development Program,China(2022YFF1000300 to Z.Y.and 2022YFD2401800 to G.Z.)Foundation of Hubei Hongshan Laboratory(2021hszd021 to Z.Y.and 2021hskf013 to G.Z.)。
文摘Chorionic gonadotropinα(Cgα)functions as the shared subunit for thyroid-stimulating hormone subunitβ(Tshβ),luteinizing hormone subunitβ(Lhβ),and follicle-stimulating hormone subunitβ(Fshβ).While theseβ-subunits have been extensively studied using effective gene knockout models in zebrafish,the biological role of Cgαremains elusive.In this study,cgα-deficient zebrafish generated via transcription activator-like effector nucleases(TALENs)exhibited viability but displayed pronounced developmental abnormalities,including growth retardation,hyperpigmentation,reduced thyroxine(T4)levels,and defective anterior swim bladder inflation during juvenile stages.In adults,cgαdeficiency led to disrupted gonadal development,impaired secondary sex characteristics(SSCs),and severely impacted reproductive behavior in both female and male fish.Notably,both testicular and ovarian differentiation were observed in cgα-deficient fish and lhβ^(−/−);fshβ^(−/−)mutants.Gonadal sex differentiation in cgα-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fshβ(cgα^(−/−);fshβ^(−/−)),marked by elevated anti-Müllerian hormone(amh)expression,or following loss of follicle-stimulating hormone receptor(fshr)(cgα^(−/−);fshr^(−/−)).In vitro assays in Chinese hamster ovary(CHO)cells revealed increased cAMP response element(CRE)promoter activity following transfection with constructs encoding Fshr,Fshβ/Fshr,or Cgα/Fshβ/Fshr.Collectively,the phenotypes observed in cgα-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models,highlighting the essential role of Cgαin thyroid and gonadal function.Importantly,these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish,including Cgα-independent Fshβactivity and the constitutive functionality of Fshr.
基金funded by the Natural Science Foundation of Heilongjiang Province(No.LH2023H012)Postdoctoral Research Initiation Fund(No.LBH-Q20152)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-078)。
文摘Ovarian cancer poses a significant threat to women's health,necessitating effective therapeutic strategies.Emd-D,an emodin derivative,demonstrates enhanced pharmaceutical properties and bioavailability.In this study,Cell Counting Kit 8(CCK8)assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D.Migration and invasion experiments confirmed its inhibitory effects on OVHM cells,while flow cytometry analysis demonstrated Emd-D-induced apoptosis.Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4.This was corroborated by alterations in intracellular lactate and pyruvate levels,as well as glucose transporter 1(GLUT1)and hexokinase 2(HK2)expression.PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis.In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment,accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors.In conclusion,our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis.These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
基金National Natural Science Foundation of China(31930103)National Center of Technology Innovation for Pigs(NCTIP-XD/B03)+2 种基金Ningbo Major Science and Technology Project(2021Z112)National Key R&D Program(2022YFD1300303)Beijing Innovation Consortium of Livestock Research System BAIC05-2024.
文摘Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.
