Oncological and Reproductive Outcomes of Fertility-sparing Surgery in Women with Early-stage Epithelial Ovarian Carcinoma:A Multicenter Retrospective Study

Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life.In order to evaluate oncological safety,attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS,this multicenter retrospective study was conducted.Between January 2005 and December 2014,total of 87 young women with FIGO stage I EOC were included,with their clinicopathologic parameters in relation to disease-free survival(DFS)and overall survival(OS)assessed.Attitudes toward childbearing,ovarian function and fertility were studied in women undergoing FSS(n=36).As a result,in contrast to radical sur ery,FSS did not affect prognosis by Kaplan-Meier curves(log-rank test;DFS:P=0.484;OS:P=0.125).However,two of the three recurrence cases and both death cases were in FSS group stage IC.All women undergoing FSS resumed regular menstrual periods after chemotherapy.Only 16(44.44%)had tried to conceive,and 17 pregnancies occurred in 15(93.75%)women.Among 20 women who did not attempt conception,the most common reason was not being married(70%),followed by already having children(15%).In summary,FSS is considered safe in young women with stage IA EOC.Regular menstruation and good obstetric outcomes can be achieved.This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.

The Impact of Seasonal Variation on Clinical Pregnancy and Live Birth Rates in Assisted Reproductive Technology: A Retrospective Cohort Study in Hainan

Objective:To investigate the influence of season on live birth and clinical pregnancy rates,as well as assisted reproductive technology(ART)outcomes,in the Hainan region.Methods:Patients were categorized into four groups based on the dates of artificial insemination and transplantation:spring,summer,autumn,or winter.The main outcome measures were clinical pregnancy rates and live birth rates.Secondary outcomes included body mass index(BMI),oocyte number,two pronuclei(2PN)cleavage rate,total gonadotropin(Gn)dosage and days,age,2PN fertilization rate,sperm concentration,sperm PR rate,anti-Müllerian hormone(AMH),and endometrial thickness.Outpatient semen quality indicators included sperm PR rate,total sperm count,sperm concentration,and total sperm motility.Results:This retrospective cohort study analyzed 2,016 artificial insemination cycles and 1,783 ovarian retrieval cycles from January 2017 to October 2022,and assessed the semen quality of 6,651 outpatients from May 2017 to October 2022.In artificial insemination cycles,sperm PR rate and clinical pregnancy rate were highest in winter,with a statistically significant difference between groups(P<0.05).Clinical pregnancy rate was influenced by both age and sperm PR rate(P<0.05).In ovarian retrieval cycles,the winter group had significantly higher clinical pregnancy,2PN fertilization,and 2PN cleavage rates than the other groups.The autumn group had higher live birth rates,though not significantly different.Additionally,winter months showed higher total sperm concentration and total sperm number compared to other seasons.Conclusion:Seasonality affected clinical pregnancy and live birth rates in artificial insemination cycles but not in ovarian retrieval cycles in the Hainan region.These findings suggest that while there is no need to choose a specific season for ovarian retrieval cycles,artificial insemination in winter may be preferable for patients.

Reproductive Outcomes in Women with Prior Cesarean Section Undergoing In Vitro Fertilization:A Retrospective Case-control Study

The impact of prior cesarean section（CS） on the pregnancy and neonatal outcomes of in vitro fertilization and embryo transfer（IVF-ET） was investigated. A retrospective analysis was performed on 144 patients with prior CS between January 2013 and December 2015. The pregnancy, delivery, and neonatal outcomes of patients who had previous CS delivery and received IVF-ET were analyzed. The control group comprised 166 patients who had only previous vaginal delivery（VD） and received IVF-ET during the same period. The results showed that the basal follicle stimulating hormone level, estradiol level on human chorionic gonadotropin（h CG） day, gonadotrophin dosage, duration of stimulation, retrieved oocytes, fertilization rate, high-quality embryo rate, multiple birth rate, abortion rate and ectopic pregnancy rate had no significant difference between the two groups（P〉0.05）. The pregnancy rate（40.28% vs. 54.22%） and implantation rate（24.01% vs. 34.67%） were significantly lower（P〈0.05）, and the ratio of embryo difficulty transfer（9/144 vs. 0/166） was significantly higher in CS group than in VD group. The risk of pernicious placenta previa and postpartum hemorrhage in twin deliveries was significantly increased in CS group as compared with that in VD group（P〈0.05）, and gestational age and neonatal birth weight were significantly reduced in twin deliveries as compared with singleton deliveries in both groups（P〈0.05）. It was suggested that the existence of CS scar may impact embryo implantation and clinical pregnancy outcome, and increase the difficulty of ET. We should limit the number of transfer embryos to avoid multiple pregnancies and strengthen gestational supervision in patients with cesarean scar.

Influence of Acupuncture on Idiopathic Male Infertility in Assisted Reproductive Technology

The clinical effects of acupuncture on idio pathic male infertility in sperm parameter and on therapeutic results in assiste d reproductive technology were investigated. 22 patients failed in intracytoplas mic sperm injection (ICSI) with idiopathic male infertility were treated with ac upuncture twice weekly for 8 weeks, followed by ICSI treatment again. The sperm concentration, motility, morphology, fertilization rates and embryo quality were observed. Quick sperm motility after acupuncture(18.3 %±9.6 %) was significa ntly improved as compared with that before treatment (11.0 %±7.5 %, P <0.01) . The normal sperm ratio was increased after acupuncture (21.1 %±10.4 % vs 16.2 %± 8.2 %, P <0.05). The fertilization rates after acupuncture (66.2 %) were obviously higher than that before treatment (40.2 %, P <0.01). There was no significant difference in sperm concentration and general sperm motility between before and after acupuncture. The embryo quality after acupuncture was improved , but the difference between them was not significant ( P >0.05). Acupuncture can improve sperm quality and fertilization rates in assisted reproductive techn ology.

Melatonin and its protective role against male reproductive toxicity induced by heavy metals,environmental pollutants,and chemotherapy:A review

Melatonin,as a ubiquitous indoleamine hormone,is synthesized primarily by the pineal gland.It has diverse biological effects through quite complex mechanisms.More recently,studies have focused on the mechanism of melatonin in anti-reproductive toxicity/damage.Since melatonin possesses strong antioxidant and anti-apoptotic properties,researchers have examined its potential role in protecting against male reproductive toxicity/damage,which may be induced by chemotherapy or environmental toxicants and can lead to male infertility.In this article,recent progress regarding the protective effects of melatonin on male reproductive toxicity/damage is reviewed.

Heterotopic pregnancy after assisted reproductive techniques with favorable outcome of the intrauterine pregnancy:A case report

BACKGROUND Heterotopic pregnancy(HP)is a rare condition in which both ectopic and intrauterine pregnancies occur.HP is uncommon after natural conception but has recently received more attention due to the widespread use of assisted reproductive techniques(ART)such as ovulation promotion therapy.CASE SUMMARY Here,we describe a case of HP that occurred after ART with concurrent tubal and intrauterine singleton pregnancies.This was treated successfully with surgery to preserve the intrauterine pregnancy,resulting in the birth of a low-weight premature infant.This case report aims to increase awareness of the possibility of HP during routine first-trimester ultrasound examinations,especially in pregnancies resulting from ART and even if multiple intrauterine pregnancies are present.CONCLUSION This case alerts us to the importance of comprehensive data collection during regular consultations.It is important for us to remind ourselves of the possibility of HP in all patients presenting after ART,especially in women with an established and stable intrauterine pregnancy that complain of constant abdominal discomfort and also in women with an unusually raised human chorionic gonadotropin level compared with simplex intrauterine pregnancy.This will allow symptomatic and timeous treatment of patients with better results.

Expression of Attractin in Male Reproductive Tract of Human and Mice and Its Correlation with Male Reproduction

The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Reumin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 nor- mal human semen samples were obtained from those cases of semen analysis. Adult mice testis tis- sues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups （day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each）. The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting re- spectively. Human semen samples were centrifuged into sperm plasma （SP） and sperm extract （SE）, and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen sam- pies, Attractin protein was expressed in both SP and SE, but didn＇t exist in samples from the epidi- dymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different ex- pression profile in different mammal species.

Teaching reproductive endocrinology in Iran: Pilot assessment of hospital-based clinical modules for medical students at Tehran University of Medical Sciences

This pilot study evaluated effectiveness and acceptance of a new hospital-based reproductive endocrinology curriculum among Iranian medical students. A voluntary, anonymous questionnaire was used to compare two teaching methods as applied to junior medical students at Tehran University of Medical Sciences. Students were randomly assigned to one of two clinical teaching settings;no student experienced both modules. Coursework for the pilot (experimental) group (n = 19) utilized a teaching approach comprising lectures, genetics laboratory, pelvic ultrasound, small group sessions, and opportunities to observe advanced reproductive technologies such as in vitro fertilization, ICSI, and embryo transfer. A control group (n = 34) received reproductive endocrinology instruction by the ‘traditional curriculum’, consisting mainly of lectures. Students were sampled at baseline and again atthe conclusion of their reproductive endocrinology session. Pre- and post-test data were analyzed for both groups;post-test differences between groups were also compared. No significant differences in mean age or gender mix were identified between the two study groups. Overall, the ques- tionnaire did not identify any significant intergroup differences for any parameter investigated. Although student acceptance rate appeared similar for both educational modules, the ratio of students having a “favorable regard” for reproductive medicine declined only among students randomized to the control group (41.2% vs. 32.3%). This report offers the first data on teaching reproductive endocrinology to medical students in Iran. Both traditional and innovative approaches to teaching reproductive endocrinology were well-accepted by students, although negative post-test responses were more common among students in the control group. While periodic quality assessments for existing clinical teaching methods are necessary, introduction of alternative teaching approaches is also important. Additional studies are planned to evaluate the impact this initiative may have on results on standardized tests measuring reproductive endocrinology knowledge, as well as election of further specialization in training.

Clinical study of different fertilization methods of assisted reproductive technology on neonatal birth defects

Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases of singleton deliver by infertile patients under 35 years old who received IVF/ICSI-ET in our center were analyzed.According to different fertilization methods,they were divided into IVF group(2967 cases)and ICSI group(1262 cases).The general situation of birth,birth defects and the location of defects were compared between the two groups.Results:a total of 38 cases of neonatal birth defects were found,the incidence of birth defects was 0.89%,including 30 cases(1.01%)in IVF group and 8 cases(0.64%)in ICSI group.There was no significant difference in the incidence of birth defects between the two groups(P>0.05).There was also no significant difference in birth weight,gestational age and gender ratio between the two groups(P>0.05).Conclusion:Different fertilization methods in assisted reproductive technology do not increase the incidence of neonatal birth defects.

Effects and safety of Ding Kun Dan on IVF/ICSI-ET outcomes in patients with predicted poor ovarian response:A multicenter randomized clinical trial

Objective:To evaluate whether Ding Kun Dan(DKD)can improve the vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET)outcomes in patients with predicted poor ovarian response(POR)safely and effectively.Methods:Prospective,multicenter,randomized controlled trial;A total of 278 POR patients were randomized in DKD group or immediate treatment group.Both groups received IVF or ICSI as a standard treatment while in the DKD group,DKD was administrated for 3 months before the IVF/ICSI cycle.The primary outcome was the ongoing pregnancy rate.The secondary outcomes include clinical pregnancy rate,biochemical pregnancy rate,total gonadotropin(Gn)dosage and duration,estradiol(E2)and progesterone(P)levels on human chorionic gonadotropin(hCG)trigger day,cycle cancellation rate,number of oocytes retrieved,high-quality embryo rate and any adverse events.Results:Compared to the immediate IVF treatment group,oral administration of DKD for 3 months before IVF led to a significant increase in ongoing pregnancy rate(30.0%v.s.17.6%,P<0.05),biochemical pregnancy rate(39.2%vs.25.2%,P<0.05),clinical pregnancy rate(36.7%vs.22.7%,P<0.05)and high-quality embryo rate(40.8%vs.32.4%,P<0.05),and a significant decrease in Gn duration(P<0.05).However,no significant differences were found in total dosage of Gn,number of retrieved oocytes,cycle cancellation rate,E2 level and P level on hCG trigger days(P>0.05).No serious adverse events occurred during the intervention period in either group.Conclusion:DKD is a safe and effective intervention to improve the IVF/ICSI-ET outcomes in patients with POR.

Stem cells of the reproductive tract of women

Research in stem cells is one of the most rapidly evolving fields of investigation in medicine today. Stem cells are defined as cells that have the capacity to both generate daughter cells identical to the cell of origin (self-renewal) and to produce progeny with more restricted, specialized potential (differentiated cells). This dual ability to self-renew and differentiate offers great promise for expanding our understanding of organ systems, elucidating disease pathophysiology, and creating therapeutic approaches to difficult diseases. The goal of this review is to offer an overview of the different types of stem cells and to provide an introduction to the applications of stem cells to the field of obstetrics and gynecology.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts

BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and neurodegeneration.Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops.Likewise,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders.Currently,no treatment can effectively reverse these neurodegenerative pathologies.However,some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes.In the previous framework,Vanadium species have demonstrated a notable antidiabetic effect.Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome.The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms.This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss

Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.

Early embryonic failure caused by a novel mutation in the TUBB8 gene:A case report

BACKGROUND This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure.CASE SUMMARY Here,we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital.We also detected the whole-exon gene of the patient's spouse and parents,and conducted bioinformatics analysis to determine the pathogenesis of the gene.CONCLUSION A novel mutant of the TUBB8 gene[c.602G>T(p.C201F)]was identified,and this mutant provided new data on the genotype-phenotype relationships of related diseases.

Targeting CXCR4 and EDN1 for the treatment of recurrent miscarriage using stearic acid from traditional Chinese medicine

Background:Recurrent miscarriage(RM)affects an estimated 1-3%of couples attempting to conceive,and its molecular components stay ineffectively caught on.This study aims to explore potential therapeutic targets for RM by examining gene expression patterns and biological pathways in both mouse and human RM models.Meanwhile,explore relevant traditional Chinese medicine(TCM)components targeting potential therapeutic targets.Methods:We utilized the GSE211251 mouse and the GSE26787 human datasets,employing gene set enrichment analysis and gene metaphysics analysis to examine differentially expressed genes and enriched pathways.Single-cell RNA analysis uncovered cellular heterogeneity and arranged pharmacology-mapped potential drug-target intelligence.We employed molecular docking strategies to assess the affinity of TCM components for key proteins.Results:In the mouse model,genes such as Ly6f1 and Gpr26 were upregulated,while Stc5a and Galca exhibited downregulation.Gene set enrichment analysis identified key pathways,including the tumor necrosis factor-mediated signaling pathway.In human samples,Gene Ontology analysis highlighted processes such as apoptosis and cell adhesion.Single-cell RNA analysis revealed distinct cellular populations between normal and RM samples.Systems pharmacology identified C-X-C motif chemokine receptor 4(CXCR4)and endothelin 1(EDN1)as potential key targets,and molecular docking confirmed that stearic acid from TCM appears to regulate these proteins.Conclusion:This study presents a comprehensive analysis of the genetic and cellular underpinnings of RM,identifying CXCR4 and EDN1 as promising therapeutic targets.Stearic acid from TCM could provide targeted treatment by modulating these key proteins,paving the way for new RM treatment strategies.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Protective effects of quercetin against H2O2 induced KGN cells injury

Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.

Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.