At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients be...At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.展开更多
Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in Chi...Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014–2020were recruited in this multicenter study.Two indices(i.e.,hot night excess [HNE] and hot night duration[HND]) were used to estimate the heat intensity and duration during nighttime.Linear mixed models were used to examine the association between hot nights and semen quality parameters.Results The exposure-response relationship revealed that HNE and HND during 0–90 days before semen collection had a significantly inverse association with sperm motility.Specifically,a 1 ℃ increase in HNE was associated with decreased sperm progressive motility of 0.0090(95% confidence interval[CI]:–0.0147,–0.0033) and decreased total motility of 0.0094(95% CI:–0.0160,–0.0029).HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021(95% CI:–0.0040,–0.0003) and 0.0023(95% CI:–0.0043,–0.0002),respectively.Consistent results were observed at different temperature thresholds on hot nights.Conclusion Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.展开更多
Background:The National Chest Pain Center Program(NCPCP)is a nationwide,quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China.The benefits of chest pain ...Background:The National Chest Pain Center Program(NCPCP)is a nationwide,quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China.The benefits of chest pain center(CPC)accreditation on acute coronary syndrome have been demonstrated.However,there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection(AAD).Methods:We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China,using data from the NCPCP spanning the period from January 1,2016 to December 31,2022.The patients were divided into 2 groups:pre-accreditation and post-accreditation admissions.The outcomes examined included in-hospital mortality,misdiagnosis,and Stanford type A AAD surgery.Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes.Furthermore,we stratified the hospitals based on their geographical location(Eastern/Central/Western regions)or administrative status(provincial/non-provincial capital areas)to assess the impact of CPC accreditation on AAD patients across various regions.Results:The analysis encompassed a total of 40,848 patients diagnosed with AAD.The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis(12.1%vs.16.3%,P<0.001 and 2.9%vs.5.4%,P<0.001,respectively)as well as a notably higher rate of Stanford type A AAD surgery(61.1%vs.42.1%,P<0.001)compared with the pre-accreditation group.After adjusting for potential covariates,CPC accreditation was associated with substantially reduced risks of in-hospital mortality(adjusted OR=0.644,95%CI 0.599-0.693)and misdiagnosis(adjusted OR=0.554,95%CI 0.493-0.624),along with an increase in the proportion of patients undergoing Stanford type A AAD surgery(adjusted OR=1.973,95%CI 1.797-2.165).Following CPC accreditation,there were significant reductions in in-hospital mortality across various regions,particularly in Western regions(from 21.5%to 14.1%).Moreover,CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities(adjusted OR:0.607 vs.0.713).Conclusion:CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.展开更多
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 patien...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.展开更多
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 gro...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.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
Objective Heat wave exposure significantly impacts human health.Nevertheless,studies on the long-term effects of heat wave exposure during adolescence on adverse pregnancy outcomes(APOs)are rare.This study aimed to in...Objective Heat wave exposure significantly impacts human health.Nevertheless,studies on the long-term effects of heat wave exposure during adolescence on adverse pregnancy outcomes(APOs)are rare.This study aimed to investigate the relationship between the long-term effects of heat wave exposure during adolescence and APOs.Methods We analyzed data from 3,376 female and 3,013 male participants across 31 provinces in China.All adolescents(10–19 years old),early adolescents(10–14),and late adolescents(15–19)were chosen as exposure windows.Heat waves were defined as periods lasting 2‒4 consecutive days with the daily temperature exceeding the 75th,90th,and 92.5th percentiles.We employed multivariate logistic regression models to assess the associations between exposure to heat waves during adolescence and APOs.Results The results revealed significant associations between male exposure to heat wave events during late adolescence and spontaneous abortion(P<0.05),which was more pronounced in South China.In contrast,no statistically significant associations were detected between males’exposure to heat wave events during adolescence and their partners’preterm birth(P>0.05 for all comparisons).The exposure of females to heat waves during adolescence was not significantly associated with subsequent spontaneous abortion or preterm birth(P>0.05 for all comparisons).Conclusions This study demonstrates that spontaneous abortion in females is associated with heat wave exposure in their male partner during adolescence.展开更多
BACKGROUND Carriers of chromosomal balanced translocations are often physically healthy with no obvious developmental problems.However,potential chromosomal imbalance in their gametes can lead to implantation failure,...BACKGROUND Carriers of chromosomal balanced translocations are often physically healthy with no obvious developmental problems.However,potential chromosomal imbalance in their gametes can lead to implantation failure,miscarriage,or the birth of a child with a chromosomal abnormality.CASE SUMMARY We report six cases of chromosomal translocations involving three families,including the specific Robertson(Roche)translocation.Case 1:The karyotype of the proband was 46,XX,t(18;19)(q22;p12).Case 2:Interventional prenatal diagnosis at 18 weeks of gestation confirmed that the karyotype of the fetus was 46,XY,t(18;19)(q22;p12).Case 3:The karyotype of the proband was 46,XY,t(5;18)(p13;p11).Case 4:Interventional prenatal diagnosis at 14+6 weeks confirmed that the karyotype of the fetus was 46,XX,der(18)t(5;18)(p13;p11)pat.Case 5:The karyotype of the proband was 45,XY,der(14;22)(q10;q10).Case 6:Interventional prenatal diagnosis at 19+4 weeks confirmed that the karyotype of the fetus was 45,XX,rob(14;22)(q10;q10).CONCLUSION Carriers of chromosomal translocations have a high risk of adverse pregnancy outcomes,though they can still have normal offspring.This report on six cases of chromosomal translocations from three families could serve as a reference for future prenatal diagnosis of chromosomal translocations and decision-making on whether to continue the pregnancy.展开更多
Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated wi...Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated with immune disorders that may affect the endometrial immune micro-environment.However,the effect of STRIGs on RIF remains unknown.Methods:Training(GSE111974)and validation(GSE106602)cohorts were acquired from the Gene Expression Omnibus database.STIRGs were extracted from the Molecular Signatures Database and relevant studies.Consensus clustering analysis was used to identify RIF molecular subtypes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and immune infiltration analyses were performed between RIF subtypes.Drug-related potential therapeutic target genes were discovered.Results:Two distinct molecular subtypes were discovered in both the training and validation groups according to STIRGs.In subtype C2,there was a notable decrease in the presence of different types of immune cells,such as natural killer cells and macrophages.Furthermore,the examination of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated a decrease in numerous immune-related biological processes within subtype C2.Finally,nine hub genes(CXCR4,POU5F1,PPARG,TLR2,EGFR,CSF1,BCL2A1,BTK,and SRGN)were identified as potential therapeutic targets for RIF.Conclusion:Based on STIRGs,we identified a new molecular subtype with significantly reduced immune infiltration in RIF.Nine genes might be potential therapeutic targets for RIF.展开更多
Objective The effects of prolonged exposure to persistently elevated atmospheric pollutants,commonly termed air pollution waves,on fertility intentions remain inadequately understood.This study aims to investigate the...Objective The effects of prolonged exposure to persistently elevated atmospheric pollutants,commonly termed air pollution waves,on fertility intentions remain inadequately understood.This study aims to investigate the association between particulate matter(PM)exposure and fertility intentions.Methods In this nationwide cross-sectional study,we analyzed data from 10,747 participants(5496 females and 5251 males).PM waves were defined as periods lasting 3‒6 consecutive days during which the daily average concentrations exceeded China’s Ambient Air Quality Standards Grade II thresholds(PM2.5>75μg/m3 and PM10>150μg/m3).We employed multivariate logistic regression models to assess the association between exposure to PM waves and fertility intentions.Results Significant inverse associations were detected between exposure to PM2.5 wave events(characterized by concentrations exceeding 75μg/m3 for durations of 4‒6 days,P<0.05)and PM10 wave events(defined as concentrations exceeding 150μg/m3 for 6 consecutive days,P<0.05)and fertility intentions among females.In contrast,neither the PM2.5 wave nor the PM10 wave events demonstrated statistically significant correlations with fertility intentions in males(P>0.05 for all comparisons).The potentially susceptible subgroup was identified as females aged 20–30 years.Conclusions Our results provide the first evidence that PM2.5 and PM10 waves are associated with a reduction in female fertility intentions,offering critical insights for the development of public health policies and strategies aimed at individual protection.展开更多
Objective:To explore the association between acupuncture during controlled ovarian hyperstimulation(COH)and the live birth rate(LBR)using different propensity score methods.Methods:In this retrospective cohort study,e...Objective:To explore the association between acupuncture during controlled ovarian hyperstimulation(COH)and the live birth rate(LBR)using different propensity score methods.Methods:In this retrospective cohort study,eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups.The primary outcome was LBR,as determined by propensity score matching(PSM).LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer.The propensity score model encompassed 16 confounding variables.To validate the results,sensitivity analyses were conducted using three additional propensity score methods:propensity score adjustment,inverse probability weighting(IPW),and IPW with a"doubly robust”estimator.Results:The primary cohort encompassed 9751 patients(1830[18.76%]in the acupuncture group and7921[81.23%]in the non-acupuncture group).Following 1:1 PSM,a higher LBR was found in the acupuncture cohort(41.4%[755/1824]vs 36.4%[664/1824],with an odds ratio of 1.23[95%confidence interval,1.08-1.41]).Three additional propensity score methods produced essentially similar results.The risk of serious adverse events did not significantly differ between the two groups.Conclusion:This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH,and that acupuncture is a safe and valuable treatment option.展开更多
This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias.We retrospectively analyzed the clinical data of patients with severe hypospadi...This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias.We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between October 2012 and October 2022.In total,31 patients underwent the conventional Byars procedure(conventional group),and 45 patients underwent the modified Byars staged procedure(modified group).Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage.Notably,there were no statistically significant differences in the preoperative baseline characteristics,duration of surgery,amount of blood loss,or occurrence of postoperative complications,including urethral fistula,stricture and diverticulum,or penile curvature,between the conventional and modified groups.However,there was a significantly lower incidence of coronal sulcus fistula(0 vs 16.1%,P=0.02)and glans dehiscence(0 vs 12.9%,P=0.02)in the surgical group than that in the conventional group.In addition,the modified group exhibited a notably greater rate of normotopic urethral opening(100.0%vs 83.9%,P=0.01)and a higher mean score on the Hypospadias Objective Penile Evaluation(HOPE;mean±standard error of mean:8.6±0.2 vs 7.9±0.3,P=0.02)than did the conventional group.In conclusion,the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula.Consequently,it offers a promising approach for achieving favorable penile esthetics,thereby providing a reliable therapeutic option for severe hypospadias.展开更多
BACKGROUND The identification of key regulators ofβcell mass and function is crucial in developing effective therapeutic interventions for diabetes.Ras homolog enriched in brain 1(Rheb1),an upstream binding protein o...BACKGROUND The identification of key regulators ofβcell mass and function is crucial in developing effective therapeutic interventions for diabetes.Ras homolog enriched in brain 1(Rheb1),an upstream binding protein of mTOR,is a potential thera-peutic target forβcell in diabetes,while the underlying mechanisms remains un-known.METHODS Islets samples were collected from mouse and human donors.Min6 transformed cell line and mouse models including pancreatic orβ-cell specific knockout of Rheb1mice were established.Rapamycin(an mTORC1 inhibitor)and AICAR(an AMPK activator)was used to investigate mTORC1 or AMPK signaling inβcells.The effect of Rheb1 onβcell function via mTORC1,AMPK or other pathways were assessed using western blotting and immunofluorescence,etc.RESULTS In this study,we demonstrate that Rheb1 is highly expressed in islets from young human donors(below the age of 18)compared to adults.Furthermore,our findings reveal that Rheb1 facilitatesβ-cell proliferation through both mTORC1 and AMPK signaling pathways,rather than solely relying on mTORC1.Specifically,we observed that either AICAR or rapamycin alone could partially inhibit Rheb1-inducedβcell proliferation,while the combination of AICAR and rapamycin fully inhibits Rheb1-inducedβcell proliferation in Min6 transformed cell line and mouse islets.In addition,our study highlights the role of Rheb1 in maintainingβcell identity through activation of mTORC1 and Notch1 signaling pathways.Moreover,we also found that Rheb1 could positively regulate HNF4αinβcells,which is a significant transcription factor forβ-cell development and differentiation.CONCLUSION Overall,our findings reveal that Rheb1 regulatesβcell proliferation and identity andβ-cell development related significant marker,providing a promising novel therapeutic target for diabetes.展开更多
Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen qu...Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017–2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 106 (0.09 × 106–0.27 × 106) ml and 12.21 × 106 (4.52 × 106–19.91 × 106) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.展开更多
Erectile dysfunction(ED)is prevalent among men,but its relationship with dietary habits is uncertain.The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature pu...Erectile dysfunction(ED)is prevalent among men,but its relationship with dietary habits is uncertain.The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1,2022,via PubMed,Web of Science,and EMBASE databases.The data compiled included author details;publication dates,countries,treatments,patient numbers,ages,follow-ups,and clinical trial outcomes,such as ED cases,odds ratios(ORs),confidence intervals(CIs),and International Index of Erectile Function-5(IIEF-5)scores with means and standard deviations.An analysis of 14 studies with 27389 participants revealed that plant-based diets(OR=0.71,95%CI:0.66-0.75;P<0.00001),low-fat diets(OR=0.27,95%CI:0.13-0.53;P=0.0002),and alternative diets such as intermittent fasting and organic diets(OR=0.54,95%CI:0.36-0.80;P=0.002)significantly reduced ED risk.High-protein low-fat diets(hazard ratio[HR]=1.38,95%CI:1.12-1.64;P<0.00001)and high-carb low-fat diets(HR=0.79,95%CI:0.55-1.04;P<0.00001)improved IIEF-5 scores.Combined diet and exercise interventions decreased the likelihood of ED(OR=0.49,95%CI:0.28-0.85;P=0.01)and increased the IIEF-5 score(OR=3.40,95%CI:1.69-5.11;P<0.0001).Diets abundant in fruits and vegetables(OR=0.97,95%CI:0.96-0.98;P<0.00001)and nuts(OR=0.54,95%CI:0.37-0.80;P=0.002)were also correlated with lower ED risk.Our meta-analysis underscores a strong dietary-ED association,suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.展开更多
Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products...Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products,paints,food,and cosmetics.In this study,we found a substantial elevation of Ti in the follicular fluid of females diagnosed with nonhyperandrogenic PCOS(non-HA PCOS).Therefore,we orally subjected female rats to nTiO_(2) at 10 and 100 mg/kg body weight for 10 weeks.We found that nTiO_(2) triggered non-HA PCOS-like symptoms,including the increase of cystic follicles,estrous cycle disorder,and abnormal ovulation,but without high testosterone.By transcriptome sequencing,we identified that nTiO_(2) exposure inhibited the steroid hormone synthesis and activated the proapoptotic pathways.Upon validating these altered pathways,we discovered that aromatase(Cyp19a1)overexpression contributed to the decline in testosterone/estradiol ratio.Mean-while,the apoptosis of granulosa cells was increased by nTiO_(2) exposure,which might result in the disorder of follicular development.This study presents the evidences revealing a pronounced correlation between nTiO_(2) exposure and the emergence of non-HA PCOS,urging people to promote the safe utilization of nTiO_(2).展开更多
Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with ...Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with chronic comorbidities.Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019(COVID-19).Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential.Here,in this study,we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus(db/db),and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters.SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters.Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters,and may induce serious complications such as diabetic kidney disease and cardiac lesions.Our findings demonstrated that despite the decreased respiratory pathogenicity,the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters,suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected.This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes.It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.展开更多
Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We ...Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells(m ESCs).Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation;mice treated with only normal saline served as controls.Hyperstimulation resulted in high serum estrogen levels,enlarged ovaries,an increased number of aberrant oocytes,and decreased embryo formation.The messenger RNA(m RNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b(Kdm6b),which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos.In vitro,Kdm6b expression was downregulated in m ESCs treated with high-dose estrogen;treatment with an estrogen receptor antagonist could reverse this downregulated expression level.Furthermore,treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation(H3K27me3)and phosphorylated H2A histone family member X(γ-H2AX).Notably,knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies,with a concomitant increase in the expression of H3K27me3 andγ-H2AX.Collectively,our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression.Accordingly,Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.展开更多
OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three...OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three Chinese hospitals were randomly divided into an HYKT treatment group(n = 55) or a dehydroepiandrosterone(DHEA) treatment group(n =53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a3-month period.RESULTS: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment(P < 0.05) especially in the HYKT group(P < 0.05). Serum follicle stimulating hormone(FSH) levels and FSH/luteinizing hormone ratios decreased(P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased(P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively(not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer(IVF-ET) and the number of retrieved oocytes was(5.1 ± 1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was(4.2 ± 1.9)(not significant); clinical pregnancy rates were 38% in the HYKT group and 20%in DHEA group(not significant). No significant adverse reactions were observed.CONCLUSION: HYKT can improve the ovarian re-serve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA treatment.HYKT might be an alternative to the treatment of infertility caused by DOR.展开更多
Recent research indicates that the human infertility rate is increasing. Although various reasons have been hypothesized for the growing infertility rate, environmental contaminants are potentially important causal ag...Recent research indicates that the human infertility rate is increasing. Although various reasons have been hypothesized for the growing infertility rate, environmental contaminants are potentially important causal agents associated with this change.Chemical contaminants are widespread throughout our environment and human exposure is virtually unavoidable. The overall contribution of environmental exposure to infertility is unknown, but studies involving occupational exposure, together with results from animal experiments, suggest that environmental contaminants may adversely affect fertility. We reviewed the adverse effects of environmental exposure on fertility and related reproductive outcomes. Environmental contaminants covered in this review include heavy metals, organic solvents, pesticides and endocrine disrupting chemicals. It is hoped that this review will highlight the need for further research in this area.展开更多
基金supported by a grant from the Beijing Municipal NaturalScience Foundation(No.7194332)the Shandong Province Natural ScienceFoundation(No.ZR2022ZD19).
文摘At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.
基金funded by the Guangdong Provincial Natural Science Foundation of China(No.2022A1515011517).
文摘Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014–2020were recruited in this multicenter study.Two indices(i.e.,hot night excess [HNE] and hot night duration[HND]) were used to estimate the heat intensity and duration during nighttime.Linear mixed models were used to examine the association between hot nights and semen quality parameters.Results The exposure-response relationship revealed that HNE and HND during 0–90 days before semen collection had a significantly inverse association with sperm motility.Specifically,a 1 ℃ increase in HNE was associated with decreased sperm progressive motility of 0.0090(95% confidence interval[CI]:–0.0147,–0.0033) and decreased total motility of 0.0094(95% CI:–0.0160,–0.0029).HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021(95% CI:–0.0040,–0.0003) and 0.0023(95% CI:–0.0043,–0.0002),respectively.Consistent results were observed at different temperature thresholds on hot nights.Conclusion Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
基金supported by the National Key Research and Development Program of China(2023YFC2506500,2021YFC2500500)the Program of Shanghai Academic Research Leader(22XD1423300)the National Natural Science Foundation of China(T2288101,82370357,82100470)。
文摘Background:The National Chest Pain Center Program(NCPCP)is a nationwide,quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China.The benefits of chest pain center(CPC)accreditation on acute coronary syndrome have been demonstrated.However,there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection(AAD).Methods:We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China,using data from the NCPCP spanning the period from January 1,2016 to December 31,2022.The patients were divided into 2 groups:pre-accreditation and post-accreditation admissions.The outcomes examined included in-hospital mortality,misdiagnosis,and Stanford type A AAD surgery.Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes.Furthermore,we stratified the hospitals based on their geographical location(Eastern/Central/Western regions)or administrative status(provincial/non-provincial capital areas)to assess the impact of CPC accreditation on AAD patients across various regions.Results:The analysis encompassed a total of 40,848 patients diagnosed with AAD.The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis(12.1%vs.16.3%,P<0.001 and 2.9%vs.5.4%,P<0.001,respectively)as well as a notably higher rate of Stanford type A AAD surgery(61.1%vs.42.1%,P<0.001)compared with the pre-accreditation group.After adjusting for potential covariates,CPC accreditation was associated with substantially reduced risks of in-hospital mortality(adjusted OR=0.644,95%CI 0.599-0.693)and misdiagnosis(adjusted OR=0.554,95%CI 0.493-0.624),along with an increase in the proportion of patients undergoing Stanford type A AAD surgery(adjusted OR=1.973,95%CI 1.797-2.165).Following CPC accreditation,there were significant reductions in in-hospital mortality across various regions,particularly in Western regions(from 21.5%to 14.1%).Moreover,CPC accreditation demonstrated a more pronounced impact on in-hospital mortality in non-provincial cities compared to provincial cities(adjusted OR:0.607 vs.0.713).Conclusion:CPC accreditation is correlated with improved management and in-hospital outcomes for patients with AAD.
基金This work was supported by National Key Technology Research and Development Program of China(No.2019YFC1005200,No.2019YFC1005202 and No.2018YFC1002103)National Natural Science Foundation of China(No.81802896)Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019M127).
文摘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.
文摘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.
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.
基金funded by the Key Project of the University Outstanding Youth Backbone Talented Person Foreign Visits Study Does Research of Anhui Province(No.gxgwfx2020025).
文摘Objective Heat wave exposure significantly impacts human health.Nevertheless,studies on the long-term effects of heat wave exposure during adolescence on adverse pregnancy outcomes(APOs)are rare.This study aimed to investigate the relationship between the long-term effects of heat wave exposure during adolescence and APOs.Methods We analyzed data from 3,376 female and 3,013 male participants across 31 provinces in China.All adolescents(10–19 years old),early adolescents(10–14),and late adolescents(15–19)were chosen as exposure windows.Heat waves were defined as periods lasting 2‒4 consecutive days with the daily temperature exceeding the 75th,90th,and 92.5th percentiles.We employed multivariate logistic regression models to assess the associations between exposure to heat waves during adolescence and APOs.Results The results revealed significant associations between male exposure to heat wave events during late adolescence and spontaneous abortion(P<0.05),which was more pronounced in South China.In contrast,no statistically significant associations were detected between males’exposure to heat wave events during adolescence and their partners’preterm birth(P>0.05 for all comparisons).The exposure of females to heat waves during adolescence was not significantly associated with subsequent spontaneous abortion or preterm birth(P>0.05 for all comparisons).Conclusions This study demonstrates that spontaneous abortion in females is associated with heat wave exposure in their male partner during adolescence.
基金Supported by The Science and Technology Department of Jilin Province,China,No.YDZJ202301ZYTS002The Jilin Province Medical and Health Talents Project,No.2019SRCJ010.
文摘BACKGROUND Carriers of chromosomal balanced translocations are often physically healthy with no obvious developmental problems.However,potential chromosomal imbalance in their gametes can lead to implantation failure,miscarriage,or the birth of a child with a chromosomal abnormality.CASE SUMMARY We report six cases of chromosomal translocations involving three families,including the specific Robertson(Roche)translocation.Case 1:The karyotype of the proband was 46,XX,t(18;19)(q22;p12).Case 2:Interventional prenatal diagnosis at 18 weeks of gestation confirmed that the karyotype of the fetus was 46,XY,t(18;19)(q22;p12).Case 3:The karyotype of the proband was 46,XY,t(5;18)(p13;p11).Case 4:Interventional prenatal diagnosis at 14+6 weeks confirmed that the karyotype of the fetus was 46,XX,der(18)t(5;18)(p13;p11)pat.Case 5:The karyotype of the proband was 45,XY,der(14;22)(q10;q10).Case 6:Interventional prenatal diagnosis at 19+4 weeks confirmed that the karyotype of the fetus was 45,XX,rob(14;22)(q10;q10).CONCLUSION Carriers of chromosomal translocations have a high risk of adverse pregnancy outcomes,though they can still have normal offspring.This report on six cases of chromosomal translocations from three families could serve as a reference for future prenatal diagnosis of chromosomal translocations and decision-making on whether to continue the pregnancy.
文摘Background:Recurrent implantation failure(RIF)is a difficult problem with a multifaceted cause.Recent studies have demonstrated that stimulator of interferon genes-induced immune-related genes(STIRGs)are associated with immune disorders that may affect the endometrial immune micro-environment.However,the effect of STRIGs on RIF remains unknown.Methods:Training(GSE111974)and validation(GSE106602)cohorts were acquired from the Gene Expression Omnibus database.STIRGs were extracted from the Molecular Signatures Database and relevant studies.Consensus clustering analysis was used to identify RIF molecular subtypes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment and immune infiltration analyses were performed between RIF subtypes.Drug-related potential therapeutic target genes were discovered.Results:Two distinct molecular subtypes were discovered in both the training and validation groups according to STIRGs.In subtype C2,there was a notable decrease in the presence of different types of immune cells,such as natural killer cells and macrophages.Furthermore,the examination of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated a decrease in numerous immune-related biological processes within subtype C2.Finally,nine hub genes(CXCR4,POU5F1,PPARG,TLR2,EGFR,CSF1,BCL2A1,BTK,and SRGN)were identified as potential therapeutic targets for RIF.Conclusion:Based on STIRGs,we identified a new molecular subtype with significantly reduced immune infiltration in RIF.Nine genes might be potential therapeutic targets for RIF.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFC2705700)Guangdong Basic and Applied Basic Research Foundation(No.2024A1515012355)+1 种基金the Shenzhen Science and Technology Program(No.JCYJ20220530140609020)the Scientific Research Project of Wuhan Municipal Health Commission(No.WX21Q36).
文摘Objective The effects of prolonged exposure to persistently elevated atmospheric pollutants,commonly termed air pollution waves,on fertility intentions remain inadequately understood.This study aims to investigate the association between particulate matter(PM)exposure and fertility intentions.Methods In this nationwide cross-sectional study,we analyzed data from 10,747 participants(5496 females and 5251 males).PM waves were defined as periods lasting 3‒6 consecutive days during which the daily average concentrations exceeded China’s Ambient Air Quality Standards Grade II thresholds(PM2.5>75μg/m3 and PM10>150μg/m3).We employed multivariate logistic regression models to assess the association between exposure to PM waves and fertility intentions.Results Significant inverse associations were detected between exposure to PM2.5 wave events(characterized by concentrations exceeding 75μg/m3 for durations of 4‒6 days,P<0.05)and PM10 wave events(defined as concentrations exceeding 150μg/m3 for 6 consecutive days,P<0.05)and fertility intentions among females.In contrast,neither the PM2.5 wave nor the PM10 wave events demonstrated statistically significant correlations with fertility intentions in males(P>0.05 for all comparisons).The potentially susceptible subgroup was identified as females aged 20–30 years.Conclusions Our results provide the first evidence that PM2.5 and PM10 waves are associated with a reduction in female fertility intentions,offering critical insights for the development of public health policies and strategies aimed at individual protection.
基金funded by the National Natural Science Foundation of China(No.81973966)。
文摘Objective:To explore the association between acupuncture during controlled ovarian hyperstimulation(COH)and the live birth rate(LBR)using different propensity score methods.Methods:In this retrospective cohort study,eligible women who underwent a COH were divided into acupuncture and non-acupuncture groups.The primary outcome was LBR,as determined by propensity score matching(PSM).LBR was defined as the delivery of one or more living infants that reached a gestational age over 28 weeks after embryo transfer.The propensity score model encompassed 16 confounding variables.To validate the results,sensitivity analyses were conducted using three additional propensity score methods:propensity score adjustment,inverse probability weighting(IPW),and IPW with a"doubly robust”estimator.Results:The primary cohort encompassed 9751 patients(1830[18.76%]in the acupuncture group and7921[81.23%]in the non-acupuncture group).Following 1:1 PSM,a higher LBR was found in the acupuncture cohort(41.4%[755/1824]vs 36.4%[664/1824],with an odds ratio of 1.23[95%confidence interval,1.08-1.41]).Three additional propensity score methods produced essentially similar results.The risk of serious adverse events did not significantly differ between the two groups.Conclusion:This retrospective study revealed an association between acupuncture and an increased LBR among patients undergoing COH,and that acupuncture is a safe and valuable treatment option.
基金supported by funding from the Medical Research Funding of Guangdong(No.A2022499 to QGX)the National Natural Science Foundation of China(No.82301796 to PL)the Guangdong Province Regional Joint Fund-Youth Fund Project of China(No.2022A1515111201 to PL).
文摘This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias.We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between October 2012 and October 2022.In total,31 patients underwent the conventional Byars procedure(conventional group),and 45 patients underwent the modified Byars staged procedure(modified group).Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage.Notably,there were no statistically significant differences in the preoperative baseline characteristics,duration of surgery,amount of blood loss,or occurrence of postoperative complications,including urethral fistula,stricture and diverticulum,or penile curvature,between the conventional and modified groups.However,there was a significantly lower incidence of coronal sulcus fistula(0 vs 16.1%,P=0.02)and glans dehiscence(0 vs 12.9%,P=0.02)in the surgical group than that in the conventional group.In addition,the modified group exhibited a notably greater rate of normotopic urethral opening(100.0%vs 83.9%,P=0.01)and a higher mean score on the Hypospadias Objective Penile Evaluation(HOPE;mean±standard error of mean:8.6±0.2 vs 7.9±0.3,P=0.02)than did the conventional group.In conclusion,the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula.Consequently,it offers a promising approach for achieving favorable penile esthetics,thereby providing a reliable therapeutic option for severe hypospadias.
基金Supported by National Natural Science Foundation of China,No.82430029,No.82330025,No.82370807,and No.82070807Leading Talents Program of Hunan Province,No.2022RC3078Natural Science Foundation of Hunan Province,China,No.2021JJ30976.
文摘BACKGROUND The identification of key regulators ofβcell mass and function is crucial in developing effective therapeutic interventions for diabetes.Ras homolog enriched in brain 1(Rheb1),an upstream binding protein of mTOR,is a potential thera-peutic target forβcell in diabetes,while the underlying mechanisms remains un-known.METHODS Islets samples were collected from mouse and human donors.Min6 transformed cell line and mouse models including pancreatic orβ-cell specific knockout of Rheb1mice were established.Rapamycin(an mTORC1 inhibitor)and AICAR(an AMPK activator)was used to investigate mTORC1 or AMPK signaling inβcells.The effect of Rheb1 onβcell function via mTORC1,AMPK or other pathways were assessed using western blotting and immunofluorescence,etc.RESULTS In this study,we demonstrate that Rheb1 is highly expressed in islets from young human donors(below the age of 18)compared to adults.Furthermore,our findings reveal that Rheb1 facilitatesβ-cell proliferation through both mTORC1 and AMPK signaling pathways,rather than solely relying on mTORC1.Specifically,we observed that either AICAR or rapamycin alone could partially inhibit Rheb1-inducedβcell proliferation,while the combination of AICAR and rapamycin fully inhibits Rheb1-inducedβcell proliferation in Min6 transformed cell line and mouse islets.In addition,our study highlights the role of Rheb1 in maintainingβcell identity through activation of mTORC1 and Notch1 signaling pathways.Moreover,we also found that Rheb1 could positively regulate HNF4αinβcells,which is a significant transcription factor forβ-cell development and differentiation.CONCLUSION Overall,our findings reveal that Rheb1 regulatesβcell proliferation and identity andβ-cell development related significant marker,providing a promising novel therapeutic target for diabetes.
基金supported by the Guangdong Natural Science Foundation(No.2022A1515011705).
文摘Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017–2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 106 (0.09 × 106–0.27 × 106) ml and 12.21 × 106 (4.52 × 106–19.91 × 106) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
基金supported by the grant from National Natural Science Foundation of China(grant No.81602236).
文摘Erectile dysfunction(ED)is prevalent among men,but its relationship with dietary habits is uncertain.The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1,2022,via PubMed,Web of Science,and EMBASE databases.The data compiled included author details;publication dates,countries,treatments,patient numbers,ages,follow-ups,and clinical trial outcomes,such as ED cases,odds ratios(ORs),confidence intervals(CIs),and International Index of Erectile Function-5(IIEF-5)scores with means and standard deviations.An analysis of 14 studies with 27389 participants revealed that plant-based diets(OR=0.71,95%CI:0.66-0.75;P<0.00001),low-fat diets(OR=0.27,95%CI:0.13-0.53;P=0.0002),and alternative diets such as intermittent fasting and organic diets(OR=0.54,95%CI:0.36-0.80;P=0.002)significantly reduced ED risk.High-protein low-fat diets(hazard ratio[HR]=1.38,95%CI:1.12-1.64;P<0.00001)and high-carb low-fat diets(HR=0.79,95%CI:0.55-1.04;P<0.00001)improved IIEF-5 scores.Combined diet and exercise interventions decreased the likelihood of ED(OR=0.49,95%CI:0.28-0.85;P=0.01)and increased the IIEF-5 score(OR=3.40,95%CI:1.69-5.11;P<0.0001).Diets abundant in fruits and vegetables(OR=0.97,95%CI:0.96-0.98;P<0.00001)and nuts(OR=0.54,95%CI:0.37-0.80;P=0.002)were also correlated with lower ED risk.Our meta-analysis underscores a strong dietary-ED association,suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
基金supported by the National Natural Science Foundation of China(Nos.81871161 and 32301082)Fujian Provincial Health Technology Project for their attribution from(No.2023GGB01)the Natural Science Foundation of Fujian Province(No.2021J01343).
文摘Polycystic ovarian syndrome(PCOS)is a frequently encountered disease with hormonal and metabolic dysfunction in women of reproductive age.Nano-sized titanium dioxide(nTiO_(2))has been widely used in skin care products,paints,food,and cosmetics.In this study,we found a substantial elevation of Ti in the follicular fluid of females diagnosed with nonhyperandrogenic PCOS(non-HA PCOS).Therefore,we orally subjected female rats to nTiO_(2) at 10 and 100 mg/kg body weight for 10 weeks.We found that nTiO_(2) triggered non-HA PCOS-like symptoms,including the increase of cystic follicles,estrous cycle disorder,and abnormal ovulation,but without high testosterone.By transcriptome sequencing,we identified that nTiO_(2) exposure inhibited the steroid hormone synthesis and activated the proapoptotic pathways.Upon validating these altered pathways,we discovered that aromatase(Cyp19a1)overexpression contributed to the decline in testosterone/estradiol ratio.Mean-while,the apoptosis of granulosa cells was increased by nTiO_(2) exposure,which might result in the disorder of follicular development.This study presents the evidences revealing a pronounced correlation between nTiO_(2) exposure and the emergence of non-HA PCOS,urging people to promote the safe utilization of nTiO_(2).
基金supported by the National Natural Science Foundation of Jiangsu Province(BE20197310 to J-M.L.)the National Key R&D Program of China(2021YFF0702500 to J-M.L.and A-M.S.,and the Start-up Funding of Scientific Researches for Postdoc in Guangzhou,Guangdong Province to H-F.L.).
文摘Being widespread across the globe,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)keeps evolving and generating new variants and continuously poses threat to public health,especially to the population with chronic comorbidities.Diabetes mellitus is one of high-risk factors for severe outcome of coronavirus disease 2019(COVID-19).Establishment of animal models that parallel the clinical and pathological features of COVID-19 complicated with diabetes is thus highly essential.Here,in this study,we constructed leptin receptor gene knockout hamsters with the phenotype of diabetes mellitus(db/db),and revealed that the diabetic hamsters were more susceptible to SARS-CoV-2 and its variants than wild-type hamsters.SARS-CoV-2 and its variants induced a stronger immune cytokine response in the lungs of diabetic hamsters than in wild-type hamsters.Comparative histopathology analyses also showed that infection of SARS-CoV-2 and the variants caused more severe lung tissue injury in diabetic hamsters,and may induce serious complications such as diabetic kidney disease and cardiac lesions.Our findings demonstrated that despite the decreased respiratory pathogenicity,the SARS-CoV-2 variants were still capable of impairing other organs such as kidney and heart in diabetic hamsters,suggesting that the risk of evolving SARS-CoV-2 variants to diabetic patients should never be neglected.This hamster model may help better understand the pathogenesis mechanism of severe COVID-19 in patients with diabetes.It will also aid in development and testing of effective therapeutics and prophylactic treatments against SARS-CoV-2 variants among these high-risk populations.
基金supported by the National Key Research and Development Program of China(No.2018YFC1004900)the National Natural Science Foundation of China(No.82101799)the Health Science and Technology Foundation of Zhejiang Province of China(No.2022KY186).
文摘Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells(m ESCs).Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation;mice treated with only normal saline served as controls.Hyperstimulation resulted in high serum estrogen levels,enlarged ovaries,an increased number of aberrant oocytes,and decreased embryo formation.The messenger RNA(m RNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b(Kdm6b),which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos.In vitro,Kdm6b expression was downregulated in m ESCs treated with high-dose estrogen;treatment with an estrogen receptor antagonist could reverse this downregulated expression level.Furthermore,treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation(H3K27me3)and phosphorylated H2A histone family member X(γ-H2AX).Notably,knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies,with a concomitant increase in the expression of H3K27me3 andγ-H2AX.Collectively,our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression.Accordingly,Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
基金Supported by The Scientific research project of Administration of Traditional Chinese Medicine of Hebei Province:The Clinical Study of Kuntai Capsule in the Treatment of Infertility Women with Diminished Ovarian Reserve Diagnosed Liver-kidney Yin Deficiency and Heart-kidney Imbalance Syndrome(No.2016068)
文摘OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three Chinese hospitals were randomly divided into an HYKT treatment group(n = 55) or a dehydroepiandrosterone(DHEA) treatment group(n =53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a3-month period.RESULTS: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment(P < 0.05) especially in the HYKT group(P < 0.05). Serum follicle stimulating hormone(FSH) levels and FSH/luteinizing hormone ratios decreased(P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased(P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively(not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer(IVF-ET) and the number of retrieved oocytes was(5.1 ± 1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was(4.2 ± 1.9)(not significant); clinical pregnancy rates were 38% in the HYKT group and 20%in DHEA group(not significant). No significant adverse reactions were observed.CONCLUSION: HYKT can improve the ovarian re-serve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA treatment.HYKT might be an alternative to the treatment of infertility caused by DOR.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB14010300)the Beijing Municipal Science and Technology Commission(No.Z151100004015167)+1 种基金the Beijing Municipal Health Technology High-level Talent Project(No.2014-3-076)the Open fund of State Key Laboratory of Environmental Chemistry and Ecotoxicology(No.KF-2017-13)
文摘Recent research indicates that the human infertility rate is increasing. Although various reasons have been hypothesized for the growing infertility rate, environmental contaminants are potentially important causal agents associated with this change.Chemical contaminants are widespread throughout our environment and human exposure is virtually unavoidable. The overall contribution of environmental exposure to infertility is unknown, but studies involving occupational exposure, together with results from animal experiments, suggest that environmental contaminants may adversely affect fertility. We reviewed the adverse effects of environmental exposure on fertility and related reproductive outcomes. Environmental contaminants covered in this review include heavy metals, organic solvents, pesticides and endocrine disrupting chemicals. It is hoped that this review will highlight the need for further research in this area.
