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
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
Objective To investigate the reproduction-assisting effects of laparoscopic ＂corepulling＂ salpingectomy for patients with hydrosalpinx on ovarian reserve,responsiveness to stimuli and outcomes of in vitro fertilizat...Objective To investigate the reproduction-assisting effects of laparoscopic ＂corepulling＂ salpingectomy for patients with hydrosalpinx on ovarian reserve,responsiveness to stimuli and outcomes of in vitro fertilization and embryo transfer（IVF-ET）.Methods Infertile females receiving treatment in Reproductive Medicine Center of Yantai Yuhuangding Hospital due to fallopian tube disorders（n=214） were enrolled from July 2006 to December 2007 and further divided into three groups.＂Core-pulling＂ procedure group（group A） consisted of patients receiving pretreatment with ＂corepulling＂ salpingectomy due to hydrosalpinx in our center（n=31）,wherein 16 patients received IVF-ET.Conventional procedure group（group B） consisted of patients receiving conventional salpingectomy for hydrosalpinx or ectopic pregnancy in our center or other institutes prior to IVF-ET（n=59）.Control group（group C） consisted of patients receiving IVF-ET without the history of previous hydrosalpinx or salpingectomy（n=124）.Results At baseline,the antral follicle count of group B was significantly less than that of groups A and C（8.6±2.5 vs 8.3±2.0 vs 9.8±2.4）.The mature oocytes retrieved numbered less than the other two groups,in a statistically significant manner compared with group C（13.1±5.7 vs 10.6±5.0 vs 12.0±6.2）.Patients of groups A and B received more gonadotropin while the dosage of group B differed significantly from group C（31.0±17.7 vs 37.6±8.3 vs 30.0±4.6）.E2 level on hCG injection day was slightly lower in group B than in the other two groups,statistically significant compared with that of group C,but not compared with that of group A.After receiving IVF-ET,patients of group A showed significantly higher conception rate than groups B and C（62.5% vs 43.6% vs 39.2%）.Conclusion Compared with the conventional procedure,laparoscopic ＂core-pulling＂ salpingectomy should be recommended for patients with hydrosalpinx intending to receive IVF-ET,which did not interfere with the ovarian reserve or responsiveness but improve the conception rate in clinical practice.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
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...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.展开更多
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 ...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.展开更多
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 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
Trophectoderm(TE)biopsy has become the preferred approach in preimplantation genetic testing,providing clear advantages over polar body and cleavage-stage biopsy.However,the optimal timing and methodology for blastocy...Trophectoderm(TE)biopsy has become the preferred approach in preimplantation genetic testing,providing clear advantages over polar body and cleavage-stage biopsy.However,the optimal timing and methodology for blastocyst biopsy remain subjects of ongoing debate.McArthur et al in 2005 were the first to demonstrate the safety of TE biopsy at the hatching blastocyst stage with laser-assisted opening in the zona pellucida(ZP)on Day 3,reporting 100%survival of 1050 biopsied blastocysts,all of which re-expanded,with an implantation rate of 41%[1].Nearly a decade later,Capalbo et al in 2014 introduced a modified strategy,performing biopsy on fully expanded blastocysts by creating a laser-assisted ZP opening and immediately aspirating TE cells on Day 5.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
Objective Although immune dysregulation is implicated in the pathogenesis of endometriosis(EMs),the specific role of prostate transmembrane protein androgen induced 1(PMEPA1)in modulating the function of regulatory T ...Objective Although immune dysregulation is implicated in the pathogenesis of endometriosis(EMs),the specific role of prostate transmembrane protein androgen induced 1(PMEPA1)in modulating the function of regulatory T cells(Tregs)remains inadequately understood.This study aimed to elucidate the regulatory mechanisms by which PMEPA1 influences the activity of Tregs,thereby facilitating the invasion of endometrial stromal cells(ESCs).Methods Single-cell RNA sequencing(scRNA-seq)was performed on matched ectopic ovarian lesions and eutopic endometria from 3 patients.Clinical specimens from patients with EMs and control subjects were examined for PMEPA1 expression.Primary human Tregs isolated from peripheral blood mononuclear cells were subjected to PMEPA1 overexpression(via plasmid)or knockdown(via siRNA).Modulation of the PI3K pathway was conducted via the activator 740Y-P or the inhibitor LY294002.The secretion of IL-10 and TGF-βby Tregs was quantified using an enzyme-linked immunosorbent assay.Ectopic ESCs cocultured with modified Tregs were assessed for their proliferation,migration,and invasion capabilities.Results scRNA-seq data revealed significant upregulation of PMEPA1 in Tregs from ectopic ovarian lesions compared with paired eutopic endometria.PMEPA1 expression was increased in the ectopic lesions and peritoneal fluid mononuclear cells of patients with EMs.Tregs overexpressing PMEPA1 demonstrated reduced secretion of IL-10 and TGF-βbut exhibited hyperactivation of the PI3K/AKT signaling pathway.Treatment with LY294002 ameliorated the impairment in cytokine secretion.Coculture experiments with Tregs expressing high levels of PMEPA1 resulted in increased invasion,migration,and proliferation of ESCs.Conclusion PMEPA1 impairs Treg-mediated immunosuppression by hyperactivating the PI3K/AKT pathway,thereby facilitating the invasiveness of ESCs in EMs.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
Assisted hatching(AH)is commonly performed before trophectoderm(TE)biopsy for preimplantation genetic testing for aneuploidy(PGT-A),yet whether AH timing influences the detection of chromosomal mosaicism remains uncer...Assisted hatching(AH)is commonly performed before trophectoderm(TE)biopsy for preimplantation genetic testing for aneuploidy(PGT-A),yet whether AH timing influences the detection of chromosomal mosaicism remains uncertain.Beyond timing,procedural choices in PGT-A must balance diagnostic yield against potential harm from additional handling(e.g.,repeat TE biopsy or cryopreservation steps),as underscored by a recent systematic review and meta-analysis[1].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
Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread applicati...Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread application in industry.Herein,an engineered IRED from Streptomyces viridochromogenes was developed through four rounds of directed evolution.The engineered SvIRED displayed a significant increase in specific activity to 136.8 U mg^(-1),the highest reported for an IRED to date.Molecular dynamics simulations elucidated the surge in specific activity during mutations.The best mutant can also catalyse the reductive coupling of aldehyde homologs and primary amines with up to 66.9 U mg^(-1).Additionally,we established an in-situ product adsorption system using resin,which significantly alleviated substrate/product inhibition and enhanced substrate loading to 100 g L^(-1).Under optimal conditions,a wide range of chiral 2-aryl-pyrrolidines were successfully produced at high substrate loadings(50-100 g L^(-1))with enantiomeric excess over 99%.The usefulness of this biocatalytic system was further demonstrated by preparation of pharmaceutically relevant chiral 2-aryl pyrrolidines,particularly the decagram-scale synthesis of the key chiral aticaprant intermediate with 90%isolated yield,>99%ee,and 438 g L^(-1) d^(-1) space-time yield.展开更多
Polycystic ovarian syndrome(PCOS)is the most principal reason for infertility in reproductive women,but no versatile treatment is feasible.Although trans-10-hydroxy-2-decenoic acid(10H2DA)exhibits the anti-inflammator...Polycystic ovarian syndrome(PCOS)is the most principal reason for infertility in reproductive women,but no versatile treatment is feasible.Although trans-10-hydroxy-2-decenoic acid(10H2DA)exhibits the anti-inflammatory,anti-cancerous and immunomodulatory properties,its role in improving PCOS remains elusive.This present study examined the effects of 10H2DA on the estrous cycle,ovarian morphology,reproductive hormone,glucose and insulin tolerances of PCOS mice,analyzed the binding between 10H2DA and free fatty acid receptor 4(FFAR4),and explored the regulation of 10H2DA on the c-Jun N-terminal kinase(JNK)/JUN(Jun proto-oncogene)signaling,cytosolic calcium ion(Ca2),endoplasmic reticulum(ER)Ca2release,mitochondrial Ca2+,mitochondrial function,autophagy,lysosomal acidification,mitochondrial fission,secretion function and apoptosis of ovarian granulosa cells(GCs)using enzyme-linked immunosorbent assay,flow cytometry,Western blotting,molecular docking,various fluorescent probes or plasmid,etc.The results showed that 10H2DA alleviated the symptom of PCOS mice through improving the secretion dysfunction of GCs and protecting GCs against apoptosis.After binding to FFAR4 and inactivation of JNK/JUN signaling,10H2DA restricted the release of ER Ca2through targeting ryanodine receptors(RYRs)which had been identified as the downstream targets of JUN,diminished cytosolic Ca^(²+) accumulation and prevented Ca^(²+) influx into mitochondria via adjusting the mitochondrial calcium uptake 1 and mitochondrial calcium uniporter.Concurrently,10H2DA kept the integrity of mitochondrial function through maintaining mitochondrial Ca2 homeostasis and suppressed the discharge of mitochondrial reactive oxygen species into the cytosol through blocking the mitochondrial permeability transition pore opening to avoid the lipid peroxidation and ameliorate the secretory function and apoptosis of GCs.Furthermore,1OH2DA rescued the defective autophagic flux along with the decline of autophagosomes and sequestosome 1 aggregation,restored the mitophagy flux with the abatement of mitophagosomes and Parkin recruitment to mitochondria,and accelerated the lysosomal degradation for depolarized mitochondria with the recovery of lysosomal acidification,whereas activation of JNK antagonized the amelioration of 10H2DA on above effectiveness,but this antagonism was counteracted by the attenuation of intracellular Ca2+.After application of 10H2DA,dynamin-related protein 1 phosphorylation was diminished and its recruitment to mitochondrial surface was impeded concomitant with the improvement of mitochondrial fragmentation,whereas inhibition of late-stage autophagy caused the failure of 10H2DA in improving mitochondrial fission.Collectively,10H2DA might ameliorate PCOS mice through modulating autophagy-mediated mitochondrial fission dependent on the maintenance of Ca^(2+) homeostasis between ER and mitochondria.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
BACKGROUND Enhanced recovery after surgery(ERAS)guidelines have been established for multiple types of adult surgeries.However,ERAS guidelines tailored to pediatric surgeries remain to be developed.AIM To evaluate the...BACKGROUND Enhanced recovery after surgery(ERAS)guidelines have been established for multiple types of adult surgeries.However,ERAS guidelines tailored to pediatric surgeries remain to be developed.AIM To evaluate the clinical outcomes of ERAS protocols in pediatric laparoscopic Meckel’s diverticulum resection.METHODS This retrospective cohort study analyzed 78 consecutive pediatric cases treated between January 2017 and March 2025.Patients were divided into:Traditional care group(n=38):January 2017-December 2020;ERAS protocol group(n=40):January 2021-March 2025.We compared perioperative outcomes,including clinical recovery parameters and laboratory markers,to assess protocol efficacy.RESULTS All procedures were completed laparoscopically by the same surgical team without conversion.Baseline characteristics,including demographics,diverticulum location,and intraoperative parameters(operative time,blood loss),were comparable between groups(all P>0.05).The ERAS protocol demonstrated significantly shorter postoperative length of stay(7.55±1.52 days vs 10.40±3.59 days,P<0.001)while complication rates were numerically lower in the ERAS group(17.50%vs 13.16%,P=0.595).Additional benefits of ERAS implementation included:Reduced intravenous fluid requirements(5.00 mL/kg/hour vs 8.00 mL/kg/hour),accelerated gastrointestinal recovery(first flatus:2.00 days vs 3.00 days),lower pain scores(P<0.001),earlier total enteral nutrition achievement(5.00 days vs 6.50 days)and shorter intravenous therapy duration(6.00 days vs 8.00 days;all P<0.001).ERAS patients also showed reduced drainage utilization(P<0.05)and improved inflammatory marker profiles postoperatively[neutrophils:(5.98±2.02)×10^(9)/L vs(8.01±3.98)×10^(9)/L];median Creactive protein:13.6 mg/L 7 vs 19.63 mg/L).Glycemic control was superior in the ERAS group despite higher induction levels(both P<0.05).Parental satisfaction(92.50%vs 86.84%)and 30-day readmission rates(2.50%vs 2.63%)showed no significant differences.CONCLUSION ERAS protocols safely optimize recovery in children undergoing laparoscopic Meckel’s diverticulum resection,significantly reducing length of stay while improving pain management and overall clinical outcomes.These findings support the adoption of ERAS in pediatric intestinal surgery.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
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.
文摘Objective To investigate the reproduction-assisting effects of laparoscopic ＂corepulling＂ salpingectomy for patients with hydrosalpinx on ovarian reserve,responsiveness to stimuli and outcomes of in vitro fertilization and embryo transfer（IVF-ET）.Methods Infertile females receiving treatment in Reproductive Medicine Center of Yantai Yuhuangding Hospital due to fallopian tube disorders（n=214） were enrolled from July 2006 to December 2007 and further divided into three groups.＂Core-pulling＂ procedure group（group A） consisted of patients receiving pretreatment with ＂corepulling＂ salpingectomy due to hydrosalpinx in our center（n=31）,wherein 16 patients received IVF-ET.Conventional procedure group（group B） consisted of patients receiving conventional salpingectomy for hydrosalpinx or ectopic pregnancy in our center or other institutes prior to IVF-ET（n=59）.Control group（group C） consisted of patients receiving IVF-ET without the history of previous hydrosalpinx or salpingectomy（n=124）.Results At baseline,the antral follicle count of group B was significantly less than that of groups A and C（8.6±2.5 vs 8.3±2.0 vs 9.8±2.4）.The mature oocytes retrieved numbered less than the other two groups,in a statistically significant manner compared with group C（13.1±5.7 vs 10.6±5.0 vs 12.0±6.2）.Patients of groups A and B received more gonadotropin while the dosage of group B differed significantly from group C（31.0±17.7 vs 37.6±8.3 vs 30.0±4.6）.E2 level on hCG injection day was slightly lower in group B than in the other two groups,statistically significant compared with that of group C,but not compared with that of group A.After receiving IVF-ET,patients of group A showed significantly higher conception rate than groups B and C（62.5% vs 43.6% vs 39.2%）.Conclusion Compared with the conventional procedure,laparoscopic ＂core-pulling＂ salpingectomy should be recommended for patients with hydrosalpinx intending to receive IVF-ET,which did not interfere with the ovarian reserve or responsiveness but improve the conception rate in clinical practice.
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.
基金supported by the National Natural Science Foundation of China(No.30570769)Funds of Health and Family Planning Commission of Hubei Province(No.JS2013009)the Fundamental Research Funds for Central Universities(No.2042014kf0120)
文摘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.
基金This study was supported by the National Natural Science Foundation of China Nos.81774351the Tianjin Health&Family Planning Commission(Tianjin scientific research project of priority area of traditional Chinese medicine,Nos.2018008)Shanxi Guangyuyuan TCM Co.,Ltd.
文摘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.
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.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
文摘Trophectoderm(TE)biopsy has become the preferred approach in preimplantation genetic testing,providing clear advantages over polar body and cleavage-stage biopsy.However,the optimal timing and methodology for blastocyst biopsy remain subjects of ongoing debate.McArthur et al in 2005 were the first to demonstrate the safety of TE biopsy at the hatching blastocyst stage with laser-assisted opening in the zona pellucida(ZP)on Day 3,reporting 100%survival of 1050 biopsied blastocysts,all of which re-expanded,with an implantation rate of 41%[1].Nearly a decade later,Capalbo et al in 2014 introduced a modified strategy,performing biopsy on fully expanded blastocysts by creating a laser-assisted ZP opening and immediately aspirating TE cells on Day 5.
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.
文摘Objective Although immune dysregulation is implicated in the pathogenesis of endometriosis(EMs),the specific role of prostate transmembrane protein androgen induced 1(PMEPA1)in modulating the function of regulatory T cells(Tregs)remains inadequately understood.This study aimed to elucidate the regulatory mechanisms by which PMEPA1 influences the activity of Tregs,thereby facilitating the invasion of endometrial stromal cells(ESCs).Methods Single-cell RNA sequencing(scRNA-seq)was performed on matched ectopic ovarian lesions and eutopic endometria from 3 patients.Clinical specimens from patients with EMs and control subjects were examined for PMEPA1 expression.Primary human Tregs isolated from peripheral blood mononuclear cells were subjected to PMEPA1 overexpression(via plasmid)or knockdown(via siRNA).Modulation of the PI3K pathway was conducted via the activator 740Y-P or the inhibitor LY294002.The secretion of IL-10 and TGF-βby Tregs was quantified using an enzyme-linked immunosorbent assay.Ectopic ESCs cocultured with modified Tregs were assessed for their proliferation,migration,and invasion capabilities.Results scRNA-seq data revealed significant upregulation of PMEPA1 in Tregs from ectopic ovarian lesions compared with paired eutopic endometria.PMEPA1 expression was increased in the ectopic lesions and peritoneal fluid mononuclear cells of patients with EMs.Tregs overexpressing PMEPA1 demonstrated reduced secretion of IL-10 and TGF-βbut exhibited hyperactivation of the PI3K/AKT signaling pathway.Treatment with LY294002 ameliorated the impairment in cytokine secretion.Coculture experiments with Tregs expressing high levels of PMEPA1 resulted in increased invasion,migration,and proliferation of ESCs.Conclusion PMEPA1 impairs Treg-mediated immunosuppression by hyperactivating the PI3K/AKT pathway,thereby facilitating the invasiveness of ESCs in EMs.
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Assisted hatching(AH)is commonly performed before trophectoderm(TE)biopsy for preimplantation genetic testing for aneuploidy(PGT-A),yet whether AH timing influences the detection of chromosomal mosaicism remains uncertain.Beyond timing,procedural choices in PGT-A must balance diagnostic yield against potential harm from additional handling(e.g.,repeat TE biopsy or cryopreservation steps),as underscored by a recent systematic review and meta-analysis[1].
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.
文摘Imine reductases(IREDs)have been extensively used for the imine reduction and reductive amination to access various amines.However,poor activity and severe substrate/product inhibition limit their widespread application in industry.Herein,an engineered IRED from Streptomyces viridochromogenes was developed through four rounds of directed evolution.The engineered SvIRED displayed a significant increase in specific activity to 136.8 U mg^(-1),the highest reported for an IRED to date.Molecular dynamics simulations elucidated the surge in specific activity during mutations.The best mutant can also catalyse the reductive coupling of aldehyde homologs and primary amines with up to 66.9 U mg^(-1).Additionally,we established an in-situ product adsorption system using resin,which significantly alleviated substrate/product inhibition and enhanced substrate loading to 100 g L^(-1).Under optimal conditions,a wide range of chiral 2-aryl-pyrrolidines were successfully produced at high substrate loadings(50-100 g L^(-1))with enantiomeric excess over 99%.The usefulness of this biocatalytic system was further demonstrated by preparation of pharmaceutically relevant chiral 2-aryl pyrrolidines,particularly the decagram-scale synthesis of the key chiral aticaprant intermediate with 90%isolated yield,>99%ee,and 438 g L^(-1) d^(-1) space-time yield.
基金supported by Natural Science Foundation of Jilin Province(20220101287JC)National Natural Science Foundation of China(31873003 and 31472158)Graduate Innovation Fund of Jilin University(2022140).
文摘Polycystic ovarian syndrome(PCOS)is the most principal reason for infertility in reproductive women,but no versatile treatment is feasible.Although trans-10-hydroxy-2-decenoic acid(10H2DA)exhibits the anti-inflammatory,anti-cancerous and immunomodulatory properties,its role in improving PCOS remains elusive.This present study examined the effects of 10H2DA on the estrous cycle,ovarian morphology,reproductive hormone,glucose and insulin tolerances of PCOS mice,analyzed the binding between 10H2DA and free fatty acid receptor 4(FFAR4),and explored the regulation of 10H2DA on the c-Jun N-terminal kinase(JNK)/JUN(Jun proto-oncogene)signaling,cytosolic calcium ion(Ca2),endoplasmic reticulum(ER)Ca2release,mitochondrial Ca2+,mitochondrial function,autophagy,lysosomal acidification,mitochondrial fission,secretion function and apoptosis of ovarian granulosa cells(GCs)using enzyme-linked immunosorbent assay,flow cytometry,Western blotting,molecular docking,various fluorescent probes or plasmid,etc.The results showed that 10H2DA alleviated the symptom of PCOS mice through improving the secretion dysfunction of GCs and protecting GCs against apoptosis.After binding to FFAR4 and inactivation of JNK/JUN signaling,10H2DA restricted the release of ER Ca2through targeting ryanodine receptors(RYRs)which had been identified as the downstream targets of JUN,diminished cytosolic Ca^(²+) accumulation and prevented Ca^(²+) influx into mitochondria via adjusting the mitochondrial calcium uptake 1 and mitochondrial calcium uniporter.Concurrently,10H2DA kept the integrity of mitochondrial function through maintaining mitochondrial Ca2 homeostasis and suppressed the discharge of mitochondrial reactive oxygen species into the cytosol through blocking the mitochondrial permeability transition pore opening to avoid the lipid peroxidation and ameliorate the secretory function and apoptosis of GCs.Furthermore,1OH2DA rescued the defective autophagic flux along with the decline of autophagosomes and sequestosome 1 aggregation,restored the mitophagy flux with the abatement of mitophagosomes and Parkin recruitment to mitochondria,and accelerated the lysosomal degradation for depolarized mitochondria with the recovery of lysosomal acidification,whereas activation of JNK antagonized the amelioration of 10H2DA on above effectiveness,but this antagonism was counteracted by the attenuation of intracellular Ca2+.After application of 10H2DA,dynamin-related protein 1 phosphorylation was diminished and its recruitment to mitochondrial surface was impeded concomitant with the improvement of mitochondrial fragmentation,whereas inhibition of late-stage autophagy caused the failure of 10H2DA in improving mitochondrial fission.Collectively,10H2DA might ameliorate PCOS mice through modulating autophagy-mediated mitochondrial fission dependent on the maintenance of Ca^(2+) homeostasis between ER and mitochondria.
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.
文摘BACKGROUND Enhanced recovery after surgery(ERAS)guidelines have been established for multiple types of adult surgeries.However,ERAS guidelines tailored to pediatric surgeries remain to be developed.AIM To evaluate the clinical outcomes of ERAS protocols in pediatric laparoscopic Meckel’s diverticulum resection.METHODS This retrospective cohort study analyzed 78 consecutive pediatric cases treated between January 2017 and March 2025.Patients were divided into:Traditional care group(n=38):January 2017-December 2020;ERAS protocol group(n=40):January 2021-March 2025.We compared perioperative outcomes,including clinical recovery parameters and laboratory markers,to assess protocol efficacy.RESULTS All procedures were completed laparoscopically by the same surgical team without conversion.Baseline characteristics,including demographics,diverticulum location,and intraoperative parameters(operative time,blood loss),were comparable between groups(all P>0.05).The ERAS protocol demonstrated significantly shorter postoperative length of stay(7.55±1.52 days vs 10.40±3.59 days,P<0.001)while complication rates were numerically lower in the ERAS group(17.50%vs 13.16%,P=0.595).Additional benefits of ERAS implementation included:Reduced intravenous fluid requirements(5.00 mL/kg/hour vs 8.00 mL/kg/hour),accelerated gastrointestinal recovery(first flatus:2.00 days vs 3.00 days),lower pain scores(P<0.001),earlier total enteral nutrition achievement(5.00 days vs 6.50 days)and shorter intravenous therapy duration(6.00 days vs 8.00 days;all P<0.001).ERAS patients also showed reduced drainage utilization(P<0.05)and improved inflammatory marker profiles postoperatively[neutrophils:(5.98±2.02)×10^(9)/L vs(8.01±3.98)×10^(9)/L];median Creactive protein:13.6 mg/L 7 vs 19.63 mg/L).Glycemic control was superior in the ERAS group despite higher induction levels(both P<0.05).Parental satisfaction(92.50%vs 86.84%)and 30-day readmission rates(2.50%vs 2.63%)showed no significant differences.CONCLUSION ERAS protocols safely optimize recovery in children undergoing laparoscopic Meckel’s diverticulum resection,significantly reducing length of stay while improving pain management and overall clinical outcomes.These findings support the adoption of ERAS in pediatric intestinal surgery.
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.
