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
BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been pr...BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.展开更多
This is an erratum to the published paper titled“Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts”.We have discovered that Reference 4 was cited incorrect...This is an erratum to the published paper titled“Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts”.We have discovered that Reference 4 was cited incorrectly.We sincerely apologize for this inadvertent error.Please note that these corrections do not impact our results.展开更多
Social and environmental factors render premature ovarian failure(POF) as a major cause of decline or loss of female fertility. The natural pregnancy rate of patients with POF is only 5%-10%. Follicular atresia is the...Social and environmental factors render premature ovarian failure(POF) as a major cause of decline or loss of female fertility. The natural pregnancy rate of patients with POF is only 5%-10%. Follicular atresia is the main factor in the pathogenesis of POF.Due to the unique ovarian physiological environment and follicular developmental processes, the apoptosis of ovarian granulosa cells and oocytes together cause follicular atresia, which involves the apoptosis-related internal and external pathways.Furthermore, during POF, apoptosis and oxidative stress forms a "vicious circle", which involves a variety of changes between the molecules. The existing pharmaceutical preparations such as gonadal hormones are the basic methods for the treatment of POF, and the curative effect was affirmative;however, it was ineffective after withdrawn, while the long-term application led to adverse reactions. Traditional Chinese Medicine(TCM) has a history of treating gynecological diseases and infertility and has gained increasing attention. Studies have shown that compounds isolated from herbal medicine exerted a positive effect on follicular atresia caused by cell apoptosis that also improved the POF. The present study reviewed the mechanisms underlying the apoptosis in POF and elaborated the internal mechanism of TCM in the treatment of the condition.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
The aim of our study was to compare the sperm retrieval rates(SRRs)and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sper...The aim of our study was to compare the sperm retrieval rates(SRRs)and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI).We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI.Patients with azoospermia were classified into Group A(Klinefelter syndrome,n=284,125 cycles),Group B(azoospermia Y chromosome factor c[AZFc]microdeletion,n=91,64 cycles),Group C(cryptorchidism,n=52,39 cycles),Group D(previous mumps and bilateral orchitis,n=23,23 cycles),and Group E(idiopathic azoospermia,n=319,96 cycles).Clinical characteristics,SRR,embryonic development,and pregnancy outcomes of the patients were compared between all groups.Patients in Group D had the highest and most successful SRR.The average SRR for all patients was 46.0%.The rates of clinical pregnancy,implantation,and live birth in Group D were 78.3%,65.0%,and 74.0%,respectively,which were higher than those in all other groups(P<0.05).Group B patients had the lowest clinical pregnancy,implantation,and live birth rates of all groups(P<0.05).No differences were found in the miscarriage rate or birth defects among the groups(P>0.05).Patients with orchitis had the highest SRR and best clinical outcomes.Although AZFc microdeletion patients had a higher SRR,their clinical outcomes were worse.展开更多
Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microar...Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.展开更多
Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous s...Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury （CNI） by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage （2 × 105 cells） of ADSCs for intracavernous injection （ICI） and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs （NanoADSCs） were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.展开更多
Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory.The new hypoglycemic drug dapagliflozin has shown c...Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory.The new hypoglycemic drug dapagliflozin has shown certain benefits,such as decreasing the risk of cardiovascular and renal events in patients with diabetes.Even so,until now,the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification.Here,we found that dapagliflozin lowered blood glucose levels,alleviated seminiferous tubule destruction,and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice.Moreover,the glucagon-like peptide-1 receptor(GLP-1R)antagonist exendin(9-39)had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice.We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2(BCL2)and X-linked inhibitor of apoptosis protein(XIAP)and inhibiting oxidative stress by enhancing the antioxidant status,including total antioxidant capacity,total superoxide dismutase(SOD)activity,and glutathione peroxidase(GPx)activity,as well as decreasing the level of 4-hydroxynonenal(4-HNE).Exendin(9-39)administration partially reversed these effects.Furthermore,dapagliflozin upregulated the glucagon-like peptide-1(GLP-1)level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog(Akt)phosphorylation in testicular tissue.Exendin(9-39)partially inhibited Akt phosphorylation.These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway.Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.展开更多
We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients wi...We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia(NOA).A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles(Group A).Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles(Group B).We compared patient characteristics,embryonic development,and pregnancy outcomes between Groups A and B.There was no statistical difference in the patient characteristics,and no differences were observed with fertilization or quality embryo rates between Groups A and B.The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B(both P<0.05).In conclusion,fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.展开更多
Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing m...Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE.This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021.The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval.The prediction model was constructed using acquired regression coefficients,and its predictive performance was assessed using the receiver operating characteristic curve.In all,67 patients(sperm retrieval rate:33.5%)underwent successful micro-TESE.Follicle-stimulating hormone,anti-Miillerian hormone,and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE.Binary logistic regression analysis yielded the following six predictors:anti-Mullerian hormone(odds ratio[OR]=0.902,95%confidence interval[Cl]:0.821-0.990),inhibin B(OR=1.012,95%Cl:1.001-1.024),Klinefelter’s syndrome(OR=0.022,95%Cl:0.002-0.243),Y chromosome microdeletion(OR=0.050,95%Cl:0.005-0.504),cryptorchidism with orchiopexy(OR=0.085,95%Cl:0.008-0.929),and idiopathic nonobstructive azoospermia(OR=0.031,95%Cl:0.003-0.277).The prediction model had an area under the curve of 0.720(95%Cl:0.645-0.794),sensitivity of 65.7%,specificity of 72.2%,Youden index of 0.379,and cut-off value of 0.305 overall,indicating good predictive value and accuracy.This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.展开更多
Previous studies suggest that air pollution has a negative effect on semen quality.However,most studies are cross-sectional and the results are controversial.This study investigated the associations between air pollut...Previous studies suggest that air pollution has a negative effect on semen quality.However,most studies are cross-sectional and the results are controversial.This study investigated the associations between air pollutants(PM25,PM10,SO2,NO2,CO,and O3)and seme n quality among sperm donation candidates,especially when the air pollution was artificially con trolled in Beijing,China.We an a lyzed 8945 semen samples in the human sperm bank of Peki ng Un iversity Third Hospital(Beijing,China)from October 2015 to May 2018.Air pollution data during the entire period(0-90 days prior)and key stages(0-9,10-14,and 70-90 days prior)of sperm development were collected from the China National Environmental Monitoring Centre.The association between air pollutants and seme n parameters(sperm con centrati on and progressive motility)was an a lyzed by a mixed model adjusted for age,abstinence duration,month,and average ambient temperature.Only O3 during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018(P v 0.01).During the period of air pollution control from November 2017 to January 2018,except for the in crease in O3 concentration,other five pollutants'concentrations decreased compared to those in previous years.In this period,the sperm concentration decreased(P<0.001).During the pollution-control period,O3 exposure 10-14 days prior was negatively associated with sperm concentration(95%Cl:-0.399—0.111;P<0.001).No significant association was found between the other five pollutants and semen quality during that period?Our study suggested that only O3 exposure was harmful to semen quality.Therefore,O3 should not be neglected during pollution control operation.展开更多
This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measu...This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that （1） The mean serum P level in LUF group （7.32±2.56 ng/mL） was significantly lower than that in control group （11.17±3.17 ng/mL） （P0.01）. But there was no significant difference in the mean serum E2 levels between LUF group （179.35±81.60 pg/mL） and the control group （198.58±75.23 pg/mL） （P0.05）; （2） The mean expression intensities of ER, PR in endometrium of LUF group （183.86±2.43, 167.94±3.04） were significantly higher than those in control group （109.35±6.31, 105.98±4.07） （P0.01）; （3） The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients （114.90±11.38） were significantly lower than those in control group （191.34±1.82） （P0.01）; （4） The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level （r=0.77, P0.01）, but bore no significant relationship with serum E2 level （r=0.01, P0.05）. It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.展开更多
Summary:The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain.To investigate the role of intrauterine insemination(IUI)in the treatment of inferti...Summary:The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain.To investigate the role of intrauterine insemination(IUI)in the treatment of infertile women with unilateral tubal occlusion,the data of 148 couples were retrospectively collected and analyzed.Seventy-eight infertile women with unilateral occlusion diagnosed by hysterosalpingography(HSG)were categorized as the study group and 70 others with unexplained infertility as the control group.The study group was divided into a proximal occlusion subgroup and a mid-distal occlusion subgroup for further analysis.The main outcomes,namely the clinical pregnancy rate(CPR),ongoing pregnancy rate(OPR),and live birth rate(LBR)per cycle,were analyzed.Our results showed a tendency of lower CPR,OPR,and LBR in the study group than in the control group,without statistical significance.Further investigations revealed that the unilateral proximal occlusion subgroup had similar CPR,OPR,and LBR as the control group,while the unilateral mid-distal occlusion subgroup had significantly lower CPR(5.1%vs.20.0%,P=0.035),OPR(5.1%vs.20.0%,P=0.035),and LBR(5.1%vs.20.0%,P=0.035)than the control group.In conclusion,the clinical outcomes of IUI were worse in patients with unilateral tubal occlusion than in those with unexplained infertility.This might be primarily caused by the worse outcome of patients with unilateral mid-distal tubal occlusion instead of proximal occlusion.展开更多
Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the...Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia(NOA)remain elusive.In this study,according to a circRNA array,a total of 37881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls,including 19874 upregulated circRNAs and 18007 downregulated circRNAs.Using quantitative real-time polymerase chain reaction(qRT-PCR)analysis,we confirmed that the change tendency of some specific circRNAs,including hsa_circ_0137890,hsa_circ_0136298,and hsa_circ_0007273,was consistent with the microarray data in another larger sample.The structures and characteristics of these circRNAs were confirmed by Sanger sequencing,and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm.Bioinformatics analysis was used to construct the competing endogenous RNA(ceRNA)network,and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly,microtubule-based processes,and cell proliferation were significantly enriched.Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers forNoA patients.展开更多
BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investi...BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.展开更多
RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to...RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical application.Herein,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA delivery.EGFR antibody was also modified to the surface of nanodrug to enhance the delivery effect.Our results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious cytotoxicity.Besides,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging capacity.The study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.展开更多
Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various age...Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.展开更多
Objective:To explore the clinical outcomes of the infertile women with retrieved oocytes less than or equal to 5 undergoing in vitro fertilization-embryo transfer（IVF-ET） or intracytoplasmic sperm injection（1CSI）....Objective:To explore the clinical outcomes of the infertile women with retrieved oocytes less than or equal to 5 undergoing in vitro fertilization-embryo transfer（IVF-ET） or intracytoplasmic sperm injection（1CSI）. Methods:The clinical data of 216 embryo transfer cycles with retrieved oocytes less than or equal to 5 during the procedure of IVF/ICSI in Reproductive Medicine Center of the 105th Hospital of PLA from Jul.2008 to Dec.2011 were analyze retrospectively.All the patients were divided into group A（< 35 years）,group B（35-39 years） and group C（≥40 years） according to the ages,and 409 IVF/ICSI cycles with patients’ age less than 35 years old and 6-15 retrieved oocytes in the same period were served as controlled group.Then the patients≥35 years were subdivided into gonadotropin-releasing hormone agonist（GnRH-a） long protocol group,GnRH-a short group and GnRH antagonist group according to the protocols of controlled ovarian hyperstimulation（COH）.The clinical date and the outcomes were analyzed and compared among all groups. Results:There were significantly differences in clinical pregnancy rate（38.3%vs.19.4%） and early abortion rate（16.1%vs.50.0%） between group A and group C（P<0.05）,and there were no significant differences in clinical pregnancy rate（38.3%vs.41.6%）and early abortion rate（16.1%vs.10.0%） between group A and control group（P>0.05）.There were no significant differences in clinical pregnancy rates（29.01%vs.26.1%vs.25.9%） and early abortion rates（33.3%vs.33.3%vs.40.0%） among GnRH-a long protocol group,GnRH-a short group and GnRH antagonist group（P>0.05）. Conclusions:Relatively satisfactory clinical outcomes of IVF/ICSI would still be got for the patients <35 years with retrieved oocytes less than or equal to 5,but whatever COH protocols such as GnRH-a long protocol,GnRH-a short and GnRH antagonist could not improve the outcomes of IVF/ICSI for the patients aged≥35 with retrieved oocytes less than or equal to 5.展开更多
BACKGROUND This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure....BACKGROUND This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure.CASE SUMMARY Here,we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital.We also detected the whole-exon gene of the patient's spouse and parents,and conducted bioinformatics analysis to determine the pathogenesis of the gene.CONCLUSION A novel mutant of the TUBB8 gene[c.602G>T(p.C201F)]was identified,and this mutant provided new data on the genotype-phenotype relationships of related diseases.展开更多
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 Suzhou Science and Technology Project,No.SYS2019053.
文摘BACKGROUND Prostate cancer(PCa)is a widespread malignancy,predominantly affecting elderly males,and current methods for diagnosis and treatment of this disease continue to fall short.The marker Ki-67(MKI67)has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells,including those of PCa.Hence,verifying the association between MKI67 and the diagnosis and prognosis of PCa,using bioinformatics databases and clinical data analysis,carries significant clinical implications.AIM To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa.METHODS For cohort 1,the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.For cohort 2,the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa.RESULTS In cohort 1,MKI67 expression was correlated with prostate-specific antigen(PSA),Gleason Score,T stage,and N stage.The receiver operating characteristic(ROC)curve showed a strong diagnostic ability,and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval(PFI).The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa.In cohort 2,MKI67 expression was significantly related to the Gleason Score,T stage,and N stage;however,it was negatively associated with the PFI.The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa.Multivariate COX regression analysis was performed to select risk factors,including PSA level,N stage,and MKI67 expression.A nomogram was established to predict the 3-year PFI.CONCLUSION MKI67 expression was positively associated with the Gleason Score,T stage,and N stage and showed a strong diagnostic and prognostic ability in PCa.
文摘This is an erratum to the published paper titled“Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts”.We have discovered that Reference 4 was cited incorrectly.We sincerely apologize for this inadvertent error.Please note that these corrections do not impact our results.
基金Supported by the National Natural Science Foundation of China (NSFC)(No.81170571)Excellent Talents Training Program of Shanghai Health System (No.XBR2011067)。
文摘Social and environmental factors render premature ovarian failure(POF) as a major cause of decline or loss of female fertility. The natural pregnancy rate of patients with POF is only 5%-10%. Follicular atresia is the main factor in the pathogenesis of POF.Due to the unique ovarian physiological environment and follicular developmental processes, the apoptosis of ovarian granulosa cells and oocytes together cause follicular atresia, which involves the apoptosis-related internal and external pathways.Furthermore, during POF, apoptosis and oxidative stress forms a "vicious circle", which involves a variety of changes between the molecules. The existing pharmaceutical preparations such as gonadal hormones are the basic methods for the treatment of POF, and the curative effect was affirmative;however, it was ineffective after withdrawn, while the long-term application led to adverse reactions. Traditional Chinese Medicine(TCM) has a history of treating gynecological diseases and infertility and has gained increasing attention. Studies have shown that compounds isolated from herbal medicine exerted a positive effect on follicular atresia caused by cell apoptosis that also improved the POF. The present study reviewed the mechanisms underlying the apoptosis in POF and elaborated the internal mechanism of TCM in the treatment of the condition.
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This research was sponsored by the National Key Research and Development Project(SQ2018YFC100243)National Key Research and Development Project(2016YFC1000302)+4 种基金National Key Research and Developmental Program of China(2018YFC1003600)Young Scientists Fund of the National NaturalScience Foundation of China(Grant No.81601272)Clinical MedicinePlusX-Young Scholars Project,Peking University(Grant No.2102018237)Beijing Municipal Natural Science Foundation(7182177)National KeyResearch and Development Program of China(Grant No.2017YFC1002001).
文摘The aim of our study was to compare the sperm retrieval rates(SRRs)and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI).We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI.Patients with azoospermia were classified into Group A(Klinefelter syndrome,n=284,125 cycles),Group B(azoospermia Y chromosome factor c[AZFc]microdeletion,n=91,64 cycles),Group C(cryptorchidism,n=52,39 cycles),Group D(previous mumps and bilateral orchitis,n=23,23 cycles),and Group E(idiopathic azoospermia,n=319,96 cycles).Clinical characteristics,SRR,embryonic development,and pregnancy outcomes of the patients were compared between all groups.Patients in Group D had the highest and most successful SRR.The average SRR for all patients was 46.0%.The rates of clinical pregnancy,implantation,and live birth in Group D were 78.3%,65.0%,and 74.0%,respectively,which were higher than those in all other groups(P<0.05).Group B patients had the lowest clinical pregnancy,implantation,and live birth rates of all groups(P<0.05).No differences were found in the miscarriage rate or birth defects among the groups(P>0.05).Patients with orchitis had the highest SRR and best clinical outcomes.Although AZFc microdeletion patients had a higher SRR,their clinical outcomes were worse.
文摘Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
基金This research was supported by the Beijing Natural Science Foundation （Grant No. 7174362） and the National Natural Science Foundation of China （Grant No. 81601272）.
文摘Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury （CNI） by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage （2 × 105 cells） of ADSCs for intracavernous injection （ICI） and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs （NanoADSCs） were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.
基金This work was supported by the National Natural Science Foundation of China(81901535 and 82071698)the Natural Science Foundation of Beijing Municipality(7222208)the National Key Research&Developmental Program of China(2021YFC2700203).
文摘Male diabetic individuals present a marked impairment in fertility;however,knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory.The new hypoglycemic drug dapagliflozin has shown certain benefits,such as decreasing the risk of cardiovascular and renal events in patients with diabetes.Even so,until now,the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification.Here,we found that dapagliflozin lowered blood glucose levels,alleviated seminiferous tubule destruction,and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice.Moreover,the glucagon-like peptide-1 receptor(GLP-1R)antagonist exendin(9-39)had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice.We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2(BCL2)and X-linked inhibitor of apoptosis protein(XIAP)and inhibiting oxidative stress by enhancing the antioxidant status,including total antioxidant capacity,total superoxide dismutase(SOD)activity,and glutathione peroxidase(GPx)activity,as well as decreasing the level of 4-hydroxynonenal(4-HNE).Exendin(9-39)administration partially reversed these effects.Furthermore,dapagliflozin upregulated the glucagon-like peptide-1(GLP-1)level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog(Akt)phosphorylation in testicular tissue.Exendin(9-39)partially inhibited Akt phosphorylation.These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway.Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.
基金This research was sponsored by the National Key Research and Development Projects(No.2018YFC1003600,2016YFC1000302,2017YFC1002001 and SQ2018YFC100243)the Clinical Medicine PlusX Young Scholars Project,Peking University(No.2102018237)the Beijing Municipal Natural Science Foundation(No.7182177).
文摘We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia(NOA).A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles(Group A).Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles(Group B).We compared patient characteristics,embryonic development,and pregnancy outcomes between Groups A and B.There was no statistical difference in the patient characteristics,and no differences were observed with fertilization or quality embryo rates between Groups A and B.The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B(both P<0.05).In conclusion,fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.
基金supported by a grant from the Peking University Clinical Medicine Youth Special Fund(PKU20222LCXQ042).
文摘Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE.This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021.The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval.The prediction model was constructed using acquired regression coefficients,and its predictive performance was assessed using the receiver operating characteristic curve.In all,67 patients(sperm retrieval rate:33.5%)underwent successful micro-TESE.Follicle-stimulating hormone,anti-Miillerian hormone,and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE.Binary logistic regression analysis yielded the following six predictors:anti-Mullerian hormone(odds ratio[OR]=0.902,95%confidence interval[Cl]:0.821-0.990),inhibin B(OR=1.012,95%Cl:1.001-1.024),Klinefelter’s syndrome(OR=0.022,95%Cl:0.002-0.243),Y chromosome microdeletion(OR=0.050,95%Cl:0.005-0.504),cryptorchidism with orchiopexy(OR=0.085,95%Cl:0.008-0.929),and idiopathic nonobstructive azoospermia(OR=0.031,95%Cl:0.003-0.277).The prediction model had an area under the curve of 0.720(95%Cl:0.645-0.794),sensitivity of 65.7%,specificity of 72.2%,Youden index of 0.379,and cut-off value of 0.305 overall,indicating good predictive value and accuracy.This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.
基金This research was supported by the Key Program of National Natural Science Foundation of China(Grant No.81630087 and 81601272)the National Key Research and Development Program of China(Grant No.2017YFC1002001).All these sponsors had no role in the study design,in the collection,analysis,and interpretation of data,in the writing of the report,or in the decision to submit the article for publication.
文摘Previous studies suggest that air pollution has a negative effect on semen quality.However,most studies are cross-sectional and the results are controversial.This study investigated the associations between air pollutants(PM25,PM10,SO2,NO2,CO,and O3)and seme n quality among sperm donation candidates,especially when the air pollution was artificially con trolled in Beijing,China.We an a lyzed 8945 semen samples in the human sperm bank of Peki ng Un iversity Third Hospital(Beijing,China)from October 2015 to May 2018.Air pollution data during the entire period(0-90 days prior)and key stages(0-9,10-14,and 70-90 days prior)of sperm development were collected from the China National Environmental Monitoring Centre.The association between air pollutants and seme n parameters(sperm con centrati on and progressive motility)was an a lyzed by a mixed model adjusted for age,abstinence duration,month,and average ambient temperature.Only O3 during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018(P v 0.01).During the period of air pollution control from November 2017 to January 2018,except for the in crease in O3 concentration,other five pollutants'concentrations decreased compared to those in previous years.In this period,the sperm concentration decreased(P<0.001).During the pollution-control period,O3 exposure 10-14 days prior was negatively associated with sperm concentration(95%Cl:-0.399—0.111;P<0.001).No significant association was found between the other five pollutants and semen quality during that period?Our study suggested that only O3 exposure was harmful to semen quality.Therefore,O3 should not be neglected during pollution control operation.
文摘This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that （1） The mean serum P level in LUF group （7.32±2.56 ng/mL） was significantly lower than that in control group （11.17±3.17 ng/mL） （P0.01）. But there was no significant difference in the mean serum E2 levels between LUF group （179.35±81.60 pg/mL） and the control group （198.58±75.23 pg/mL） （P0.05）; （2） The mean expression intensities of ER, PR in endometrium of LUF group （183.86±2.43, 167.94±3.04） were significantly higher than those in control group （109.35±6.31, 105.98±4.07） （P0.01）; （3） The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients （114.90±11.38） were significantly lower than those in control group （191.34±1.82） （P0.01）; （4） The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level （r=0.77, P0.01）, but bore no significant relationship with serum E2 level （r=0.01, P0.05）. It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.
基金This study was supported by grants from the Research Team of Female Reproductive Health and Fertility Preservation(No.SZSM201612065)Project for Medical Discipline Advancement of Health and Family Planning Commission of Shenzhen Municipality(No.SZXJ2017003).
文摘Summary:The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain.To investigate the role of intrauterine insemination(IUI)in the treatment of infertile women with unilateral tubal occlusion,the data of 148 couples were retrospectively collected and analyzed.Seventy-eight infertile women with unilateral occlusion diagnosed by hysterosalpingography(HSG)were categorized as the study group and 70 others with unexplained infertility as the control group.The study group was divided into a proximal occlusion subgroup and a mid-distal occlusion subgroup for further analysis.The main outcomes,namely the clinical pregnancy rate(CPR),ongoing pregnancy rate(OPR),and live birth rate(LBR)per cycle,were analyzed.Our results showed a tendency of lower CPR,OPR,and LBR in the study group than in the control group,without statistical significance.Further investigations revealed that the unilateral proximal occlusion subgroup had similar CPR,OPR,and LBR as the control group,while the unilateral mid-distal occlusion subgroup had significantly lower CPR(5.1%vs.20.0%,P=0.035),OPR(5.1%vs.20.0%,P=0.035),and LBR(5.1%vs.20.0%,P=0.035)than the control group.In conclusion,the clinical outcomes of IUI were worse in patients with unilateral tubal occlusion than in those with unexplained infertility.This might be primarily caused by the worse outcome of patients with unilateral mid-distal tubal occlusion instead of proximal occlusion.
基金supported by the National Natural Science Foundation of China(No.81901535,No.82071698)the National Key Research and Developmental Program of China(No.2021YFC2700203)the Natural Science Foundation of Beijing Municipality(No.722208).
文摘Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia(NOA)remain elusive.In this study,according to a circRNA array,a total of 37881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls,including 19874 upregulated circRNAs and 18007 downregulated circRNAs.Using quantitative real-time polymerase chain reaction(qRT-PCR)analysis,we confirmed that the change tendency of some specific circRNAs,including hsa_circ_0137890,hsa_circ_0136298,and hsa_circ_0007273,was consistent with the microarray data in another larger sample.The structures and characteristics of these circRNAs were confirmed by Sanger sequencing,and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm.Bioinformatics analysis was used to construct the competing endogenous RNA(ceRNA)network,and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly,microtubule-based processes,and cell proliferation were significantly enriched.Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers forNoA patients.
基金Supported by China Postdoctoral Science Foundation,No.2019M661521and National Natural Science Foundation of China,No.82001634.
文摘BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.
基金financially supported by the National Natural Science Foundation of China (Nos. 52173125 and 21805314)the Key Areas Research and Development Program of Guangzhou (No.202007020006)Natural Science Foundation of the Guangdong Province (No. 2021A1515010250)
文摘RNA interference(RNAi),known for the highly efficient targeted gene silencing,has been demonstrated to be a promising means for cancer treatment.Meanwhile,an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical application.Herein,we constructed a polymeric vector labeled with superparamagnetic iron oxide(SPIO)for magnetic resonance imaging(MRI)visible siRNA delivery.EGFR antibody was also modified to the surface of nanodrug to enhance the delivery effect.Our results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious cytotoxicity.Besides,both in vitro and in vivo studies evidenced the vector could effectively deliver siRNA into tumor cells,exert highly interfering effect,and show potent MR imaging capacity.The study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.
文摘Objective This study examined humanin expression in rat ovarian tissue,its cellular localization,and its correlation with rat age under physiological conditions.Methods A total of 40 Sprague-Dawley rats of various ages(2,12,30,and 60 days old and 1 year old)were grouped by age.Immunofluorescence and immunohistochemical techniques were used to observe humanin expression and cellular location in the ovarian tissues of rats from each age group.In addition,Western blotting and Real-time quantitative reverse transcription PCR(qRT-PCR)techniques were used to measure humanin expression level in the ovarian tissues of rats from each age group.Results The immunofluorescence and immunohistochemical results confirmed that humanin was expressed in rat ovarian tissues.In addition,cellular localization analysis showed that humanin was expressed in the cytoplasm of oocytes,interstitial cells,granulosa cells and theca cells in all levels of follicles after the primary follicles,and in the corpus luteum.The qRT-PCR results revealed that the level of humanin expression in the ovarian tissues of 12-day-old rats was non-significantly higher than that in the ovarian tissues of 2-day-old rats(P>0.05),whereas the levels of humanin expression in the ovarian tissues of 30-day-old,60-day-old,and 1-year-old rats were significantly lower than that in the ovarian tissues of 2-day-old rats(P<0.05).The Western blotting results demonstrated that the levels of humanin protein expression in the ovarian tissues of 60-day-old and 1-year-old rats were significantly lower than those of 2-day-old rats(P<0.01),whereas there was no significant difference in the level of humanin protein expression between the ovarian tissues of 12-day-old and 30-day-old rats.Conclusion This study confirmed that humanin is expressed in the cytoplasm of various cells in rat ovarian tissues.Moreover,the level of humanin expression was highest in the ovarian tissues of 12-day-old rats,and it subsequently decreased with age.The changes in the expression of humanin in the ovary of rats at different ages will lay the foundation for the role of humanin in ovarian aging.The effect of humanin on ovarian function is worthy of further study in the future.
文摘Objective:To explore the clinical outcomes of the infertile women with retrieved oocytes less than or equal to 5 undergoing in vitro fertilization-embryo transfer（IVF-ET） or intracytoplasmic sperm injection（1CSI）. Methods:The clinical data of 216 embryo transfer cycles with retrieved oocytes less than or equal to 5 during the procedure of IVF/ICSI in Reproductive Medicine Center of the 105th Hospital of PLA from Jul.2008 to Dec.2011 were analyze retrospectively.All the patients were divided into group A（< 35 years）,group B（35-39 years） and group C（≥40 years） according to the ages,and 409 IVF/ICSI cycles with patients’ age less than 35 years old and 6-15 retrieved oocytes in the same period were served as controlled group.Then the patients≥35 years were subdivided into gonadotropin-releasing hormone agonist（GnRH-a） long protocol group,GnRH-a short group and GnRH antagonist group according to the protocols of controlled ovarian hyperstimulation（COH）.The clinical date and the outcomes were analyzed and compared among all groups. Results:There were significantly differences in clinical pregnancy rate（38.3%vs.19.4%） and early abortion rate（16.1%vs.50.0%） between group A and group C（P<0.05）,and there were no significant differences in clinical pregnancy rate（38.3%vs.41.6%）and early abortion rate（16.1%vs.10.0%） between group A and control group（P>0.05）.There were no significant differences in clinical pregnancy rates（29.01%vs.26.1%vs.25.9%） and early abortion rates（33.3%vs.33.3%vs.40.0%） among GnRH-a long protocol group,GnRH-a short group and GnRH antagonist group（P>0.05）. Conclusions:Relatively satisfactory clinical outcomes of IVF/ICSI would still be got for the patients <35 years with retrieved oocytes less than or equal to 5,but whatever COH protocols such as GnRH-a long protocol,GnRH-a short and GnRH antagonist could not improve the outcomes of IVF/ICSI for the patients aged≥35 with retrieved oocytes less than or equal to 5.
基金Supported by the Shandong Provincial Traditional Chinese Medicine Science and Technology Development Program,No.C-262the 2021 Science and Technology Innovation Research Project of Shandong Maternal and Child Health Association,No.2021-19-24.
文摘BACKGROUND This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure.CASE SUMMARY Here,we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital.We also detected the whole-exon gene of the patient's spouse and parents,and conducted bioinformatics analysis to determine the pathogenesis of the gene.CONCLUSION A novel mutant of the TUBB8 gene[c.602G>T(p.C201F)]was identified,and this mutant provided new data on the genotype-phenotype relationships of related diseases.
