In this study, we aimed to determine the effects of hepatitis B virus （HBV） infection on sperm quality and the outcome of assisted reproductive technology （ART）. A total of 916 men （457 HBV-positive and 459 HBV-n...In this study, we aimed to determine the effects of hepatitis B virus （HBV） infection on sperm quality and the outcome of assisted reproductive technology （ART）. A total of 916 men （457 HBV-positive and 459 HBV-negative） seeking fertility assistance from January 2008 to December 2009 at the Women＇s Hospital in the School of Medicine at Zhejiang University were analysed for semen parameters. Couples in which the men were hepatitis B surface antigen （HBsAg）-seropositive were categorized as HBV-positive and included 587 in vitrofertilisation （IVF） and 325 intracytoplasmic sperm injection （ICSI） cycles from January 2004 to December 2009; negative controls were matched for female age, date of ova retrieval, ART approach used （IVF or ICSI） and randomized in a ratio of 1：1 according to the ART treatment cycles （587 for IVF and 325 for ICSI）. HBV-infected men exhibited lower semen volume, lower total sperm count as well as poor sperm motility and morphology （P〈O.05） when compared to control individuals. Rates of two-pronuclear （2PN） fertilisation, high-grade embryo acquisition, implantation and clinical pregnancy were also lower among HBV-positive patients compared to those of HBV-negative patients after ICSI and embryo transfer （P〈0.05）; IVF outcomes were similar between the two groups （P〉0.05）. Logistic regression analysis showed that HBV infection independently contributed to increased rates of asthenozoospermia and oligozoospermia/azoospermia （P〈0.05） as well as decreased rates of implantation and clinical pregnancy in ICSI cycles （P〈0.05）. Our results suggest that HBV infection in men is associated with poor sperm quality and worse ICSI and embryo transfer outcomes but does not affect the outcome of IVF and embryo transfer.展开更多
Over the course of the past 35 years,assisted reproductive technologies(ARTs)have been increasingly used worldwide,while debates on their safety have been generated.Birth defects and imprinting disorders were reported...Over the course of the past 35 years,assisted reproductive technologies(ARTs)have been increasingly used worldwide,while debates on their safety have been generated.Birth defects and imprinting disorders were reported in previous research.Thus,the psychological development of children born following ARTs has become a major concern nowadays.This review gives a systematic view of psychological well-being of children conceived by different types of ART,including in vitro fertilization,intracytoplasmic sperm injection(ICSI),preimplantation genetic diagnosis/screening,and in vitro maturation.The previous studies are analyzed in three sections:(1)cognitive,motor,and language developments,(2)behavior problems and socio-emotional development,and(3)parent-child relationship.We conclude that although the majority of the studies on cognitive,motor,and language developments reported comparable achievements in the ART group vs.the naturally conceived group,lower intelligence quotient(IQ)scores,worse visual-motor ability or locomotor development,and delayed receptive language competence were found in the ART group.The results on the socio-emotional development were reassuring.As for the behavior problems,a higher prevalence of behavior problems existed in ART children;moreover,ICSI children were found to be at a higher risk of autism than the general population.Meanwhile,ART parents tended to have positive parental attitudes and be more protective of their children.Some suggestions for further research are also given in this review.展开更多
Objective To evaluate the impacts of reproductive tract infections （RTIs） intervention on RTIs-related knowledge, attitudes, practices and prevalence of married women at reproductive age. Methods Four sub-districts ...Objective To evaluate the impacts of reproductive tract infections （RTIs） intervention on RTIs-related knowledge, attitudes, practices and prevalence of married women at reproductive age. Methods Four sub-districts from Xuhui district, Shanghai were selected by multistage cluster random sampling and residence committees were randomly assigned to either an intervention group or a control one. RTIs intervention was implemented in intervention group, while routine family planning program was conducted in control group. Results Compared with control group, intervention group have improved the following targets： the increment of RTI knowledge score was higher than that in control group （OR=9. 22, 95%CI： 7.01 - 2.14）; the increment score of individual health behaviors （6. 31） was higher than that in control group （4.50） （OR=1.60, 95%CI： 1.21 -2.10）; the increase of condom use frequency in intervention group was higher than that in control group （4.12% vs 0.69%） （OR=1.84, 95%CI： 1.31-2.57）; the decreased RTIs rate was higher than that in control group （7.45% vs 0.96%） （OR=0.68, 95%CI： 0.49-0.95）. Conclusion It is an effective way to conduct community-based intervention to increase women＇s RTIs knowledge, improve RTIs-related attitudes, promote good individual health behaviors, so as to decrease RTIs prevalence.展开更多
Objectives:To investigate the effect of sperm DNA fragmentation on outcomes of in vitro fertilization(IVF) and intracytoplasmic sperm injection(ICSI). Methods:A total of 242 cycles(154 IVF and 88 ICSI) from 235 couple...Objectives:To investigate the effect of sperm DNA fragmentation on outcomes of in vitro fertilization(IVF) and intracytoplasmic sperm injection(ICSI). Methods:A total of 242 cycles(154 IVF and 88 ICSI) from 235 couples were included.Sperm DNA fragmentation(SDF) and routine semen analysis were performed on the retrieval day.The rates of fertilization, embryo cleavage,good quality embryos,implantation and clinical pregnancy were measured. Results:Sperm DNA fragmentation index(DFI) in ICSI group was significantly higher than that in IVF group (P<0.01).The rates of fertilization,implantation and clinical pregnancy in ICSI were significantly higher than those in IVF with DFI≥24%(P<0.05).When DFI exceeded 24%,the OR for clinical pregnancy was 3.85(95% CI 1.40-10.59) comparing ICSI with IVF,and the OR for clinical pregnancy increased to 4.61(95%CI 1.09- 19.57) after inclusion of sperm concentration,progressively motile sperm percentage and female age as covariates. Conclusions:High DNA fragmentation might affect the outcome of ICSI and IVF.When DFI exceeds 24%, ICSI should be chosen instead of IVF.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
Background:Shilajit is mentioned in the“Kama Sutra”as a potent enhancer of sexual desire.This study aimed to investigate the effects of oral Shilajit tablets on sexual function and sexual quality of life among women...Background:Shilajit is mentioned in the“Kama Sutra”as a potent enhancer of sexual desire.This study aimed to investigate the effects of oral Shilajit tablets on sexual function and sexual quality of life among women of reproductive age.Methods:Forty-eight reproductive-aged women participated in a placebo-controlled triple-blind clinical trial.The intervention group took oral Shilajit tablets(200 mg)twice daily for 60 days and the control group took the placebo.Data collection tools were Sexual Quality of Life-Female and Female Sexual Function Index.Data were collected before the intervention,30,60,and 90 days after the start of the study.Results:Forty-three women completed the study.The mean score of total sexual function in the intervention group was significantly higher than before the intervention(P<0.001).The mean score of sexual function was 28.93 after 90 days in the intervention group while it was 22.09 in the control group.This finding was observed in most domains of the sexual function index.The mean score of sexual quality of life increased after 60 days of intervention in both groups;however,the difference was not statistically significant(P=0.094).Conclusion:The study indicated that Shilajit,as a complementary therapy,may improve sexual function and most of its domains;while there was no effect on improving the quality of sexual life.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parame...This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parameters.These pathogens included Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,Pseudomonas aeruginosa,and Staphylococcus aureus.A total of 1951 men of infertile couples were recruited between 23 March 2023,and 17 May 2023,at the Department of Reproductive Medicine of The First People’s Hospital of Yunnan Province(Kunming,China).Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping.Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs.The overall prevalence of HPV infection was 12.4%.The top five prevalent HPV subtypes were types 56,52,43,16,and 53 among those tested positive for HPV.Other common infections with high prevalence rates were Ureaplasma urealyticum(28.3%),Ureaplasma parvum(20.4%),and Enterococcus faecalis(9.5%).The prevalence rates of HPV coinfection with Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,and Staphylococcus aureus were 24.8%,25.4%,10.6%,6.4%,2.4%,7.9%,5.9%,0.9%,and 1.3%,respectively.The semen volume and total sperm count were greatly decreased by HPV infection alone.Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability.Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters,emphasizing the necessity of semen screening for STIs.展开更多
Objective:To assess whether personalized embryo transfer guided by endometrial receptivity array(ERA)improves implantation and pregnancy rates in women with implantation failure.Methods:This retrospective case-control...Objective:To assess whether personalized embryo transfer guided by endometrial receptivity array(ERA)improves implantation and pregnancy rates in women with implantation failure.Methods:This retrospective case-control study was conducted on women with previous implantation failure.The women were divided into two groups,i.e,women who underwent ERA and those who underwent embryo transfer without ERA testing.ERA was performed using Igenomix.ERA results were interpreted as receptive or non-receptive.Women underwent frozen embryo transfer on the 6th day of progesterone(P+5).The primary outcomes were implantation rate,clinical pregnancy rate,abortion rate,and negative pregnancy rate.Results:This study included 229 women with previous implantation failure,with 154 in the ERA group and 75 in the no ERA group.The mean age of the women of the ERA group was(32.2±4.1)years,and that of the no ERA group was(31.5±4.8)years.Women in the ERA group had a higher implantation rate(60.4%)and clinical pregnancy rate(57.1%)compared to those in the no ERA group(48.0%and 46.7%,respectively).In addition,implantation rate of the nonreceptive ERA group was higher than the no ERA group(65%vs.48%),and clinical pregnancy rate was also higher in the non-receptive ERA group than the no ERA group(65%vs.47%).The abortion rate of the no ERA group was 9%and that of the non-receptive ERA group was 10%.52%no ERA group women and 35%non-receptive ERA group women had negative pregnancy results.Conclusions:Women who have undergone personalised embryo transfer guided by ERA have a higher clinical pregnancy rate than women who have not after previous implantation failure.展开更多
Insulin-like growth factor 2(IGF2)is a critical endocrine mediator implicated in male reproductive physiology.To investigate the correlation between IGF2 protein levels and various aspects of male infertility,specific...Insulin-like growth factor 2(IGF2)is a critical endocrine mediator implicated in male reproductive physiology.To investigate the correlation between IGF2 protein levels and various aspects of male infertility,specifically focusing on sperm quality,inflammation,and DNA damage,a cohort of 320 male participants was recruited from the Women’s Hospital,Zhejiang University School of Medicine(Hangzhou,China)between 1^(st) January 2024 and 1^(st) March 2024.The relationship between IGF2 protein concentrations and sperm parameters was assessed,and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility.Enzyme-linked immunosorbent assay(ELISA)was used to measure IGF2 protein levels in seminal plasma,alongside markers of inflammation(tumor necrosis factor-alpha[TNF-α]and interleukin-1β[IL-1β]).The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX(γ-H2AX)was also explored.Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia.Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters,and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm.The observed correlations between IGF2 protein levels and specific sperm parameters,along with its connection to inflammation and DNA damage,underscore the importance of IGF2 in the broader context of male reproductive health.These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.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
Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal ves...Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.展开更多
BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermat...BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermatitis who developed a nonhealing wound after lumbar spinal surgery.The wound was successfully treated with vacuum sealing drainage therapy,confirming its feasibility in complex wound healing.CASE SUMMARY The patient was a 76-year-old female with lung cancer,positron emission tomography/computed tomography showed bone metastasis in L2 and L3 vertebrae.After 2 months of local radiotherapy to the lumbar spine,symptoms did not improve and pain worsened.She had lumbar lesion clearance and internal fixation surgery,but developed a nonhealing wound of approximately 15 cm postoperatively.After 12 rounds of clearing necrotic and unhealthy tissue,78 days of negative pressure therapy promoted granulation tissue growth and wound healing,resulting in wound healing.CONCLUSION Vacuum sealing drainage therapy has shown efficacy in treating nonhealing wounds after radiotherapy,promoting wound healing and reducing infection risk.展开更多
Periplocin,periplocymarin and periplogenin are the main active components of Cortex Periplocae.The most cytotoxic constituent of Cortex Periplocae,periplocin is an alpha cardiac glycoside with a steroid core and an un...Periplocin,periplocymarin and periplogenin are the main active components of Cortex Periplocae.The most cytotoxic constituent of Cortex Periplocae,periplocin is an alpha cardiac glycoside with a steroid core and an unsaturated five-membered lactone ring structure.Periplocymarin is a secondary alpha cardiac glycoside,which is produced by removing one molecule of glucose from periplocin,and periplogenin is the glycosidic portion and the basic unit of periplocin and periplocymarin.These three cardiac glycosides,by virtue of their unique pharmacological activities and mechanisms of action,mediate signaling pathways,mainly the retinoblastoma and p53 signaling pathways,and regulate cell cycle proteins,thereby hindering the proliferation of cancer cells and altering the cell cycle process.These glycosides also regulate caspase proteins by mediating endogenous and exogenous pathways,thereby inducing the apoptosis of cancer cells.This minireview focuses on the inhibitory effects of periplocin,periplocymarin and periplogenin on cancer,and explores their potential antitumor mechanisms.展开更多
Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the dev...Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.展开更多
Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We ...Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells(m ESCs).Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation;mice treated with only normal saline served as controls.Hyperstimulation resulted in high serum estrogen levels,enlarged ovaries,an increased number of aberrant oocytes,and decreased embryo formation.The messenger RNA(m RNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b(Kdm6b),which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos.In vitro,Kdm6b expression was downregulated in m ESCs treated with high-dose estrogen;treatment with an estrogen receptor antagonist could reverse this downregulated expression level.Furthermore,treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation(H3K27me3)and phosphorylated H2A histone family member X(γ-H2AX).Notably,knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies,with a concomitant increase in the expression of H3K27me3 andγ-H2AX.Collectively,our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression.Accordingly,Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.展开更多
BACKGROUND Carriers of chromosomal balanced translocations are often physically healthy with no obvious developmental problems.However,potential chromosomal imbalance in their gametes can lead to implantation failure,...BACKGROUND Carriers of chromosomal balanced translocations are often physically healthy with no obvious developmental problems.However,potential chromosomal imbalance in their gametes can lead to implantation failure,miscarriage,or the birth of a child with a chromosomal abnormality.CASE SUMMARY We report six cases of chromosomal translocations involving three families,including the specific Robertson(Roche)translocation.Case 1:The karyotype of the proband was 46,XX,t(18;19)(q22;p12).Case 2:Interventional prenatal diagnosis at 18 weeks of gestation confirmed that the karyotype of the fetus was 46,XY,t(18;19)(q22;p12).Case 3:The karyotype of the proband was 46,XY,t(5;18)(p13;p11).Case 4:Interventional prenatal diagnosis at 14+6 weeks confirmed that the karyotype of the fetus was 46,XX,der(18)t(5;18)(p13;p11)pat.Case 5:The karyotype of the proband was 45,XY,der(14;22)(q10;q10).Case 6:Interventional prenatal diagnosis at 19+4 weeks confirmed that the karyotype of the fetus was 45,XX,rob(14;22)(q10;q10).CONCLUSION Carriers of chromosomal translocations have a high risk of adverse pregnancy outcomes,though they can still have normal offspring.This report on six cases of chromosomal translocations from three families could serve as a reference for future prenatal diagnosis of chromosomal translocations and decision-making on whether to continue the pregnancy.展开更多
Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion...Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.展开更多
Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and mi...Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and microdissection testicular sperm extraction(micro-TESE)is the procedure of choice for men with NOA desiring to father children with their own gametes.Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection(ICSI)in comparison to all other techniques for surgical sperm retrieval in men with NOA.Several factors may affect sperm retrieval rate and ICSI outcomes,including the patient’s age,testicular volume,histopathological and genetic profile,and serum hormone levels.This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.展开更多
基金This work was supported by a grant from the Natural Science Foundation of Zhejiang Province, China （Y206148）. The authors gratefully acknowledge the members of the Department of Reproductive Endocrinology in the Women＇s Hospital at Zhejiang University for their continued assistance.
文摘In this study, we aimed to determine the effects of hepatitis B virus （HBV） infection on sperm quality and the outcome of assisted reproductive technology （ART）. A total of 916 men （457 HBV-positive and 459 HBV-negative） seeking fertility assistance from January 2008 to December 2009 at the Women＇s Hospital in the School of Medicine at Zhejiang University were analysed for semen parameters. Couples in which the men were hepatitis B surface antigen （HBsAg）-seropositive were categorized as HBV-positive and included 587 in vitrofertilisation （IVF） and 325 intracytoplasmic sperm injection （ICSI） cycles from January 2004 to December 2009; negative controls were matched for female age, date of ova retrieval, ART approach used （IVF or ICSI） and randomized in a ratio of 1：1 according to the ART treatment cycles （587 for IVF and 325 for ICSI）. HBV-infected men exhibited lower semen volume, lower total sperm count as well as poor sperm motility and morphology （P〈O.05） when compared to control individuals. Rates of two-pronuclear （2PN） fertilisation, high-grade embryo acquisition, implantation and clinical pregnancy were also lower among HBV-positive patients compared to those of HBV-negative patients after ICSI and embryo transfer （P〈0.05）; IVF outcomes were similar between the two groups （P〉0.05）. Logistic regression analysis showed that HBV infection independently contributed to increased rates of asthenozoospermia and oligozoospermia/azoospermia （P〈0.05） as well as decreased rates of implantation and clinical pregnancy in ICSI cycles （P〈0.05）. Our results suggest that HBV infection in men is associated with poor sperm quality and worse ICSI and embryo transfer outcomes but does not affect the outcome of IVF and embryo transfer.
基金Project supported by the National Basic Research Program(973)of China(No.2012CB944901)the National Natural Science Foundation of China(Nos.81070532 and 81070541)the Zhejiang Provincial Natural Science Foundation of China(Nos.Y2100822 andLZ13H040001)
文摘Over the course of the past 35 years,assisted reproductive technologies(ARTs)have been increasingly used worldwide,while debates on their safety have been generated.Birth defects and imprinting disorders were reported in previous research.Thus,the psychological development of children born following ARTs has become a major concern nowadays.This review gives a systematic view of psychological well-being of children conceived by different types of ART,including in vitro fertilization,intracytoplasmic sperm injection(ICSI),preimplantation genetic diagnosis/screening,and in vitro maturation.The previous studies are analyzed in three sections:(1)cognitive,motor,and language developments,(2)behavior problems and socio-emotional development,and(3)parent-child relationship.We conclude that although the majority of the studies on cognitive,motor,and language developments reported comparable achievements in the ART group vs.the naturally conceived group,lower intelligence quotient(IQ)scores,worse visual-motor ability or locomotor development,and delayed receptive language competence were found in the ART group.The results on the socio-emotional development were reassuring.As for the behavior problems,a higher prevalence of behavior problems existed in ART children;moreover,ICSI children were found to be at a higher risk of autism than the general population.Meanwhile,ART parents tended to have positive parental attitudes and be more protective of their children.Some suggestions for further research are also given in this review.
文摘Objective To evaluate the impacts of reproductive tract infections （RTIs） intervention on RTIs-related knowledge, attitudes, practices and prevalence of married women at reproductive age. Methods Four sub-districts from Xuhui district, Shanghai were selected by multistage cluster random sampling and residence committees were randomly assigned to either an intervention group or a control one. RTIs intervention was implemented in intervention group, while routine family planning program was conducted in control group. Results Compared with control group, intervention group have improved the following targets： the increment of RTI knowledge score was higher than that in control group （OR=9. 22, 95%CI： 7.01 - 2.14）; the increment score of individual health behaviors （6. 31） was higher than that in control group （4.50） （OR=1.60, 95%CI： 1.21 -2.10）; the increase of condom use frequency in intervention group was higher than that in control group （4.12% vs 0.69%） （OR=1.84, 95%CI： 1.31-2.57）; the decreased RTIs rate was higher than that in control group （7.45% vs 0.96%） （OR=0.68, 95%CI： 0.49-0.95）. Conclusion It is an effective way to conduct community-based intervention to increase women＇s RTIs knowledge, improve RTIs-related attitudes, promote good individual health behaviors, so as to decrease RTIs prevalence.
文摘Objectives:To investigate the effect of sperm DNA fragmentation on outcomes of in vitro fertilization(IVF) and intracytoplasmic sperm injection(ICSI). Methods:A total of 242 cycles(154 IVF and 88 ICSI) from 235 couples were included.Sperm DNA fragmentation(SDF) and routine semen analysis were performed on the retrieval day.The rates of fertilization, embryo cleavage,good quality embryos,implantation and clinical pregnancy were measured. Results:Sperm DNA fragmentation index(DFI) in ICSI group was significantly higher than that in IVF group (P<0.01).The rates of fertilization,implantation and clinical pregnancy in ICSI were significantly higher than those in IVF with DFI≥24%(P<0.05).When DFI exceeded 24%,the OR for clinical pregnancy was 3.85(95% CI 1.40-10.59) comparing ICSI with IVF,and the OR for clinical pregnancy increased to 4.61(95%CI 1.09- 19.57) after inclusion of sperm concentration,progressively motile sperm percentage and female age as covariates. Conclusions:High DNA fragmentation might affect the outcome of ICSI and IVF.When DFI exceeds 24%, ICSI should be chosen instead of IVF.
基金supported by a grant from the Beijing Municipal NaturalScience Foundation(No.7194332)the Shandong Province Natural ScienceFoundation(No.ZR2022ZD19).
文摘At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.
基金received financial support from Tarbiat Modares University and Shahid Beheshti University of Medical Sciences,Tehran,Iran。
文摘Background:Shilajit is mentioned in the“Kama Sutra”as a potent enhancer of sexual desire.This study aimed to investigate the effects of oral Shilajit tablets on sexual function and sexual quality of life among women of reproductive age.Methods:Forty-eight reproductive-aged women participated in a placebo-controlled triple-blind clinical trial.The intervention group took oral Shilajit tablets(200 mg)twice daily for 60 days and the control group took the placebo.Data collection tools were Sexual Quality of Life-Female and Female Sexual Function Index.Data were collected before the intervention,30,60,and 90 days after the start of the study.Results:Forty-three women completed the study.The mean score of total sexual function in the intervention group was significantly higher than before the intervention(P<0.001).The mean score of sexual function was 28.93 after 90 days in the intervention group while it was 22.09 in the control group.This finding was observed in most domains of the sexual function index.The mean score of sexual quality of life increased after 60 days of intervention in both groups;however,the difference was not statistically significant(P=0.094).Conclusion:The study indicated that Shilajit,as a complementary therapy,may improve sexual function and most of its domains;while there was no effect on improving the quality of sexual life.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金supported by the Yunnan Provincial Key Laboratory of Clinical Virology(No.202002AG070062)the Key Projects of Yunnan Province Science and Technology Department(No.202302AA310044)the National Natural Science Foundation of China(No.82060664).
文摘This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parameters.These pathogens included Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,Pseudomonas aeruginosa,and Staphylococcus aureus.A total of 1951 men of infertile couples were recruited between 23 March 2023,and 17 May 2023,at the Department of Reproductive Medicine of The First People’s Hospital of Yunnan Province(Kunming,China).Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping.Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs.The overall prevalence of HPV infection was 12.4%.The top five prevalent HPV subtypes were types 56,52,43,16,and 53 among those tested positive for HPV.Other common infections with high prevalence rates were Ureaplasma urealyticum(28.3%),Ureaplasma parvum(20.4%),and Enterococcus faecalis(9.5%).The prevalence rates of HPV coinfection with Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,and Staphylococcus aureus were 24.8%,25.4%,10.6%,6.4%,2.4%,7.9%,5.9%,0.9%,and 1.3%,respectively.The semen volume and total sperm count were greatly decreased by HPV infection alone.Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability.Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters,emphasizing the necessity of semen screening for STIs.
文摘Objective:To assess whether personalized embryo transfer guided by endometrial receptivity array(ERA)improves implantation and pregnancy rates in women with implantation failure.Methods:This retrospective case-control study was conducted on women with previous implantation failure.The women were divided into two groups,i.e,women who underwent ERA and those who underwent embryo transfer without ERA testing.ERA was performed using Igenomix.ERA results were interpreted as receptive or non-receptive.Women underwent frozen embryo transfer on the 6th day of progesterone(P+5).The primary outcomes were implantation rate,clinical pregnancy rate,abortion rate,and negative pregnancy rate.Results:This study included 229 women with previous implantation failure,with 154 in the ERA group and 75 in the no ERA group.The mean age of the women of the ERA group was(32.2±4.1)years,and that of the no ERA group was(31.5±4.8)years.Women in the ERA group had a higher implantation rate(60.4%)and clinical pregnancy rate(57.1%)compared to those in the no ERA group(48.0%and 46.7%,respectively).In addition,implantation rate of the nonreceptive ERA group was higher than the no ERA group(65%vs.48%),and clinical pregnancy rate was also higher in the non-receptive ERA group than the no ERA group(65%vs.47%).The abortion rate of the no ERA group was 9%and that of the non-receptive ERA group was 10%.52%no ERA group women and 35%non-receptive ERA group women had negative pregnancy results.Conclusions:Women who have undergone personalised embryo transfer guided by ERA have a higher clinical pregnancy rate than women who have not after previous implantation failure.
基金supported by grants from the National Natural Science Foundation of China(No.82370846)the Zhejiang Provincial Natural Science Foundation of China(No.LY24H070002).
文摘Insulin-like growth factor 2(IGF2)is a critical endocrine mediator implicated in male reproductive physiology.To investigate the correlation between IGF2 protein levels and various aspects of male infertility,specifically focusing on sperm quality,inflammation,and DNA damage,a cohort of 320 male participants was recruited from the Women’s Hospital,Zhejiang University School of Medicine(Hangzhou,China)between 1^(st) January 2024 and 1^(st) March 2024.The relationship between IGF2 protein concentrations and sperm parameters was assessed,and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility.Enzyme-linked immunosorbent assay(ELISA)was used to measure IGF2 protein levels in seminal plasma,alongside markers of inflammation(tumor necrosis factor-alpha[TNF-α]and interleukin-1β[IL-1β]).The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX(γ-H2AX)was also explored.Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia.Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters,and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm.The observed correlations between IGF2 protein levels and specific sperm parameters,along with its connection to inflammation and DNA damage,underscore the importance of IGF2 in the broader context of male reproductive health.These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
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National Natural Science Foundation of China(Grant Nos.32070838 and 82301874)Open Fund of State Key Laboratory of Reproductive Medicine,Nanjing Medical University(Grant No.SKLRM K202102)。
文摘Meiotic resumption in mammalian oocytes involves nuclear and organelle structural changes,notably the chromatin configuration transition from a non-surrounding nucleolus(NSN)to surrounding nucleolus(SN)in germinal vesicle oocytes.In the current study,we found that nuclear speckles(NSs),a subnuclear structure mainly composed of serine-arginine(SR)proteins,changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregated pattern in SN oocytes.We also found that the SR protein-specific kinase 1(SRPK1),an enzyme that phosphorylates SR proteins,co-localized with NSs at the SN stage,and that NSN oocytes failed to transition to SN oocytes after the inhibition of SRPK1 activity.Furthermore,the typical structure of the chromatin ring around the nucleolus in SN oocytes collapsed after treatment with an SRPK1 inhibitor.Mechanistically,phosphorylated SR proteins were found to be related to chromatin as shown by a salt extraction experiment,and in situ DNaseⅠassay showed that the accessibility of chromatin was enhanced in SN oocytes when SRPK1 was inhibited,accompanied by a decreased repressive modification on histone and the abnormal recurrence of a transcriptional signal.In conclusion,our results indicated that SRPK1-regulated phosphorylation of SR proteins was involved in the NSN-SN transition and played an important role in maintaining the condensed nucleus of SN oocytes via interacting with chromatin.
文摘BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermatitis who developed a nonhealing wound after lumbar spinal surgery.The wound was successfully treated with vacuum sealing drainage therapy,confirming its feasibility in complex wound healing.CASE SUMMARY The patient was a 76-year-old female with lung cancer,positron emission tomography/computed tomography showed bone metastasis in L2 and L3 vertebrae.After 2 months of local radiotherapy to the lumbar spine,symptoms did not improve and pain worsened.She had lumbar lesion clearance and internal fixation surgery,but developed a nonhealing wound of approximately 15 cm postoperatively.After 12 rounds of clearing necrotic and unhealthy tissue,78 days of negative pressure therapy promoted granulation tissue growth and wound healing,resulting in wound healing.CONCLUSION Vacuum sealing drainage therapy has shown efficacy in treating nonhealing wounds after radiotherapy,promoting wound healing and reducing infection risk.
基金Supported by Traditional Chinese Medicine Science and Technology Project of Shandong Province,China,No.M-2023131The Science and Technology Development Fund Project of the Affiliated Hospital of Xuzhou Medical University,China,No.XYFM202348.
文摘Periplocin,periplocymarin and periplogenin are the main active components of Cortex Periplocae.The most cytotoxic constituent of Cortex Periplocae,periplocin is an alpha cardiac glycoside with a steroid core and an unsaturated five-membered lactone ring structure.Periplocymarin is a secondary alpha cardiac glycoside,which is produced by removing one molecule of glucose from periplocin,and periplogenin is the glycosidic portion and the basic unit of periplocin and periplocymarin.These three cardiac glycosides,by virtue of their unique pharmacological activities and mechanisms of action,mediate signaling pathways,mainly the retinoblastoma and p53 signaling pathways,and regulate cell cycle proteins,thereby hindering the proliferation of cancer cells and altering the cell cycle process.These glycosides also regulate caspase proteins by mediating endogenous and exogenous pathways,thereby inducing the apoptosis of cancer cells.This minireview focuses on the inhibitory effects of periplocin,periplocymarin and periplogenin on cancer,and explores their potential antitumor mechanisms.
文摘Methylenetetrahydrofolate reductase(MTHFR)is a key enzyme in folate metabolism.Its genetic polymorphisms affect the metabolism of methyl donors,including folate and betaine,and are consequently associated with the development of various chronic diseases such as stroke and neoplasms.Methods This umbrella review,covering the period from 2006 to 2025,searched PubMed,Embase,Web of Science,Medline,CNKI,WanFang,and Cochrane Library databases for published systematic reviews and meta-analyses of polymorphisms relating to the MTHFR C677T and A1298C gene polymorphisms and various chronic diseases.Subsequently,this study assessed methodological quality with AMSTAR-2,while the strength of evidence for each outcome was graded according to the GRADE and the credibility evaluation.This umbrella review included 39 studies related to 8 diseases classified according to the ICD-10 classification.Results Overall,C677T exhibited a positive correlation with depression(allele:OR=1.18,95%CI:1.13-1.24;dominant:OR=1.16,95%CI:1.09-1.23;recessive:OR=1.42,95%CI:1.30-1.56;homozygote:OR=1.48,95%CI:1.34-1.63),and polycystic ovary syndrome(allele:OR=1.35,95%CI:1.24-1.46;dominant:OR=1.46,95%CI:1.30-1.64;recessive:OR=1.39,95%CI:1.19-1.62;homozygote:OR=1.63,95%CI:1.38-1.93),and exhibited a negative correlation with oral cancer(allele:OR=0.24,95%CI:0.22-0.26;dominant:OR=0.14,95%CI:0.12-0.16;recessive:OR=0.31,95%CI:0.28-0.35;homozygote:OR=0.14,95%CI:0.12-0.16).A1298C was positively associated with polycystic ovary syndrome in four models(allele:OR=1.93,95%CI:1.67-2.21;dominant:OR=1.93,95%CI:1.64-2.27;recessive:OR=3.72,95%CI:2.47-5.61;homozygote:OR=4.38,95%CI:2.90-6.62).Conclusion The MTHFR C677T and A1298C gene polymorphisms demonstrated significant associations with non-communicable diseases,thereby contributing to the advancement of precision medicine.
基金supported by the National Key Research and Development Program of China(No.2018YFC1004900)the National Natural Science Foundation of China(No.82101799)the Health Science and Technology Foundation of Zhejiang Province of China(No.2022KY186).
文摘Given that ovarian stimulation is vital for assisted reproductive technology(ART)and results in elevated serum estrogen levels,exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary.We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells(m ESCs).Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation;mice treated with only normal saline served as controls.Hyperstimulation resulted in high serum estrogen levels,enlarged ovaries,an increased number of aberrant oocytes,and decreased embryo formation.The messenger RNA(m RNA)-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b(Kdm6b),which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos.In vitro,Kdm6b expression was downregulated in m ESCs treated with high-dose estrogen;treatment with an estrogen receptor antagonist could reverse this downregulated expression level.Furthermore,treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation(H3K27me3)and phosphorylated H2A histone family member X(γ-H2AX).Notably,knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies,with a concomitant increase in the expression of H3K27me3 andγ-H2AX.Collectively,our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression.Accordingly,Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
基金Supported by The 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.
基金CAMS Innovation Fund for Medical Sciences,Grant/Award Number:CIFMS,2021-I2M-1-024The Joint Fund for the Department of Science and Technology of Yunnan Province-Kunming Medical University,Grant/Award Number:202201AY070001-007+1 种基金Open Research Fund Project of Yunnan Provincial Key Laboratory of Pharmacology of Natural Medicines,Grant/Award Number:YKLPNP-G2403The Science and Technology Leading Talent Program of Yunnan Province,Grant/Award Number:202405AB350002。
文摘Background:Spinocerebellar ataxia type 2(SCA2)is a neurodegenerative disease marked by significant clinical and genetic heterogeneity,primarily caused by expanded CAG mutations in the ATXN2 gene.The unstable expansion of CAG repeats disrupts the genetic stability of animal models,which is detrimental to disease research.Methods:In this study,we established a mouse model in which CAG repeats do not undergo microsatellite instability(MSI)across generations.A humanized ATXN2 cDNA with four CAA interruptions within 73 CAG expansions was inserted into the Rosa26 locus of C57BL/6J mice.A 23 CAG control mouse model was also generated to verify ATXN2 integration and expression.Results:In our model,the number of CAG repeats remained stable during transmission,with no CAG repeat expansion observed in 64 parent-to-offspring transmissions.Compared with SCA2-Q23 mice,SCA2-Q73 mice exhibited progressive motor impairment,reduced Purkinje cell count and volume(indicative of cell atrophy),and muscle atrophy.These observations in the mice suggest that the behavioral and neuropathological phenotypes may reflect the features of SCA2 patients.RNA-seq analysis of the gastrocnemius muscle in SCA2-Q73 mice showed significant changes in muscle differentiation and development gene expression at 56 weeks,with no significant differences at 16 weeks compared to SCA2-Q23 mice.The expression level of the Myf6 gene significantly changed in the muscles of aged mice.Conclusion:In summary,the establishment of this model not only provides a stable animal model for studying CAG transmission in SCA2 but also indicates that the lack of long-term neural stimulation leads to muscle atrophy.
文摘Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and microdissection testicular sperm extraction(micro-TESE)is the procedure of choice for men with NOA desiring to father children with their own gametes.Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection(ICSI)in comparison to all other techniques for surgical sperm retrieval in men with NOA.Several factors may affect sperm retrieval rate and ICSI outcomes,including the patient’s age,testicular volume,histopathological and genetic profile,and serum hormone levels.This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.
