Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patien...Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life.In order to evaluate oncological safety,attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS,this multicenter retrospective study was conducted.Between January 2005 and December 2014,total of 87 young women with FIGO stage I EOC were included,with their clinicopathologic parameters in relation to disease-free survival(DFS)and overall survival(OS)assessed.Attitudes toward childbearing,ovarian function and fertility were studied in women undergoing FSS(n=36).As a result,in contrast to radical sur ery,FSS did not affect prognosis by Kaplan-Meier curves(log-rank test;DFS:P=0.484;OS:P=0.125).However,two of the three recurrence cases and both death cases were in FSS group stage IC.All women undergoing FSS resumed regular menstrual periods after chemotherapy.Only 16(44.44%)had tried to conceive,and 17 pregnancies occurred in 15(93.75%)women.Among 20 women who did not attempt conception,the most common reason was not being married(70%),followed by already having children(15%).In summary,FSS is considered safe in young women with stage IA EOC.Regular menstruation and good obstetric outcomes can be achieved.This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.展开更多
The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel prote...The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.展开更多
Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidat...Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.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
Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to iden...Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.展开更多
Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases...Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases of singleton deliver by infertile patients under 35 years old who received IVF/ICSI-ET in our center were analyzed.According to different fertilization methods,they were divided into IVF group(2967 cases)and ICSI group(1262 cases).The general situation of birth,birth defects and the location of defects were compared between the two groups.Results:a total of 38 cases of neonatal birth defects were found,the incidence of birth defects was 0.89%,including 30 cases(1.01%)in IVF group and 8 cases(0.64%)in ICSI group.There was no significant difference in the incidence of birth defects between the two groups(P>0.05).There was also no significant difference in birth weight,gestational age and gender ratio between the two groups(P>0.05).Conclusion:Different fertilization methods in assisted reproductive technology do not increase the incidence of neonatal birth defects.展开更多
Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ...Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis.Differentially expressed miRNAs were identified using RNA sequencing.Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs.The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101.DGL5 expression was detected using qRT-PCR and Western blot analyses.Results:The migration of breast cancer cells was significantly inhibited after addition of exosomes.RNA sequencing results showed that miR-101-3p expression was significantly upregulated.Targetscan analysis predicted that miR-101-3p could target DLG5,and this prediction was verified using the luciferase assay.The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p,and the mRNA and protein levels of DLG5 were suppressed.In contrast,inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5.Furthermore,the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells.Conclusions:Macrophage exosomes can inhibit the migration of breast cancer cells,and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process,which needs further investigation.展开更多
The human skin has the ability to sense tactile touch and a great range of pressures.Therefore,in prosthetic or robotic systems,it is necessary to prepare pressure sensors with high sensitivity in a wide measurement r...The human skin has the ability to sense tactile touch and a great range of pressures.Therefore,in prosthetic or robotic systems,it is necessary to prepare pressure sensors with high sensitivity in a wide measurement range to provide human-like tactile sensation.Herein,we developed a flexible piezoresistive pressure sensor that is highly sensitive in a broad pressure range by using lotus leaf micropatterned polydimethylsiloxane and multilayer superposition.By superposing four layers of micropatterned constructive substrates,the multilayer piezoresistive pressure sensor achieves a broad pressure range of 312 kPa,a high sensitivity of 2.525 kPa^(−1),a low limit of detection(LOD)of<12 Pa,and a fast response time of 45 ms.Compared with the traditional flexible pressure sensor,the pressure range of this sensor can be increased by at least an order of magnitude.The flexible piezoresistive pressure sensor also shows high robustness:after testing for at least 1000 cycles,it shows no sign of fatigue.More importantly,these sensors can be potentially applied in various human motion detection scenarios,including tiny pulse monitoring,throat vibration detection,and large under-feet pressure sensing.The proposed fabrication strategy may guide the design of other kinds of multifunctional sensors to improve the detection performance.展开更多
Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive t...Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.展开更多
Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patie...Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors.A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center.Results The clinical pregnancy rate(CPR)and live birth rate(LBR)were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers,in terms of the same embryo quality.For FBT cycles with good-quality embryo,the CPR at day 5 and 6 was 61.30%and 57.56%,respectively(P=0.045),and the LBR was 44.79%and 36.16%,respectively(P<0.001).For FBT cycles with poor-quality embryo,the CPR at day 5 and 6 was 48.61%and 40.89%,respectively(P=0.006),and the LBR was 31.71%and 25.74%,respectively(P=0.019).The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred(57.56%vs.48.61%,P=0.001).Maternal age,anti-Müllerian hormone(AMH),endometrial thickness,embryo quality,and the day of blastocyst expansion were independently correlated with the CPR and LBR.The FBT cycles at day 5 had significantly higher CPR(adjusted odds ratio[OR]=1.246,95%confidence intervals[CI]:1.097–1.415,P=0.001)and LBR(adjusted OR=1.435,95%CI:1.258–1.637,P<0.001)than those at day 6.Conclusion The embryo quality is the primary indicator for FBT cycles.Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.展开更多
Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for...Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.展开更多
Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls we...Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls were obtained from the Gene Expression Omnibus database.Significant differentially expressed genes were screened using the limma package.Correlation pathways were screened by Spearman correlation analysis on the echinoderm microtubule-associated protein-like 4(EML4)and enrichment in endometriosis pathways and estimated by the GSVA package.Immune characteristics were assessed by the“ESTIMATE”R package.Potential regulatory pathways were determined by enrichment analysis.The SWISS-MODE website was used in homology modeling with EML4 and EML4 protein activity was predicted.VarElect was employed in molecular docking for screening potential compound inhibitors targeting endometriosis.Results:Ten endometriosis and 10 normal samples were included.EML4 was significantly upregulated in endometriosis(p<0.05).Thirty significantly correlated pathways involving 18 positive and 12 negative correlations,including GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE and GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES were screened between EML4 and endometriosis.Immunocorrelation analysis showed a significant difference in immune-related pathways in endometriosis and normal samples(p<0.05).In endometriosis,EML4 was associated with T-cell CD4 resting memory,activated mast cells,plasma cells,activated NK cells,M2 macrophages,and follicular helper T cells(p<0.05).Molecular docking identified five potential inhibitors of EML4,and compound DB05104(asimadoline)bound well to EML4 protein to exert its physiological effects.Conclusion:Differential gene expression and immune correlation analyses revealed that EML4 may affect endometriosis through multiple targets and pathways,the mechanism of which involved immune cell activation and infiltration.Molecular docking and dynamics simulation verified DB05104 as a potential inhibitor of EML4 and a powerful target for endometriosis treatment.展开更多
For men with severe oligozoospermia, sperm cryopreservation can preserve surgically obtained sperm. How to cryopreserve single sperm in men is still a hot topic in assisted reproduction technology. Aim to analyze the ...For men with severe oligozoospermia, sperm cryopreservation can preserve surgically obtained sperm. How to cryopreserve single sperm in men is still a hot topic in assisted reproduction technology. Aim to analyze the laboratory and pregnancy outcomes of single sperm cryopreservation group, we retrospectively selected 38 cycles underwent single sperm cryopreservation and thawing as the study group and 618 cycles underwent conventional sperm cryopreservation and thawing as the control group, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yatsen University, from April 2014 to October 2023. All the sperm came from microdissection testicular sperm extraction (micro-TESE), and performed intracytoplasmic sperm injection (ICSI) for fertilization. Zygotes were cultured to Day 3 embryo, which were freshly transferred to female uterus. Surplus embryos were cultured to blastosphere and cryopreserved. There was no statistical difference in female/male age, female BMI, infertility duration and female basal sex hormone (FSH, LH E2, AMH), No. of oocytes retrieved per cycle, No. of ICSI oocytes per cycle and No. of embryos transferred per cycle between the two groups (P > 0.05). No significant difference was found in two-pronuclear oocyte fertilization rate (59.23% VS 58.84%), Day 3 available embryo rate (61.81% VS 63.55%), Day 3 good-quality embryo rate (45.73% VS 50.27%), blastocyst formation rate (47.83% VS 49.46%), the implantation rate (47.37% VS 52.16%), clinical pregnancy rate (36.84% VS 47.18%), miscarriage rate (14.29% VS 12.68%) and live birth rate (85.71% VS 81.70%) between two groups (P > 0.05). In conclusion, single-sperm cryopreservation was the optimal method to preserve sperm after micro-TESE. It can increase the utilization of each sperm and lead to clinical pregnancy.展开更多
Purpose: We aimed to analyze the pregnancy outcomes and perinatal follow-up of mosaic embryo transfer in the preimplantation genetic testing (PGT) cycles. Method: We retrospectively selected 27 mosaic embryo transfer ...Purpose: We aimed to analyze the pregnancy outcomes and perinatal follow-up of mosaic embryo transfer in the preimplantation genetic testing (PGT) cycles. Method: We retrospectively selected 27 mosaic embryo transfer cycles as the study group and 97 euploid embryo transfer cycles as the control group after propensity score matching, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yat-sen University, from March 2019 to September 2023. The biopsy cells from blastocyst were undertaken next generation sequencing (NGS). Results: No significant difference in pregnancy outcomes compared between the two groups. According to the size of aneuploid, fragment the level of mosaicism or blastocyst morphological gradings, there were no significant difference in mosaic embryo transfers. Conclusion: Mosaic embryo detected in the PGT cycle can lead to clinical pregnancy and live birth of healthy offspring, which can be considerate suitable for transfer.展开更多
Embryos with a poor morphological score at cleavage stage are usually discarded because they are considered unsuitable for transfer and cryopreservation. This study examined the in vitro blastocyst development after e...Embryos with a poor morphological score at cleavage stage are usually discarded because they are considered unsuitable for transfer and cryopreservation. This study examined the in vitro blastocyst development after extended culture of these embryos and the clinical outcomes after transfer of these blastocysts in warming cycles. A total of 597 blastocysts (24.7%) were obtained from 2421 embryos with low morphological scores after extended culture. One hundred and sixty blastocysts (6.6%) with optimal morphology were vitrified. Embryo utilization rate was increased from 30.8% to 32.6%. After warming, 61 out of 92 blastocysts (66.3%) survived and were transferred in 44 cycles. The clinical pregnancy rate and the implantation rate were 40.9% (18/44) and 32.8% (20/61) respectively. Thirteen healthy babies were born, and 5 pregnancies aborted spontaneously. Our study suggested that some blastocysts derived from embryos with a poor morphological score can be successfully vitrified and give rise to live births. Selection and vitrification of viable embryos after extended culture of embryos with a poor morphological score may constitute a proposal to avoid embryo wastage.展开更多
This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-E...This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.展开更多
The debate exists whether or not gonadotropin-releasing hormone(GnRH) analogs used in controlled ovarian hyperstimulation(COH) impair endometrial receptivity.Homeobox A11(Hoxa11),Meis homeobox 1(Meis1),cadherin 1(Cdh1...The debate exists whether or not gonadotropin-releasing hormone(GnRH) analogs used in controlled ovarian hyperstimulation(COH) impair endometrial receptivity.Homeobox A11(Hoxa11),Meis homeobox 1(Meis1),cadherin 1(Cdh1),and catenin beta 1(Ctnnb1) are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization(IVF) mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin(HMG)(GnRH agonist group),GnRH antagonist plus HMG(GnRH antagonist group),and HMG alone(HMG group).The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.展开更多
The aim of this study was to determine the association between thyroid-stimulating hormone (TSH) level and pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm injectio...The aim of this study was to determine the association between thyroid-stimulating hormone (TSH) level and pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI).A total of 1185 women were enrolled in the retrospective study,and 12 studies with a total of 6624 women were included in the meta-analysis (including the data of the present retrospective study).Participants in the retrospective study were divided into two groups in terms of their serum TSH levels:TSH <2.5 mIU/L group (w=830) and TSH >2.5 mIU/L group (h=355).They were monitored for the status of clinical pregnancy or miscarriage.In the TSH <2.5 mIU/L group,441 (53.1%) women achieved clinical pregnancy,while 48 (5.8%) had early pregnancy loss and 12 (1.4%) had ectopic pregnancy.In the TSH >2.5 mIU/ L group,175 (49.3%) women achieved clinical pregnancy,while 21 (5.9%) had early pregnancy loss and 3 (0.8%) had ectopic pregnancy.No significant differences were observed between the two groups in pregnancy outcomes (P=0.126,P=0.512,P=0.297).The meta-analysis also revealed no significant difference in the clinical pregnancy rate and the miscarriage rate between women with serum TSH <2.5 mIU/L and those with serum TSH >2.5 mIU/L.In conclusion,high TSH levels (TSH level >2.5 mIU/L) did not affect clinical pregnancy rate or increase miscarriage rate in euthyroid women undergoing IVF/ICSI.展开更多
基金This work was supported by National Key Technology Research and Development Program of China(No.2019YFC1005200,No.2019YFC1005202 and No.2018YFC1002103)National Natural Science Foundation of China(No.81802896)Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019M127).
文摘Summary:With delayed childbearing in women,preservation of fertility is an important issue for reproductive-age patients with epithelial ovarian carcinoma(EOC).Fertility-sparing surgery(FSS)can be considered in patients with early-stage disease in order to preserve fertility and improve quality of life.In order to evaluate oncological safety,attitudes toward childbearing and reproductive outcomes in women with EOC who underwent FSS,this multicenter retrospective study was conducted.Between January 2005 and December 2014,total of 87 young women with FIGO stage I EOC were included,with their clinicopathologic parameters in relation to disease-free survival(DFS)and overall survival(OS)assessed.Attitudes toward childbearing,ovarian function and fertility were studied in women undergoing FSS(n=36).As a result,in contrast to radical sur ery,FSS did not affect prognosis by Kaplan-Meier curves(log-rank test;DFS:P=0.484;OS:P=0.125).However,two of the three recurrence cases and both death cases were in FSS group stage IC.All women undergoing FSS resumed regular menstrual periods after chemotherapy.Only 16(44.44%)had tried to conceive,and 17 pregnancies occurred in 15(93.75%)women.Among 20 women who did not attempt conception,the most common reason was not being married(70%),followed by already having children(15%).In summary,FSS is considered safe in young women with stage IA EOC.Regular menstruation and good obstetric outcomes can be achieved.This study also provides some insight into the attitudes and social factors regarding fertility in EOC patients.
基金the National Key Research and Development Program of China(Grant Nos.2022YFC3401500 and 2020YFA0803201 to P.W.,and 2021YFA1302200 to L.F.)the National Natural Science Foundation of China(Grant Nos.31830053,31920103007,and 82341028 to P.W.+1 种基金82122056,82073153,and 31871398 to L.F.and 31900568 to P.W.)the Natural Science Foundation of Shanghai(Grant No.22ZR1450700 to Z.J.W.)。
文摘The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.
基金supported by the Natural Science Foundation of Gansu Province(No.21JR7RA376)Lanzhou University First Hospital Youth Foundation(No.ldyyyn2021-86)Traditional Chinese Medicine Bureau of Guangdong Province(20231003).
文摘Background:Oxidative stress is one of the key contributors to cellular senescence and ovarian aging.Quercetin has a variety of physiological activities such as antioxidant.Given that hydrogen peroxide can cause oxidative damage to cells,the present study is designed to verify the protective effect of quercetin on human ovarian granulosa tumor cell line under oxidative stress.Methods:Cell counting kit-8 and lactate dehydrogenase assays examined cell viability and toxicity.Flow cytometry detected reactive oxygen species accumulation.Glutathione level was measured to analyze the oxidation resistance.Cell apoptosis was evaluated by Hoechst 33258 staining,acridine orange/Ethidium Bromide staining and western blot.The mitochondrial structure was observed under a transmission electron microscope.Mitochondrial membrane integrity was detected by JC-1 staining and western blot.Results:Hydrogen peroxide could induce cell injury,promote reactive oxygen species accumulation,and lead to glutathione depletion.hydrogen peroxide also resulted in mitochondrial morphological damage and depolarization,which activate caspase3/9 subsequently.However,quercetin could mitigate these damages.Conclusions:Present study found that hydrogen peroxide induced oxidative stress and mitochondrial apoptosis of human ovarian granulosa tumor cell line cells,which could be attenuated by quercetin.
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Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain elusive.This study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with obesity.Methods:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate genes.Subsequently,we validated the protein levels of these candidates using immunohistochemistry.Finally,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression models.Results:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight patients.The expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,respectively.The 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(P<0.05).Furthermore,the 8-year recurrence-free survival rates were 66.2%and 76.4%,and the 8-year overall survival rates were 79.9%and 86.3%in the low and high PER2 expression groups,respectively(P<0.05).The unadjusted hazard ratio for PER2 was 1.550(95%confidence interval,1.029–2.335),and the adjusted hazard ratio was 3.003(95%confidence interval,1.838–4.907).Conclusions:Our findings indicate that low PER2 expression serves as an independent risk factor for breast cancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.
基金Major Science and Technology Project of Hainan Province(No.ZDKJ2017007)Key Research and Development Project of Hainan Provincial Science and Technology Department(No.ZDYF2019158)Scientific Research Project of Health and Family Planning Industry in Hainan Province(No.19A200124)。
文摘Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases of singleton deliver by infertile patients under 35 years old who received IVF/ICSI-ET in our center were analyzed.According to different fertilization methods,they were divided into IVF group(2967 cases)and ICSI group(1262 cases).The general situation of birth,birth defects and the location of defects were compared between the two groups.Results:a total of 38 cases of neonatal birth defects were found,the incidence of birth defects was 0.89%,including 30 cases(1.01%)in IVF group and 8 cases(0.64%)in ICSI group.There was no significant difference in the incidence of birth defects between the two groups(P>0.05).There was also no significant difference in birth weight,gestational age and gender ratio between the two groups(P>0.05).Conclusion:Different fertilization methods in assisted reproductive technology do not increase the incidence of neonatal birth defects.
基金supported by the Key Research and Development Program of Hainan Province(ZDYF2020139,ZDYF2018158)the Science and Technology Funding Project of Hainan Province(821MS129).
文摘Objective:To investigate the role of macrophages in regulating breast cancer cell migration and its related mechanisms.Methods:Human leukemia monocytic cell line THP-1-secreted exosomes were isolated using multi-step ultracentrifugation and verified using nanoparticle tracking analysis.Differentially expressed miRNAs were identified using RNA sequencing.Overexpression of inhibitors of hsa-miR-101-3p in breast cancer MDA-MB-231 cells was performed by infecting their lentiviral constructs.The luciferase reporter assay was used to evaluate the interaction of DLG5 and miR-101.DGL5 expression was detected using qRT-PCR and Western blot analyses.Results:The migration of breast cancer cells was significantly inhibited after addition of exosomes.RNA sequencing results showed that miR-101-3p expression was significantly upregulated.Targetscan analysis predicted that miR-101-3p could target DLG5,and this prediction was verified using the luciferase assay.The addition of the miR-101-3p precursor significantly increased the expression of miR-101-3p,and the mRNA and protein levels of DLG5 were suppressed.In contrast,inhibiting the expression of miR-101-3p increased the mRNA and protein levels of DLG5.Furthermore,the scratch assay showed that inhibiting miR-101-3p could promote the migration of MDA-MB-231 cells.Conclusions:Macrophage exosomes can inhibit the migration of breast cancer cells,and increasing the expression of miR-101-3p to inhibit DLG5 expression may play an important role in this process,which needs further investigation.
基金the Project of National Key Research and Development Program of China(No.2018YFC2001300)the National Natural Science Foundation of China(Nos.52175271,51822504,52021003,52105299,51905207,and 91948302)+2 种基金Science and Technology Development Plan Project of Jilin Province(No.20210508057RQ)Program for JinlinUniversity Science and Technology Innovative Research Team(No.2017TD-04)Scientific Research Project of EducationDepartment of Jilin Province(No.JJKH20211084KJ).
文摘The human skin has the ability to sense tactile touch and a great range of pressures.Therefore,in prosthetic or robotic systems,it is necessary to prepare pressure sensors with high sensitivity in a wide measurement range to provide human-like tactile sensation.Herein,we developed a flexible piezoresistive pressure sensor that is highly sensitive in a broad pressure range by using lotus leaf micropatterned polydimethylsiloxane and multilayer superposition.By superposing four layers of micropatterned constructive substrates,the multilayer piezoresistive pressure sensor achieves a broad pressure range of 312 kPa,a high sensitivity of 2.525 kPa^(−1),a low limit of detection(LOD)of<12 Pa,and a fast response time of 45 ms.Compared with the traditional flexible pressure sensor,the pressure range of this sensor can be increased by at least an order of magnitude.The flexible piezoresistive pressure sensor also shows high robustness:after testing for at least 1000 cycles,it shows no sign of fatigue.More importantly,these sensors can be potentially applied in various human motion detection scenarios,including tiny pulse monitoring,throat vibration detection,and large under-feet pressure sensing.The proposed fabrication strategy may guide the design of other kinds of multifunctional sensors to improve the detection performance.
基金the Guangdong Medical Science and Technology Research Foundation(No.A2021345).
文摘Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.
基金supported by the National Natural Science Foundation of China(No.81701509).
文摘Objective This study aimed to determine whether the day of blastocyst expansion affects pregnancy outcomes in frozen-thawed blastocyst transfer(FBT)cycles.Methods A retrospective match-cohort study was conducted.Patients who underwent blastocyst transfer in frozen-thawed cycles at day 5 or 6 were matched for potential confounding factors.A total of 2207 matched pairs of FBT cycles were included from January 2016 to December 2019 in our Reproductive Medicine Center.Results The clinical pregnancy rate(CPR)and live birth rate(LBR)were significantly increased in day 5 blastocyst transfers when compared to day 6 blastocyst transfers,in terms of the same embryo quality.For FBT cycles with good-quality embryo,the CPR at day 5 and 6 was 61.30%and 57.56%,respectively(P=0.045),and the LBR was 44.79%and 36.16%,respectively(P<0.001).For FBT cycles with poor-quality embryo,the CPR at day 5 and 6 was 48.61%and 40.89%,respectively(P=0.006),and the LBR was 31.71%and 25.74%,respectively(P=0.019).The CPR for FBT cycles with good-quality embryo was statistically higher at day 6 than that at day 5 with poor-quality embryo transferred(57.56%vs.48.61%,P=0.001).Maternal age,anti-Müllerian hormone(AMH),endometrial thickness,embryo quality,and the day of blastocyst expansion were independently correlated with the CPR and LBR.The FBT cycles at day 5 had significantly higher CPR(adjusted odds ratio[OR]=1.246,95%confidence intervals[CI]:1.097–1.415,P=0.001)and LBR(adjusted OR=1.435,95%CI:1.258–1.637,P<0.001)than those at day 6.Conclusion The embryo quality is the primary indicator for FBT cycles.Day 5 blastocysts should be preferred when the quality of embryo at day 5 is the same as that at day 6.
基金Supported by The National Natural Science Foundation of China,No.82171604。
文摘Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.
基金funded by the Role and Mechanism of EML4 in Regulating Oocyte Meiosis and Leading to the Infertility Project(SDFEYJGL2103).
文摘Objective:Key genes were screened to analyze molecular mechanisms and their drug targets of endometriosis by applying a bioinformatics approach.Methods:Gene expression profiles of endometriosis and healthy controls were obtained from the Gene Expression Omnibus database.Significant differentially expressed genes were screened using the limma package.Correlation pathways were screened by Spearman correlation analysis on the echinoderm microtubule-associated protein-like 4(EML4)and enrichment in endometriosis pathways and estimated by the GSVA package.Immune characteristics were assessed by the“ESTIMATE”R package.Potential regulatory pathways were determined by enrichment analysis.The SWISS-MODE website was used in homology modeling with EML4 and EML4 protein activity was predicted.VarElect was employed in molecular docking for screening potential compound inhibitors targeting endometriosis.Results:Ten endometriosis and 10 normal samples were included.EML4 was significantly upregulated in endometriosis(p<0.05).Thirty significantly correlated pathways involving 18 positive and 12 negative correlations,including GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE and GLYCOSPHINGOLIPID_BIOSYNTHESIS_GANGLIO_SERIES were screened between EML4 and endometriosis.Immunocorrelation analysis showed a significant difference in immune-related pathways in endometriosis and normal samples(p<0.05).In endometriosis,EML4 was associated with T-cell CD4 resting memory,activated mast cells,plasma cells,activated NK cells,M2 macrophages,and follicular helper T cells(p<0.05).Molecular docking identified five potential inhibitors of EML4,and compound DB05104(asimadoline)bound well to EML4 protein to exert its physiological effects.Conclusion:Differential gene expression and immune correlation analyses revealed that EML4 may affect endometriosis through multiple targets and pathways,the mechanism of which involved immune cell activation and infiltration.Molecular docking and dynamics simulation verified DB05104 as a potential inhibitor of EML4 and a powerful target for endometriosis treatment.
文摘For men with severe oligozoospermia, sperm cryopreservation can preserve surgically obtained sperm. How to cryopreserve single sperm in men is still a hot topic in assisted reproduction technology. Aim to analyze the laboratory and pregnancy outcomes of single sperm cryopreservation group, we retrospectively selected 38 cycles underwent single sperm cryopreservation and thawing as the study group and 618 cycles underwent conventional sperm cryopreservation and thawing as the control group, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yatsen University, from April 2014 to October 2023. All the sperm came from microdissection testicular sperm extraction (micro-TESE), and performed intracytoplasmic sperm injection (ICSI) for fertilization. Zygotes were cultured to Day 3 embryo, which were freshly transferred to female uterus. Surplus embryos were cultured to blastosphere and cryopreserved. There was no statistical difference in female/male age, female BMI, infertility duration and female basal sex hormone (FSH, LH E2, AMH), No. of oocytes retrieved per cycle, No. of ICSI oocytes per cycle and No. of embryos transferred per cycle between the two groups (P > 0.05). No significant difference was found in two-pronuclear oocyte fertilization rate (59.23% VS 58.84%), Day 3 available embryo rate (61.81% VS 63.55%), Day 3 good-quality embryo rate (45.73% VS 50.27%), blastocyst formation rate (47.83% VS 49.46%), the implantation rate (47.37% VS 52.16%), clinical pregnancy rate (36.84% VS 47.18%), miscarriage rate (14.29% VS 12.68%) and live birth rate (85.71% VS 81.70%) between two groups (P > 0.05). In conclusion, single-sperm cryopreservation was the optimal method to preserve sperm after micro-TESE. It can increase the utilization of each sperm and lead to clinical pregnancy.
文摘Purpose: We aimed to analyze the pregnancy outcomes and perinatal follow-up of mosaic embryo transfer in the preimplantation genetic testing (PGT) cycles. Method: We retrospectively selected 27 mosaic embryo transfer cycles as the study group and 97 euploid embryo transfer cycles as the control group after propensity score matching, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yat-sen University, from March 2019 to September 2023. The biopsy cells from blastocyst were undertaken next generation sequencing (NGS). Results: No significant difference in pregnancy outcomes compared between the two groups. According to the size of aneuploid, fragment the level of mosaicism or blastocyst morphological gradings, there were no significant difference in mosaic embryo transfers. Conclusion: Mosaic embryo detected in the PGT cycle can lead to clinical pregnancy and live birth of healthy offspring, which can be considerate suitable for transfer.
文摘Embryos with a poor morphological score at cleavage stage are usually discarded because they are considered unsuitable for transfer and cryopreservation. This study examined the in vitro blastocyst development after extended culture of these embryos and the clinical outcomes after transfer of these blastocysts in warming cycles. A total of 597 blastocysts (24.7%) were obtained from 2421 embryos with low morphological scores after extended culture. One hundred and sixty blastocysts (6.6%) with optimal morphology were vitrified. Embryo utilization rate was increased from 30.8% to 32.6%. After warming, 61 out of 92 blastocysts (66.3%) survived and were transferred in 44 cycles. The clinical pregnancy rate and the implantation rate were 40.9% (18/44) and 32.8% (20/61) respectively. Thirteen healthy babies were born, and 5 pregnancies aborted spontaneously. Our study suggested that some blastocysts derived from embryos with a poor morphological score can be successfully vitrified and give rise to live births. Selection and vitrification of viable embryos after extended culture of embryos with a poor morphological score may constitute a proposal to avoid embryo wastage.
基金This work was supported by the Natural Science Foundation of Hubei Province (No.2017CFB262).
文摘This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.
基金supported by a grant from the Major State Basic Research Development Program of China (973 Program)(No. 2007-CB948100)
文摘The debate exists whether or not gonadotropin-releasing hormone(GnRH) analogs used in controlled ovarian hyperstimulation(COH) impair endometrial receptivity.Homeobox A11(Hoxa11),Meis homeobox 1(Meis1),cadherin 1(Cdh1),and catenin beta 1(Ctnnb1) are well known to be involved in successful implantation.In this study,the endometrial expression of Hoxa11,Meis1,Cdh1,and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization(IVF) mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11,Meis1,Cdh1,and Ctnnb1 expression and the impact of the COH on endometrial receptivity.The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin(HMG)(GnRH agonist group),GnRH antagonist plus HMG(GnRH antagonist group),and HMG alone(HMG group).The expression levels of Hoxa11,Meis1,Cdh1,and Ctnnb1 mRNA and protein were decreased in all of the COH groups.The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group,and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group.There were positive correlations between the expression of Hoxa11 and Ctnnb1,as well as the expression of Meis1 and Cdh1 among all the groups.In conclusion,the COH protocols,particularly with GnRH analogs,suppressed Hoxa11,Meis1,Ctnnb1 and Cdh1 expression,in mouse endometrium during the peri-implantation period.Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.
基金This work was supported by grants from the National Key Research and Development Program of China (No.2018YFC1002103)the National Natural Science Foundation of China (No.81601348).
文摘The aim of this study was to determine the association between thyroid-stimulating hormone (TSH) level and pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI).A total of 1185 women were enrolled in the retrospective study,and 12 studies with a total of 6624 women were included in the meta-analysis (including the data of the present retrospective study).Participants in the retrospective study were divided into two groups in terms of their serum TSH levels:TSH <2.5 mIU/L group (w=830) and TSH >2.5 mIU/L group (h=355).They were monitored for the status of clinical pregnancy or miscarriage.In the TSH <2.5 mIU/L group,441 (53.1%) women achieved clinical pregnancy,while 48 (5.8%) had early pregnancy loss and 12 (1.4%) had ectopic pregnancy.In the TSH >2.5 mIU/ L group,175 (49.3%) women achieved clinical pregnancy,while 21 (5.9%) had early pregnancy loss and 3 (0.8%) had ectopic pregnancy.No significant differences were observed between the two groups in pregnancy outcomes (P=0.126,P=0.512,P=0.297).The meta-analysis also revealed no significant difference in the clinical pregnancy rate and the miscarriage rate between women with serum TSH <2.5 mIU/L and those with serum TSH >2.5 mIU/L.In conclusion,high TSH levels (TSH level >2.5 mIU/L) did not affect clinical pregnancy rate or increase miscarriage rate in euthyroid women undergoing IVF/ICSI.
