Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF ...Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF cases remain unclear.To reveal the genetic causes of MMAF in an infertile patient,whole-exome sequencing was performed to screen for pathogenic genes,and electron microscope was used to reveal the sperm flagellar ultrastructure.A novel heterozygous missense mutation in the outer dense fiber protein 2(ODF2)gene was detected,which was inherited from the patient’s mother and predicted to be potentially damaging.Transmission electron microscopy revealed that the outer dense fibers were defective in the patient’s sperm tail,which was similar to that of the reported heterozygous Odf2 mutation mouse.Immunostaining of ODF2 showed severe ODF2 expression defects in the patient’s sperm.Therefore,it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case.To evaluate the possibility of assisted reproductive technology(ART)treatment for this patient,intracytoplasmic sperm injection(ICSI)was performed,with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection(LAISS)for available sperm screening,and artificial oocyte activation with ionomycin was applied to improve the fertilization rate.Four ICSI cycles were performed,and live birth was achieved in the LAISS-applied cycle,suggesting that LAISS would be valuable in ART treatment for MMAF.展开更多
Objective To compare the results of a novel regimen of human menopausal gonadotrophin （hMG） in combination with clomiphene citrate （CC） in mid-to-late follicular phase with those of a short protocol of GnRH agoni...Objective To compare the results of a novel regimen of human menopausal gonadotrophin （hMG） in combination with clomiphene citrate （CC） in mid-to-late follicular phase with those of a short protocol of GnRH agonist （GnRHa） and hMG used for IVF. Methods In the retrospective study, 842 patients undergoing IVF were collected and classified into two groups： hMG in combination with CC in mid-to-late follicular phase （group A, n=319） and short protocol of GnRHa-hMG （group B, n=523）. The main outcome measures were ovarian responses in stimulation cycles and pregnancy outcomes in subsequent frozen-thawed embryo transfer （FET） cycles. Results In group A, the serum LH concentration on day 8 -10 was similar with that on the day of hCG administration （2.43 ± 1.92 IU vs 2.51 ±2.05 IU）. The number of mature follicles and oocytes retrieved was significantly lower in group A than in group B while the fertilization rate and the cleavage rate were comparable. The clinical pregnancy rate （47. 79% vs 48.04%）, the implantation rate （32.49% vs 33.11%） and the cumulative pregnancy rate （58.09% vs 60.22%） were respectively similar in group A and group B. Conclusion hMG in combination with CC in mid-to-late follicular phase results in the same pregnancy outcome as short protocol. The novel protocol may take the advantage of eliminating the occurrehce of a premature endogenous LH Surge.展开更多
Objective To compare the clinical characteristics in a gonadotropin （Gn） and medroxyprogestrone acetate （MPA） protocol using three types of Gn in normal ovulatory women undergoing IVF/ICSI treatments. Methods A to...Objective To compare the clinical characteristics in a gonadotropin （Gn） and medroxyprogestrone acetate （MPA） protocol using three types of Gn in normal ovulatory women undergoing IVF/ICSI treatments. Methods A total of 258 normal ovulatory IVF/ICSI patients undergoing ovarian stimulation in a Gn and MPA protocol were analyzed in this retrospective study and allocated into three groups according to the Gn used： group A, hMG-A （brand name： Fengyuan, n=105）; group B, hMG-B （brand name： Lebaode, n=90）; group C： u-FSH （brand name： Lishenbao, n=63）. The hormone profile, embryological characteristics, and the pregnant results after frozen-thawed embryo transfer （FET） were compared among the three groups. Results There was no significant difference in the number of oocytes retrieved among the three groups （12.1± 6.9 vs 12.1±5.6 vs 13.1 ±8.8, P〉0.05）. Other indicators such as the number of mature oocyte, fertilization, cleavage and viable embryo were similar （P〉0.05）. No premature LH surges were detected, with a range of 0.04-7.38 IU/L. No differences were found in the clinical pregnancy rate per transfer （43.48% vs 37.93% vs 40. 74%, P〉0.05） and the implantation rate （34.88% vs 22.22% vs 26.42%, P〉O.05）. Conclusion MPA is an effective oral alternative for the prevention of premature LH surges. Progestin-primed ovarian stimulation （PPOS） is a novel regimen of ovarian stimulation in combination with embryo cryopreservation, in which the two types of hMG are as effective as u-FSH.展开更多
BACKGROUND The outcomes of the use of commercial in vitro maturation(IVM)medium to culture immature oocytes obtained from conventional ovulation induction,followed by rescue intracytoplasmic sperm injection(RICSI),are...BACKGROUND The outcomes of the use of commercial in vitro maturation(IVM)medium to culture immature oocytes obtained from conventional ovulation induction,followed by rescue intracytoplasmic sperm injection(RICSI),are not ideal.It is thus difficult to widely adopt this approach in clinical practice.Therefore,it is necessary to explore methods for improving the clinical outcome of IVM.AIM To study the effect of sperm on the developmental potential of in vitro-matured oocytes in conventional culture.METHODS This was a retrospective study of patients whose immature oocytes were harvested from conventional oocyte stimulation cycles and underwent ICSI at our hospital between June 2018 and August 2020.RICSI was performed using sperm collected on the day of oocyte harvest(old)and sperm collected on the day of RICSI(fresh)and oocytes matured in vitro after 24 h of culture in conventional medium.The rates of in vitro oocyte maturation,normal fertilization,normal cleavage,day-3 top-quality embryos,and useful blastocyst formation were compared between the two groups.RESULTS In total,102 germinal vesicle(GV)-stage immature oocytes were cultured in the old sperm group.In the fresh sperm group,122 GV-stage immature oocytes were collected and cultured in vitro for 24 h.There were no significant differences in the general conditions of males and females between the two groups(P>0.05).The oocyte maturation,normal fertilization,and normal cleavage rates of the old and fresh groups were 51.0%vs 55.7%,61.5%vs 64.7%,and 93.8%vs 93.2%,respectively.None of the rates differed significantly(P>0.05)between the two groups.However,the day-3 top-quality embryo and useful blastocyst rates of the old and fresh sperm groups were 16.6%vs 63.4%;6.67%vs 34.6%,respectively.The day-3 top-quality embryos and useful blastocyst rates of the old sperm group were significantly lower than those of the fresh group(P<0.05).CONCLUSION In vitro maturation with conventional culture medium combined with the use of fresh sperm collected on the day of RICSI is an easy-to-implement strategy for patients whose oocytes are completely or mostly immature.展开更多
To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IV...To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IVF/ICSI and the subsequent pregnancy outcome in frozen-thawed embryo transfer （FET）. Methods In the retrospective cohort study, 2 166patients undergoing IVF/ICSI with moderate or high response were recruited and classified into three groups according to the trigger dose of hCG： 2 000 IU （group A, n=722）, 3 000 IU （group B, n=722） and 5 000 IU （group C, n= 722）. The main outcome was the proportion of mature oocytes retrieved, fertilization rates, clinical pregnancy rates, cumulative pregnancy rates and incidence of ovarian hyperstimulation syndrome （OHSS）. Results No evidence of statistically difference was found in the proportion of mature oocytes retrieved （89.92%, 91.40%, 90.20%, respectively） and fertilization rate （79.8%, 80.07%, 80.51%, respectively） among groups A, B and C. Serum E2 level on the day of hCG injection, the number of mature oocytes retrieved and good-quality embryos in group A were significantly higher than those in group B and group C. Clinical pregnancy rates per transfer cycle （45.95%, 43.97% and 44.25%）, ongoing pregnancy rates （43.17%, 40.91% and 42,53%）, implantation rates （30, 74%, 2Z 78% and 29.86%） and cumulative pregnancy rates per patient （58.31%, 53.6% and 54.85%）A reduced hCG dose of 2 000 IUfor moderate or high responders leads展开更多
Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide.Therapeutic failure in lung cancer(LUAD)is heavily influenced by drug resistance.This challenge stems from the diverse...Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide.Therapeutic failure in lung cancer(LUAD)is heavily influenced by drug resistance.This challenge stems from the diverse cell populations within the tumor,each having unique genetic,epigenetic,and phenotypic profiles.Such variations lead to varied therapeutic responses,thereby contributing to tumor relapse and disease progression.Methods:The Genomics of Drug Sensitivity in Cancer(GDSC)database was used in this investigation to obtain the mRNA expression dataset,genomic mutation profile,and drug sensitivity information of NSCLS.Machine Learning(ML)methods,including Random Forest(RF),Artificial Neurol Network(ANN),and Support Vector Machine(SVM),were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods.The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods,and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype.Finally,the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets.Results:Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs.Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response(area under the curve[AUC]0.875)using CIT,GAS2L3,STAG3L3,ATP2B4-mut,and IL15RA-mut as molecular features.Furthermore,the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance(AUC 0.780)in Gefitinib with CCL23-mut.Conclusion:This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.展开更多
BACKGROUND Twin reversed arterial perfusion(TRAP) sequence is an extremely rare congenital anomaly in monochorionic(MC) twins.The condition is characterized by a malformed fetus(acardiac twin) without cardiac activiti...BACKGROUND Twin reversed arterial perfusion(TRAP) sequence is an extremely rare congenital anomaly in monochorionic(MC) twins.The condition is characterized by a malformed fetus(acardiac twin) without cardiac activities being perfused by a structurally normal one(pump twin) via an artery-to-artery anastomosis in a reverse direction.CASE SUMMARY We described the first case of TRAP to receive laser surgery in Vietnam.The 26-wk pregnancy was originally misdiagnosed in another hospital as MC twins with single intrauterine fetal death.Following admission to our center,the diagnosis was amended to a 26-wk TRAP sequence stage IIb.The acardiac twin was 7.5 cm at the longest length,the ratio of the weight of the acardiac twin to the weight of the pump twin was more than 90%,the pump twin showed fetal distress with absent diastolic flow in umbilical artery of pump twin,and the peak systolic velocity in the middle cerebral artery = 1.6 Mo M.We performed emergency laser photocoagulation of the acardiac twin’s umbilical cord.After surgery,we successfully maintained the pregnancy for 8 wk and ended it electively by cesarean section at 34 wk of gestation due to rupture of membranes.CONCLUSION TRAP should be appropriately diagnosed and treated early to avoid complications of the pump twin.Fetoscopic laser photocoagulation is a new and effective treatment for this condition.展开更多
Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prola...Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prolactine levels in patients with high risk for ovarian hyperstimulation syndrome (OHSS). Material and Methods: 163 in vitro fertilisation (IVF) patients with high risk for OHSS were enrolled in the study. The criteria for inclusion were more than 15 oocytes retrieved at oocyte pick up. A standard antagonist protocol was used for ovulation induction. Cabergoline treatments (0.5 mg/day) were started on the day of oocyte retrieval and continued for eight days. Prolactine levels were measured at the day of oocyte retrieval and the 9th day after the oocyte retrieval. Results: Of the 163 patients, 26 (15.9%) had OHSS. Prolactine levels on the day of oocyte retrieval were 44.22 ± 24.78 ng/mL and 37.6 ± 22.5 ng/mL in patients with OHSS and without OHSS, respectively (P > 0.05). In contrary prolactine levels were significantly higher in patients with OHSS patients (3.9 ± 5.07 ng/mL) than in patients without OHSS (2.1 ± 2.92 ng/mL) at the 9th day after oocyte retrieval (P < 0.05). Conclusion: Prolactine levels were higher in patients with OHSS than without OHSS who were treated with cabergoline for the prevention of OHSS.展开更多
Objective: In this study, we aimed to investigate umbilical cord blood CD33 and erythropoietin (EPO) levels of pregnants with abnormal umbilical and uterine artery doppler waveforms and to compare with normal pregnanc...Objective: In this study, we aimed to investigate umbilical cord blood CD33 and erythropoietin (EPO) levels of pregnants with abnormal umbilical and uterine artery doppler waveforms and to compare with normal pregnancies. Materials and Methods: Total 40 pregnant women were included in this study. Of these 40 women, while 20 patients had abnormal umbilical and uterine artery doppler waveforms, the other 20 patients had normal umbilical and uterine artery doppler waveforms. After the delivery, blood samples were taken from umbilical artery of double clemped umbilical cord for blood gas parameters, EPO and CD33 levels. Sociodemographic findings, antepartum, intrapartum test results, labor and delivery characteristics and newborn examination results were recorded. Blood gas parameters, EPO and CD33 levels between groups were analyzed. Mann-Whitney U test and t-test were used as statistical methods. Results: There were no differences between parity, gestational ages and newborn weights of the groups. Cord blood CD33 and EPO levels of group with abnormal umbilical and uterine artery doppler waveforms were significantly higher than group with normal umbilical and uterine artery doppler waveforms (p < 0.01). Conclusion: Pathology on doppler screen shows to us a connection between chronic hypoxemia and abnormal on doppler screen. Preference of high blood CD33 levels for cord blood transplantation especially during last years can also be used with preference of cord blood with abnormal doppler findings.展开更多
The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phase...The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated.Cell cycle proteins enhance the activity of CDKs,while natural CDK inhibitors(CDKIs)suppress them.The cell cycle continues in cycles under normal conditions,but when conditions change,cells halt or terminate the cell cycle.Tumors are tissues that grow out of control,and the mechanisms of various types of tumors are different;however,almost all tumor cells share several common characteristics,including proliferation,prevention of apoptosis and genomic instability.Cellular division is essential in the progression of cancer.A key characteristic of cancer is the uncontrolled growth of tumor cells,which is due to the erratic behavior of several proteins during the cell cycle.Therefore,cell cycle regulators are considered attractive targets for the treatment of cancer.The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle,such as CDKs,and provides a brief overview of checkpoint kinases.The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.展开更多
Since the early days of assisted reproductive technology(ART),the importance of sperm processing,employed to separate the motile,morphologically normal sperm from the semen,has been shown to be beneficial.The aim of t...Since the early days of assisted reproductive technology(ART),the importance of sperm processing,employed to separate the motile,morphologically normal sperm from the semen,has been shown to be beneficial.The aim of the semen processing technique has been to remove seminal plasma and facilitate capacitation.Additionally,the presence of leukocytes,bacteria,and dead spermatozoa has been shown to be detrimental as it may cause oxidative stress that has an adverse effect on oocyte fertilization and embryo development.Hence,removal of leukocytes,bacteria,and dead spermatozoa is an important step of sperm processing for assisted reproduction.Currently,several sperm processing techniques have been evolved and optimized in the field of assisted reproduction.The requirements for in vitro fertilization(IVF),intracytoplasmic sperm injection(ICSI),and testicular sperm extraction(TESE)are different than those of intrauterine insemination(IUI).The yield of as many motile,morphologically normal sperm as possible is a prerequisite for the success of IVF insemination procedure.In ICSI,where injection of a single spermatozoon into the oocyte is performed by the embryologist,sperm selection techniques play a crucial role in the ICSI procedure.Finally,sperm retrieval in TESE samples with very low number of sperm may be challenging and requires extra care during sample processing.Additionally,sperm cryopreservation is necessary in TESE cases in order to avoid multiple biopsies.展开更多
In this study, we examined the relationship between sex hormone levels and lower urinary tract symptoms （LUTS） in men with benign prostatic hyperplasia （BPH） who underwent transurethral surgery. The study was cond...In this study, we examined the relationship between sex hormone levels and lower urinary tract symptoms （LUTS） in men with benign prostatic hyperplasia （BPH） who underwent transurethral surgery. The study was conducted in 158 patients who came to our hospital for surgery. Clinical conditions were assessed by body mass index （BMI）, digital rectal examination, International Prostate Symptom Score （IPSS） and transrectal ultrasound （TRUS）. The levels of sex hormones （including total testosterone （TT）, estradiol （E2）, progesterone （P）, luteinizing hormone （LH）, follicle-stimulating hormone （FSH） and prolactin （PRL）） and prostate-specific antigen （PSA） were reviewed. Correlations were determined through statistical analysis. The mean age was 72.06 _＋ 8.68 years. The total IPSS was significantly associated with the TT level （r = -0.21, P = 0.01）. Other sex hormone levels were not correlated with total IPSS. However, some ratios such as E2/TT （r = 0.23, P = 0o00） and FSH/LH （r = -0.17, P = 0.04） were associated with total IPSS. Further analysis showed that the nocturia was associated with age （r = 0.16, P = 0.04）, BMI （r = 0.21, P = 0.01）, and TT （r = -0.19, P = 0.02）. Moreover, we divided the patients into two subgroups based on IPSS severity （〈20 or 〉20）. The mean TT level was in the normal range, but it was significantly related to the presence of severe LUTS. In summary, our study has shown that the severity of LUTS is associated with TT, EJTT and FSH/LH in men who underwent prostate surgery. Increasing nocturia was observed in lower testosterone patients. Additional larger studies are needed to elucidate the potential mechanisms.展开更多
Objective To explore the different endometrial preparation for frozen-thawed embryo transfer （FET） in women with advanced endometriosis （EMS）. Methods The pregnancy outcomes of patients with advanced EMS （542 cyc...Objective To explore the different endometrial preparation for frozen-thawed embryo transfer （FET） in women with advanced endometriosis （EMS）. Methods The pregnancy outcomes of patients with advanced EMS （542 cycles）, who were prepared for FET, were retrospectively assessed. Included patients underwent a total of 233 FET cycles （180 patients） using natural cycle （NC）, a total of 142 FET cycles （115 patients） using letrozole （LE） ovulation induction, and a total of 167 FET cycles （137 patients） using hormonal replacement treatment （HRT） for endometrial preparation.Results There were no significant diffenences in the clinical pregnancy rate （LE： 49.30%, NC： 50.21%, and HRT： 43.11~/o, P=0.343）, the implantation rate （LE： 29.26%, NC： 36.03%, and HRT： 29.55%, P=0.084）, and the live birth rate （LE： 38.02%, NC： 39.11%, and HR T.＂ 35.33 %, P=O. 648） among the three groups. No statistically signifi- cant differences were observed in the ongoing pregnancy rate, the miscarriage rate, and the pregnancy complication rate. The single birth weight in patients using NC- FET was lower than that in patients using HRT-FET （P=0.044） and a higher twin birth weight in patients using LE-FET were observed compared with other groups （P=O. 022）. The rate of birth weight 〈2 500 g was also higher in the NC-FET group than in other groups. No congenital birth defects were found in the three groups. Conclusion Different endometrial preparation protocols without ultra-long GnRH-a down-regulation for FET yield similar pregnancy outcomes in patients with EMS. A tailored endometrial preparation protocol should be recommended according to different patients＇ situation.展开更多
Human pluripotent stem cells(PSCs),encompassing embryonic stem cells and induced pluripotent stem cells,proliferate extensively and differentiate into virtually any desired cell type.PSCs endow regenerative medicine w...Human pluripotent stem cells(PSCs),encompassing embryonic stem cells and induced pluripotent stem cells,proliferate extensively and differentiate into virtually any desired cell type.PSCs endow regenerative medicine with an unlimited source of replacement cells suitable for human therapy.Several hurdles must be carefully addressed in PSC research before these theoretical possibilities are translated into clinical applications.These obstacles are:(1) cell proliferation;(2) cell differentiation;(3) genetic integrity;(4) allogenicity;and(5) ethical issues.We discuss these issues and underline the fact that the answers to these questions lie in a better understanding of the biology of PSCs.To contribute to this aim,we have developed a free online expression atlas,Amazonia!,that displays for each human gene a virtual northern blot for PSC samples and adult tissues(http://www.amazonia.transcriptome.eu).展开更多
T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs...T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well established.Here,we report a family with 15 CVM patients distributed across 4 generations.All affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and phenotype.In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the wild-type.To determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM phenotype.Most heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral deformities.Overall,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.展开更多
Monoclonal antibodies and antibody-based agents are undergoing remarkable development in cancer immunotherapy.Based on their structural components,these antibodies mediate the crosslinking of tumor cells and the immun...Monoclonal antibodies and antibody-based agents are undergoing remarkable development in cancer immunotherapy.Based on their structural components,these antibodies mediate the crosslinking of tumor cells and the immune system,enabling specific antigen targeting and broad immune responses.Novel engineering strategies are aimed at improving both specificity and affinity of antigen recognition and enhancing the recruitment and activation of immune cells.Antibody-based therapeutics have been expanded for use in combination with other immunotherapies such as cellular immunotherapy and therapeutic vaccines.In this review,we provide comprehensive updates on the ongoing clinical development and evolving practices in the field,with a specific emphasis on the intricate mechanisms of action.展开更多
The microtubule organizing centers(MTOCs)of human and mouse oocytes are essential for meiotic spindle assembly and for ensuring precise chromosome segregations.Previous studies mainly focus on investigating MTOCs chan...The microtubule organizing centers(MTOCs)of human and mouse oocytes are essential for meiotic spindle assembly and for ensuring precise chromosome segregations.Previous studies mainly focus on investigating MTOCs changes in metaphase I oocyte.However,the detailed dynamic changes and underlying mechanisms of the MTOCs in germinal vesicle(GV)oocytes—a stage that early events of MTOC maturation happened—remain unclear.Here we explored the dynamics of MTOCs maturation in human and mouse GV oocytes and found that MTOCs maturation is a largely conserved process,consisting of two tightly coupled processes referred to as MTOCs activation and migration.We found that cytoskeleton associated protein 5(CKAP5)and transforming acidic coiled-coil containing protein 3(TACC3)play key roles in MTOCs maturation in oocytes.The activation of the MTOCs is a prerequisite for migration initiation,and the migration of the MTOCs is facilitated by dynein/dynactin in oocytes.The disruption of MTOC maturation resulted in spindle assembly failure.Importantly,impaired MTOCs maturation is associated with the physiological aging of oocytes.This study provides a comprehensive understanding of MTOCs dynamics in human and mouse oocytes.展开更多
Objectives： To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney （Shen） and Spleen （Pi） in advance] in Chinese medicine （CM） an...Objectives： To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney （Shen） and Spleen （Pi） in advance] in Chinese medicine （CM） and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure （RIF）; and to study the differences in patients＇ endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. Methods： In the clinical study, 168 frozen-thawed embryo transfer （FET） cycles for couples with RIF conforming to the research protocol were randomly divided into three groups： a CM group with 56 cycles （CM combined with FET）, a hysteroscopy group with 55 cycles （hysteroscopic endometfial mechanical stimulation）, and a control group with 57 cycles （conventional FET）. Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol （E2） and progesterone （P） on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. Results： Endometrial thickness, E2 and P levels, and the EJP ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group （P〈0.05）, and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. Conclusions： Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of RIF-FET cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.展开更多
Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour metastasis.SIRT6 can promote the migration of pancreatic cancer and could be ...Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour metastasis.SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer.However,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be discovered.Here,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/L.Moreover,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/L.The allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural analyses.Importantly,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver metastasis.To our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic cancer.It not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.展开更多
基金supported by grant from the National Key Research and Development Program of China(No.2017YFC1002003).
文摘Numerous genes have been associated with multiple morphological abnormalities of the sperm flagella(MMAF),which cause severe asthenozoospermia and lead to male infertility,while the causes of approximately 50%of MMAF cases remain unclear.To reveal the genetic causes of MMAF in an infertile patient,whole-exome sequencing was performed to screen for pathogenic genes,and electron microscope was used to reveal the sperm flagellar ultrastructure.A novel heterozygous missense mutation in the outer dense fiber protein 2(ODF2)gene was detected,which was inherited from the patient’s mother and predicted to be potentially damaging.Transmission electron microscopy revealed that the outer dense fibers were defective in the patient’s sperm tail,which was similar to that of the reported heterozygous Odf2 mutation mouse.Immunostaining of ODF2 showed severe ODF2 expression defects in the patient’s sperm.Therefore,it was concluded that the heterozygous mutation in ODF2 caused MMAF in this case.To evaluate the possibility of assisted reproductive technology(ART)treatment for this patient,intracytoplasmic sperm injection(ICSI)was performed,with the help of a hypo-osmotic swelling test and laser-assisted immotile sperm selection(LAISS)for available sperm screening,and artificial oocyte activation with ionomycin was applied to improve the fertilization rate.Four ICSI cycles were performed,and live birth was achieved in the LAISS-applied cycle,suggesting that LAISS would be valuable in ART treatment for MMAF.
基金supported by National Natural Science Foundation of China (No. 31071275, No. 81270749 and No. 31101070)
文摘Objective To compare the results of a novel regimen of human menopausal gonadotrophin （hMG） in combination with clomiphene citrate （CC） in mid-to-late follicular phase with those of a short protocol of GnRH agonist （GnRHa） and hMG used for IVF. Methods In the retrospective study, 842 patients undergoing IVF were collected and classified into two groups： hMG in combination with CC in mid-to-late follicular phase （group A, n=319） and short protocol of GnRHa-hMG （group B, n=523）. The main outcome measures were ovarian responses in stimulation cycles and pregnancy outcomes in subsequent frozen-thawed embryo transfer （FET） cycles. Results In group A, the serum LH concentration on day 8 -10 was similar with that on the day of hCG administration （2.43 ± 1.92 IU vs 2.51 ±2.05 IU）. The number of mature follicles and oocytes retrieved was significantly lower in group A than in group B while the fertilization rate and the cleavage rate were comparable. The clinical pregnancy rate （47. 79% vs 48.04%）, the implantation rate （32.49% vs 33.11%） and the cumulative pregnancy rate （58.09% vs 60.22%） were respectively similar in group A and group B. Conclusion hMG in combination with CC in mid-to-late follicular phase results in the same pregnancy outcome as short protocol. The novel protocol may take the advantage of eliminating the occurrehce of a premature endogenous LH Surge.
文摘Objective To compare the clinical characteristics in a gonadotropin （Gn） and medroxyprogestrone acetate （MPA） protocol using three types of Gn in normal ovulatory women undergoing IVF/ICSI treatments. Methods A total of 258 normal ovulatory IVF/ICSI patients undergoing ovarian stimulation in a Gn and MPA protocol were analyzed in this retrospective study and allocated into three groups according to the Gn used： group A, hMG-A （brand name： Fengyuan, n=105）; group B, hMG-B （brand name： Lebaode, n=90）; group C： u-FSH （brand name： Lishenbao, n=63）. The hormone profile, embryological characteristics, and the pregnant results after frozen-thawed embryo transfer （FET） were compared among the three groups. Results There was no significant difference in the number of oocytes retrieved among the three groups （12.1± 6.9 vs 12.1±5.6 vs 13.1 ±8.8, P〉0.05）. Other indicators such as the number of mature oocyte, fertilization, cleavage and viable embryo were similar （P〉0.05）. No premature LH surges were detected, with a range of 0.04-7.38 IU/L. No differences were found in the clinical pregnancy rate per transfer （43.48% vs 37.93% vs 40. 74%, P〉0.05） and the implantation rate （34.88% vs 22.22% vs 26.42%, P〉O.05）. Conclusion MPA is an effective oral alternative for the prevention of premature LH surges. Progestin-primed ovarian stimulation （PPOS） is a novel regimen of ovarian stimulation in combination with embryo cryopreservation, in which the two types of hMG are as effective as u-FSH.
基金Supported by Science and Technology Collaborative Innovation Project of Guangzhou,No.201704020217
文摘BACKGROUND The outcomes of the use of commercial in vitro maturation(IVM)medium to culture immature oocytes obtained from conventional ovulation induction,followed by rescue intracytoplasmic sperm injection(RICSI),are not ideal.It is thus difficult to widely adopt this approach in clinical practice.Therefore,it is necessary to explore methods for improving the clinical outcome of IVM.AIM To study the effect of sperm on the developmental potential of in vitro-matured oocytes in conventional culture.METHODS This was a retrospective study of patients whose immature oocytes were harvested from conventional oocyte stimulation cycles and underwent ICSI at our hospital between June 2018 and August 2020.RICSI was performed using sperm collected on the day of oocyte harvest(old)and sperm collected on the day of RICSI(fresh)and oocytes matured in vitro after 24 h of culture in conventional medium.The rates of in vitro oocyte maturation,normal fertilization,normal cleavage,day-3 top-quality embryos,and useful blastocyst formation were compared between the two groups.RESULTS In total,102 germinal vesicle(GV)-stage immature oocytes were cultured in the old sperm group.In the fresh sperm group,122 GV-stage immature oocytes were collected and cultured in vitro for 24 h.There were no significant differences in the general conditions of males and females between the two groups(P>0.05).The oocyte maturation,normal fertilization,and normal cleavage rates of the old and fresh groups were 51.0%vs 55.7%,61.5%vs 64.7%,and 93.8%vs 93.2%,respectively.None of the rates differed significantly(P>0.05)between the two groups.However,the day-3 top-quality embryo and useful blastocyst rates of the old and fresh sperm groups were 16.6%vs 63.4%;6.67%vs 34.6%,respectively.The day-3 top-quality embryos and useful blastocyst rates of the old sperm group were significantly lower than those of the fresh group(P<0.05).CONCLUSION In vitro maturation with conventional culture medium combined with the use of fresh sperm collected on the day of RICSI is an easy-to-implement strategy for patients whose oocytes are completely or mostly immature.
基金supported by National Natural Science Foundation of China(No.31071275)Natural Science Foundation of Shanghai of China(No.09411962900)
文摘To compare the efficacy of human chorionic gonadotrophin （hCG） at reduced doses of 2 000 IU and 3 000 IU for moderate or high responders with the dose of 5 000 IU in term of inducing final oocyte maturation for IVF/ICSI and the subsequent pregnancy outcome in frozen-thawed embryo transfer （FET）. Methods In the retrospective cohort study, 2 166patients undergoing IVF/ICSI with moderate or high response were recruited and classified into three groups according to the trigger dose of hCG： 2 000 IU （group A, n=722）, 3 000 IU （group B, n=722） and 5 000 IU （group C, n= 722）. The main outcome was the proportion of mature oocytes retrieved, fertilization rates, clinical pregnancy rates, cumulative pregnancy rates and incidence of ovarian hyperstimulation syndrome （OHSS）. Results No evidence of statistically difference was found in the proportion of mature oocytes retrieved （89.92%, 91.40%, 90.20%, respectively） and fertilization rate （79.8%, 80.07%, 80.51%, respectively） among groups A, B and C. Serum E2 level on the day of hCG injection, the number of mature oocytes retrieved and good-quality embryos in group A were significantly higher than those in group B and group C. Clinical pregnancy rates per transfer cycle （45.95%, 43.97% and 44.25%）, ongoing pregnancy rates （43.17%, 40.91% and 42,53%）, implantation rates （30, 74%, 2Z 78% and 29.86%） and cumulative pregnancy rates per patient （58.31%, 53.6% and 54.85%）A reduced hCG dose of 2 000 IUfor moderate or high responders leads
文摘Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide.Therapeutic failure in lung cancer(LUAD)is heavily influenced by drug resistance.This challenge stems from the diverse cell populations within the tumor,each having unique genetic,epigenetic,and phenotypic profiles.Such variations lead to varied therapeutic responses,thereby contributing to tumor relapse and disease progression.Methods:The Genomics of Drug Sensitivity in Cancer(GDSC)database was used in this investigation to obtain the mRNA expression dataset,genomic mutation profile,and drug sensitivity information of NSCLS.Machine Learning(ML)methods,including Random Forest(RF),Artificial Neurol Network(ANN),and Support Vector Machine(SVM),were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods.The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods,and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype.Finally,the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets.Results:Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs.Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response(area under the curve[AUC]0.875)using CIT,GAS2L3,STAG3L3,ATP2B4-mut,and IL15RA-mut as molecular features.Furthermore,the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance(AUC 0.780)in Gefitinib with CCL23-mut.Conclusion:This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.
文摘BACKGROUND Twin reversed arterial perfusion(TRAP) sequence is an extremely rare congenital anomaly in monochorionic(MC) twins.The condition is characterized by a malformed fetus(acardiac twin) without cardiac activities being perfused by a structurally normal one(pump twin) via an artery-to-artery anastomosis in a reverse direction.CASE SUMMARY We described the first case of TRAP to receive laser surgery in Vietnam.The 26-wk pregnancy was originally misdiagnosed in another hospital as MC twins with single intrauterine fetal death.Following admission to our center,the diagnosis was amended to a 26-wk TRAP sequence stage IIb.The acardiac twin was 7.5 cm at the longest length,the ratio of the weight of the acardiac twin to the weight of the pump twin was more than 90%,the pump twin showed fetal distress with absent diastolic flow in umbilical artery of pump twin,and the peak systolic velocity in the middle cerebral artery = 1.6 Mo M.We performed emergency laser photocoagulation of the acardiac twin’s umbilical cord.After surgery,we successfully maintained the pregnancy for 8 wk and ended it electively by cesarean section at 34 wk of gestation due to rupture of membranes.CONCLUSION TRAP should be appropriately diagnosed and treated early to avoid complications of the pump twin.Fetoscopic laser photocoagulation is a new and effective treatment for this condition.
文摘Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prolactine levels in patients with high risk for ovarian hyperstimulation syndrome (OHSS). Material and Methods: 163 in vitro fertilisation (IVF) patients with high risk for OHSS were enrolled in the study. The criteria for inclusion were more than 15 oocytes retrieved at oocyte pick up. A standard antagonist protocol was used for ovulation induction. Cabergoline treatments (0.5 mg/day) were started on the day of oocyte retrieval and continued for eight days. Prolactine levels were measured at the day of oocyte retrieval and the 9th day after the oocyte retrieval. Results: Of the 163 patients, 26 (15.9%) had OHSS. Prolactine levels on the day of oocyte retrieval were 44.22 ± 24.78 ng/mL and 37.6 ± 22.5 ng/mL in patients with OHSS and without OHSS, respectively (P > 0.05). In contrary prolactine levels were significantly higher in patients with OHSS patients (3.9 ± 5.07 ng/mL) than in patients without OHSS (2.1 ± 2.92 ng/mL) at the 9th day after oocyte retrieval (P < 0.05). Conclusion: Prolactine levels were higher in patients with OHSS than without OHSS who were treated with cabergoline for the prevention of OHSS.
文摘Objective: In this study, we aimed to investigate umbilical cord blood CD33 and erythropoietin (EPO) levels of pregnants with abnormal umbilical and uterine artery doppler waveforms and to compare with normal pregnancies. Materials and Methods: Total 40 pregnant women were included in this study. Of these 40 women, while 20 patients had abnormal umbilical and uterine artery doppler waveforms, the other 20 patients had normal umbilical and uterine artery doppler waveforms. After the delivery, blood samples were taken from umbilical artery of double clemped umbilical cord for blood gas parameters, EPO and CD33 levels. Sociodemographic findings, antepartum, intrapartum test results, labor and delivery characteristics and newborn examination results were recorded. Blood gas parameters, EPO and CD33 levels between groups were analyzed. Mann-Whitney U test and t-test were used as statistical methods. Results: There were no differences between parity, gestational ages and newborn weights of the groups. Cord blood CD33 and EPO levels of group with abnormal umbilical and uterine artery doppler waveforms were significantly higher than group with normal umbilical and uterine artery doppler waveforms (p < 0.01). Conclusion: Pathology on doppler screen shows to us a connection between chronic hypoxemia and abnormal on doppler screen. Preference of high blood CD33 levels for cord blood transplantation especially during last years can also be used with preference of cord blood with abnormal doppler findings.
文摘The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate.Cyclin-dependent kinases(CDKs)play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated.Cell cycle proteins enhance the activity of CDKs,while natural CDK inhibitors(CDKIs)suppress them.The cell cycle continues in cycles under normal conditions,but when conditions change,cells halt or terminate the cell cycle.Tumors are tissues that grow out of control,and the mechanisms of various types of tumors are different;however,almost all tumor cells share several common characteristics,including proliferation,prevention of apoptosis and genomic instability.Cellular division is essential in the progression of cancer.A key characteristic of cancer is the uncontrolled growth of tumor cells,which is due to the erratic behavior of several proteins during the cell cycle.Therefore,cell cycle regulators are considered attractive targets for the treatment of cancer.The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle,such as CDKs,and provides a brief overview of checkpoint kinases.The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.
文摘Since the early days of assisted reproductive technology(ART),the importance of sperm processing,employed to separate the motile,morphologically normal sperm from the semen,has been shown to be beneficial.The aim of the semen processing technique has been to remove seminal plasma and facilitate capacitation.Additionally,the presence of leukocytes,bacteria,and dead spermatozoa has been shown to be detrimental as it may cause oxidative stress that has an adverse effect on oocyte fertilization and embryo development.Hence,removal of leukocytes,bacteria,and dead spermatozoa is an important step of sperm processing for assisted reproduction.Currently,several sperm processing techniques have been evolved and optimized in the field of assisted reproduction.The requirements for in vitro fertilization(IVF),intracytoplasmic sperm injection(ICSI),and testicular sperm extraction(TESE)are different than those of intrauterine insemination(IUI).The yield of as many motile,morphologically normal sperm as possible is a prerequisite for the success of IVF insemination procedure.In ICSI,where injection of a single spermatozoon into the oocyte is performed by the embryologist,sperm selection techniques play a crucial role in the ICSI procedure.Finally,sperm retrieval in TESE samples with very low number of sperm may be challenging and requires extra care during sample processing.Additionally,sperm cryopreservation is necessary in TESE cases in order to avoid multiple biopsies.
文摘In this study, we examined the relationship between sex hormone levels and lower urinary tract symptoms （LUTS） in men with benign prostatic hyperplasia （BPH） who underwent transurethral surgery. The study was conducted in 158 patients who came to our hospital for surgery. Clinical conditions were assessed by body mass index （BMI）, digital rectal examination, International Prostate Symptom Score （IPSS） and transrectal ultrasound （TRUS）. The levels of sex hormones （including total testosterone （TT）, estradiol （E2）, progesterone （P）, luteinizing hormone （LH）, follicle-stimulating hormone （FSH） and prolactin （PRL）） and prostate-specific antigen （PSA） were reviewed. Correlations were determined through statistical analysis. The mean age was 72.06 _＋ 8.68 years. The total IPSS was significantly associated with the TT level （r = -0.21, P = 0.01）. Other sex hormone levels were not correlated with total IPSS. However, some ratios such as E2/TT （r = 0.23, P = 0o00） and FSH/LH （r = -0.17, P = 0.04） were associated with total IPSS. Further analysis showed that the nocturia was associated with age （r = 0.16, P = 0.04）, BMI （r = 0.21, P = 0.01）, and TT （r = -0.19, P = 0.02）. Moreover, we divided the patients into two subgroups based on IPSS severity （〈20 or 〉20）. The mean TT level was in the normal range, but it was significantly related to the presence of severe LUTS. In summary, our study has shown that the severity of LUTS is associated with TT, EJTT and FSH/LH in men who underwent prostate surgery. Increasing nocturia was observed in lower testosterone patients. Additional larger studies are needed to elucidate the potential mechanisms.
基金supported in part by grants from the National Natural Science Foundation of China(No.81270749 and No.81470064)the Natural Science Foundation of Shanghai,China(No.15411953000,No.15411964500 and No.14ZR1423900)
文摘Objective To explore the different endometrial preparation for frozen-thawed embryo transfer （FET） in women with advanced endometriosis （EMS）. Methods The pregnancy outcomes of patients with advanced EMS （542 cycles）, who were prepared for FET, were retrospectively assessed. Included patients underwent a total of 233 FET cycles （180 patients） using natural cycle （NC）, a total of 142 FET cycles （115 patients） using letrozole （LE） ovulation induction, and a total of 167 FET cycles （137 patients） using hormonal replacement treatment （HRT） for endometrial preparation.Results There were no significant diffenences in the clinical pregnancy rate （LE： 49.30%, NC： 50.21%, and HRT： 43.11~/o, P=0.343）, the implantation rate （LE： 29.26%, NC： 36.03%, and HRT： 29.55%, P=0.084）, and the live birth rate （LE： 38.02%, NC： 39.11%, and HR T.＂ 35.33 %, P=O. 648） among the three groups. No statistically signifi- cant differences were observed in the ongoing pregnancy rate, the miscarriage rate, and the pregnancy complication rate. The single birth weight in patients using NC- FET was lower than that in patients using HRT-FET （P=0.044） and a higher twin birth weight in patients using LE-FET were observed compared with other groups （P=O. 022）. The rate of birth weight 〈2 500 g was also higher in the NC-FET group than in other groups. No congenital birth defects were found in the three groups. Conclusion Different endometrial preparation protocols without ultra-long GnRH-a down-regulation for FET yield similar pregnancy outcomes in patients with EMS. A tailored endometrial preparation protocol should be recommended according to different patients＇ situation.
基金Supported by Grants from the Association Franaise contreles Myopathies (AFM),the Agence nationale de la recherche (ANR) and the Région Languedoc-Roussillon
文摘Human pluripotent stem cells(PSCs),encompassing embryonic stem cells and induced pluripotent stem cells,proliferate extensively and differentiate into virtually any desired cell type.PSCs endow regenerative medicine with an unlimited source of replacement cells suitable for human therapy.Several hurdles must be carefully addressed in PSC research before these theoretical possibilities are translated into clinical applications.These obstacles are:(1) cell proliferation;(2) cell differentiation;(3) genetic integrity;(4) allogenicity;and(5) ethical issues.We discuss these issues and underline the fact that the answers to these questions lie in a better understanding of the biology of PSCs.To contribute to this aim,we have developed a free online expression atlas,Amazonia!,that displays for each human gene a virtual northern blot for PSC samples and adult tissues(http://www.amazonia.transcriptome.eu).
基金supported by the National Key R&D Program of China(2021YFC2701101 to H.W.and X.Y.)the National Natural Science Foundation of China(81930036 and 82150008 to H.W.,and 31000542 to X.Y.)the Commission of Science and Technology of Shanghai Municipality(20JC1418500 to H.W.).
文摘T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal development.Although it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well established.Here,we report a family with 15 CVM patients distributed across 4 generations.All affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and phenotype.In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the wild-type.To determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM phenotype.Most heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral deformities.Overall,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.
基金supported by the National Natural Science Foundation of China(82322055,82272792,81903140,and 92169115)the Shanghai Rising-Star Program(23QA1405800)+1 种基金the Shanghai Outstanding Academic Leader Program(23XD1424800)the Shanghai Chenguang Program(17CG35).
文摘Monoclonal antibodies and antibody-based agents are undergoing remarkable development in cancer immunotherapy.Based on their structural components,these antibodies mediate the crosslinking of tumor cells and the immune system,enabling specific antigen targeting and broad immune responses.Novel engineering strategies are aimed at improving both specificity and affinity of antigen recognition and enhancing the recruitment and activation of immune cells.Antibody-based therapeutics have been expanded for use in combination with other immunotherapies such as cellular immunotherapy and therapeutic vaccines.In this review,we provide comprehensive updates on the ongoing clinical development and evolving practices in the field,with a specific emphasis on the intricate mechanisms of action.
基金supported by the National Natural Science Foundation of China(82325021,82288102,32130029,82422033,82271685,82171643,and 82171685)the Shanghai Rising-Star Program(23QA1401800)+3 种基金the New Cornerstone Science Foundation through the XPLORER PRIZE,the Fund of Fudan University and Cao’ejiang Basic Research(24FCB01)the SANS Exploration Scholarthe Fund for Excellent Young Scholars of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYYQ004)the Shanghai JIAI Genetics and IVF Institute Found(JA-2025033).
文摘The microtubule organizing centers(MTOCs)of human and mouse oocytes are essential for meiotic spindle assembly and for ensuring precise chromosome segregations.Previous studies mainly focus on investigating MTOCs changes in metaphase I oocyte.However,the detailed dynamic changes and underlying mechanisms of the MTOCs in germinal vesicle(GV)oocytes—a stage that early events of MTOC maturation happened—remain unclear.Here we explored the dynamics of MTOCs maturation in human and mouse GV oocytes and found that MTOCs maturation is a largely conserved process,consisting of two tightly coupled processes referred to as MTOCs activation and migration.We found that cytoskeleton associated protein 5(CKAP5)and transforming acidic coiled-coil containing protein 3(TACC3)play key roles in MTOCs maturation in oocytes.The activation of the MTOCs is a prerequisite for migration initiation,and the migration of the MTOCs is facilitated by dynein/dynactin in oocytes.The disruption of MTOC maturation resulted in spindle assembly failure.Importantly,impaired MTOCs maturation is associated with the physiological aging of oocytes.This study provides a comprehensive understanding of MTOCs dynamics in human and mouse oocytes.
基金Supported by Shanghai Municipal Health Bureau Foundation of Chinese Traditional Medicine(No.2010L026A)
文摘Objectives： To investigate the clinical effect of sequential therapeutic intervention Yupei Qisun [compensating for weakness by invigorating Kidney （Shen） and Spleen （Pi） in advance] in Chinese medicine （CM） and hysteroscopic endometrial mechanical stimulation on the treatment of infertile patients with repeated implantation failure （RIF）; and to study the differences in patients＇ endometrial thickness and type on the day of embryo transfer, serum hormone levels on embryo transfer day and clinical pregnancy outcomes. Methods： In the clinical study, 168 frozen-thawed embryo transfer （FET） cycles for couples with RIF conforming to the research protocol were randomly divided into three groups： a CM group with 56 cycles （CM combined with FET）, a hysteroscopy group with 55 cycles （hysteroscopic endometfial mechanical stimulation）, and a control group with 57 cycles （conventional FET）. Differences in endometrial thickness on the embryo transfer day, levels of serum estradiol （E2） and progesterone （P） on the embryo transfer day, the E2/P ratio on the embryo transfer day, biochemical and clinical pregnancy rates, implantation rate, abnormal pregnancy rate and other indices were compared among the three groups. Results： Endometrial thickness, E2 and P levels, and the EJP ratio on embryo transfer day and other factors had no significant differences among groups. The biochemical pregnancy, clinical pregnancy, and implantation rates of the CM and hysteroscopy groups were significantly higher than the control group （P〈0.05）, and there were no significant differences between these two groups. The abnormal pregnancy rate had no significant difference among the three groups. Conclusions： Sequential therapy of Yupei Qisun could significantly improve the clinical outcomes of RIF-FET cycles, being equivalent to hysteroscopic endometrial mechanical stimulation, and provided a reliable method to treat such infertile couples.
基金supported by the National Key R&D Program of China(grant no.2022YFF1203005)the National Natural Science Foundation of China(22237005,81903458,82273425)+1 种基金Innovative research team of high-level local universities in Shanghai(SHSMU-ZDCX20212700,China)China Postdoctoral Science Foundation(2019M660090)。
文摘Pancreatic cancer,one of the most aggressive malignancies,has no effective treatment due to the lack of targets and drugs related to tumour metastasis.SIRT6 can promote the migration of pancreatic cancer and could be a potential target for antimetastasis of pancreatic cancer.However,highly selective and potency SIRT6 inhibitor that can be used in vivo is yet to be discovered.Here,we developed a noveSIRT6 allosteric inhibitor,compound 11e,with maximal inhibitory potency and an IC_(50) value of 0.98±0.13μmol/L.Moreover,compound 11e exhibited significant selectivity against other histone deacetylases(HADC1-11 and SIRT1-3)at concentrations up to 100μmol/L.The allosteric site and the molecular mechanism of inhibition were extensively elucidated by cocrystal complex structure and dynamic structural analyses.Importantly,we confirmed the antimetastatic function of such inhibitors in four pancreatic cancer cell lines as well as in two mouse models of pancreatic cancer liver metastasis.To our knowledge,this is the first study to reveal the in vivo effects of SIRT6 inhibitors on liver metastatic pancreatic cancer.It not only provides a promising lead compound for subsequent inhibitor developmentargeting SIRT6 but also provides a potential approach to address the challenge of metastasis in pancreatic cancer.
