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Deletion of CHD8 in cerebellar granule neuron progenitors leads to severe cerebellar hypoplasia,ataxia,and psychiatric behavior in mice

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Journal of Genetics and Genomics 2022年第9期49卷 859-869页

作者： Xiang Chen Tong Chen Chen Dong Huiyao Chen Xinran Dong Lin Yang Liyuan Hu Huijun Wang Bingbing Wu Ye Yao Yu Xiong Man Xiong Yifeng Lin Wenhao Zhou departments of Neonatology Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai201102China Institutes of Biomedical Sciences Fudan UniversityShanghai200032China Key Laboratory of Birth Defects Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai201102China department of Biostatistics School of Public HealthFudan UniversityShanghai200032China department of obstetrics Obstetrics and Gynecology Hospital of Fudan UniversityShanghai200090China Stem Cell Center Children's Hospital of Fudan UniversityShanghai201102China MOE Frontiers Center for Brain Science Fudan UniversityShanghai201102China

CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not been comprehensively investigated.The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear.In this study,we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development.Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected.Genetic deletion of Chd8 in cerebellar granule neuron progenitors(GNPs)leads to cerebellar hypoplasia,absent of proliferation layer and ectopic of Purkinje neuron.However,no substantial cerebellar dysplasia is detected in mice with Purkinje neuron-or oligodendrocyte-specific Chd8 ablation.Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs,indicating the potential mechanism.Importantly,in addition to the ataxia phenotype,mice with GNPspecific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests.Taken together,our results provide insights not only into the function of CHD8 in cerebellar development,but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.

关键词： Cerebellum Granule neuron CHD8 Autism spectrum disorder

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A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2023年第1期24卷 64-77页

作者： Jiahang MO Shunyi RUAN Baicai YANG Yunfeng JIN Keyi LIU Xukai LUO Hua JIANG obstetrics and gynecology Hospital Fudan UniversityShanghai 200011China shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China department of Oncology Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China department of gynecology Jiaxing University Affiliated Women and Children HospitalJiaxing 314050China department of Pathology Women’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310006China

Endoplasmic reticulum(ER)stress,as an emerging hallmark feature of cancer,has a considerable impact on cell proliferation,metastasis,invasion,and chemotherapy resistance.Ovarian cancer(OvCa)is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis.Studies have explored the influence of ER stress on OvCa in recent years,while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored.Here,we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)cohorts for the screening of prognosis-related genes.The least absolute shrinkage and selection operator(LASSO)regression was applied to establish an ER stress-related risk signature based on the TCGA cohort.A seven-gene signature revealed a favorable predictive efficacy for the TCGA,International Cancer Genome Consortium(ICGC),and another GEO cohort(P<0.001,P<0.001,and P=0.04,respectively).Moreover,functional annotation indicated that this signature was enriched in cellular response and senescence,cytokines interaction,as well as multiple immune-associated terms.The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group.In conclusion,ER stress-related genes are vital factors predicting the prognosis of OvCa,and possess great application potential in the clinic.

关键词： Ovarian cancer(OvCa) Endoplasmic reticulum(ER)stress Risk signature Prognosis Immune infiltration

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Altered Expression of COMP,Collagen 1,and MMP9 in Pelvic Organ Prolapse

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Biomedical and Environmental Sciences 2023年第10期36卷 979-982页

作者： CHEN Yi Fei XU Hai Nan DUAN Yi Nan XIA Zhi Jun department of obstetrics and gynecology Shengjing Hospital of China Medical UniversityShenyang 110004LiaoningChina department of obstetrics and gynecology Liaoning Province Hospital for Women and ChildrenShenyang 110004LiaoningChina department of gynecology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Female pelvic organ prolapse(POP)is a common disorder that affects the quality of life of women considerably.Studies in China have reported a 9.6%prevalence of symptomatic POP in adult women[1],with a higher prevalenc... 详细信息

关键词： Collagen MMP9 COMP POP

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Diffuse uterine leiomyomatosis: A case report and review of literature

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World Journal of Clinical Cases 2022年第24期10卷 8797-8804页

作者： Hui-Min Ren Qing-Zhu Wang Jia-Nan Wang Gang-Jie Hong Shuang Zhou Jun-Yan Zhu Shan-Ji Li department of gynecology Zhoushan Branch Ruijin HospitalShanghai Jiaotong University School of MedicineZhoushan 316000Zhejiang ProvinceChina department of obstetrics and gynecology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina department of Pathology Zhoushan Branch Ruijin HospitalShanghai Jiaotong University School of MedicineZhoushan 316000Zhejiang ProvinceChina department of obstetrics and gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 200090China department of obstetrics and gynecology Renji HospitalShanghai Jiaotong University School of MedicineShanghai 200127China

BACKGROUND Diffuse uterine leiomyomatosis(DUL)is a benign uterine smooth muscle neoplasm with unknown etiology.Since DUL is rarely reported,knowledge regarding it is limited.The rate of early diagnosis is low,and DUL is often misdiagnosed as common multiple uterine leiomyomas before surgery.CASE SUMMARY A 27-year-old patient with no sexual activity presented to the Emergency department of our hospital complaining of heavy vaginal bleeding.She had a history of uterine fibroids and menorrhagia.Pelvic examination showed a regularly enlarged uterus,similar in size to that associated with a 4-mo pregnancy.Pelvic magnetic resonance imaging(MRI)revealed numerous multiple uterine fibroids,and a transabdominal myomectomy(TM)was performed.Intraoperative exploration revealed that the myometrium was full of myoma nodules of variable sizes.Over 50 leiomyomas were removed.The pathology report confirmed leiomyoma.The patient was discharged and received a gonadotropin-releasing hormone analog(3.75 mg)for 6 mo.Ten months after surgery,the patient presented to the hospital again for abnormal uterine bleeding.MRI showed an irregular mass with a diameter of 5.2 cm without sharp demarcation in the uterine cavity.Submucosal leiomyoma was considered first,and the patient underwent a hysteroscopic myomectomy plus hymen repair.Intraoperative exploration showed that there were several leiomyomatosis masses in the cavity.Postoperative pathological exam-ination confirmed submucosal leiomyoma and necrotic and generative tissue.Although the menstrual cycle was still irregular,the patient did not have symptoms of menorrhagia for a period of 28 mo after the second surgery.CONCLUSION Individuals with DUL are easily misdiagnosed due to the lack of specific manifestations of this disease.MRI is helpful for early identification and preoperative evaluation.There is currently no unified method of diagnosis.For women who want to preserve fertility,conservative surgery should be made an option.When TM is chosen,a modified new myomectomy should be consi

关键词： Diffuse uterine leiomyomatosis Leiomyoma Myomectomy Uterine-sparing surgery Case report

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Focal adhesion kinase signaling is necessary for the hydrogen sulfide-enhanced proliferation,migration,and invasion of HTR8/SVneo human trophoblasts

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Reproductive and Developmental Medicine 2023年第2期7卷 75-82页

作者： Xian-Li Wang Jing Tang department of Pharmacy Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Objective:Hydrogen sulfide(H_(2)S)has been elucidated that it promotes migration and invasion in human placenta trophoblasts.However,the signaling pathway underlying H_(2)S-based regulation of trophoblasts remains unknown.Hence,we investigated the potential effect of sodium hydrosulfide(NaHS),an exogenous H_(2)S donor,on extravillous trophoblasts.Methods:The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS.The migration and invasion of HTR8/SVneo cells were measured by Transwell assays.Gene expression was determined by quantitative real-time PCR analysis.Protein expression was determined by western blot.Results:We found that NaHS could promote the proliferation,migration,and invasion of HTR8/SVneo cells.The phosphorylation of focal adhesion kinase(FAK),Src,and extracellular signal-regulated kinase(ERK)were activated by NaHS.Moreover,NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2)and MMP-9,downregulated the expression of E-cadherin in HTR8/SVneo cells.The application of NaHS could increase the expression of cystathionine-β-synthase.Conclusion:Both FAK-Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation,migration,and invasion via upregulating activity of MMP-2,MMP-9,and downregulating E-cadherin in HTR8/SVneo cells.These novel findings may provide a strong foundation for the clinical application of H_(2)S donor drugs.

关键词： Hydrogen sulfide Trophoblast Proliferation Migration Invasion Focal adhesion kinase signaling

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NLRP3 inhibitor dopamine receptors agonist as a potential therapeutic strategy for treatment of overactive immune responses in COVID-19

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Reproductive and Developmental Medicine 2023年第2期7卷 65-67页

作者： Jia-Lei Zhu Jing Jin Jing Tang department of Pharmacy Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China

Patients infected with coronavirus disease 2019(COVID-19)have high serum levels of proinflammatory cytokines.The"cytokine storm"has become one of the major causes of death for critically ill patients infected by COVID-19.Glucocorticoids,plasma from convalescent patients,blood purification,and tocilizumab are currently recommended for use when the body’s inflammatory response is overactivated.However,there are limitations in terms of medicinal effects,equipment reserves,and treatment expense.These challenges prompted us to assess classical agents with good safety and mature production technology.A recent study showed that nucleotide-binding oligomerization domain(NOD)-,leucine-rich repeat(LRR)-,and pyrin domain-containing protein 3(NLRP3)inflammasomes drive COVID-19 pathology.We speculate that suppression of NLRP3 inflammasome-derived cytokine production may be beneficial in COVID-19-infected patients.Dopamine receptors are present in almost all immune cells and can modulate their activation,proliferation,and cytokine production of immune cells.Previous studies have shown that dopamine receptor agonists can control systemic inflammation through inhibition of the NLRP3 inflammasome.This suggests that dopamine receptor agonists may be a new strategy for the treatment of overactive immune responses in COVID-19 patients.This is worthy of further investigation in clinical practice.

关键词： NLRP3 inflammasome Cytokine storm COVID-19 Dopamine receptors Medication regimen Interleukin

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Reliability and validity of generalized anxiety disorder 7-item scale in early pregnant women

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Reproductive and Developmental Medicine 2022年第4期6卷 249-253页

作者： Li-Li Gong Xiao-Long Xie Si-Tong Liu Wei-Hong Hu Yu-Jie Niu Yi Sun Jun-Sheng Liu Xian Xia department of obstetrics Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China school of Psychology and Cognitive Science East China Normal UniversityShanghai 200062China

Objective:This study aimed to evaluate the structural reliability and validity of generalized anxiety disorder 7-item(GAD-7)scale in early pregnant women.Methods:In this cross-sectional study,30,823 patients in early pregnancy registered in the obstetrics and gynecology Hospital of fudan university completed the GAD-7 scale and patient health questionnaire-9 item(PHQ-9).The discriminative ability,reliability,construct validity,and criterion validity were assessed to evaluate the psychometric properties and factor structures.Items with a discrimination parameter(α)of0.40 in two or more factors simultaneously were deleted from the scale.Results:All GAD-7 scale items exhibited a high discrimination power.The reliability of the GAD-7 scale was good(Cronbach’s alpha coefficient=0.891).Exploratory factor analysis extracted one factor with eigenvalues of greater than 1.0,which explained 61.930%of the common variance.Confirmatory factor analysis confirmed that the one-factor structure fitted the data well.The correlation coefficient with the PHQ-9 was 0.639.Conclusion:The Chinese version of the GAD-7 scale can be used as a screening tool for early pregnant women.It performs well in terms of discriminative ability,reliability,construct validity,and criterion validity.Pregnant women who screen positive may require more attention and investigation to confirm the presence of generalized anxiety disorder.

关键词： Reliability Validity GAD-7 PHQ-9 Early pregnancy

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Epidemiology and region-specific risk factors for low Apgar scores in China:a nationwide study

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World Journal of Pediatrics 2022年第2期18卷 135-141页

作者： Yi-Wen Wang Yan Chen Yan-Hong Ming Jin-Wen Zhang Kun Sun Jun Zhang Yong-Jun Zhang department of Neonatology Xinhua HospitalShanghai Jiao Tong University School of Medicine1665 Kongjiang RoadShanghai 200092China department of obstetrics and gynecology Hospital of Obstetrics and GynecologyFudan UniversityShanghaiChina shanghai Key Laboratory of Embryo Original Diseases The International Peace Maternity&Child Health HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Pediatrics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Ministry of Educaticn-shanghai Key Laboratory of Children's Env ironmental Health Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background Neonatal asphyxia is a serious public health issue.This study aimed to determine the epidemiology and region-specific risk factors for low Apgar scores,an important proxy for neonatal asphyxia,in China from 2015 to 2016.Methods The China Labor and Delivery Survey was a multicenter cross-sectional study including 96 hospitals distributed in 24(out of 34)provinces.Logistic regression analysis was performed to examine the risk factors for a low Apgar score(<7).Correspondence analyses were performed among neonates with low Apgar scores to explore the relationship between risk factors and geographical regions.The population attributable risk percentage(PAR%)was calculated for each region-specific risk factor.Results A total of 72,073 live births,including 320 births with low Apgar scores,were used for the analysis,giving a weighted rate of 3.9/1000 live births.There was a substantial difference in the incidence of low Apgar scores by geographic region,from 2.3/1000 live births in East China to 10.9/1000 live births in Northeast China.Maternal and obstetric factors are the major region-specific risk factors.In Southwest China,hypertensive disorders in pregnancy were more important contributors,with PAR% being 74.47%;in North and Northwest China,pre-pregnancy underweight was a more significant factor,with PAR% of 62.92%;in East China,infants born between 0:00 a.***.and 7:59 a.***.were a key factor,with PAR% of 80.44%.Conclusion Strategies based on region-specific risk factors should be considered to reduce the burden of low Apgar scores in China.

关键词： Apgar score China Epidemiology Risk factor

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Xiaotan Sanjie recipe,a compound Chinese herbal medicine,inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation

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Journal of Integrative Medicine 2023年第6期21卷 561-574页

作者： Nian Huang Hai-wei He Yu-yu He Wei Gu Ming-juan Xu Long Liu department of Integrative Medicine Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China department of obstetrics and gynecology Changhai HospitalNaval Medical UniversityShanghai 200433China school of Traditional Chinese Medicine Naval Medical UniversityShanghai 200433China department of Traditional Chinese Medicine Tianyou HospitalTongji UniversityShanghai 200333China

Objective:Xiaotan Sanjie recipe(XTSJ),a Chinese herbal compound medicine,exerts a significant inhibitory effect on gastric cancer(GC)metastasis.This work investigated the mechanism underlying the XTSJmediated inhibition of GC metastasis.Methods:The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro,using GC cell lines,and in vivo,using a GC mouse model,by focusing on the expression of Glc-N-Actransferase V(GnT-V;encoded by MGAT5).Results:The migration and invasion ability of GC cells decreased significantly after XTSJ administration,which confirmed the efficacy of XTSJ in treating GC in vitro.XTSJ increased the accumulation of Ecadherin at junctions between GC cells,which was reversed by MGAT5 overexpression.XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell–cell junctions,while MGAT5 overexpression had the opposite effect.MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex.Furthermore,the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5+XTSJ mice than in those of BGC-823-MGAT5+solvent mice,indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.Conclusion:XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell–cell junctions.

关键词： Xiaotan Sanjie Recipe Gastric cancer Traditional Chinese medicine E-cadherin Metastasis Glc-N-Ac-transferase V

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How fertility preservation guidelines have progressed worldwide:Potential implications and inspiration

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Reproductive and Developmental Medicine 2022年第1期6卷 34-41页

作者： Min-Xin Chen Ying Zhang Qing-Qing Cai Shuo Zhang Ran Xu Hua Chen Yu Kang Yue Wu Ri-Cheng Chian Cong-Jian Xu President Office Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Fertility Preservation Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China department of Genetics Shanghai JIAI Genetics and IVF InstituteShanghai 200011China department of International Law China Foreign Affairs UniversityBeijing 100032China department of Infertility Shanghai JIAI Genetics and IVF InstituteShanghai 200011China Clinical Research Center Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200090China Center for Reproductive Medicine Shanghai 10th People's Hospital of Tongji UniversityShanghai 200072China

To summarize fertility preservation (FP) guidelines and consensus provided by medical facilities worldwide. Five reference databases (PubMed/Embase, China Biomedical Literature Database, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women’s and Children’s Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian medical Association infobase) were searched. Official websites of societies were searched to find relevant guidelines and consensus, and guidelines and published systematic reviews and consensus were reviewed from inception through May 2021. A literature search was performed regarding guidance offered in professional facilities, and 304 records (including 4 in Chinese) of existing guidelines for full-text review were found. Moreover, 55 guidelines were identified after a manual search. The literature review demonstrated that FP guidance and options were unevenly distributed worldwide for women who wanted to post-pone pregnancy or had impaired fertility after gonadal toxicity. With promising cancer survival rates and diversified family decisions, more attention should be paid to the improvement and update of accessible guidelines and regulatory infrastructure to inform patients about the available options and empower them to make informed choices. Restrictions to such services can be gradually eased due to the efficacy and safety of certain FP techniques for the right candidates to initiate pregnancy conception.

关键词： Fertility preservation Cancer patient Aging Guidance

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