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Acta Pharmaceutica Sinica B 2024年第4期14卷 1592-1604页

作者： Yuanjin Zhang Junze Huang Shengbo Huang Jie Liu Luyao Deng Chenmeizi Liang Yuanqing Guo Bingyi Yao Xin Wang changning maternity and infant health hospital and School of Life Sciences Shanghai Key Laboratory of Regulatory BiologyEast China Normal UniversityShanghai 200241China

Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of statins.However,there are too few animal models related to OATPIB1,especially humanized animal models.In this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 technology.Pharmacokinetic characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,respec-tively.The results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport function.Furthermore,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the body.These results were consistent with those obtained from in vitro experiments using overexpressed cell lines.In conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different statins.The different uptake mediated by OATPIB1 may be an important reason for the different efficacy of statins.The hOATPIB1 rat is a promising model for improving the prediction of human drug transport.

关键词： CRISPR/Cas9 Drug transport Drug disposition Geneediting Humanized rat model OATP1B1 SLCO1B1 Statins

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & Cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang Shaorong Gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing maternity and Child health Care hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant women.However,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood.Here,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy.Compared to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection.However,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface.Notably,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester.Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

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Genes & Diseases 2024年第4期11卷 411-425页

作者： Mengmeng Guo Pan Hu Jiayi Xie Kefu Tang Shixiu Hu Jialiang Sun Yundong He Jing Li Weiqiang Lu Huirong Liu Mingyao Liu Zhengfang Yi Shihong Peng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai 200241China Prenatal Diagnosis Center Department of Clinical LaboratoryChangning Maternity and Infant Health HospitalEast China Normal UniversityShanghai 200051China Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 201203China Fengxian hospital Affiliated to Southern Medical University Shanghai 201400China Shanghai Yuyao Biotech Co. Ltd.Shanghai 200241China

Gastric cancer is highly prevalent among digestive tract tumors.Due to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric cancer.However,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric cancer.In our previous study,we identified a novel small molecule EP4 receptor antagonist called YY001.Treatment with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model.Furthermore,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 macro-phages.Additionally,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than fluorouracil.These findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关键词： EP4 Immunomodulation Synergy Tumor microenvironment YY001

A novel preimplantation genetic testing strategy for a subtelomeric genetic disorder:A case study

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Genes & Diseases 2024年第4期11卷 13-15页

作者： Songchang Chen Li Wanng Luting Chen Weihui Shi Junyu Zhang Yuting Hu Yinyu Wang Li Jin Jianzhong Sheng Feng Zhang Yanting Wu Hefeng Huang Chenming Xu Obstetrics and Gynecology hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200090China The International Peace maternity and Child health hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200030China Research Units of Embryo Original Diseases Chinese Academy of Medical SciencesShanghai 200030China Key Laboratory of Reproductive Genetics(Ministry of Education) Department of Reproductive EndocrinologyWomen's HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China Shanghai Key Laboratory of Embryo Original Diseases Shanghai 200030China Shanghai First maternity and infant hospital Tongji University School of MedicineShanghai 200030China

Preimplantation genetic testing(PGT)is a precise and effective technique for detecting inherited pathogenic mutations to prevent birth defects.However,there are few reports on PGT for pseudo-autosomal genetic diseases.

关键词： implantation testing precise

Effect of SARS-CoV-2 infection in early pregnancy on placental development

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Science China(Life Sciences) 2024年第3期67卷 622-625页

作者： Shanru Yi Liping Wang Mengting Wang Wei Hong Ben Xu Xiaoying He Mengtian Yang Zhiping Wu Beiying Wang Guang Yang Shijun Shen Xinyu Cui Ruixue Wang Kai Wang Hong Wang Xiaocui Li Shaorong Gao Cizhong Jiang Jiayu Chen Clinical and Translation Research Center of Shanghai First maternity and infant hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji UniversityShanghai 200065China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai 201204China

Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ... 详细信息

关键词： pregnancy fetal Effect

Delivery room resuscitation intensity and associated neonatal outcomes of 24^(+0)-31^(+6) weeks'preterm infants in China:a retrospective cross-sectional study

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World Journal of Pediatrics 2024年第1期20卷 64-72页

作者： Si-Lu Wang Chun Chen Xin-Yue Gu Zhao-Qing Yin Le Su Si-Yuan Jiang Yun Cao Li-Zhong Du Jian-Hua Sun Jiang-Qin Liu Chuan-Zhong Yang Department of Neonatology Shanghai Key Laboratory of Maternal Fetal MedicineShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityNo.2699Gaoke Western RoadPudong DistrictShanghai 201204China Department of Neonatology Affiliated Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityNo.2004Hongli RoadFutian DistrictShenzhen 518028China NHC Key Laboratory of Neonatal Diseases Fudan UniversityChildren's Hospital of Fudan UniversityShanghaiChina Department of Neonatology People's Hospital of DehongKunming Medical UniversityDehongChina Department of Neonatology Children's Hospital of Fudan UniversityShanghaiChina Department of Neonatology Children's HospitalZhejiang University School of MedicineHangzhouChina Department of Neonatology Shanghai Children's Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background The aim of this study was to review current delivery room(DR)resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0_31+6 weeks gestation age(GA).Methods This was a retrospective cross-sectional study.The source population was infants born at 24+0_31+6 weeks'GA who were enrolled in the Chinese Neonatal Network 2019 cohort.Eligible infants were categorized into five groups:(1)regular care;(2)oxygen supplementation and/or continuous positive airway pressure(O2/CPAP);(3)mask ventilation;(4)endotracheal intubation;and(5)cardiopulmonary resuscitation(CPR).The association between DR resuscitation and shortterm outcomes was evaluated by inverse propensity score-weighted logistic regression.Results Of 7939 infants included in this cohort,2419(30.5%)received regular care,1994(25.1%)received O,/CPAP,1436(18.1%)received mask ventilation,1769(22.3%)received endotracheal intubation,and 321(4.0%)received CPR in the DR.Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation,and antenatal steroid use tended to be associated with a lower need for resuscitation(Pinfants in eight centers requiring higher intensity resuscitation.Conclusions Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China.There is wide variation in resuscitative approaches across delivery centers,and ongoing quality improvement to standardize resuscitation practices is needed.

关键词： Cardiopulmonary resuscitation Delivery room Endotracheal intubation Neonatal resuscitation Preterm

Intrauterine Treatment of Monochorionic Triamniotic Triplet Pregnancy with Twin Reverse Arterial Perfusion Sequence

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Maternal-Fetal Medicine 2024年第2期6卷 120-123页

作者： Xiaomin Zhao Yongmei Shen Lying Yao Lei Zhang Shanshan Li Wen Li Hong Yu Ling Chen Ying Chang Tianjin Key Laboratory of Human Development and Reproductive Regulation Tianjin Central Hospital of Obstetrics and Gynecology/Nankai University Affiliated Maternity HospitalTianjin 300100China Prenatal Diagnosis Center Tianjin Central Hospital of Obstetrics and Gynecology/Nankai University Affiliated Maternity HospitalTianjin 300100China Radiology Department Tianjin Central Hospital of Obstetrics and Gynecology/Nankai University Affiliated Maternity HospitalTianjin 300100China Pathology Department Tianjin Central Hospital of Obstetrics and Gynecology/Nankai University Affiliated Maternity HospitalTianjin 300100China.

To editor:This study reports a pregnant woman who was naturally conceived with monochorionic triamniotic(MCTA)combined with twin reversed arterial perfusion(TRAP).An ultrasound revealed that one of the fetuses had a cardiac malformation,and a connection between the umbilical arteries was suspected.To reduce the acardiac fetus,radiofrequency ablation was performed at 17+3 weeks of pregnancy.At 36+4 weeks,two healthy infants were delivered via elective cesarean section.Postoperative examination revealed a direct connection between the umbilical arteries,with the placental perfusion acting as a direct pump.It is essential to identify the intrauterine status of the blood-supplying infant and vascular connections in order to achieve successful outcomes in pregnancies with complications,such as edema and heart failure.The studies involving human participants were reviewed and approved by Human Research Ethics Committee of Tianjin Central hospital of Obstetrics and Gynecology.The patient provided her written informed consent to participate in this study.

关键词： Twinning Embryonic Monochorionic triamniotic Twin reversed arterial perfusion sequence Fetus reduction Placental perfusion

LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis

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Oncology Research 2024年第7期32卷 1221-1229页

作者： YUANLIN LIU YAN LIU YAN WANG QIANG WANG YAN YAN DANDAN ZHANG HUIQIN LIU Department of Obstetrics and Gynecology Shanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityShanghai200092China Department of Obstetrics and Gynecology The Second People’s Hospital of Nantong CityNantong226002China Department of Obstetrics and Gynecology Affiliated Hospital of Nantong UniversityNantong226002China

At present,the role of many long non-coding RNAs(lncRNAs)as tumor suppressors in the formation and development of cervical cancer(CC)has been studied.However,lncRNA prostate cancer gene expression marker 1(PCGEM1),whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression,has not been studied in CC.The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC.The relative expression of PCGEM1 in CC cells was detected by real-time PCR.After the suppression of PCGEM1 expression by shRNA,the changes in the proliferation,migration,and invasion capacities were detected via CCK-8 assay,EdU assay,and colony formation assay wound healing assay.Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition(EMT)markers were determined by western blot and immunoﬂuorescence.The interplay among PCGEM1,miR-642a-5p,and kinesin family member 5B(KIF5B)was conﬁrmed by bioinformatics analyses and luciferase reporter assay.Results showed that PCGEM1 expressions were up-regulated within CC cells.Cell viabilities,migration,and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells.N-cadherin was silenced,but E-cadherin expression was elevated by sh-PCGEM1.Moreover,by sponging miR-642a-5p in CC,PCGEM1 was veriﬁed as a competitive endogenous RNA(ceRNA)that modulates KIF5B levels.MiR-642a-5p down-regulation partially rescued sh-PCGEM1’s inhibitory effects on cell proliferation,migration,invasion,and EMT process.In conclusion,the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC.This study provides a research basis and new direction for targeted therapy of CC.

关键词： Cervical cancer PCGEM1 KIF5B MiR-642a-5p tumorigenesis

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key Laboratory of Metabolic Remodeling and health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key Laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful fertilization.Severe deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental potential.However,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is limited.Here,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are infertile.The Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF phenotypes.We find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO sperm.Further analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in sperm.We finally show that intracytoplasmic sperm injection overcomes Ccdc38-related infertility.Our study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling

Effects of combined spinal-epidural anesthesia on anxiety,labor analgesia and motor blocks in women during natural delivery

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World Journal of Psychiatry 2023年第11期13卷 838-847页

作者： Ling Cai Jiao-Jiao Jiang Ting-Ting Wang Shuang Cao Department of Anesthesiology Shanghai Changning Maternity&Infant Health HospitalShanghai 200050China

BACKGROUND The background of this study was analgesia in natural delivery.The combined spinal-epidural anesthesia has obvious analgesic effect on the parturients in natural labor,and combined spinal-epidural anesthesia has been widely used in anesthesia for various diseases.AIM To study the effects of combined spinal-epidural anesthesia on anxiety,labor analgesia,and motor blocks in parturients during natural delivery.METHODS A total of 120 women who gave birth at changning District Maternal and Child health hospital between December 2021 to December 2022 were included;a random number table approach was employed to divide the women into a control group and a joint group,with each group consisting of 60 women.The control group was given epidural anesthesia,while the joint group was given combined spinal-epidural anesthesia.The visual analog scale(VAS)was used to evaluate the degree of maternal pain.Comparisons were made between the two groups’conditions of childbirth and the duration of labor.Apgar scores were used to evaluate the status of the newborns at birth;Self-rating Anxiety Scale(SAS)and General Self-Efficacy Scale(GSES)scores,umbilical artery blood gas analysis indices and stress indices were compared between the two groups;and the frequencies of motor block and postpartum complications were analyzed.RESULTS In comparison to the control group,in the joint group,the VAS scores for the first,second,and third stages of labor were lower(P0.05).The second and third stages of labor in the joint group were shorter than those in the control group(P<0.05).When compared to the control group,the postpartum SAS score of the joint group was lower,while the GSES score was greater(P<0.05).Between the control group and the

关键词： Combined spinal-epidural anesthesia Natural delivery Anxiety level Labor analgesia Motor block