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Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes: An analysis of 15,124 normal ovarian responders in China

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中华医学杂志(英文版) 2024年第7期137卷 837-845页

作者： Zheng Danlei Wang Yuanyuan Chen Lixue Zeng Lin Li Rong Department of obstetrics and gynecology center for Reproductive Medicine Peking University Third Hospital Beijing 100191 China research center of clinical Epidemiology

Background: High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth inin vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response.Methods: We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results: High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 yea

关键词： Obesity Body mass index In vitro fertilization Live birth Decision trees Normal ovarian response

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Histological Features of Uterine Myometrial Dysfunction:Possible Involvement of Localized Inflammation

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Current Medical Science 2024年第3期44卷 633-641页

作者： Sheng-lan ZHU Hui-ting ZHANG Yuan-yuan DU Yi JIANG Shao-shuai WANG Wen-cheng DING Ling FENG national clinical research center for obstetrics and gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of obstetrics and gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage.Lipopolysaccharide(LPS)has been widely used to induce inflammation in animal models.Therefore,this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium,as well as the potential underlying molecular mechanisms involved.Methods In vivo,an animal model was established by intraperitoneal injection of 300μg/kg LPS in rats on gestational day 21.Hematoxylin-eosin(H&E)staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory cytokines.Immunohistochemistry,tissue fluorescence,and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4(TLR4)and the nuclear factor kappa-B(NF-κB)signaling pathway.In vitro,human uterine smooth muscle cells(HUtSMCs)were exposed to 2μg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation.Results In this study,LPS induced uterine myometrial dysfunction in rats,leading to a disorganized arrangement,a significant increase in collagen fiber deposition,and widespread infiltration of inflammatory cells.In both in vivo animal models and in vitro HUtSMCs,LPS elevated IL-6,IL-1β,and TNF-αlevels while concurrently suppressing the expression of connexin 43(Cx43)and oxytocin receptor(OXTR).Mechanistically,the LPS-treated group exhibited TLR4 activation,and the phosphorylation levels of p65 and IκBαwere notably increased.Conclusion LPS triggered the TLR4/NF-κB signaling pathway,inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

关键词： lipopolysaccharide inflammatory response TLR4 NF-κB myometrium

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DNA Damage-driven Inflammatory Cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

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Current Medical Science 2024年第2期44卷 261-272页

作者： Meng-jie WANG Yu XIA Qing-lei GAO Department of obstetrics and gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Cancer Invasion and Metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage and provide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

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Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & Diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of gynecology and obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of obstetrics and gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological malig-nancies.Studies have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the microenvironment.Colony-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid tumors.There are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor microenvironment.Here,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian cancer.We found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor prognosis.Treatment by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in vivo.Blockade of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

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Predictors of Adverse Pregnancy Outcomes Following Traumatic Injuries

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Current Medical Science 2024年第3期44卷 642-647页

作者： Wan-rong LU Ping WU Gong SONG Mei-qi GU Zhe XU Li HE national clinical research center for gynecology and obstetrics Cancer Biology Research CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Traumatic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective After traumatic injury in pregnant women,providing timely and appropriate management for high-risk patients is crucial for both pregnant women and fetuses.This study aimed to identify risk factors that predict adverse pregnancy outcomes after traumatic injury.Methods A retrospective cohort study including 317 pregnant patients who experienced trauma was conducted.The collected data included general demographics,injury mechanisms and adverse pregnancy outcomes.Patients were divided into two subgroups based on the absence or presence of trauma-related adverse pregnancy outcomes.Univariate and multivariate logistic regressions were conducted to estimate the associations between clinical variables and adverse pregnancy outcomes.Results A total of 41(12.93%)patients experienced adverse pregnancy outcomes within the first 24 h post-trauma.This study revealed that age>35 years(OR=14.995,95%CI:5.024–44.755,P<0.001),third trimester trauma(OR=3.878,95%CI:1.343–11.204,P=0.012),abdominal pain(OR=3.032,95%CI:1.221–7.527,P=0.017),vaginal bleeding(OR=3.226,95%CI:1.093–9.523,P=0.034),positive scan in focused assessment with sonography for trauma(FAST)positive(OR=8.496,95%CI:2.825–25.555,P<0.001),9≤injury severity score(ISS)<16(OR=3.039,95%CI:1.046–8.835,P=0.041)and ISS≥16(OR=5.553,95%CI:1.387–22.225,P=0.015)increased the probability of posttraumatic adverse pregnancy outcomes.Maternal age,gestational age at delivery,vaginal bleeding and positive FAST results were risk factors for abnormal delivery.Conclusion Advanced maternal age,third trimester,and positive FAST results should alert multidisciplinary trauma teams to closely monitor patients to prevent adverse pregnancy outcomes.

关键词： adverse pregnancy outcomes predictive factors abnormal delivery trauma

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Pregnancy Complicated With a Giant Pancreatic Tumor and Decompensation of Liver Cirrhosis:A Case Report and Literature Review

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Maternal-Fetal Medicine 2024年第1期6卷 50-53页

作者： Yi Yu Lirong Teng Juntao Liu Xinyan Liu Ping Peng Qian Zhou Congcong Liu Department of obstetrics and gynecology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China national clinical research center for Obstetric and Gynecologic Diseases Beijing 100730China

Pregnancy with solid pseudopapillary tumor of the pancreas(SPTP)is rare.Because pregnancy hormones may cause tumor progression,the management and treatment of SPTP need to balance the safety of pregnant women and fetuses with surgical treatment.We reported a case of a giant pancreatic tumor diagnosed during pregnancy that was considered to be SPTP.Examinations also showed hepatitis B virus infection and severe decompensation of liver cirrhosis.Medical termination of pregnancy was performed.The patient has lived with the tumor until now without surgery.We retrieved the published case reports,summarized the clinical characteristics of pregnancy with SPTP,and explored its management during the perinatal period.Most patients with SPTP have a good prognosis with good maternal and fetal outcomes,and it is important to choose an appropriate treatment method and timing.However,pregnancy combined with decompensated liver cirrhosis needs to be terminated in a timely manner because of its high-risk status.

关键词： Pregnancy complications Pancreatic tumor Solid pseudopapillary tumor of the pancreas Liver cirrhosis decompensation Abnormal coagulation function

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Noteworthy impacts of COVID-19 pandemic on cancer screening:A systematic review

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Fundamental research 2024年第3期4卷 484-494页

作者： Huilin Wang Min Yang Wei Xiong Quan Wang Bobo Zheng Yang Bai Kaiyong Zou Jibin Li Jiansong Ren Wanqing Chen Jingbo Zhai Jiang Li Office for Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Comprehensive Intervention National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of gynecology Endocrine&Reproductive center National Clinical Research Center for Obstetric&Gynecologic Diseases Department of Obstetrics and GynecologyPeking Union Medical College HospitalPeking Union Medical College/Chinese Academy of Medical SciencesBeijing 100005China Ambulatory Surgery center of Xijing Hospital Fourth Military Medical UniversityXi'an 710068China Department of General Surgery Shaanxi Provincial People’s HospitalXi'an 710068China College of clinical Medicine Capital Medical UniversityBeijing 100069China School of Public Health Tianjin University of Traditional Chinese MedicineTianjin 301617China

The sudden onset of the coronavirus disease 2019(COVID-19)in January 2020 has affected essential global health services.Cancer-screening services that can reduce cancer mortality are strongly affected.However,the specific role of COVID-19 in cancer screening is not fully understood.This study aimed to assess the efficiency of global cancer screening programs before and during the COVID-19 pandemic and to promote potential cancer-screening strategies for the next pandemic.Electronic searches in PubMed,Embase,and Web of Science,and manual searches were performed between January 1,2020 and March 1,2023.Cohort studies that reported the number of participants who underwent cancer screening before and during the COVID-19 pandemic were included.The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale.Differences in cancer-screening rates were estimated using the incidence rate ratio(IRR).Fifty-five cohort studies were included in this meta-analysis.The screening rates of colorectal cancer using invasive screening methods(Pooled IRR=0.52,95%CI:0.42 to 0.65,p<0.01),cervical cancer(Pooled IRR=0.56,95%CI:0.47 to 0.67,p<0.01),breast cancer(Pooled IRR=0.57,95%CI:0.49 to 0.66,p<0.01)and prostate cancer(Pooled IRR=0.71,95%CI:0.56 to 0.90,p<0.01)during the COVID-19 pandemic were significantly lower than those before the COVID-19 pandemic.The screening rates of lung cancer(Pooled IRR=0.77,95%CI:0.58 to 1.03,p=0.08)and colorectal cancer using noninvasive screening methods(Pooled IRR=0.74,95%CI:0.50 to 1.09,p=0.13)were reduced with no statistical differences.The subgroup analyses revealed that the reduction in cancer-screening rates varied across economies.Our results suggest that the COVID-19 pandemic has had a noteworthy impact on colorectal,cervical,breast,and prostate cancer screening.Developing innovative cancer-screening technologies is important to promote the efficiency of cancer-screening services in the post-COVID-19 era and prepare for the next pandemic.

关键词： Cancer screening COVID-19 pandemic Cohort study Incidence rate ratio Meta-analysis

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Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up

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Science China(Life Sciences) 2024年第5期67卷 1061-1068页

作者： Zhibo Zhang Jianbin Guo Weijie Tian Ye Zhang Yuelun Zhang Tianshu Sun Jiali Duan Xinmiao Bao Yuan Wang Yang Ye Qianqian Gao Honghui Shi Abraham Nick Morse Juan Chen Lan Zhu Departmentof obstetrics and gynecology Peking Union MedicalCollege HospitalChinese Academyof Medical Sciences&Peking Union MedicalCollegeNational Clinical Research Center for Obstetricand Gynecologic DiseasesBeijing 100730China Department of gynecology Guizhou Provincial People’s HospitalMedical College of Guizhou UniversityGuiyang 550002China Department of obstetrics and gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Medical research center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Medical Doctor Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pathology Peking Union Medical College HospitalBeijing 100730China Tufts University School of Medicine Boston MA 02111USA

Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.

关键词： complication efficacy long-term follow-up pelvic organ prolapse safety transvaginal mesh

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Emerging mechanisms and implications of c GAS-STING signaling in cancer immunotherapy strategies

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Cancer Biology & Medicine 2024年第1期21卷 45-64页

作者： Jiawen Zhang Sihui Yu Qiao Peng Ping Wang Lan Fang Tongji University Cancer center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072China Reproductive Medicine center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China Department of obstetrics and gynecology Zhongshan HospitalFudan UniversityShanghai 200032China

The intricate interplay between the human immune system and cancer development underscores the central role of immunotherapy in cancer treatment.Within this landscape,the innate immune system,a critical sentinel protecting against tumor incursion,is a key player.The cyclic GMP-AMP synthase(c GAS)and stimulator of interferon genes(STING)pathway has been found to be a linchpin of innate immunity:activation of this signaling pathway orchestrates the production of type I interferon(IFN-α/β),thus fostering the maturation,differentiation,and mobilization of immune effectors in the tumor microenvironment.Furthermore,STING activation facilitates the release and presentation of tumor antigens,and therefore is an attractive target for cancer immunotherapy.Current strategies to activate the STING pathway,including use of pharmacological agonists,have made substantial advancements,particularly when combined with immune checkpoint inhibitors.These approaches have shown promise in preclinical and clinical settings,by enhancing patient survival rates.This review describes the evolving understanding of the c GAS-STING pathway's involvement in tumor biology and therapy.Moreover,this review explores classical and non-classical STING agonists,providing insights into their mechanisms of action and potential for optimizing immunotherapy strategies.Despite challenges and complexities,the c GAS-STING pathway,a promising avenue for enhancing cancer treatment efficacy,has the potential to revolutionize patient outcomes.

关键词： cGAS-STING pathway type I interferon cyclic dinucleotide STING agonist cancer immunotherapy

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Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

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Protein & Cell 2024年第1期15卷 6-20页

作者： Ning Wu Ling Wei Zhipeng Zhu Qiang Liu Kailong Li Fengbiao Mao Jie Qiao Xiaolu Zhao State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China national clinical research center for obstetrics and gynecology Peking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Institute of Medical Innovation and research Peking University Third HospitalBeijing 100191China Cancer center Peking University Third HospitalBeijing 100191China Department of Biochemistry and Biophysics Beijing Key Laboratory of Protein Posttranslational Modifications and Cell FunctionSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Beijing Advanced Innovation center for Genomics Beijing 100191China Peking-Tsinghua center for Life Sciences Peking UniversityBeijing 100191China

Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular eukaryotes.Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are available.Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research hotspot.Several mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification models.Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health.The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites.The present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction.We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic tumors.This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

关键词： extrachromosomal circular DNAs gynecologic tumors reproduction liquid biopsy non-invasive prena-tal testing

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