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

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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Curcumin modulates oxidative stress to inhibit pyroptosis and improve the inflammatory microenvironment to treat endometriosis

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Genes & Diseases 2024年第3期11卷 102-105页

作者： Jie Ding Shanshan Mei Kaili Wang Wen Cheng Shuai Sun Zhexin Ni Xiaoqiu Wang Chaoqin Yu department of gynecology of Traditional Chinese Medicine Changhai Hospital Affiliated to Naval Medical UniversityShanghai 200433China obstetrics and gynecology department The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouZhejiang 310006China department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China obstetrics and gynecology Hospital of Fudan University Shanghai 200433China

Endometriosis(EM)is a common disease that affects approximately 10%-15%of women of childbearing age.The pathogenesis of EM is unclear,but studies have shown a strong association between EM and inflammation,as well as oxidative stress.^(1) Pyroptosis is also called inflammatory cell death.When pyroptosis occurs,it activates a strong inflammatory response.Pyroptosis is associated with oxidative stress,and Ros act as intermediate triggers to activate pyroptosi.

关键词： inflammatory death oxidative

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Development of immature ovarian teratoma after mature teratoma in a girl with familial ovarian teratoma:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1442-1447页

作者： U Chul Ju Woo Dae Kang Seok Mo Kim department of obstetrics and gynecology Chonnam National University Medical SchoolGwangju 61469South Korea

BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.

关键词： Familial ovarian teratomas Adolescent female Immature ovarian teratoma Management Case report

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Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1967-1973页

作者： Guang-Di Zhou Qin Li Affiliated to shanghai Jiao Tong University school of Medicine Xinhua HospitalShanghai 200092China department of obstetrics and gynecology Shanghai Changhai HospitalShanghai 200433China

BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

关键词： Anti-programmed cell death-1 Tislelizumab Ovarian cancer Relapsed cancer treatment Immunotherapy Case report

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Identifying Comprehensive Genomic Alterations and Potential Neoantigens for Cervical Cancer Immunotherapy in a Cohort of Chinese Squamous Cell Carcinoma of the Cervix

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Biomedical and Environmental Sciences 2024年第6期37卷 565-580页

作者： Meng Wu Jialu Zhou Zhe Zhang Yuanguang Meng school of Medicine Nankai UniversityTianjin 300071China department of obstetrics and gynecology The First Medical Center of Chinese PLA General HospitalBeijing 100853China department of obstetrics and gynecology Chinese PLA Medical SchoolBeijing 100853China department of obstetrics and gynecology The Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China

Objective Genomic alterations and potential neoantigens for cervical cancer immunotherapy were identified in a cohort of Chinese patients with cervical squamous cell carcinoma(CSCC).Methods Whole-exome sequencing was used to identify genomic alterations and potential neoantigens for CSCC immunotherapy.RNA Sequencing was performed to analyze neoantigen expression.Results Systematic bioinformatics analysis showed that C>T/G>A transitions/transversions were dominant in CSCCs.Missense mutations were the most frequent types of somatic mutation in the coding sequence regions.Mutational signature analysis detected signature 2,signature 6,and signature 7 in CSCC samples.PIK3CA,FBXW7,and BICRA were identified as potential driver genes,with BICRA as a newly reported gene.Genomic variation profiling identified 4,960 potential neoantigens,of which 114 were listed in two neoantigen-related databases.Conclusion The present findings contribute to our understanding of the genomic characteristics of CSCC and provide a foundation for the development of new biotechnology methods for individualized immunotherapy in CSCC.

关键词： Cervical squamous cell carcinoma Genome alteration Neoantigens Immunotherapy

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The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa

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Asian Journal of Andrology 2024年第1期26卷 107-111页

作者： Liu Liu Jing Yang Wen-Jing Zhang Yi-Ling Zhou Gui-Jun Zhao Ya Huang Shu-Yan Tang obstetrics and gynecology Hospital Fudan UniversityShanghai 200011China shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development Department of Computational BiologySchool of Life SciencesFudan UniversityShanghai 200436China shanghai Towako Hospital Shanghai 200131China shanghai Institute of medical Genetics Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200040China

Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.

关键词： AMZ2 male infertility sperm quality teratozoospermia

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Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

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Neural Regeneration Research 2024年第2期19卷 316-323页

作者： Yiyang Chen Wenxuan Tang Xinqi Huang Yumei An Jiawen Li Shengye Yuan Haiyan Shan Mingyang Zhang Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina shanghai Key Lab of Forensic Medicine Key Lab of Forensic ScienceMinistry of Justice(Academy of Forensic Science)ShanghaiChina department of obstetrics and gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

关键词： intracerebral hemorrhage mitochondrial dysfunction mitophagy neuroinflammation neuroprotection reactive oxygen species secondary brain injury therapeutic target

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The role of snapin in regulation of brain homeostasis

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Neural Regeneration Research 2024年第8期19卷 1696-1701页

作者： Jiawen Li Xinqi Huang Yumei An Xueshi Chen Yiyang Chen Mingyuan Xu Haiyan Shan Mingyang Zhang shanghai Key Lab of Forensic Medicine Key Lab of Forensic ScienceMinistry of JusticeChina(Academy of Forensic Science)ShanghaiChina Institute of Forensic Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu ProvinceChina department of obstetrics and gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhouJiangsu ProvinceChina

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

关键词： brain homeostasis diabetes neurological diseases snapin traumatic brain injury vesicle fusion

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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

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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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