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Can NogoA Be a Suitable Target to Treat Ischemic Stroke?

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Neuroscience Bulletin 2024年第4期40卷 557-560页

作者： Suliman Khan Abdul Nasir Medical research center The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou540014China

Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent experiments to the clinical setting;however,these have been typified by several failures[2].It is known that astrocytes play a crucial role in the pathogenesis of ischemic stroke[3,4].They are activated in response to stimuli arising from injury,characterized by drastic changes to their morphology and function-associated gene *** astrocytes exacerbate secondary neurodegeneration(repair of nervous tissue by the generation of new neurons,glial cells,axons,myelin,or synapses)[5]as well as provide neuroprotection during CNS pathologies[6].It is worth noting that myelin-related neurite growth inhibitors induce the suppression of axon regeneration after stroke[7].

关键词： protective NogoA clinical

The evolution of cancer genomic medicine in Japan and the role of the National Cancer center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue Cancer center of Peking University Third hospital Beijing 100191China center of Basic Medical research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Peking University Third hospital Cancer center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed *** ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism *** a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian ***,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related *** 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the *** data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian *** of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian ***,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian *** findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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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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Chinese Medical Journal 2024年第7期137卷 837-845页

作者： Danlei Zheng Yuanyuan Wang Lixue Chen Lin Zeng Rong Li Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China research center of Clinical Epidemiology Peking University Third HospitalBeijing 100191China

Background:High body mass index(BMI)results in decreased fecundity,and women with high BMI have reduced rates of clinical pregnancy and live birth in in vitro fertilization/intra-cytoplasmic sperm injection(IVF/ICSI).Meanwhile,ovarian responses show great heterogeneity in patients with a high *** study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian ***: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 *** live birth rate(CLBR)was used as the primary ***,a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the *** used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI ***:High BMI was associated with poor IVF/ICSI outcomes,both in cumulative cycles and in separate fresh ET or FET *** 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/m^(2)as an inflection *** the decision tree,BMI only made a difference in the population aged≤34.5 years,with anti-Muller

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

Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical research center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and Clinical research center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration

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Genes & Diseases 2024年第3期11卷 351-367页

作者： Xinzhu Quiu Hongbo He Hao Zeng Xiaopeng Tongg Can Zhang Yupeng Liu Zhan Liao Qing Liu Department of Orthopaedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National Clinical research center for Geriatric Disorders Xiangya HospitalChangshaHunan 410008China Department of Sports Medicine Research Center of Sports MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China

MYBL2(MYB proto-oncogene like 2)is an emerging prognostic marker for malignant tumors,and its potential role in osteosarcoma and its relationship with immune infiltration in pan-cancer is yet to be *** constructed a transcription factor activity profile of os-teosarcoma using the single-cell regulatory network inference algorithm based on single-cell RNA sequencing data obtained from the Gene Expression ***,we calcu-lated the extent of MYBL2 activation in malignant proliferative *** also explored the association between MYBL2 and chemotherapy resistance in ***,we systematically correlated MYBL2 with immunological signatures in the tumor microenviron-ment in pan-cancer,including immune cell infiltration,immune checkpoints,and tumor immu-notherapy ***,we developed and validated a risk score(MRGS),derived an osteosarcoma risk score nomogram based on MRGS,and tested its ability to predict ***2 and gene enrichment analyses in osteosarcoma and pan-cancer revealed that MYBL2 was positively correlated with cell proliferation and tumor immune ***2 expres-sion positively correlated with SLC19A1 in pan-cancer and osteosarcoma cell ***-cancer immune infiltration analysis revealed that MYBL2 was correlated with myeloid-derived sup-pressor cells,Th2 cell infiltration,CD276,RELT gene expression,and tumor mutation burden.

关键词： Biomarker Immunecheckpoint MYBL2 Osteosarcoma Pan-cancer

Endoscopic features and treatments of gastric cystica profunda

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World Journal of Gastroenterology 2024年第7期30卷 673-684页

作者： Zi-Han Geng Yan Zhu Pei-Yao Fu Yi-Fan Qu Wei-Feng Chen Xia Yang Ping-Hong Zhou Quan-Lin Li Endoscopy center and Endoscopy research Institute Zhongshan HospitalFudan UniversityShanghai 200032China

BACKGROUND Gastric cystica profunda(GCP)represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal *** is often linked to,or may progress into,early gastric cancer(EGC).AIM To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment,thereby offering guidance for diagnosis and *** This retrospective study involved 104 patients with GCP who underwent endoscopic *** demographic and clinical data,regular patient followups were conducted to assess local *** Among the 104 patients diagnosed with GCP who underwent endoscopic resection,12.5%had a history of previous gastric *** primary site predominantly affected was the cardia(38.5%,n=40).GCP commonly exhibited intraluminal growth(99%),regular presentation(74.0%),and ulcerative mucosa(61.5%).The leading endoscopic feature was the mucosal lesion type(59.6%,n=62).The average maximum diameter was 20.9±15.3 mm,with mucosal involvement in 60.6%(n=63).Procedures lasted 73.9±57.5 min,achieving complete resection in 91.3%(n=95).Recurrence(4.8%)was managed via either surgical intervention(n=1)or through endoscopic resection(n=4).Final pathology confirmed that 59.6%of GCP cases were associated with *** analysis indicated that elderly males were more susceptible to GCP associated with ***,multivariate analysis identified lesion morphology and endoscopic features as significant risk *** analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC(P=0.72).CONCLUSION The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.

关键词： Gastric cystica profunda Early gastric cancer Endoscopic features Endoscopic resection Endoscopy

Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu 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

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine