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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie Xing Zhang Xiaoxuan Wang Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei Wang Fagui Jiang Caixing sun Yuanyuan Chen Ming Chen Department of Radiation Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation Oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation Oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation Oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Oncology Maoming People’s HospitalMaoming 525000China Department of Radiation Oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of sun yat-sen university&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

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High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p

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Science China(Life Sciences) 2024年第2期67卷 286-300页

作者： Bi-Ang Kang Hua-Ming Li Ya-Ting Chen Meng-Jie Deng Yan Li Yue-Ming Peng Jian-Jun Gao Zhi-Wei Mo Jia-Guo Zhou Zhi-Jun Ou Jing-Song Ou Division of Cardiac Surgery Cardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China NHC key Laboratory of Assisted Circulation(sun yat-sen university) Guangzhou 510080China Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Guangzhou 510080China Division of Vascular Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Pharmacology Cardiac and Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Division of Hypertension and Vascular Diseases Department of CardiologyCardiovascular Diseases InstituteThe First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

We previously demonstrated that normal high-density lipoprotein(nHDL)can promote angiogenesis,whereas HDL from patients with coronary artery disease(d HDL)is dysfunctional and impairs *** plays a critical role in angiogenesis,and HDL regulates ***,it is unclear whether n HDL and d HDL regulate angiogenesis by affecting *** cells(ECs)were treated with n HDL and d HDL with or without an autophagy ***,endothelial nitric oxide synthase(e NOS)expression,miRNA expression,nitric oxide(NO)production,superoxide anion(O2^(·-))generation,EC migration,and tube formation were evaluated.n HDL suppressed the expression of miR-181a-5p,which promotes autophagy and the expression of e NOS,resulting in NO production and the inhibition of O2^(·-)generation,and ultimately increasing in EC migration and tube formation.d HDL showed opposite effects compared to n HDL and ultimately inhibited EC migration and tube *** found that autophagy-related protein 5(ATG5)was a direct target of ***5 silencing or miR-181a-5p mimic inhibited n HDL-induced autophagy,e NOS expression,NO production,EC migration,tube formation,and enhanced O2^(·-)generation,whereas overexpression of ATG5 or miR-181a-5p inhibitor reversed the above effects of d ***5 expression and angiogenesis were decreased in the ischemic lower limbs of hypercholesterolemic low-density lipoprotein receptor null(LDLr^(-/-))mice when compared to C57BL/6 ***5 overexpression improved angiogenesis in ischemic hypercholesterolemic LDLr^(-/-)*** together,nHDL was able to stimulate autophagy by suppressing miR-181a-5p,subsequently increasing e NOS expression,which generated NO and promoted *** contrast,d HDL inhibited angiogenesis,at least partially,by increasing miR-181a-5p expression,which decreased autophagy and e NOS expression,resulting in a decrease in NO production and an increase in O2^(·-)*** findings reveal a nov

关键词： high-density lipoprotein angiogenesis autophagy ATG5 miRNA endothelial nitric oxide synthase

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Viral hepatitis E:clinical manifestations,treatment,and prevention

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肝脏研究（英文） 2024年第1期8卷 11-21页

作者： Qiumin Luo Jia Chen Yeqiong Zhang Wenxiong Xu Ying Liu Chan Xie Liang Peng Department of Infectious Disease The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Key Laboratory of Liver Disease research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing *** the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)*** acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver ***,some immunocompromised patients are at risk of developing chronic HEV infection and *** screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis *** review focused on the clinical presentation,management,and prevention of hepatitis E.

关键词： Hepatitis E Chronic hepatitis Screening Antiviral therapy Vaccination

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Cdc42 deletion yielded enamel defects by disrupting mitochondria and producing reactive oxygen species in dental epithelium

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Genes & Diseases 2024年第5期11卷 335-349页

作者： Jinxuan Zheng Rongcheng Yu Yiqi Tang Sihui Su Sainan Wang Chenxi Liao Xuecong Li Jiabin Liao Dongsheng Yu Tingting Ai Wei Zhao Vicky Yau Chufeng Liu Liping Wu Yang Cao Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong 510055China Guangdong Provincial Key Laboratory of Oral Diseases GuangzhouGuangdong 510055China Department of Cariology and Endodontology 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 Oral and Maxillofacial Surgery University at BuffaloBuffaloNY 14214USA Department of Orthodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Developmental defects of enamel are common due to genetic and environmental factors before and after ***42,a Rho family small GTPase,regulates prenatal tooth development in ***,its role in postnatal tooth development,especially enamel formation,remains ***,we investigated Cdc42 functions in mouse enamel development and tooth repair after ***42 showed highly dynamic temporospatial patterns in the developing incisors,with robust expression in ameloblast and odontoblast ***,epithelium-specific Cdc42 deletion resulted in enamel defects in *** differentiation was inhibited,and hypomineralization of enamel was observed upon epithelial Cdc42 *** analysis showed that abnormal mitochondrial components,phosphotransferase activity,and ion channel regulator activity occurred in the Cdc42 mutant dental *** oxygen species accumulation was detected in the mutant mice,suggesting that abnormal oxidative stress occurred after Cdc42 ***,Cdc42 mutant mice showed delayed tooth repair and generated less calcified *** dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression,increased Atp5j2 levels,and reactive oxygen species overproduction in the mutant repair ***-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical *** Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth *** findings suggested that mitochondrial dysfunction,up-regulated oxidative stress,and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant ***,Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

关键词： Cdc42 Enamel defects Mitochondrial dysfunction Rho GTPase Tooth repair

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Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1787-1795页

作者： Jiao-Jie Xue Su-Tian Hu Chong-Chong Wang Zhi-Chong Chen Shi-Yao Cheng Shu-Qi Yu Hua-Jing Peng Yi-Tao Zhang Wei-Jie Zeng Department of Cardiovascular Internal Medicine Sun Yat-sen University Sixth Affiliated HospitalGuangzhou 510655Guangdong ProvinceChina Department of Cardiovascular Internal Medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina Department of Ultrasound Fuwai HospitalChinese Academy of Medical Sciences ShenzhenShenzhen 518052Guangdong ProvinceChina Department of Kidney Internal Medicine Sun Yat-sen University First Affiliated HospitalGuangzhou 510062Guangdong ProvinceChina

BACKGROUND Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular *** which,ventricular arrhythmia is a prevalent clinical *** suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal *** To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving *** We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor *** patients were evaluated by a 24-h ambulatory electrocardiogram(ECG)at the Sixth Affiliated Hospital of sun yat-sen university from January 2018 to June ***,41 general healthy age-matched and sexmatched controls were *** were categorized into survival and non-survival *** primary endpoint was all-cause mortality,and secondary endpoints included major adverse cardiovascular events(MACEs).RESULTS Colorectal tumors comprised 90%of *** ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors,100(76.92%)exhibited varying degrees of premature ventricular contractions(PVCs).Ten patients(7.69%)manifested non-sustained ventricular tachycardia(NSVT).The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG[27(21.3)vs 1(2.5),P=0.012]and 24-h ambulatory ECG[14(1.0,405)vs 1(0,6.5),P35/24 h to all-cause mortality,and NSVT was associated with ***,neither PVC burden nor NSVT independently predicted outcomes according to multivariate *** Patients with gastrointestinal tumors exhibited elevated ***>35/24 h and NSVT detected by 24-h ambulatory ECG were prognos

关键词： Ventricular arrhythmia Gastrointestinal tumor Major adverse cardiovascular events Prognostic Surgery

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Changing the 3-decade routine of preoperative radiotherapy for locally advanced rectal cancer: New wine for new bottle?

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中华医学杂志(英文版) 2024年第16期137卷 1891-1893页

作者： Dou Ruoxu Zhang Jianwei Wang Jianping Deng Yanhong Department of Gastrointestinal Surgery The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai Guangdong China Department of Medical Oncology The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Biomedical Innovation Center The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Department of General Surgery The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong China

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Knowledge-embedded spatio-temporal analysis for euploidy embryos identification in couples with chromosomal rearrangements

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Chinese Medical Journal 2024年第6期137卷 694-703页

作者： Fangying Chen Xiang Xie Du Cai Pengxiang Yan Chenhui Ding Yangxing Wen Yanwen Xu Feng Gao Canquan Zhou Guanbin Li Qingyun Mai Reproductive Medicine Center The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of Reproductive Medicine GuangzhouGuangdong 510080China School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong 510006China Department of General Surgery(Colorectal Surgery) The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510655China Shanghai Artificial Intelligence Laboratory Shanghai 200232China

Background:The goal of the assisted reproductive treatment is to transfer one euploid blastocyst and to help infertile women giving birth one healthy *** algorithms have been used to assess the ploidy status of embryos derived from couples with normal chromosome,who subjected to preimplantation genetic testing for aneuploidy(PGT-A)***,it is currently unknown whether artificial intelligence model can be used to assess the euploidy status of blastocyst derived from populations with chromosomal ***:From February 2020 to May 2021,we collected the whole raw time-lapse videos at multiple focal planes from in vitro cultured embryos,the clinical information of couples,and the comprehensive chromosome screening results of those blastocysts that had received PGT ***,we developed a novel deep learning model called the Attentive Multi-Focus Selection Network(AMSNet)to analyze time-lapse videos in real time and predict blastocyst *** upon AMSNet,we integrated additional clinically predictive variables and created a second deep learning model,the Attentive Multi-Focus Video and clinical Information Fusion Network(AMCFNet),to assess the euploidy status of *** efficacy of the AMCFNet was further tested in embryos with parental chromosomal *** receiver operating characteristic curve(ROC)was used to evaluate the superiority of the ***:A total of 4112 embryos with complete time-lapse videos were enrolled for the blastocyst formation prediction task,and 1422 qualified blastocysts received PGT-A(n=589)or PGT for chromosomal structural rearrangement(PGT-SR,n=833)were enrolled for the euploidy assessment task in this *** AMSNet model using seven focal raw time-lapse videos has the best real-time *** real-time accuracy for AMSNet to predict blastocyst formation reached above 70%on the day 2 of embryo culture,and then increased to 80%on the day 4 of embryo ***

关键词： Euploidy status Embryo Time-lapse imaging Deep learning Spatio-temporal analysis Preimplantation genetic testing for chromosomal structural rearrangement

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TMB相关免疫浸润调控评分(MOTIF)预测免疫治疗响应并指导联合增效

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Science Bulletin 2024年第6期69卷 803-822页

作者：钱政宇潘艺芊李薛鑫陈衍行吴灏祥刘泽先 Martin Kosar Jiri Bartek 王梓贤徐瑞华 Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Provincial Clinical Research Center for CancerResearch Unit of Precision Diagnosis and Treatment for Gastrointestinal CancerChinese Academy of Medical SciencesGuangzhou 510060China Science for Life Laboratory Division of Genome BiologyDepartment of Medical Biochemistry and BiophysicsKarolinska InstituteStockholm S-17121Sweden Department of General Surgery The Fourth Affiliated HospitalChina Medical UniversityShenyang 110032China Bioinformatics Platform Sun Yat-sen University Cancer CenterGuangzhou 510060China Zhejiang university-university of Edinburgh Institute Zhejiang University School of MedicineHaining 314400China Edinburgh Medical School Biomedical SciencesCollege of Medicine and Veterinary MedicineThe University of EdinburghEdinburgh EH11LTUK Danish Cancer Society research Center Copenhagen DK-2100Denmark Laboratory of Artificial Intelligence and Data Science Sun Yat-sen University Cancer CenterGuangzhou 510060China

Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T *** bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB *** confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity *** analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell *** pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI *** the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo ***,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.

关键词： Tumor mutational burden Immunotherapy Cancer-immunity cycle Treatment efficacy prediction CD8^(+)T cell infiltration Combination therapy

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State Key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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clinical practice of sepsis-induced immunosuppression:Current immunotherapy and future options

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Chinese Journal of Traumatology 2024年第2期27卷 63-70页

作者： Fei Pei Bin Gu Shu-Min Miao Xiang-Dong Guan Jian-Feng Wu Department of Critical Care Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China Guangdong clinical research Center for Critical Care Medicine Guangzhou510080China

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to *** development of sepsis is closely linked to immune *** a result,immunotherapy has gained traction as a promising approach to sepsis treatment,as it holds the potential to reverse immunosuppression and restore immune balance,thereby improving the prognosis of septic ***,due to the highly heterogeneous nature of sepsis,it is crucial to carefully select the appropriate patient population for *** review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians'understanding and practical application of immunotherapy in the management of sepsis.

关键词： Sepsis Sepsis-induced immunosuppression Immunotherapy Enrichment Classifier

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