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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina Department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina Department of General Surgery Tianjin Medical University General HospitalTianjinChina Department of Anorectal Tianjin People's HospitalTianjinChina Department of Radiology Beijing Friendship hospital Capital Medical UniversityBeijingChina Department of Pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Thoracic Surgery/institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

Clinical characteristics and genetic mutations of 10 Chinese children with cystic fibrosis or cystic frbrosis transmembrane conductance regulator-related disorders

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中华医学杂志(英文版) 2024年第14期137卷 1753-1755页

作者： Tan Shanshan Cao Ling Department of Pulmonology The Children’s Hospital Affiliated to the Capital Institute of Pediatrics Beijing China

To the Editor: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, over 2000 CFTR mutations have been identified. CF mostly occurs in the Caucasian population, and its incidence is approximately 1/25,000 to 1/1800. However, the number of CF cases in China is small. To discover the gene mutations and clinical characteristics of Chinese children with CF, as well as their correlation, the clinical data of 10 children with CF or CFTR-related disorders (CFTR-RD) were retrospectively analyzed in this study.

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Co-immunoprecipitation for identifying protein–protein interaction on lipid droplets

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Biophysics Reports 2024年第2期10卷 102-110页

作者： Xiaochuan Fu Shuyan Zhang Pingsheng Liu institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences institute of Infectious diseases Beijing Key Laboratory of Emerging Infectious Diseases Beijing Ditan HospitalCapital Medical University Beijing institute of Infectious diseases

The lipid droplet(LD) is a conserved organelle that exists in almost all organisms, ranging from bacteria to mammals. Dysfunctions in LDs are linked to a range of human metabolic syndromes. The formation of protein complexes on LDs is crucial for maintaining their function. Investigating how proteins interact on LDs is essential for understanding the role of LDs. We have developed an effective method to uncover protein–protein interactions and protein complexes specifically on LDs. In this method, we conduct co-immunoprecipitation(co-IP) experiments using LD proteins extracted directly from isolated LDs, rather than utilizing proteins from cell lysates. To elaborate, we begin by purifying LDs with high-quality and extracting LD-associated proteins. Subsequently, the co-IP experiment is performed on these LD-associated proteins directly, which would enhance the co-IP experiment specificity of LDassociated proteins. This method enables researchers to directly unveil protein complexes on LDs and gain deeper insights into the functional roles of proteins associated with LDs.

关键词： Lipid droplet Co-immunoprecipitation Protein interaction

The roles of macrophage migration inhibitory factor in retinal diseases

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Neural Regeneration Research 2024年第2期19卷 309-315页

作者： Hongbing Zhang Xianjiao Zhang Hongsong Li Bing Wang Pei Chen Jiamin Meng Shaanxi institute of Ophthalmology Xi’anShaanxi ProvinceChina Department of Ophthalmology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina Department of Pathology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive *** are some evidences that MIF is involved in many vitreoretinal *** example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis *** also alleviates trauma-induced and glaucoma-induced optic nerve ***,MIF is critical for retinal/choroidal neovascularization,especially complex *** exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal *** protects uveal melanoma from attacks by natural killer *** mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt *** also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling *** review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

关键词： diabetic retinopathy glaucoma macrophage migration inhibitory factor migration inhibitory factor receptor optic neuropathy retinal degeneration retinal neovascular uveal melanoma uveitis

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Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

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Neural Regeneration Research 2024年第4期19卷 833-845页

作者： Xiaoyan Liu Yi Liu Junlin Liu Hantao Zhang Chaofan Shan Yinglu Guo Xun Gong Mengmeng Cui Xiubin Li Min Tang School of Life Sciences Jiangsu University institute of Animal Husbandry Jiangsu Academy of Agricultural Sciences Department of Rheumatology&Immunology Affiliated Hospital of Jiangsu University Department of Neurology The Second Affiliated Hospital of Shandong First Medical University

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain *** a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral ***-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine ***,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut *** pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also ***,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

关键词： biomarker diet pattern gut microbiota gut-brain axis metagenomics mitochondrial dysfunction multi-omics neurodegenerative disease neuroinflammation probiotic

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Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia

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Cellular & Molecular Immunology 2024年第1期21卷 19-32页

作者： Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu Department of Immunology School of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan hospital institute of Clinical Science Zhongshan HospitalShanghaiChina Zhaotong Health Vocational College ZhaotongYunnanChina Department of digestive diseases Huashan HospitalFudan UniversityShanghaiChina Shanghai Fifth People’s hospital Fudan UniversityShanghaiChina

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains *** a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated *** cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon *** of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell ***,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B ***,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell ***,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

关键词： IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia

RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2

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Science China Life Sciences 2024年第10期67卷 2186-2197页

作者： Lili Zhi Chaoqun Chen Ge Zhang Tian Huang Wenxia He Jinrui Zhang Dan Chen Jiayi Liu Jinyao Zhao Yangfan Qi Guiying Wang Wenjing Zhang Yang Wang Sino-US Research Center for Cancer Translational Medicine of the Second affiliated hospital of Dalian Medical University & institute of Cancer Stem Cell Dalian Medical University Department of Immunology College of Basic Medical SciencesDalian Medical University institute of Cancer Stem Cell Dalian Medical University Department of Pathology the First Affiliated Hospital of Dalian Medical UniversityDalian Medical University Department of General Surgery the Second Hospital of Hebei Medical University The Second Department of General Surgery the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Etiology Tracing and Individualized Diagnosis and Treatment for digestive System Carcinoma

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3'splice site(ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3′ ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

关键词： RBM25 colon cancer alternative splicing MNK2

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miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

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BIOCELL 2024年第4期48卷 581-590页

作者： LIJUAN ZHANG QINGYIN MENG LI ZHUANG QUAN GONG XIANDA HUANG XUEQIN LI SHIJUAN LI GUOQIN WANG XICAI WANG Department of Rehabilitation and Palliative Medicine The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Emergency Department(Outpatient Chemotherapy Center) The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Cancer BioTreatment Center The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Cancer institute The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective *** this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung ***:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal *** experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma ***,we examined tumorigenesis and metastasis in a nude mouse ***:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma *** of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant ***,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal ***,PHTF2 was found to be a molecular target of *** PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p ***:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung ***,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

关键词： Lung cancer Malignant phenotype Tumor formation Tumor suppressor Oncogene

Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China Organ Transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China institute of Organ Donation and Transplantation of Qingdao University Qingdao 266000China Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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