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Helicobacter pylori and immunotherapy for gastrointestinal cancer

The Innovation 2024年第2期5卷 51-60页

作者： Keren Jia Yang Chen Yi Xie Xicheng Wang Yajie Hu Yu Sun Yanshuo Cao Liyan Zhang Yakun Wang Zhenghang Wang Zhihao Lu Jian Li Xiaotian Zhang Lin Shen Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Helicobacter pylori infection is associated with the risk of gastrointestinal(GI)cancers;however,its impact on immunotherapy for GI cancers remains *** this study,we included 10,122 patients who underwent ^(13)C-urea breath *** 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer(GC)who were treated with anti-PD-1/PD-L1 therapy,***–positive patients exhibited significantly longer immune-related progression-free survival(irPFS)compared with ***–negative patients(6.97 months versus 5.03 months,p<0.001,hazard ratio[HR]0.76,95%confidence interval[CI]0.62–0.95,p=0.015).Moreover,the ***–positive group demonstrated a trend of 4 months longer median immune-related overall survival(irOS)than the ***–negative ***–positive GC displayed higher densities of PD-L1+cells and nonexhausted CD8+T cells,indicative of a“hot”tumor *** analysis revealed that ***–positive GC shared molecular characteristics similar to those of immunotherapy-sensitive ***,***–positive patients with DNA mismatch repair–deficient(dMMR)/microsatellite instability–high(MSI-H)colorectal adenocarcinoma and esophageal squamous cell carcinoma(ESCC)had shorter irPFS compared with ***–negative patients(16.13 months versus not reached,p=0.042,HR 2.26,95%CI 1.13–4.50,p=0.021 and 5.57 months versus 6.97 months,p=0.029,HR 1.59,95%CI 1.14–2.23,p=0.006,respectively).The difference in irOS between ***–positive and–negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC *** also identified a trend of shorter irPFS and irOS in ***–positive liver cancer and pancreatic cancer *** summary,our findings supported that *** infection is a beneficial factor for GC immunotherapy by shaping hot tumor ***,in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients,*** adversely affects the efficacy of immunothera

关键词： immunotherapy gastrointestinal pylori

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Global research landscape of Peutz-Jeghers syndrome and successful endoscopic management of intestinal intussusception in patients with recurrent laparotomies

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2702-2718页

作者： Qi Sun Xiao-Ying Wang Guang-Jin Guo Lei Wang Li-Min Meng Yun-Fei Guo Tao Sun Shou-Bin Ning department of Gastroenterology Air Force Medical CenterBeijing 100142China College of Life Science Northwest UniversityXi'an 710069Shaanxi ProvinceChina clinical Medical laboratory Air Force Medical CenterBeijing 100142China department of Medical Imaging Air Force Medical CenterBeijing 100142China department of pathology Air Force Medical CenterBeijing 100142China

BACKGROUND Peutz-Jeghers syndrome(PJS)has brought significant physical,psychological and economic burdens on the patients and their families due to its early onset,diagnostic and therapeutic challenges and increased recurrence *** To explore the current research status and emerging hotspots of *** Studies on PJS published during 1994-2023 were gathered based on Web of Science Core ***,a case of PJS-induced intestinal intussusception,successfully treated with endoscopic methods despite three laparotomies,was *** bibliometric and visual analysis were conducted with VOSviewer,R and *** Altogether 1760 studies were identified,indicating a steady increase in the publication *** United States had the highest influence,whereas the University of Helsinki emerged as the leading institution,and Aaltonen LA from the University of Helsinki was the most prolific *** Research,Oncogene and Endoscopy were the top three journals based on *** burst direction analysis revealed that"cancer risk","management","surveillance"and"familial pancreatic cancer"were the potential hotspots for ***,"early detection","capsule endoscopy","clinical management","double-balloon endoscopy","familial pancreatic cancer"and"molecular genetic basis"were identified as the key clusters of co-cited *** polypectomy remained effective on resolving intestinal intussusception in patients who underwent three previous *** In the last three decades,global publications related to PJS show a steadily increasing trend in *** management is currently a research hotspot.

关键词： Peutz-Jeghers syndrome Endoscopy Management Cancer Microbiota Bibliometric

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Mechanical sensor PDLIM5 promotes the osteogenesis of human adipose-derived stem cells through microfilament alterations

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Genes & Diseases 2024年第3期11卷 136-139页

作者： Yuchao Yang Shutong Wu Rongmei Qu Congrong Wang Jinyang Wang Asmat Ullah Khan You Pan Wenqing Liu Jinhui Zhu Muhammad Akram Khan Chujiang Xu Jingxing Dai Jun Ouyang Guangdong Provincial Key laboratory of Medical Biomechanics&National Key Discipline of Human Anatomy Schoolof BasicMedical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China department of laboratory medicine Nanfang Hospital of Southern Medical UniversityGuangzhouGuangdong 510515China department of pathology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510080China department of Breast Surgery Guangxi Medical University Cancer HospitalNanningGuangxi 530000China department of Veterinary pathology Faculty of Veterinary and Animal SciencesPMAS Arid Agriculture UniversityRawalpindi 46300Pakistan department of Orthopedics TCM-Integrated HospitalSouthern Medical UniversityGuangzhouGuangdong 510000China

Bone regeneration is a multifaceted,abstract,and wellcoordinated physiological progression of bone formation that participates in continuous regeneration and remodeling throughout ***,when it comes to complex clinical situations requiring extensive bone regeneration,such as massive bone defects caused by injuries,infection,or tumor removal,traditional methods do not often yield good treatment strategies or protocols due to their limitations.

关键词： alterations injuries massive

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Deciphering the role of FSCN family genes in cancer:a pan-cancer bioinformatics study

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Medical Data Mining 2024年第4期7卷 10-18页

作者： Wen-Shuai Zhang Dan-Yang Ren Xin Li department of pathology Tianjin Cancer Hospital Airport HospitalTianjin 300308China National clinical Research Center for Cancer Tianjin Medical University Cancer Institute and HospitalKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China

Background:The Fascin(FSCN)family,comprising actin-bundling proteins,plays vital roles in cytoskeletal reorganization and cell ***1,FSCN2,and FSCN3 are implicated in cancer progression through cell motility,invasion,and ***,their specific contributions across different cancer types remain ***:We conducted a pan-cancer bioinformatics analysis of FSCN genes using data from The Cancer Genome *** included differential expression patterns,copy number variations(CNVs),mutations,methylation status,and correlations with tumor mutational burden,microsatellite instability,and immune checkpoint molecule *** expression was analyzed using DESeq2,while CNV and mutation analyses utilized GISTIC2.0 and *** data were assessed using the Illumina Human Methylation 450K ***:FSCN1 and FSCN2 showed significant differential expression in multiple cancers,often correlating with poor ***3 exhibited less variability but a protective role in certain *** analysis indicated frequent gene gains in FSCN genes,correlating with increased ***3 had a higher mutation rate,suggesting genetic *** analysis showed hypomethylation of FSCN1 and FSCN2 in tumors compared to normal tissues,whereas FSCN3 had minor *** associations were found between FSCN gene expression and tumor mutational burden,microsatellite instability,and immune checkpoint molecules,suggesting their involvement in tumor immunogenicity and the immune ***:This pan-cancer analysis highlights the multifaceted roles of FSCN genes in cancer biology,emphasizing their potential as biomarkers and therapeutic ***1 and FSCN2 are associated with poor prognosis and aggressive phenotypes,while FSCN3 shows protective roles in specific *** findings offer new avenues for cancer diagnosis and treatment,particularly in personalized *** studie

关键词： Fascin family pan-cancer analysis gene expression copy number variation tumor mutational burden

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Congophilic fibrils in the glomeruli with polyclonal immunoglobulin gamma staining-another cause for diagnostic overlap:A case report

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World Journal of clinical Cases 2024年第17期12卷 3200-3205页

作者： Maria Bernadette Che-Ying Chow Lucas Bushrow Irmeen Siddiqui April Chiu Mirza Hamirani Anjali A Satoskar department of pathology The Ohio State University Medical CenterColumbusOH 43210United States department of pathology North District HospitalSheung ShuiHong KongChina department of laboratory medicine and pathology Mayo ClinicRochesterMN 55905United States department of Internal medicine S.Joseph's HospitalParkersburgWV 26101United States

BACKGROUND Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice,with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered *** amyloid heavy and light chain(AHL)is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin(Ig)heavy chain and a single light chain,further supported by mass spectrometry(MS)and serum studies for monoclonal *** polyclonal light chain staining can pose a *** SUMMARY Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma(IgG)staining pattern by *** patient is a 62-yearold Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range *** the finding of a polyclonal and polytypic staining pattern on immunofluorescence,ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 *** red was positive while DNAJB9 was *** suggested a diagnosis of amyloid AHL type with IgG and lambda,but kappa light chains were also present supporting the immunofluorescence staining *** immunofixation studies demonstrated IgG lambda monoclonal *** patient was started on *** chronic renal injury however was quite advanced and he ended up needing dialysis shortly *** Tissue diagnosis of AHL amyloid can be *** confirmation using other available diagnostic techniques is recommended in such cases.

关键词： Heavy and light chain amyloid Fibrillary glomerulonephritis DNAJB9 Serum immunofixation Protein electrophoresis Mass spectrometry Congo red Case report

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The lactylation index predicts the immune microenvironment and prognosis of pan-cancer patients

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BIOCELL 2024年第8期48卷 1223-1239页

作者： XUEJIA ZHAI JIE LIU JINWEI XIAO TAO ZHANG JUN WANG JIANJUN LI SHICANG YU department of Oncology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing400038China department of Stem Cell and Regenerative medicine Institute of Pathology and Southwest Cancer CenterSouthwest HospitalThird Military Medical University(Army Medical University)Chongqing400038China Key laboratory of Cancer Immunopathology Ministry of EducationChongqing400038China International Joint Research Center for Precision Biotherapy Ministry of Science and TechnologyChongqing400038China Jin-feng laboratory Chongqing401329China

Background:Protein lactylation is a new way for the“metabolic waste”lactic acid to perform novel ***,our understanding of the contribution of protein lactylation to both tumor progression and therapeutic interventions remains *** construction of a scoring system for lactylation to predict the prognosis of pancancer patients and to evaluate the tumor immune microenvironment(TIME)would improve our understanding of the clinical significance of ***:Consensus clustering analysis of lactylation-related genes was used to cluster 177 pancreatic adenocarcinoma(PAAD)***,a scoring system was developed using the least absolute shrinkage and selection operator(LASSO)*** validation and external validation were both conducted to assess and confirm the predictive accuracy of the scoring ***,leucine rich repeat containing 1(LRRC1),a newly discovered lactylation-related gene,was analyzed in PAAD in ***:Utilizing the profiles of 332 lactylation-related genes,a total of 177 patients with PAAD were segregated into two distinct ***^(high) patients had a poorer prognosis than LacCluster^(low) *** the differential analysis between the LacCluster^(high) and LacCluster^(low) groups,we identified additional genes associated with *** genes were then integrated to construct the LacCluster-enhanced system,which enabled more accurate prognosis prediction for patients with ***,a lactylation index containing three genes(LacI-3)was constructed using LASSO *** was done to enhance the usability of the LacCluster-enhanced system in the *** to those in the LacI-3^(high) subgroup,patients in the LacI-3^(low) subgroup exhibited increased expression of immune checkpoint-related genes,more immune cell infiltration,lower tumor mutation burdens,and better prognoses,indicating a“hot tumor”***,knocking down the expression of LRRC1,

关键词： Pancreatic adenocarcinoma Pan-cancer Lactylation Prognosis Tumor immune microenvironment LRRC1

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Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction

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Precision clinical medicine 2024年第2期7卷 132-145页

作者： Zehua Wang Ruichong Lin Yanchun Li Jin Zeng Yongjian Chen Wenhao Ouyang Han Li Xueyan Jia Zijia Lai Yunfang Yu Herui Yao Weifeng Su Guangdong Key laboratory of Cross-Application of Data Science and Technology Beijing Normal University-Hong Kong Baptist University United International CollegeZhuhai 519087China Faculty of Innovation Engineering Macao University of Science and TechnologyTaipaMacao 999078China department of Computer and Information Engineering Guangzhou Huali CollegeGuangzhou 511325China department of pathology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Guangzhou National laboratory Guangzhou 510005China Dermatology and Venereology Division Department of Medicine SolnaCenter for Molecular MedicineKarolinska InstitutetStockholm 17177Sweden Guangdong Provincial Key laboratory of Malignant Tumor Epigenetics and Gene Regulation Department of Medical OncologyBreast Tumor CentrePhase I Clinical Trial CentreSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China The Second clinical Medical College Southern Medical UniversityGuangzhou 510515China Faculty of medicine Macao University of Science and TechnologyTaipaMacao 999078China

Background:The prognosis of breast cancer is often unfavorable,emphasizing the need for early metastasis risk detection and accurate treatment *** study aimed to develop a novel multi-modal deep learning model using preoperative data to predict disease-free survival(DFS).Methods:We retrospectively collected pathology imaging,molecular and clinical data from The Cancer Genome Atlas and one independent institution in *** developed a novel Deep Learning clinical medicine Based Pathological Gene Multi-modal(DeepClinMed-PGM)model for DFS prediction,integrating clinicopathological data with molecular *** patients included the training cohort(n=741),internal validation cohort(n=184),and external testing cohort(n=95).Result:Integrating multi-modal data into the DeepClinMed-PGM model significantly improved area under the receiver operating characteristic curve(AUC)*** the training cohort,AUC values for 1-,3-,and 5-year DFS predictions increased to 0.979,0.957,and 0.871,while in the external testing cohort,the values reached 0.851,0.878,and 0.938 for 1-,2-,and 3-year DFS predictions,*** DeepClinMed-PGM's robust discriminative capabilities were consistently evident across various cohorts,including the training cohort[hazard ratio(HR)0.027,95%confidence interval(CI)0.0016-0.046,Pclinical data for enhanced predictive accuracy,offering promise for personalized treatment strategies.

关键词： breast cancer multi-modality deep learning pathological disease-free survival

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Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li Shaohong Chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of clinical medicine Tsinghua University100084 BeijingChina Chigenovo Co. Ltd.102206 BeijingChina department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available ***,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 *** open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/***,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were *** with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the *** conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： cor dystrophy crystalline

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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao Xue Cai Yan-Yan Xue Weigang Ge Liang Yue Xiao-Yan Li Rong-Rong Lin Guo-Ping Peng Wenhao Jiang Sainan Li Kun-Mu Zheng Bin Jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu department of Neurology and Research Center of Neurology in the Second Affiliated Hospital and Key laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China Liangzhu laboratory Zhejiang UniversityHangzhou 311100China Westlake laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzho 310024China department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation Center for Neurological Disorders and department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic *** ADspecific early diagnostic and disease staging biomarkers are *** this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 *** biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 *** quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,*** the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,*** 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,*** 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative ***,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD *** findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid

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Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第11期30卷 1524-1532页

作者： Yi-Fan Chang Jia-Jing Li Tao Liu Chong-Qing Wei Li-Wei Ma Vladimir N Nikolenko Wei-Long Chang department of Gastrointestinal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of clinical laboratory The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of Human Anatomy and Histology I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia

Autophagy is a cellular catabolic process characterized by the formation of double-membrane *** electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)***,the role of autophagy in GI diseases remains *** article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

关键词： Autophagy Morphological study Biochemical characteristics Subcellular structure Transmission electron microscopy Gastrointestinal diseases

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