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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li Xinjuan Fan Zaiyi Liu Department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China guangdong provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application GuangzhouGuangdong 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis *** spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI ***:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation *** facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was *** the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was ***:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI *** CD3_(CT) confirmed as a stage-independent predictor for OS in CRC ***,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

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Neural Regeneration Research 2024年第2期19卷 324-330页

作者： Xi Chen Yuhu Zhang Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially *** dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and *** contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial *** from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s *** research has reported evidence that the cerebellum receives both dopaminergic and cholinergic ***,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully ***,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains ***,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional *** findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

关键词： anterior brain system cerebellum cholinergic cognitive impairment dopaminergic dual syndrome hypothesis neuroimage neurotransmitter Parkinson’s disease posterior brain system therapeutic targets

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Prognostic implications of overt congestion in heart failure with preserved ejection fraction and the interaction with spironolactone:Insights from TOPCAT

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Chinese Medical Journal 2024年第10期137卷 1249-1251页

作者： Yingwen Lin Hengli Zhao Dongtu Hu Jia Huang You Peng Juncong Li Dingli Xu Qingchun Zeng State Key Laboratory of Organ Failure Research Department of CardiologyNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China guangdong provincial Key Laboratory of Clinical Pharmacology Medical Research InstituteGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510515China Department of Radiology The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510150China Department of Obstetrics and Gynecology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

To the Editor:Heart failure with preserved ejection fraction(HFpEF)is a clinical entity characterized by impaired diastolic *** recently,there have been few studies directly evaluating how volume status impacts future cardiac events for patients with *** supporting the application of spironolactone in HFpEF is mainly derived from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist(TOPCAT)*** though primary analysis of the trial reached a neutral result,subgroup and subsequent post hoc analyses have confirmed its efficacy in selected groups of patients,suggesting that identifying the potential subgroups of patients who would benefit from spironolactone treatment is important.[1]Data regarding the impact of congestion status on the efficacy of spironolactone in HFpEF are lacking.

关键词： function. fraction impaired

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Functional gastrointestinal disorders,mental health,genetic susceptibility,and incident chronic kidney disease

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Chinese Medical Journal 2024年第9期137卷 1088-1094页

作者： Mengyi Liu Panpan He Ziliang Ye Sisi Yang Yanjun Zhang Qimeng Wu Chun Zhou Yuanyuan Zhang Fan Fan Hou Xianhui Qin Division of Nephrology Nanfang HospitalSouthern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologyGuangdong Provincial Key Laboratory of Renal Failure ResearchGuangzhouGuangdong 510515China

Background:Whether functional gastrointestinal disorders(FGIDs)are associated with the long-term risk of chronic kidney disease(CKD)remains *** aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the ***:About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were *** with FGIDs(including irritable bowel syndrome[IBS],dyspepsia,and other functional intestinal disorders[FIDs;mainly composed of constipation])were the exposure group,and non-FGID participants were the non-exposure *** primary outcome was incident CKD,ascertained from hospital admission and death registry records.A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD,and the mediation analysis was performed to investigate the mediation proportions of mental ***:At baseline,33,156(8.0%)participants were diagnosed with FGIDs,including 21,060(5.1%),8262(2.0%),and 6437(1.6%)cases of IBS,dyspepsia,and other FIDs,*** a mean follow-up period of 12.1 years,11,001(2.6%)participants developed *** were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs(hazard ratio[HR],1.36;95%confidence interval[CI],1.28-1.44).Similar results were observed for IBS(HR,1.27;95%CI,1.17-1.38),dyspepsia(HR,1.30;95%CI,1.17-1.44),and other FIDs(HR,1.60;95%CI,1.43-1.79).Mediation analyses suggested that the mental health score significantly mediated 9.05%of the association of FGIDs with incident CKD and 5.63-13.97%of the associations of FGID subtypes with ***,the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of ***:Participants with FGIDs had a higher risk of incident CKD,which was partly explained by mental health scores and was more pronounced in those with high gen

关键词： Functional gastrointestinal disorders Chronic kidney diseases Genetic susceptibility Mental health

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CARD11 serves as a therapeutic biomarker for the drug therapies of ccRCC

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BIOCELL 2024年第5期48卷 817-834页

作者： KAIWEN TIAN HANZHONG CHEN QIANQIAN WANG FENGLIAN JIANG CHUNXIANG FENG TENG LI XIAOYONG PU YANLIN TANG JIUMIN LIU Department of Urology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou510080China

Background:The incidence of clear cell renal cell carcinoma(ccRCC)is globally high;however,despite the introduction of innovative drug therapies,there remains a lack of effective biomarkers for evaluating treatment ***,Caspase recruiting domain-containing protein 11(CARD11)has garnered attention due to its significant association with tumor development and the immune ***:The expression of CARD11 mRNA and protein in ccRCC were analyzed by public database and *** focus of this study is on the epigenomic modifications of CARD11,its expression of ccRCC immunophenotype,and its correlation with response to immunotherapy and targeted ***,to investigate the mechanism of this molecule’s influence on different biological behaviors of cells,cell tests in vitro have been conducted to observe the impact of its expression ***:CARD11 expression was upregulated which may be mainly modified by body methylation and was correlated with poor prognosis in *** the tumor microenvironment of ccRCC,CARD11 expression was positively correlated with increased T lymphocyte infiltration and increased expression of inhibitory immune ***,ccRCC patients with high CARD11 expression had a better response to immunotherapy and targeted *** knockdown of CARD11 ultimately suppressed the proliferation,migration,and invasion capabilities of ccRCC cells while simultaneously enhancing tumor cell ***:We identified CARD11 as a novel therapeutic biomarker for immunotherapy and targeted therapy in ccRCC.

关键词： Clear cell renal cell carcinoma Tumor microenvironment CARD11 Immune checkpoint inhibitor Tyrosine kinase inhibitor

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Weakly Supervised Object Localization with Background Suppression Erasing for Art Authentication and Copyright Protection

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Machine Intelligence Research 2024年第1期21卷 89-103页

作者： Chaojie Wu Mingyang Li Ying Gao Xinyan Xie Wing W.Y.Ng Ahmad Musyafa School of Computer Science and Engineering South China University of TechnologyGuangzhou 511442China guangdong provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application Guangdong Provincial People's HospitalGuangzhou 510180China

The problem of art forgery and infringement is becoming increasingly prominent,since diverse self-media contents with all kinds of art pieces are released on the Internet every *** art paintings,object detection and localization provide an efficient and ef-fective means of art authentication and copyright ***,the acquisition of a precise detector requires large amounts of ex-pensive pixel-level *** alleviate this,we propose a novel weakly supervised object localization(WSOL)with background su-perposition erasing(BSE),which recognizes objects with inexpensive image-level ***,integrated adversarial erasing(IAE)for vanilla convolutional neural network(CNN)dropouts the most discriminative region by leveraging high-level semantic ***,a background suppression module(BSM)limits the activation area of the IAE to the object region through a self-guidance ***,in the inference phase,we utilize the refined importance map(RIM)of middle features to obtain class-agnostic loc-alization *** experiments are conducted on paintings,CUB-200-2011 and ILSVRC to validate the effectiveness of our BSE.

关键词： Weakly supervised object localization erasing method deep learning computer vision art authentication and copyright protection

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Outcomes in pediatric recipients of single kidney transplantation from pediatric donors with acute kidney injury:A single-center pilot study

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Chinese Medical Journal 2024年第12期137卷 1489-1491页

作者： Qiang Zhang Yanxu Chen Haiyue Yu Jun Li Chenglin Wu Sizhe Long Pengan Li Qian Fu Huanxi Zhang Xiaojun Su Bowen Xu Longshan Liu Changxi Wang Organ Transplant Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Stomatological hospital Southern Medical UniversityGuangzhouGuangdong 510280China Center for Information Technology and Statistics The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China guangdong provincial Key Laboratory of Organ Donation and Transplant Immunology GuangzhouGuangdong 510080China guangdong provincial Key Laboratory guangdong provincial International Cooperation Base of Science and Technology(Organ Transplantation) GuangzhouGuangdong 510080China

To the Editor:The shortage of deceased donor(DD)kidneys for transplantation remains a persistent *** the potential reversibility of acute kidney injury(AKI)lesions,kidneys from pediatric donors with AKI are often underutilized,especially in the context of pediatric *** implementing single kidney transplantation(SKT)from pediatric donors to pediatric recipients(PTP),we can optimize the utilization of available kidneys and increase the number of pediatric recipients.

关键词： pediatric kidney acute

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Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang Department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Organ Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Renal Transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China Department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury Liver transplantation

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Endogenous Candida albicans endophthalmitis in a patient with chronic renal failure on hemodialysis

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 979-981页

作者： Meng-Ya Liu Zhi-Fan Chen Hao-Sheng Liu Qian-Li Meng Department of Ophthalmology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080Guangdong ProvinceChina The Fourth Affiliated hospital of Guangzhou Medical University Guangzhou 511400Guangdong ProvinceChina

Dear Editor,We report a rare case of endogenous endophthalmitis caused by Candida albicans in a patient with chronic renal failure concomitant hemodialysis.A 71-year-old man with a history of hypertension and 2-year chronic renal failure on hemodialysis via a native arteriovenous fistula(AVF)was presented to the local hospital due to fever 3wk *** pathogens were detected through blood culture on admission,and his fever gradually subsided with intravenous ceftriaxone *** a week of fever,he experienced progressive blurred vision in both eyes,accompanied by pain and *** magnetic resonance imaging(MRI)of the brain revealed *** had not undergone any previous eye surgeries or trauma.

关键词： hemodialysis albicans fever

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