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Bortezomib depended on PRDM1 and TP53 to exert therapeutic effect in activated B-cell-like diffuse large B-cell lymphoma

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Genes & Diseases 2024年第2期11卷 550-553页

作者： Jing Tang Yue Li Jiazhu Wu Haorui Shen Hua Yin Jinhua Liang Li Wang Jianyong Li Yi Xia Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

PR/SET domain 1(PRDM1)gene is located on chromosome 6q21,encoding the B lymphocyte-induced maturation protein 1(BLIMP1).1 It is reported that loss of PRDM1 function is exacerbated in activated B-cell-like(ABC)-diffuse large B cell lymphoma(DLBCL)and associated with inferior ***,it remains unclear what leads to PRDM1 inactivation and the drug resistance mechanism caused by abnormal inactivation of *** investigated the contribution of PRDM1 gene as a prognosis and potential therapeutic target for ABC-DLBCL patients and further clarified the possible mechanism of PRDM1 abnormal *** first proposed that TP53 could regulate PRDM1 by histone ubiquitination modification at the post-transcriptional level.

关键词： PRDM1 TP53 therapeutic

Artificial intelligence in individualized retinal disease management

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1519-1530页

作者： Zi-Ran Zhang Jia-Jun Li Ke-Ran Li The Affiliated Eye hospital of nanjing Medical University Nanjing 210029Jiangsu ProvinceChina nanjing Medical University Nanjing 210029Jiangsu ProvinceChina

Owing to the rapid development of modern computer technologies,artificial intelligence(AI)has emerged as an essential instrument for intelligent analysis across a range of *** has been proven to be highly effective in ophthalmology,where it is frequently used for identifying,diagnosing,and typing retinal *** increasing number of researchers have begun to comprehensively map patients’retinal diseases using AI,which has made individualized clinical prediction and treatment *** include prognostic improvement,risk prediction,progression assessment,and interventional therapies for retinal *** have used a range of input data methods to increase the accuracy and dependability of the results,including the use of tabular,textual,or image-based input *** also combined the analyses of multiple types of input *** give ophthalmologists access to precise,individualized,and high-quality treatment strategies that will further optimize treatment outcomes,this review summarizes the latest findings in AI research related to the prediction and guidance of clinical diagnosis and treatment of retinal diseases.

关键词： artificial intelligence artificial intelligence in ophthalmology retinal disease

Phosphatidic acid-enabled MKL1 contributes to liver regeneration:Translational implication in liver failure

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Acta Pharmaceutica Sinica B 2024年第1期14卷 256-272页

作者： Jiawen Zhou Xinyue Sun Xuelian Chen Huimin Liu Xiulian Miao Yan Guo Zhiwen Fan Jie Li Yong Xu Zilong Li State Key Laboratory of Natural Medicines Department of PharmacologyChina Pharmaceutical UniversityNanjing 211198China Institute of Biomedical Research Liaocheng UniversityLiaocheng 252200China Department of Pathology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Infectious Diseases Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical SchoolNanjing 210008China Institute of Viruses and Infectious Diseases Nanjing UniversityNanjing 210008China

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver *** the present study we investigated the contribution of megakaryocytic leukemia 1(MKL1),a transcriptional modulator,to liver *** report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure *** with MKL1 deletion exhibited defective regenerative response in the *** analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative ***2 mediated phosphorylation primed MKL1 for its interaction with *** interest,phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid(PA).PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver ***,PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure *** conclusion,our data reveal a novel mechanism whereby MKL1 contributes to liver *** for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

关键词： Liver failure Liver regeneration Transcription regulation Transcription factor Hepatocytes Phosphatidic acid Phospholipase d2 Translational medicine

Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice

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Chinese Journal of Integrative Medicine 2024年第8期30卷 692-700页

作者： LU Chao GAO Zi-wei XING Shan WANG Hui-hui HUANG Yun-ke ZHOU Hang WU Lei Department of Chinese Medicine Preparations Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjing210029China College of Chinese Medicine Nanjing University of Chinese MedicineNanjing210046China Department of Chinese Medicine Women’s HospitalSchool of MedicineZhejiang UniversityHangzhou310000China

Objective To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San(CSS)in female *** Liquid chromatography mass spectrometry(LC-MS)/MS was used to determine the content of main components in CSS to determine its *** C57BL/6J mice were randomly divided into 4 groups,including control(saline),vehicle(saline),CSS(4 g/kg)and ketamine(30 mg/kg)*** were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress(CMS)model,then received a single administration of *** hours later,the behavioral tests were performed,including open field test,tail suspension test(TST),forced swimming test(FST),novelty suppression feeding test(NSF),and sucrose preference test(SPT).Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor(NMDA)subtypes[N-methyl-D-aspartate receptor 1(NR1),NR2A,NR2B],synaptic proteins[synapsin1 and post synaptic density protein 95(PSD95)],and brain-derived neurotrophic factor(BDNF).Moreover,the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors,*** Compared with the vehicle group,a single administration of CSS(4 g/kg)reversed all behavioral defects in TST,FST,SPT and NSF caused by CMS(P2A,NR2B)at 2 h in hippocampus of mice(all P<0.01).In addition,similar to ketamine,CSS increased levels of synaptic proteins and BDNF(P<0.05 or P<0.01).Furthermore,the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus(all P<0.01).Conclusion Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.

关键词： Chaihu Shugan San female rapid antidepressant potential N-methyl-D-aspartate receptor synapticprotein optogenetic Chinesemedicine

N-glycan biosignatures as a potential diagnostic biomarker for earlystage pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 659-669页

作者： Yan-Rong Wen Xia-Wen Lin Yu-Wen Zhou Lei Xu Jun-Li Zhang Cui-Ying Chen Jian He Department of Nuclear Medicine Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Research and Development Sysdiagno(Nanjing)Biotech Co.LtdNanjing 210008Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis,with a 5-year survival rate of less than 10%,owing to its late-stage *** detection of pancreatic cancer(PC)can significantly increase survival *** To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan *** An extensive patient cohort was used to determine a biomarker signature,in-cluding patients with PDAC that was well-defined at an early stage(stages I and II).The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I,22 with stage II,4 with stage III,16 with stage IV PDAC,and 88 *** used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan sig-nature-based diagnosis model called the“Glyco-model”.RESULTS The biomarker signature was created to discriminate samples derived from patients with PC from those of controls,with a receiver operating characteristic area under the curve of *** addition,the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls,with a receiver operating characteristic area under the curve of ***-model demonstrated favorable diagnostic performance in all stages of *** diagnostic sensitivity for stage I PDAC was 89.66%.Core Tip:This study employed a patient cohort to investigate the N-glycan signature of early-stage pancreatic cancer(PC).Serum N-glycans analysis was conducted to identify the serum biomarker signature associated with early-stage pancreatic ductal adenocarcinoma(PDAC),resulting in the identification of nine early-stage PDAC N-glycan ***,utilizing these biosignatures,a diagnostic model named the“Glyco-model”was developed,demonstrating promising diagnostic performance across all stages of *** study revealed that the diagnostic sensitivity for stage I PDAC was determined to be 89.66%.Co

关键词： Glycomics N-glycans Biomarkers Pancreatic cancer Predictive modeling

Genotyping on circulating tumor DNA improves mutation detection rate in high-risk diffuse large B-cell lymphoma

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Genes & Diseases 2024年第4期11卷 116-119页

作者： Yi Xia Li Wang Jinhua Liang Haorui Shen Jiazhu Wu Hua Yin Yue Li Huayuan Zhu Jianyong Li Wei Xu Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingJiangsu 210029China Key Laboratory of Hematology of nanjing Medical University NanjingJiangsu 210029China Collaborative Innovation Center for Cancer Personalized Medicine NanjingJiangsu 210029China

Diffuse large B-cell lymphoma(DLBCL)is the most common lymphoma with heterogeneous clinical *** who are primarily refractory to the frontline therapy or relapse less than 12 months after diagnosis have an extremely di... 详细信息

关键词： lymphoma diagnosis clinical

LSM6 promotes cell proliferation and migration regulated by HMGB1 in laryngeal squamous cell carcinoma

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Engineered Regeneration 2024年第2期5卷 247-254页

作者： Dengbin Ma Jiayi Li Hui Li Yao Tang Xia Gao Hong Chen Xiaoyun Qian Xiaohui Shen Department of Otolaryngology Head and Neck Surgery Research Institute of OtolaryngologyNanjing Drum Tower HospitalJiangsu Provincial Key Medical DisciplineAffiliated Hospital of medical SchoolNanjing UniversityNanjing210008China Department of Otorhinolaryngology Minda Hospital of Hubei Minzu UniversityEnshi445000China nanjing Drum Tower hospital Clinical College of nanjing Medical University 321 Zhongshan RoadNanjing210008China

Elevated levels of high mobility group protein B1(HMGB1)play a significant role in the pathogenesis of many diseases,but is particularly important for the formation of malignant ***,the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma(LSCC)remain incompletely understood,causing *** we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upreg-ulated,which was associated with poor ***1 knockdown could significantly inhibit wound closure and colony *** full-genome gene expression microarray was performed to investigate the *** knockdown of HMGB1 by siRNA,among the expressed differential genes,10 genes were ran-domly selected for ***,shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation ***6 downregulation was dramatically promoted by HMGB1 knockdown,resulting in higher expression in LSCC ***,downregulation of LSM6 could significantly suppress cell proliferation,migration and colony *** study indicated that HMGB1 promoted LSCC cell malig-nant phenotypes through regulation of *** anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.

关键词： HMGB1 LSM6 Laryngeal squamous cell carcinoma Cell proliferation Migration

Ethanol extract of Abelmoschus manihot suppresses endoplasmic reticulum stress in contrast-induced nephropathy

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 17-27,I0002,I0003页

作者： Xin Lin Xin Lu Yun-He Zhao Yi-Bei Wang Ru-Ge Niu Xiao-Hu Chen Department of Cardiology Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjingJiangsu 210004China

Objective:To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot(L.)Medic in contrast-induced nephropathy(CIN).Methods:CIN rat models and human renal proximal tubular cells(HK-2)with iopromide-induced injury were employed to mimic CIN *** effect of Abelmoschus manihot extract on the rat models and HK-2 cells was *** rat models,kidney function,histology,oxidative stress and apoptosis were *** HK-2 cells,cell viability,apoptosis,mitochondrial membrane potential,and endoplasmic reticulum stress were ***:Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN ***,the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid *** investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein ***:Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

关键词： Contrast-induced nephropathy Abelmoschus manihot extract ER stress Apoptosis GRP78 CHOP

The value of toxicological analysis in acute poisoning patients with uncertain exposure histories:a retrospective and descriptive study from an institute of poisoning

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World Journal of Emergency Medicine 2024年第2期15卷 98-104页

作者： Qifang Shi Gen Ba Zhenyu Xia Zhengsheng Mao Hao Sun Jinsong Zhang Institute of Poisoning Nanjing Medical UniversityNanjing 211100China Department of Emergency Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Forensic Medicine Nanjing Medical UniversityNanjing 211166China The Key Laboratory of Modern Toxicology of Ministry of Education Nanjing Medical UniversityNanjing 211166China

BACKGROUND:In clinical practice,some patients might not be able or unwilling to provide a thorough history of medication and poison *** aim of this study was to use toxicological analysis to examine the clinical characteristics of patients with acute poisoning whose exposure history was uncertain from a toxicological analysis ***:This was a retrospective and descriptive study from an institute of *** registration information and test reports spanning the period from April 1,2020 to March 31,2022,were *** with uncertain exposure histories and who underwent toxicological analysis were *** manifestations and categories of toxics were ***:Among the 195 patients with positive toxicological analysis results,the main causes of uncertain exposure history was disturbance of consciousness(62.6%),unawareness(23.6%)and unwillingness or lack of cooperation(13.8%).The predominant clinical manifestations were disturbed consciousness(62.6%),followed by vomiting and nausea(14.4%)and liver function abnormalities(8.7%).A comparison of clinical manifestations between patients with positive and negative(n=99)toxicological analyses results revealed significantly different proportions of disturbances in consciousness(63%vs.21%),dizziness(1.5%vs.5.1%),multi-organ failure(1.5%vs.7.1%),and local pain(0 vs 4%).The main categories of substances involved were psychiatric medications(23.1%),sedatives(20.5%),insecticides(13.8%),and herbicides(12.8%).CONCLUSION:The clinical manifestations of acute poisoning in patients with an uncertain exposure history are diverse and nonspecific,and toxicological analysis plays a pivotal role in the diagnosis and differential diagnosis of such patients.

关键词： Acute poisoning Toxic exposure Toxicological analysis Clinical manifestation