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PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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World Journal of Gastroenterology 2024年第9期30卷 1237-1249页

作者： Yue-Hong Kong Mei-Ling Xu Jun-Jun Zhang Guang-Qiang Chen Zhi-Hui Hong Hong Zhang Xiao-Xiao Dai Yi-Fu Ma Xiang-Rong Zhao Chen-Yang Zhang Rong-Zheng Chen Peng-Fei Xing Li-Yuan Zhang Center for Cancer Diagnosis and Treatment The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of radiotherapy&Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Institution of radiotherapy&Oncology Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Radiology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Nuclear Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Clinical Laboratory The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Pathology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line *** human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in *** SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 *** had not developed any grade 2 or above treatment-related adverse events at any *** of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no *** PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

关键词： Pancreatic ductal adenocarcinoma PRaG 3.0 therapy Human epidermal growth factor receptor 2 Novel combination therapy Case report

Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

Dry eye disease in systemic lupus erythematosus: a cross sectional study

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1255-1261页

作者： Sui-Fang Kang Ying-Xue Wang Qi-Chen Zhang Zhi-Lun Wang Guo-Ling Chen department of Ophthalmology the Second Hospital of Shandong UniversityJinan 250033Shandong ProvinceChina department of Rheumatology the Second Hospital of Shandong UniversityJinan 250033Shandong ProvinceChina

AIM:To explore ocular surface manifestations of dry eye disease(DED)and its influencing factors in systemic lupus erythematosus(SLE)***:Ophthalmological examinations were conducted in SLE patients(n=43)and controls(n=41),including Ocular Surface Disease Index(OSDI),objective scatter index(OSI),tear meniscus height(TMH),lipid layer thickness(LLT),non-invasive Keratograph tear breakup time(NIKBUT),corneal fluorescein score(CFS),Schirmer I *** was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II *** patients were further divided into DED group and non-DED group,the disease activity,clinical manifestations and laboratory investigations were compared between the two *** disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K).Receiver operative characteristic(ROC)curve and multiplefactor binary logistic regression were ***:SLE patients showed higher OSDI[9.1(2.8-15.9)vs 6.3(2.2-7.5),P=0.035],higher OSI[1.67(1.09-2.60)vs 0.96(0.87-1.60),P=0.001],higher CFS[1(0-2)vs 0(0-1),P=0.001],lower LLT[65(42-100)vs 100(79.5-100),P=0.010],and lower NIKBUT[8.03(4.02-9.73)vs 9.67(5.26-12.71),P=0.030]than *** 32.6%of SLE patients had DED,which was higher than 12.2%of healthy *** group showed higher SLEDAI-2K score[9.7±6.1 vs 5.4±3.4,P=0.025],higher anti-cardiolipin antibody(ACL)[8.7(3.5-13.2)vs 3.6(2.0-6.9),P=0.035],and higher proportion of patients with cutaneous eruption[42.9%vs 6.9%,P=0.015]than non-DED *** to multiple-factor binary logistic regression analysis,the SLEDAI-2K score(OR=1.194,P=0.041)and cutaneous eruption(OR=7.094,P=0.045)could be consider as risk factors for DED in SLE *** ROC curve of the combined factors including age,disease duration,SLEDAI-2K score,ACL,and cutaneous eruption was analyzed,with a sensitivity of 0.786,a specificity of 0.793,and an area under curve of ***:Ocular surface affec

关键词： autoimmune disease systemic lupus erythematosus dry eye disease

Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

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Oncology Research 2024年第5期32卷 899-910页

作者： YIWEN ZHU LIU YANG YING YU YING XIONG PING XIAO XIAO FU XIN LUO department of Rehabilitation Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China department of General Practice The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal *** there is no permanent therapy for this condition,it is necessary to develop a ***,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were *** experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were *** MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity *** reduced the Warburg effect and induced ferroptosis(FPT)in MG63 *** ferroptosis diminished HYSA’s anti-cancer activities in MG63 *** stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 ***-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°*** significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand ***,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 *** is a possible therapeutic option for OC or other cancers.

关键词： Hydroxysafflor yellow A Osteosarcoma HIF-1α FPT

BMI1 overexpression is correlated with a poor prognosis and immune infiltration in hepatocellular carcinoma

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Oncology and Translational Medicine 2024年第2期10卷 60-65页

作者： Min-Cong Wang Peng-Tao Yang Yang Zhang Hong-Bing Ma department of radiotherapy Second Affiliated HospitalMedical School of Xi'an Jiaotong UniversityXi'an 710004China

Background:Owing to the occurrence of primary or secondary tolerance,the efficacy of immunotherapy for hepatocellular carcinoma(HCC)patients is ***,the mechanism underlying this tolerance needs to be further investigated.B cell–specific Moloney murine leukemia virus integration site 1(BMI1)is associated with cancer stem cell tumorigenesis,progression,and the maintenance of the ***,the effect of BMI1 expression on immune infiltration and prognosis in HCC is still ***:To assess the relationship between BMI1 expression and HCC prognosis and immune infiltration,the GEPIA database,TIMER database,and K-M plotter were *** database was used to determine the levels ofBMI1 in various tumor tissues and corresponding normal tissues,and examine the association between BMI1 expression and tumor-infiltrating immune *** database was applied to determine BMI1 expression in various tumor tissues and corresponding normal tissues.K-M Plotter was used to study the relationships among BMI1 expression,clinicopathological features,and survival ***:BMI1 expression was markedly higher in various solid tumors compared with that in the respective normal tissues,including HCC,and high expression led to poor relapse-free survival and overall survival in HCC ***1 overexpression was also correlated with the infiltration of immune cells(eg,B cells,CD8+T cells,CD4+T cells,dendritic cells,neutrophils,and macrophages)and positively associated with different subsets of T cells,monocytes,and M1 macrophages,among ***:This study demonstrates that high BMI1 expression is strongly correlated with immune infiltration and poor prognosis in *** expression of BMI1 might thus be a potential mechanism of immune tolerance in this disease.

关键词： BMI1 Hepatocellular carcinoma Prognosis Immune infiltrates

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

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World Journal of Gastroenterology 2024年第10期30卷 1295-1312页

作者： Hui Ma Qing-Zhu Yan Jing-Ru Ma Dong-Fu Li Jun-Ling Yang department of Clinical Laboratory The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Ultrasound Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina Digestive Diseases Center Department of Hepatopancreatobiliary MedicineThe Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina department of Respiratory and Critical Care Medicine The Second Hospital of Jilin UniversityChangchun 130000Jilin ProvinceChina

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease *** review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and *** delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive *** factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are ***,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease *** reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is *** strategies,including anti-viral and immunomodulatory approaches,are critically *** role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent *** conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV *** a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge *** more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient *** dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory *** role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

关键词： Hepatitis B virus reactivation Immunological mechanisms Disease progression Management strategies Immune response

Macroscopic on-site magnifier-based evaluation to estimate visible tissue core cut-off lengths using EUS-FNA with 22-gauge needles

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Chinese Medical Journal 2024年第4期137卷 493-495页

作者： Jialiang Huang Guilian Cheng Wei Wu Liming Xu Longjiang Xu Duanmin Hu department of Gastroenterology Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China department of Pathology Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China

To the Editor:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^([1])To further improve the effectiveness and safety of EUS-FNA,pathologists may perform rapid on-site cytology evaluation(ROSE),but this process requires the presence of *** on-site evaluation(MOSE)has gained attention as it resolve the shortage of pathologist resources.^([2])Endoscopists can inspect the tissue core in real time and assess the adequacy of the punctured *** this study,we conducted a single-center and single-arm exploratory study to explore the value of MOSE in assessing specimen quality during magnifier-based EUS-FNA and to confirm the cut-off length of visible tissue core(VTC)for EUS-FNA to help endosonographers independently predict the adequacy of punctured *** VTC was defined as a white or incarnadine tissue core obtained from focal lesions with a relatively complete histological structure.

关键词： EUS needle visible

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Undifferentiated high-grade pleomorphic sarcoma of the common bile duct:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2253-2260页

作者： Li-Ping Zheng Wen-Yan Shen Chun-Dong Hu Chun-Hua Wang Xu-Jian Chen Jing Wang Yi-Yu Shen department of General Surgery The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina department of Pathology The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina

BACKGROUND Undifferentiated pleomorphic sarcoma(UPS)is a rare malignant mesenchymal tumor with a poor *** mainly occurs in the extremities,trunk,head and neck,and retroperitoneum *** to the lack of specific clinical manifestations and imaging features,UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive *** we report an extremely rare case of high-grade UPS in the common bile duct(CBD).There are limited available data on such *** SUMMARY A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 *** laboratory data suggested significantly elevated hepatorenal function *** imaging data revealed calculous cholecystitis,intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi,and a space-occupying lesion at the distal *** endoscopic biliary stenting and symptomatic support therapy,CBD exploration and biopsy were *** frozen section indicated malignant spindle cell tumor of the CBD mass,and further radical pancreaticoduodenectomy was ***,the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical *** This extremely rare case highlighted the need for increasing physicians'vigilance,reducing the odds of misdiagnosis,and providing appropriate treatment strategies.

关键词： Undifferentiated pleomorphic sarcoma Soft tissue sarcoma Common bile duct Extrahepatic bile duct Immunohistochemistry Case report