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Continuous Expression of Interferon Regulatory Factor 4 Sustains CD8^(+)T Cell Immunity against Tumor

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Research 2024年第3期2023卷 433-444页

作者： Anze Yu Jinfei Fu Zheng Yin Hui Yan Xiang Xiao Dawei Zou Xiaolong Zhang Xiongbing Zu Xian C.Li Wenhao Chen Immunobiology and Transplant Science Center Department of SurgeryHouston Methodist Research Institute and Institute for Academic MedicineHouston Methodist HospitalHoustonTXUSA Department of Urology First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongChina Systems Medicine and Bioengineering Department Houston Methodist Neal Cancer CenterHoustonTXUSA Department of radiology Houston Methodist HospitalWeill Cornell MedicineHoustonTXUSA Department of Urology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Surgery Weill Cornell MedicineCornell UniversityNew YorkNYUSA.

T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains *** objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma *** achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of *** exhibited a more differentiated PD-1high cell *** administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted ***^(+)TILs and observed an accelerated tumor *** specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)***,depleting ***^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor ***,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ***,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor ***,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.

关键词： sustained immunity implantation

The impact of new technology on surgery for colorectal cancer

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World Journal of Gastroenterology 2001年第5期7卷 612-621页

作者： GregoryBMakin DavidJBreen JohnRTMonson University of Hull academic Surgical unit and Depanment of radiology Castle Hill HospitalCastle RoadCottingham HU16 5JQUnited Kingdom

Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and localisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for *** investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets, which can be stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding. Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient's overall condition before definitive surgery. Transanal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum. Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging. Robotics and telemedicine are taking surgery well into the 21(st) century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer.

关键词： Catheter Ablation Colonoscopy Colorectal Neoplasms Humans

Differentiation of malignant and benign proximal bile duct strictures: The diagnostic dilemma

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World Journal of Gastroenterology 2008年第32期14卷 5032-5038页

作者： Jaap Jacob Kloek Otto Marinus van Delden Deha Erdogan Fibo Jan ten Kate Erik Anthoni Rauws Olivier Robert Busch Dirk Joan Gouma Thomas Mathijs van Gulik Department of Surgery Academic Medical Center University of Amsterdam Department of radiology Academic Medical Center University of Amsterdam Department of Pathology Academic Medical Center University of Amsterdam Department of Gastroenterology Academic Medical Centre University of Amsterdam

AIM: To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These fi ndings were analyzed to obtain the fi nal diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group Ⅰ) whereas 10 patients (15%, groupⅡ) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group Ⅰvs 60% group Ⅱ P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group Ⅰcompared to group Ⅱ The various imaging modalities showed vascular involvement exclusively in the malignant group (36%,P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group Ⅰ whereas none in group Ⅱ showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.

关键词： Biliary stricture Hilar cholangiocarcinoma Benign Radiological Vascular involvement cholangio

Results of percutaneous sclerotherapy and surgical treatment in patients with symptomatic simple liver cysts and polycystic liver disease

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World Journal of Gastroenterology 2007年第22期13卷 3095-3100页

作者： Deha Erdogan Otto M van Delden Erik AJ Rauws Olivier RC Busch Johan S Lameris Dirk J Gouma Thomas M van Gulik Department of Surgery Academic Medical Center University of Amsterdam The Netherlands Department of radiology Academic Medical Center University of Amsterdam The Netherlands Department of Gastroenterology Academic Medical Center University of Amsterdam The Netherlands

AIM: To evaluate the results of the treatment of simple liver cysts (solitary and multiple) and polycystic liver disease (PLD) using percutaneous sclerotherapy and/or surgical procedures in a single tertiary referral centre. METHODS: Retrospective analysis of 54 patients referred for evaluation and possible treatment of simple liver cysts (solitary and multiple) and PLD, from January 1997 to July 2006. RESULTS: Simple liver cysts were treated in 41 pts (76/) with a mean size of 12.6 cm. The most common reason for referral was abdominal pain or discomfort (85/). Percutaneous sclerotherapy was performed as initial treatment in 30 pts, showing cyst recurrence in 6 pts (20/). Surgical treatment was initially performed in 11 pts with cyst recurrence in 3 pts (27/). PLD was treated in 13 pts (24/) with a mean size of the dominant cyst of 13 cm. Percutaneous sclerotherapy for PLD was performed in 9 pts with recurrence in 7 pts (77.8/). Surgical treatment for PLD was undertaken in 4 pts (30.8/) with recurrence in all. Eventually, 2 pts with PLD in the presence of polycystic kidney disease underwent liver-and kidney transplantation because of deterioration of liver and kidney function. CONCLUSION: The majority of patients with simple liver cysts and PLD are referred for progressive abdominal pain. As initial treatment, percutaneous sclerotherapy is appropriate. Surgical deroofing is indicated in caseof cyst recurrence after percutaneous sclerotherapy. However, the results of percutaneous sclerotherapy and surgical treatment for PLD are disappointing. Partial liver resection is indicated when there is suspicion of a pre-malignant lesion.

关键词： Simple liver cyst Polycystic liver disease Percutaneous sclerotherapy Deroofing Complications

Obstructive jaundice due to hepatobiliary cystadenoma or cystadenocarcinoma

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World Journal of Gastroenterology 2006年第35期12卷 5735-5738页

作者： Deha Erdogan Olivier RC Busch Erik AJ Rauws Otto M van Delden Dirk J Gouma Thomas M van Gulik Department of Surgery Academic Medical Center University of Amsterdam The Netherlands Department of Hepatology Academic Medical Center University of Amsterdam The Netherlands Department of Surgery radiology Academic Medical Center University of Amsterdam The Netherlands

Hepatobiliary cystadenomas (HBC) and cystadenocarci- nomas are rare cystic lesions. Most patients with these lesions are asymptomatic, but presentation with ob- structive jaundice may occur. The first patient presented with intermittent colicky pain and recurrent obstructive jaundice. Imaging studies revealed a polypoid lesion in the left hepatic duct. The second patient had recurrent jaundice and cholangitis. Endoscopic retrograde cholan- giopancreatography (ERCP) showed a cystic lesion at the confluence of the hepatic duct. In the third patient with intermittent jaundice and cholangitis, cholangioscopy re- vealed a papillomatous structure protruding into the left bile duct system. In the fourth patient with obstructive jaundice, CT-scan showed slight dilatation of the intrahe- patic bile ducts and dilatation of the common bile duct of 3 cm. ERCP showed filling of a cystic lesion. All patients underwent partial liver resection, revealing HBC in the specimen. In the fifth patient presenting with obstructive jaundice, ultrasound examination showed a hyperecho- genic cystic lesion centrally in the liver. The resection specimen revealed a hepatobiliary cystadenocarcinoma. HBC and cystadenocarcinoma may give rise to obstruc- tive jaundice. Evaluation with cross-sectional imaging techniques is useful. ERCP is a useful tool to differentiate extraductal from intraductal obstruction.

关键词： Liver Hepatobiliary cystadenoma Cystadenocarcinoma Obstructive jaundice Endoscopic retrograde cholangiopancreatography

A network-based cognitive training induces cognitive improvements and neuroplastic changes in patients with relapsing-remitting multiple sclerosis:an exploratory case-control study

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Neural Regeneration Research 2021年第6期16卷 1111-1120页

作者： Riccardo Manca Micaela Mitolo Iain D.Wilkinson David Paling Basil Sharrack Annalena Venneri Department of Neuroscience University of SheffieldSheffieldUK Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna Diagnostica Funzionale NeuroradiologicaBolognaItaly academic unit of radiology University of SheffieldSheffieldUK academic Department of Neuroscience Sheffield Teaching HospitalNational Health Service Foundation TrustSheffieldUK

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of *** consensus has been reached on how to tackle effectively cognitive decline in this clinical population *** exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple ***-five patients(36 females and 9 males,mean age 44.62±8.80 years)with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups(sham training and nonactive control).The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain *** sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed *** non-active control group received no cognitive *** patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 *** and resting-state magnetic resonance imaging data were analyzed using repeated measures *** reassessment,the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training:the Buschke Selective Reminding Test and the Semantic Fluency *** standard training group showed reductions in functional connectivity of the salience network,in the anterior cingulate cortex,associated with improvements on the Buschke Selective Reminding *** changes were observed in the sham training *** findings suggest that multi-domain tr

关键词： cognitive training magnetic resonance imaging multiple sclerosis neuroplasticity neuropsychology rehabilitation salience network

Furin Enzyme-Responsive siRNA Delivery System for Efficient Anti-Hypoxia-Assisted Cancer Photodynamic Therapy

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CCS Chemistry 2024年第4期6卷 999-1010页

作者： Shuyue Ye Yali Feng Yuqi Zhang Jing Fang Anna Wang Chaoxiang Cui Jinfeng Zhu Liangsheng Guo Guohua Fan Haibin Shi State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou 215123 Department of radiology The Second Affiliated Hospital of Soochow UniversitySuzhou 215004 Department of Obstetrics and Gynecology The Second Affiliated Hospital of Soochow UniversitySuzhou 215004

RNA interfering therapy has emerged as a promising therapeutic modality to treat *** specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge ***,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and *** advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor ***,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living *** work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.

关键词： self-assembly RNA interfering enzymeresponsive delivery anti-hypoxia photodynamic therapy

Percutaneous embolization by direct puncture for the treatment of high-flow priapism

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Asian Journal of Urology 2023年第2期10卷 208-209页

作者： Quentin Holay Michael Baboudjian Eric Lechevallier Marc Andre Pierre-Henri Savoie Department of radiology Conception Academic HospitalMarseilleFrance Department of Urology Conception Academic HospitalMarseilleFrance Department of Urology Sainte Anne HospitalToulonFrance

Dear Editor,High-flow priapism is a persistent erection,usually caused by blunt perineal trauma,resulting in pathologically increased arterial inflow to the corpora cavernosa[1].The therapeutic strategy of high-flow priapism,although codified,leaves room for a wide choice of techniques,ranging from conservative management,selective arterial embolization to surgical management[2].The aim of this letter was to report an alternative approach of percutaneous embolization by direct puncture for the treatment of high-flow priapism.

关键词： embolization puncture arterial

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

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World Journal of Psychiatry 2024年第5期14卷 715-725页

作者： Jing Li Wing-Yi Ng Li-Chao Qiao Fen Yuan Xing Lan Li-Bei Zhu Bo-Lin Yang Zhong-Qiu Wang Department of radiology Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Acupuncture and Rehabilitation Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and ***,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with *** To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with *** The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical *** symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment *** basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also *** regression analysis was ultimately used to ascertain the risk factors of depression associated with *** A total of 123 patients with PFCD were involved,and 56.91%were suffering from *** to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high *** score,modified Van Assche index,quality of life,and fatigue severity

关键词： Crohn’s disease Fistula Depression Inflammatory bowel diseases Risk factors