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Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 563-570页

作者： Yu-Qing Cheng Geng-Fang Wang Xiao-Li Zhou Min Lin Xin-Wen Zhang Qin Huang Department of Pathology The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhou 213164Jiangsu ProvinceChina Gastroenterology center The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhou 213164Jiangsu ProvinceChina Graduate school Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical SchoolBostonMA 02215United States

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young ***,we report such a case in a 29-year-old Chinese *** SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and *** endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric *** nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 ***,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and ***-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 *** patient was alive without evidence of the disease 36 mo after *** Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

关键词： Adenocarcinoma Neuroendocrine carcinoma Gastroesophageal junction Next generation sequencing Case report

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Global geoepidemiology of gastrointestinal surgery rates in Crohn’s disease

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1835-1844页

作者： Simcha Weissman Muhammad Aziz Ayrton Bangolo Vignesh K Nagesh Htat Aung Midhun Mathew Lino Garcia Shiva A Chandar Praveena Karamthoti Harinder Bawa Aseel Alshimari Yabets Kejela Nazish Mehdi Chrishanti A Joseph Athri Kodali Rohan Kumar Priya Goyal Sanya Satheesha Fnu Nivedita Nicole Tesoro Tanni Sethi Gurpreet Singh Areej Belal Alina Intisar Hirra Khalid Samuel Cornwell Suchith B Suresh Kareem Ahmed Karabo K Marole Om P Anand Rahat B Reshi Tej I Mehta Sameh Elias Joseph D Feuerstein Department of Medicine Hackensack Meridian Health Palisades Medical CenterNorth BergenNJ 07047United States Division of Gastroenterology and Hepatology University of Toledo Medical CenterToledoOH 43614United States Department of Medicine University of WashingtonSeattleWA 98195United States Department of Radiology Johns Hopkins University HospitalBaltimoreMD 21218United States Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States

BACKGROUND Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn’s disease(CD)remains *** To systematically review the global variation in the rates of surgery in *** A comprehensive search analysis was performed using multiple electronic databases from inception through July 1,2020,to identify all full text,randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with *** included continent based demographic data,CD surgery rates over time,as well as the geoepidemiologic variation in CD surgery *** analyses were conducted using *** Twenty-three studies spanning four continents were *** median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America,Europe,Asia,and Oceania were 30%(range:1.7%-62.0%),40%(range:0.6%-74.0%),17%(range:16.0%-43.0%),and 38%*** clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America(R^(2)=0.035)and Europe(R^(2)=0.100).A moderate,negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time(R^(2)=0.520)in *** There appears to be significant inter-continental variation regarding surgery rates in *** evidencebased guidelines accounting for the geographic differences in managing patients with CD is ***,as a paucity of data on surgery rates in CD exists outside the North American and European continents,future studies,particularly in less studied locales,are warranted.

关键词： Gastrointestinal surgery Crohn’s disease Geoepidemiology Inflammatory bowel disease Prevalence

Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina China National Clinical Research center for Neurological Diseases BeijingChina Department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA Department of Neurology and Comprehensive Stroke center Massachusetts General HospitalBostonMassachusettsUSA Department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volumemedical ***,we will exclude patients who are intended for direct *** will be followed up for 90 *** outcomes Primary efficacy outcome is modified Rankin Scale(mRS)score≤1 at 90 *** efficacy outcomes include ordinal distribution of mRS at 90 days,major neurological improvement defined by a decrease≥8 points compared with the initial deficit or a score≤1 on the National Institutes of Health Stroke Scale(NIHSS)at 72 hours,mRS score≤2 at 90 days,the rate of improvement on Tmax>6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NCT05141305.

关键词： Therapy random Rational

Encapsulating peritoneal sclerosis

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World Journal of Gastroenterology 2018年第28期24卷 3101-3111页

作者： Christopher J Danford Steven C Lin Martin P Smith Jacqueline L Wolf Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center Harvard Medical School Department of Radiology Beth Israel Deaconess Medical Center Harvard Medical School

Encapsulating peritoneal sclerosis(EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents(i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPSspecific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is timeconsuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease.

关键词： Abdominal cocoon Sclerosing encapsulating peritonitis Peritoneal sclerosis Peritonectomy Enterolysis Peritoneal dialysis Tamoxifen Corticosteroids

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第12期22卷 3404-3411页

作者： Parham Safaie Mugilan Poongkunran Ping-Ping Kuang Asad Javaid Carl Jacobs Rebecca Pohlmann Imad Nasser Daryl TY Lau Liver center Division of Gastroenterology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School Department of Pathology Beth Israel Deaconess Medical Center Harvard Medical School

AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular ***: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification ***: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with “diffuse” distribution (79%) and “mixed cytoplasmic/nuclear” pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had “patchy” HBsAg distribution compared to “rare” distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient ***: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antivir

关键词： Hepatitis B virus Chronic hepatitis B Hepatocellular carcinoma Hepatitis B core antigen Hepatitis B surface antigen

The deacetylase SIRT2 contributes to autoimmune disease pathogenesis by modulating IL-17A and IL-2 transcription

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Cellular & Molecular Immunology 2022年第6期19卷 738-750页

作者： Ryo Hisada Nobuya Yoshida Masataka Umeda Catalina Burbano Rhea Bhargava Marc Scherlinger Michihito Kono Vasileios C.Kyttaris Suzanne Krishfield George C.Tsokos Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Aberrant IL-17A expression together with reduced IL-2 production by effector CD4^(+)T cells contributes to the pathogenesis of systemic lupus erythematosus(SLE).Here,we report that Sirtuin 2(SIRT2),a member of the family of NAD^(+)-dependent histone deacetylases,suppresses IL-2 production by CD4^(+)T cells while promoting their differentiation into Th17 ***,we show that SIRT2 is responsible for the deacetylation of p70S6K,activation of the mTORC1/HIF-1α/RORγt pathway and induction of Th17-cell ***,SIRT2 was shown to be responsible for the deacetylation of c-Jun and histones at the Il-2 gene,resulting in decreased IL-2 *** found that the transcription factor inducible cAMP early repressor(ICER),which is overexpressed in T cells from people with SLE and lupus-prone mice,bound directly to the Sirt2 promoter and promoted its ***-7,a SIRT2 inhibitor,limited the ability of adoptively transferred antigen-specific CD4^(+)T cells to cause autoimmune encephalomyelitis in mice and limited disease in lupus-prone MRL/lpr ***,CD4^(+)T cells from SLE patients exhibited increased expression of SIRT2,and pharmacological inhibition of SIRT2 in primary CD4^(+)T cells from patients with SLE attenuated the ability of these cells to differentiate into Th17 cells and promoted the generation of IL-2–producing T ***,these results suggest that SIRT2-mediated deacetylation is essential in the aberrant expression of IL-17A and IL-2 and that SIRT2 may be a promising molecular target for new SLE therapies.

关键词： SIRT2 Systemic lupus erythematosus IL-17A IL-2

Inhibitory Receptors of the Immune System:Functions and Therapeutic Implications

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Cellular & Molecular Immunology 2009年第6期6卷 407-414页

作者： Jian Zhang Xiang Xiao Wentao Liu Gulcin Demirci Xian C.Li The Transplant Institute Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215USA beth israel deaconess medical center Harvard Medical School330 Brookline AvenueCLS-605BostonMA 02215USA

The immune system has a remarkable ability to respond to seemingly endless *** essence,a productive immune response takes place along a well defined but treacherous line,that is to effectively eradicate pathogens,and at the same time avoid causing damage to self *** type of response is fine-tuned,at least in part,by a complex array of pathways that either promote or inhibit the activation of innate and adaptive immune *** effort has been focused on pathways that can support immune *** this article,we review specifically pathways that can inhibit immune responses and maintain immune homeostasis,highlighting our recent understanding on the role of inhibitory receptors that selectively engage the self MHC class I molecules and the B7 superfamily members,we also discuss the inhibitory Fc receptors and inhibitory cytokines and how such pathways,either individually or collectively,regulate innate and adaptive immune ***,we summarize new emerging approaches on how such negative pathways can be therapeutically modulated in various disease settings.

关键词： immunity tolerance regulation inflammation negative pathways

Intranasal insulin neuroprotection in ischemic stroke

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Neural Regeneration Research 2016年第3期11卷 400-401页

作者： Vasileios-Arsenios Lioutas Vera Novak Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical School

Acute ischemic stroke（AIS）is a leading cause of death and long-term disability in the USA and *** advances in the last two decades have resulted in the introduction of intravenous tissue plasminogen activator and more recently catheter based endovascular interventions in selected patients（Berkhemer et al.,2015;Goyal et al.,2015）.

关键词： disability endovascular intravenous administration advances plasminogen cascade homeostasis hemorrhagic simplicity