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Advances in Infectious Diseases 2014年第1期4卷 1-7页

作者： David B. Huang Han Lee Tom Chiang Department of Internal Medicine Yale University School of Medicine New Haven USA Division of Infectious Diseases Department of Medicine Rutgers New Jersey Medical School Newark USA

We conducted a study to assess the characteristics, treatment and outcomes associated with Clostridium difficile associated diarrhea in a veterans affairs medical center. Fifty-eight consecutive individual cases of C. difficile infection in 2013 were observed within the veterans affairs New Jersey Health Care System (VA NJHCS). We molecularly typed all 58 individual strains and identified the associated characteristics, treatment and outcomes. Forty-four out of 58 specimens (76%) which were probed had characteristics of the epidemic strain BI/NAP1/027 making this virulent strain to be the predominate strain at the VA NJHCS. All C. difficile BI/NAP1/027 strains were resistant to fluoroquinolones and sensitive to fidaxomicin, metronidazole and vancomycin. Fidaxomicin had the most potent in vitro activity (MIC90 = 0.5 μg/ml) against the BI/NAP1/027 strain. Twenty-six of 44 patients (59%) with the virulent strain were from a long-term care facility (LTCF). Patients possessing the virulent strain from the LTCF had a mean APACHE II score of 14.1 and a predicted death rate of 21.9%. Two-third of patients were treated with metronidazole alone (mean APACHE II scores 9.6), and one-third required oral vancomycin and metronidazole (mean APACHE II scores 14.1). There were no C. difficile infection related deaths. C. difficile BI/NAP1/027, an epidemic strain, is the endemic strain at the VA NJHCS, but no increased mortality was seen with infection with this strain.

关键词： Clostridium difficile BI/NAP1/027 Treatment Outcomes

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King Department of Neurology and center for Neurodegeneration and Experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham veterans affairs medical center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

Digesting gluten with oral endopeptidases to improve the management of celiac disease

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World Journal of Gastroenterology 2024年第26期30卷 3201-3205页

作者： Katelin Durham Mirac Nedim Ince Department of Internal Medicine Division of Gastroenterology and HepatologyUniversity of IowaCarver College of Medicineand the Iowa City Veterans Affairs Medical CenterIowa CityIA 52242United States

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed *** avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel *** villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid *** administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under *** article is about the utility of one endopeptidase isolated from Aspergillus *** critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

关键词： Celiac disease Gluten-free diet Endopeptidase Villous atrophy Aspergillus niger Adjunct therapy

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

Dysregulated bile acid homeostasis:unveiling its role in metabolic diseases

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medical Review 2024年第4期4卷 262-283页

作者： Yanyan Wang Huangru Xu Xiqiao Zhou Weidong Chen Huiping Zhou Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmond Veterans Affairs Medical CenterRichmondVAUSA School of Pharmaceutical Science Anhui University of Chinese MedicineHefeiAnhuiChina School of Life Science Nanjing UniversityNanjingJiangsuChina Department of Endocrinology Jiangsu Province Hospital of Chinese MedicineNanjing University of Chinese MedicineNanjingJiangsuChina Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmond Veterans Affairs Medical CenterRichmondVA 23298-0678USA

Maintaining bile acid homeostasis is essential for metabolic *** acid homeostasis encompasses a complex interplay between biosynthesis,conjugation,secretion,and *** their vital role in digestion and absorption of lipid-soluble nutrients,bile acids are pivotal in systemic metabolic *** studies have linked bile acid dysregulation to the pathogenesis of metabolic diseases,including obesity,type 2 diabetes melli-tus(T2DM),and metabolic dysfunction-associated steatotic liver disease(MASLD).Bile acids are essential signaling molecules that regulate many critical biological processes,including lipid metabolism,energy expenditure,insulin sensitivity,and glucose *** in bile acid homeostasis contributes to metabolic disease via altered bile acid feedback mechanisms,hormonal dysregu-lation,interactions with the gut microbiota,and changes in the expression and function of bile acid transporters and *** review summarized the essential molecular pathways and regulatory mechanisms through which bile acid dysregulation contributes to the pathogenesis and progression of obesity,T2DM,and *** aim to underscore the signiﬁcance of bile acids as potential diag-nostic markers and therapeutic agents in the context of metabolic diseases,providing insights into their application in translational medicine.

关键词： bile acids metabolic diseases obesity takeda G protein-coupled receptor 5 type 2 diabetes mellitus metabolic dysfunction-associated steatotic liver disease

CD200Rhigghh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells

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Cellular & Molecular Immunology 2024年第4期21卷 349-361页

作者： Ye Seon Kim Yu Sun Jeong Geon Ho Bae Ji Hyeon Kang Mingyu Lee Brian A.Zabel Yoe-Sik Bae Department of Biological Sciences Sungkyunkwan UniversitySuwon16419Republic of Korea Department of Health Science and Technology SAIHSTSungkyunkwan UniversitySeoul06351Republic of Korea Palo Alto veterans Institute for Research Veterans Affairs HospitalPalo AltoCA94304USA

Distinct neutrophil populations arise during certain pathological *** generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain *** this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))*** to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-α*** soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) *** administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased *** analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection *** together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.

关键词： Sepsis Neutrophils CD200R Autophagy IGF-1 Regulatory T cells

Impact of surgical management of upper tract urothelial cancer in octogenarians:A population-based study

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Current Urology 2024年第3期18卷 225-231页

作者： Shu Wang Michael Phelan Mohummad Minhaj Siddiqui Division of Urology Department of SurgeryUniversity of Maryland School of MedicineBaltimoreMDUSA veterans affairs Maryland Healthcare System BaltimoreMDUSA

Background Upper tract urothelial carcinoma(UTUC)is an aggressive disease with a high progression *** standardmanagement for this disease is *** sparing nonradical surgery is an alternative therapeutic *** men with limited life expectancy,the potential harm of UTUC progression must be weighed against surgical morbidity and mortality,and thus,more conservative approaches may be *** study aims to investigate the comparative benefits of radical and conservative surgical management in patients older than 80 years with localized *** and methods A search was conducted in the Surveillance,Epidemiology,and End Results database for patients older than 80 years who were diagnosed with localized(T1–2N0M0)cancer in the renal pelvis or ureter as the only malignancy from 2004 to *** were divided into 3 therapeutic groups:no surgery,local intervention(ie,local tumor excision or segmented ureterectomy),and radical surgery(nephroureterectomy).Demographic and cancer-related parameter data were *** regression analysis was conducted to investigate predictors for surgical ***-Meier curves and Cox regression were used to analyze survival *** Data from 774 patients were analyzed,including 205 in the no-surgery group,181 in the local intervention group,and 388 in the radical surgery ***,African American patients with T1 stage disease were less likely to receive surgical *** surgically treated patients,renal pelvic tumors,and high-grade and T2 stage disease were associated with radical *** treated patients had a longer median overall survival(OS)than in those treated nonsurgically(13,35,and 47 months in no-surgery,local intervention,and radical surgery groups,respectively;p<0.001).Although surgically treated patients demonstrated higher 5-year OS(8.8%[no surgery],23.2%[local intervention],and 23.5%[radical surgery],p<0.001)and 5-year disease-specif

关键词： Older adults Surgery Surveillance,Epidemiology,and End Results Survival Upper tract urothelial carcinoma

Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy Alexandra Kovar Teresa S Jones Krzysztof J Wikiel Edward L Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

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World Journal of Gastroenterology 2024年第3期30卷 268-279页

作者： Lie-Qi Tang Johnathan Fraebel Shi Jin Steven P Winesett Jane Harrell Wen-Han Chang Sam Xianjun Cheng Department of Pediatrics University of FloridaGainesvilleFL 32610United States College of Medicine University of FloridaGainesvilleFL 32610United States Applied Physiology and Kinesiology University of FloridaGainesvilleFL 32610United States Brain Rehabilitation Research center Malcom Randall VA Medical CenterGainesvilleFL 32610United States Department of Medicine Endocrine Research UnitVeterans Affairs Medical CenterUniversity of CaliforniaSan FranciscoSan FranciscoCA 94121United States Department of Pediatric Gastroenterology Hepatologyand NutritionUniversity of Florida Shands Children’s HospitalGainesvilleFL 32608United States

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous ***-sensing receptor(CaSR)inhibits both *** latter has been well documented in vitro but not in *** hypothesis to be tested was that activating CaSR inhibits diarrhea in *** To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in *** CTX was given orally to C57BL/6 mice to induce *** and calci-mimetic R568 were used to activate *** maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal *** verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR *** outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight *** CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in ***,calcium and R568 were each able to ameliorate diarrhea when applied to diseased *** CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global *** advances in diarrhea research,few have been made in the realm of diarrhea *** therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by *** is no cost-effective therapeutic for *** and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might

关键词： Cholera Enteric nervous system Secretory diarrhea Oral rehydration solution Calcium-sensing receptor Gene knockout

Rapid and Sensitive Biosensing of Salmonella Using Mechanical Step Rotation and Gold@platinum Nanozymatic Amplification

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Journal of Analysis and Testing 2024年第3期8卷 262-269页

作者： Meixuan Li Lei Wang Ai Xu Ying Ding Fengzhen Yang Yanbin Li Jianhan Lin Key Laboratory of Agricultural Information Acquisition Technology Ministry of Agriculture and Rural AffairsChina Agricultural University center of Excellence for Poultry Science University of Arkansas

Inspired by ballpoint pen, an optical biosensor is developed for detection of Salmonellausing a mechanical step rotator with a dropper to greatly simplify operation, a high gradient magnetic field with immune magnetic nanobeads to specifically separate bacteria, and immune gold@platinum nanozymes with a smartphone to sensitively detect bacteria. First, the preloaded bacterial sample is drawn by the dropper to react with the immune magnetic nanobeads through repeated squeezing and releasing of the dropper, and the rotator is successively rotated and the dropper is repeatedly squeezed and released to achieve mixing of the bacteria, magnetic nanobeads and gold@platinum nanozymes, followed by magnetic separation to remove the background. Then, the conjugates are eff ectively washed with skim milk and ultrapure water, and the substrate are rapidly catalyzed into the product. Finally, the blue product is photographed and analyzed using a smartphone to obtain the Salmonella concentration. This biosensor could detect Salmonellaas low as 56 CFU/mL in～25 min.

关键词： gold@platinum nanozyme magnetic grid separation mechanical step rotator optical biosensor Salmonella detection