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Signal Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya Joanne K.Tobacman Jesse Brown va medical center and University of Illinois at Chicago ChicagoIL 60612USA

Immunostaining in lungs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase(Arylsulfatase B;ARSB).To explain these findings,human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional mechanisms were ***-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11,which contributed to chondroitin sulfate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-E2F1 binding and decline in E2F1 binding to the ARSB *** increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as well as antihistamine desloratadine and antibiotic *** the mouse model of carrageenan-induced systemic inflammation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and declines in DNA-E2F binding and ARSB expression occurred in the lung,similar to theobserved effects in this SPRBD model of COVID-19 *** accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage,increased attention to p38-MAPK inhibition may be beneficial in amelioratingCovid-19infections.

关键词： ACE2 lung inhibited

Metabolites and micronutrition in modulating amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第6期19卷 1183-1184页

作者： Katerina Claud Jun Sun Department of Medicine University of Illinois ChicagoChicagoILUSA Jesse Brown va medical center Chicago ChicagoILUSA

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative *** majority of ALS cases are sporadic with only about 20%of familial *** in families with genetic predisposition,there is significant phenotypic va... 详细信息

关键词： sclerosis amyotrophic cases

ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： Lei Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke va medical center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

Mixed neuroendocrine and adenocarcinoma of gastrointestinal tract:A complex diagnosis and therapeutic challenge

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2295-2299页

作者： Santosh Shenoy Department of General Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansas CityMO 64128United States

In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal *** neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor *** to the rarity of these cancers,the standard therapy is poorly *** diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell *** endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is *** cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and *** of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine *** services and strategies are required for the management of these mixed malignancies to provide the best oncological *** etiopathogenesis of these mixed tumors remains obscure but poses interesting *** briefly discuss a few salient points in this editorial.

关键词： Mixed adenocarcinoma and neuroendocrine carcinoma Mixed neuroendocrine and non-neuroendocrine neoplasm Mixed adeno-neuroendocrine cancer Cell reprograming Tumor plasticity

Synchronous gastric and colon cancers:Important to consider hereditary syndromes and chronic inflammatory disease associations

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 571-576页

作者： Santosh Shenoy Department of General Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansasMO 64128United States

In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon *** or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic *** services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological *** this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump *** addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel *** and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic *** will briefly discuss these in this editorial.

关键词： Synchronous gastric Colon cancers Gene mutation Chronic inflammation

Distribution of licensed acupuncturists and educational institutions in the United States at the start of 2023,during the late stage of the COVID-19 pandemic

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Journal of Integrative Medicine 2024年第4期22卷 379-384页

作者： Arthur Yin Fan De-guang He Anu Sangraula Sarah Faggert Alemi Amy Matecki American Traditional Chinese Medicine Association ViennaVA 22182USA McLean center for Complementary and Alternative Medicine ViennaVA 22182USA New England School of Acupuncture Massachusetts College of Pharmacy and Health SciencesBostonMA 02115USA Lombardi Comprehensive Cancer center Cancer Prevention and Control ProgramGeorgetown UniversityWashington DC 20057USA Eastern Roots Wellness PLCMcLeanVA 22101USA Sutter Health Alta Bates Summit Medical CenterOaklandCA 94609USA

This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active LAcs as of January 1,2023 was 34,524,potentially33,364 after removing license duplication in multiple states,among which the largest three states were California(with 7317 LAcs[21.19%of the total]),New York(5024[14.55%])and Florida(2644[7.66%]).The total number of LAcs decreased by 8.87%from 2018,and fell short of our projected number of LAcs in 2023 by 9037,or 20.75%.The overall LAc density in the *** as the number of LAcs per 100,000 populationDwas 10.36,less than in *** were 56 active,accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing[entry-level],12 for an advanced practicing degree[advanced-level],and 14 for certifications).Broken down further,offerings included 50 master's degrees in acupuncture,40 master's degrees in Oriental medicine,31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine),and 12advanced-level doctorate degrees in *** certification programs included one in East-Asian medical Bodywork and 13 in *** these schools in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national ***,Florida and Illinois represented 39.29%.There were 48 jurisdictions with acupuncture practice laws in *** data suggests that the acupuncture profession in the *** been significantly impacted during the coronavirus disease 2019 pandemic.

关键词： Acupuncturist Acupuncture educational institution Distribution Density Oriental medicine United States

New Nurse Perceptions of Preparedness: Elements of Academic-Practice Gap

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Open Journal of Nursing 2024年第7期14卷 298-320页

作者： Bonnie Crumley Aybar Manchester va medical center Manchester NH USA

The education-practice gap, also known as the academic-practice gap is recognized as the difference between what a nursing student is taught and what the new nurse will experience in practice. This study evaluated specific education outcomes of schools of nursing in New Hampshire through surveys of new nurses and their employers. The responses were explored in relation to identified factors such as curriculum and clinical hours. The findings suggest that the new nurses felt prepared for practice, except in relationship to provision of care and medication administration for six or more patients. Of note is that 61% percent of participants were involved in errors and of these, 37.5% indicated that their education did not prepare them to administer medications to large groups. Evaluation of employer responses points to at least one and sometimes two levels of lower perception of perceived preparedness by the employer. The results highlight the differences between perceptions of preparedness of new nurse and employer, differences in perception of preparedness based on program type for specific gap elements, and the high rate of errors among new nurses. These results underscore the need for further research regarding the education practice gap, error factors, perceptions of preparedness for practice, and practice-readiness expectations of employers.

关键词： Nurse Education-Gap Education Program Preparedness Competency

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei Zhang Yongguo Zhang Yinglin Xia Jun Sun Division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown va medical center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 *** CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized *** infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection *** with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental ***,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long *** highlight the potential mechanisms and possible treatment based on Gl health and ***,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin Xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological *** is emerging as a powerful tool generally for pre-cision ***,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and ***,metabo-lomics data are very ***/pretreating and normalizing procedures on metabolomics data are usually required before statistical *** this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data *** discuss the advantages and limitations of each *** choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis *** then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

Skin neuropathy and immunomodulation in diseases

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Fundamental Research 2024年第2期4卷 218-225页

作者： Manze Zhang Tingting Liu Jing Yang Department of Biology Stanford UniversityStanfordCA 94305USA Department of Biochemistry Weill Cornell Medical CollegeNew YorkNY 10065USA IDG/McGovern Institute for Brain Research Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China Peking University Third Hospital Cancer center Beijing 100191China

Skin is a vital barrier tissue of the *** responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic *** evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin ***,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological *** in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic ***,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.

关键词： Skin Neuropathy Neuroimmune Psoriasis Atopic dermatitis Pathogenic infection