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

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

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Return to work in young and middle-aged colorectal cancer survivors:Factors influencing self-efficacy,fear,resilience,and financial toxicity

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World Journal of Gastroenterology 2025年第1期31卷 79-92页

作者： Dan Hu Yue Li Hua Zhang Lian-Lian Wang Wen-Wen Liu Xin Yang Ming-Zhao Xiao Hao-Ling Zhang Juan Li department of Nursing The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Nursing National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Biomedical Science Advanced Medical and Dental InstituteUniversity Sains MalaysiaPenang 13200Malaysia Academic affairs Office The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social ***,these survivors encounter significant challenges during their RTW ***,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC *** To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW *** A cross-sectional investigation was adopted in this *** September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in *** investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and *** analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were *** A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 *** regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(P<0.05).Furthermore,Cox regression multivariate analysis identified per capita family monthly income,job type,RTW-SE,and FR as independent influencing factors for RTW(P<0.05).CONCLUSION The RTW rate requires further *** levels of RTW-SE and FR were found to significantly increase RTW among young and middle-aged CRC *** professionals should focus on modifiable factors,such as RTW-SE and FR,to design targeted RTW support programs,thereby facilitating their timely reintegration into mainstream society.

关键词： Return to work Colorectal neoplasms Return-to-work self-efficacy Fear of progression Family resilience Financial toxicity

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Substrate topography as a powerful tool to modify glial cell biology and interactions

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Neural Regeneration Research 2025年第5期20卷 1390-1391页

作者： Pascal Achenbach Haktan Altinova Gary A.Brook Institute of Neuropathology RWTH Aachen University Hospital department of Neurosurgery RWTH Aachen University Hospital Aachen Germany Berlin State Office for Health and Social affairs(LAGeSo) BerlinGermany

Traumatic injuries to the central nervous system(CNS) result in disruption of the intricate network of axons which connect functionally related neurons that are widely distributed throughout the brain and spinal *** normal conditions,maintenance of this complex system is structurally and functionally supported by astrocytes (ACs)and other glial cells,the processes of which form a framework surrounding neuronal cell bodies,dendrites,axons,and synapses.

关键词： injuries topography system

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Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules Mjanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud University medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud University medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

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Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia:a subgroup analysis of the TITAN trial

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Asian Journal of Andrology 2022年第2期24卷 161-166页

作者： Byung Ha Chung Jian Huang Zhang-Qun Ye Da-Lin He Hirotsugu Uemura Gaku Arai Choung Soo Kim Yuan-Yuan Zhang Yusoke Koroki SuYeon Jeong Suneel Mundle Spyros Triantos Sharon McCarthy Kim N Chi Ding-Wei Ye department of Urology Gangnam Severance HospitalYonsei University College of Medicine211 Eonju-roGangnam-guSeoul 135-271Korea Sun Yat-Sen Memorial Hospital Sun Yat-sen UniversityGuangzhou 510120China Wuhan Tongji Hospital Tongji Medical CollegeWuhan 430030China First Affiliated Hospital of Xi’an Jiaotong University Xi’an 719054China Kindai University Hospital Ōsakasayama 589-8511Japan Dokkyo medical University Saitama medical Center Saitama 2-1-50Japan Asian medical Center University of UlsanSeoul 138-040Korea janssen medical affairs department Beijing 100025China janssen medical affairs department Tokyo 101-0065Japan janssen medical affairs department Seoul 140-012Korea janssen Global medical affairs department HorshamPA 08869USA janssen Research and Development Spring HousePA 19477USA janssen Research and Development RaritanNJ 08869USA BC Cancer and Vancouver Prostate Centre VancouverBC V5Z 1G1Canada Fudan University Shanghai Cancer Center Shanghai 200032China

Ethnicity might be associated with treatment outcomes in advanced prostate *** study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 *** subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and *** progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian *** intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,*** 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,*** most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for *** efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

关键词： apalutamide East Asia metastasis prostatic neoplasm survival

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Thinking in three's: Changing surgical patient safety practices in the complex modern operating room

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World Journal of Gastroenterology 2012年第46期18卷 6712-6719页

作者： Verna C Gibbs department of Surgery San Francisco Veterans Affairs Medical Center

The three surgical patient safety events, wrong site surgery, retained surgical items (RSI) and surgical fires are rare occurrences and thus their effects on the complex modern operating room (OR) are difficult to study. The likelihood of occurrence and the magnitude of risk for each of these surgical safety events are undefined. Many providers may never have a personal experience with one of these events and training and education on these topics are sparse. These circumstances lead to faulty thinking that a provider won't ever have an event or if one does occur the provider will intuitively know what to do. Surgeons are not preoccupied with failure and tend to usually consider good outcomes, which leads them to ignore or diminish the importance of implementing and following simple safety practices. These circumstances contribute to the persistent low level occurrence of these three events and to the difficulty in generating sufficient interest to resource solutions. Individual facilities rarely have the time or talent to understand these events and develop lasting solutions. More often than not, even the most well meaning internal review results in a new line to a policy and some rigorous enforcement mandate. This approach routinely fails and is another reason why these problems are so persistent. Vigilance actions alone havebeen unsuccessful so hospitals now have to take a systematic approach to implementing safer processes and providing the resources for surgeons and other stake-holders to optimize the OR environment. This article discusses standardized processes of care for mitigation of injury or outright prevention of wrong site surgery, RSI and surgical fires in an action-oriented framework illustrating the strategic elements important in each event and focusing on the responsibilities for each of the three major OR agents-anesthesiologists, surgeons and nurses. A Surgical Patient Safety Checklist is discussed that incorporates the necessary elements to brin

关键词： Complex adaptive systems Wrong site surgery Retained surgical items Retained foreign objects Retained foreign bodies Surgical patient safety Surgical fires Safety checklist

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Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy

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Acta Pharmaceutica Sinica B 2018年第4期8卷 511-517页

作者： Xiao-Mei Qi Fang Wang Matthew Mortensen Ryan Wertz Guan Chen department of Pharmacology and Toxicology Medical College of Wisconsin Zablocki Veterans affairs medical Center Medical College of Wisconsin

Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38γ is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZcoupled binding is required for both PTPH1 dephosphorylation and inactivation of p38γ and for p38γ phosphorylation and activation of PTPH1. Moreover, the p38γ/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38γ/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.

关键词： Kinase/phosphatase signaling network PDZ-coupled protein-protein complex Phosphorylation and dephosphorylation Cancer development and progression Targeted cancer therapy

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Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea:A multi-center observational study in Shanghai,China

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Journal of Integrative Medicine 2023年第4期21卷 369-376页

作者： Shun-xian Zhang Xiao-xu Chen Yong Zheng Bing-hua Cai Wei Shi Ming Ru Hui Li Dan-dan Zhang Yu Tian Yue-lai Chen Clinical Research Center Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China medical affairs department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China medical affairs department of Minhang District Health Committee Shanghai 201199China medical affairs department of Fengxian District Health Committee Shanghai 201499China medical affairs department of Jinshan District Health Committee Shanghai 200540China medical affairs department of Xuhui District Health Committee Shanghai 200030China medical affairs department of Changning District Health Committee Shanghai 200050China medical affairs department Jinshan TCM-Integrated HospitalShanghai 201501China Sleep Medicine Center Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

Objective:Omicron,a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant,is responsible for numerous infections in *** study investigates the association between the use of Seven-Flavor Herb Tea(SFHT)and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019(COVID-19).Methods:This case-control study was conducted at shelter hospitals and quarantine hotels in China.A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31,2022,while 2190 uninfected individuals served as healthy *** questionnaires were used to collect data on demographics,underlying diseases,vaccination status,and use of *** were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity ***,a conditional logistic regression model was used for data ***:Overall,7538 eligible subjects were recruited,with an average age of[45.54±16.94]*** age of COVID-19 patients was significantly higher than that of uninfected individuals([48.25±17.48]years vs[38.92±13.41]years;t=22.437,P<0.001).A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 *** use of SFHT(odds ratio=0.753,95%confidence interval:0.692,0.820)was associated with a lower risk of SARS-CoV-2 infection compared to untreated ***:Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 *** is a useful study in the larger picture of COVID-19 management,but data from large-sample multi-center,randomized clinical trial are warranted to confirm the finding.

关键词： COVID-19 SARS-CoV-2 Seven-Flavor Herb Tea

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Neuroendocrine and squamous colonic composite carcinoma:Case report with molecular analysis

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World Journal of Gastroenterology 2011年第42期17卷 4729-4733页

作者： Sabrina C Wentz Cindy Vnencak-Jones William V Chopp department of Pathology Vanderbilt University Medical Center Molecular Genetics Laboratory Vanderbilt University Medical Center department of Pathology Veterans Affairs Medical Center

Composite colorectal carcinomas are rare. There are amodest number of cases in the medical literature,with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There areto our knowledge no reports of composite carcinomamolecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau-casian male to investigate the presence and prognos-tic significance of molecular alterations in rare coloniccarcinoma subtypes. Formalin-fixed paraffin-embedded(FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol,and immuno-stained with cytokeratin(CK) 7,CK20,CDX2,AE1/AE3,chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performed according to lab-developed methods,followed by capil-lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squamous cells. Positive nuclear CDX2 expression confirme dintestinal derivation. CK7 and CK20 were *** cells stained positively for synaptophysin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar immunohistochemical profile. Molecular analysis revealeda G13D KRAS mutation. BRAF mutational testing wasnegative and microsatellite instability was not *** patient had rapid disease progression on chemotherapy and died 60 d after presentation. Although theG13D KRAS mutation normally predicts an intermed iateoutcome,the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

关键词： Composite carcinoma Neuroendocrine Squamous KRAS BRAF Microsatellite instability

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Calpain mediated cisplatin-induced ototoxicity in mice

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Neural Regeneration Research 2013年第21期8卷 1995-2002页

作者： Liang Chang Aimei Wang Party and Government affairs Office Jinzhou Central Hospital department of Physiology Liaoning Medical University

Ototoxic drug-induced apoptosis of inner ear cells has been shown to be associated with calpain expression. Cisplatin has severe ototoxicity, and can induce cochlear cell apoptosis. This study assumed that cisplatin activated calpain expression in apoptotic cochlear cells. A mouse model of cisplatin-induced ototoxicity was established by intraperitoneal injection with cisplatin （2.5, 3.5, 4.5, 5.5 mg/kg）. Immunofluorescence staining, image analysis and western blotting were used to detect the expression of calpain 1 and calpain 2 in the mouse cochlea. At the same time, the auditory brainstem response was measured to observe the change in hearing. Results revealed that after intraperitoneal injection with cisplatin for 5 days, the auditory brainstem response threshold shifts increased in mice. Calpain 1 and calpain 2 expression significantly increased in outer hair cells, the spiral ganglion and stria vascularis. Calpain 2 protein expression markedly increased with an increased dose of cisplatin. Results suggested that calpain 1 and calpain 2 mediated cisplatin-induced ototoxicity in BALB/c mice. During this process, calpain 2 plays a leading role.

关键词： neural regeneration biological factor cisplatin mice cochlea apoptosis calpain auditory brainstem response ototoxicity immunofluorescence staining image analysis technique western blotting grants-supported paper neuroregeneration

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