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Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration Research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati Sang Chul Lee Jae Il Shin Yong Wook Kim department and Research Institute of Rehabilitation medicine Yonsei University College of MedicineSeoulSouth Korea department of Physical Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran department of Pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease *** cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s *** stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of *** performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal *** searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,*** study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control *** use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the *** with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational *** the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

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Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun Jae Park Seong Kyun Na Sang Min Park Byung-Cheol Song Yun Hwan Oh department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea department of Internal medicine Inje University College of MedicineSeoul 50834Korea department of family medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea department of Internal medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea department of family medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea department of family medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus ***:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),*** addition,the HSI was less predictive for Fibroscan®-defined fatty *** K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and ***:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty *** addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease Fatty liver index Hepatic steatosis index

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Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents:a systematic review and meta-analysis

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World Journal of Pediatrics 2024年第6期20卷 569-580页

作者： Eun Joo Lee Miyoung Choi Sang Bong Ahn Jeong-Ju Yoo Seong Hee Kang Yuri Cho Do Seon Song Hong Koh Dae Won Jeon Hye Won Lee department of Pediatrics Yonsei University College of MedicineSeoulKorea Clinical Evidence Research National Evidence-Based Healthcare Collaborating Agency(NECA)SeoulKorea department of Internal medicine Nowon Eulji Medical CenterEulji University College of MedicineSeoulKorea department of Internal medicine Soonchunhyang University Bucheon HospitalBucheonKorea department of Internal medicine Sangkye Paek HospitalInje University College of MedicineSeoulKorea Center for Liver and Pancreatobiliary Cancer National Cancer CenterGoyangKorea department of Internal medicine College of MedicineSt.Vincent's HospitalThe Catholic University of KoreaSuwonKorea department of Internal medicine Hanyang University College of MedicineSeoulKorea department of Internal medicine Yonsei University College of MedicineSeoulKorea

Background As childhood obesity escalates worldwide,the prevalence of nonalcoholic fatty liver disease(NAFLD)in pediatric and adolescent populations is also ***,systematic studies and meta-analyses evaluating the prevalence of pediatric NAFLD remain *** The MEDLINE,Korean Medical Database(KMBASE),Embase,Global Health,and Cochrane Library databases were searched from January 1997 to April *** terms included NAFLD or steatosis;nonalcoholic or steatohepatitis;child(ren),adolescent,or teenager;and prevalence,incidence,or epidemiology.A random-effects meta-analysis model was used to estimate the prevalence of pediatric *** A total of 2116 publications were found,of which 62 were included in the *** them,27 reported the prevalence in the general population and 39 in the obese *** worldwide pooled prevalence of pediatric NAFLD was 13%[95%confidence interval(CI)9-18%]in the general population and 47%(95%CI 41%–53%)in the obese *** 16 studies in the general population and 18 in the obese population,NAFLD prevalence varied by *** the general population,the prevalence of NAFLD was 15%(95%CI 8%–23%)in males and 10%(95%CI 6%–15%)in *** the obese population,it was 54%(95%CI 46%–61%)in males and 39%(95%CI 30%–49%)in *** The global prevalence of pediatric NAFLD is rising in both the general and obese *** the increasing rates of childhood obesity,epidemiological studies on the prevalence and incidence of NAFLD are needed.

关键词： Meta-analysis Nonalcoholic fatty liver disease Pediatric Prevalence

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Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG SUN KIM YUN SUN LEE SEUNG MYUNG DONG HYO JUNG KIM DA EUN LEE HYEON WOONG KANG MYEONG JIN KIM JOON SEONG PARK department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea department of Surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

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Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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World Journal of Stem Cells 2024年第3期16卷 257-266页

作者： Min Young Park Yong Sik Yoon Jae Ha Park Jong Lyul Lee Chang Sik Yu Division of Colon and Rectal Surgery Department of SurgeryYonsei University College of MedicineSeoul 03722South Korea Division of Colon and Rectal Surgery Department of SurgeryUniversity of Ulsan College of MedicineAsan Medical CenterSeoul 05505South Korea

BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as ***,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula *** This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and *** The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were *** data were compared according to anti-TNF therapy and CPF *** A total of 65 patients were *** median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)*** closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for *** cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,*** Anti-TNF therapy does not increase CPF closure rates in patients with stem cell ***,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF *** tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.

关键词： Crohn’s disease Anus Fistula Stem cell transplantation Tumor necrosis factor-alpha inhibitors Infliximab

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Tongqiao Yizhi granule(通窍益智颗粒) repress the nuclear factor kappa-b/nucleotide oligomerization domain-like receptors 3/caspase-1 pyroptosis pathway in the hippocampus to counter vascular dementia in rats

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Journal of Traditional Chinese medicine 2024年第4期44卷 680-687页

作者： LI Yanjiao HAO Linyao LI Shuangyang LUO Yanqi WANG Juan WANG Raoqiong BAI Xue college of Integrative medicine Southwest Medical University department of Neurology and National Traditional Chinese medicine Clinical Research Base the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University Institute of Integrated Chinese and Western medicine Southwest Medical University

OBJECTIVE: To explore the mechanism by which Tongqiao Yizhi granule（通窍益智颗粒, TQYZKL） intervenes pyroptosis to treat vascular dementia（VaD） in a rat model. METHODS: The rat model of VaD was established by two-vessel occlusion（2VO）. The rats were randomly divided into Sham group, Model group, Nimodipine group, TQYZKL（6.2 g·kg-1·d-1）, TQYZKL(12.4 g·kg-1·d-1), TQYZKL(24.8 g·kg-1·d-1). The Morris water maze（MWM） test was carried out to test the learning and memory function; Hematoxylin-eosin staining and transmission electron microscopy（TEM） to observe the pathological damage in the hippocampus; Tunel fluorescence staining to detect neuronal pyroptosis in the hippocampus. The expression levels of pyroptosis-related proteins, namely Golgi peripheral membrane protein p65（P65）, nucleotide oligomerization domain-like receptors 3（NLRP3）, caspase-1 and Gasdermin D（GSDMD）, were detected using Western blotting and reverse transcription polymerase chain reaction. Moreover, the serum levels of interleukin-1β（IL-1β） and interleukin-18（IL-18） were determined through the enzyme-linked immunosorbent assay. RESULTS: The study revealed that TQYZKL effectively improved the ability of VaD ratsto learn and memorize, relieved the pathological damage in the hippocampus, restored neuronal morphology, and reduced the expression of pyroptosis-related proteins P65, NLRP3, caspase-1, GSDMD-N, IL-18 and IL-1β（P < 0.05）. CONCLUSION: TQYZKL inhibits neuronal pyroptosis in the hippocampus of VaD rats by regulating nuclear factor kappa-B/NLRP3/caspase-1 signaling pathway, thus exerting a therapeutic effect on VaD in the rats.

关键词： NF-kappa B NLR family, pyrin domain-containing 3 protein Tongqiao Yizhi granule caspase 1 dementia, vascular pyroptosis

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Short- and long-term outcomes of surgical treatment in patients with intestinal Behcet’s disease

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 429-437页

BACKGROUND Behcet’s disease(BD),a chronic vasculitic disorder affecting multiple organs,is characterized by recurrent oral and genital ulcers,arthritis,vasculitis,and intes-tinal *** intestinal involvement of BD is common in East Asia,the efficacy and long-term outcomes of surgical treatment of intestinal BD still remain to be *** To evaluate the postoperative clinical course of intestinal BD and determine factors associated with its *** Data from patients who underwent surgical treatment for intestinal BD between January 2010 and August 2021 were retrospectively ***’demo-graphics,clinical features,postoperative course,complications,and follow-up data were *** We analyzed 39 surgeries in 31 *** mean patient age was 45.1 years,and the mean interval between the diagnosis of intestinal BD and surgical treatment was 4.9 years(range 1.0-8.0 years).The most common indication for surgery was medical intractability(n=16,41.0%),followed by fistula or abscess(n=11,28.2%).Laparoscopic approaches were used in 19 patients(48.7%),and 5 patients(12.8%)underwent emergency *** most common surgical procedure was ileocecal resection(n=18,46.2%),followed by right colectomy(n=11,28.2%).A diverting stoma was created in only one patient(2.6%).During a mean follow-up period of 45(range 8-72)months,eight cases(20.5%)of recurrence in five patients required *** interval between operations was 12.1 months(range 6.3-17.8 mo).Four patients(10.3%)experienced recurrence within 1 year postoperatively,and all eight recurrences occurred within 2 years of the initial *** reoperation rates at 1 and 3 years were 10.3%and 20.5%,respectively.A redo ileocolic anastomosis was performed in all recurrent *** multivariate Cox regression analysis,emergency surgery[hazard ratio(HR)9.357,95%confidence interval(CI):1.608-54.453,P=0.013]and elevated C-reactive protein(CRP)levels(HR 1.154,95%CI:1.002–1.328,

关键词： Behcet syndrome Intestinal General surgery Recurrence Risk factors

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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

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Genes & Diseases 2024年第1期11卷 321-334页

作者： Md Rakibul Alam Md Mizanur Rahman Zhiguo Li department of Toxicology and Cancer Biology College of MedicineUniversity of KentuckyLexingtonKY 40506USA department of medicine(Nephrology) Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6E2H7Canada

Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient *** cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune *** evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune ***,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 *** notable treatment outcomes,some pa-tients show poor drug *** PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface *** enhance therapeutic response,inhibition of exosomal PD-L1 is *** signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion ***-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 ***,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic *** this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词： Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis Immunosuppression Immunotherapy

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Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

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World Journal of Transplantation 2024年第1期14卷 32-41页

作者： Shahzaib Maqbool Maryam Farhan Baloch Muhammad Abdul Khaliq Khan Azeem Khalid Kiran Naimat department of medicine Holy Family HospitalRawalpindi 46000Pakistan department of Community medicine Allama Iqbal Medical CollegeLahore 45000Pakistan department of Community Dentistry Baqai Medical UniversityKarachi 43000Pakistan department of medicine Allama lqbal Medical CollegeLahore 45000Pakistan department of medicineLiaquat university of Medical and Health Sciences Karachi 43000Pakistan

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been *** conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and *** regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning *** multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/*** comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding *** case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of ***,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and *** respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding ***-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising ***,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

关键词： Conditioning regimens Multiple myeloma Lymphoma Hodgkin Non-Hodgkin Acute leukemia

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Monogenic features of urolithiasis: A comprehensive review

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Asian Journal of Urology 2024年第2期11卷 169-179页

作者： Kyo Chul Koo Abdulghafour Halawani Victor K.F.Wong Dirk Lange Ben H.Chew department of Urology Yonsei University College of MedicineSeoulRepublic of Korea department of Urology King Abdulaziz UniversityJeddahSaudi Arabia department of Urological Sciences University of British ColumbiaStone Centre at Vancouver General HospitalVancouverBritish ColumbiaCanada

Objective: Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis formation. Advancements in the identification of monogenic causes using high-throughput sequencing technologies have shown that urolithiasis has a strong heritable ***: This review describes monogenic factors implicated in a genetic predisposition to urolithiasis. Peer-reviewed journals were evaluated by a PubMed search until July 2023 to summarize disorders associated with monogenic traits, and discuss clinical implications of identification of patients genetically susceptible to urolithiasis ***: Given that more than 80% of urolithiases cases are associated with calcium accumulation, studies have focused mainly on monogenetic contributors to hypercalciuric urolithiases, leading to the identification of receptors, channels, and transporters involved in the regulation of calcium renal tubular reabsorption. Nevertheless, available candidate genes and linkage methods have a low resolution for evaluation of the effects of genetic components versus those of environmental, dietary, and hormonal factors, and genotypes remain undetermined in the majority of urolithiasis ***: The pathophysiology underlying urolithiasis formation is complex and multifactorial, but evidence strongly suggests the existence of numerous monogenic causes of urolithiasis in humans.

关键词： Gene Genetic expression Inheritance pattern Urolithiasis

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