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Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao Zhu Xiaoxia Chen Kwok-Fai So Anding Xu Lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University Department of Neurology and Stroke Center The First Affiliated HospitalJinan University Department of Psychiatry The First Affiliated HospitalJinan University Co-innovation Center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative *** also represent a potential source of transplanted cells for therapeutic *** vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal *** evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons *** SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic *** obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of *** increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing *** further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 ***,we have established three induction protocols for dopaminergic *** on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis

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Oncology Research 2024年第4期32卷 727-736页

作者： GUOQIANG HOU XINHANG XU WEIXING HU Department of Neurosurgery First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of Neurosurgery Renji HospitalShanghai Jiao Tong UniversityShanghaiChina

Primary tumors of the central nervous system(CNS)are classified into over 100 different histological *** most common type of glioma is derived from astrocytes,and the most invasive glioblastoma(WHO IV)accounts for over 57%of these ***(GBM)is the most common and fatal tumor of the CNS,with strong growth and invasion capabilities,which makes complete surgical resection almost *** various treatment methods such as surgery,radiotherapy,and chemotherapy,glioma is still an incurable disease,and the median survival time of patients with GBM is shorter than 15 ***,molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor *** ionotropic receptor kainate type subunit 1(GRIK1)is essential for brain function and is involved in many mental and neurological ***,GRIK1’s pathogenic roles and mechanisms in GBM are still ***-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent ***,immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM,consistent with The Cancer Genome Atlas *** of GRIK1 retarded GBM cells growth,migration,and *** together,these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.

关键词： Glioblastoma GRIK1 Invasion Proliferation Prognosis

Silvestrol alleviates glioblastoma progression through ERK pathway modulation and MANBA and NRG-1 expression

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BIOCELL 2024年第7期48卷 1081-1093页

作者： LAN ZHOU QI ZHANG BO TIAN FENG YANG Neurosurgery Department The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina Neurosurgery Department Changdu People’s Hospital of TibetChangduChina

Background:Glioblastoma,a notably malignant tumor within the central nervous system,is distinguished by its aggressive ***,a robust inhibitor of the RNA helicase eukaryotic initiation factor 4A(eIF4A),has shown significant potential as an anticancer ***,the impact of silvestrol on glioblastoma,especially its molecular mechanisms,has not been fully ***:This investigation employed a variety of in vitro assays,such as cell counting kit-8(CCK-8),clonogenic,5-ethynyl-2′-deoxyuridine(EDU),wound healing,and flow cytometry,to evaluate cell cycle progression,apoptosis,cell viability,and *** blot analysis was also performed to study the apoptosis and extracellular regulated kinase(ERK)*** the ERK pathway was inhibited,differentially expressed genes(DEGs)in U87 cells were identified,followed by an analysis of target genes using the gene expression profiling interactive analysis(GEPIA)***:Silvestrol significantly suppressed the proliferation,migration,and colony formation of glioma *** caused cell cycle arrest and enhanced apoptosis in these ***,silvestrol stimulated the ERK pathway,with these effects being reversible by an ERK phosphorylation *** combined with GEPIA,GSCA,UALCAN,TIMER database screened 4 potential drug targets of silvestrol:chromosome 1 open reading frame 226(C1ORF226),mannosidase beta A(MANBA),IQ motif and Sec7 domain 2(IQSEC2),neuregulin 1(NRG-1).Among them,C1ORF226 was lower risk gene while MANBA,IQSEC2,and NRG-1 were high-risk ***,silvestrol notably reduced MANBA mRNA levels,which could be reversed by inhibiting ERK ***,silvestrol markedly decreased NRG-1 protein levels,with an additional reduction observed when the ERK pathway was ***:Silvestrol’s anti-glioma effects are primarily due to the suppression of MANBA expression via the ERK pathway and possibly by hindering the translation of N

关键词： Glioblastoma Silvestrol ERK pathway MANBA NRG-1

Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

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Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao Jiaojiao Huang Xianglin Wu Yanan Huo Qin Wan Yingfen Qin Ruying Hu Lixin Shi Qing Su Xuefeng Yu Li Yan Guijun Qin Xulei Tang Gang Chen Min Xu Tiange Wang Zhiyun Zhao Zhengnan Gao Guixia Wang Feixia Shen Zuojie Luo Li Chen Qiang Li Zhen Ye Yinfei Zhang Chao Liu Youmin Wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng Jiajun Zhao Yiming Mu Shengli Wu Yuhong Chen Jieli Lu Weiqing Wang Guang Ning Yu Xu Yufang Bi Mian Li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China Sun Yat-sen Memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong University Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with *** included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life *** isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD ***-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working *** stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long *** pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active *** U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical *** divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction

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World Journal of Psychiatry 2024年第5期14卷 644-652页

作者： Tian-Shu Wang Li-Jun Jing Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and *** or improper treatment greatly affects patient *** To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI *** We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two ***,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),*** Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after *** Aspirin plus edaravone had a good curative effect on *** can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.

关键词： Aspirin Edaravone Cerebral infarction Efficacy Quality of life

Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma

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World Journal of Clinical Cases 2024年第6期12卷 1111-1119页

作者： Xiao-Yu Xing Wei Zhang Li-Ya Liu Li-Ping Han Department of Gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina

BACKGROUND Neuroendocrine neoplasms of the female genital tract are *** To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the *** A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival *** The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell *** cases were stage I tumors,one case was stage IV,and six cases were stage *** patients underwent surgery as part of their *** patients received adjuvant *** the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after *** median progression-free survival was 13 months,and the median overall survival was 19.5 *** cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease *** NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical *** resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.

关键词： Neuroendocrine carcinoma Ovary Pathology Treatment

Incidence of surgical site infection in minimally invasive colorectal surgery

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1121-1129页

作者： Lu-Ting Ni Ru Zhao Yi-Ru Ye Yi-Ming Ouyang Xin Chen Department of Surgery The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Surgical site infection(SSI)is a common complication of colorectal *** invasive surgery notably reduces the incidence of *** study aimed to compare the incidences of SSI after robot-assisted colorectal surgery(RACS)vs that after laparoscopic assisted colorectal surgery(LACS)and to analyze associated risk factors for SSI in minimally invasive colorectal *** To compare the incidences of SSI after RACS and LACS,and to analyze the risk factors associated with SSI after minimally invasive colorectal *** Clinical data derived from patients who underwent minimally invasive colorectal surgery between October 2020 and October 2022 at the first affiliated hospital of Soochow University were *** in clinical characteristics and surgeryrelated information associated with RACS and LACS were compared,and possible risk factors for SSI were *** A total of 246 patients(112 LACS and 134 RACS)were included in the ***(17.5%)developed *** proportions of patients who developed SSI were similar in the two groups(17.9%vs 17.2%,P=0.887).Diabetes mellitus,intraoperative blood loss≥100 mL,and incision length were independent risk factors for *** additional risk factors included neoadjuvant therapy,lesion site,and operation *** There was no difference in SSI incidence in the RACS and LACS *** mellitus,intraoperative blood loss≥100 mL,and incision length were independent risk factors for postoperative SSI.

关键词： Colorectal surgery Minimally invasive surgery Surgical site infection

Clinical experience sharing on gastric microneuroendocrine tumors: A case report

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World Journal of Clinical Cases 2024年第4期12卷 795-800页

作者： You-Jun Wang Da-Ming Fan Yu-Shuang Xu Qi Zhao Zhen-Fang Li Department of Gastroenterology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina Department of Pathology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

BACKGROUND The majority of gastric neuroendocrine tumors(G-NENs)are present in various lesions under endoscopy,and they can be polypoid uplifts,submucosal tumors or papules,erosions,and *** lesions are mostly confined to the mucosal or submucosal layer,usually less than 2 cm,and exclusively localized to the gastric body or *** type 1 G-NENs,about 22%of cases have no visible lesions under an endoscope,and such lesions can only be detected via biopsies(microcar-cinoids).CONCLUSION In the case under study,the patient did not have any visible raised lesions under a gastroscope,and the lesions were found only after a random *** article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

关键词： Neuroendocrine tumor Micro carcinoids Endoscopy Case report

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

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Journal of Geriatric Cardiology 2024年第5期21卷 506-522页

作者： Yi XU Tian XU Jia-Cong NONG Xiao-Han KONG Meng-Yao ZHAO Zhi-Jing GAO Yi-Fei WANG Wei YOU Pei-Na MENG Yu-He ZHOU Xiang-Qi WU Zhi-Ming WU Mei-En ZHAN Yan-Qing WANG De-Feng PAN Fei YE Department of Cardiology Nanjing First HospitalNanjing Hospital Affiliated to Nanjing Medical UniversityNanjing Medical UniversityNanjingChina Department of Cardiology Clinical Medicine School of Nanjing UniversityNanjingChina Department of Cardiology Tianchang People’s HospitalTianchangChina Department of Cardiology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent *** A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of *** In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR *** The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

关键词： lesions remodeling intravascular