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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina school of Integrative medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong Xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing Xu Yan Liu Jian Zhang Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes

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Ileal pouch anal anastomosis with modified double-stapled mucosectomy-the experience in China

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World Journal of Gastroenterology 2013年第8期19卷 1299-1305页

作者： Ya-Jie Zhang Yi Han Mou-Bin Lin Yong-Gang He Hao-Bo Zhang Lu Yin Liang Huang Department of General Surgery RuiJin Hospital Affiliated Shanghai Jiaotong University School of Medicine Department of Emergency and Trauma Surgery RuiJin Hospital Affiliated Shanghai Jiaotong University School of Medicine

AIM:To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled ***:From January 2002 to March 2011,fourtyfive patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were ***:Patients with ulcerative colitis(n = 29) and familial adenomatous polyposis(n = 16) underwent ileal pouch-anal anastomosis with modified doublestapled ***-eight patients underwent one-stage restorative proctocolectomy,ileal pouch anal anastomosis,protective ileostomy and the ileostomy was closed 4-12 mo ***-stage procedures were performed in seventeen urgent patients,proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with *** within the first 30 d of surgery occurred in 10(22.2%) patients,all of them could be treated *** the median follow-up of 65 mo,mild to moderate anastomotic narrowing was occurred in 4 patients,one patient developed persistent anastomotic stricture and need surgical *** percent of patients developed at least 1 episode of *** was no incontinence in our patients,the median functional Oresland score was 6,3 and 2 after 1 year,2.5 years and 5 years *** half patients(44.4%) reported "moderate functioning",37.7% reported "good functioning",whereas in 17.7% of patients "poor functioning" was observed after 1 *** years later,79.2% of patients with good function,16.7% with moderate function,only 4.2% of patients with poor ***:The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising,with a low complication rate and good long-term functional results.

关键词： Ileal pouch anal anastomosis Stapled mucosectomy Ulcerative colitis Familial adenomatous polyposis Surgical technique

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Obstructive sleep apnea increases heart rhythm disorders and worsens subsequent outcomes in elderly patients with subacute myocardial infarction

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Journal of Geriatric Cardiology 2021年第1期18卷 30-38页

作者： Ling-Jie WANG Li-Na PAN Ren-Yu YAN Wei-Wei QUAN Zhi-Hong XU Department of Cardiology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Geriatrics Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiChina

OBJECTIVE Obstructive sleep apnea(OSA)is a potential cardiovascular *** aimed to investigate the association of OSA with heart rhythm disorders and prognosis in elderly patients with new-onset acute myocardial infarction(AMI).METHODS We prospectively enrolled 252 AMI elderly patients(mean age,68.5±6.9 years)who were undergoing revascularization and completed a sleep study during their *** subjects were categorized into non-OSA(apnea–hypopnea index(AHI)<15,n=130)and OSA(AHI≥15,n=122)groups based on the *** changes in the autonomic nervous system,incidence of arrhythmia during nocturnal sleep,and major adverse cardiovascular and cerebrovascular events(MACCEs)were compared between the *** The mean AHI value in all AMI patients was 22.8±*** patients showed higher levels of body mass index and peak high-sensitivity C-reactive protein and lower levels of minimum nocturnal oxygen saturation(Min Sa O2),as well as greater proportion of multivessel coronary artery disease(all P<0.05).The OSA group also showed significant increases in heart rate variability and heart rate turbulence onset(both P<0.05)and higher incidence of arrhythmia(including sinus,atrial,and ventricular in origin).At a median follow-up of 6 months(mean 0.8–1.6 years),OSA(AHI≥15)combined with hypoxia(Min Sa O2≤80%)was independently associated with the incidence of MACCEs(hazard ratio[HR]:4.536;95%confidence interval[CI]:1.461-14.084,P=0.009)after adjusting for traditional risk *** OSA and OSA-induced hypoxia may correlate with the severity of myocardial infarction,increase the occurrence of heart rhythm disorders in elderly subacute MI patients,and worsen their short-term poor outcomes.

关键词： OSA Obstructive sleep apnea increases heart rhythm disorders and worsens subsequent outcomes in elderly patients with subacute myocardial infarction

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The revised Atlanta criteria 2012 altered the classification,severity assessment and management of acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2016年第3期15卷 310-315页

作者： Jie Huang Hong-Ping Qu Yun-Feng Zheng Xu-Wei Song Lei Li Zhi-Wei Xu En-Qiang Mao Er-Zhen Chen Department of Intensive Care Unit ruijin hospital Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Radiology ruijin hospital Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Surgery ruijin hospital Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Emergency ruijin hospital Shanghai Jiaotong University School of MedicineShanghai 200025China

BACKGROUND： The Atlanta criteria for acute pancreatitis （AP） has been revised recently. This study was to evaluate its practical value in classification of AP, the severity assessment and management. METHODS： The clinical features, severity classification, out- come and risk factors for mortality of 3212 AP patients who had been admitted in ruijin hospital from 2004 to 2011 were analyzed based on the revised Atlanta criteria （RAC） and the original Atlanta criteria （OAC）.

关键词： acute pancreatitis Atlanta criteria classification outcome

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Inhibition of Girdin enhances chemosensitivity of colorectal cancer cells to oxaliplatin

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World Journal of Gastroenterology 2014年第25期20卷 8229-8236页

作者： Ya-Jie Zhang A-Jian Li Yi Han Lu Yin Mou-Bin Lin Department of General Surgery RuiJin Hospital Affiliated Shanghai Jiaotong University School of Medicine

AIM: To investigate the effect of Girdin knockdown on the chemosensitivity of colorectal cancer cells to oxaliplatin and the possible mechanisms involved.

关键词： Oxaliplatin Chemosensitivity Girdin Colorectal cancer TOP2B

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RAGE gene three polymorphisms with Crohn's disease susceptibility in Chinese Han population

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World Journal of Gastroenterology 2014年第9期20卷 2397-2402页

作者： Zheng-Ting Wang Jia-Jia Hu Rong Fan Jie Zhou Jie Zhong Department of Gastroenterology Ruijin Hospital School of MedicineShanghai Jiaotong University Department of Nuclear medicine Ruijin HospitalSchool of Medicine Shanghai Jiaotong University

AIM: To investigate the association of three polymorphisms in the receptor for advanced glycation end product (RAGE) gene with Crohn’s disease (CD) risk in a Chinese population.

关键词： Receptor for advanced glycation end product, Polymorphism, Crohn’ s diseases, Susceptibility, Association study

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Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases:An update

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World Journal of Gastroenterology 2015年第12期21卷 3492-3498页

作者： Sheng Yan Xue-Feng Yang Hao-Lei Liu Nian Fu Yan Ouyang Kai Qing Department of Gastroenterology Affiliated Nanhua Hospital of University of South China Department of Nephrology Ruijin Hospital Shanghai Jiaotong University School of Medicine Department of Hematology Ruijin Hospital Shanghai Jiaotong University School of Medicine

Long-chain acyl-Co A synthetase(ACSL) family members include five different ACSL isoforms, each encoded by a separate gene and have multiple spliced variants. ACSLs on endoplasmic reticulum and mitochondrial outer membrance catalyze fatty acids with chain lengths from 12 to 20 carbon atoms to form acyl-Co As, which are lipid metabolic intermediates and involved in fatty acid metabolism, membrane modifications and various physiological processes. Gain- or lossof-function studies have shown that the expression of individual ACSL isoforms can alter the distribution and amount of intracellular fatty acids. Changes in the types and amounts of fatty acids, in turn, can alter the expression of intracellular ACSLs. ACSL family members affect not only the proliferation of normal cells, but the proliferation of malignant tumor cells. They also regulate cell apoptosis through different signaling pathways and molecular mechanisms. ACSL members have individual functions in fatty acid metabolism in different types of cells depending on substrate preferences, subcellular location and tissue specificity, thus contributing to liver diseases and metabolic diseases, such as fatty liver disease, obesity, atherosclerosis and diabetes. They are also linked to neurological disorders and other diseases. However, the mechanisms are unclear. This review addresses new findings in the classification and properties of ACSLs and the fatty acid metabolismassociated effects of ACSLs in diseases.

关键词： Long-chain acyl-Co A synthetase Fatty acid Prolife

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Roles of functional catechol-Omethyltransferase genotypes in Chinese patients with Parkinson’s disease

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Translational Neurodegeneration 2017年第1期6卷 108-118页

作者： Yiwei Qian Jiujiang Liu Shaoqing Xu Xiaodong Yang Qin Xiao ruijin hospital affiliated to shanghai jiaotong university school of medicine No.197Ruijin Er RoadShanghai 200025China

Background:Recent studies have found that the functional catechol-O-methyltransferase(COMT)gene may be associated with the susceptibility to and pharmacotherapy of Parkinson’s disease(PD).In this case–control study,we investigated the most common functional COMT gene haplotypes that had been shown to influence COMT enzymatic activity and the association of the single and combined COMT haplotypes with clinical symptoms and pharmacotherapy in Chinese patients with ***:One hundred forty-three patients with idiopathic PD and 157 healthy individuals were enrolled in this *** single nucleotide polymorphisms(SNPs)in the COMT gene(formed by SNPs)were genotyped in each participant:rs6269 A>G;rs4633 C>T;rs4818 C>G;and rs4680 G>***:The frequencies of rs4633 T carriers,rs4680 A carriers and the two linked rs4633-rs4680 T/A carriers were significantly higher in the early onset PD group than in the healthy controls(all P<0.05).Homozygosity for rs4633(TT),rs4680(AA)and of the two linked rs4633-rs4680(TT/AA)was significantly more frequent in patients who exhibited the“wearing-off”phenomenon,longer disease duration,higher levodopa equivalent doses(LED)and higher Unified Parkinson’s Disease Rating Scale(UPDRS)scores(P<0.05).No significant differences were observed in the clinical features of patients who carried individual rs6269 and rs4818,the two linked rs6269-rs4818 and the four combined COMT ***:The results showed a possible association of combined functional COMT SNPs with PD risk,disease duration,the“wearing-off”phenomenon,daily LEDs and higher UPDRS scores,which may be useful in instituting individualized therapy for patients with PD.

关键词： Parkinson’s disease COMT SNP Pharmacotherapy

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Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes mellitus

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 141-145页

作者： Cai-Hong Zhu Shi-Sheng Zhang Yan Kong Yu-Fang Bi Ling Wang Qiong Zhang Department of Ophthalmology Ruijin Hospital School of Medicine Shanghai Jiaotong University New Vision Eye Clinic Ruijin Hospital School of Medicine Shanghai Jiaotong University Department of Hypertension Ruijin Hospital School of Medicine Shanghai Jiaotong University Department of Endocrinology Ruijin Hospital School of Medicine Shanghai Jiaotong University

AIM: To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with type Ⅱ diabetes. METHODS: A total of 107 patients with type Ⅱ diabetes were randomly assigned into intensive and standard treatment groups. Patients in the intensive treatment group received preterax (perindopril/ indapamide) to control blood pressure, and gliclazide (diamicron) MR to control blood glucose. Patients in the standard treatment group received routine medications or placebo. Urinary microalbumin (UMA), urinary creatinine (UCR), the UMA/ UCR ratio, and visual acuity were monitored according to the study design of the ADVANCE trial. Direct ophthalmoscopy and seven-field stereoscopic retinal photography were used to examine the fundi at baseline,and repeated after 5 years of treatment. RESULTS: The characteristics of patients in both groups were well balanced at baseline. After 5 years of treatment, visual acuity was found to be decreased in the standard group (P=0.04), but remained stable in the intensive group. The severity of diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group (P=0.0006). The UMA/UCR ratio was not obviously changed in patients in the intensive group, whereas it was significantly increased in the standard group (P=0.00). CONCLUSION: Intensive control of blood glucose and blood pressure can decrease the incidence or slow the progression of microvascular complications in patients with type Ⅱ diabetes, and maintain stable vision.

关键词： diabetes mellitus intensive therapy microvascular complications diabetic retinopathy

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