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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National clinical research center for Ocular disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Effect of cholesterol metabolism on hepatolithiasis

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World Journal of Gastroenterology 2025年第1期31卷 157-162页

作者： Lin Zheng Zi-Yu Ye Jun-Ji Ma Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesNo.215 Heping West RoadShijiazhuang 050000Hebei ProvinceChina

Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after *** metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of ***,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after *** dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating *** article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.

关键词： Hepatolithiasis Cholesterol metabolism High-fat diet 3-hydroxy-3-methylglutaryl-coenzyme A reductase Interlobular bile duct

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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha Department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina Fujian provincial Key Laboratory of Brain Aging and Neurodegenerative diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Institute of Laboratory Animal center Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina Department of Hyperbaric Oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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Exploring the performance of large language models on hepatitis B infection-related questions:A comparative study

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World Journal of Gastroenterology 2025年第3期31卷 103-112页

作者： Yu Li Chen-Kai Huang Yi Hu Xiao-Dong Zhou Cong He Jia-Wei Zhong Department of Gastroenterology Jiangxi Provincial Key Laboratory of Digestive DiseasesJiangxi Clinical Research Center for GastroenterologyDigestive Disease HospitalThe First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina HuanKui Academy Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Patients with hepatitis B virus(HBV)infection require chronic and personalized care to improve *** language models(LLMs)can potentially provide medical information for *** To examine the performance of three LLMs,ChatGPT-3.5,ChatGPT-4.0,and Google Gemini,in answering HBV-related *** LLMs’responses to HBV-related questions were independently graded by two medical professionals using a four-point accuracy scale,and disagreements were resolved by a third *** question was run three times using three *** was assessed via the Gunning Fog index and Flesch-Kincaid grade *** Overall,all three LLM chatbots achieved high average accuracy scores for subjective questions(ChatGPT-3.5:3.50;ChatGPT-4.0:3.69;Google Gemini:3.53,out of a maximum score of 4).With respect to objective questions,ChatGPT-4.0 achieved an 80.8%accuracy rate,compared with 62.9%for ChatGPT-3.5 and 73.1%for Google *** the six domains,ChatGPT-4.0 performed better in terms of diagnosis,whereas Google Gemini demonstrated excellent clinical ***,in the readability analysis,the mean Gunning Fog index and Flesch-Kincaid grade level scores of the three LLM chatbots were significantly higher than the standard level eight,far exceeding the reading level of the normal *** Our results highlight the potential of LLMs,especially ChatGPT-4.0,for delivering responses to HBV-related *** may be an adjunctive informational tool for patients and physicians to improve ***,current LLMs should not replace personalized treatment recommendations from physicians in the management of HBV infection.

关键词： ChatGPT-3.5 ChatGPT-4.0 Google Gemini Hepatitis B infection Accuracy

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Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population:a cross-sectional study

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Journal of Geriatric Cardiology 2022年第6期19卷 418-427页

作者： Fu-Yu JING Xiu-Ling WANG Jia-Li SONG Yan GAO Jian-Lan CUI Wei XU Yang YANG Li-Juan SONG Hai-Bo ZHANG Jia-Peng LU Xi LI Xin ZHENG National clinical research center for cardiovascular diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina National clinical research center for cardiovascular diseases ShenzhenCoronary Artery Disease CenterFuwai Hospital Chinese Academy of Medical SciencesShenzhenChina

BACKGROUND Epidemiologic studies have explored the association between a single cardiovascular risk factor(CVRF)and resting heart rate(RHR),but the research on the relation of multiple risk factors with RHR remains *** study aimed to explore the associations between CVRFs clustering and the risk of elevated *** In this cross-sectional study,adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August *** focused on seven risk factors:hypertension,diabetes mellitus,dyslipidemia,obesity,smoking,alcohol use,and low physical *** logistic regression was used to calculate odds ratios(OR)for elevated RHR(>80 beats/min).RESULTS Among 1,045,405 participants,the mean age was 55.67±9.86 years,and 60.4%of participants were *** OR(95%CI)for elevated RHR for the groups with 1,2,3,4 and≥5 risk factor were 1.11(1.08-1.13),1.36(1.33-1.39),1.68(1.64-1.72),2.01(1.96-2.07)and 2.58(2.50-2.67),respectively(Ptrend<0.001).The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex *** comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk *** There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR,particularly in young *** clusters comprising more behavioral risk factors,clusters comprising more metabolic risk factors were associated with a higher risk of elevated *** may serve as an indicator of the cumulative effect of multiple risk factors.

关键词： elevated cardiovascular sectional

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Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

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Journal of Geriatric Cardiology 2024年第3期21卷 340-348页

作者： Jia-Yin CAI Xin WANG Cong-Yi ZHENG Xue CAO Zhen HU Run-Qing GU Yi-Xin TIAN Ye TIAN Lan SHAO Lin-Feng ZHANG Zeng-Wu WANG Division of Prevention and Community Health National Center for Cardiovascular DiseaseNational Clinical Research Center of Cardiovascular DiseaseState Key Laboratory of Cardiovascular DiseaseFuwai HospitalPeking Union Medical College&Chinese Academy of Medical SciencesBeijingChina

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally *** conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple *** Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS *** data for 15 CVDs were also obtained from the IEU GWAS *** used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on ***'s Q test and MR-Egger intercept test were used to evaluate the heterogeneity and *** MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this *** Causal relationship of loneliness and isolation with CVDs were found in this study.

关键词： diseases cardiovascular angina

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Long-term outcome of percutaneous or surgical revascularization with and without prior stroke in patients with threevessel disease

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Journal of Geriatric Cardiology 2022年第8期19卷 583-593页

作者： Na XU Ce ZHANG Lin JIANG Jing-Jing XU Ru LIU Ying SONG Xue-Yan ZHAO Lian-Jun XU Run-Lin GAO Bo XU Jin-Qing YUAN Lei SONG center for Coronary Heart disease National Clinical Research Center for Cardiovascular DiseasesNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVE To determine whether high-risk patients with three-vessel disease(TVD)with and without prior stroke preferen-tially benefit from three strategies[percutaneous coronary intervention(PCI),coronary artery bypass grafting(CABG)and medical therapy(MT)].METHODS A total of 8943 patients with TVD were included in the *** enrolled were stratified into two categories according to the presence or absence of prior stroke *** primary endpoint was all-cause *** endpoints in-cluded stroke and major adverse cardiac and cerebrovascular event(MACCE),a composite of death,myocardial infarction(MI),unplanned revascularization and *** Prior stroke was present in 888 patients(9.9%).These patients were older and had higher rates of ***-ring a median follow-up of 7.5 years,patients with prior stroke were strongly associated with increased risks of all-cause death,cardiac death,stroke and MACCE,even after adjusting for confounding variables and results been consistent across either treat-ment subgroup(PCI,CABG and MT)(all adjusted Pclinical *** is essential to balance benefit and risk when determining the optimal treatment strategy for TVD with and without prior stroke.

关键词： patients prior founding

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Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation

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Journal of Geriatric Cardiology 2021年第9期18卷 728-738页

作者： Fu-Wei XING Li-Hua ZHANG Hai-Bo ZHANG Xue-Ke BAI Dan-Li HU Xin ZHENG Jing LI National clinical research center for cardiovascular diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina

OBJECTIVE To assess the association between beta-blockers and 1-year clinical outcomes in heart failure(HF)patients with atrial fibrillation(AF),and further explore this association that differs by left ventricular ejection fraction(LVEF)*** We enrolled hospitalized HF patients with AF from China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure *** proportional hazard regression models were employed to calculate hazard ratio of *** primary outcome was all-cause *** Among 1762 HF patients with AF(756 women[41.4%]),1041(56%)received beta-blockers at discharge and 1272(72.2%)had an LVEF>40%.During one year follow up,all-cause death occurred in 305(17.3%),cardiovascular death occurred in203 patients(11.5%),and rehospitalizations for HF occurred in 622 patients(35.2%).After adjusting for demographic characteristics,social economic status,smoking status,medical history,anthropometric characteristics,and medications used at discharge,the use of beta-blockers at discharge was not associated with all-cause death[hazard ratio(HR):0.86;95%Confidence Interval(CI):0.65-1.12;P=0.256],cardiovascular death(HR:0.76,95%CI:0.52-1.11;P=0.160),or the composite outcome of all-cause death and HF rehospitalization(HR:0.97,95%CI:0.82-1.14;P=0.687)in the entire *** were no significant interactions between use of beta-blockers at discharge and LVEF with respect to all-cause death,cardiovascular death,or composite *** the adjusted models,the use of beta-blockers at discharge was not associated with all-cause death,cardiovascular death,or composite outcome across the different levels of LVEF:reduced(clinical outcomes,regardless of LVEF.

关键词： Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation center for Human Brain Protection and National clinical research center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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Journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui LIU Meng ZHANG Yuan-Lin GUO Cheng-Gang ZHU Na-Qiong WU Ying GAO Rui-Xia XU Jie QIAN Ke-Fei DOU Jian-Jun LI Cardiometabolic center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were *** admission,ABG,SHR,and GG were assessed and all participants were classified according to their ***-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and *** adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

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