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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina Department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus:A case report

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World Journal of clinical Cases 2024年第8期12卷 1497-1503页

作者： Jiang-Bo Liu Shi-Lei Zhang Wen-Long Jiang Hai-Kuan Sun Hao-Chen Yang Department of Thyroid and Breast Surgery The First Affiliated HospitalCollege of Clinical MedicineHenan University of Science and TechnologyLuoyang 471000Henan ProvinceChina clinical medicine School The First Clinical CollegeChongqing Medical UniversityChongqing 400016China

BACKGROUND Patients rarely develop complicated infections in thyroid ***,we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus(DM).CASE SUMMARY A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of *** ultrasound and computed tomography scan showed a giant lump in the left thyroid gland *** was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical *** exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles,the nodule and glandular ***,inflammatory lesions did not affect major neck ***,a left partial thyroidectomy was *** observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent *** pathology confirmed benign thyroid cyst with chronic *** The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM,and identifying blood vessels involvement can prevent serious complications during operation.

关键词： Thyroid nodule Infection Diabetes mellitus Surgery Case report

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Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

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Chinese Journal of Integrative medicine 2024年第5期30卷 421-432页

作者： YUE Tong-tong CAO Ying-jie CAO Ya-xuan LI Wei-xia WANG Xiao-yan SI Chun-ying XIA Han ZHU Ming-jun TANG Jin-fa WANG He The first clinical Medical college of Henan University of Chinese medicine Zhengzhou 450046China Department of Pharmacy the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China Department of Cardiovascular Diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was

关键词： myocardial ischemia reperfusion injury PI3K/AKT signaling pathway Shuxuening Injection apoptosis Ginkgo biloba leaves

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Cancer cachexia:Focus on cachexia factors and inter-organ communication

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Chinese Medical Journal 2024年第1期137卷 44-62页

作者： Yongfei Wang Zikai Dong Ziyi An Weilin Jin The first clinical Medical college of Lanzhou University LanzhouGansu 730000China Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhouGansu 730000China

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia *** cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer *** cachexia factors are also a potential target for the diagnosis and *** pathogenesis of cachexia is unclear and no clear effective treatment is ***,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently *** the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and *** review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia *** summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

关键词： Cancer cachexia Cancer cachexia factors Inter-organ communication Tumor ecosystem Tumor microenvironment

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Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

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Chinese Journal of Natural medicines 2024年第3期22卷 224-234页

作者： WU Yuanyuan ZHOU Jingwen ZUO Xinchen KUANG Yufeng SUN Lixia ZHANG Xiaolong The first clinical Medical college Nanjing University of Chinese MedicineNanjing 210023China The Affiliated Hospital of Nanjing University of Chinese medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as *** Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely *** study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological *** simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were *** severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine *** results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid ***,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and ***,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo *** preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.

关键词： Non-alcoholic steatohepatitis Nuclear factor kappa B NLRP3 inflammasome Yanggan Jiangmei Formula

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Benefit-Risk Assessment of Chinese medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis

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Chinese Journal of Integrative medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The first clinical Medical college of Henan University of Traditional Chinese medicine Zhengzhou450046China Personal Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical *** controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation *** total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, *** on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

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Efficacy and safety of Yangxinshi tablet for chronic heart failure:A systematic review and meta-analysis

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World Journal of clinical Cases 2024年第13期12卷 2218-2230页

作者： Sheng-Hua Lu Yun-Feng Yu Si-Si Dai Ya-Qi Hu Jian-He Liu The first clinical college of Chinese medicine Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina Branch of National clinical Research Center for Chinese medicine Cardiology The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina

BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain *** To systematically evaluate the efficacy and safety of YXST in the treatment of *** Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November ***-analyses of the included clinical studies were conducted using Review Manager *** Twenty RCTs and 1845 patients were *** meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(Pclinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.

关键词： Yangxinshi tablet Chronic heart failure Cardiac function Systematic evaluation Meta-analysis

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The first clinical Medical college of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular Department and Gansu clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome *** dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the *** In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni ***,no significant relationships were observed between other iron and LV *** Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the *** We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 844-856页

作者： Yu-Liang Zhang Zi-Rong Liu Zhi Liu Yi Bai Hao Chi Da-Peng Chen Ya-Min Zhang Zi-Lin Cui first Central clinical college Tianjin Medical UniversityTianjin 300070China Department of Hepatobiliary Surgery Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of cancers worldwide,ranking fifth among men and seventh among women,resulting in more than 7 million deaths *** the development of medical tech-nology,the 5-year survival rate of HCC patients can be increased to 70%.How-ever,HCC patients are often at increased risk of cardiovascular disease(CVD)death due to exposure to potentially cardiotoxic treatments compared with non-HCC ***,CVD and cancer have become major disease burdens ***,further research is needed to lessen the risk of CVD death in HCC patient *** This study was conducted on the basis of the Surveillance,Epidemiology,and End Results database and included HCC patients with a diagnosis period from 2010 to *** independent risk factors were identified using the Fine-Gray model.A nomograph was constructed to predict the CVM in HCC *** nomograph performance was measured using Harrell’s concordance index(C-index),calibration curve,receiver operating characteristic(ROC)curve,and area under the ROC curve(AUC)***,the net benefit was estimated via decision curve analysis(DCA).RESULTS The study included 21545 HCC patients,of whom 619 died of ***(5 cm:2.090(1.543-2.830),P<0.001],surgery(no)[0.376(0.297-0.476),P<0.001],and chemotherapy(none/unknown)[0.578(0.472-0.709),P<0.001]were independent risk factors for CVD death in HCC *** discrimination and calibration of the nomograph were *** C-index values for the training and validation sets were 0.736 and 0.665,*** AUC values of the ROC curves at 2,4,and 6 years were 0.702,0.725,0.740 in the training set and 0.697,0.710,0.744 in the validation set,*** calibration curves showed that the

关键词： Hepatocellular carcinoma Cardiovascular disease deaths Fine-Gray model Risk factor Nomograph Predict

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Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interferewith 5-HT Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第2期30卷 152-162页

作者： YANG Ying QU Jin-yu GUO Hua ZHOU Hai-ying RUAN Xia PENG Ying-chun SHEN Xue-fang XIONG Jin WANG Yi-li School of clinical medicine Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation medicine the First Affliated Hospital of Chengdu Medical CollegeChengdu(610500)China Department of Rehabilitation medicine West China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu(610041)China Department of Neurology the First Affiliated Hospital of Chengdu Medical CollegeChengdu(610500)China

Objective:To investigate whether electroacupuncture(EA) at sensitized acupoints could reduce sympathetic-sensory coupling(SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine(5-HT)ergic neural pathways to relieve colitis and somatic referred pain,and explore the underlying ***:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis *** rats were randomly divided into the control and model groups according to a random number table(n=6).According to the Research on Rat Acupoint Atlas",sensitized acupoints and non-sensitized acupoints were *** were randomly divided into the control,model,Zusanli-EA(ST 36),Dachangshu-EA(BL 25),and Xinshu(BL 15) groups(n=6),as well as the control,model,EA,and EA+GR113808(a 5-HT inhibitor)groups(n=6).The rats in the control group received no *** was administered on 2 days after modeling using the stimulation pavameters:1 mA,2 Hz,for 30 min,with sparse and dense waves,for 14 consecutive ***113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive *** sensitivity was assessed with von Frey *** weight and disease activity index(DAI) scores of rats were *** and eosin staining was performed to observe colon *** was analyzed by immunofluorescence *** staining was performed to detect 5-HT and substance P(SP) *** calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western *** levels of hyaluronic acid(HA),bradykinin(BK),prostaglandin I2(PGI2) in skin tissue,5-HT,tryptophan hydroxylase 1(TPH1),serotonin transporters(SERT),5-HT 3 receptor(5-HT3R),and 5-HT 4 receptor(5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints,and BL 1

关键词： electroacupuncture sensitized acupoints sympathetic-sensory coupling 5-hydroxytryptamine neurogenic inflammation somaticreferredpain

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