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N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation

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Asian Journal of Andrology 2024年第1期26卷 99-106页

作者： Wei Ding Jun-Hong Fan li-Ren Zhong Nan-Xiong Wang Lu-Hao liu Hai-Bo Zhang li Wang Ming-Qiang Wang Bing-lin He An-Yang Wei Department of Urology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China Department of Urology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510000China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China Department of Urology Shenzhen Immigration Inspection General Station HospitalShenzhen 518000China Department of Organ Transplantation The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510000China Department of Endocrinology The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang 550002China

Hyperlipidemia is a major risk factor for erectile dysfunction(ED).Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells(CcSMCs)are the key pathological factors of ED.N-acetylcysteine(NAC)can inhibit oxidative stress;however,whether NAc can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear.A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley(SD)rats fed a high-fat and high-cholesterol diet(hyperlipidemic rats,HR).In addition,9 male SD rats were fed a normal diet to serve as controls(NC).HR rats were divided into three groups:HR,HR+normal saline(NS),and HR+NAC(n=9 for each group;NS or NAc intraperitoneal injections were administered daily for 16 weeks).Subsequently,the lipid profiles,erectile function,oxidative stress,phenotypic modulation markers of ccsMCs,and tissue histology were *** experimental results revealed that erectile function was significantly impaired in the HR and HR+NS groups,but enhanced in the HR+NAC *** lipid levels,over-activated oxidative stress,and multi-organ lesions observed in the HR and HR+NS groups were improved in the HR+NAC ***,the HR group showed significant phenotypic modulation of CCSMCs,which was also inhibited by NAC *** report focuses on the therapeutic effect of NAc in restoring erectile function using a hyperlipidemic rat model by preventing CcSMC phenotypic modulationand attenuating oxidativestress.

关键词： erectile dysfunction hyperlipidemia N-acetylcysteine oxidative stress henotypic modulation

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Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients

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Current Medical Science 2024年第4期44卷 771-788页

作者： Hong-xiang HUANG Pei-yuan ZHONG Ping li Su-juan PENG Xin-jing DING Xiang-lian CAI Jin-hong CHEN Xie ZHUI Zhi-hui LUI Xing-yu TAO Yang-yang liU li CHEN Department of Oncology The First Affiliated Hospital of Nanchang UniversityNanchang330006China Jiangxi Institute of Respiratory Disease The First Affiliated Hospital of Nanchang UniversityNanchang330006China Department of Oncology Jiangxi Provincial People’s HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchang330006China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Nanchang UniversityNanchang330006China

Objective The activities and products of carbohydrate metabolism are involved in key processes of ***,its relationship with hepatocellular carcinoma(HCC)is *** The cancer genome atlas(TCGA)-HCC and ICGC-liRI-JP datasets were acquired via public *** expressed genes(DEGs)between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes(CRGs)to obtain differentially expressed CRGs(DE-CRGs).Then,univariate Cox and least absolute shrinkage and selection operator(LASSO)analyses were applied to identify risk model genes,and HCC samples were divided into high/low-risk groups according to the median risk ***,gene set enrichment analysis(GSEA)was performed on the risk model *** sensitivity of the risk model to immunotherapy and chemotherapy was also *** A total of 8 risk model genes,namely,G6PD,PFKFB4,ACAT1,ALDH2,ACYP1,OGDHL,ACADS,and TKTL1,were ***,the risk score,cancer status,age,and pathologic T stage were strongly associated with the prognosis of HCC *** the stromal score and immune score had significant negative/positive correlations with the risk score,reflecting the important role of the risk model in immunotherapy ***,the stromal and immune scores had significant negative/positive correlations with risk scores,reflecting the important role of the risk model in immunotherapy ***,we found that high-/low-risk patients were more sensitive to 102 drugs,suggesting that the risk model exhibited sensitivity to chemotherapy *** results of the experiments in HCC tissue samples validated the expression of the risk model *** Through bioinformatic analysis,we constructed a carbohydrate metabolism-related risk model for HCC,contributing to the prognosis prediction and treatment of HCC patients.

关键词： hepatocellular carcinoma carbohydrate metabolism the cancer genome atlas bioinformatics

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Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits

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Chinese Journal of Integrative Medicine 2024年第9期30卷 809-817页

作者： LU Man MENG De-hong SHE Ze-yu WU Xian XIA Shuai YANG Kai-ning liU Cun-bin li Tao YANG Yong-hui The First Affiliated hospital of Anhui University of Chinese Medicine Hefei230031China The Second Affiliated hospital of Anhui University of Chinese Medicine Hefei230038China Department of Acupotomy Rehabilitation Anhui Provincial Hospital of Integrated Traditional Chinese and Western MedicineHefei230031China

Objective:To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis(KOA),and to determine the possible mechanisms of acupotomy to alleviate cartilage ***:The modified Videman method was used to construct a KOA rabbit *** modeling,40 rabbits were randomly divided into 4 groups by a random number table:control;KOA(model);KOA+acupotomy(acupotomy),and KOA+sham acupotomy(sham),10 in each *** a 3-week treatment course,the knee joint activity was determined by the modified Lequesne MG ***-eosin staining staining was used to examine the morphological changes of *** of chondrocytes was observed by transmission electron *** surface morphology of cartilage tissue was observed by scanning electron *** mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51(AMPK/mTOR/ULK1)signal pathway key proteins,autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3(LC3)in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot,***:The modified Lequesne MG score of acupotomy group was significantly lower than that of model group(Plin-1 and the protein levels of p-AMPK,p-ULK1,Beclin-1,and LC3Ⅱ/LC3Ⅰwere decreased in the model group,while the mRNA and protein expressions of mTOR were increased(Plin1,reduce the expression of mTOR,promote autophagy,and alleviate joint *** is a promising complementary and alternative therapy for KOA.

关键词： acupotomy knee asteoarthritis autophagy AMPK/mTOR/ULK1 signaling pathway rabbit

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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong li Wei li Yanli Zhang linping Xu Yongping Song Department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 18-34页

作者： Yuankai Sun Xinchi Jiang Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China Department of Pharmacy The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Ischemic stroke(IS)causes severe disability and high mortality *** cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current ***’s cell homing,differentiation and paracrine abilities give hope for *** studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and *** improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic ***,many problems must be resolved before SC therapy can be clinically *** issues include production quality and quantity,stability during transportation and storage,as well as usage ***,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy *** aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

关键词： Ischemic stroke Stem cell therapy Stem cell modification Cell therapy challenge

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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： Kevin Tak-Pan Ng li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau Lo Kwan Man Tan To Cheung Department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State Key Laboratory of liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not *** study was to find out whether systemic inflammation plays an important ***:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex *** relationships of the cytokines and the postoperative outcomes were compared between LLR and ***:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative *** to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSF),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly *** POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during *** levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital ***,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver ***:Significantly lower level of GM-CSF,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation

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Neuroscience Bulletin 2024年第2期40卷 255-267页

作者： Yuan Zhang Fanglei Ye Xiaolong Fu Shen li Le Wang Yutian Chen Hongmin li Shaojuan Hao Kun Zhao Qi Feng Peipei li Department of Otology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Shandong Provincial hospital Shandong First Medical UniversityJinan 250000China Department of Neurology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Department of Endovascular Surgery The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Integrated Traditional and Western Nephrology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Province Research Center of Kidney Disease Zhengzhou 450052China

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and *** regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear *** distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related ***,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains ***,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune *** particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic *** hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

关键词： Macrophage Mitochondria Innate immunity Cochlea Infammation

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Sinomenine increases osteogenesis in mice with ovariectomyinduced bone loss by modulating autophagy

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World Journal of Stem Cells 2024年第5期16卷 486-498页

作者： Hai-Xiang Xiao Lei Yu Yu Xia Kai Chen Wen-Ming li Gao-Ran Ge Wei Zhang Qing Zhang Hong-Tao Zhang De-Chun Geng Department of Orthopedics The Fourth Affiliated Hospital of Soochow UniversitySuzhou Dushu Lake HospitalMedical Centre of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Jingjiang People’s Hospital Affiliated to Yangzhou UniversityJingjiang 214500Jiangsu ProvinceChina Department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Hai’an People’s HospitalHai’an 226600Jiangsu ProvinceChina Department of Orthopedics The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an Second People’s HospitalXuzhou 223002Jiangsu ProvinceChina Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate *** To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying *** For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor *** vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse *** SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in *** The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.

关键词： Sinomenine Osteogenesis Autophagy Ovariectomy Osteoporosis

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Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

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World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan Sun Can Wang Pei‑Quan lin Lei Hu Jing Ye Zhi‑Gang Gao Ru lin Hao‑Min li Qiang Shu li‑Su Huang lin‑Hua Tan Children's hospital Zhejiang University School of MedicineHangzhou 310052China The Second Affiliated hospital Zhejiang University School of MedicineHangzhou 310030China Surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal life Support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in ***,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from ***,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely *** sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang *** keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated *** respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be *** immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical *** inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric *** the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult *** Severe pediatric COVID-19 can affect multiple organ *** dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the

关键词： Immunopathophysiology MIS-C Pediatric critical care Severe pediatric COVID-19

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