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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 86-102页

作者： Xiaoling Fu Yutong Song Xianquan Feng Zhihong Liu Wenhao Gao Hongtao Song Qian Zhang school of Pharmacy Fujian Medical UniversityFuzhou 350108China Fuzong clinical medical College of Fujian medical University Fuzhou 350025China first school of clinical medicine Nanjing Medical UniversityNanjing 211166China

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

关键词： Polydopamine Thermosensitive liposomes Photothermal therapy Oxygen generation Rheumatoid arthritis

CD209 signaling pathway as a biomarker for cisplatin chemotherapy response in small cell lung cancer

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Genes & Diseases 2024年第3期11卷 11-14页

作者： Anqi Lin Hong Yang Jian Zhang Peng Luo Department of Oncology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510282China The first clinical medical school Southern Medical UniversityGuangzhouGuangdong 510515China

One of the bottlenecks in the clinical treatment of small cell lung cancer(SCLC)is its susceptibility to multidrug resistance.While SCLC is sensitive to platinum-based chemotherapy at the initial stage of treatment,it can rapidly become drug-resistant,allowing tumor growth to accelerate.A significant decrease in drug sensitivity after recurrence and multidrug resistance can seriously interfere with the effectiveness of treatment,making sensitivity maintenance one of the urgent challenges to be solved.Therefore,discovering prognostic markers for cisplatin chemotherapy and understanding the mechanisms of cisplatin resistance have great practical significance for improving the outcomes of sCLC patients.

关键词： cisplatin chemotherapy lung

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 annually.With 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 patients.Moreover,CVD and cancer have become major disease burdens worldwide.Thus,further research is needed to lessen the risk of CVD death in HCC patient survivors.METHODS 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 2015.The independent risk factors were identified using the Fine-Gray model.A nomograph was constructed to predict the CVM in HCC patients.The 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)value.Moreover,the net benefit was estimated via decision curve analysis(DCA).RESULTS The study included 21545 HCC patients,of whom 619 died of CVD.Age(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 patients.The discrimination and calibration of the nomograph were better.The C-index values for the training and validation sets were 0.736 and 0.665,respectively.The 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,respectively.The calibration curves showed that the predicted probab-ilities of the CVM prediction

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

High glucose promotes macrophage M1 polarization through miR-32/Mef2d/cAMP signaling pathway

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Genes & Diseases 2024年第2期11卷 539-541页

作者： Cong Chen Jingsong Cao Yan Gao Xiaoping Xie Zhibo Zhao Qing Yuan Yuqi He Xuyu Zu Jianghua Liu The first Affiliated Hospital Institute of Endocrinology and MetabolismCenter for Clinical Research in DiabetesHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China The first Affiliated Hospital Department of Laboratory MedicineHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China The first Affiliated Hospital Institute of OncologyHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China

Chronic inflammation is a crucial inducerof diabetesvascular complications.Onereason is that high glucose easily induces macrophage activation.1 Macrophages are the principal participants in innate immunity and exist in all human tissues.In pathological vascular,infiltrated macrophages secrete inflammatory factors leading to an increase in plaque stability.?In macrophage polarization,autophagy plays an important role.Enhancement of macrophage autophagy could induce macrophage polarization from the M1 phenotype to M2 phenotype and inhibit inflammatory reactions.3 Our previous research found that high glucose condition promotes miR-32 expression and macrophage M1 polarization,4 but the mechanism of miR-32 promoting macrophage M1 polarization is unclear.In this study,we found that,under a high-glucose condition,miR-32/Mef2d/cAMP signaling promoted M1 macrophage polarization via inhibited autophagy.These results provide a theoretical and experimental basis for the prevention and treatment of T2D vascular inflammation.

关键词： macrophage miR prevention

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 cysts.Here,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 DM.Doppler ultrasound and computed tomography scan showed a giant lump in the left thyroid gland lobe.He was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical indications.Surgical exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles,the nodule and glandular tissue.Fortunately,inflammatory lesions did not affect major neck vessels.Finally,a left partial thyroidectomy was performed.Macroscopic 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 matter.Postoperative pathology confirmed benign thyroid cyst with chronic infection.CONCLUSION 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

Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin Center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The first Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China school of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of Gastroenterology and Hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

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World Journal of clinical Cases 2024年第9期12卷 1685-1690页

作者： Xuan Xu Jing-Wen Jiang Bing-Yun Lu Xia-Xi Li Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhen 518100Guangdong ProvinceChina The first clinical medical school Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

关键词： Upadacitinib Refractory ulcerative colitis Primary nonresponse Infliximab Vedolizumab Case report

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 mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate(DSS) solution for 7 days to establish a colitis model.Twelve 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 determined.Rats 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 treatment.Acupuncture 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 days.GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days.Mechanical sensitivity was assessed with von Frey filaments.Body weight and disease activity index(DAI) scores of rats were determined.Hematoxylin and eosin staining was performed to observe colon histopathology.SSC was analyzed by immunofluorescence staining.Immunohistochemical staining was performed to detect 5-HT and substance P(SP) expressions.The calcitonin gene-related peptide(CGRP) in skin tissue and tyrosine hydroxylase(TH) protein levels in DRG were detected by Western blot.The 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 15 acupoint was used as a non-sensitized acupoint

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

Brain Pathology in COVID-19:clinical Manifestations and Potential Mechanisms

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Neuroscience Bulletin 2024年第3期40卷 383-400页

作者： Zhixing Xu Hui Wang Siya Jiang Jiao Teng Dongxu Zhou Zhong Chen Chengping Wen Zhenghao Xu first school of clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China school of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Second school of clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Afliated Lin’an People’s Hospital of Hangzhou medical College First People’s Hospital of Hangzhou Lin’an DistrictLin’anHangzhou 311300China school of Life Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Laboratory of Rheumatology and Institute of TCM clinical Basic Medicine College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in COVID-19.Even though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is similar.More than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging outcomes.In this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza infection.We also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 invasion.In addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment ideas.This review may offer new insights into preventing or treating brain damage in COVID-19.

关键词： COVID-19 SARS-CoV-2 Brain Neurological pathology

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1213-1226页

作者： Guo-Le Nie Jun Yan Ying Li Hong-Long Zhang Dan-Na Xie Xing-Wang Zhu Xun Li The first school of clinical Medicine Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of General Surgery The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the first Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibr

关键词： Portal vein thrombosis Liver cirrhosis Nomogram Inflammatory markers Aspartate aminotransferase to neutrophil ratio index Platelet-to-lymphocyte ratio