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Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 815-821页

作者： Ibrahim Cicek Ahmet Mehmet Somuncu Durdu Altuner Bahadir Suleyman Renad Mammadov Seval Bulut Taha Abdulkadir Coban Tugba Bal Tastan Halis Suleyman department of Ophthalmology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of Pharmacology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of Clinical Biochemistry Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey department of Histology and Embryology Faculty of MedicineErzincan Binali Yildirim University ErzincanErzincan 24100Turkey

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

关键词： ocular ischemic syndrome lacidipine thiamine pyrophosphate oxidative stress

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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative medicine 2024年第4期22卷 503-514页

作者： Li-hua Zhu Yu-pei Liang Lian Yang Feng Zhu Li-jun Jia He-gen Lia department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine department of Laboratory medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

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Olfactory immune response to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 134-143页

作者： Sebastian A.Wellford E.Ashley Moseman department of Integrative Immunobiology Duke University School of MedicineDurhamNCUSA

Numerous pathogens can infect the olfactory tract,yet the pandemic caused by SARS-CoV-2 has strongly emphasized the importance of the olfactory mucosa as an immune barrier.Situated in the nasal passages,the olfactory mucosa is directly exposed to the environment to sense airborne odorants;however,this also means it can serve as a direct route of entry from the outside world into the brain.As a result,olfactotropic infections can have serious consequences,including dysfunction of the olfactory system,CNS invasion,dissemination to the lower respiratory tract,and transmission between individuals.Recent research has shown that a distinctive immune response is needed to protect this neuronal and mucosal tissue.A better understanding of innate,adaptive,and structural immune barriers in the olfactory mucosa is needed to develop effective therapeutics and vaccines against olfactotropic microbes such as SARS-CoV-2.Here,we summarize the ramifications of SARS-CoV-2 infection of the olfactory mucosa,review the subsequent immune response,and discuss important areas of future research for olfactory immunity to infectious disease.

关键词： Mucosal immunology Neuroimmunology Infectious Disease Sars-CoV-2

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Effectivenss of electroacupuncture for skeletal muscle pain in Parkinson's disease:a Clinical randomized controlled trial

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Journal of Traditional Chinese medicine 2024年第2期44卷 388-395页

作者： WANG Shaosong SUN Jingqing FENG Qingyin LI Bin WANG Xin YUAN Fan CUI Yingxue department of acupuncture Beijing Hospital of Traditional Chinese MedicineBeijing 100010China

OBJECTIVE:To explore the effect of electroacupuncture on skeletal muscle pain in Parkinson's disease(PD).METHODS:A single-center randomized controlled trial was conducted with sixty patients with Parkinson's disease with skeletal muscle pain were randomly divided into electroacupuncture group and sham acupuncture control group with 30 patients each.The electric acupuncture group was treated with electric acupuncture,while the control group was treated with Park needle pseudoacupuncture.Both groups were treated 5 times a week for a total of 4 weeks,and both groups completed 20 treatments.King's Parkinson's Pain Scale(KPPS)and visual analog scale(VAS)were used before and after treatment to evaluate the pain degree of patients.Realtime shear wave elastography(SWE)and modified Ashworth score(MAS)were used to evaluate the changes of muscle tone.Parkinson's comprehensive Score Scale(MDS-UPDRS,including UPDRS Ⅱ and UPDRS Ⅲ)was used to evaluate exercise ability.Hamilton Depression Scale(HAMD)score was used to evaluate the emotional changes of patients.Spearman correlation analysis was used to explore the correlation between pain degree and muscle tone,exercise ability and emotion.RESULTS:During the study,one case fell off in the control group,and 30 cases were eventually included in the analysis and treatment group and 29 cases in the control group.After treatment,Young's modulus of biceps and quadriceps and shear wave velocity of biceps were decreased in electroacupuncture group compared with before treatment,while KPPS score,VAS score,UPDRS Ⅱ,UPDRS Ⅲ and modified Ashworth score were decreased,with statistical significance(P0.05).After treatment,KPPS score,VAS score,UPDRS Ⅱ and UPDRS Ⅲ,MAS,HAMD score,Young's modulus of biceps and shear wave velocity in electroacupuncture group were significantly lower than those in control group(P<0.05).Spearman correlation analysis showed that KPPS score was positively correlated with UPDRS Ⅲ(r=0.414,P<0.05).KPPS score was

关键词： Parkinson disease muscle skeletal pain electroacupuncture muscle tention mood disorders randomized controlled trial

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Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

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World Journal of Emergency medicine 2024年第3期15卷 190-196页

作者： Huixin Zhao Yiming Dong Sijia Wang Jiayuan Shen Zhenju Song Mingming Xue Mian Shao department of Emergency medicine Zhongshan HospitalFudan UniversityShanghai 200032China

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

关键词： Sepsis Disseminated intravascular coagulation Sepsis-induced coagulopathy Sepsis-associated coagulopathy

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Mechanism of Cu entry into the brain:many unanswered questions

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Neural Regeneration Research 2024年第11期19卷 2421-2429页

作者： Shubhrajit Roy Svetlana Lutsenko department of Physiology Johns Hopkins University School of MedicineBaltimoreMDUSA

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

关键词： ATOX1 ATP7A ATP7B blood-brain barrier brain choroid plexus copper SLC31A1

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Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2024年第13期30卷 1899-1910页

作者： Ante Tonkic Marko Kumric Ivna Akrapovic Olic Doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic Biology of Neoplasms University of Split School of MedicineSplit 21000Croatia department of Pathophysiology University of Split School of MedicineSplit 21000Croatia department of Gastroenterology University Hospital of SplitSplit 21000Croatia department of Pharmacy University of Split School of MedicineSplit 21000Croatia department of Medical Laboratory Diagnostics University Hospital of SplitSplit 21000Croatia department of Health Studies University of SplitSplit 21000Croatia department of Internal medicine University of Split School of MedicineSplit 21000Croatia department of Surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality.Growth-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many others.AIM To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases.An additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with IBD.METHODS This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched controls.All patients underwent an extensive workup,including colonoscopy with subsequent histopathological analysis.Disease activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring systems.GDF-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence immunoassay.RESULTS In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was established.Specifically,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to IBD patients with normal hemoglobin levels,GDF-15

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Growth-differentiation factor-15 Anemia Extraintestinal manifestations

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Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine department of Molecular and Cellular Biology Section of Endocrinology Diabetes and Metabolism Department of Medicine Baylor College of Medicine Brain Glycemic and Metabolism Control department Pennington Biomedical Research Center Louisiana State University

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological range.Certainly,the body necessitates a stable supply of energy mainly provided by glucose for various bodily functions.High or low blood glucose levels would impair the physiological functions of various organs of the body.Prolonged high blood glucose(i.e.,

关键词： HYPOGLYCEMIA

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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 decision-making.MethodsRandomized 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 results.ResultsA 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%, respectively.ConclusionBased 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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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang Nan Hu Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China department of preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： Osteoporosis Spermine Rac1 Zebrafish Mice

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