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Engineering nanomedicine. for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar Samir Hagar E.Emam Ahmed Soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr division of Engineering in medicine.and division of Renal medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicine. for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicine. for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicine.,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicine. were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicine. Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens Synergistic immune response

Treatment strategy for erythropoietic protoporphyria accompanied by severe abdominal pain and liver injury

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Portal Hypertension & Cirrhosis 2024年第1期3卷 36-38页

作者： Xiaoxin Wu Xiumei Zhou Shuai Zhao Keting He Wenxin Zhoudi Shangci Chen Xiaowei Xu State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Centre for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of infectious diseases People's Hospital of Pujiang CountyJinhuaZhejiangChina

To the Editor,Erythropoietic protoporphyria(EPP)is a genetic disease caused by a lack of the enzyme ferrochelatase(FECH)in the heme biosynthesis pathway due to genetic *** deficiency is caused by a deleterious FECH variant in transposition to the frequently occurring hypomorphic allele or by the presence of biallelic pathogenic variants.1 EPP could lead to abnormal production and excretion of protoporphyrin IX,2 causing clinical manifestations such as skin damage and liver injury.3–5.

关键词： liver damage clinical

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian Jiang Yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-Ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang Jiang Yuan Xue Jian Zhang Yi-Huai He department of infectious diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of infectious diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina department of Respiratory medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Intervention Radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina department of Liver diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina department of Digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous ***,its contribution to the progression of liver damage remains *** To determine the role and mechanism of UGT1A1 in liver damage *** We investigated the relationship between UGT1A1 expression and liver injury through clinical ***,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model *** Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic *** suggests that low UGT1A1 levels may be associated with the progression of liver *** mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be *** mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ***1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid *** UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver ***1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

Is medical management useful in Moyamoya disease?

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World Journal of Clinical Cases 2024年第3期12卷 466-473页

作者： Sombat Muengtaweepongsa Vatcharasorn Panpattanakul Center of Excellence in Stroke Division of NeurologyDepartment of MedicineFaculty of MedicineThammasat UniversityRangsit CampusKlonglaung 12120Pathum ThaniThailand division of Neurology Department of Internal MedicineSchool of MedicineUniversity of PhayaoPhayao 56000Thailand

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral *** antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic *** doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic ***,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension ***,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains ***-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and *** protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

关键词： Moyamoya disease Cerebral infarction Antithrombotic management Transcranial doppler Revascularization Intracerebral hemorrhage Antihypertensive intervention Lipid-lowering therapies

Antifungal pipeline:Is there light at the end of the tunnel?

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World Journal of Clinical Cases 2024年第16期12卷 2686-2691页

作者： Georgios Schinas Nikolaos Spernovasilis Karolina Akinosoglou department of medicine University of PatrasPatras 26504Greece department of infectious diseases German Oncology CenterLimassol 4108Cyprus

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms,diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative *** this pressing need for new treatments,the antifungal drug pipeline has been largely stagnant for the past three decades,primarily due to the high risks and costs associated with antifungal drug development,compounded by uncertain market *** research durations,special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to *** response,the“push-pull”incentive model has emerged as a vital strategy to invigorate the pipeline and encourage *** editorial critically examines the current clinical landscape and spotlights emerging antifungal agents,such as Fosmanogepix,Ibrexafungerp,and Olorofim,while also unraveling the multifaceted challenges faced in new antifungal drug *** generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance,but it is premature to declare them as definitive *** future role hinges on thorough clinical validation,costeffectiveness assessments,and continuous post-marketing *** through strategic implementation and integration with market strategies we can transform the landscape of antifungal development,addressing both the resistance crisis and the treatment challenges.

关键词： Antifungals Resistance Fosmanogepix Ibrexafungerp Olorofim

Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

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Journal of Biomedical Research 2024年第3期38卷 269-277页

作者： Kannan Sridharan Shamik Shah Mona Al Hammad Fatima Ali Mohammed Sindhan Veeramuthu Mona Abdulla Taher Mustafa Mohamed Hammad Lamees Jawad Eman Farid department of Pharmacology and Therapeutics College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain department of Nephrology Salmaniya Medical ComplexManamaKingdom of Bahrain department of Internal medicine College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Salmaniya Medical Complex ManamaKingdom of Bahrain department of Laboratory medicine Salmaniya Medical ComplexManamaKingdom of Bahrain department of Microbiology Immunologyand Infectious DiseasesCollege of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for *** creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney ***,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney *** used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 *** observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum *** estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all *** KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 *** observed a significant correlation between serum creatinine and Cys C in our renal transplant ***,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

关键词： KIM-1 cystatin C mycophenolate mofetil tacrolimus everolimus sirolimus cyclosporine

Basic Research Advances in China on Embryo Implantation,Placentation,and Parturition

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Maternal-Fetal medicine 2024年第1期6卷 37-49页

作者： Haili Bao Haibin Wang Fujian Provincial Key Laboratory of Reproductive Health Research Department of Obstetrics and GynecologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for infectious diseases Xiang An Biomedicine LaboratorySchool of MedicineXiamen UniversityXiamen 361102China

This review aimed to summarize the major progress in maternal-fetal medicine.achieved by Chinese scientists in recent *** was systematically searched from January 2020 to November *** that reported the progress in embryo implantation,placentation,and parturition made by Chinese scientists in the last 3 years were *** milestone events during gestation,embryo implantation,endometrial decidualization,placentation,and parturition are pivotal to a successful *** implantation requires intricate interactions between implantation-competent blastocysts and receptive *** adapt to pregnancy,endometrial stromal cells transform into specialized decidual cells,which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in *** embryonic development,the placenta forms to support fetal growth until *** maternal-fetal interface is composed of diverse cell types,including endometrial decidual cells,placental trophoblast cells,endothelial cells,and various immune cells,a sophisticated interplay among which contributes to the maintenance of *** term,the uterus transitions from quiescence to contractility,in preparation for *** to these events lead to pregnancy-related disorders such as repeated implantation failure,recurrent pregnancy loss,preeclampsia,fetal growth restriction,preterm birth,and *** recent years,Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy *** scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine.research in recent years,highlighting future research directions in this field.

关键词： Embryo implantation Decidualization Placentation Maternal-fetal interface Parturition

Concomitant and sequential administration of nirmatrelvir-ritonavir and azvudine in patients with COVID-19 caused by the Omicron variant: Safety and efficacy

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iLABMED 2024年第2期2卷 88-97页

作者： Guang-Bin Chen You-Rou Zheng Yun-Ni Yu Li-Mian Liang Chao Chen Ying-Xia Liu Hong-Zhou Lu department of Clinical Pharmacy Third People's Hospital of ShenzhenShenzhenGuangdongChina National Clinical Research Center for infectious diseases Division of Infectious DiseasesThe Third People's Hospital of ShenzhenShenzhenGuangdongChina

Background:This study assessed the safety and efficacy of nirmatrelvir-ritonavir(Paxlovid®)and azvudine when administered sequentially or concomitantly in patients with coronavirus 2019(COVID-19)caused by the Omicron ***:Ninety-three patients confirmed to be infected with the Omicron variant by nucleic acid detection were retrospectively ***-tion was collected on general health status,medication,and adverse drug reactions(ADRs)according to whether nirmatrelvir-ritonavir and azvudine were administered sequentially or *** on times of onset,clinical manifestations,and outcomes of ADRs and on conversion to a nega-tive nucleic acid test were also ***:Possible ADRs were recorded in 41 patients(44.1%).There were 22 gastrointestinal reactions in 18 patients and 18 hematological abnormalities in 16 after sequential or concomitant treatment with nirmatrelvir-ritonavir and *** enzyme levels increased in nine cases and creatinine clearance decreased in *** of atrial fibrillation(n=1),sleep disorder(n=2),rash(n=2),dizziness(n=1),and weakness(n=5)were also *** vomiting,poor appetite,diarrhea,xerostomia,bitter taste,and rash were considered probable ADRs;others were thought to be possible *** all cases,the nucleic acid test did not turn negative after the first antiviral was *** nucleic acid test of 28 patients did not turn negative before *** remaining 65 patients(69.9%)returned a negative nucleic acid test after receiving the second antiviral ***:Treatment with nirmatrelvir-ritonavir and azvudine is safe and effective whether administered sequentially or concomitantly in patients with COVID-19 caused by the Omicron variant.

关键词： adverse drug reactions azvudine efficacy nirmatrelvir-ritonavir Omicron variant safety

Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2128-2133页

作者： Mi Il Kang Hyeok Chan Kwon division of Rheumatology Department of Internal MedicineDankook University College of MedicineCheonan-si 31116South Korea division of Rheumatology Department of Internal MedicineDankook University HospitalDankook University College of MedicineCheonan-si 31116South Korea

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic inflammatory disease primarily affecting young *** can invade any organ,and various forms of splenic invasion have been *** include splenomegaly and splenic infarction,rupture,and *** study encountered a rare case of splenic involvement,with nodules of various sizes without calcifications or *** SUMMARY A 15-year-old girl presented with arthralgia,weight loss,fever,increased levels of inflammatory markers,and positive antinuclear antibody test *** patient was diagnosed with *** was asymptomatic while taking steroids and *** months after discharge,the patient developed a fever and abdominal *** enteritis was suspected,and abdominopelvic computed tomography(AP-CT)was *** were no specific findings in the gastrointestinal tract,but multiple splenic nodules were *** or hemangioma was considered;however,no specific radiological findings were observed.A biopsy of the spleen was performed to determine the possibility of *** histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic *** on the biopsy results,the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and *** As disease activity increased,multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically *** invasion by SLE can appear in multiple nodular forms and ***,physicians should consider these findings when differentiating these nodules from infections and malignancies.

关键词： Multiple nodules Spleen Splenectomy Systemic lupus erythematosus Differential diagnosis Case report