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World Journal of Hepatology 2024年第2期16卷 126-134页

作者： Dmitry Victorovich Garbuzenko department of Faculty Surgery South Ural State Medical UniversityChelyabinsk 454092Russia

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

关键词： Liver cirrhosis Portal hypertension Gastroesophageal variceal bleeding Prevention Management

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

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Oncology Research 2024年第5期32卷 831-847页

作者： EFFAT ALEMZADEH LEILA ALLAHQOLI AFROOZ MAZIDIMORADI ESMAT ALEMZADEH FAHIMEH GHASEMI HAMID SALEHINIYA IBRAHIM ALKATOUT Infectious Diseases Research Center Birjand University of Medical SciencesBirjandIran department of Midwifery Ministry of Health and Medical EducationTehranIran Student Research Committee Shiraz University of Medical SciencesShirazIran department of Biotechnology Faculty of MedicineBirjand University of Medical SciencesBirjandIran Cellular and Molecular Research Center Birjand University of Medical SciencesBirjandIran Social Determinants of Health Research Center Birjand University of Medical SciencesBirjandIran Kiel School of Gynaecological Endoscopy Campus KielUniversity Hospitals Schleswig-HolsteinKielGermany

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

关键词： Chemotherapy Drug resistance mechanisms Ovarian cancer PARP inhibitors VEGF inhibitor

Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model

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Zoological Research 2024年第1期45卷 108-124页

作者： Huanpeng Lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang Xiaowen Huang Xi Chen Haishan Jiang Shaogang Qu Xueqing Xu department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence GuangzhouGuangdong 510515China Key Laboratory of Mental Health of the Ministry of Education Southern Medical UniversityGuangzhouGuangdong 510515China department of Dermatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China department of Neurology Ganzhou Hospital-Nanfang HospitalSouthern Medical UniversityGanzhouJiangxi 341001China

Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关键词： Cath-KP Peptide Parkinson’s disease Oxidative stress Neuroprotection

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

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Acta Pharmaceutica Sinica B 2024年第1期14卷 365-377页

作者： Dandan Ling Xueli Jia Ke Wang Qiucheng Yan Bochuan Yuan Lina Du Miao Li Yiguang Jin Anhui medical University Hefei 230032China department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer drugs.Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response syndrome.Here,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung cancer.The preparation processes were simple,only involving film formation,electroporation,and pore extrusion.LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells.In the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its precursors.Moreover,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the lung.LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

关键词： Apoptosis Bacterial ghost Cancer cell membrane Immune stimulation Liposome Lung targeting Metastatic lung cancer Paclitaxel

Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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Chinese Journal of Natural Medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China State Key Laboratory of medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs Cytoskeleton ECM deposition

A risk assessment method considering risk attributes and work safety informational needs and its application

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Chinese Journal of Chemical Engineering 2024年第4期68卷 253-262页

作者： Cong Luo Yunsheng Zhao Ke Xu School of Political Science and Public administration Shandong UniversityQingdao 266200China Faculty of Engineering China University of GeosciencesWuhan 430074China department of Emergency Management of Hubei Province Wuhan 430064China

The technological revolution has spawned a new generation of industrial systems,but it has also put forward higher requirements for safety management accuracy,timeliness,and systematicness.Risk assessment needs to evolve to address the existing and future challenges by considering the new demands and advancements in safety management.The study aims to propose a systematic and comprehensive risk assessment method to meet the needs of process system safety management.The methodology first incorporates possibility,severity,and dynamicity(PSD)to structure the“51X”evaluation indicator system,including the inherent,management,and disturbance risk factors.Subsequently,the four-tier(risk point-unit-enterprise-region)risk assessment(RA)mathematical model has been established to consider supervision needs.And in conclusion,the application of the PSD-RA method in ammonia refrigeration workshop cases and safety risk monitoring systems is presented to illustrate the feasibility and effectiveness of the proposed PSD-RA method in safety management.The findings show that the PSD-RA method can be well integrated with the needs of safety work informatization,which is also helpful for implementing the enterprise's safety work responsibility and the government's safety supervision responsibility.

关键词： Risk assessment Safey “51X”evaluation indicator system Four-tier risk assessment model Risk attributes Process system

New progress of small-molecule drugs in the treatment of inflammatory bowel disease

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Chinese medical Journal 2024年第5期137卷 556-558页

作者： Dongying Yao Zhihua Ran department of Gastroenterology Zhou Pu Hospital affiliated to Shanghai University of Health&Medical SciencesShanghai 201318China

With the advent of small-molecule drugs,treatment of inflammatory bowel disease(IBD)has reached a new stage.In contrast to biologics,small-molecule drugs can be made into oral dosage forms with a short half-life and are suitable for administration 1–2 times a day.Small-molecule drugs work by inhibiting the transmission of key intracellular signaling pathways in the pathogenesis of ulcerative colitis(UC)and Crohn’s disease(CD)[Figure 1].They do not induce anti-drug antibodies in patients or lead to loss of response after treatment.

关键词： drugs treatment inflammatory

Influence of Irregular Coastlines on a Tornadic Mesovortex in the Pearl River Delta during the Monsoon Season. Part Ⅰ:Pre-storm Environment and Storm Evolution

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Advances in Atmospheric Sciences 2024年第6期41卷 1115-1131页

作者： Lanqiang BAI Dan YAO Zhiyong MENG Yu ZHANG Xianxiang HUANG Zhaoming LI Xiaoding YU Foshan Tornado Research Center and China Meteorological Administration Tornado Key LaboratoryGuangdong Meteorological Serviceand Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Guangdong 528000China Meteorological Observation Centre CMABeijing 100081China department of Atmospheric and Oceanic Sciences and China Meteorological Administration Tornado Key LaboratorySchool of PhysicsPeking UniversityBeijing 100871China Guangzhou Meteorological Observatory CMAGuangdong 511430China Foshan Tornado Research Center and China Meteorological Administration Tornado Key LaboratoryCMAGuangdong 528000China China Meteorological administration Training Center CMABeijing 528000China

The Pearl River Delta(PRD),a tornado hotspot,forms a distinct trumpet-shaped coastline that concaves toward the South China Sea.During the summer monsoon season,low-level southwesterlies over the PRD’s sea surface tend to be turned toward the west coast,constituting a convergent wind field along with the landward-side southwesterlies,which influences regional convective weather.This two-part study explores the roles of this unique land–sea contrast of the trumpet-shaped coastline in the formation of a tornadic mesovortex within monsoonal flows in this region.Part I primarily presents observational analyses of pre-storm environments and storm evolutions.The rotating storm developed in a lowshear environment(not ideal for a supercell)under the interactions of three air masses under the influence of the land–sea contrast,monsoon,and storm cold outflows.This intersection zone(or“triple point”)is typically characterized by local enhancements of ambient vertical vorticity and convergence.Based on a rapid-scan X-band phased-array radar,finger-like echoes were recognized shortly after the gust front intruded on the triple point.Developed over the triple point,they rapidly wrapped up with a well-defined low-level mesovortex.It is thus presumed that the triple point may have played roles in the mesovortex genesis,which will be demonstrated in Part II with multiple sensitivity numerical simulations.The findings also suggest that when storms pass over the boundary intersection zone in the PRD,the expected possibility of a rotating storm occurring is relatively high,even in a low-shear environment.Improved knowledge of such environments provides additional guidance to assess the regional tornado risk.

关键词： tornado mesovortex surface boundary land–sea contrast monsoon

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 228-238页

作者： Yu-Ze Zhao Xue-Ning Zhang Yi Yin Pei-Lun Xiao Meng Gao Lu-Ming Zhang Shuan-Hu Zhou Shu-Na Yu Xiao-Li Wang Yan-Song Zhao department of Ophthalmology Affiliated Hospital of Weifang Medical UniversityWeifang 261031Shandong ProvinceChina School of medical Imaging Weifang Medical UniversityWeifang 261053Shandong ProvinceChina department of Anatomy Weifang Medical UniversityWeifang 261053Shandong ProvinceChina departments of Orthopedic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

关键词： retinal diseases retinal ischemia—reperfusion injury N-acetylserotonin high mobility group box 1 receptor for advanced glycation end-products nuclear factor-κB rats

Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

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Biosafety and Health 2024年第1期6卷 28-34页

作者： Xiaoliang Li Xizhu Xu Jichen Li Huanhuan Lu Congcong Wang Rui Wang Jinbo Xiao Ying Liu Yang Song Jingdong Song Qiang Sun Yong Zhang department of Public Health and Health administration Shandong First Medical UniversityJinan 250117China National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Polio Laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosafetyNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China department of medical Microbiology Weifang Medical UniversityWeifang 261053China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

关键词： Coxsackievirus A6 D3 genotype Virus‐like particle Immunoprotective effect