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Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 135-146页

作者： Sujie Huang Yuxuan gao ling Ma Bo jia Wenhao Zhao Yufan Yao Wenyuan Li Tongyi lin Rui Wang Jingjing Song Wei Zhang Institute of Pharmacology School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China Key Laboratory of Preclinical Study for New Drugs of gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China State Key Laboratory of Veterinary Etiological Biology College of Veterinary MedicineLanzhou UniversityLanzhou 730000China Lanzhou University Second Hospital Lanzhou UniversityLanzhou 730000China

Melittin,a classical antimicrobial peptide,is a highly potent antitumor ***,its significant toxicity seriously hampers its application in tumor *** this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with *** conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic ***,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the ***-AAM-1 significantly suppressed melanoma growth in vivo with relatively low ***,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.

关键词： Antimicrobial peptide Peptide-drug conjugate Cell-penetrating activity Membrane disruption Antitumor activity

Multimodal abnormalities of brain structures in adolescents and young adults with major depressive disorder:An activation likelihood estimation meta-analysis

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World Journal of Psychiatry 2024年第7期14卷 1106-1117页

作者： Yan-Ping Shu Qin Zhang Yong-Zhe Hou Shuang Liang Zu-Li Zheng jia-lin Li gang Wu Department of Psychiatry of Women and Children The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Guizhou Provincial People’s HospitalGuiyang 550000Guizhou ProvinceChina Medical Humanities College Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

BACKgROUND Major depressive disorder(MDD)in adolescents and young adults contributes significantly to global morbidity,with inconsistent findings on brain structural changes from structural magnetic resonance imaging *** likeli-hood estimation(ALE)offers a method to synthesize these diverse findings and identify consistent brain *** We performed a comprehensive literature search in PubMed,Web of Science,Embase,and Chinese National Knowledge Infrastructure databases for neuroi-maging studies on MDD among adolescents and young adults published up to November 19,*** independent researchers performed the study selection,quality assessment,and data *** ALE technique was employed to synthesize findings on localized brain function anomalies in MDD patients,which was supplemented by sensitivity *** Twenty-two studies comprising fourteen diffusion tensor imaging(DTI)studies and eight voxel-based morphome-try(VBM)studies,and involving 451 MDD patients and 465 healthy controls(HCs)for DTI and 664 MDD patients and 946 HCs for VBM,were ***-based ALE demonstrated significant reductions in fractional anisotropy(FA)values in the right caudate head,right insula,and right lentiform nucleus putamen in adolescents and young adults with MDD compared to HCs,with no regions exhibiting increased FA ***-based ALE did not demonstrate significant alterations in gray matter *** analyses highlighted consistent findings in the right caudate head(11 of 14 analyses),right insula(10 of 14 analyses),and right lentiform nucleus putamen(11 of 14 analyses).CONCLUSION Structural alterations in the right caudate head,right insula,and right lentiform nucleus putamen in young MDD patients may contribute to its recurrent nature,offering insights for targeted therapies.

关键词： Major depressive disorder Adolescent Young adults Neuroimaging Diffusion tensor imaging Voxel-based morphometry Activation likelihood estimation Meta-analysis

Analysis of plant resources and diversity in the southeast area of Taihang Mountains

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Asian Journal of Traditional Medicines 2024年第2期19卷 88-98页

作者： Junpeng lin Jingming jia Anhua Wang School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of Functional Food and Wine Shenyang Pharmaceutical UniversityShenyang 110016China

Taihang Mountains are situated between Shanxi Province and the North China Plain,spanning Beijing,Hebei,Shanxi,and Henan provinces and *** mountains extend from northeast to southwest for over 400 km,naturally deviding the second step from the third one in *** southeastern area of Taihang Mountains specifically refers to Changzhi City and Jincheng Administrative Region of Shanxi *** Shanxi Province’s robust development plans for the southeast area of Taihang Mountains,the medicinal plant resources in this area will be ***,it is imperative and urgent to conduct a comprehensive investigation and study on the medicinal plant resources in the southeast area of Taihang *** means of field investigation,literature review,and specimen identification,the plant resources and diversity of two counties in the southeast of Taihang Mountains were *** findings revealed 234 plants species across 172 genera in 70 families,primarily comprising *** families with more species included Compositae,Leguminosae,Rosaceae,Labiatae,*** the genera,those with more species were Cynanchum,Selaginella,Clematis,Thalictrum,and Rhamnus.A total of 114 medicinal plants were identified,constituting 48.72%of the *** medicinal parts,the concentration is in roots and rhizomes,followed by whole plants and *** the basis of investigation and study,some suggestions on the development,utilization,and protection of medicinal plant resources in southeast Taihang Mountains were *** suggestions provide valuable insights for the study on medicinal plant resources and vegetation in the southeast of Taihang Mountains,serving as a scientific basis for the protection and sustainable utilization of wild medicinal plant resources.

关键词： plant resources diversity medicinal use protection and utilization Taihang Mountains

Laryngopharyngeal reflux disease:Updated examination of mechanisms,pathophysiology,treatment,and association with gastroesophageal reflux disease

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World Journal of gastroenterology 2024年第16期30卷 2209-2219页

作者： Na Cui Ting Dai Yang Liu Ya-Yu Wang jia-Yu lin Qing-Fan Zheng Dong-Dong Zhu Xue-Wei Zhu Department of Otorhinolaryngology Head and Neck Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Ultrasound China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of gastroenterology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina

Laryngopharyngeal reflux disease(LPRD)is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the *** commonly presents with symptoms such as hoarseness,cough,sore throat,a feeling of throat obstruction,excessive throat *** complex condition is thought to involve both reflux and reflex mechanisms,but a clear understanding of its molecular mechanisms is still ***,there is no standardized diagnosis or treatment *** strategies for LPRD mainly include lifestyle modifications,proton pump inhibitors and endoscopic *** paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms,pathophysiology and treatment of *** also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

关键词： Laryngopharyngeal reflux gastroesophageal reflux Head neck surgery Laryngitis Otolaryngology

Optimization of tracheoesophageal fistula model established with Tshaped magnet system based on magnetic compression technique

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World Journal of gastroenterology 2024年第16期30卷 2272-2280页

作者： Miao-Miao Zhang jian-Qi Mao lin-Xin Shen Ai-Hua Shi Xin Lyu jia Ma Yi Lyu Xiao-Peng Yan Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Shaanxi Provincial Key Laboratory of Magnetic Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Zonglian College Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Pulmonary and Critical Care Medicine The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of Surgical Oncology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKgROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model *** designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal *** To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle *** Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under *** time,operation success rate,and accidental injury were *** operation,the presence and timing of cough and the time of magnet shedding were *** in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were *** in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were *** size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome *** The operation success rate was 100%for both *** time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the *** the early postoperative period,all dogs ate freely and were generally in good *** in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF *** specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed s

关键词： Magnetic surgery Magnetic compression technique Tracheoesophageal fistula Magnet Animal model Beagles

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

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World Journal of gastroenterology 2024年第4期30卷 318-331页

作者： Yu-Zhe Cao guang-Lei Zheng Tian-Qi Zhang Hong-Yan Shao jia-Yu Pan Zi-lin Huang Meng-Xuan Zuo Department of Minimally Invasive Interventional Therapy Sun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive Interventional Therapy State Key Laboratory of Oncology in South ChinaGuangzhou 510060Guangdong ProvinceChina Department of Minimally Invasive Interventional Therapy Guangdong Provincial Clinical Research Center for CancerGuangzhou 510060Guangdong ProvinceChina

BACKgROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating ***,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are *** To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world *** Several electronic databases were searched to identify eligible randomized controlled trials for this ***-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were *** was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April *** score matching(PSM)was performed to balance the bias between the *** Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the *** A total of 13 randomized controlled trials were *** alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the *** triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,Pgreater incidence of adverse events(94.3%vs 75.4%,Pggests that HAIC-based treatments are likely to be the best choice for *** findings confirm that triple therapy is more effective for uHCC patients than AIPB.

关键词： Unresectable hepatocellular carcinoma Hepatic arterial infusion chemotherapy Angiogenesis inhibitors Programmed cell death protein 1 Programmed death ligand 1

Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics

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Journal of Integrative Medicine 2024年第5期22卷 588-599页

作者： Wei-wei jia Hua-wei lin Min-guang Yang Ya-ling Dai Yan-yi Ding Wen-shan Xu Si-nuo Wang Ya-jun Cao Sheng-xiang Liang Zhi-fu Wang Cong Chen Wei-lin Liu College of Rehabilitation Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina The Institute of Rehabilitation Industry Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina Traditional Chinese Medicine Rehabilitation Research Center of State Administration of Traditional Chinese Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122Fujian ProvinceChina

Objective Studies have shown that electroacupuncture(EA)can alleviate cognitive impairments from Alzheimer’s disease(AD)by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK),but the specific mechanism involved remains to be ***,this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial *** The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKα1-subunit conditional knockout(AMPKα1-cKO)were used for *** evaluate the effects of EA treatment on cognitive function,the T-maze and Morris water maze were *** addition,chemical exchange saturation transfer,thioflavin staining,transmission electron microscopy,mitochondrial membrane potential,and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 *** Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory *** of the AMPK/peroxisome proliferator-activated receptor-γcoactivator-1α(PgC-1α)pathway increased pathological amyloid-β(Aβ)deposition and aggravated the dysfunction in mitochondrial *** addition,EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PgC-1αpathway,specifically by reducing pathological Aβdeposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission ***,the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 *** The regulation of hippocampal mitochondrial dynamics and reduction in Aβdeposition via the AMPK/PgC-1αpathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

关键词： Adenosine monophosphate-activated protein kinase Alzheimer’s disease Cognitive impairment Electroacupuncture Hippocampus Mitochondrial dynamics

Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

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World Journal of gastroenterology 2024年第15期30卷 2128-2142页

作者： gui-Xiang Qian Zi-ling Xu Yong-Hai Li jian-lin Lu Xiang-Yi Bu Ming-Tong Wei Wei-Dong jia Department of Hepatic Surgery Anhui Provincial HospitalThe First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Hepatic Surgery Anhui Provincial Hospital Affiliated to Anhui Medical UniversityAnhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Anorectal Surgery the First People’s Hospital of HefeiHefei 230001Anhui ProvinceChina

BACKgROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of *** To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of *** In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were *** feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination ***-radiologic features were selected through univariate and multivariate logistic regression *** machine learning methods were used for model comparison,aiming to identify the optimal *** model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve ***,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient *** Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic *** the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of *** K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’*** The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with *** K-M curves assessing OS revealed statistically significant differences.

关键词： Machine learning Radiomics Hepatocellular carcinoma Cirrhosis Early recurrence Overall survival Computed tomography Prognosis Risk factor Delta-radiomics

Slc43a2^(+)T cell metastasis from spleen to brain in RgNNV infected teleost

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Science China(Life Sciences) 2024年第4期67卷 733-744页

作者： Qing Wang Yali Liu Minlin Zhang Min Yang jiantao Liang Xiaoling Zuo Shaowen Wang Xianze jia Huihong Zhao Han jia.g Qiang lin Qiwei Qin College of Marine Sciences South China Agricultural UniversityGuangzhou 510642China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China Nansha-South China Agricultural University Fishery Research Institute Guangzhou 511457China Joint University Laboratory of guangdong Province Hong Kong and Marco Region on Marine Bioresource Conservation and ExploitationGuangzhou 510642China University of Chinese Academy of Sciences Beijing 100101China

The origin of T cells in the teleost's brain is *** viewing the central nervous system(CNS)as immune privileged has been widely accepted,previous studies suggest that T cells residing in the thymus but not in the spleen of the teleost play an essential role in communicating with the peripheral ***,we identified nine T cell subpopulations in the thymus and spleen of orange-spotted grouper(Epinephelus coioices)through single-cell RNA-sequencing *** viral CNS infection with red-spotted grouper nervous necrosis virus(RgNNV),the number of slc43a2^(+)T cells synchronously increased in the spleen and *** the infection tests in asplenic zebrafish(tlx1^▲zebrafish model),no increase in the number of slc43a2^(+)T cells was observed in the ***-cell transcriptomic analysis indicated that slc43a2^(+)T cells mature and functionally differentiate within the spleen and then migrate into the brain to trigger an immune *** study suggests a novel route for T cell migration from the spleen to the brain during viral infection in fish.

关键词： central nervous system slc43a2^(+)T cell RgNNV T cell migration teleost