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Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3507-3518页

作者： Si Chen Zhengyuan Zhang Qian Wang Qi Yang Li Yin Lishan Ning Zhilong Chen Jielin Tang Weiqi Deng Ping He Hengchun Li Linjing Shi yjun Deng Zijian Liu Hemeng Bu Yaohui Zhu Wenming Liu Linbing Qu Ligiang Feng Xiaoli Xiong Baoqing Sun Nanshan Zhong Feng Li ingchao Li Xinwen Chen Ling Chen guangzhou Institute of Infectious Disease Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina guangzhou National Laboratory GuangzhouChina State Key Laboratory of Respiratory Disease Center for Cell Lineage ResearchGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Xiamen United Institute of Respiratory Health XiamenChina

The upper respiratory tract is the initial site of SARS-CoV-2.*** spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough *** report that intranasal vaccination using human adenovirus serotype 5(Ad5)vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing slgA in the nasal *** slgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40%of total proteins in nasal mucosal lining fluids(NMLFs).A low-level IgG could also be detected in NMLFs but not IgM,IgD,and *** a complete nasal wash,slgA in the nasal passage could be replenished rapidly within a few hours.A comparison of purified paired serum IgA,serum IgG,and nasal slgA from the same individuals showed that slgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron *** IgG and IgA failed to neutralize XBB and BA.2.86,while nasal slgA retained potent neutralization against these newly emerged *** analysis showed that slgA Was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2.mice from XBB *** a slgA monoclonal antibody as a reference,we estimated that the total nasal slgA contains about 2.6-3.9%spikespecific slgA in NMLFs collected approximately one month after intranasal *** study provided insights for developing intranasal vaccines that can induce slgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

关键词： nasal antibodies neutral

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PD-L1-driven efficient enrichment and elimination of circulating cancer cells by magnetic MoSe_(2. nanosheet

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Nano Research 2024年第5期17卷 4350-4358页

作者： Hongjie Huang Binhua Zou Shanlin Zhu Xingchen Zhang Jiale Huang Jinlin Wang Xiaoling Li Tianfeng Chen The Sixth Affiliated hospital Jinan UniversityDongguan 523566China Department of Chemistry Institute of Food Safety and NutritionJinan UniversityGuangzhou 510632China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Pulmonary and Critical Care Medicine Guangzhou Institute of Respiratory HealthNational Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineState Key Laboratory of Respiratory DiseasesThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer *** presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer ***,magnetic MoSe_(2. nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing *** summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.

关键词： circulating tumor cells selenide photothermal therapy(PTT) natural killer(NK)cell immunotherapy

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Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies

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Cancer Biology & Medicine 2024年第6期21卷 445-450页

作者： Hanhao Zheng Daiyin Liu Zhicong Liu Mingjie An Yuming Luo Changhao Chen Tianxin Lin Department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510003China Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalState Key Laboratory of Oncology in South ChinaGuangzhou 510003China Department of general Surgery Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510003China

Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.

关键词： metastasis lymphatic landscape

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Hematochezia due to rectal invasion by an internal iliac artery aneurysm: A case report

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World Journal of Clinical Cases 2024年第11期12卷 1980-1989页

作者： Fang Li Bin Zhao Yong-Qiang Liu Guo-Qing Chen Rong-Feng Qu Chao Xu Zhui Long Jin-Song Wu Mao Xiong Wei-Hang Liu Li Zhu Xiao-Ling Feng Lei Zhang Department of general Surgery Chongqing General HospitalChongqing 401147China

BACKGROUND This case report presents the rare occurrence of hematochezia due to an internal iliac artery aneurysm leading to an arterioenteric fistula,expanding the differential diagnosis for gastrointestinal *** emphasizes the importance of considering vascular origins in cases of atypical hematochezia,particularly in the absence of common gastrointestinal causes,and highlights the role of imaging and multidisciplinary management in diagnosing and treating such unusual *** SUMMARY A 75-year-old man with a history of hypertension presented with 12.d of hematochezia,experiencing bloody stools 7-8 times per *** computed tomography(CT)scans revealed an aneurysmal rupture near the right internal iliac artery with suspected hematoma *** levels progressively decreased to 7 g/*** arterial angiography and iliac arterycovered stent placement were performed,followed by balloon *** initial stabilization,minor rectal bleeding and abdominal pain persisted,leading to further diagnostic *** identified a neoplasm and potential perforation at the proximal *** exploratory laparotomy confirmed the presence of a hematoma and an aneurysm invading the rectal wall,necessitating partial rectal resection,intestinal anastomosis,and *** recovery was successful,with no further bleeding incidents and normal follow-up CT and colonoscopy results after six *** In cases of unusual gastrointestinal bleeding,it is necessary to consider vascular causes for effective diagnosis and intervention.

关键词： Iliac artery aneurysm Hematoma Rectum Hematochezia Case report

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Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte Chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei Chen Ming Zhou Wenjian Mo Caixia Wang Qinghua Cai Yumiao Li Ruiqing Zhou Shilin Xu Wei Zhou Tingfen Deng Shiyi Pan Yanli Xu Shunqing Wang Yuping Zhang Department of Hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon

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Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades

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World Journal of Diabetes 2024年第7期15卷 1627-1644页

作者： Jian-Ping Wen Shuan-Ji Ou Jia-Bao Liu Wei Zhang Yu-Dun Qu Jia-Xuan Li Chang-Liang Xia Yang Yang Yong Qi Chang-Peng Xu Department of Orthopaedics The Affiliated Guangdong Second Provincial General Hospital of Jinan UniversityGuangzhou 510000Guangdong ProvinceChina The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Diabetic foot ulcers(DFUs)are one of the most severe and popular complications of *** persistent non-healing of DFUs is the leading cause of amputation,which causes significant mental and financial stress to patients and their *** are critical cells in wound healing and perform essential roles in all phases of wound ***,no studies have been carried out to systematically illustrate this area from a scientometric point of *** there have been some bibliometric studies on diabetes,reports focusing on the investigation of macrophages in DFUs are *** To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related *** The publications of macrophage-related DFUs from January 1,2.04,to December 31,2.2.,were retrieved from the Web of Science Core Collection on January 9,*** different analytical tools:VOSviewer(v1.6.19),CiteSpace(v6.2.R4),HistCite(v12.03.07),and Excel 2.2. were used for the scientometric *** A total of 330 articles on macrophage-related DFUs were *** most published countries,institutions,journals,and authors in this field were China,Shanghai Jiao Tong University of China,Wound Repair and Regeneration,and Aristidis *** the analysis of keyword co-occurrence networks,historical direct citation networks,thematic maps,and trend topics maps,we synthesized the prevailing research hotspots and emerging trends in this *** Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

关键词： Diabetic foot ulcers Macrophage Macrophage polarization Bibliometrics Wound healing Inflammation

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Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

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World Journal of Gastroenterology 2024年第10期30卷 1461-1465页

作者： Efstathios T Pavlidis Ioannis N Galanis Theodoros E Pavlidis 2.(nd) Propedeutic Department of Surgery Hippokration General HospitalSchool of MedicineAristotle University of ThessalonikiThessaloniki 54642Greece

Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and *** advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment *** imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and *** intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant *** balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk *** of the bile duct is more aggressive;thus,early diagnosis and surgery are *** conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

关键词： Biliary tree diseases Pancreatic cystic neoplasms Biliary tract neoplasms Extrahepatic cholangiocarcinoma Pancreatic adenocarcinoma

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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao general Surgery Center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 72. patients with primary LT between January 2.15 and December 2.2.. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 72. patients, 2.(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2.. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2., and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872.and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model Liver transplantation

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FGF7 enhances the expression of ACE2.in human islet organoids aggravating SARS-CoV-2.infection

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2260-2274页

作者： Hao Meng Zhiying Liao Yanting Ji Dong Wang Yang Han Chaolin Huang Xujuan Hu Jingyi Chen Hengrui Zhang Zonghong Li Changliang Wang Hui Sun Jiaqi Sun Lihua Chen Jiaxiang Yin Jincun Zhao Tao Xu Huisheng Liu School of Biomedical Engineering Guangzhou Medical UniversityGuangzhou 511495 GuangdongChina guangzhou National Laboratory Guangzhou 510320 GuangdongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Center for Translational Medicine Wuhan Jinyintan HospitalWuhan 430023 HubeiChina School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou 510006 GuangdongChina

The angiotensin-converting enzyme 2.ACE2.is a primary cell surface viral binding receptor for SARS-CoV-2.so finding new regulatory molecules to modulate ACE2.expression levels is a promising strategy against *** the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2.expression within the islets,facilitating SARS-CoV-2.infection and resulting in impaired insulin *** hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2.FGFR2.and FGFR1 to upregulate ACE2.expression predominantly inβ*** upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2.*** FGFR counteracts the FGF7-induced ACE2.upregulation,subsequently reducing viral infection and replication in the ***,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild ***,animal experiments indicated that SARS-CoV-2.infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in *** together,our research offers a potential regulatory strategy for ACE2.by controlling FGF7,thereby protecting islets from SARS-CoV-2.infection and preventing the progression of diabetes in the context of COVID-19.

关键词： ACE2 FGF7 islet

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Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through b-catenin/CREB interruption

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4118-4133页

作者： Mengyi Yan Xiayun Chen Xiaotong Li Qianqian Liu Baixue Yu Yi Cen Wei Zhang Yibin Liu Xinxuan Li Ying Chen Tao Wang Shiying Li The Fifth Affiliated hospital Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacologythe NMPA and State Key Laboratory of Respiratory Diseasethe School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China Department of Anesthesiology the Second Clinical School of Guangzhou Medical UniversityGuangzhou 511436China State Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular DiseasesGuangzhou Institute of Respiratory Healththe first Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China Department of Pulmonary and Critical Care Medicine Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional *** this work,a transferrin receptor(TfR)targeted immunostimulant(PTI)is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting b-catenin signal *** synthesize PTI,the photosensitizer conjugated TfR targeting peptide moiety(Palmitic-K(PpIX)-HAIYPRH)is unitized to encapsulate the transcription interrupter of *** the one hand,the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumorassociated *** the other hand,PTI will interrupt the binding between b-catenin andcAMP response element-binding protein(CREB),regulating the gene transcription to downregulate programmed death ligand 1(PD-L1)while upregulating CeC motif chemokine ligand 4(CCL4).Furthermore,the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration,and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung *** work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

关键词： Transferrin receptor b-Catenin signal pathway Tumor targeting Photodynamic therapy Immunotherapy Immunogenic cell death Programmed death ligand 1

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