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Tissue-resident macrophages exacerbate lung injury after remote sterile damage

Cellular & Molecular Immunology 2024年第4期21卷 332-348页

作者： Hanhui Zhong Jingjing Ji Jinling Zhuang Ziying Xiong Pengyun Xie Xiaolei Liu Jundi Zheng Wangli Tian Xiaoyang Hong Jing Tang The Department of Anesthesiology Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdongChina The Department of Critical Care Medicine General Hospital of Southern Theater Command of PLAGuangzhouChina The Department of Respiratory Medicine Guangdong Provincial Hospital of Integrated Chinese and Western MedicineFoshanChina Pediatric Intensive Care Unit Senior Department of Pediatricsthe Seventh Medical Center of PLA General HospitalBeijingChina

Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to ***,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory *** found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or *** findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating *** study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung ***,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.

关键词： tissue-resident macrophage RAGE remote sterile damage

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Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

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Neural Regeneration research 2024年第9期19卷 2075-2080页

作者： Rui Zong Xuemei Li Chunyu Yin Jianfeng He Dekang Zhang Xiangbing Bian Lichao Huang Jiayou Zhou Zhipei Ling Lin Ma Xin Lou Longsheng Pan Xinguang Yu Seniro Department of Neurosurgery The First Medical Center of the PLA General HospitalBeijingChina Clinics of Cadre Department of OutpatientThe First Medical Center of the PLA General HospitalBeijingChina Department of Radiology The First Medical Center of the PLA General HospitalBeijingChina

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential *** 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First medical center of the PLA general *** prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(*** Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local *** 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm *** treatment efficacy was determined using the Clinical Rating Scale for *** was evaluated according to the incidence and severity of adverse *** of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate *** the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as *** most common intraoperative adverse events were nausea and *** most frequent postoperative adverse events were paresthesia and equilibrium *** of the adverse events were mild and usually disappeared within a few *** findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

关键词： efficacy essential tremor magnetic resonance-guided focused ultrasound(MRgFUS) movement disorder safety stereotactic therapy thalamotomy ventral intermediate nucleus

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Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2219-2224页

作者： Wen-Tao Zhong Yuan Lv Qian-Yu Wang Ran An Gang Chen Jun-Feng Du The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of general Surgery The 7^(th)Medical Center of PLA General HospitalBeijing 100700China Department of Pathology The 7^(th)Medical Center of PLA General HospitalBeijing 100700China

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality *** of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and *** SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old *** received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also *** pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

关键词： Rectal cancer Metastasis Chemoradiotherapy Immunotherapy Prognosis Case report

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Small nucleolar RNA and its potential role in the oncogenesis and development of colorectal cancer

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World Journal of Gastroenterology 2024年第2期30卷 115-127页

作者： Yang-Zheng Lan Zheng Wu Wen-Jia Chen Ze-Xuan Fang Xin-Ning Yu Hua-Tao Wu Jing Liu The Breast center Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of general Surgery The First Affiliated Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

Small nucleolar RNAs(snoRNAs)represent a class of non-coding RNAs that play pivotal roles in post-transcriptional RNA processing and modification,thereby contributing significantly to the maintenance of cellular functions related to protein *** have been discovered to possess the ability to influence cell fate and alter disease progression,holding immense potential in controlling human *** is suggested that the dysregulation of snoRNAs in cancer exhibits differential expression across various cancer types,stages,metastasis,treatment response and/or prognosis in *** the other hand,colorectal cancer(CRC),a prevalent malignancy of the digestive system,is characterized by high incidence and mortality rates,ranking as the third most common cancer *** research indicates that snoRNA dysregulation is associated with CRC,as snoRNA expression significantly differs between normal and cancerous ***,assessing snoRNA expression level and function holds promise for the prognosis and diagnosis of ***,current comprehension of the potential roles of snoRNAs in CRC remains *** review offers a comprehensive survey of the aberrant regulation of snoRNAs in CRC,providing valuable insights into the discovery of novel biomarkers,therapeutic targets,and potential tools for the diagnosis and treatment of CRC and furnishing critical cues for advancing research into CRC and the judicious selection of therapeutic targets.

关键词： Small nucleolar RNAs Colorectal cancer Dysregulation Biomarker

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Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China medical research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Department of Pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer *** RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still *** bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and *** evidence suggests a connection between PBs dynamics and cancer *** the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in ***,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient *** MEX3A accelerates malignance and inhibits autophagy of CRC ***,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the ***,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs *** MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC ***,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall *** findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li Xinjuan Fan Zaiyi Liu Department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China guangdong Provincial Key Laboratory of Artificial Intelligence in medical Image Analysis and Application GuangzhouGuangdong 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China medical research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of Clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis *** spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI ***:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation *** facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was *** the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was ***:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,P<0.001)and validation cohort(HR=0.21,95%CI:0.05–0.92,P=0.037).Conclusions:We quantify the spatial distribution of CD3^(+)and CD8^(+)T cells within tissue regions in WSIs using AI *** CD3_(CT) confirmed as a stage-independent predictor for OS in CRC ***,CD3_(CT) shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang Kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong Yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang Clinical Biobank center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in *** designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of *** Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time *** The beta diversities of the NP,NN,and NC groups were all *** comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time *** Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small *** sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

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Functional gastrointestinal disorders,mental health,genetic susceptibility,and incident chronic kidney disease

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Chinese medical Journal 2024年第9期137卷 1088-1094页

作者： Mengyi Liu Panpan He Ziliang Ye Sisi Yang Yanjun Zhang Qimeng Wu Chun Zhou Yuanyuan Zhang Fan Fan Hou Xianhui Qin Division of Nephrology Nanfang HospitalSouthern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologyGuangdong Provincial Key Laboratory of Renal Failure ResearchGuangzhouGuangdong 510515China

Background:Whether functional gastrointestinal disorders(FGIDs)are associated with the long-term risk of chronic kidney disease(CKD)remains *** aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the ***:About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were *** with FGIDs(including irritable bowel syndrome[IBS],dyspepsia,and other functional intestinal disorders[FIDs;mainly composed of constipation])were the exposure group,and non-FGID participants were the non-exposure *** primary outcome was incident CKD,ascertained from hospital admission and death registry records.A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD,and the mediation analysis was performed to investigate the mediation proportions of mental ***:At baseline,33,156(8.0%)participants were diagnosed with FGIDs,including 21,060(5.1%),8262(2.0%),and 6437(1.6%)cases of IBS,dyspepsia,and other FIDs,*** a mean follow-up period of 12.1 years,11,001(2.6%)participants developed *** were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs(hazard ratio[HR],1.36;95%confidence interval[CI],1.28-1.44).Similar results were observed for IBS(HR,1.27;95%CI,1.17-1.38),dyspepsia(HR,1.30;95%CI,1.17-1.44),and other FIDs(HR,1.60;95%CI,1.43-1.79).Mediation analyses suggested that the mental health score significantly mediated 9.05%of the association of FGIDs with incident CKD and 5.63-13.97%of the associations of FGID subtypes with ***,the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of ***:Participants with FGIDs had a higher risk of incident CKD,which was partly explained by mental health scores and was more pronounced in those with high gen

关键词： Functional gastrointestinal disorders Chronic kidney diseases Genetic susceptibility Mental health

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Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the Second medical center of the PLA general hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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Safety,immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly:a prospective longitudinal study

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2738-2747页

作者： Hong-Hong Liu Yunbo Xie Bao-Peng Yang Huan-Yue Wen Peng-Hui Yang Jin-E Lu Yan Liu Xi Chen Meng-Meng Qu Yang Zhang Wei-Guo Hong Yong-Gang Li Junliang Fu Fu-Sheng Wang Out-patient Department of Day Diagnosis and Treatment The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Senior Department of Infectious Diseases The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China Chinese PLA medical School Chinese PLA General HospitalBeijing 100039China Hunyuan County People’s hospital Datong 037499 Shanxi ProvinceChina Faculty of Hepato-Pancreato-Biliary Surgery Institute of Hepatobiliary SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China

The safety and efficacy of COVID-19 vaccines in the elderly,a high-risk group for severe COVID-19 infection,have not been fully *** clarify these issues,this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety,immunogenicity,and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine *** results showed that this vaccination protocol was safe and tolerable in the *** administering two doses of the BBIBP-CorV,the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young *** the ZF2001 booster dose,the antibody-positive rates in the elderly were comparable to those in the young;however,the antibody titers remained ***,age,and underlying diseases were independently associated with vaccine immunogenicity in elderly *** pseudovirus neutralization assay showed that,compared with those after receiving two doses of BBIBP-CorV priming,some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 *** infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection *** antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the *** data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

关键词： vaccination vaccine doses

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