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Treg Immunomodulation Contributes to the Anti-atherosclerotic Effects of Huxin Formula in ApoE^(-/-)Mice

Chinese Journal of Integrative medicine 2024年第10期30卷 896-905页

作者： OU Xiao-min CAI Jing HU Xiao-yue ZENG Qiao-huang LAN Tao-hua JIANG Wei The Second Clinical College of Guangzhou University of Chinese medicine Guangzhou510405China Department of Cardiology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510020China guangdong provincial Key Laboratory of Chinese medicine for Prevention and Treatment of Refractory Chronic Diseases Guangzhou510020China

Objective:To explore the effects of Huxin formula(HXF)in curtailing atherosclerosis and its underlying ***:According to random number table method,24 specific pathogen free male ApoE^(-/-)mice were randomly divided into model group,HXF low-dose(HXF-L)group(8.4 g/kg daily),HXF high-dose(HXF-H)group(16.8 g/kg daily),and pravastatin(8 mg/kg daily)group in ExperimentⅠ(n=6 per group).C57BL/6J mice served as the control group(n=6).ApoE^(-/-)mice in HXF-L,HXF-H,pravastatin groups were fed a Western diet and administered continuously by gavage for 12 weeks,while C57BL/6J mice in the control group were fed conventional lab mouse chow for 12 ***,Tregs were depleted by weekly intraperitoneal injection of purified anti-mouse CD25 antibody(PC61,250μg per mouse)for 4 weeks in ExperimentⅡ(n=6 per group).Oil Red O and Masson staining were used to evaluate the plaque area and aortic root *** CD4^(+)CD25^(+)Foxp3^(+)Treg counts in the lymph nodes and spleen cells were detected using flow cytometric *** transforming growth factor-β1(TGF-β1),interleukin(IL)-10,and IL-6 serum levels were examined by MILLIPLEX?MAP *** real-time reverse transcription PCR(qRT-PCR)and Western blot were utilized to assess the expression of TGF-βmRNA and protein in the *** expression of CD4^(+)T lymphocytes,macrophages and smooth muscle cells in the aortic root were detected by immunofluorescence ***:HXF reduced plaque area in ApoE^(-/-)mice(P0.05).Also,HXF upregulated the expression of TGF-βmRNA and protein in the aorta(P<0.05).Additionally,HXF attenuated CD4^(+)T lymphocytes,macrophages and smooth muscle cells in aortic root plaque(P<0.01).Furthermore,the depletion of Tregs with CD25

关键词： atherosclerosis Huxin Formula Tregs immune responses inflammation

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Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions,MET exon skipping or de novo MET amplification

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Frontiers of medicine 2024年第4期18卷 735-743页

作者： Rui Fu Yuanyuan Xiong Miao Cai Fang Li Rongrong Chen Yilong Wu Wenzhao Zhong School of medicine South China University of TechnologyGuangzhou510006China guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou510080China Geneplus-Beijing Beijing102206China

Gene fusions and MET alterations are rare and difficult to detect in plasma *** clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains *** prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET *** analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,*** MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,*** with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET *** with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

关键词： ctDNA molecular residual disease operable NSCLC gene fusion MET exon skipping MET amplification

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Tissue-resident macrophages exacerbate lung injury after remote sterile damage

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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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Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma

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Frontiers of medicine 2024年第4期18卷 708-720页

作者： Fan Zou Jialiang Wei Jialang Zhuang Yafang Liu Jizhou Tan Xianzhang Huang Ting Liu guangdong Cardiovsacular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical ScienceGuangzhou510080China The Second Clinical Medical College Guangzhou University of Chinese MedicineDepartment of Laboratory Medicine/State Key Laboratory of Traditional Chinese Medicine SyndromeGuangdong Provincial Hospital of Chinese MedicineGuangzhou510120China Department of Medical Oncology The First Affiliated Hospital of Guangxi Medical UniversityNanning530021China Department of Stomatology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Science)Southern Medical UniversityGuangzhou510080China School of Food and Drug Shenzhen Polytechnic UniversityShenzhen518055China Shenzhen Second People’s hospital First Affiliated Hospital of Shenzhen UniversityShenzhen518055China

CD39 serves as a crucial biomarker for neoantigen-specific CD8^(+)T cells and is associated with antitumor activity and ***,the relationship between CD39 expression levels and the function of chimeric antigen receptor T(CAR-T)cells remains *** study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma(HCC)and explore the therapeutic potential of CD39 modulators,such as mitochondrial division inhibitor-1(mdivi-1),or knockdown CD39 through short hairpin *** findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity,while high and low levels of CD39 led to an impaired cellular *** modulating the proportion of CD39 intermediate(CD39^(int))-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function,*** combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39^(int)CAR-T cells and demonstrated a robust antitumor activity in *** conclusion,this study revealed the crucial role of CD39 in CAR-T cell function,demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC,and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy.

关键词： CD39 CAR-T cells mdivi-1 hepatocellular carcinoma antitumor activity

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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

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Cancer Innovation 2024年第3期3卷 49-64页

作者： Huiyi Liu Lu Fu Shuyu Jin Xingdong Ye Yanlin Chen Sijia Pu Yumei Xue Department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina The Second School of Clinical medicine Southern Medical UniversityGuangzhouGuangdongChina School of medicine South China University of TechnologyGuangzhouGuangdongChina guangdong provincial Key Laboratory of Clinical Pharmacology Research Center of Medical SciencesGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved ***,the incidence of cardiovascular adverse events has also increased,which can affect tumor *** this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor ***:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed *** included trials examined all grade and grades 3–5 cardiac and vascular adverse *** involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target *** odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel ***:Overall,20 trials were ***-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular *** incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically ***:Our findings suggest that the

关键词： cardiovascular toxicity CTLA-4 inhibitors malignancies

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Assessment of the Respiratory Disease Mortality Risk from Single and Composite Exposures to PM_(2.5)and Ozone—Guangzhou City,guangdong Province,China,2018-2021

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China CDC weekly 2024年第34期6卷 857-861,I0001-I0006页

作者： Hongwei Tu Yijun Hu Keqi Hu Peipei Dong Yue Wen Jing Jiang Xuedan Xu Jinxu Huang Jiemin Zhu Changyun He Qiuxia Chen Yongying Liu guangdong provincial Center for Disease Control and Prevention Guangzhou CityGuangdong ProvinceChina Jinan University Guangzhou CityGuangdong ProvinceChina Department of Science and Education Guangdong Second Provincial General HospitalGuangzhou CityGuangdong ProvinceChina Sun Yat-sen University Guangzhou CityGuangdong ProvinceChina

Summary What is already known about this topic?Fine particulate matter(PM_(2.5))and ozone(O_(3))are prevalent pollutants in the atmosphere,which threaten human health,especially the respiratory ***,people are exposed to a mixture of various pollutants in the ***,the single and combined effects of both pollutants need to be investigated.

关键词： environment. ozone guangdong

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Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome in a patient with Guillain-Barré syndrome

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World Journal of Emergency medicine 2024年第5期15卷 413-415页

作者： Juhao Zeng Yin Wen Hongguang Ding Dongxin Li Hongke Zeng Department of Critical Care medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Emergency Department Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China

Strongyloidiasis stercoralis can cause disease when larvae invade the human body through the skin or mucosa and can also infect a host when the host ingests its eggs.[1]Strongyloidiasis lacks characteristic manifestations,and its clinical symptoms are related to the immune response of the host and the degree of *** cient patients with underlying disease or who are receiving long-term corticosteroid treatment are more prone to developing severe disease.[2]The present study reports a case of Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome(ARDS)in a patient with Guillain-Barrésyndrome.

关键词： distress Barr sepsis

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Recent progress of gastroesophageal reflux after endoscopic myotomy

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World Journal of Gastroenterology 2024年第34期30卷 3926-3928页

作者： Xuan Yan Wei-Hong Sha The First School of Clinical medicine Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Gastroenterology and Hepatology Guangdong Provincial People’s HospitalGuangzhou 510080Guangdong ProvinceChina

Per-oral endoscopic myotomy(POEM)is an innovative minimally invasive technique and has emerged as the preferred modality for treating achalasia and spastic esophageal disorders in numerous specialized centers *** reflux(GER)is a common complication following POEM ***,an article in the World Journal of Gastroenterology,providing a comprehensive update on post-POEM *** this article,the authors present novel insights and strategies that offer valuable implications for endoscopy.

关键词： Per-oral endoscopic myotomy Gastroesophageal reflux Progress Treatment Update

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Efficacy and safety of Chinese herbal medicine as adjunctive therapy in sepsis patients with bloodstream infection:a propensity-matched analysis

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Journal of traditional Chinese medicine 2024年第1期44卷 197-204页

作者： ZHOU Xianshi ZHONG Minlin XI Xiaotu LI Jun TANG Guanghua the Second Clinical College of Guangzhou University of Chinese medicine Guangzhou 510120China Emergency Department Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120China guangdong provincial Key Laboratory of Research on Emergency in TCM Guangzhou 510120China Guangzhou Key Laboratory of traditional Chinese medicine for Prevention and Treatment of Emerging Infectious Diseases Guangzhou 510120China Administration Department the First Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China

OBJECTIVE:To investigate the efficacy and safety of Chinese herbal medicine in treating sepsis patients with bloodstream ***:A 6-year retrospective study was carried out at a university hospital in *** sepsis patients with bloodstream infection were *** primary outcome was 28-day mortality after *** score method was used to adjust for possible confounding.28-day mortality was estimated by KaplanMeier analysis and compared using the log-rank *** regression analysis was carried out to identify factors impacting in-hospital mortality ***:Following the application of the propensity score method,a total of 176 patients were *** all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6%and 14.8%,***-Meier survival analysis showed that Chinese herbal medicine was associated with a lower hazard ratio(HR)in all-cause 28-day death compared with the control group[HR=0.44,95%CI(0.22,0.90),P0.05).Blood-activating and stasis-eliminating herb administration was associated with reduced inhospital mortality among sepsis patients with bloodstream infection[HR=0.54,95%CI(0.34,0.94),Pmedicine,especially the blood-activating and stasis-eliminating herb,might have certain efficacy and safety in treating sepsis patients with bloodstream *** should prescribe blood-activating and stasis-eliminating herb in treating these two coalescent critical diseases as long as no contraindications ***,further studies are needed to validate our results.

关键词： bacteremia medicine Chinese traditional herbal medicine sepsis propensity-matched analysis

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