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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of Cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan Ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang Department of Pathology Department of Minimally Invasive Tumor Therapies Center Department of Thoracic Surgery Department of Oncology Department of respiratory and critical care Medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy Diagnostics Co. Ltd.Xiamen 361027China

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:Of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type ***-positive NSCLC displayed higher tumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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Heterogeneous hybrid immunity against Omicron variant JN.1 at 11 months following breakthrough infection

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3170-3172页

作者： Xuan He Jingyou Yu Jiajing Jiang Jinyuan Liu Qi Qi Dan Liu Weimin Li Department of Pulmonary and critical care Medicine Precision Medicine Key Laboratory of Sichuan ProvinceState Key Laboratory of Respiratory Health and MultimorbidityWest China HospitalSichuan UniversityChengduSichuanChina Guangzhou National Laboratory Bio-lslandGuangzhouGuangdongChina Sichuan Center for Disease Control and Prevention ChengduSichuanChina

Dear Editor,Due to the ongoing evolution of SARS-CoV-2 and waning immunity following COVID-19 vaccination,breakthrough infections have become common *** exposure to viral antigens during different COVID-19 waves and vaccination contribute to the unique"hybrid immunity"-immune protection conferred by the combined vaccination and natural infection in individuals.

关键词： immunity vaccination infection

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Knockdown of the nucleoporin Nup50 protects cells against ionizing radiation through enhancing DNA-PKcs-mediated DNA damage repair

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Radiation Medicine and Protection 2024年第3期5卷 194-200页

作者： Zhijie Wan Jingwen Gu Songyun Zhao Hang Jia Tingting Liu Yuanyuan Chen Yanyong Yang Department of Radiation Medicine Faculty of Naval MedicineNaval Medical UniversityShanghai200433China Department of respiratory and critical care Medicine the Second Naval Hospital of Southern Theater CommandSanyaHainan572000China Department of Colorectal Surgery Changhai HospitalNaval Medical UniversityShanghai200433China

Objective:To investigate the effect and mechanism of Nup50 on radiation-induced DNA damage repair to radiation and explore the potential role of Nup50 as radioprotective ***:The Nup50 gene was knocked down in HUVEC cells using *** formation,CCK-8,and flow cytometry were performed to determine the viability,proliferation and apoptosis of HUVEC cells treated withγ-rays,*** extent of DNA damage was evaluated by using comet assay and immu-nofluorescence staining againstγ-*** addition,we explored the role of Nup50 in DNA damage response(DDR)pathways through western blotting ***,nuclear and chromatin fractionation were performed to determine the potential molecular mechanism underlying the radiation protection function of Nup50 ***:Nup50 knockdown increased the cellular resistance to ionizing *** CCK-8 data showed that cell viability was significantly increased in the Nup50 knockdown group after radiation(t=4.23,P<0.01).The Nup50 knockdown group also showed more survived colonies(t=10.06,P<0.001),less apoptosis rate(t=3.78,P<0.05)and less unrepaired DNA ***,Nup50 knockdown increased radiation-activated phosphorylation levels of DNA-PKcs in HUVEC ***,the nuclear and chromatin fractionation data showed that inhibiting Nup50 increased the recruitment of DNA-PKcs to chromatin after DNA ***:Our findings revealed that Nup50 knockdown promoted radioresistance in normal HUVEC cells by regulating DNA-PKcs pathway,suggesting Nup50 as a potential target for radiation protection.

关键词： damage protective p50

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Efficacy and safety of Qingfei Huatan formula in the treatment of acute exacerbation of chronic obstructive pulmonary disease:A multi-centre,randomised,double-blind,placebo-controlled trial

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Journal of Integrative Medicine 2024年第5期22卷 561-569页

作者： Hui-zhi Zhu Cheng-yi Li Liang-ji Liu Jia-bing Tong Zhi-hui Lan Shu-guang Tian Qiao Li Xiang-li Tong Ji-feng Wu Zhen-gang Zhu Su-yun Li Jian-sheng Li Department of respiratory Medicine the First Affiliated Hospital of Anhui University of Traditional Chinese MedicineHefei 230031Anhui ProvinceChina Graduate School Anhui University of Traditional Chinese MedicineHefei 230012Anhui ProvinceChina Department of respiratory Medicine Affiliated Hospital of Jiangxi University of Traditional Chinese MedicineNanchang 330006Jiangxi ProvinceChina Department of respiratory Diseases the First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Pulmonary Diseases Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Traditional Chinese MedicineFuyang 236600Anhui ProvinceChina Department of respiratory and critical care Medicine Jiangxi Province Hospital of Integrated Chinese and Western MedicineNanchang 330002Jiangxi ProvinceChina Department of respiratory Medicine the First Affiliated Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300381China Collaborative Innovation Center for respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province Zhengzhou 450046Henan ProvinceChina

Background Chronic obstructive pulmonary disease(COPD),a common respiratory disease,can be effectively treated by traditional Chinese medicine(TCM).Qingfei Huatan,a TCM formula,has been reported to effectively alleviate the clinical symptoms of COPD ***,there is a lack of multi-centre,randomised,double-blind,controlled clinical trials documenting the clinical efficacy and safety of this formula in the treatment of acute exacerbation of COPD(AECOPD).Objective This study evaluated the efficacy and safety of Qingfei Huatan formula in the treatment of AECOPD,thereby providing high-quality clinical ***,setting,participants and interventions A total of 276 patients with AECOPD were included in this multi-centre,randomised,double-blind,placebo-controlled trial and were randomised into treatment and control groups at a ratio of 1:*** in the treatment and control groups took Qingfei Huatan granules or simulated Qingfei Huatan granules twice a day,for 14 days,in addition to Western medicine *** patients were followed up for 3 *** outcome measures The primary outcome was time taken to symptom *** secondary outcomes included duration of antibiotic use,clinical symptom and sign score,TCM syndrome score,dyspnoea score,and quality of life(QOL)***,the safety of the formula was assessed through routine urine and stool tests,electrocardiograms,liver and kidney function tests,and the observation of adverse events throughout the *** The time taken for effective stabilisation(P<0.05)and obvious stabilisation(P<0.01),and the duration of antibiotic use(P<0.05)were significantly shorter in the treatment group than in the control *** days 6,9,12 and 14 of treatment,clinical symptom and sign score decreased in both groups,particularly in the treatment group(P<0.01).On days 9,12 and 14 of treatment,the TCM syndrome scores of both groups were reduced(P<0.01),with more significant reductions in the treatm

关键词： Acute exacerbation of chronic obstructive pulmonary disease Clinical trial Syndrome of phlegm-heat congesting lung Qingfei Huatan formula Traditional Chinese medicine

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Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

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World Journal of Diabetes 2024年第4期15卷 645-653页

作者： Tian-Zheng Fang Xian-Qiao Wu Ting-Qi Zhao Shan-Shan Wang Guo-Mei-Zhi Fu Qing-Long Wu Cheng-Wei Zhou Department of Thoracic Surgery The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Department of Endocrine The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina Department of respiratory and critical care Medicine The First Affiliated Hospital of Ningbo UniversityNingbo 315020Zhejiang ProvinceChina

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor *** hyperglycemia may have important therapeutic implications for cancer *** To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively *** patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases *** indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively *** correlation analysis was performed to analyze the correlation between BG fluctuations and tumor *** The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor *** incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after

关键词： Blood glucose fluctuation Type 2 diabetes mellitus Lung carcinoma Tumor markers

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Secular trends of asthma mortality in China and the United States from 1990 to 2019

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Chinese Medical Journal 2024年第3期137卷 273-282页

作者： Xiaochen Li Mingzhou Guo Yang Niu Min Xie Xiansheng Liu Department of Pulmonary and critical care Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China NHC Key Laboratory of respiratory Diseases WuhanHubei 430030China

Background:Asthma imposes a large healthcare burden in China and the United States(US).However,the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the *** aim of this study was to compare the mortality and risk factors between China and the ***:The deaths,and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study *** age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age,period,and cohort *** population attributable fractions of risk factors for asthma were ***:In 1990–2019,the asthma mortality rate was higher in China than in the *** crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to *** decline in mortality was more obvious in *** gap between the two countries was narrowing.A sex difference in asthma mortality was observed with higher mortality in males in China and females in the *** age effects showed that mortality increased with age in adults older than 20 years,particularly in the *** trends were generally observed in the period and cohort rate ratios in both countries,with China experiencing a more obvious *** and high body mass index(BMI)were the leading risk factors for asthma mortality in China and the US,*** attributable to occupational asthmagens and smoking decreased the most in China and the US,***:In 1990–2019,the asthma mortality rate was higher in China than in the US;however,the mortality gap has *** increased with age in *** improvements in asthma death risk with period and birth cohort were more obvious in China than in the ***,high BMI,and aging are major health problems associated with asthma *** role of occupational asthmagens in asthma mortality under

关键词： Asthma Mortality Global disease burden China the United States Age–period–cohort model

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Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

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World Journal of Stem Cells 2024年第8期16卷 811-823页

作者： Qi-Hong Chen Ying Zhang Xue Gu Peng-Lei Yang Jun Yuan Li-Na Yu Jian-Mei Chen Department of critical care Medicine Jiangdu People’s Hospital of YangzhouJiangdu People’s Hospital Affiliated to Yangzhou UniversityYangzhou 225200Jiangsu ProvinceChina Department of critical care Medicine Jiangdu People’s Hospital of YangzhouYangzhou 225200Jiangsu ProvinceChina Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225000Jiangsu ProvinceChina

BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)*** stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung *** To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse *** MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse *** intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function *** of MSC-MVs in lung tissues was investigated by near-infrared live ***,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related *** The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model *** with MSC-MVs significantly reduced lung injury and pulmonary fibrosis ***,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these *** addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

关键词： Microvesicles derived from mesenchymal stem cells Acute respiratory distress syndrome Pulmonary fibrosis Hepatocyte growth factor Mesenchymal stromal cells

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The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

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Journal of Clinical and Nursing Research 2024年第9期8卷 249-260页

作者： Qian Lv Qiaoli Yu Lihua Wei Jili Su Yan Zhou Department of respiratory and critical care Medicine Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi ProvinceChina Laboratory of respiratory Disease Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi ProvinceChina

Aim:To study the relationship between NLRP3(nucleotide oligomerization domain[NOD]-,leucine-rich repeats[LRR]-,and pyrin domain-containing protein 3)inflammasome and its downstream inflammatory factors in obstructive sleep apnea(OSA)patients with carotid atherosclerosis(CAS)under cigarette exposure,further exploring the risk factors of CAS in OSA ***:A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were *** to the detection results,they were divided into the OSA group,the CAS group,and the OSA combined CAS group;additionally,29 healthy subjects who underwent a physical examination were also *** to whether they were smoking,the groups were further divided into smoking and non-smoking *** age,body mass index(BMI),blood pressure,apnea-hypopnea index(AHI),lowest blood oxygen saturation(LSaO2),carotid intima-media thickness(CIMT),levels of blood sugar,blood low-density lipoprotein cholesterol(LDLc),and serum NLRP3,interleukin-1β(IL-1β),and interleukin-18(IL-18)of all subjects were ***:The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS *** levels of serum NLRP3,IL-1β,and IL-18 in the OSA group were higher than those in the normal control group(P<0.05);and those in the OSA combined CAS group were higher than the OSA group and CAS group(P<0.05),regardless of cigarette *** cigarette exposure,serum NLRP3,IL-1β,and IL-18 levels were higher in the OSA,CAS,and OSA combined CAS smoking groups than those in the non-smoking group(P<0.05).Under cigarette exposure,AHI,LDLc,NLRP3,IL-1β,and IL-18 were significantly positively correlated(P<0.05),and LSaO2 was negatively correlated with CAS in OSA(P<0.05).AHI,LSaO2,LDLc,NLRP3,and IL-1βare the risk factors for OSA combined with ***:LSaO2,AHI,LDLc,NLRP3,and IL-1βare the important risk factors for OSA co

关键词： Obstructive sleep apnea Smoking NLRP3 Carotid atherosclerosis

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Research Progress of microRNA in the Diagnosis of Tuberculous Pleurisy

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Journal of Biosciences and Medicines 2024年第7期12卷 160-169页

作者： Surui Chen Xinyu Li Jiale Chen Yunnan Shen Boyu Hui Wei Wu Clinical Medicine School Xian Medical University Xian China Department of respiratory and critical care Medicine The Second Affiliated Hospital of Xian Medical University Xian China

Tuberculosis has become a major public health and social problem threatening human health, and a large proportion of pulmonary tuberculosis patients are associated with tuberculous pleurisy (TP). Therefore, it is of great significance to find markers with high specificity and sensitivity for the rapid and accurate diagnosis and differential diagnosis of TP under the severe background of high infectivity and mortality due to the occult nature of TP. The extraction of microRNA (miRNA) from pleural effusion satisfies the characteristics of strong operability. miRNA exists not only in cells, but also in various body fluids and participates in the pathophysiological process of various diseases including infectious diseases. miRNA is a highly specific biomarker in pleural fluid in patients with TP. Therefore, this article provides a review of the research progress of mRNA in tuberculous pleurisy.

关键词： Tuberculous Pleurisy miRNA Diagnosis

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A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections

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Frontiers of Medicine 2024年第1期18卷 169-179页

作者： Xu Hao Zhiyao Bao Ranran Dai Xiaojing Wu Xin Li Muyin Zhang Hao Li Lili Xu Panpan Qiao Xuefei Liu Weiting Hu Ze Zhang Jie Fang Min Zhou Weiming Wang Jieming Qu Department of Nephrology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Department of Pulmonary and critical care Medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Institute of respiratory Diseases Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Pharmacy Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were *** parameters and chest CT(computed tomography)imaging were *** treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic *** serious adverse reactions or safety events were *** control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day ***,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 *** the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day *** therapy showed a potential therapeutic effect with good tolerance in hemodialysis *** optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

关键词： Paxlovid hemodialysis SARS-CoV-2 viral load chest CT scan

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