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Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

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Current medical Science 2024年第1期44卷 102-109页

作者： Tian-ci LIU Mo-han ZHENG Xing-yue ZENG Rui KANG Ayibaota Bahabayi Bulidierxin Tuerhanbayi Song-song LU Chen LIU Department of clinical Laboratory Peking University People's HospitalBeijing 100044China school of Basic medical Sciences Peking University Health Science CenterBeijing 100191China

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

关键词： non-small cell lung cancer follicular helper T cells follicular regulatory T cells progression

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Systemic low-grade inflammation associated with specific depressive symptoms:insights from network analyses of five independent NHANES samples

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General Psychiatry 2024年第2期37卷 284-288页

作者： Jingyu Lin Haiming Huang Tianmei Si Lin Chen Jingxu Chen Yun-Ai Su Beijing huilongguan Hospital BeijingChina Department of clinical Laboratory Peking University First HospitalBeijingChina Neuropsychopharmacology Peking University Institute of Mental HealthBeijingChina National clinical Research Center for Mental Disorders BeijingChina

To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoami... 详细信息

关键词： inflammation depress pituitary

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Comparison of various prediction models in the effect of laparoscopic sleeve gastrectomy on type 2 diabetes mellitus in the Chinese population 5 years after surgery

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Chinese medical Journal 2024年第3期137卷 320-328页

作者： Chengyuan Yu Liang Wang Guangzhong Xu Guanyang Chen Qing Sang Qiqige Wuyun Zheng Wang Chenxu Tian Nengwei Zhang Surgery Centre of Diabetes Mellitus Peking University Ninth School of Clinical MedicineBeijing 100038China Department of Surgery Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

Background:The effect of bariatric surgery on type 2 diabetes mellitus(T2DM)control can be assessed based on predictive models of T2DM remission.Various models have been externally verified internationally.However,long-term validated results after laparoscopic sleeve gastrectomy(LSG)surgery are lacking.The best model for the Chinese population is also unknown.Methods:We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016.The independent t-test,Mann–Whitney U test,and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups.We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve(AUC),sensitivity,specificity,Youden index,positive predictive value(PPV),negative predictive value(NPV),and predicted-to-observed ratio,and performed calibration using Hosmer–Lemeshow test for 11 prediction models.Results:We enrolled 108 patients,including 44(40.7%)men,with a mean age of 35.5 years.The mean body mass index was 40.3±9.1 kg/m^(2),the percentage of excess weight loss(%EWL)was(75.9±30.4)%,and the percentage of total weight loss(%TWL)was(29.1±10.6)%.The mean glycated hemoglobin A1c(HbA1c)level was(7.3±1.8)%preoperatively and decreased to(5.9±1.0)%5 years after LSG.The 5-year postoperative complete and partial remission rates of T2DM were 50.9%[55/108]and 27.8%[30/108],respectively.Six models,i.e.,"ABCD",individualized metabolic surgery(IMS),advanced-DiaRem,DiaBetter,Dixon et al’s regression model,and Panunzi et al’s regression model,showed a good discrimination ability(all AUC>0.8).The"ABCD"(sensitivity,74%;specificity,80%;AUC,0.82[95%confidence interval[CI]:0.74–0.89]),IMS(sensitivity,78%;specificity,84%;AUC,0.82[95%CI:0.73–0.89]),and Panunzi et al’s regression models(sensitivity,78%;specificity,91%;AUC,0.86[95%CI:0.78–0.92])showed good discernibility.In the Hosmer–Lemeshow goodness-of-fit test,except for DiaRem(P<0.01),Di

关键词： Type 2 diabetes mellitus Risk prediction models External validation Sleeve gastrectomy Bariatric surgery

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Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up

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Science China(Life Sciences) 2024年第5期67卷 1061-1068页

作者： Zhibo Zhang Jianbin Guo Weijie Tian Ye Zhang Yuelun Zhang Tianshu Sun Jiali Duan Xinmiao Bao Yuan Wang Yang Ye Qianqian Gao Honghui Shi Abraham Nick Morse Juan Chen Lan Zhu Departmentof Obstetrics and Gynecology Peking Union MedicalCollege HospitalChinese Academyof Medical Sciences&Peking Union MedicalCollegeNational Clinical Research Center for Obstetricand Gynecologic DiseasesBeijing 100730China Department of Gynecology Guizhou Provincial People’s HospitalMedical College of Guizhou UniversityGuiyang 550002China Department of Obstetrics and Gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China medical Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China medical Doctor Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Pathology Peking Union Medical College HospitalBeijing 100730China Tufts university school of Medicine Boston MA 02111USA

Although transvaginal mesh(TVM)repair is no longer used in some countries,long-term outcomes after TVM surgery are of great importance globally.However,reports with follow-up>10 years are limited.Thus,this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up.Women with stageⅢ–Ⅳsymptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital.The main outcome measure was symptomatic failure.Secondary outcomes included anatomic failure,recurrence,patient satisfaction,complications,and reoperation.The Kaplan-Meier curve was used to estimate the cumulative failure rate.Of the 121 patients enrolled in the study,103(85.1%)completed a median follow-up of 11 years.The estimated probability rates of symptomatic and anatomic failure were 17.6%and 8.8%in 11 years,respectively.The estimated incidence of symptomatic failure increased by 8.2%between 5 and 11 years;however,the corresponding rate for anatomic failure was 3.7%.The most common complication was vaginal mesh exposure,and its estimated probability increased from 19.3%to 28.4%from 5 to 11 years,respectively.Office trimming resolved 80.0%of vaginal exposures.These patients did not report decreased overall satisfaction.Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room(5.8%by 11 years)had lower satisfaction rates(P<0.01)and were defined as having severe mesh exposure.The rates of postoperative pain,reoperation,and Patient Global Impression of Improvement≥2 were 2.5%,3.3%,and 94.2%,respectively.The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall.Vaginal mesh exposure was common in women who were largely not sexually active;however,80%of the cases could be managed in the outpatient clinic,which did not affect patient satisfaction.

关键词： complication efficacy long-term follow-up pelvic organ prolapse safety transvaginal mesh

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The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

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Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

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Animal Models and Experimental Medicine 2024年第3期7卷 208-221页

作者： Da-zhuang Lu Li-jun Zeng Yang Li Ran-li Gu Meng-long Hu Ping Zhang Peng Yu Xiao Zhang Zheng-wei Xie Hao Liu Yong-sheng Zhou Department of Prosthodontics Peking University School and Hospital of StomatologyBeijingChina National Center of Stomatology BeijingChina National clinical Research Center for Oral Diseases BeijingChina Beijing Key Laboratory of Digital Stomatology BeijingChina Department of Cariology and Endodontology Peking University School and Hospital of StomatologyBeijingChina peking university International Cancer Institute Peking University Health Science CenterPeking UniversityBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina National Engineering Research Center of Oral Biomaterials and Digital medical Devices BeijingChina

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

关键词： BMPs/SMAD bone loss cinobufotalin hBMMSCs osteogenesis osteoporosis Wnt/β-catenin signaling pathways

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A 12-month follow-up study of discharged patients with acute pancreatitis:An acute condition with prolonged sequela

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Chinese medical Journal 2024年第2期137卷 250-252页

作者： Hanyue Ding Jiayuan Dai Jiaye Lin Liang Gong Han Sun Kai Song Feng Xie Dong Wu Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing 100730China school of Population Medicine and Public Health Peking Union Medical College and Chinese Academy of Medical ScienceBeijing 100730China JC school of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative RegionChina Emergency Department Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing 100730China Department of Health Research Methods Evidence and ImpactMcMaster UniversityHamiltonCanada Centre for Health Economics and Policy Analysis McMaster UniversityHamiltonCanada State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing 100730China clinical Epidemiology Unit International Clinical Epidemiology NetworkBeijing 100730China

To the Editor:Acute pancreatitis(AP)is the most common gastrointestinal condition that leads to acute hospitalization.[1]The incidence of AP has increased in recent decades,with a current global incidence of 34/100,000,probably due to a rising trend of obesity and gallstone disease.AP is associated with remarkable pain,reduced quality of life(QoL),and even death,thus posing a heavy socioeconomic burden.In addition,approximately 22%of AP patients experience recurrent AP(RAP)and 10%of AP patients progress to chronic pancreatitis.[2]Petrov and Yadav[3]have,therefore,argued that AP should not be considered as an acute and self-limiting disease.Treatment and long-term care after AP have drawn widespread attention,which has improved patients’physical and mental health.

关键词： patients pancreatitis acute

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Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

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Signal Transduction and Targeted Therapy 2024年第1期9卷 105-149页

作者： Yumin Wang Jing Hu Shuang Wu Joshua S.Fleishman Yulin Li Yinshi Xu Wailong Zou Jinhua Wang Yukuan Feng Jichao Chen Hongquan Wang Department of Respiratory and Critical Care Medicine Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Department of Pathogen Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300060PR China Department of Neurology Zhongnan Hospital of Wuhan UniversityWuhan 430000PR China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA Department of Outpatient Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050PR China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060PR China

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance.Aberrant epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and metastasis.Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney diseases.In this review,we first summarize the core molecular mechanisms of ferroptosis.Then,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely discussed.The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in detail.Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases.In addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

关键词： diseases epigenetic overcome

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Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway

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Chinese medical Journal 2024年第6期137卷 711-719页

作者： Bo Jin Yemei Gao Yixian Fu Suxin Zhang Ke Zhang Yibing Su Department of Neurosurgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Department of Traditional Chinese Medicine Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China school of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Breast Surgical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:Mild traumatic brain injury(mTBI)is a common neurological trauma that can lead to cognitive impairment.The sirtuin-1(SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)pathway has been reported to have neuroprotective effects in rats with craniocerebral injury.We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI,focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods:We included forty 6-week-old male Sprague-Dawley rats in this study.Rats were randomly divided into four groups:controlled cortical impactor(CCI,n=10),sham operation(sham,n=10),electroacupuncture-treated CCI(CCI+EA,n=10),and electroacupuncture-treated sham(sham+EA,n=10)group.Randomization was performed by assigning a random number to each rat and using a random number table.The mTBI rat model was established using a controllable cortical impactor.Electroacupuncture therapy was performed on the back of rats,by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment.We evaluated spatial learning and memory functions with the Morris water maze test.We performed quantitative real-time polymerase chain reaction(qRT-PCR),western blotting,adenosine triphosphate(ATP)determination,and mitochondrial respiratory chain complex I(MRCC I)determination on rat hippocampal tissue.We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays,and compared differences between groups using bilateral Student’s t-tests.Results:Compared with the sham group,SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group(P<0.01).Although this expression was upregulated following electroacupuncture,it did not reach the levels observed in the sham group(P<0.05).Compared with the sham group,MRCC I and ATP levels in the CCI group were significantly reduced,and increased after electroacupuncture(P<0.01).In the Morris water maze,electroacupuncture reduced the incubation period of rats and

关键词： Electroacupuncture Cognitive impairment Sirtuin-1 Mild traumatic brain injury SIRT-1/PGC-1α/mitochondrial pathway

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Vaccination against coronavirus disease 2019 in patients with pulmonary hypertension:A national prospective cohort study

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Chinese medical Journal 2024年第6期137卷 669-675页

作者： Xiaohan Wu Jingyi Li Jieling Ma Qianqian Liu Lan Wang Yongjian Zhu Yue Cui Anyi Wang Cenjin Wen Luhong Qiu Yinjian Yang Dan Lu Xiqi Xu Xijie Zhu Chunyan Cheng Duolao Wang Zhicheng Jing Department of Cardiology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Echocardiography National Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Pulmonary Circulation Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Department of Cardiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of clinical Sciences Liverpool School of Tropical MedicineLiverpoolUnited Kingdom

Background:Coronavirus disease 2019(COVID-19)has potential risks for both clinically worsening pulmonary hypertension(PH)and increasing mortality.However,the data regarding the protective role of vaccination in this population are still lacking.This study aimed to assess the safety of approved vaccination for patients with PH.Methods:In this national prospective cohort study,patients diagnosed with PH(World Health Organization[WHO]groups 1 and 4)were enrolled from October 2021 to April 2022.The primary outcome was the composite of PH-related major adverse events.We used an inverse probability weighting(IPW)approach to control for possible confounding factors in the baseline characteristics of patients.Results:In total,706 patients with PH participated in this study(mean age,40.3 years;mean duration after diagnosis of PH,8.2 years).All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China.Among them,278 patients did not receive vaccination,whereas 428 patients completed the vaccination series.None of the participants were infected with COVID-19 during our study period.Overall,398 patients received inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine,whereas 30 received recombinant protein subunit vaccine.After adjusting for baseline covariates using the IPW approach,the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase(27/428[6.3%]vs.24/278[8.6%],odds ratio=0.72,P=0.302).Approximately half of the vaccinated patients reported at least one post-vaccination side effects,most of which were mild,including pain at the injection site(159/428,37.1%),fever(11/428,2.6%),and fatigue(26/428,6.1%).Conclusions:COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH,although there were some tolerable side effects.A large-scale randomized controlled trial is warranted to confirm this finding.The final approval

关键词： Coronavirus disease COVID-19 Pulmonary hypertension Vaccination

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