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Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve Pneumonia

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Cellular & Molecular Immunology 2024年第1期21卷 19-32页

作者： Ying Fu Baichao Yu Qi Wang Zhou Lu Hushan Zhang Dan Zhang Feifei Luo Ronghua Liu Luman Wang Yiwei Chu Department of Immunology School of Basic Medical SciencesShanghai Key Laboratory of Medical Epigenetics and MetabolismInstitutes of Biomedical SciencesFudan UniversityShanghaiChina Zhongshan Hospital Institute of Clinical Science Zhongshan HospitalShanghaiChina Zhaotong Health Vocational College ZhaotongYunnanChina Department of Digestive Diseases Huashan HospitalFudan UniversityShanghaiChina Shanghai Fifth People’s Hospital Fudan UniversityShanghaiChina

The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced Pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious Pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.

关键词： IL-10-producing B cell Reactive oxygen species One-carbon metabolism H3K4me Pneumonia

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Development and validation of a CT-based radiomics model for differentiating Pneumonia-like primary pulmonary lymphoma from infectious Pneumonia: A multicenter study

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Chinese Medical Journal 2023年第10期136卷 1188-1197页

作者： Xinxin Yu Bing Kang Pei Nie Yan Deng Zixin Liu Ning Mao Yahui An Jingxu Xu Chencui Huang Yong Huang Yonggao Zhang Yang Hou Longjiang Zhang Zhanguo Sun Baosen Zhu Rongchao Shi Shuai Zhang Cong Sun Ximing Wang Department of Radiology Shandong Provincial HospitalShandong UniversityJinanShandong 250021China Department of Radiology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandong 250021China Department of Radiology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266000China Department of Radiology Qilu HospitalShandong UniversityJinanShandong 250012China Department of Medicine Graduate SchoolKyung Hee UniversitySeoul 446701Republic of Korea Department of Radiology Yantai Yuhuangding HospitalAffiliated Hospital of Qingdao UniversityYantaiShandong 164000China Department of Research Collaboration R&D CenterBeijing Deepwise&League of PHD Technology Co.LtdBeijing 100080China Department of Radiology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinanShandong 250117China Department of Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Radiology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110004China Department of Medical Imaging Jinling HospitalMedical School of Nanjing UniversityNanjingJiangsu 210002China Department of Radiology Affiliated Hospital of Jining Medical UniversityJiningShandong 272029China

Background:Pneumonia-like primary pulmonary lymphoma(PPL)was commonly misdiagnosed as infectious Pneumonia,leading to delayed treatment.The purpose of this study was to establish a computed tomography(CT)-based radiomics model to differentiate Pneumonia-like PPL from infectious Pneumonia.Methods:In this retrospective study,79 patients with Pneumonia-like PPL and 176 patients with infectious Pneumonia from 12 medical centers were enrolled.Patients from center 1 to center 7 were assigned to the training or validation cohort,and the remaining patients from other centers were used as the external test cohort.Radiomics features were extracted from CT images.A three-step procedure was applied for radiomics feature selection and radiomics signature building,including the inter-and intra-class correlation coefficients(ICCs),a one-way analysis of variance(ANOVA),and least absolute shrinkage and selection operator(LASSO).Univariate and multivariate analyses were used to identify the significant clinicoradiological variables and construct a clinical factor model.Two radiologists reviewed the CT images for the external test set.Performance of the radiomics model,clinical factor model,and each radiologist were assessed by receiver operating characteristic,and area under the curve(AUC)was compared.Results:A total of 144 patients(44 with Pneumonia-like PPL and 100 infectious Pneumonia)were in the training cohort,38 patients(12 with Pneumonia-like PPL and 26 infectious Pneumonia)were in the validation cohort,and 73 patients(23 with Pneumonia-like PPL and 50 infectious Pneumonia)were in the external test cohort.Twenty-three radiomics features were selected to build the radiomics model,which yielded AUCs of 0.95(95%confidence interval[CI]:0.94-0.99),0.93(95%CI:0.85-0.98),and 0.94(95%CI:0.87-0.99)in the training,validation,and external test cohort,respectively.The AUCs for the two readers and clinical factor model were 0.74(95%CI:0.63-0.83),0.72(95%CI:0.62-0.82),and 0.73(95%CI:0.62-0.84)in the external test cohort,respectively.The

关键词： Primary pulmonary lymphoma Pneumonia Computed tomography Radiomics Differentiation

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Muscular tissue desaturation and Pneumonia in patients receiving lung cancer surgery:a cohort study

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Chinese Medical Journal 2023年第1期136卷 65-72页

作者： Wei Zhao Caijuan Zhang Dongliang Mu Fan Cui Huiqun Jia Department of Anesthesiology The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei 050000China Department of Anesthesiology Peking University First HospitalBeijing 100034China Department of Anesthesiology Tangshan Gongren HospitalTangshanHebei 063000China

Background:Post-operative Pneumonia(POP)is a common complication of lung cancer surgery,and muscular tissue oxygenation is a root cause of post-operative complications.However,the association between muscular tissue desaturation and POP in patients receiving lung cancer surgery has not been specifically studied.This study aimed to investigate the potential use of intra-operative muscular tissue desaturation as a predictor of POP in patients undergoing lung cancer surgery.Methods:This cohort study enrolled patients(≥55 years)who had undergone lobectomy with one-lung ventilation.Muscular tissue oxygen saturation(SmtO_(2))was monitored in the forearm(over the brachioradialis muscle)and upper thigh(over the quadriceps)using a tissue oximeter.The minimum SmtO_(2)was the lowest intra-operative measurement at any time point.Muscular tissue desaturation was defined as a minimum baseline SmtO_(2)of15 s.The area under or above the threshold was the product of the magnitude and time of desaturation.The primary outcome was the association between intra-operative muscular tissue desaturation and POP within seven post-operative days using multivariable logistic regression.The secondary outcome was the correlation between SmtO_(2)in the forearm and that in the thigh.Results:We enrolled 174 patients.The overall incidence of muscular desaturation(defined as SmtO_(2)Pneumonia than those without desaturation(28.0%[23/82]vs.12.0%[11/92];P=0.008).The multivariable analysis revealed that muscular desaturation was associated with an increased risk of Pneumonia(odds ratio:2.995,95%confidence interval:1.080-8.310,P=0.035)after adjusting for age,American Society of Anesthesiologists status,Assess Respiratory Risk in Surgical Patients in Catalonia score,smoking,use of peripheral nerve block,propofol,and study center.Conclusion:Muscular tissue desaturation,defined as a baseline SmtO_(2)<80%in the forearm,m

关键词： Association Lung neoplasms Muscular tissue oxygenation One-lung ventilation Post-operative complications Pneumonia Propofol Oxygen saturation

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Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet

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Chinese Journal of Integrative Medicine 2023年第8期29卷 714-720页

作者： WANG Yun-hui YU He LIU Tie-gang Teck Chuan Kong ZHENG Zi-an WAN Yu-xiang BAI Chen HAO Yu MAO Ying-qiu WU Jun XU Jing-nan CUI Li-jun WANG Yu-han SHAN Yan-ran SHAO Ying-jun GU Xiao-hong College of Chinese Medicine Beijing University of Chinese MedicineBeijing(100029)China Nanyang Technological University Singapore

Objective To investigate the effect of Yinlai Decoction(YD)on the microstructure of colon,and activity of D-lactic acid(DLA)and diamine oxidase(DAO)in serum of Pneumonia mice model fed with high-calorie and high-protein diet(HCD).Methods Sixty male Kunming mice were randomly divided into 6 groups by the random number table method:normal control,Pneumonia,HCD,HCD with Pneumonia(HCD-P),YD(229.2 mg/mL),and dexamethasone(15.63 mg/mL)groups,with 10 in each group.HCD mice were fed with 52%milk solution by gavage.Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water,twice daily,for 3 days.After hematoxylin-eosin staining,the changes in the colon structure were observed under light microscopy and transmission electron microscope,respectively.Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.Results The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact.The colonic mucosal goblet cells in the Pneumonia group tended to increase,and the size of the microvilli varied.In the HCD-P group,the mucosal goblet cells showed a marked increase in size with increased secretory activity.Loose mucosal epithelial connections were also observed,as shown by widened intercellular gaps with short sparse microvilli.These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment,while there was no significant improvement after dexamethasone treatment.The serum DLA level was significantly higher in the Pneumonia,HCD,and HCD-P groups as compared with the normal control group(P0.05).Conclusions YD can protect function of intestinal

关键词： Yinlai Decoction Chinese medicine Pneumonia microstructure D-lactic acid diamine oxidase

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Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia

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Biomedical and Environmental Sciences 2023年第5期36卷 397-405页

作者： YAN Wei SUN Xiao Yan WANG Meng ZHAO Fei Fan ZHOU Qing Tao Department of Respiratory and Critical Care Medicine Peking University Third HospitalBejing 100191China

Objective This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.Methods This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe Pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values.The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycinassociated acute kidney injury(VA-AKI) occurrence.Results All patients were at least 60 years old(median age = 81 years). The proportion of patients with target trough concentration achievement(≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group(75.8% vs. 42.4%, P = 0.006).Forty-five patients(68.2%) achieved clinical success, the median duration of vancomycin therapy was10.0 days, and VA-AKI occurred in eight patients(12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration(mg/L) = 17.194-0.104 × creatinine clearance rate(mL/min) + 0.313 × vancomycin daily dose [mg/(kg·d)].Conclusion A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe Pneumonia.

关键词： Pneumonia Clinical trials Vancomycin Trough concentration Elderly patients

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Renin-angiotensin system antagonists and mortality due to Pneumonia,influenza,and chronic lower respiratory disease in patients with hypertension

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Journal of Geriatric Cardiology 2022年第7期19卷 511-521页

作者： Heng-Xuan CAI Chen-Chen LIANG Shan-Jie WANG Jun-Chen GUO Ye WANG Bo YU Xue-Qin GAO Shao-Hong FANG Department of Cardiology the Second Affiliated Hospital of Harbin Medical UniversityHarbinChina The Key Laboratory of Myocardial Ischemia Chinese Ministry of EducationHarbinChina

BACKGROUND It is controversial whether angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ ARB) have a potentially beneficial role in the respiratory system. This study investigated the association between ACEI/ARB medications and respiratory-related mortality in hypertensive patients in a real-world nationally representative cohort. METHODS This was a retrospective analysis based on a prospective cohort study. A total of 10,530 patients with hypertension aged ≥ 20 years were included. The data was extracted from the US National Health and Nutrition Examination Survey during 1988-1994 and 1999-2006. The study was approved by the Institutional Review Boards. Moreover, inform concent was taken form all the participants. RESULTS Overall, 27.7% (n = 2920) patients took ACEI/ARB agents. During a median follow-up of 12.4 years, 278 individuals died of respiratory disease, including chronic lower respiratory disease (n = 155) and influenza or Pneumonia (n = 123). Com-pared with the patients without ACEI/ARB use, those taking ACEI/ARB were not associated with respiratory-specific mortality in a multivariable-adjusted Cox model. After 1: 1 matching, taking ACEI/ARB was also not related to respiratory mortality (Haz-ard ratio (HR) = 1.07, 95% CI: 0.79-1.43), influenza- or Pneumonia-related (HR = 1.00, 95% CI: 0.65-1.54) and chronic pulmonary mortality (HR = 1.13, 95% CI: 0.75-1.69). After separating ACEI and ARB from anti-hypertensive medications, those associations remained unchanged. CONCLUSIONS We discovered no significant link between ACEI or ARB medication and pulmonary-related mortality in hy-pertensive patients. In hypertensive patients, standard ACEI/ARB administration may have little effect on the respiratory system .

关键词： Pneumonia influenza hypertension

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Predictors of dysphagia screening and Pneumonia among patients with acute ischaemic stroke in China:findings from the Chinese Stroke Center Alliance(CSCA)

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Stroke & Vascular Neurology 2022年第4期7卷 294-301,I0005-I0008页

作者： Jianshu Liang Zhike Yin Zixiao Li Hongqiu Gu Kaixuan Yang Yunyun Xiong Yongjun Wang Chunjuan Wang Nursing Department Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Vascular NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina Department of Neurology Vascular NeurologyChina National Clinical Research Center for Neurological DiseasesBeijing Tiantan HospitalCapital Medical UniversityBeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background and purpose Guidelines recommend dysphagia screening to identify those at high risk of Pneumonia.However,little is known about the prevalence and predictors of dysphagia screening and Pneumonia among patients with acute ischaemic stroke in China.Methods Using data from the Chinese Stroke Center Alliance,which is a multicentre,prospective,consecutive patient enrolment programme,univariate and multivariate analyses were conducted to identify patient and hospital characteristics associated with dysphagia screening and Pneumonia during acute hospitalisation.Results Of 790811 patients admitted to 1476 hospitals,622718(78.7%)underwent dysphagia screening,and 64398(8.1%)developed Pneumonia.Patients in stroke units were more likely to be screened for dysphagia than those not in stroke units(OR 1.50;95%CI 1.48 to 1.52),while patients with a past history of stroke were less likely to be screened(OR 0.87;95%CI 0.86 to 0.88).Dysphagia screening(OR 1.46;95%CI 1.30 to 1.65),dysphagia(OR 7.31;95%CI 7.15 to 7.46),and admission to stroke units(OR 1.17;95%CI 1.14 to 1.19)were significantly associated with a greater risk of Pneumonia.Conclusions Dysphagia was a critical factor in the development of Pneumonia.Nearly one in five patients with acute ischaemic stroke in the Chinese Stroke Center Alliance were not screened for dysphagia.Pneumonia prevention during acute hospitalisation is dependent not only on dysphagia screening but also on the effectiveness of subsequent dysphagia management interventions.Further studies are needed to elucidate the relationship between dysphagia screening,stroke unit care and Pneumonia in patients with acute ischaemic stroke.

关键词： Pneumonia prevention likely

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Clinical features and risk factors for viral Pneumonia complicated with invasive pulmonary aspergillosis in adult patients

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Chinese Medical Journal 2023年第11期136卷 1361-1363页

作者： Lijuan Li Chuan Wang Yali Ren Jiangbo Liu Feifei Liu Xiaoqi Zhang Department of Pulmonary and Critical Care Medicine National Centre for Clinical Research on Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100029China Department of Pulmonary and Critical Care Medicine First Hospital of ShijiazhuangShijiazhuangHebei 050011China Department of Pulmonary and Critical Care Medicine Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050000China Department of Pulmonary and Critical Care Medicine Tianjin First Central HospitalTianjin 300192China Department of Respiratory and Critical Care Medicine First Hospital of Qin Huang DaoQinhuangdaoHebei 066000China Department of Pulmonary and Critical Care Medicine Second People’s Hospital of WeifangWeifangShandong 261041China

Viral Pneumonia has recently been defined as a risk factor for invasive pulmonary aspergillosis(IPA).Wauters et al[1]reported that 23%of critically ill patients who were admitted to the intensive care unit(ICU)with swine-origin influenza A(H1N1)viral infection had developed invasive aspergillosis.IPA was diagnosed in 83 of 432(19%)patients who were admitted with influenza;for patients with influenza who were immunocompromised,the incidence of IPA reached up to 32%(38 of 117 patients).

关键词： patients admitted Pneumonia

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Legionella Pneumonia complicated with rhabdomyolysis and acute kidney injury diagnosed by metagenomic nextgeneration sequencing: a case report

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World Journal of Emergency Medicine 2023年第4期14卷 322-324页

作者： Bin Deng Junjie Hua Yufei Zhou Duoxian Zhan Lijuan Zhu Yixing Zhan Yumin Fang Yun Ji Libin Li Department of Intensive Care Unit Suichang People's HospitalLishui 323300China Department of Emergency Medicine Suichang People's HospitalLishui 323300China Department of Surgical Intensive Care Unit the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310009China

The triad of Legionella Pneumonia,rhabdomyolysis,and acute kidney injury(AKI)is uncommon but can be devastating.[1]It is vital to recognize Legionella species early as a potential cause of Pneumonia.Legionella infection remains underdiagnosed because of the nonspecific nature of clinical features and the shortcomings of routinely available diagnostic tests.[2]Metagenomic next-generation sequencing(mNGS)is a culture-free and hypothesis-free diagnostic method that can rapidly identify almost all known pathogens in a sample.[3]Here,we present a successfully cured case of rhabdomyolysis and AKI caused by Legionella pneumophila with etiologic diagnosis aided by the use of mNGS.

关键词： Pneumonia routine kidney

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Current Mycoplasma Pneumoniae epidemic among children in Shanghai:unusual Pneumonia caused by usual pathogen

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World Journal of Pediatrics 2024年第1期20卷 5-10页

作者： Xiao-Bo Zhang Wen He Yong-Hao Gui Quan Lu Yong Yin Jian-Hua Zhang Xiao-Yan Dong Ying-Wen Wang Ying-Zi Ye Hong Xu Jia-Yu Wang Bing Shen Dan-Ping Gu Li-Bo Wang Yi Wang Department of Respiratory Medicine Children's Hospital of Fudan University399 Wanyuan RoadShanghai 201102China State Key Laboratory of Genetic Engineering at School of Life Sciences Institute of Reproduction&DevelopmentChildren's Hospital of Fudan UniversityShanghaiChina Department of Respiratory Medicine Children's Hospital of Shanghai Jiao Tong UniversityShanghaiChina Department of Respiratory Medicine Shanghai Children's Medical CenterAffiliated to Shanghai Jiaotong University School of MedicineShanghaiChina Department of Pediatric Respiratory Xinhua HospitalAffiliated to Shanghai Jiaotong University School of MedicineShanghaiChina Department of Nursing Children's Hospital of Fudan UniversityShanghaiChina Department of Infectious Diseases Children's Hospital of Fudan UniversityShanghaiChina Department of Nephrology Children's Hospital of Fudan UniversityShanghaiChina NHC Key Laboratory of Neonatal Diseases Children's Hospital of Fudan UniversityShanghaiChina Shanghai Shenkang Hospital Development Center ShanghaiChina Center for Medical Quality Control Management of Shanghai ShanghaiChina Department of Neurology Children's Hospital of Fudan University399Wanyuan RoadShanghai 201102China

Mycoplasma Pneumoniae(M.Pneumoniae),primarily transmitted through respiratory droplets when infected individuals cough or sneeze,is a common cause of communityacquired Pneumonia,especially among school-age children and adolescents.The infection occurs endemically with an epidemic peak every few years.The worldwide incidence confirmed by direct test methods was reported to be 8.61%between 2017 and 2020 across all age groups[1].

关键词： Pneumonia epidemic respiratory

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