Formulation of international standards of Chinese medicine technology:clinical practice guide of Chinese medicine for cough

OBJECTIVE:To formulate the first clinical practice guideline for the treatment of cough using Chinese medicine based on the grading of recommendations assessment,development,and evaluation(GRADE)systematic approach,including clinical evidence,evaluation of ancient literature,and expert consensus.METHODS:In the process of development,the regulation of"evidence-based,consensus-assisted,and empirical"was followed,and a comprehensive systematic approach of recommendation assessment,GRADE,evidence-based evaluation,expert consensus,and the Delphi method was used.In the process of guideline development,evidence-based evaluation of ancient literature was included for the first time,and clinical evidence was fully integrated with clinical expert consensus.RESULTS:The clinical practice guidelines for the treatment of cough with Chinese herbal medicine were developed after a comprehensive consideration of evidence-based evaluation and expert opinions.The guideline recommendations focused on recommending herbal compound decoctions and Chinese patent medicines for cough in different conditions.Based on the GRADE systematic approach,we conducted an evidence-based evaluation of the recommended Chinese patent medicines one by one;meanwhile,the expert consensus method was used to unify the recommendations of both.CONCLUSION:Based on clinical evidence,ancient literature evaluation,and expert consensus,a clinical practice guideline for Traditional Chinese Medicine(TCM)in the treatment of cough was developed,providing the first current clinical practice guideline for domestic and foreign TCM and Western medicine practitioners,especially respiratory professionals at home and abroad.

Prognostic-related genes for pancreatic cancer typing and immunotherapy response prediction based on single-cell sequencing data and bulk sequencing data

Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies,but studies have not fully evaluated its molecular subtypes,prognosis and response to immunotherapy of different subtypes.The purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype,prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data,and data retrieved from GEO and TCGA databases.Methods:Single-cell seq data and bioinformatics methods were used in this study.Pancreatic cancer data were retrieved from GEO and TCGA databases,the molecular subtypes of pancreatic cancer were determined using the six cGAS-STING related pathways,and the clinical phenotype,mutation,immunological characteristics and pathways related to pancreatic cancer were evaluated.Results:Pancreatic cancer was classified into 3 molecular subtypes,and survival analysis revealed that patients in Cluster3(C3)had the worst prognosis,whereas Cluster1(C1)had the best prognosis.The clinical phenotype and gene mutation were statistically different among the three molecular subtypes.Analysis of immunotherapy response revealed that most immune checkpoint genes were differentially expressed in the three subtypes.A lower risk of immune escape was observed in Cluster1(C1),indicating higher sensitivity to immunotherapeutic drugs and subjects in this Cluster are more likely to benefit from immunotherapy.The pathways related to pancreatic cancer were differentially enriched among the three subtypes.Five genes,namely SFRP1,GIPR,EMP1,COL17A and CXCL11 were selected to construct a prognostic signature.Conclusions:Single-cell seq data were to classify pancreatic cancer into three molecular subtypes based on differences in clinical phenotype,mutation,immune characteristics and differentially enriched pathways.Five prognosis-related genes were identified for prediction of survival of pancreatic cancer patients and to evaluate the efficacy of immunotherapy in various subtypes.

“Guidezilla”extension catheter combined with balloon technique for treating pulmonary artery stenosis caused by Takayasu arteritis

Takayasu arteritis(TA)is a rare systemic vasculitis of the aorta and its primary branches,which usually occurs in young women.Due to its insidious onset and lack of specific symptoms,this disease can be easily misdiagnosed or missed.Approximately 50%of the patients having TA with pulmonary artery involvement develop pulmonary hypertension(PH).The 3-year survival rate among patients with TA-related PH is lower than that among patients with TA alone.Early balloon pulmonary angioplasty(BPA)can improve the clinical symptoms and survival of patients with stable TA.To the best of our knowledge,this is the first case reported in the English literature in which a“Guidezilla”catheter was used during BPA to treat stenosis and occlusion of the pulmonary artery caused by Takayasu arteritis(TA).

National survey of the awareness and implementation status of early pulmonary rehabilitation for patients with critical illness in departments of pulmonary and critical care medicine in 2019

To the Editor:The aim of early pulmonary rehabilitation(PR)in the intensive care unit(ICU)is to reduce the incidence of post-ICU syndrome,increase the number of ventilator-free days,reestablish and improve functional capacity,improve health-related life quality,promote mental health,and enhance participation in everyday life.PR in the ICU is highly effective and plays an important role in recovery of patients with reduced exercise endurance,functional capacity,and health-related life quality.Several surveys outside China have assessed the implementation of early rehabilitation in the ICU,[1]but there are few data from China.This study aimed to investigate the awareness and implementation of early PR in secondary-and tertiary-class hospitals with pulmonary and critical care medicine(PCCM)standardized certification.PCCM staff members were recruited to fill out a selfdesigned questionnaire.We defined early PR as PR within 5 days of ICU admission.

Study on the Correlation between Syndrome Differentiation of Malignant Pleural Effusion Treated by External Treatment of Traditional Chinese Medicine and Immunohistochemistry of Biopsy Tissue Based on Medical Video-assisted Thoracoscope

Objective:Guided by the theory of syndrome differentiation of yin and yang in traditional Chinese medicine surgery,through visual observation of internal medicine thoracoscope,comprehensive observation of pleural cavity and immunohistochemistry of biopsy tissue,to classify malignant pleural effusion according to syndrome differentiation,and to explore the scientific nature of its theory.Methods:From March 1,2014 to February 28,2015,40 cases of malignant pleural effusion were treated in Beijing Chaoyang Hospital affiliated to Capital Medical University.According to the proposed TCM diagnostic criteria for yin and yang syndrome differentiation,and collect age,gender,course of disease,clinical symptoms,tumor primary focus,histomorphological manifestations and immunohistochemical results and other related information,and carry out statistical data processing.Results:The positive syndrome was mainly metastatic lung adenocarcinoma,which accounted for the majority of all MPE cases,up to 75%.The immunohistochemical results of biopsy tissues were mainly CEA and TTF-1 positive;While pleural effusion caused by pleural mesothelioma was the main type of yin syndrome,and the results of immunohistochemistry combined with biopsy were mainly positive for D2-40,Calretinin,WT-1 and CK5/6.Conclusion:TCM syndrome differentiation of MPE based on internal thoracoscopy combined with biopsy immunohistochemical results has sufficient theoretical basis and certain scientific nature,and further clinical research is needed to verify its effectiveness and practicability in the future.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease

Drug-induced interstitial lung disease(DILD)is the most common pulmonary adverse event of anticancer drugs.In recent years,the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents.Due to the diverse clinical manifestations and the lack of specific diagnostic criteria,DILD is difficult to diagnose and may even become fatal if not treated properly.Herein,a multidisciplinary group of experts from oncology,respiratory,imaging,pharmacology,pathology,and radiology departments in China has reached the“expert consensus on the diagnosis and treatment of anticancer DILD”after several rounds of a comprehensive investigation.This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening,diagnosis,and treatment of anticancer DILD.This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose APE.Thereafter,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart failure.Among eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinical assessment strategies,the RF model achieved better diagnostic efficacy and accuracy.Therefore,the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Advances in lung cancer screening and early detection

Lung cancer is associated with a heavy cancer-related burden in terms of patients’physical and mental health worldwide.Two randomized controlled trials,the US-National Lung Screening Trial(NLST)and Nederlands-Leuvens Longkanker Screenings Onderzoek(NELSON),indicated that low-dose CT(LDCT)screening results in a statistically significant decrease in mortality in patients with lung cancer,LDCT has become the standard approach for lung cancer screening.However,many issues in lung cancer screening remain unresolved,such as the screening criteria,high false-positive rate,and radiation exposure.This review first summarizes recent studies on lung cancer screening from the US,Europe,and Asia,and discusses risk-based selection for screening and the related issues.Second,an overview of novel techniques for the differential diagnosis of pulmonary nodules,including artificial intelligence and molecular biomarker-based screening,is presented.Third,current explorations of strategies for suspected malignancy are summarized.Overall,this review aims to help clinicians understand recent progress in lung cancer screening and alleviate the burden of lung cancer.

为有效防控新冠病毒肺炎争取时间——抗疫假期政策对疫情传播的影响

在新发突发传染病的早期阶段,快速应对对于疫情防控至关重要。用于控制疫情的公共假期能为大规模、迅速地进行社会隔离和其他举措提供关键的时间窗口期。本研究的目的是探讨抗疫假期的起始时间节点和持续时间对中国早期新冠病毒肺炎疫情传播的影响。我们开发了一个房室模型来模拟从2020年1月开始中国新冠病毒肺炎疫情的动态传播;预测并比较了春节期间在有抗疫假期和没有抗疫假期下的疫情传播;考虑了抗疫假期在不同持续时间、不同起始时间节点,以及在关于病毒传播率的不同假设下的多种情况;估计了在不同情况下达到某些感染阈值所需的天数延迟。结果表明,中国的抗疫假期使新冠病毒肺炎疫情的传播停滞了许多天。与不设抗疫假期的场景相比,基础场景的抗疫假期(湖北省为21 d,中国所有其他省为10 d)可使确诊感染100000例的时间延迟7.54 d。持续时间更长的抗疫假期会对疫情防控产生更大的影响。为期21 d的全国性抗疫假期可使确诊感染100000例的时间延迟近10 d。此外,研究发现,在新发突发传染病较早阶段实施抗疫假期比较晚阶段实施对遏制疫情蔓延更有效,抗疫假期期间采取额外的控制措施可以增强疫情控制效果。总之,抗疫假期能够通过有效地减少人群的社交接触频率及范围,从而减缓疫情的传播。抗疫假期使得新冠病毒肺炎传播暂时停滞,为疫情防控争取了时间,科学家可用争取的时间来发现传播途径并确定有效的公共卫生干预措施,政府可用争取的时间来完善基础设施、调配医疗用品、培训和部署专业人力资源,从而为长期防控做好准备。

Pharmacological therapy for stable chronic obstructive pulmonary disease

In recent years,emphasis has shifted from preventing and treating chronic obstructive pulmonary disease(COPD)to early prevention,early treatment,and disease stabilization,with the main goal of improving patients’quality of life and reducing the frequency of acute exacerbations.This review summarizes pharmacological therapies for stable COPD.

Cold exposure and capsaicin promote 1,2-dimethylhyrazine-induced colon carcinogenesis in rats correlates with extracellular matrix remodeling

BACKGROUND Extracellular matrix(ECM)remodeling and stiffening,which are correlated with tumor malignancy,drives tumor development.However,the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine(DMH)-induced colorectal cancer(CRC)imposed by cold and capsaicin exposure remains unclear.AIM To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.METHODS For histopathological analysis,the sections of colon tissues were stained with hematoxylin and eosin,Masson’s trichrome,Picrosirius red,and Weigert’s Resorcin-Fuchsin to observe the remodeling of collagen and elastin.Additionally,the protein expression level of type I collagen(COL I),type 3 collagen(COL III0,elastin,matrix metalloproteinase(MMP)1,MMP2,MMP9,and tissue-specific matrix metalloproteinase 1(TIMP1)was assessed by immunohistochemistry.The messenger RNA(mRNA)levels of COL I,COL III,elastin,and lysyl oxidase-like-2(LOXL2)in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.RESULTS Although no differences were observed in the proportion of adenomas,a trend towards the increase of invasive tumors was observed in the cold and capsaicin group.The cold exposure group had a metastasis rate compared with the other groups.Additionally,abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group.Specifically,collagen quantitative analysis showed increased length,width,angle,and straightness compared with the DMH group.Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group.Cold exposure and capsaicin significantly increased the protein levels of COL I,elastin,and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group,while COL III did not show a significant difference.Furthermore,in immunohistochemical evaluations,MMP1,MMP2,MMP9,and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.CONCLUSION These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue.Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue.The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.

Evolution of the newest diagnostic methods for COVID-19:a Chinese perspective

Coronavirus disease 2019(COVID-19)has continued to spread globally since late 2019,representing a formidable challenge to the world's healthcare systems,wreaking havoc,and spreading rapidly through human contact.With fever,fatigue,and a persistent dry cough being the hallmark symptoms,this disease threatened to destabilize the delicate balance of our global community.Rapid and accurate diagnosis of COVID-19 is a prerequisite for understanding the number of confirmed cases in the world or a region,and an important factor in epidemic assessment and the development of control measures.It also plays a crucial role in ensuring that patients receive the appropriate medical treatment,leading to optimal patient care.Reverse transcription-polymerase chain reaction(RT-PCR)technology is currently the most mature method for detecting viral nucleic acids,but it has many drawbacks.Meanwhile,a variety of COVID-19 detection methods,including molecular biological diagnostic,immunodiagnostic,imaging,and artificial intelligence methods have been developed and applied in clinical practice to meet diverse scenarios and needs.These methods can help clinicians diagnose and treat COVID-19 patients.This review describes the variety of such methods used in China,providing an important reference in the field of the clinical diagnosis of COVID-19.

Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies

To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and b-agonists,and sometimes oral corticosteroid(OCS)therapy.Type-2(T2)high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE,anti-interleukin(IL)5,or anti-IL5Ra and anti-IL4Ra monoclonal antibodies,which are currently available in Europe and North America,and are currently introduced in the rest of the world.[1]

PD-L1-driven efficient enrichment and elimination of circulating cancer cells by magnetic MoSe_(2) nanosheet

Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer progression.The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments.Therefore,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing effect.In summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.

评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational studies.In order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in 2023.The patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–ritonavir.The primary outcome was time to sustained clinical recovery through day 28.SHG significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and fatigue.No participants in either group died and incidence of severe COVID-19 showed no difference between two groups.Participants who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);P<0.001).Most adverse events were mild in both groups.In summary,SHG was superior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(Chinese Clinical Trial Registry Identifier:Chi CTR2300067872).

Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in China.This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed.The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years.To ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this study.Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors.The independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were compared.Results:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),respectively.In multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were positively associated with vaccination.Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated(OR:0.65,95%CI:0.45-0.96).Compared with unvaccinated participants,vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions:Influenza and pneumococcal vaccination coverage are extremely low.Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

EGFR-mutant non-small cell lung cancer patients harboring CDK4 amplification show favorable response to afatinib:Two case reports

To the Editor:Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)show significant efficacy in patients with advanced-stage non-small cell lung cancer(NSCLC)with sensitive EGFR mutations and significantly prolong the survival of these patients.However,drug resistance emerges in most patients.Previous studies indicated that cyclin-dependent kinase 4/6(CDK4/6)gene amplification was one of the resistance mechanisms of the EGFR-TKI osimertinib,weakening its efficacy.Treatment options for EGFR-mutant NSCLC patients with CDK4 amplification are limited to add CDK4 inhibitors.

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway inflammation.The envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this process.Pathogens could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)signaling.However,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be elucidated.Here,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial barrier.In addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial cells.This elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein.Overall,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Non-invasive estimation of pulmonary hypertension and clinical deterioration risk in pediatric congenital heart disease:Development and validation of predictive tools

To the Editor:Owing to the heterogeneity of congenital heart disease-associated pulmonary hypertension(CHDPH)disease and the development of the pulmonary vascular system in pediatric patients,the management of CHD-PH in children is signicantly different from that in adults.[1]Early identication and intervention of CHD-PH are of great signicance for disease management in children with CHD,and non-invasive,accurate clinical tools are urgently needed to predict PH risk in children with CHD.However,the applicability of the current risk-scoring system to pediatric CHD-PH remains unclear.Furthermore,there are presently no user-friendly,non-invasive online tools available for predicting CHD-PH,and there is a scarcity of related studies in Asian populations.This study aimed to develop and validate the prediction tools for estimating the risk of pulmonary hypertension and clinical deterioration in children with congenital heart disease.