Deep learning-based lung sound analysis for intelligent stethoscope

Auscultation is crucial for the diagnosis of respiratory system diseases.However,traditional stethoscopes have inherent limitations,such as inter-listener variability and subjectivity,and they cannot record respiratory sounds for offline/retrospective diagnosis or remote prescriptions in telemedicine.The emergence of digital stethoscopes has overcome these limitations by allowing physicians to store and share respiratory sounds for consultation and education.On this basis,machine learning,particularly deep learning,enables the fully-automatic analysis of lung sounds that may pave the way for intelligent stethoscopes.This review thus aims to provide a comprehensive overview of deep learning algorithms used for lung sound analysis to emphasize the significance of artificial intelligence(AI)in this field.We focus on each component of deep learning-based lung sound analysis systems,including the task categories,public datasets,denoising methods,and,most importantly,existing deep learning methods,i.e.,the state-of-the-art approaches to convert lung sounds into two-dimensional(2D)spectrograms and use convolutional neural networks for the end-to-end recognition of respiratory diseases or abnormal lung sounds.Additionally,this review highlights current challenges in this field,including the variety of devices,noise sensitivity,and poor interpretability of deep models.To address the poor reproducibility and variety of deep learning in this field,this review also provides a scalable and flexible open-source framework that aims to standardize the algorithmic workflow and provide a solid basis for replication and future extension:https://github.com/contactless-healthcare/Deep-Learning-for-Lung-Sound-Analysis.

Strategies and Advances in Combating COVID-19 in China

新型冠状病毒肺炎(COVID-19)是21世纪第三次由冠状病毒引发的流行病,并导致全球大规模感染和死亡,造成全球性公共卫生事件。基于在防控重症急性呼吸综合征(SARS)和中东呼吸综合征(M ERS)两次疫情中积累的经验,中国迅速确定病毒传播途径,总结临床特点,提出治疗干预措施并开展疫苗研发,在科学界发挥了关键作用。尽管针对COVID-19的研究取得了快速进展,但在追溯病毒起源、明确传播途径和解析致病机制等方面仍有待进一步研究。目前仍需建立更具针对性的临床治疗方案以及研发特效药。本文总结了中国针对COVID-19防控的主要策略及研究进展,以期为全球疫情防控提供有用的信息。

Efficacy and safety of Phillyrin(KD-1)capsule in the treatment of moderate COVID-19:protocol for a randomized controlled trial

Objective Phillyrin(KD-1)is a traditional Chinese monomer and the main active component in Lianhua Qingwen.At present,sufficient studies have confirmed that KD-1 has significant anti-SARS-CoV-2 activity and antiinflammatory effects in vitro and in vivo.However,evidence-based studies to evaluate its therapeutic effect on COVID-19 are lacking.Therefore,we designed a clinical trial to evaluate the efficacy and safety of KD-1 in the treatment of moderate COVID-19 infection.Methods This is a multicenter,randomized,double-blind,placebo-controlled clinical trial.A total of 120 participants will be recruited and randomized to receive KD-1 capsule or placebo treatment for 14 days,50 mg per capsule,four capsules each time,three times a day.If the SARS-CoV-2 nucleic acid test results are negative twice within 14 days,the KD-1 capsule will be stopped the following day.Symptoms,patient compliance,and adverse reactions will be recorded,and nucleic acid testing will be conducted daily.Primary and secondary outcomes,as well as safety indicators,will be used to evaluate the efficacy and safety of the KD-1 capsule in the treatment of COVID-19.Discussion Herein,we describe the first clinical trial in China to treat COVID-19 using a traditional Chinese medicine monomer.A randomized,double-blind,placebo-controlled clinical trial is the best way to evaluate the efficacy and safety of KD-1 against moderate COVID-19 infection.If a good clinical benefit is observed,this represents the first step toward the use of KD-1 capsules to treat COVID-19.This clinical trial can serve as a model for other evidence-based research of traditional herbal medicines.Trial registration This study is registered at chinadrugtrials.org.cn,with registration number:CTR20211800.

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.

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells(AECs)is a quick way to find novel treatments for COVID-19.Computational screening has found dicoumarol(DCM),a natural anticoagulant,to be a potential SARS-CoV-2 inhibitor,but its inhibitory effects and possible working mechanisms remain unknown.Using air-liquid interface culture of primary human AECs.

Prevalence of sensitization to weed pollens of Humulus scandens,Artemisia vulgaris,and Ambrosia artemisiifolia in northern China

Objective:Weed pollens are common sources of allergens worldwide.The prevalence of weed pollen sensitization is not yet fully known in China.The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia,Ambrosia,and Humulus in northern China.Methods:A total of 1144 subjects(aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources.Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris,Ambrosia artemisiifolia,and Humulus scandens,and against the purified allergens,Art v 1 and Amb a 1.Results:Of 1144 subjects,170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing.The prevalence of positive intradermal responses to pollens of Artemisia sieversiana,Artemisia annua,A.artemisiifolia,and H.scandens was 11.0%,10.2%,3.7%,and 6.6%,respectively.Among the intradermal positive subjects,the prevalence of specific IgE antigens to A.vulgaris was 58.3%,to A.artemisiifolia 14.7%,and to H.scandens 41.0%.The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%,and to Amb a 1 was 11.2%.The correlation between the presence of IgE antibodies specific to A.vulgaris and to the Art v 1 antigen was very high.Subjects with A.artemisiifolia specific IgE also had A.vulgaris specific IgE,but with relatively high levels of A.vulgaris IgE antibodies.There were no correlations between the presence of IgE antibodies to H.scandens and A.vulgaris or to H.scandens and A.artemisiifolia.Conclusions:The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%.Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.

Prevention and treatment of chronic respiratory diseases in China

The Healthy China Initiative(2019—2030)states that chronic non-communicable diseases are now the main cause of death and represent the largest disease burden in China.Deaths due to cardiovascular and cerebrovascular diseases,cancers,chronic respiratory diseases,diabetes,and other chronic noncommunicable diseases account for 88% of the total deaths and more than 70% of the total disease burden.1 In China,the three principal causes of chronic respiratory diseases are severe air pollution,smoking and second-hand smoke,and major acute respiratory diseases.

SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl^(−) accumulation in respiratory epithelium

SARS-CoV-2,the culprit pathogen of COVID-19,elicits prominent immune responses and cytokine storms.Intracellular Cl^(−)is a crucial regulator of host defense,whereas the role of Cl^(−)signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear.By using human respiratory epithelial cell lines,primary cultured human airway epithelial cells,and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge,we demonstrated that SARS-CoV-2 nucleocapsid(N)protein could interact with Smad3,which downregulated cystic fibrosis transmembrane conductance regulator(CFTR)expression via microRNA-145.The intracellular Cl^(−)concentration([Cl^(−)]i)was raised,resulting in phosphorylation of serum glucocorticoid regulated kinase 1(SGK1)and robust inflammatory responses.Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation.Moreover,N protein promoted a sustained elevation of[Cl^(−)]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4(PDE4).Rolipram,a selective PDE4 inhibitor,countered airway inflammation by reducing[Cl^(−)]i.Our findings suggested that Cl^(−)acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection.Targeting the Cl^(−)signaling pathway might be a novel therapeutic strategy for COVID-19.

Veno-venous extracorporeal membrane oxygenation for patient with a history of open cholecystectomy and acute respiratory distress syndrome caused by coinfection of avian influenza A (H7N9) and Epstein-Barr virus

To the Editor:Most patients infected with avian influenza A (H7N9) rapidly develop progressive pneumonia and acute respiratory distress syndrome (ARDS), a heterogeneous disorder that is refractory to conventional mechanical ventilation. Most H7N9 patients also have underlying disease such as chronic obstructive pulmonary disease, hypertension, diabetes mellitus, and heart diseases, and are more susceptible to coinfections. For these patients with such serious complications, extracorporeal membrane oxygenation (ECMO) support can be adopted as a feasible life-saving therapy Here, we present our successful experience with ECMO utilized in a patient with ARDS and also with H 7N9 and Epstein-Barr virus (EBV) infection.

Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension： An Early Stage of Disease？

A 14-year-old male visited the Guangzhou Medical University First Affiliated Hospital of with a complaint of a 2-year history of progressive exertional dyspnea and fingertips cyanosis. Physical examination revealed remarkable desaturation measured by pulse oximetry （80% at rest） and marked cyanosis of lips.