BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marke...BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP.METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis.RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM.CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.展开更多
We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent g...We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.展开更多
Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could re...Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could reflect early progression of atherosclerosis.Based on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.展开更多
Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly...Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.展开更多
The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially...The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be investigated.We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing.We found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(P.aeruginosa)(24.2%),Staphylococcus aureus(S.aureus)(14.0%),andKlebsiella pneumoniae(K.pneumonia)(13.4%)ranked as the top three coinfected bacteria.Aspergillus fumigatus(A.fumigatus)(39.5%),Pneumocystis jirovecii(P.jirovecii)(24.4%)andCanidia albicans(C.albicans)(22.1%)were the top three coinfected fungi.Epstein-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected viruses.Of note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease severity.Our study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.展开更多
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 respirator...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.展开更多
Isatis indigotica Fort.(Ban-Lan-Gen)is an herbal medicine prescribed for influenza treatment.However,its active components and mode of action remain mostly unknown.In the present study,erucic acid was isolated from Is...Isatis indigotica Fort.(Ban-Lan-Gen)is an herbal medicine prescribed for influenza treatment.However,its active components and mode of action remain mostly unknown.In the present study,erucic acid was isolated from Isatis indigotica Fort.,and subsequently its underlying mechanism against influenza A virus(IAV)infection was investigated in vitro and in vivo.Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity.Erucic acid was found to exert inhibitory effects on IAV or viral(v)RNA-induced pro-inflam-matory mediators as well as interferons(IFNs).The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-kB and p38 MAPK signaling.Furthermore,the NF-kB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3(ISGF-3),and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized cells.Additionally,IAV-or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid.In vivo,erucic acid administration consistently displayed decreased lung viral load and viral antigens expression.Meanwhile,erucic acid markedly reduced CD8+cytotoxic T lymphocyte(CTL)recruitment,pro-apoptotic signaling,hyperactivity of multiple signaling pathways,and exacerbated immune inflammation in the lung,which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1)strain infection.Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury,suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.展开更多
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 antiinflam...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.展开更多
Background:From early experience,some Traditional Chinese Medicine and Arbidol had effects of against COVID-19,infer that the combination of Liushen capsules and Arbidol may further increase the therapeutic.Methods/De...Background:From early experience,some Traditional Chinese Medicine and Arbidol had effects of against COVID-19,infer that the combination of Liushen capsules and Arbidol may further increase the therapeutic.Methods/Design:We conducted a randomized,blank parallel-controlled,open-label,multi-center,basal therapy-loaded design clinical trial.A total of 40 patients are going to be recruited after satisfying the criteria.Participants will be allocated randomly into the treatment group with the combination of Arbidol and Liushen capsules and the control group with the basic therapy.Each group will receive treatment at least 7-days or until the virus becomes negative,and visits after drug administration at day 3(visit 1),the day when the virus becomes negative(visit 2),day 7(visit 3),the day before discharge(visit 4)and day 28(visit 5),to collect their survival status and disease prognosis so that the efficacy and safety of a combination of Arbidol and Liushen capsule will be evaluated.Discussion:We described the protocol of the first clinical trial for treatment COVID-19 by using a combination of Arbidol and Liushen capsules.The results of this study will provide a basis for the design and sample size estimate of subsequent large-scale clinical trials.Trial registration:This study has been registered at Chinese clinical trial Registry(chictr.org.cn):ChiCTR2000029993.展开更多
Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and West.This study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer...Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and West.This study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national levels.Methods:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 database.Age-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian countries.Results:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer increased.Smoking was the leading specific risk factor for deaths from both TBL and larynx cancers.The burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central Asia.Deaths,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent years.Conclusions:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in Asia.SDI and smoking were the main factors influencing the disease burden of TBL cancer in Asian countries.This study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.展开更多
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 c...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.展开更多
Human adenoviruses(HAdVs)can cause acute hepatitis in immunocompromised patients.However,it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children.In this study,the liver function test(LFT)...Human adenoviruses(HAdVs)can cause acute hepatitis in immunocompromised patients.However,it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children.In this study,the liver function test(LFT)results were retrospectively analyzed among children hospitalized(age<14 years)between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses.Alanine transaminase(ALT)and aspartate aminotransferase(AST)levels were elevated in 7.74%and 46.89%of patients,respectively.All patients with>2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55.Significantly higher levels of ALT,AST,γ-glutamyl transpeptidase(γ-GT),and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group.HAdV-55 infection led to significantly higherγ-GT,total bilirubin,and direct bilirubin levels than the other infection types.The records of four patients with serial monitoring of the LFT results were further analyzed.Multiple indicators remained abnormal during the entire hospitalization in these patients.These results indicate that HAdV infection is often accompanied by abnormal liver function,and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.展开更多
Corona virus disease 2019(COVID-19)has exerted a profound adverse impact on human health.Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome...Corona virus disease 2019(COVID-19)has exerted a profound adverse impact on human health.Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people.Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks.Monitoring of pathogenic microorganisms in the air,especially in densely populated areas,may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage.The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation,allocate health resources,and formulate epidemic response policies.This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission,which lays a theoretical foundation for the monitoring and prediction of epidemic development.Secondly,the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized.Subsequently,this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology,atmospheric sciences,environmental sciences,sociology,demography,etc.By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere,this review proposes suggestions for epidemic response,namely,the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.展开更多
The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life.Despite its vital role in severe acute respiratory syndrome coronavirus 2(SA...The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life.Despite its vital role in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)assembly and host inflammatory response,it remains an unexplored target for drug development.In this study,we identified a small-molecule compound(ciclopirox)that promotes NP degradation using an FDA-approved library and a drug-screening cell model.Ciclopirox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation.Ciclopirox induced abnormal NP aggregation through indirect interaction,leading to the formation of condensates with higher viscosity and lower mobility.These condensates were subsequently degraded via the autophagy-lysosomal pathway,ultimately resulting in a shortened NP half-life and reduced NP expression.Our results suggest that NP is a potential drug target,and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.展开更多
Cough is one of the most common symptoms observed in patients presenting with COVID-19,persisting for an extended duration following SARS-CoV-2 infection.We aim to describe the distribution of airway microbiota and ex...Cough is one of the most common symptoms observed in patients presenting with COVID-19,persisting for an extended duration following SARS-CoV-2 infection.We aim to describe the distribution of airway microbiota and explore its role in patients with post-CovID-19 chronic cough.A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China.Airway microbiota profiling is assessed in nasopharyngeal swab,nasal lavage,and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection.Our findings reveal that bacterial families Staph-ylococcaceae,Corynebacteriaceae,and Enterobacteriaceae are the most prevalent in the upper airway,while Streptococcaceae,Lachnospiraceae,and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway.An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month.Furthermore,the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity.In conclusion,dynamic alterations in the airway microbial composition may contribute to the post-coviD-19 chronic cough progression,while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.展开更多
Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for n...Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China.Although a variety of small‑molecule antiviral drugs against COVID‑19 have been listed in China,there is no specific drug recommendation for special populations.Society of Bacterial Infection and Resistance of Chinese Medical Association,together with the National Clinical Research Center for Respiratory Disease,and the National Center for Respiratory Medicine,organized domestic experts in various fields such as respiratory,virology,infection,critical care,emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small‑Molecule Antiviral Drugs against COVID‑19.The main content of this consensus includes the introduction of seven small‑molecule antiviral drugs against COVID‑19,focusing on the drug recommendations for 14 special groups such as the elderly,patients with complicated chronic diseases,tumor patients,pregnant women,and children,and providing suggestions for clinicians to standardize drug use.展开更多
Chronic obstructive pulmonary disease(COPD),the third leading cause of death worldwide,led to approximately 3.23 million deaths in 2019 and imposed significant economic and health burdens.However,cardiovascular mortal...Chronic obstructive pulmonary disease(COPD),the third leading cause of death worldwide,led to approximately 3.23 million deaths in 2019 and imposed significant economic and health burdens.However,cardiovascular mortality accounts for approximately one-third of deaths in patients with COPD,[1]particularly in those with mild or moderate disease severity.[2]Studies have also identified a substantial increase in the risk of cardiovascular events in patients with COPD.[3,4]Given the notable risk of cardiopulmonary(pulmonary and cardiovascular)events in COPD,the management of COPD should incorporate strategies aiming at reducing the risk of cardiopulmonary events.Optimized treatment of patients with COPD may reduce their risk of cardiopulmonary events and potentially enhance survival benefit.Fully understanding the risk of cardiovascular events in patients with COPD is crucial for comprehensive management of disease.Thus,this article aims to offer an update on the risk of cardiovascular events in COPD and emphasize the importance of cooperation between pulmonologists and cardiologists.展开更多
The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic population.Here,we evaluated i...The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic population.Here,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMI<25 were enrolled in the study.Among them,119 were successfully treated with either direct acting antiviral(DAA)drugs or pegylated interferon/ribavirin(IFN/RBV)anti-HCV therapy.Fasting state-and oral glucose tolerance test(OGTT)-derived indexes were used to evaluateβ-cell function and insulin sensitivity.Among all subjects,19(13%)had T2DM and 21%exhibited pre-diabetes including 8%isolated impaired fasting glucose(IFG)and 13%combined IFG and impaired glucose tolerance(IGT).Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCVuninfected individuals.Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity andβ-cell function in CHC patients who achieved sustained virologic response(SVR),regardless of fasting or OGTT state.These findings emphasize the role of HCV in the development ofβ-cell dysfunction,while also suggesting that viral eradication can improve insulin secretion,reverse insulin resistance,and ameliorate glycemic control.These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.展开更多
The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19....The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.展开更多
基金supported by the National Key Research and Development Program of China(2021YFC2501800)Leader Project of Henan Province Health Young and Middle-aged Professor(HNSWJW2020013).
文摘BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP.METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis.RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM.CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.
文摘We comment on an article by GrubićRotkvićet al published in the recent issue of the World Journal of Cardiology.We specifically focused on possible factors affecting the therapeutic effectiveness of sodium-dependent glucose transporter inhibitors(SGLT2i)in patients with type 2 diabetes mellitus(T2DM)and their impact on comorbidities.SGLT2i inhibits SGLT2 in the proximal tubules of the kidneys,lowering blood glucose levels by inhibiting glucose reabsorption by the kidneys and causing excess glucose to be excreted in the urine.Previous studies have demonstrated a role of SGLT2i in cardiovascular function in patients with diabetes who take metformin but still have poor glycemic control.In addition,SGLT2i has been shown to be effective in anti-apoptosis,weight loss,and cardiovascular protection.Accordingly,it is feasible to treat patients with T2DM with cardiovascular or renal diseases using SGLT2i.
基金supported by the National Natural Science Foundation of China[grant nos.82073646,82273707 and 82373675]the Guangdong Basic and Applied Basic Research Foundation[grant nos.2022A1515010503 and 2024A1515010972]the Shenzhen Science and Technology Program[grant nos.JCYJ20220818095818040,JCYJ20230807142801003].
文摘Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could reflect early progression of atherosclerosis.Based on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.
基金supported by the following grants and funding:the National Science Foundation-Outstanding Youth Fund(No.82222001)the Emergency Key Program of Guangzhou Laboratory(Grant No.EKPG22-02)+2 种基金the Guangzhou Institute for Respiratory Health Open Project(funded by China Evergrande Group)with Project No,2020GIRHHMS09 and 2020GIRHHMS19the Zhongnanshan Medical Foundation of Guangdong Province(funding number not applicable)the Penghua Care Fund to the Medical Pioneers against Covid-19 of Shenzhen Social Commonweal Foundation(funding number not applicable,Guan W J).
文摘Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.
基金supported by the National Key R&D Program of China(No.2023YFC3041500 and 2023YFC3041700)the Key-Area R&D Program of Guangdong Province(No.2022B1111020002)+1 种基金the R&D Program of Guangzhou Laboratory(No.SRPG23-001)the Guangzhou Scienceand Technology Planning Project(No.202103000026 and 202201020316).
文摘The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be investigated.We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing.We found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(P.aeruginosa)(24.2%),Staphylococcus aureus(S.aureus)(14.0%),andKlebsiella pneumoniae(K.pneumonia)(13.4%)ranked as the top three coinfected bacteria.Aspergillus fumigatus(A.fumigatus)(39.5%),Pneumocystis jirovecii(P.jirovecii)(24.4%)andCanidia albicans(C.albicans)(22.1%)were the top three coinfected fungi.Epstein-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected viruses.Of note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease severity.Our study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.
基金This work is supported by the National Key Research and Development Program of China(2022YFC2407800)the General Program of National Natural Science Foundation of China(62271241)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(2023A1515012983)the Shenzhen Fundamental Research Program(JCYJ20220530112601003).
文摘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.
基金funded by the National Natural Science Foundation of China(Grantno.81873065)the Secondary Development Projects of Guangdong Famous and Excellent TraditionalChinese Patent Medicines(Grant no.20174005)+1 种基金the Natural Science Foundation of Guangdong Province(Grant no.2018A030310172)the China Postdoctoral Science Foundation(Grant no.2017M622652,2019M652987)。
文摘Isatis indigotica Fort.(Ban-Lan-Gen)is an herbal medicine prescribed for influenza treatment.However,its active components and mode of action remain mostly unknown.In the present study,erucic acid was isolated from Isatis indigotica Fort.,and subsequently its underlying mechanism against influenza A virus(IAV)infection was investigated in vitro and in vivo.Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity.Erucic acid was found to exert inhibitory effects on IAV or viral(v)RNA-induced pro-inflam-matory mediators as well as interferons(IFNs).The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-kB and p38 MAPK signaling.Furthermore,the NF-kB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3(ISGF-3),and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized cells.Additionally,IAV-or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid.In vivo,erucic acid administration consistently displayed decreased lung viral load and viral antigens expression.Meanwhile,erucic acid markedly reduced CD8+cytotoxic T lymphocyte(CTL)recruitment,pro-apoptotic signaling,hyperactivity of multiple signaling pathways,and exacerbated immune inflammation in the lung,which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1)strain infection.Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury,suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.
基金This work was supported in part by the National Natural Science Foundation of China(No.82174053)This research received a grant from Dalian Fusheng Pharmaceutical Co.,Ltd.(Liaoning province,China)。
文摘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.
基金This work was supported by the Science research project of the Guangdong Province[Grant No.2020B111110001]Guangzhou Medical University High-level University Clinical Research and Cultivation Program(Guangzhou Medical University released[2017]No.159,160).
文摘Background:From early experience,some Traditional Chinese Medicine and Arbidol had effects of against COVID-19,infer that the combination of Liushen capsules and Arbidol may further increase the therapeutic.Methods/Design:We conducted a randomized,blank parallel-controlled,open-label,multi-center,basal therapy-loaded design clinical trial.A total of 40 patients are going to be recruited after satisfying the criteria.Participants will be allocated randomly into the treatment group with the combination of Arbidol and Liushen capsules and the control group with the basic therapy.Each group will receive treatment at least 7-days or until the virus becomes negative,and visits after drug administration at day 3(visit 1),the day when the virus becomes negative(visit 2),day 7(visit 3),the day before discharge(visit 4)and day 28(visit 5),to collect their survival status and disease prognosis so that the efficacy and safety of a combination of Arbidol and Liushen capsule will be evaluated.Discussion:We described the protocol of the first clinical trial for treatment COVID-19 by using a combination of Arbidol and Liushen capsules.The results of this study will provide a basis for the design and sample size estimate of subsequent large-scale clinical trials.Trial registration:This study has been registered at Chinese clinical trial Registry(chictr.org.cn):ChiCTR2000029993.
文摘Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and West.This study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national levels.Methods:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 database.Age-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian countries.Results:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer increased.Smoking was the leading specific risk factor for deaths from both TBL and larynx cancers.The burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central Asia.Deaths,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent years.Conclusions:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in Asia.SDI and smoking were the main factors influencing the disease burden of TBL cancer in Asian countries.This study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.
基金supported by the National Natural Science Fund for Distinguished Young Scholars(No.82225025)the National Natural Science Foundation of China(Nos.21877049,32171296)+1 种基金China Postdoctoral Science Foundation(No.2021M690066)Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110300).
文摘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.
基金This study was supported by the National Natural Science Foundation of China(82072264,81970003)Natural Science Foundation of Guangdong Province,China(2021A1515011071)The study sponsors had no involvement in the study design,in the collection,analysis and interpretation of data,in the writing of the manuscript,and in the decision to submit the manuscript for publication.
文摘Human adenoviruses(HAdVs)can cause acute hepatitis in immunocompromised patients.However,it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children.In this study,the liver function test(LFT)results were retrospectively analyzed among children hospitalized(age<14 years)between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses.Alanine transaminase(ALT)and aspartate aminotransferase(AST)levels were elevated in 7.74%and 46.89%of patients,respectively.All patients with>2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55.Significantly higher levels of ALT,AST,γ-glutamyl transpeptidase(γ-GT),and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group.HAdV-55 infection led to significantly higherγ-GT,total bilirubin,and direct bilirubin levels than the other infection types.The records of four patients with serial monitoring of the LFT results were further analyzed.Multiple indicators remained abnormal during the entire hospitalization in these patients.These results indicate that HAdV infection is often accompanied by abnormal liver function,and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.
基金the Collaborative Research Project of the National Natural Science Foundation of China(L2224041)the Chinese Academy of Sciences(XK2022DXC005)+2 种基金Frontier of Interdisciplinary Research on Monitoring and Prediction of Pathogenic Microorganisms in the AtmosphereSelf-supporting Program of Guangzhou Laboratory(SRPG22-007)Fundamental Research Funds for the Central Universities(lzujbky-2022-kb09).
文摘Corona virus disease 2019(COVID-19)has exerted a profound adverse impact on human health.Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people.Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks.Monitoring of pathogenic microorganisms in the air,especially in densely populated areas,may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage.The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation,allocate health resources,and formulate epidemic response policies.This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission,which lays a theoretical foundation for the monitoring and prediction of epidemic development.Secondly,the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized.Subsequently,this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology,atmospheric sciences,environmental sciences,sociology,demography,etc.By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere,this review proposes suggestions for epidemic response,namely,the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.
基金supported by grants from Shenzhen Science and Technology Program(Grant No.JCYJ20220530163206015,China)National Key Research and Development Program of China(Grant No.2021YFA0910900)+4 种基金Shenzhen Science and Technology Program(Grant No.JCYJ20220818103017036,China)the National Science Fund for Distinguished Young Scholars(Grant No.82025022,China)Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515110033,China)Guangdong Science and Technology Plan Project,construction of high-level biosafety laboratories(Grant No.2021B1212030010,China)Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515110033,China).
文摘The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long half-life.Despite its vital role in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)assembly and host inflammatory response,it remains an unexplored target for drug development.In this study,we identified a small-molecule compound(ciclopirox)that promotes NP degradation using an FDA-approved library and a drug-screening cell model.Ciclopirox significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP degradation.Ciclopirox induced abnormal NP aggregation through indirect interaction,leading to the formation of condensates with higher viscosity and lower mobility.These condensates were subsequently degraded via the autophagy-lysosomal pathway,ultimately resulting in a shortened NP half-life and reduced NP expression.Our results suggest that NP is a potential drug target,and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.
基金This study was supported by the Guangdong Basic and Applied Basic Research Foundation(2022B1515120055)the National Natural Science Foundation of China(82341060 and 82170024).
文摘Cough is one of the most common symptoms observed in patients presenting with COVID-19,persisting for an extended duration following SARS-CoV-2 infection.We aim to describe the distribution of airway microbiota and explore its role in patients with post-CovID-19 chronic cough.A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China.Airway microbiota profiling is assessed in nasopharyngeal swab,nasal lavage,and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection.Our findings reveal that bacterial families Staph-ylococcaceae,Corynebacteriaceae,and Enterobacteriaceae are the most prevalent in the upper airway,while Streptococcaceae,Lachnospiraceae,and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway.An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month.Furthermore,the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity.In conclusion,dynamic alterations in the airway microbial composition may contribute to the post-coviD-19 chronic cough progression,while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.
基金Emergency Key Program of Guangzhou Laboratory(EKPG21-06)the Macao Science and Technology Development Fund(0022/2021/A1)+1 种基金the Young Top Talent of Science and Technology Innovation Department of Guangdong Province(2021TQ060189)National Administration of Traditional Chinese Medicine’s Interdisciplinary Innovation Team Project(ZYYCXTU-D-202201).
文摘Although COVID‑19 no longer constitutes a“public health emergency of international concern”,which still has being spreading around the world at a low level.Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China.Although a variety of small‑molecule antiviral drugs against COVID‑19 have been listed in China,there is no specific drug recommendation for special populations.Society of Bacterial Infection and Resistance of Chinese Medical Association,together with the National Clinical Research Center for Respiratory Disease,and the National Center for Respiratory Medicine,organized domestic experts in various fields such as respiratory,virology,infection,critical care,emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small‑Molecule Antiviral Drugs against COVID‑19.The main content of this consensus includes the introduction of seven small‑molecule antiviral drugs against COVID‑19,focusing on the drug recommendations for 14 special groups such as the elderly,patients with complicated chronic diseases,tumor patients,pregnant women,and children,and providing suggestions for clinicians to standardize drug use.
文摘Chronic obstructive pulmonary disease(COPD),the third leading cause of death worldwide,led to approximately 3.23 million deaths in 2019 and imposed significant economic and health burdens.However,cardiovascular mortality accounts for approximately one-third of deaths in patients with COPD,[1]particularly in those with mild or moderate disease severity.[2]Studies have also identified a substantial increase in the risk of cardiovascular events in patients with COPD.[3,4]Given the notable risk of cardiopulmonary(pulmonary and cardiovascular)events in COPD,the management of COPD should incorporate strategies aiming at reducing the risk of cardiopulmonary events.Optimized treatment of patients with COPD may reduce their risk of cardiopulmonary events and potentially enhance survival benefit.Fully understanding the risk of cardiovascular events in patients with COPD is crucial for comprehensive management of disease.Thus,this article aims to offer an update on the risk of cardiovascular events in COPD and emphasize the importance of cooperation between pulmonologists and cardiologists.
基金supported by grants from the National Natural Science Foundation of China(grant number 82170838,82370873)Open Research Fund Program of the State Key Laboratory of Virology of China(grant number 2018IOV003).
文摘The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic population.Here,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMI<25 were enrolled in the study.Among them,119 were successfully treated with either direct acting antiviral(DAA)drugs or pegylated interferon/ribavirin(IFN/RBV)anti-HCV therapy.Fasting state-and oral glucose tolerance test(OGTT)-derived indexes were used to evaluateβ-cell function and insulin sensitivity.Among all subjects,19(13%)had T2DM and 21%exhibited pre-diabetes including 8%isolated impaired fasting glucose(IFG)and 13%combined IFG and impaired glucose tolerance(IGT).Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCVuninfected individuals.Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity andβ-cell function in CHC patients who achieved sustained virologic response(SVR),regardless of fasting or OGTT state.These findings emphasize the role of HCV in the development ofβ-cell dysfunction,while also suggesting that viral eradication can improve insulin secretion,reverse insulin resistance,and ameliorate glycemic control.These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.
基金This work was supported by grants from the National Key Research and Development Program of China(2020YFA0908200 and 2021YFA1101300)GuangDong Basic and Applied Basic Research Foundation(202201011198)+1 种基金Guangzhou Laboratory Key Research Foundation(TL22-21)R&D Program of Guangzhou National Laboratory(SRPG22-021).
文摘The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.