Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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.

Predictive value of systemic immunity index for sepsis in low-medium risk community-acquired pneumonia

Objective:To assess the predictive value of systemic immune inflammation index(SII)for sepsis in low-and medium-risk community-acquired pneumonia.Methods:A total of 589 elderly patients with low-and medium-risk community-acquired pneumonia admitted to the Emergency Department of the Second Affiliated Hospital of Hainan Medical University from January 2020 to January 2023 were included as the research subjects,and the general information and laboratory test results of the patients were collected,and the optimal cut-off value of continuous variables for predicting sepsis in elderly patients with low-and medium-risk community-acquired pneumonia was determined by plotting the receiver work characteristic(ROC)curve,which was converted into dichotomous variables and univariate and multivariate logistic Regression analysis of the influencing factors of sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.Based on this,a nomogram model is constructed to predict the risk of sepsis.The differentiation,consistency and accuracy of the model were verified by calibration curve and subject operating characteristic(ROC)curve,and the clinical utility of the model was determined by decision curve analysis.Results:A total of 589 elderly patients with low-and intermediate-risk community-acquired pneumonia were included in this study,of which 96(16.30%)developed sepsis.There were significant differences in age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,PCT,SII and other indexes between sepsis and non-sepsis groups(P<0.05).Logistics regression analysis showed that age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,and SII were independent risk factors for sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.The nomogram prediction model was used to verify the results,and the AUC was 0.826(95%CI:0.780-0.872),and the calibration curve tended to the ideal curve with good accuracy.The decision curve shows that when the threshold of the model is between 0.10~0.78,the model has the advantage of clinical benefit.Conclusion:The nomogram prediction model constructed based on SII to predict sepsis in elderly patients with low-and medium-risk community-acquired pneumonia has good accuracy,which can predict the occurrence of sepsis early,help early identification of high-risk groups and timely intervention,and thus improve the prognosis of patients.

Role of biomarkers in community-acquired pneumonia management

Community-acquired pneumonia(CAP)poses a significant global health threat,particularly affecting vulnerable populations.Biomarkers and scoring systems play a crucial role in diagnosing,assessing severity,and guiding treatment decisions for CAP patients.Biomarkers like C reactive protein,procalcitonin,and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment,while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories.Emerging biomarkers(uremia,elevated respiratory rate,hypotension,and age≥65)like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis.However,further research is needed to determine their precise roles and clinical utility in CAP management.

Pulmonary infarct masquerading as community-acquired pneumonia in the COVID-19 scenario: A case report

BACKGROUND Pulmonary embolism(PE)requires a high degree of clinical suspicion for its diagnosis and can mimic pneumonia due to its clinical,radiological,and laboratory findings.Co-existence of PE and pneumonia can also occur,which is surprisingly more common than appreciated.CASE SUMMARY Here,we report a case of a young male who initially presented during the peak of the coronavirus disease 2019 pandemic with features of pneumonia.He was kept under observation and was later diagnosed and treated for a right main pulmonary artery embolism without any identifiable source of thrombosis.CONCLUSION PE and pneumonia share common clinical,radiological,and laboratory findings that may delay the diagnosis of PE.Hypoxia disproportionate to the extent of radiological involvement could be an indicator of an underlying PE.

Clinical characteristics of community-acquired pneumonia in children caused by mycoplasma pneumoniae with or without myocardial damage:A single-center retrospective study

BACKGROUND Mycoplasma pneumoniae(MP)is a prevalent pathogen that causes respiratory infections in children and adolescents.AIM To assess the differences in the clinical features of MP-associated communityacquired pneumonia(CAP)in children who presented with mild or severe mycoplasma pneumoniae pneumonia(MPP);to identify the incidence of myocardial damage between the two groups.METHODS This work is a retrospective study.We identified children between 2 mo and 16 years of age with clinical and radiological findings consistent with CAP.We admitted patients to the inpatient department of the Second Hospital of Jilin University,Changchun,China,from January 2019 to December 2019.RESULTS A total of 409 hospitalized patients were diagnosed with MPP.Among them were 214(52.3%)males and 195(47.7%)females.The duration of fever and cough was the longest in severe MPP cases.Similarly,plasma levels of highly sensitive Creactive protein(t=-2.834,P<0.05),alanine transaminase(t=-2.511,P<0.05),aspartate aminotransferase(t=-2.939,P<0.05),and lactate dehydrogenase(LDH)(t=-2.939,P<0.05)were all elevated in severe MPP cases compared with mild MPP cases,and these elevations were statistically significant(P<0.05).Conversely,the neutrophil percentage was significantly lower in severe MPP cases than in mild MPP cases.The incidence of myocardial damage was significantly higher in severe MPP cases than in mild MPP cases(χ^(2)=157.078,P<0.05).CONCLUSION Mycoplasma pneumoniae is the main cause of CAP.The incidence of myocardial damage was higher and statistically significant in severe MPP cases than in mild MPP cases.

Heparin-binding protein combined with human serum albumin in early assessment of community-acquired pneumonia:A retrospective study

Objective:To investigate the application of heparin-binding protein along with albumin(HBP+ALB)in evaluating the severity of community-acquired pneumonia(CAP)and compares it with single HBP,white blood cells(WBCs),C-reactive protein(CRP),and procalcitonin(PCT).Methods:A total of 226 patients with CAP admitted to the Emergency Department of Zhujiang Hospital,Southern Medical University,Guangdong,China,between March 1,2021,and March 1,2022,were enrolled.The patients were grouped into two groups:mild CAP(n=175)and severe CAP(sCAP)(n=51).Patients'characteristics and laboratory data were obtained.ROC curve and the value of the area under the curve(AUC)were used to evaluate the predictive values of HBP,ALB,WBC,CRP,and PCT.Results:WBC count,CRP,PCT,HBP,creatinine,and D-dimer were higher in the sCAP group,while ALB was lower in the sCAP group(P<0.05)than those in the mild CAP group.The AUCs of WBC,CRP,PCT,HBP,and HBP+ALB were 0.633(95%CI:0.545-0.722,P<0.05),0.635(95%CI:0.542-0.729,P<0.05),0.705(95%CI:0.619-0.791,P<0.05),0.809(95%CI:0.736-0.883,P<0.05),and 0.889(95%CI:0.842-0.936,P<0.05),respectively.Conclusions:HBP+ALB has a higher predictive value than single HBP,PCT,CRP and WBC used alone for the early assessment of CAP.

Klebsiella pneumoniae infections after liver transplantation:Drug resistance and distribution of pathogens,risk factors,and influence on outcomes

BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.

Serum inflammatory markers in children with Mycoplasma pneumoniae pneumonia and their predictive value for mycoplasma severity

BACKGROUND Mycoplasma pneumoniae pneumonia(MPP)significantly impacts pediatric health,necessitating markers for early severe disease identification.AIM To investigate the correlation between serum inflammatory marker and the severity of MPP in children.METHODS A prospective study was carried out from January 2023 to November 2023.A total of 160 children with MPP who underwent treatment were selected:80 had severe MPP and 80 had mild MPP.Clinical and laboratory data were collected at the time of hospital admission and during hospitalization.Receiver operating characteristic curves were utilized to assess the diagnostic and prognostic for severe MPP.RESULTS Fever duration and length of hospitalization in pediatric patients with severe MPP exceeded those with mild MPP.The incidence of pleural effusion,lung consolidation,and bronchopneumonia on imaging was markedly elevated in the severe MPP cohort compared to the mild MPP cohort.In contrast to the mild cohort,there was a notable increase in C-reactive protein(CRP),procalcitonin(PCT),erythrocyte sedimentation rate,lactic dehydrogenase,D-dimer,and inflammatory cytokines[interleukin(IL)-6,IL-8,IL-10 and tumor necrosis factor(TNF)-α]in the severe MPP group were significantly higher.CONCLUSION Serum inflammatory markers(CRP,PCT,IL-6,D-dimer,IL-10 and TNF-α)were considered as predictors in children with severe MPP.

Serum activin A as a prognostic biomarker for community acquired pneumonia

BACKGROUND It is essential to develop new biomarker with effective prognostic roles because of the unclear clinical use of the current community-acquired pneumonia(CAP)predictors.AIM To evaluate the association between serum activin A levels and prognosis in CAP patients.METHODS A total of 168 CAP individuals grouped according to the severity and prognosis of illness condition,and 48 healthy individuals as the control group were enrolled in this study.Circulating concentrations of activin A were measured using enzymelinked immunoassays.The interaction between activin A levels and etiologies of CAP was determined.Based on the severity of CAP,110 patients(65.48%)were categorized into group-I,42(25%)cases were grouped into group-II,and 16(9.52%)cases were categorized into group-III.RESULTS Serum activin A levels were higher in patients with CAP than controls,but independent of etiology.Moreover,the scores of Pneumonia Severity Index(PSI)and CURB-65 positively correlated with the increasing levels of serum activin A,and were at their highest peak in individuals in group-III(P<0.001).Combining activin A with CURB-65 or PSI was more effective in improving predictive property(P<0.01).According to Cox proportional regression analysis,after adjusting clinical parameters,we confirmed that activin A showed a powerful predictive property for hospital mortality in CAP patients(P<0.001).CONCLUSION Higher level of serum activin A was associated with poor prognosis of CAP.Activin A can be used as a more valuable biomarker of prognosis in CAP patients.

Prevention of ventilator-associated pneumonia with inhaled antibiotics

The direct delivery of inhaled antibiotics to the respiratory tract has been a subject of enduring interest among medical practitioners and researchers due to the associated favorable pharmacokinetics.This interest has been particularly pronounced in the context of critically illpatients,wherehealthcare-associatedpulmonary infections represent a significant challenge,driving continued exploration of inhaled antibiotics for intubated patients.Recent high-level evidence has shown a very promising application in the field of ventilator-associated pneumonia (VAP) prevention.^([1]).

Chinese herbal medicine combined with Western medicine for Mycoplasma pneumoniae pneumonia in children:An overview of systematic reviews

Objective:To summarize the characteristics and evaluate the quality of the methodology and evidence within systematic reviews(SRs)of Chinese herbal medicine(CHM)for Mycoplasma pneumoniae pneumonia(MPP)inchildren.Methods:SRs of randomized controlled trials were searched using PubMed,the Cochrane Library,Embase,the Chinese National Knowledge Infrastructure Databases(CNKI),the Chinese Scientific Journals Database(VIP),Wanfang,and the SinoMed Database.SRs on the use of CHM alone or in combination with Western medications for MPP in children were included.The study compared the effects of Western medicine alone with those of CHM.The evidence quality using the A Measurement Tool to Assess Systematic Reviews(AMSTAR)2,the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020,and the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)criteria.The primary indicators were the total effective rate,fever subsidence time,and cough disappearance time.The secondary outcomes were pulmonary rale disappearance time,average hospitalization time,lung X-ray infiltrate disappearance time,immunological indices,and inflammatory cytokine levels.Results:Twelve relevant SRs were included;75%(9/12)were assessed as very low quality,and 25%(3/12)Were rated as low quality using the AMSTAR 2 criteria.According to the PRISMA 2020 checklist,the average SR score was 20.3 out of a 27 point maximum.In all SRs,CHM demonstrated improvement in symptoms and signs among children with MPP.The evidence quality using the GRADE criteria ranged from"very low"(>50%)to"moderate"(<5%).The most common downgrading factor was imprecision,followed by publication bias and inconsistency.Conclusion:This overview highlights the limited quality of the methodology and evidence of the included SRs.Although the included studies showed the beneficial effects of CHM on MPP in children,it was difficult to draw firm conclusions owing to methodological flaws.

Acute Eosinophilic Pneumonia (AEP) Due to Daptomycin: Is Autoimmunity a Clinico-Pathophysiologic Bridge to AEP?

Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

MSD-Net: Pneumonia Classification Model Based on Multi-Scale Directional Feature Enhancement

Computer-aided diagnosis of pneumonia based on deep learning is a research hotspot.However,there are some problems that the features of different sizes and different directions are not sufficient when extracting the features in lung X-ray images.A pneumonia classification model based on multi-scale directional feature enhancement MSD-Net is proposed in this paper.The main innovations are as follows:Firstly,the Multi-scale Residual Feature Extraction Module(MRFEM)is designed to effectively extract multi-scale features.The MRFEM uses dilated convolutions with different expansion rates to increase the receptive field and extract multi-scale features effectively.Secondly,the Multi-scale Directional Feature Perception Module(MDFPM)is designed,which uses a three-branch structure of different sizes convolution to transmit direction feature layer by layer,and focuses on the target region to enhance the feature information.Thirdly,the Axial Compression Former Module(ACFM)is designed to perform global calculations to enhance the perception ability of global features in different directions.To verify the effectiveness of the MSD-Net,comparative experiments and ablation experiments are carried out.In the COVID-19 RADIOGRAPHY DATABASE,the Accuracy,Recall,Precision,F1 Score,and Specificity of MSD-Net are 97.76%,95.57%,95.52%,95.52%,and 98.51%,respectively.In the chest X-ray dataset,the Accuracy,Recall,Precision,F1 Score and Specificity of MSD-Net are 97.78%,95.22%,96.49%,95.58%,and 98.11%,respectively.This model improves the accuracy of lung image recognition effectively and provides an important clinical reference to pneumonia Computer-Aided Diagnosis.

A Hybrid Classification and Identification of Pneumonia Using African Buffalo Optimization and CNN from Chest X-Ray Images

An illness known as pneumonia causes inflammation in the lungs.Since there is so much information available fromvarious X-ray images,diagnosing pneumonia has typically proven challenging.To improve image quality and speed up the diagnosis of pneumonia,numerous approaches have been devised.To date,several methods have been employed to identify pneumonia.The Convolutional Neural Network(CNN)has achieved outstanding success in identifying and diagnosing diseases in the fields of medicine and radiology.However,these methods are complex,inefficient,and imprecise to analyze a big number of datasets.In this paper,a new hybrid method for the automatic classification and identification of Pneumonia from chest X-ray images is proposed.The proposed method(ABOCNN)utilized theAfrican BuffaloOptimization(ABO)algorithmto enhanceCNNperformance and accuracy.The Weinmed filter is employed for pre-processing to eliminate unwanted noises from chest X-ray images,followed by feature extraction using the Grey Level Co-Occurrence Matrix(GLCM)approach.Relevant features are then selected from the dataset using the ABO algorithm,and ultimately,high-performance deep learning using the CNN approach is introduced for the classification and identification of Pneumonia.Experimental results on various datasets showed that,when contrasted to other approaches,the ABO-CNN outperforms them all for the classification tasks.The proposed method exhibits superior values like 96.95%,88%,86%,and 86%for accuracy,precision,recall,and F1-score,respectively.

Protective eff ect and mechanism of nanoantimicrobial peptide ND-C14 against Streptococcus pneumoniae infection

BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.

Occurrence of K1 and K2 serotypes and genotypic characteristics of extended spectrumβ-lactamases-producing Klebsiella pneumoniae isolated from selected hospitals in Malaysia

Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

iTRAQ-based proteomics reveals the mechanism of action of Yinlai decoction in treating pneumonia in mice consuming a high-calorie diet

Objective:To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie dietinduced pneumonia through proteomics analysis.Methods:Based on the Gene Expression Omnibus(GEO)database,lung tissue samples from normal and high-fat diet(HFD)fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses.In the animal experiments,mice were randomly divided into the control(N),high-calorie diet pneumonia(M),and Yinlai decoction treatment(Y)groups.Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d.The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d.Pathological evaluation of the lung tissue was performed.Differentially expressed proteins(DEPs)in the lung tissue were identified using quantitative proteomics and bioinformatics analyses.The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory(MGL)Tools.DEPs were verified by western blot.Results:GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue.The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet.A total of 47 DEPs were identified between the Y and M groups.Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle(TCA)and oxidative phosphorylation.The protein-protein interaction network revealed that Atp5a1,Pdha1,and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction.Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide,praeruptorin B,chrysoeriol,and other components in Yinlai decoction to Atp5a1.Conclusion:The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation.Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.