Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pne...Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.展开更多
Mycoplasma pneumoniae(M.pneumoniae)is a common pathogen that causes community-acquired pneumonia in children.The clinical presentation of this pathogen can range from mild self-limiting illness to severe and refractor...Mycoplasma pneumoniae(M.pneumoniae)is a common pathogen that causes community-acquired pneumonia in children.The clinical presentation of this pathogen can range from mild self-limiting illness to severe and refractory cases.Complications may occur,such as necrotizing pneumonia and respiratory failure.Extrapulmonary complications,including encephalitis,myocarditis,nephritis,hepatitis,or even multiple organ failure,can also arise.In this editorial,we dis-cuss the clinical implications of the significant findings from the article"Serum inflammatory markers in children with M.pneumoniae pneumonia and their predictive value for mycoplasma severity"published by Wang et al.They reported that measuring lactic dehydrogenase,interleukin-6 levels,and D-dimer effectively predicts refractory M.pneumoniae pneumonia cases.展开更多
Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(S...Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].展开更多
Background: Mycoplasma pneumoniae (MP) is the primary causative agent of community-acquired pneumonia, which has increasingly become resistant to macrolides, complicating treatment regimens, especially with the co-inf...Background: Mycoplasma pneumoniae (MP) is the primary causative agent of community-acquired pneumonia, which has increasingly become resistant to macrolides, complicating treatment regimens, especially with the co-infection factor. Its worldwide prevalence has fluctuated due to the influence of the COVID-19 pandemic. The study investigated co-infection patterns in children diagnosed with Mycoplasma pneumoniae pneumonia (MPP). Methods: From June 2022 to December 2023, we retrospectively analyzed the clinical data for hospitalized children with Mycoplasma pneumoniae pneumonia in Wuhan, China. We collected data on age, sex, clinical information, and pathogenic results. We also collected sputum or bronchoalveolar lavage fluid (BALF) samples to test respiratory pathogens and macrolide resistance using targeted microbial next-generation sequencing (tNGS). We analyzed the data using SPSS. Results: The study involved 417 patients diagnosed with MPP, of whom 86.33% had co-infections. Co-infections were notably linked to lobar pneumonia, prominent imaging shadows and higher macrolide resistance rate. Key bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, rhinoviruses, and human adenoviruses (HADV). In MPP cases, Candida albicans was the fungal pathogen related to co-infections. The co-infection with HADV and human bocavirus 1 (HBoV1) correlated with prolonged fever, whereas Bordetella pertussis was linked to prolonged cough. In contrast, Candida albicans exhibited a weaker association with diffuse large-area infiltration on chest imaging, and its co-infection was less likely to result in severe disease. Conclusion: These results offer valuable insight into Mycoplasma pneumoniae pneumonia in children, highlighting the impact of co-infections on the disease’s clinical outcomes.展开更多
Background:Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics.Novel pneumonia therapies and biomarkers are urgently needed to improve ou...Background:Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics.Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy.Using an established baboon model of S.pneumoniae pneumonia,we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.Methods:We performed whole blood transcriptomics,unbiased proteomics,and peripheral cytokine measurements serially in baboons inoculated with S.pneumoniae(n=23)or saline(n=10)and modeled the peripheral blood host response using principal components analysis and complex sparse logistic regression.Differentially expressed genes were analyzed for pathway analysis.Results:Inoculated animals developed characteristic signs and symptoms of pneumonia.A 39-gene signature was derived that classified S.pneumoniae infection with high accuracy(auROC 0.9 and 0.99 at 24 and 48 h post-inoculation,respectively).Similar performance was observed for 48-h biomarker signatures derived from peripheral blood plasma proteomic and cytokine measurements(both auROC>0.9).The gene signature retained strong diagnostic performance(auROC=0.88)when transformed to human orthologs and applied to patients with acute respiratory illness(n=34)or healthy controls(n=20).Pathway analysis at 48 h identified downregulation of mitophagy and glucocorticoid signaling in peripheral blood.Conclusions:We report novel peripheral blood gene and protein expression signatures of S.pneumoniae pneumonia that could improve pneumonia diagnosis and found distinct pathways that may be amenable to modulation.Our findings illustrate how non-human primate models of bacterial pneumonia can successfully translate biomarker discoveries to patients.展开更多
Introduction: The misuse of antibiotics has driven the emergence of antimicrobial resistance, with certain bacterial species, including Klebsiella pneumoniae, initially susceptible to most antibiotics, now exhibiting ...Introduction: The misuse of antibiotics has driven the emergence of antimicrobial resistance, with certain bacterial species, including Klebsiella pneumoniae, initially susceptible to most antibiotics, now exhibiting resistance to multiple antimicrobial agents. The objective of this study was to investigate the distribution and antimicrobial resistance profiles of Klebsiella pneumoniae strains isolated at the Yaoundé Central Hospital. Methodology: The study was conducted over a period of 4 months (March 1st, 2023-July 1st, 2023) and involved 32 strains isolated from bacterial cultures performed on patients, regardless of sex. The different Klebsiella pneumoniae strains were isolated using conventional methods. Identification, antibiogram, and detection of resistance enzyme production were generated using the VITEK 2 system. The Carbapenem-resistant K.N.I.V.O. kit was used to detect carbapenemases. Data analysis was performed using EXCEL 2019 software. Results: Out of 196 samples collected from various biological products, 32 Klebsiella pneumoniae strains were isolated, representing 16.32% (196/32). Urine samples were most frequently affected, accounting for 53.125%. The emergency department was the most represented (40.63%) by these isolates. The mean age was 50 years, with a minimum of 20 years and a maximum of 80 years. The sex ratio was equal to 1. The identified strains were resistant to cefotaxime (78.13%), cefoxitin (62.50%), tobramycin (71.88%), gentamicin (56.25%), ofloxacin (81.25%), and cotrimoxazole (78.13%). 78.25% were ESBL producers. Three strains were resistant to carbapenems, accounting for 9.37%;one of which exhibited the NDM type. Conclusion: This study highlights the evolving bacterial resistance to antibiotics, which requires adequate measures through the strengthening of the Antimicrobial Resistance (AMR) program in Cameroon.展开更多
This article discusses the findings presented by Zhang et al.They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a ho...This article discusses the findings presented by Zhang et al.They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing.In this article,we focus on the connection between chronic kidney disease and the intestinal microbiota,and propose microbiota transplantation as a potential treatment for this patient group.We also examine an intriguing phenomenon related to hepatic encephalopathy,and provide insights into the future research.展开更多
Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s st...Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s study highlights risk factors,such as elevated day-one alanine aminotransferase levels and prolonged catheterization,and identifies polymyxin B and ceftazidime/avibactam as effective treatments.However,limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies.Future directions should include routine CRKP colonization surveillance,immune and genomic profiling,and the development of novel therapeutics.By integrating these approaches,we can improve the prevention,diagnosis,and treatment of KPIs in LT patients.展开更多
Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine mi...Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.展开更多
The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative ba...The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.展开更多
Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic ...Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.展开更多
AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vi...AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.展开更多
BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has...BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.展开更多
Hypervirulent Klebsiella pneumoniae(hvKp)is a major cause of severe community-acquired infection.A key plasmidencoded factor,regulator of mucoid phenotype A(RmpA),activates capsule locus gene expression to promote hyp...Hypervirulent Klebsiella pneumoniae(hvKp)is a major cause of severe community-acquired infection.A key plasmidencoded factor,regulator of mucoid phenotype A(RmpA),activates capsule locus gene expression to promote hypermucoviscosity,a phenotype that is strongly linked to increased pathogenicity.However,the precise regulatory mechanisms that control RmpA in hvKp remain poorly understood.In this study,we constructed a rmpA knockdown strain in hvKp using CRISPR interference and assessed the global regulatory role of RmpA through complementary multi-omic sequencing(RNA sequencing[RNA-seq]and chromatin immunoprecipitation sequencing[ChIP-seq]),promoter-gfp reporter assays,and phenotypic experiments.The functional role of RmpA was evaluated in Escherichia coli via heterologous expression.The RNA-seq analysis revealed that RmpA activates carbohydrate metabolism pathways,but represses pathways related to DNA replication,ribosome metabolism,and biofilm formation.The ChIP-seq analysis further confirmed the potential role of RmpA as a global regulator that enhances capsule production by activating transcripts within the capsule locus.It also upregulates genes involved in sugar metabolism and transport,which supplies essential precursors for capsule synthesis.RmpA modulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type Ⅲ fimbriae genes.Notably,RmpA overexpression in E.coli induced changes in multiple metabolic pathways.These findings position RmpA as a latent central regulator in hvKp that orchestrates the metabolic pathways and phenotypic traits essential for virulence.展开更多
Objective:To investigate the correlation between Mycoplasma pneumoniae infection and childhood asthma,and to explore the impact of Mp infection on airway inflammation and airway hyperresponsiveness in children with as...Objective:To investigate the correlation between Mycoplasma pneumoniae infection and childhood asthma,and to explore the impact of Mp infection on airway inflammation and airway hyperresponsiveness in children with asthma.Methods:58 children with bronchopneumonia admitted to the First People’s Hospital of Jintan,Changzhou from April 2024 to October 2024 were selected as the study subjects.The levels of cytokines IL-4,IL-17,TGF-β1,and INF-γ in the serum were compared between the MP group and non-MP group,as well as between the MP wheezing group and MP nonwheezing group.Results:The levels of IL-17 and IL-4 in the MP group were significantly higher than those in the non-MP group(P<0.05),while there was no statistically significant difference in the other indicators(P>0.05).Statistically significant differences in IL-17 and IL-4 were observed between the wheezing and non-wheezing groups(P<0.05),while there was no statistically significant difference in the other indicators(P>0.05).There was a significant difference in IL-17 among the groups(P<0.05).The difference in IL-17 between the MP group and non-MP group was significant(P<0.05),and the difference between the wheezing and non-wheezing groups was marginally significant(P<0.05).Conclusion:M.pneumoniae infection may be one of the risk factors for the onset of childhood asthma,but its mechanism remains unclear.Further research is needed to determine whether Mp infection can serve as a biomarker for childhood asthma and to elucidate its underlying mechanism.展开更多
BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatm...BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.展开更多
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 pneum...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.展开更多
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 ...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.展开更多
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.Metho...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.展开更多
BACKGROUND The incidence of Klebsiella pneumoniae(K.pneumoniae)infection in patients with cirrhosis has been increasing over recent years,posing certain difficulties in clinical treatment.AIM To analyze the clinical f...BACKGROUND The incidence of Klebsiella pneumoniae(K.pneumoniae)infection in patients with cirrhosis has been increasing over recent years,posing certain difficulties in clinical treatment.AIM To analyze the clinical features of patients with liver cirrhosis and identify the risk factors to help the early diagnosis and treatment of these diseases.METHODS Clinical data and laboratory tests were collected from 72 patients with cirrhosis confirmed by secretion or blood culture of K.pneumoniae infection at Beijing Ditan Hospital,Capital Medical University,between May 2016 and October 2018.Data from hospitalized patients with liver cirrhosis and K.pneumoniae infections,in-cluding age,sex,antimicrobial use,length of stay,site of infection,distribution of pathogenic bacteria,complications,invasive operations,laboratory indicators,treatment,and clinical regression,were extracted and retrospectively analyzed.Clinical data and biochemical values were included in the multivariate logistic regression analysis.RESULTS A total of 52 men and 20 women,with an age range from 29 to 85 years and an average age of 57.7±12.54,were analyzed.The incidence of hospital K.pneu-moniae infection in patients with cirrhosis was approximately 19.44%.The most common the infection site was the bloodstream,followed by the respiratory tract,abdominal cavity,and biliary tract.Risk factors for infection were old age,long hospital stays,gastrointestinal bleeding,and low serum albumin levels,while prophylactic antibiotics were protective factors.The multivariate analysis suggested that other infections,chronic diseases,and invasive procedures were independent factors.CONCLUSION In clinical practice,the length of hospital stays should be shortened as much as possible,invasive operations should be reduced,antibiotics should be rationally used,and the patients’liver function should be timely improved.This is of great significance for reducing the incidence of hospital infection.展开更多
基金supported by the National Natural Science Foundation of China(grant numbers 81991531 to M.W.,82102440 to J.J.,and 32400149 to J.Z.).
文摘Antimicrobial resistance is a global health crisis and carbapenem-resistant Klebsiella pneumoniae(CRKp)is listed as one of the top high-priority pathogens by the World Health Organization.Meanwhile,hypervirulent K.pneumoniae(hvKp)causes severe community-associated infections,such as liver abscesses and meningitis,in otherwise healthy individuals.Both CRKp and hvKp infections are associated with high mortality rates.The convergence of carbapenem resistance and hypervirulence within a single bacterial strain may lead to significantly more severe clinical outcomes.
文摘Mycoplasma pneumoniae(M.pneumoniae)is a common pathogen that causes community-acquired pneumonia in children.The clinical presentation of this pathogen can range from mild self-limiting illness to severe and refractory cases.Complications may occur,such as necrotizing pneumonia and respiratory failure.Extrapulmonary complications,including encephalitis,myocarditis,nephritis,hepatitis,or even multiple organ failure,can also arise.In this editorial,we dis-cuss the clinical implications of the significant findings from the article"Serum inflammatory markers in children with M.pneumoniae pneumonia and their predictive value for mycoplasma severity"published by Wang et al.They reported that measuring lactic dehydrogenase,interleukin-6 levels,and D-dimer effectively predicts refractory M.pneumoniae pneumonia cases.
基金Guangdong Basic and Applied Basic Research Foundation(grant number 2024A1515010319 to J.Q.)Science and Technology Program of Shenzhen(grant numbers KCXFZ20230731100901003 to J.Q.and L.L.,KJZD20230923115116032 to J.Q.,JCYJ20190809144005609 to J.Q.)+1 种基金Shenzhen Key Laboratory of Biochip(grant number ZDSYS201504301534057 to J.Q.)Shenzhen High-level Hospital Construction Fund(to J.Q.).
文摘Nosocomial pathogen carbapenem-resistant Klebsiella pneumoniae(CRKP)poses a heightened risk to public health through carbapenem resistance and virulence convergence,particularly in China’s dominant sequence type 11(ST11)clone[1,2].Monoclonal K.pneumoniae exhibits within-host diversity during prolonged infections[3–5],with certain variants surviving through adaptation[4,6].CRKP strains from the blood of a single patient are heterogeneous in terms of antibiotic susceptibility,capsular polysaccharide production,and mucoviscosity[3].Intra-host evolution drives novel resistance via cumulative mutations(e.g.,the transcriptional regulator gene ramR mutations and the outer membrane porin gene OmpK35 loss)[4].
文摘Background: Mycoplasma pneumoniae (MP) is the primary causative agent of community-acquired pneumonia, which has increasingly become resistant to macrolides, complicating treatment regimens, especially with the co-infection factor. Its worldwide prevalence has fluctuated due to the influence of the COVID-19 pandemic. The study investigated co-infection patterns in children diagnosed with Mycoplasma pneumoniae pneumonia (MPP). Methods: From June 2022 to December 2023, we retrospectively analyzed the clinical data for hospitalized children with Mycoplasma pneumoniae pneumonia in Wuhan, China. We collected data on age, sex, clinical information, and pathogenic results. We also collected sputum or bronchoalveolar lavage fluid (BALF) samples to test respiratory pathogens and macrolide resistance using targeted microbial next-generation sequencing (tNGS). We analyzed the data using SPSS. Results: The study involved 417 patients diagnosed with MPP, of whom 86.33% had co-infections. Co-infections were notably linked to lobar pneumonia, prominent imaging shadows and higher macrolide resistance rate. Key bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, rhinoviruses, and human adenoviruses (HADV). In MPP cases, Candida albicans was the fungal pathogen related to co-infections. The co-infection with HADV and human bocavirus 1 (HBoV1) correlated with prolonged fever, whereas Bordetella pertussis was linked to prolonged cough. In contrast, Candida albicans exhibited a weaker association with diffuse large-area infiltration on chest imaging, and its co-infection was less likely to result in severe disease. Conclusion: These results offer valuable insight into Mycoplasma pneumoniae pneumonia in children, highlighting the impact of co-infections on the disease’s clinical outcomes.
基金Bill and Melinda Gates Foundation,Grant/Award Number:OPP1017554。
文摘Background:Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide despite the widespread availability of antibiotics.Novel pneumonia therapies and biomarkers are urgently needed to improve outcomes and advance personalized therapy.Using an established baboon model of S.pneumoniae pneumonia,we sought to characterize the temporal dynamics of pneumonia host responses to identify novel potential diagnostic and therapeutic molecular targets.Methods:We performed whole blood transcriptomics,unbiased proteomics,and peripheral cytokine measurements serially in baboons inoculated with S.pneumoniae(n=23)or saline(n=10)and modeled the peripheral blood host response using principal components analysis and complex sparse logistic regression.Differentially expressed genes were analyzed for pathway analysis.Results:Inoculated animals developed characteristic signs and symptoms of pneumonia.A 39-gene signature was derived that classified S.pneumoniae infection with high accuracy(auROC 0.9 and 0.99 at 24 and 48 h post-inoculation,respectively).Similar performance was observed for 48-h biomarker signatures derived from peripheral blood plasma proteomic and cytokine measurements(both auROC>0.9).The gene signature retained strong diagnostic performance(auROC=0.88)when transformed to human orthologs and applied to patients with acute respiratory illness(n=34)or healthy controls(n=20).Pathway analysis at 48 h identified downregulation of mitophagy and glucocorticoid signaling in peripheral blood.Conclusions:We report novel peripheral blood gene and protein expression signatures of S.pneumoniae pneumonia that could improve pneumonia diagnosis and found distinct pathways that may be amenable to modulation.Our findings illustrate how non-human primate models of bacterial pneumonia can successfully translate biomarker discoveries to patients.
文摘Introduction: The misuse of antibiotics has driven the emergence of antimicrobial resistance, with certain bacterial species, including Klebsiella pneumoniae, initially susceptible to most antibiotics, now exhibiting resistance to multiple antimicrobial agents. The objective of this study was to investigate the distribution and antimicrobial resistance profiles of Klebsiella pneumoniae strains isolated at the Yaoundé Central Hospital. Methodology: The study was conducted over a period of 4 months (March 1st, 2023-July 1st, 2023) and involved 32 strains isolated from bacterial cultures performed on patients, regardless of sex. The different Klebsiella pneumoniae strains were isolated using conventional methods. Identification, antibiogram, and detection of resistance enzyme production were generated using the VITEK 2 system. The Carbapenem-resistant K.N.I.V.O. kit was used to detect carbapenemases. Data analysis was performed using EXCEL 2019 software. Results: Out of 196 samples collected from various biological products, 32 Klebsiella pneumoniae strains were isolated, representing 16.32% (196/32). Urine samples were most frequently affected, accounting for 53.125%. The emergency department was the most represented (40.63%) by these isolates. The mean age was 50 years, with a minimum of 20 years and a maximum of 80 years. The sex ratio was equal to 1. The identified strains were resistant to cefotaxime (78.13%), cefoxitin (62.50%), tobramycin (71.88%), gentamicin (56.25%), ofloxacin (81.25%), and cotrimoxazole (78.13%). 78.25% were ESBL producers. Three strains were resistant to carbapenems, accounting for 9.37%;one of which exhibited the NDM type. Conclusion: This study highlights the evolving bacterial resistance to antibiotics, which requires adequate measures through the strengthening of the Antimicrobial Resistance (AMR) program in Cameroon.
基金Supported by the Key Research and Development Project of the Science and Technology Department of Sichuan Province,China,No.2023YFS0280the High-level Research Initiation Fund Program of the First Affiliated Hospital of Chengdu Medical College,China,No.CYFY-GQ43.
文摘This article discusses the findings presented by Zhang et al.They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing.In this article,we focus on the connection between chronic kidney disease and the intestinal microbiota,and propose microbiota transplantation as a potential treatment for this patient group.We also examine an intriguing phenomenon related to hepatic encephalopathy,and provide insights into the future research.
基金Supported by the Second Batch of Social Development Science and Technology Program Projects of Taizhou Science and Technology Bureau in 2023,No.24ywb80.
文摘Klebsiella pneumoniae infections(KPIs),particularly carbapenem-resistant Klebsiella pneumoniae(CRKP),pose significant challenges in liver transplantation(LT)recipients,with high morbidity and mortality.Guo et al’s study highlights risk factors,such as elevated day-one alanine aminotransferase levels and prolonged catheterization,and identifies polymyxin B and ceftazidime/avibactam as effective treatments.However,limitations like the absence of pre-transplant colonization data and host-pathogen interaction insights highlight the need for enhanced strategies.Future directions should include routine CRKP colonization surveillance,immune and genomic profiling,and the development of novel therapeutics.By integrating these approaches,we can improve the prevention,diagnosis,and treatment of KPIs in LT patients.
基金supported by the National Natural Science Foundation of China(32273082 and U21A20262).
文摘Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.
基金supported by the National Natural Science Foundation of China(Nos.81860543,32360237)Guizhou Provincial Science and Technology Projects(Nos.ZK[2024]235,ZK[2023]Key Project 041).
文摘The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.
文摘Dear Editor,Central retinal artery occlusion(CRAO)is a devastating ocular event caused by obstruction of the central retinal artery,leading to a sudden and significant loss of vision.A hallmark of CRAO on funduscopic examination is a characteristic“cherry-red spot”at the fovea surrounded by a pale retina[1].The anterior segment typically appears unremarkable.
文摘AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.
基金Supported by Baoding Science and Technology Plan Project,No.2272P011Hebei Province Scientific Research Project,No.20241734Hebei Natural Science Foundation Project,No.H2024104011.
文摘BACKGROUND Mycoplasma pneumoniae(M.pneumoniae)is considered to be one of the causative agents of community acquired pneumonia in children with general or severe course of disease.Severe M.pneumoniae pneumonia(SMPP)has emerged as a crucial global health concern due to high mortality rate in children under 5 years,potentially life-threatening complications,and growing challenges in pediatric treatment associated with rising macrolide resistance.Additionally,MPP can be complicated by other bacterial and/or viral pathogens,which may exacerbate disease severity.After the lifting of strict non-pharmaceutical interventions(NPIs)worldwide,the dramatic rise of incidence of MPP in Asia and Europe was observed.AIM To perform the comprehensive study of community acquired MPP cases registered in 2023 in Baoding Hospital,China.METHODS A total of 1160 children from 1 month to 15 years old with confirmed MPP diagnosis were enrolled in the study.The blood and respiratory samples were collected within the 24 hours after admission.The hematological parameters,biochemical markers,cytokine profiles were assessed.The respiratory samples were tested for the presence of M.pneumoniae and other 23 bacterial/viral pathogens by multiplex polymerase chain reaction(PCR).The macrolide resistance mutations(A2063G,A2064G in the 23S rRNA gene of M.pneumoniae)were determined by PCR.RESULTS Number of MPP cases has dramatically increased starting August with peak in November.SMPP and general MPP(GMPP)were identified in 264 and 896 of 1160 hospitalized children.The binary logistic regression analysis identified six[C-reactive protein(CRP),lactate dehydrogenase,procalcitonin,erythrocyte sedimentation rate,fibrin and fibrinogen degradation products(FDPs),D-dimer]and four(neutrophils,CRP,FDPs,prothrombin time)predictors of SMPP in age groups 2-5 years and 6-15 years,respectively.Children with SMPP showed significantly higher levels of cytokine interleukin(IL)-17F(2-5 years),and cytokines interferon-gamma,tumor necrosis factoralpha,IL-10(6-13 years).Concomitant viral/bacterial pathogens were determined in 24.3%and 28.0%cases of SMPP and GMPP.Among them,Streptococcus pneumoniae(S.pneumoniae)and Haemophilus influenzae(H.influenzae)were predominant.93.2%cases of MPP were associated with macrolide resistant M.pneumoniae.CONCLUSION Specific MPP epidemiological pattern associated with lifting NPIs was revealed:Increase of hospitalized cases,prevalence of S.pneumoniae and H.influenzae among concomitant pathogens,93.2%of macrolide resistant M.pneumonia.
基金supported by the National Key Research and Development Program of China(grant number 2022YFC2303100 to J.F.)the International Partnership Program of the Chinese Academy of Sciences(grant number 079GJHZ2022033GC to J.F.).
文摘Hypervirulent Klebsiella pneumoniae(hvKp)is a major cause of severe community-acquired infection.A key plasmidencoded factor,regulator of mucoid phenotype A(RmpA),activates capsule locus gene expression to promote hypermucoviscosity,a phenotype that is strongly linked to increased pathogenicity.However,the precise regulatory mechanisms that control RmpA in hvKp remain poorly understood.In this study,we constructed a rmpA knockdown strain in hvKp using CRISPR interference and assessed the global regulatory role of RmpA through complementary multi-omic sequencing(RNA sequencing[RNA-seq]and chromatin immunoprecipitation sequencing[ChIP-seq]),promoter-gfp reporter assays,and phenotypic experiments.The functional role of RmpA was evaluated in Escherichia coli via heterologous expression.The RNA-seq analysis revealed that RmpA activates carbohydrate metabolism pathways,but represses pathways related to DNA replication,ribosome metabolism,and biofilm formation.The ChIP-seq analysis further confirmed the potential role of RmpA as a global regulator that enhances capsule production by activating transcripts within the capsule locus.It also upregulates genes involved in sugar metabolism and transport,which supplies essential precursors for capsule synthesis.RmpA modulates the phenotypic switch between hypermucoviscosity and biofilm formation by repressing type Ⅲ fimbriae genes.Notably,RmpA overexpression in E.coli induced changes in multiple metabolic pathways.These findings position RmpA as a latent central regulator in hvKp that orchestrates the metabolic pathways and phenotypic traits essential for virulence.
基金Research Project of Jiangsu Maternal and Child Health Care Association(Project No.:FX202335)。
文摘Objective:To investigate the correlation between Mycoplasma pneumoniae infection and childhood asthma,and to explore the impact of Mp infection on airway inflammation and airway hyperresponsiveness in children with asthma.Methods:58 children with bronchopneumonia admitted to the First People’s Hospital of Jintan,Changzhou from April 2024 to October 2024 were selected as the study subjects.The levels of cytokines IL-4,IL-17,TGF-β1,and INF-γ in the serum were compared between the MP group and non-MP group,as well as between the MP wheezing group and MP nonwheezing group.Results:The levels of IL-17 and IL-4 in the MP group were significantly higher than those in the non-MP group(P<0.05),while there was no statistically significant difference in the other indicators(P>0.05).Statistically significant differences in IL-17 and IL-4 were observed between the wheezing and non-wheezing groups(P<0.05),while there was no statistically significant difference in the other indicators(P>0.05).There was a significant difference in IL-17 among the groups(P<0.05).The difference in IL-17 between the MP group and non-MP group was significant(P<0.05),and the difference between the wheezing and non-wheezing groups was marginally significant(P<0.05).Conclusion:M.pneumoniae infection may be one of the risk factors for the onset of childhood asthma,but its mechanism remains unclear.Further research is needed to determine whether Mp infection can serve as a biomarker for childhood asthma and to elucidate its underlying mechanism.
文摘BACKGROUND Liver transplant(LT)recipients are susceptible to carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Comprehensive research addressing the incidence,timing,infection sites,resistance patterns,treatment options,and associated risk factors among LT recipients with CRKP is now lacking.AIM To assess the incidence,resistance,therapy,and risk factors of CRKP infections post-LT,and to evaluate the impact of them on prognosis.METHODS A retrospective study was conducted,including 430 consecutive patients who underwent LT between January 2015 and June 2023.This study aimed to investigate the risk factors for CRKP infections and their influence on outcomes using logistic regression analysis.RESULTS Among the 430 patients who underwent LT,20(4.7%)experienced at least one documented CRKP infection within 3 months post-transplantation.The median time from LT to the onset of CRKP infections was 6.5 days.The lungs and bloodstream were the most common sites of CRKP infections.CRKP isolates were relatively susceptible to ceftazidime/avibactam(93.7%),polymyxin B(90.6%),and tigecycline(75.0%)treatment.However,all isolates were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin treatment.Recipients with CRKP infections had a mortality rate of 35%,the rate was 12.5%for those receiving ceftazidime/avibactam therapy.Multivariate analysis identified female sex[odds ratio(OR)=3.306;95%confidence interval(CI):1.239-8.822;P=0.017],intraoperative bleeding≥3000 mL(OR=3.269;95%CI:1.018-10.490;P=0.047),alanine aminotransferase on day 1 post-LT≥1500 U/L(OR=4.370;95%CI:1.686-11.326;P=0.002),and post-LT mechanical ventilation(OR=2.772;95%CI:1.077-7.135;P=0.035)as significant variables associated with CRKP.CRKP infections were related to an intensive care unit length(ICU)of stay≥7 days and 6-month all-cause mortality post-LT.CONCLUSION CRKP infections were frequent complications following LT,with poor associated outcomes.Risk factors for post-LT CRKP infections included female sex,significant intraoperative bleeding,elevated alanine aminotransferase levels,and the need for mechanical ventilation.CRKP infections negatively impacted survival and led to prolonged ICU stays.
基金approved by the Ethics Committee of the Third Xiangya Hospital in accordance with the Declaration of Helsinki(No.24029).
文摘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.
基金The study was approved by the First People's Hospital of Linping District Ethics Commit(No:linping2023044).
文摘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.
基金supported by the Evidence-based Capacity Building Project of Traditional Chinese medicine of the National Administration of Traditional Chinese Medicine(60102)the Fundamental Research Funds for the Central Public Welfare Research Institutes(49425).
文摘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.
基金Supported by the National Key R&D Program of China,No.2021YFC2301800.
文摘BACKGROUND The incidence of Klebsiella pneumoniae(K.pneumoniae)infection in patients with cirrhosis has been increasing over recent years,posing certain difficulties in clinical treatment.AIM To analyze the clinical features of patients with liver cirrhosis and identify the risk factors to help the early diagnosis and treatment of these diseases.METHODS Clinical data and laboratory tests were collected from 72 patients with cirrhosis confirmed by secretion or blood culture of K.pneumoniae infection at Beijing Ditan Hospital,Capital Medical University,between May 2016 and October 2018.Data from hospitalized patients with liver cirrhosis and K.pneumoniae infections,in-cluding age,sex,antimicrobial use,length of stay,site of infection,distribution of pathogenic bacteria,complications,invasive operations,laboratory indicators,treatment,and clinical regression,were extracted and retrospectively analyzed.Clinical data and biochemical values were included in the multivariate logistic regression analysis.RESULTS A total of 52 men and 20 women,with an age range from 29 to 85 years and an average age of 57.7±12.54,were analyzed.The incidence of hospital K.pneu-moniae infection in patients with cirrhosis was approximately 19.44%.The most common the infection site was the bloodstream,followed by the respiratory tract,abdominal cavity,and biliary tract.Risk factors for infection were old age,long hospital stays,gastrointestinal bleeding,and low serum albumin levels,while prophylactic antibiotics were protective factors.The multivariate analysis suggested that other infections,chronic diseases,and invasive procedures were independent factors.CONCLUSION In clinical practice,the length of hospital stays should be shortened as much as possible,invasive operations should be reduced,antibiotics should be rationally used,and the patients’liver function should be timely improved.This is of great significance for reducing the incidence of hospital infection.
