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.

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.

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.

Impact of Genetic Diversity of Uropathogenic Escherichia coli and Klebsiella pneumoniae Strains on the Dissemination of Extended Spectrum Beta-Lactam Resistance Genes in Côte d’Ivoire

The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the emergence of a population of better adapted bacteria. However, there is no literature highlighting the genetic diversity and evolutionary structure of E. coli and K. pneumoniae in an environment with high selection pressure in Côte d’Ivoire. The objective of this study was to evaluate the genetic diversity of E. coli and K. pneumoniae strains circulating at the HKB Hospital in Abobo and at the Daloa Regional Hospital and its impact on the dissemination of extended spectrum beta-lactam resistance genes. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. From genomic DNA extracts, ESBL resistance genes were amplified by PCR and sequenced, in addition to genetic typing by ERIC-PCR. The data obtained were submitted to genetic and bioinformatics analyses. The results have shown a genetic diversity important in E. coli and K. pneumoniae with diversity indexs (SID) ranging from 0.5 to 0.77. The genetic structure of the bacterial species studied has shown a clonal distribution of strains with clones expressing TEM-9 and CTX-M-15 variants. Also, this clonal structure was correlated with the spread of resistance genes in E. coli and K. pneumoniae. The spread of resistant clones is a factor that might limit the fight against antibiotic resistance.

Prevalence and Antibiotic Resistance of Urinary Tract Pathogens, with Molecular Identification of Klebsiella pneumoniae, Klebsiella oxytoca, and Acinetobacter spp., Using Multiplex Real-Time PCR

Urinary tract infections (UTIs) caused by uropathogens are a significant public health problem, and their treatment primarily relies on antibiotic therapy. However, the increasing global development of antibiotic resistance necessitates updating diagnostic techniques to ensure higher sensitivity and specificity, especially with advancements in science and medicine. This study aimed to evaluate the prevalence of UTIs and antibiotic resistance profiles through urine culture, as well as to identify Klebsiella pneumoniae, Klebsiella oxytoca, and Acinetobacter spp. in urine samples using a molecular approach with multiplex real-time PCR. From May 3 to July 25, 2023, at the Pietro Annigoni Biomolecular Research Center (CERBA) and Saint Camille Hospital of Ouagadougou (HOSCO), 209 urine samples collected from patients with suspected UTIs were analyzed using both urine culture and multiplex real-time PCR. Among the 209 patients, 52.15% were male and 47.85% female, with an average age of 46.87 ± 21.33 years. Urine cultures revealed an overall UTI prevalence of 23.44%, with a prevalence of 8.13% in men versus 15.31% in women (P = 0.023). The bacterial prevalence rates were as follows: Escherichia coli (12.92%), Klebsiella spp. (7.18%), Enterobacter cloacae (1.44%), Staphylococcus aureus (0.96%), and other bacteria. Klebsiella spp. demonstrated 100% resistance to Amoxicillin and Amoxicillin/Clavulanic Acid, while Escherichia coli showed 96.2% and 65.4% resistance to Amoxicillin and Amoxicillin/Clavulanic Acid, respectively. PCR analysis of the target bacteria revealed mono-infection prevalence rates of Klebsiella pneumoniae (10.39%), Klebsiella oxytoca (7.79%), and Acinetobacter spp. (7.79%), along with a co-infection prevalence rate of Klebsiella pneumoniae/Acinetobacter spp. (1.30%). This study demonstrated that PCR, with its high sensitivity and specificity, could effectively distinguish Klebsiella pneumoniae from Klebsiella oxytoca and detect Acinetobacter spp. in less than 24 hours—something urine culture alone could not achieve. The relative ease of automating urine PCR testing, combined with its diagnostic accuracy and rapid turnaround time, makes it a valuable addition to modern medical practice for the laboratory diagnosis of UTIs.

Antibiotic Resistance Profile of Serotypes of Streptococcus pneumoniae Strains in Bangui, from 2017 to 2022: Case of Serotype 1

Goals: The aim of this study was to determine the antibiotic resistance profile of serotypes of Streptococcus pneumoniae strains circulating in Bangui. Methodology: A prospective and analytical analysis was carried out at the National Laboratory of Clinical Biology and Public Health from 2017 to 2022. The strains came from our study on the contribution to the study of antibiotic sensitivity of Streptococcus pneumoniae strains. The multiplex PCR test was used for its cost-effectiveness in terms of amplifiers which can be purified in order to be sequenced. It also makes it possible to detect several germs as well as their serotypes. For a PCR reaction, several elements are involved in the reaction medium or Master Mix. These are the desoxyribonucleotides (dNTPs), the magnesium ions (MgCl2) and the primers. A set of 14 primers divided into 3 classes were used. Class 1 primers served as an internal control by targeting the cpsA gene. It is a highly conserved gene found in capsular loci characterized to date. The primers of the second class were used to target specific serotypes by specific reactions (out of six possibilities). The group reaction was carried out using the primers of the third class in order to carry out an initial screening of the samples and to classify the pneumococcal isolates. Related serotypes were grouped based on the amplification of common genes. Using the technique of electrophoresis on agarose gel and an ultraviolet radiation device, the migration bands are then visualized and analyzed. The data collected had been entered into Excel 2010 and analyzed with Epi info 7. The exact Fischer chi2 test at the 5% threshold, the relative risk and its 95% confidence interval were used to compare the proportions and determine the associations. Results: 187 antibiotic-resistant strains of Streptococcus pneumoniae were collected. The average frequency of serotypes 1, 9A, 4 and untypeable identified were 43.59%, 18.18%, 18.27% and 39.57% respectively. The frequency of serotype 1 was predominant for the age group over five years old with 56.88%. The male sex was predominant with 55.08% for serotype 1. Resistance to penicillin and gentamicin for serotype 1 during this study, for the age group under 5 years old, was 77%. For serotypes 19A and 4, tetracycline resistance was predominant with 20% for the age group under 5 years. The resistance to penicillin and gentamicin of non-typeable serotypes was 33% for the age group under 5 years old. For the age group over 5 years old, resistance to erythromycin predominated at 37%. The distribution of serotypes by sex depending on antibiotic resistance was variable. There was a statistically significant association between identified serotypes and antibiotic resistance (p Conclusion: The study determined serotypes 1, serotypes 19A, serotypes 4 and non-typeable serotypes. These results would be due to the quality of vaccination or poor protection of vaccines.

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.

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.

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

Understanding serum inflammatory markers in pediatric Mycoplasma pneumoniae pneumonia

This editorial reflects on the research,which investigates the potential of serum markers to predict the severity of Mycoplasma pneumoniae infections.Mycoplasma pneumoniae pneumonia(MPP)is a prevalent cause of respiratory infections in children,often leading to significant morbidity.Predicting the severity of MPP can significantly enhance patient management and outcomes.This editorial reviews the role of specific laboratory markers:(1)Lactate dehydrogenase;(2)Interleukin(IL)-6;(3)IL-10;(4)Tumor necrosis factor-α;and(5)D-dimer in predicting the severity of MPP in pediatric patients.Elevated levels of these markers are strongly associated with severe cases of MPP,providing clinicians with valuable tools for early diagnosis and targeted intervention.

Acute coalescent mastoiditis in a 16-month-old child due to Streptococcus pneumoniae infection

Rationale:Acute otitis media is a common disease in early childhood,and is usually caused by Streptococcus pneumoniae(S.pneumoniae).Acute mastoiditis is a complication of acute otitis media and can involve not only the mucoperiosteum of the middle ear but can also spread to the periosteum by destroying the mastoid bone(acute coalescent mastoiditis).In addition,the infection can extend through the surrounding bones or the emissary veins beyond the mastoid’s air cells,leading to subperiosteal abscesses.Patient’s Concern:A 16-month-old female patient was hospitalized due to the purulent discharge of the left ear and the symptoms of right mastoiditis(swelling and redness of the skin).Diagnosis:Bilateral acute coalescent mastoiditis caused by S.pneumoniae infection.The computer tomography revealed bilateral bone destruction of the mastoid and abscesses found behind the auricle on both sides.Interventions:The patient underwent intravenous antibiotic therapy and surgical treatment.Outcomes:The patient was discharged 14 days after hospitalization with an improved condition.Lessons:Improperly treated acute coalescent mastoiditis can lead to extracranial and intracranial complications,sometimes serious and even life-threatening.Complications are prevalent in children under 2 years,in whom the disease progresses more rapidly and severely.The vaccination with a 13-valent vaccine may not result in sufficient immunity against S.pneumoniae,a predominant pathogen in children affected by acute coalescent mastoiditis.

Research Progress on Combined Chinese and Western Medicine Treatment of Mycoplasma pneumoniae Pneumonia in Children

With the continuous development of medical technology,combined treatment of Chinese and Western medicine has gradually become a research hotspot.As a common disease in pediatrics,the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children is also being explored and improved.This article summarizes the research progress of combined Chinese and Western medicine treatment of MPP in children in recent years,aiming to provide a useful reference for the combined treatment of MPP in children.The article firstly introduces the etiology and pathogenesis of MPP in children,thereafter briefly introduces the Western anti-infective treatment and traditional Chinese medicine(TCM)diagnosis and treatment of MPP in children,and lastly introduces the methods of combined treatment of TCM and Western medicine in detail.The article points out that the combination of Chinese and Western medicine can give full play to the overall regulation of Chinese medicine and the precise treatment advantages of Western medicine,improve the therapeutic effect,reduce the use of antibiotics,and lower the recurrence rate of the disease,which is worthy of further research and promotion.

Analysis of the Role of D-Dimer,Interleukin-6,and Interleukin-18 in Differential Diagnosis of Pediatric Refractory Mycoplasma pneumoniae Pneumonia

Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.

Prevalence and Study of the Clonality of Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Strains in Neonatology at the University Hospitals of Abidjan by the Pulsed Field Gel Electrophoresis and the Quantitative Antibiogram

Background: ESBL-producing strains of Klebsiella pneumoniae, one of the main causes of nosocomial and hospital-acquired infections, are commonly associated with therapeutic impasses. Surveillance of these multidrug-resistant pathogens is a crucial tool for controlling and preventing infections. This surveillance involves the use of appropriate molecular and phenotypic typing techniques. The choice of techniques is based on criteria such as discriminatory power, intra- and inter-laboratory reproducibility, epidemiological concordance, ease of use and cost. The aim of our study was to identify clusters of Extended-Spectrum Beta-Lactamase-producing Klebsiella pneumoniae (ESBL-K. pneumoniae) strains circulating in neonatology using quantitative antibiogram (QA) and Pulsed Field Gel Electrophoresis (PFGE). Materials and Methods: This cross-sectional study included 55 K. pneumoniae strains isolated from a total of 513 samples. These various samples are taken from newborns, healthcare personnel, and the environment. K. pneumoniae identification followed standard bacteriological procedures and was confirmed using the Vitek® 2 (bioMérieux). The detection of the ESBL phenotype was performed using the synergy test. QA and PFGE were used to identify clonal relationships between the various strains isolated. Concordance between these two methods was assessed by calculating Cohen’s KAPPA coefficient and Simpson’s diversity index. Results: Among the 55 K. pneumoniae strains included in this study, 58.2% (32/55) were found to be Extended-Spectrum Beta-Lactamase (ESBL) producers. Most of these strains were isolated from neonatal samples (blood samples and rectal swabs). The quantitative antibiogram method applied to 28 out of the 32 ESBL-producing strains revealed that the isolates were grouped into 5 clusters. Pulsed Field Gel Electrophoresis performed on a total of 16 ESBL-producing strains showed the existence of four profiles. A perfect concordance was observed between the two methods. Conclusion: The results of this study highlighted the existence of clonal strains of various origins within neonatology units.

高速铁路主跨320 m钢-混部分斜拉桥无砟轨道适应性研究

南玉高铁六景郁江特大桥设计将钢-混部分斜拉桥结构引入时速350 km高速铁路领域,而300 m级以上大跨度桥上无砟轨道的竖向变形极易超限,影响列车通过的安全性和舒适性,因此,系统研究在此大跨桥梁结构上铺设无砟轨道的适应性十分必要。通过建立有限元及动力学模型,分析不同组合工况下无砟轨道结构的变形特点及动力特性,运用60 m弦测法探究各工况下无砟轨道的线形变化规律,从而确定大跨度钢-混部分斜拉桥铺设无砟轨道的适应性,并对设计和施工提出合理化建议。主要结论如下:在各种不利组合荷载作用下,桥上无砟轨道结构强度满足规范要求,列车通过大桥的各项安全性与舒适性指标均满足规范要求;混凝土收缩徐变和斜拉索升降温是影响无砟轨道线形标准的两大主因,应在无砟轨道施工前确保足够的沉降观测期和收缩徐变释放期,并充分考虑拉索的保温设计;在温度组合荷载作用下,桥上无砟轨道的60 m弦测不平顺幅值为6.79 mm,满足高速铁路静态验收标准;但在叠加列车荷载和收缩徐变后,变形弦测值均出现Ⅱ级及以上超限,通过合理设置预拱度后可有效改善轨道平顺性标准。

M-APSK鉴相算法与并行载波同步方法

为实现M进制幅相调制(M-APSK)体制下高阶调制信号的相位精细校正,将DVB-S2标准推荐的16APSK和32APSK的Q次方无数据辅助鉴相算法进行了扩展,以应用于64APSK、128APSK和256APSK等高阶调制。针对高阶调制的有效鉴相星座点占比较低时环路工作不稳定的问题提出了改进算法,通过对功率归一化后接收符号的幅值进行阈值判决,仅在高于阈值时进行鉴相,低于阈值时则不改变滤波器状态和相位补偿值,以提高星座点的鉴相有效性和可靠性,从而降低入锁门限。针对高速数传的符号速率非常高,而处理器的工作时钟频率相对较低的问题,提出了一种适用于M-APSK的并行载波同步方法,可以满足接收机工作时钟处理需要。相对于传统固定编码调制(CCM)的载波同步环路,该并行方法还可应用于可变编码调制(VCM)体制的频率跟踪。

过表达lncRNAHEM2M改善非酒精性脂肪肝病小鼠的肝脏损伤

目的探讨过表达长链非编码RNA(lncRNA)HEM2M对非酒精性脂肪肝病(NAFLD)小鼠肝损伤的影响。方法野生型C57BL/6(WT)和条件性髓系细胞lncRNAHEM2M过表达(MYKI)小鼠分别喂饲普通饮食(ND)和高脂饮食(HFD),即为WT+ND、MYKI+ND、WT+HFD和MYKI+HFD组。12周后行腹腔糖耐量及胰岛素耐量试验后处死小鼠,检测小鼠血清和肝脏组织的肝功能指标,制备肝脏组织切片后行HE染色和F4/80免疫组化染色,ELISA法检测肝脏组织中IL-6、IL-1β和TNF-α水平,qRT-PCR检测M1型(TNF-α、iNOS和IL-6)和M2型(Arg-1、YM-1和IL-10)巨噬细胞标志物mRNA表达,免疫印迹检测肝脏组织中P-AKT、T-AKT、NLRC4、caspase-1和GSDMD蛋白表达,比色法和免疫荧光测定肝脏组织caspase-1活性。结果与HFD喂饲的WT小鼠相比,MYKI+HFD小鼠肝功能损伤减轻(P<0.01),肝脏脂肪变缓解,肝脏巨噬细胞浸润减少,糖耐量损伤及胰岛素抵抗改善(P<0.01);MYKI+HFD小鼠肝脏组织IL-6、IL-1β和TNF-α水平降低(P<0.01),M1型巨噬细胞标志物mRNA表达减少(P<0.01),M2型mRNA表达增加(P<0.01);MYKI+HFD小鼠肝脏组织NLRC4炎症小体活性降低(P<0.01),活性caspase-1减少,GSDMD-N蛋白表达降低(P<0.05)。结论过表达lncRNAHEM2M降低NAFLD小鼠肝脏炎症因子水平,进而改善胰岛素抵抗并抑制肝脏NLRC4炎症小体激活,减少肝细胞焦亡,最终改善NAFLD小鼠肝脏损伤。

儿童重症肺炎支原体肺炎危险因素的Meta分析

背景近年来,儿童肺炎支原体肺炎的发病率持续上升,重症肺炎支原体肺炎的发病人数也相应升高,引起了临床医师的广泛关注。了解与重症肺炎支原体肺炎相关的危险因素,以判断患儿病情的严重程度、预防重症发生和减少后遗症,一直是研究的热点。虽然已经有许多关于重症肺炎支原体肺炎危险因素的研究,但这些研究在时间和地理区域上存在差异,因此需要进行系统综述及分析以对其进行全面了解。目的系统评价重症肺炎支原体肺炎的危险因素。方法计算机检索中国知网(CNKI)、万方数据知识服务平台(Wanfang Data)、维普网(VIP)、中国生物医学文献数据库(CBM)、独秀学术搜索数据库(Duxiu)、中华医学期刊全文数据库(Yiigle)、Cochrane Library、PubMed、Embase、Web of Science、Science Direct和BioMed Central,检索涉及儿童重症肺炎支原体肺炎危险因素的相关研究,检索时限均从建库至2023年8月。由2位研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用Stata 14.0和RevMan 5.4软件进行Meta分析。结果共纳入22个研究,均为回顾性病例对照研究,包括4531例患儿。Meta分析结果显示,C反应蛋白(CRP)(OR=1.92,95%CI=1.72~2.15,P<0.00001)、红细胞沉降率(ESR)(OR=2.61,95%CI=2.12~3.22,P<0.00001)、降钙素原(PCT)(OR=2.60,95%CI=1.43~4.75,P=0.002)、D-二聚体(OR=4.36,95%CI=2.93~6.50,P<0.00001)、白细胞计数(WBC)(OR=1.98,95%CI=1.66~2.36,P<0.00001)、肺下叶病变(OR=5.70,95%CI=3.48~9.35,P<0.00001)、肺大片状病变(OR=6.37,95%CI=4.09~9.92,P<0.00001)、高肺炎支原体抗体滴度(OR=2.83,95%CI=1.78~4.49,P<0.0001)、乳酸脱氢酶(LDH)(OR=1.03,95%CI=1.00~1.05,P=0.05)、发热时间(OR=8.33,95%CI=3.38~20.56,P<0.00001)是儿童重症肺炎支原体肺炎的影响因素。结论炎性标志物(CRP、ESR、PCT、LDH、WBC)的升高、出现影像学特征性改变(大片状实变、下叶病变)、高肺炎支原体抗体滴度、D-二聚体升高以及发热时间延长可能为儿童重症肺炎支原体肺炎的危险因素。未来需要更高质量的研究来进一步探讨其他临床、影像学和实验室结果与儿童重症肺炎支原体肺炎之间的关系,并基于发现的危险因素建立预后模型。

RBMX通过下调PKM2抑制膀胱癌细胞的增殖、迁移、侵袭和糖酵解

目的探讨X连锁RNA结合基序蛋白(RBMX)对膀胱癌细胞(1376细胞和UC-3细胞)的增殖、迁移、侵袭的影响以及其在糖酵解中的作用。方法采用慢病毒表达系统和siRNA干扰技术,分别构建RBMX过表达和敲低的膀胱癌细胞模型(1376细胞和UC-3细胞)。采用RT-qPCR和Westernblotting分别在mRNA水平和蛋白水平上检测细胞模型是否构建成功。通过EdU增殖实验和克隆形成实验检测过表达和敲低RBMX后细胞的生长和集落形成能力,同时通过Transwell实验分析过表达和敲低RBMX后对细胞迁移、侵袭能力的影响;随后,采用Westernblotting检测过表达和敲低RBMX后糖酵解关键蛋白PKM1(M1型丙酮酸激酶)和PKM2(M2型丙酮酸激酶)的表达变化;最后,利用葡萄糖和乳酸检测试剂盒分析过表达和敲低RBMX对膀胱癌细胞糖酵解的影响。结果RT-qPCR和Westernblotting结果显示,过表达RBMX膀胱癌细胞的mRNA和蛋白表达水平显著高于阴性对照组(P<0.05),敲低RBMX膀胱癌细胞的mRNA和蛋白表达水平显著低于阴性对照组(P<0.05)。过表达RBMX明显抑制膀胱癌细胞的增殖、克隆形成、迁移和侵袭,敲低RBMX则作用相反。Westernblotting实验结果显示,过表达RBMX使PKM1表达上升,PKM2表达下降,敲低RBMX则作用相反。葡萄糖消耗及乳酸生成实验表明,过表达RBMX均能抑制膀胱癌细胞葡萄糖消耗及乳酸生成(P<0.05),敲低RBMX均能促进膀胱癌细胞葡萄糖消耗及乳酸生成(P<0.05)。结论RBMX通过下调PKM2抑制膀胱癌的发生发展和糖酵解能力,有望成为膀胱癌诊断和治疗的潜在分子靶标。

下调METTL5通过Wnt/β-catenin信号通路抑制三阴乳腺癌细胞增殖、迁移与侵袭

目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。