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1.
Front Med (Lausanne) ; 11: 1408297, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947239

RESUMO

Background: Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses. Methods: Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy. Results: Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis. Conclusion: This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

2.
Int J Antimicrob Agents ; 64(2): 107252, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908534

RESUMO

OBJECTIVES: The study aimed to develop a genotypic antimicrobial resistance testing method for Klebsiella pneumoniae using metagenomic sequencing data. METHODS: We utilized Lasso regression on assembled genomes to identify genetic resistance determinants for six antibiotics (Gentamicin, Tobramycin, Imipenem, Meropenem, Ceftazidime, Trimethoprim/Sulfamethoxazole). The genetic features were weighted, grouped into clusters to establish classifier models. Origin species of detected antibiotic resistant gene (ARG) was determined by novel strategy integrating "possible species," "gene copy number calculation" and "species-specific kmers." The performance of the method was evaluated on retrospective case studies. RESULTS: Our study employed machine learning on 3928 K. pneumoniae isolates, yielding stable models with AUCs > 0.9 for various antibiotics. GenseqAMR, a read-based software, exhibited high accuracy (AUC 0.926-0.956) for short-read datasets. The integration of a species-specific kmer strategy significantly improved ARG-species attribution to an average accuracy of 96.67%. In a retrospective study of 191 K. pneumoniae-positive clinical specimens (0.68-93.39% genome coverage), GenseqAMR predicted 84.23% of AST results on average. It demonstrated 88.76-96.26% accuracy for resistance prediction, offering genotypic AST results with a shorter turnaround time (mean ± SD: 18.34 ± 0.87 hours) than traditional culture-based AST (60.15 ± 21.58 hours). Furthermore, a retrospective clinical case study involving 63 cases showed that GenseqAMR could lead to changes in clinical treatment for 24 (38.10%) cases, with 95.83% (23/24) of these changes deemed beneficial. CONCLUSIONS: In conclusion, GenseqAMR is a promising tool for quick and accurate AMR prediction in Klebsiella pneumoniae, with the potential to improve patient outcomes through timely adjustments in antibiotic treatment.

3.
Eur J Clin Microbiol Infect Dis ; 43(7): 1461-1467, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714595

RESUMO

Providencia genus is known to harbor certain opportunistic pathogens capable of causing human infections. Here, we report two strains of multidrug-resistant bacteria initially identified as Providencia rettgeri by mass spectrometry, but genome analysis revealed their ANI (79.84-84.20%) and dDDH (21.1-25.6%) values to fall below the accepted species threshold for known Providencia species. We therefore propose that these isolates be recognized as a novel species, Providencia xianensis sp. nov. Alarmingly, both strains, isolated from locations far apart, exhibited resistance to last-resort antibiotics, indicating their possible wide distribution, underscoring the urgency for immediate attention and enhanced surveillance for this emerging multidrug-resistant pathogen.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Enterobacteriaceae , Providencia , Providencia/efeitos dos fármacos , Providencia/genética , Providencia/isolamento & purificação , Providencia/classificação , Humanos , Infecções por Enterobacteriaceae/microbiologia , Antibacterianos/farmacologia , Filogenia , Masculino , Genoma Bacteriano/genética , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Feminino , Pessoa de Meia-Idade
4.
BMC Infect Dis ; 24(1): 116, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254025

RESUMO

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.


Assuntos
Antibacterianos , Temperatura Corporal , Humanos , Estudos Transversais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cânula , Carbapenêmicos/farmacologia , Klebsiella pneumoniae
5.
Infect Drug Resist ; 16: 7809-7817, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148770

RESUMO

Purpose: To analyze the risk factors and clinical outcomes of patients isolated with polymyxin B-resistant (PR) Enterobacterales from various clinical specimens to prevent and control the spread of these strains. Methods: This retrospective case-control study included 72 PR Enterobacterales-positive cases and 144 polymyxin B-susceptible (PS) Enterobacterales controls from 2018 to 2022. Patients with PR Enterobacterales isolated in various clinical cultures were defined as cases. Patients with PS Enterobacterales cultures at similar anatomic sites during the same period were randomly selected as controls. Data were collected from clinical and laboratory test records. Bivariable logistic regression and Pearson's chi-square tests were used to assess risk factors. Results: PR strains were predominantly Klebsiella pneumoniae (72.2%) and Salmonella enteritidis (8.3%). Of the patients, 66.04% were admitted to an intensive care unit (ICU). Risk factors for isolation with PR strains included chronic heart disease (P = 0.012; odds ratio [OR] 1.15; 95% confidence interval [CI] 1.03-1.28), immunosuppressant use (P = 0.016; OR 1.04 [1.0-1.07), drainage tube [head] (P = 0.006; OR 1.1 [1.0-1.1]), and polymyxin B exposure (P = 0.007; OR 1.03 [1.0-1.06]. With respect to outcomes, admission to an ICU (P = 0.003; OR 7.1 [1.9-25.4]), hypertension (P = 0.035; OR 1.4 [1.02-1.83]), and drainage tube [head] (P = 0.044; OR 1.1 [1.0-1.15]) were associated with treatment failure. Additionally, treatment failure was more frequent in patients (45.83%) than in controls (14.58%). Conclusion: The major risk factors for isolation with PR strains were chronic heart disease, exposure to immunosuppressants, use of drainage tubes, and polymyxin B exposure. The isolation of PR strains in patients was a predictor of unfavorable outcomes. These findings provide a basis for monitoring the spread of PR Enterobacterales.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37650950

RESUMO

Pachymic acid (PA), a natural extract from Poria cocos (Schw.) Wolf, possesses anti-inflammatory and anti-oxidative properties. However, it is still unknown whether PA can protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, we investigated the effects of PA in mice administered BLM. Our results showed that PA significantly improved lung damage and pathological manifestations. Additionally, PA reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while increasing the level of IL-10. PA also decreased the levels of hydroxyproline and malondialdehyde, and increased the activities of superoxide dismutase and glutathione peroxidase in lung tissue. Furthermore, PA inhibited the increases in pyrin domain-containing protein 3 (NLRP3), ASC, IL-1ß, P20, and TXNIP induced by BLM. In conclusion, our study demonstrated the protective effects of PA against BLM-induced PF in mice by suppressing fibrotic, inflammatory, and oxidative stress pathways.

7.
Infect Drug Resist ; 16: 3917-3927, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361937

RESUMO

Purpose: To study the etiological characteristics and risk factors affecting the prognosis of patients with polymicrobial bloodstream infections. Patients and Methods: Overall, 141 patients with polymicrobial bloodstream infections in Henan Provincial People's Hospital during 2021 were included. Laboratory test indexes, department of admission, sex, age, intensive care unit (ICU) admission, surgical history, and central venous catheter placement were collected. Patients were divided into surviving and deceased groups based on outcomes at discharge. Mortality risk factors were identified by univariate and multivariable analyses. Results: Seventy-two of 141 patients survived. Patients were mainly from the ICU and the Departments of Hepatobiliary Surgery and Hematology. Overall, 312 microbial strains were detected: 119 gram-positive, 152 gram-negative, and 13 anaerobic bacteria and 28 fungi. Among the gram-positive bacteria, coagulase-negative staphylococci were most frequent (44/119, 37%), followed by enterococci (35/119, 29.4%). Among coagulase-negative staphylococci, methicillin-resistant coagulase-negative staphylococci incidence was 75% (33/44). Among gram-negative bacteria, Klebsiella pneumoniae was most common (45/152, 29.6%), followed by Escherichia coli (25/152, 16.4%) and Pseudomonas aeruginosa (13/152, 8.6%). Among K. pneumoniae, the incidence of carbapenem-resistant (CR) K. pneumoniae was 45.7% (21/45). On univariate analysis, mortality risk factors included increased white blood cells and C-reactive protein, decreased total protein and albumin, CR strains, ICU admission, central venous catheter, multiple organ failure, sepsis, shock, pulmonary diseases, respiratory failure, central nervous system diseases, cardiovascular diseases, hypoproteinemia, and electrolyte disturbances (P < 0.05). Multivariable analysis showed that ICU admission, shock, electrolyte disorders, and central nervous system diseases were independent mortality risk factors. The survival curve shows that the survival rate of patients with polymicrobial CR bloodstream infections was lower than that of patients with polymicrobial non-CR bloodstream infections (P=0.029). Conclusion: Patients with polymicrobial bloodstream infections are typically critically ill and harbor multidrug-resistant bacteria. Thus, to minimize mortality rate in critically ill patients, changes in infectious flora should be monitored, antibiotics selected reasonably, and invasive procedures reduced.

8.
Microbiol Spectr ; 11(3): e0419722, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37212684

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated globally and is difficult to treat, causing increased morbidity and mortality rates in critically ill patients. We conducted a multicenter cross-sectional study of intensive care unit (ICU) inpatients in 78 hospitals to investigate the prevalence and molecular characteristics of CRKP in Henan Province, China, a hyperepidemic region. A total of 327 isolates were collected and downsampled to 189 for whole-genome sequencing. Molecular typing revealed that sequence type 11 (ST11) of clonal group 258 (CG258) was predominant (88.9%, n = 168), followed by ST2237 (5.8%, n = 11) and ST15 (2.6%, n = 5). We used core genome multilocus sequence typing (cgMLST) to further classified the population into 13 subtypes. Capsule polysaccharide (K-antigen) and lipopolysaccharide (LPS; O-antigen) typing revealed that K64 (48.1%, n = 91) and O2a (49.2%, n = 93) were the most common. We studied isolates collected from both the airway and the gut of the same patients and showed that intestinal carriage was associated with respiratory colonization (odds ratio = 10.80, P < 0.0001). Most isolates (95.2%, n = 180) showed multiple drug resistance (MDR), while 59.8% (n = 113) exhibited extensive drug resistance (XDR), and all isolates harbored either blaKPC-2 (98.9%, n = 187) or blaCTX-M and blaSHV extended-spectrum beta-lactamases (ESBLs) (75.7%, n = 143). However, most were susceptible to ceftazidime-avibactam (CZA) (94.7%, n = 179) and colistin (97.9%, n = 185). We found mgrB truncations in isolates conferring resistance to colistin and mutations in blaSHV and OmpK35 and OmpK36 osmoporins in CZA-resistant isolates. Using a regularized regression model, we found that the aerobactin sequence type and the salmochelin sequence type, among others, were predictors of the hypermucoviscosity phenotype. IMPORTANCE In this study, we address the ongoing epidemic of carbapenem-resistant Klebsiella pneumoniae, a critical threat to public health. The alarming genotypic and phenotypic convergence of multidrug resistance and virulence highlights the increasingly aggravated threat posed by K. pneumoniae. This calls for a combined effort of physicians and scientists to study the potential mechanisms and establish guidelines for antimicrobial therapies and interventions. To this end, we have conducted a genomic epidemiology and characterization study using isolates collected in a coordinated effort of multiple hospitals. Innovative biological discoveries of clinical importance are made and brought to the attention of clinical researchers and practitioners. This study presents an important advance in the application of genomics and statistics to recognize, understand, and control an infectious disease of concern.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Colistina , Estudos Transversais , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , Pacientes Internados , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Unidades de Terapia Intensiva , Genômica , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/genética
9.
Front Immunol ; 14: 1107866, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936962

RESUMO

Introduction: In China, the long-term immunogenicity and adverse effects of inactivated vaccines produced by different or the same manufacturer remain unclear. Therefore, the objective of this study was to evaluate the cellular immune responses and neutralizing antibody kinetics of homologous and heterologous administrations of an inactivated coronavirus disease 2019 (COVID-19) vaccine 240 days after the second vaccination. Methods: This prospective, multicenter, observational, longitudinal study involved 595 participants with a negative SARS-CoV-2 polymerase chain reaction result who were serologically tested and followed for 8 months after vaccination. Neutralizing antibodies, interferon-gamma (IFN-γ), interleukin (IL)-6, CD4+ T-lymphocyte, and B-lymphocyte counts were evaluated in serum samples after stimulation with 2 µg/mL SARS-CoV-2 spike protein for 16 h at follow-up intervals of 2 months. Results: Most participants [582/595; 146 male participants, 449 female participants; mean age 35 (26-50 years)] rapidly developed neutralizing antibodies after two doses of the vaccine administered 3-weeks apart. The positive rate of neutralizing antibodies peaked at 97.7% at 60-90 days, decreased, and stabilized at 82.9% at 181-240 days post-vaccination. Lower antibody concentrations were correlated with older age, longer duration after vaccination, non-health care workers, mixed-manufacturer vaccinations, and intervals of less than 40 days between two doses of vaccination, whereas lower IFN-γ levels and B-lymphocyte counts were associated with older age, blood type A, and non-health care workers. A higher IL-6 level was associated with older age, mixed-manufacturer vaccinations, intervals of less than 40 days between two doses of vaccination, and medical staff. Adverse reactions were mild or moderate and self-limited, with no serious events reported. Discussion: Two doses of the Chinese inactivated vaccine induced robust and rapid antibody expression and cellular immune responses. Boosting vaccination is considered important, as antibodies and cellular immune responses were reduced in susceptible populations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Feminino , Humanos , Masculino , Anticorpos Neutralizantes , China , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Estudos Longitudinais , Estudos Prospectivos , SARS-CoV-2 , Imunidade Humoral , Imunidade Celular , Pessoa de Meia-Idade
10.
Infect Drug Resist ; 16: 1171-1181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875227

RESUMO

Purpose: To evaluate the performance of five widespread commercial products for colistin and polymyxin B susceptibility testing in China for mcr-positive and -negative Escherichia coli and Klebsiella pneumoniae. Methods: A total of 132 E. coli and 83 K. pneumoniae strains (including 68 mcr-1-positive E. coli and 28 mcr-8-positive K. pneumoniae) were collected. We analysed the performance of colistin susceptibility (with Vitek 2 and Phoenix M50) and the performance of polymyxin B susceptibility (with DL-96II, MA120, and a Polymyxin B Susceptibility Test strip; POL E-strip). Broth microdilution was used as the gold standard. Categorical agreement (CA), essential agreement (EA), major error (ME), and very major error (VME) were calculated for comparisons. Results: For E. coli, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 98.5%/98.5%/0%/2.9%; and Phoenix M50, 98.5%/97.7%/0%/2.9%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 99.2%/63.6%/1.6%/0%; MA120, 70.0%/-/0%/58.8%; and DL-96II, 80.2%/-/1.6%/36.8%. Only Vitek 2 and Phoenix M50 presented satisfactory performances for mcr-1-positive E. coli. For K. pneumoniae, the total CA, EA, ME, and VME to colistin were as follows: Vitek 2, 73.2%/72.0%/0%/61.6%; and Phoenix M50, 74.7%/74.7%/0%/58.3%. The total CA, EA, ME, and VME to polymyxin B were as follows: POL E-strip, 91.6%/74.7%/2.1%/16.7%; MA120, 92.8%/-/2.1%/13.9%; and DL-96II, 92.2%/-/2.1%/8.3%. All systems were unsatisfactory for mcr-8-positive K. pneumoniae. When the susceptibility of mcr-negative strains was tested, all systems presented excellent performance. Conclusion: Vitek 2 and Phoenix M50 with colistin for E. coli showed acceptable performance regardless of mcr-1 expression, while DL-96II, MA120, and the POL E-strip performed worse for mcr-1-positive strains. Furthermore, mcr-8 greatly affected the performance of all systems with both colistin and polymyxin B for K. pneumoniae isolates.

11.
Front Microbiol ; 13: 894341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187994

RESUMO

Objective: In intensive care units (ICUs), carbapenem-resistant Enterobacterales (CRE) pose a significant threat. We aimed to examine the distribution, epidemiological characteristics, and risk factors for CRE positivity in ICUs. Materials and methods: This cross-sectional study was conducted in 96 ICUs of 78 hospitals in Henan Province, China. The clinical and microbiological data were collected. A multivariable logistic regression model was used to analyze the risk factors for CRE positivity. Results: A total of 1,009 patients were enrolled. There was a significant difference in CRE positive rate between pharyngeal and anal swabs (15.16 vs. 19.13%, P < 0.001). A total of 297 carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 22 carbapenem-resistant Escherichia coli (CR-ECO), 6 carbapenem-resistant Enterobacter cloacae (CR-ECL), 19 CR-KPN/CR-ECO, and 2 CR-KPN/CR-ECL were detected. Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and a combination of KPC and NDM were detected in 150, 9, and 11 swab samples, respectively. Multivariable logistic regression analysis determined length of ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotics exposure as independent risk factors for CRE positivity. Age and cardiovascular diseases were independent risk factors for mixed infections of CRE. The occurrence of CRE in secondary and tertiary hospitals was 15.06 and 25.62%, respectively (P < 0.05). Patients from tertiary hospitals had different clinical features compared with those from secondary hospitals, including longer hospital stays, a higher rate of patients transferred from other hospitals, receiving renal replacement therapy, exposure to immunosuppressive drugs, use of antibiotics, and a higher rate of the previous infection. Conclusion: In ICUs in Henan Province, CRE positive rate was very high, mostly KPC-type CR-KPN. Patients with prolonged ICU stay, chronic neurological disease, transfer from other hospitals, previous infection, and history of antibiotic exposure are prone to CRE. Age and cardiovascular diseases are susceptibility factors for mixed infections of CRE. The CRE positive rate in tertiary hospitals was higher than that in secondary hospitals, which may be related to the source of patients, antibiotic exposure, disease severity, and previous infection.

12.
Infect Drug Resist ; 15: 3841-3845, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899082

RESUMO

Background: Ralstonia mannitolilytica, an emerging opportunistic pathogen, can infect immunocompromised patients but is a rare cause of severe sepsis and septic shock in kidney transplant recipients (KTRs). Case Presentation: We present a case of septic shock after renal transplant in a 41-year-old male, which was finally proven to be caused by Ralstonia mannitolilytica through blood cultures and mass spectrometric analysis following the negative result of metagenomic next-generation sequencing (mNGS). He was finally cured after the application of sensitive antibiotics (sulfamethoxazole-trimethoprim, amikacin and piperacillin-tazobactam) based on the drug sensitivity test results. The patient had a satisfactory recovery with no complications during a 6-month follow-up period. Conclusion: This study highlights that Ralstonia mannitolilytica is an easily overlooked cause of septic shock in KTRs requiring a detailed inquiry of medical history with inflammatory markers monitored closely. Traditional blood cultures still should be taken seriously. It also provides a cautionary tale that negative results of mNGS have to be interpreted with caution.

13.
DNA Cell Biol ; 41(5): 479-486, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35486848

RESUMO

Sepsis is a global health care issue that affects millions of people. DNA methyltransferase I (DNMT1)-mediated DNA methylation is involved in a number of human diseases by affecting many types of cellular progression events. However, the role and underlying molecular mechanism of DNMT1 in development of sepsis remain largely unknown. Lipopolysaccharide (LPS) induced lung fibrosis in the sepsis mouse model, and DNMT1 was upregulated in lung tissues of a sepsis mouse model compared with lung tissues from control mice. Then, this study demonstrated that LPS induced the production of interleukin (IL)-7 and tumor necrosis factor (TNF)-α and promoted DNMT1 expression in primary type II alveolar epithelial cells (AECII cells). Knockdown of DNMT1 inhibited IL-7 and TNF-α secretion in AECII cells exposed to LPS. Further study demonstrated that DNMT1 repressed the expression of miR-130a in AECII cells with or without LPS exposure. Next, this study demonstrated that miR-130a inhibited ZEB1 expression in AECII cells exposed to LPS. Ultimately, this study revealed the role of the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells exposed to LPS. Overall, our data revealed that LPS induced the secretion of inflammatory factors by modulating the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells, thus providing a novel theoretical basis that might be beneficial for establishment of diagnostic and therapeutic strategies for sepsis.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , MicroRNAs , Sepse , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Células Epiteliais Alveolares/metabolismo , Animais , DNA (Citosina-5-)-Metiltransferase 1/genética , Humanos , Lipopolissacarídeos , Camundongos , MicroRNAs/genética , Sepse/induzido quimicamente , Sepse/genética , Fator de Necrose Tumoral alfa/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
14.
J Microbiol Methods ; 193: 106417, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35033634

RESUMO

Many factors affecting satellitism tests are unclear, and it is difficult to avoid misidentification, even if the medium is properly selected. We investigated the factors causing false-positive results for Haemophilus influenzae and false-negative results for Haemophilus parainfluenzae in the satellitism tests using Staphylococcus aureus as the source of nicotinamide adenine dinucleotide (NAD). H. influenzae (four reference strains and 47 clinical isolates), H. parainfluenzae (two reference strains and 67 clinical isolates), four different media, and two strains of S. aureus revived on two different media were used in this study. The type of medium used to revive S. aureus was the most common factor causing false-positive results for H. influenzae, followed by different strains of S. aureus and the type of medium used for the experiment. The production of false-negative results for H. parainfluenzae was only related to the medium used in the experiment. To improve the accuracy of the tests in routine laboratories, using S. aureus as the source of NAD, tryptic soy agar, and S. aureus (ATCC 25923) revived on nutrient agar should be adopted.


Assuntos
Infecções por Haemophilus , Haemophilus influenzae , Ágar , Meios de Cultura , Haemophilus , Haemophilus parainfluenzae , Humanos , Indicadores e Reagentes , NAD , Staphylococcus aureus
15.
J Intensive Med ; 2(1): 56-60, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36789234

RESUMO

Background: The aim of this study was to assess whether satellite blood culture (SBC) can improve turnaround times, antibiotic switching, and patient prognosis, relative to laboratory blood culture (LBC).  . Methods: Patients with sepsis treated in the intensive care units (ICUs) of Henan Provincial People's Hospital from February 5, 2018 to January 19, 2019 who met the inclusion criteria were recruited to the study and divided into the SBC group and LBC group according to different blood culture methods. Patient demographics, blood culture, antibiotic adjustment, and prognosis data were collected and compared between the two groups.  . Results: A total of 204 blood culture sets from 52 ICU patients, including 100 from the medical microbiology LBC group and 104 from the SBC group, were analyzed in this study. There was no significant difference in the positive rates between the two groups. Time from specimen collection to incubation was significantly shorter in the SBC group than that in the LBC group (1.65 h vs. 3.51 h, z=-4.09, P<0.001). The median time from specimen collection to notification of blood culture positivity was 24.83 h in the SBC group and 27.83 h in the LBC group. Median times from adjustment of antibiotics according to the first report were 26.05 h and 51.71 h in the SBC and LBC groups, respectively, while those according to the final report were 97.17 h and 111.45 h, respectively. Median ICU lengths of stay were 15.00 days and 17.00 days in the SBC and LBC groups, respectively, and median ICU lengths of stay were 18.00 days and 23.50 days, respectively. Mean hospitalization costs were 157.99 and 186.73 thousand yuan in the SBC and LBC groups, respectively.  . Conclusion: SBC can significantly reduce blood culture turnaround times; however, there were no significant differences between the two blood culture methods in initial reporting of positive cultures, time to adjustment of antibiotic therapy, or medical costs, despite a trend toward improvement.

16.
17.
Infect Drug Resist ; 15: 7693-7697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36597454

RESUMO

Nocardia brain abscess is relatively rare and generally occurs in immunodeficient patients. Here, we present the first case of brain abscess due to Nocardia brevicatena in an immunocompetent patient, with unknown origin. In this case, a 49-year-old man was admitted to our hospital with limb twitching and complained of a history of intermittent headache. He was diagnosed with brain abscess through brain imaging and cured after craniotomy for abscess excision and targeted antibiotic treatment. Surgical specimens were sent for further detection. The causative organism was identified by weak acid-fast staining, culture and metagenomic next-generation sequencing (mNGS). We hope this case could provide a reference for incoming patients as well as their clinical management.

18.
DNA Cell Biol ; 40(11): 1396-1406, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34767734

RESUMO

Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Metilprednisolona/farmacologia , Sepse/tratamento farmacológico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Inflamação , Lipopolissacarídeos/farmacologia , Metilprednisolona/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Infect Drug Resist ; 14: 4783-4793, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815676

RESUMO

OBJECTIVE: This study aimed to investigate the prevalence, genetic diversity and clinical characteristics of Clostridium perfringens isolates from hospitalized clinical diarrheal patients. METHODS: A prospective study was conducted on 1108 patients with diarrhea during hospitalization. Stool samples were cultured for C. perfringens, and the toxin genes were detected by PCR. The available clinical data of 112 patients were analyzed to study the clinical features of various isolates. Multi-locus sequence typing (MLST) was performed to assess phylogenetic relationship between different isolates. RESULTS: A total of 153 (13.8%) isolates were obtained from patients' stools. C. perfringens type F (49.0%) was the major toxin type in the isolates, followed by type A (n = 59, 38.6%) and type C (n = 14, 9.2%). Patients older than 50 years and those with underlying diseases of cancer, hepatobiliary system, and ulcerative colitis (UC) were more predisposed to C. perfringens type F and type A infection than to type C. The patients infected with type C experienced more severe clinical symptoms compared to those with type A infection. There was a significant association between type FC and foodborne gastrointestinal (GI) diseases (p = 0.018), between type FP and antibiotic-associated diarrhea (AAD) (p < 0.001), and between type A and sporadic diarrhea (SD) (p < 0.001). Phylogenetic analysis indicated that type F isolates carrying a chromosomal cpe gene mainly belonged to ST77 (6/15 isolates). Type F isolates with cpe gene on a plasmid exhibited high genetic diversity. CONCLUSION: High prevalence and considerable genetic diversity of C. perfringens type F were found in clinical diarrheal patients. Elderly people and patients with cancer, hepatobiliary diseases or UC, or suspected of having food poisoning (FP) may be targeted for routine testing of C. perfringens toxin genes and may benefit from early detection of C. perfringens type C isolates that cause more severe clinical symptoms.

20.
Infect Drug Resist ; 14: 1805-1811, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017186

RESUMO

BACKGROUND: In renal transplant recipients, carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a common complication, and usually associated with severe clinical outcomes due to a lack of effective treatment. CASE PRESENTATION: A 37-year-old woman with CRKP infection one month after kidney transplantation was involved in this study. Microbial characteristics of fecal samples from the patient were analyzed. Fecal microbiota transplantation (FMT) was performed for treating the CRKP infection. One week after FMT, the patient's urine and anal swab cultures returned negative for CRKP, and 17 days after FMT, the incision showed complete healing. Moreover, the patient had no symptoms of infection two months after FMT. Alpha diversity analyses showed that before FMT, the patient was associated with obviously lower species richness and diversity than the donor, which significantly increased at one week, three weeks and two months after FMT. Beta diversity analyses showed that though the patient's microbial community post-FMT still differed from the donor composition, their distances decreased visibly, especially at one week and three weeks after FMT. Obvious shift in microbial composition could be observed before and after FMT. The microbial composition of the patient post FMT resembled the donor composition. Relative abundance of genera such as Phascolarctobacterium and Lachnoclostridium increased after FMT, while the relative abundance of Klebsiella significantly decreased. CONCLUSION: This study demonstrated the therapeutic effect of FMT on infections caused by CRKP for a renal transplant patient. Further studies are required to confirm the findings of this study.

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