Novel Providencia xianensis sp. nov.: A multidrug-resistant species identified in clinical infections.

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.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

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.

Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells.

Arborinine is a natural product isolated from G. parva leaf extracts, which displays potentially antiproliferative activity against human cervical cancer cells. In contrast, its anticancer effects against gastric cancer cells and drug-resistant gastric cancer cells remain unknown. In this work, arborinine was evaluated as a broad-spectrum antiproliferative agent, and it exhibited potently inhibitory activity against NCI-N87 (IC50 = 5.67 µM), BGC-823 (IC50 = 7.26 µM), MGC803 (IC50 = 4.75 µM), SGC-7901 (IC50 = 1.96 µM), HGC-27 (IC50 = 5.70 µM), SGC-7901/ADR (IC50 = 0.24 µM), SGC-7901/VCR (IC50 = 1.09 µM), and MGC803/PTX (IC50 = 1.32 µM) cell lines. Subsequent target verification experiments demonstrated that arborinine selectively and reversibly inhibited LSD1 in a time-dependent manner. Furthermore, it was found that arborinine suppressed the epithelial-mesenchymal transition of gastric cancer cell line SGC-7901 and adriamycin-resistant gastric cancer cell line SGC-7901/ADR in a dose-dependent manner. The in vivo antitumor study further indicated that arborinine can significantly reduce the growth of tumors both in SGC-7901 and SGC-7901/ADR xenograft mouse models. Overall, we demonstrated the potential of arborinine as an effective treatment for gastric cancer and adriamycin-resistant gastric cancer.

A circRNA-miRNA-mRNA regulatory network associated with the treatment response to tuberculosis.

OBJECTIVES: The high morbidity and mortality of tuberculosis (TB) have severe socio-economic consequences, and there is an urgent need to explore the mechanisms driving TB development and progression. The aim of this study was to analyze the regulatory RNAs and target genes involved in TB, in order to identify key genetic biomarkers for diagnosing and treating TB. METHODS: Circular RNAs (circRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) expression profiles of TB patients and healthy controls were downloaded from the GEO database. A circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed using the differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs). The DEmRNAs in this network were functionally annotated using GO and KEGG analyses, and ordinal regression analysis was used to identify the genes correlated to the treatment response in TB patients. RESULTS: We identified 133 DEmRNAs, 37 DEcircRNAs and 173 DEmiRNAs between the TB and healthy controls, from which 30 DECircRNAs, 27 DEmiRNAs and 35 DEmRNAs were used to construct the ceRNA network. CACNA1I, IGF2BP3, LPCAT2, SPOCK2 and IRF2 were significantly correlated with the anti-TB therapeutic response (P < 0.05). CONCLUSION: A TB-associated DEcircRNA-miRNA-mRNA ceRNA network was constructed, of which some DEmRNAs potentially influence the treatment response.

Association of serum asprosin concentrations with obstructive sleep apnea syndrome.

OBJECTIVE: Asprosin, a recently discovered adipokine, stimulates the release of hepatic glucose. The purpose of the current research was to determine the relation between serum asprosin and obstructive sleep apnea syndrome (OSAS). METHODS: The current investigation enrolled 152 patients with OSAS and 97 control subjects. Serum asprosin concentrations were measured and analyzed. RESULTS: Higher serum asprosin concentrations were found in patients with OSAS than in the controls. Logistic regression analysis demonstrated that serum asprosin concentrations were associated with an increased risk of OSAS. Patients with severe OSAS had significantly increased asprosin compared to mild and moderate groups. The group with moderate OSAS showed higher serum asprosin levels than the group with mild OSAS. Pearson correlation analysis demonstrated a positive relation between serum asprosin and disease severity. Simple linear regression analyses showed a significant correlation between serum asprosin with body mass index (BMI), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and apnea-hypopnea index (AHI), and negatively correlated with high-density lipoprotein cholesterol (HDL-C). Multiple linear regression analysis revealed a significant correlation between serum asprosin with BMI, FPG, HOMA-IR, TG, AHI, and HDL-C. CONCLUSION: There is a significant correlation between serum asprosin with the presence and severity of OSAS.

Evaluation of the Autof MS1000 mass spectrometer in the identification of clinical isolates.

BACKGROUND: To evaluate the accuracy and performance of the Autof MS1000 mass spectrometer in bacteria and yeast identification, 2342 isolates were obtained from microbial cultures of clinical specimens (e.g. blood, cerebrospinal fluid, respiratory tract samples, lumbar puncture fluid, wound samples, stool, and urine) collected in 2019 in Henan Provincial People's Hospital. Repetitive strains from the same patient were excluded. We tested the Autof MS1000 and Bruker Biotyper mass spectrometry systems and the classical biochemical identification system VITEK 2/API 20C AUX. Inconsistencies in strain identification among the three systems were identified by 16S rDNA and gene sequencing. RESULTS: At the species level, the Autof MS1000 and Bruker Biotyper systems had isolate identification accuracies of 98.9 and 98.5%, respectively. At the genus level, the Autof MS1000 and Bruker Biotyper systems were 99.7 and 99.4% accurate, respectively. The instruments did not significantly differ in identification accuracy at either taxonomic level. The frequencies of unreliable identification were 1.1% (26/2342) for the Autof MS1000 and 1.5% (34/2342) for the Bruker Biotyper. In vitro experiments demonstrated that the coincidence rate of the Autof MS1000 mass spectrometer in the identification of five types of bacteria was > 93%, the identification error rate was < 3%, and the no identification rate was 0. This indicates that the Autof MS1000 system is acceptable for identification. CONCLUSIONS: The Autof MS1000 mass spectrometer can be utilised to identify clinical isolates. However, an upgradation of the database is recommended to correctly identify rare strains.

Reliability and Validity of the Chinese Version of the Cognitive Distortions Questionnaire (CD-Quest) in College Students.

BACKGROUND The aim of this study was to evaluate the reliability and validity of the Chinese version of the Cognitive Distortions Questionnaire (CD-Quest) among Chinese college students. MATERIAL AND METHODS A total of 460 college students from Jining were recruited in the study. Sample 1, including 239 college students, was tested for item analysis and exploratory factor analysis. Sample 2, including 221 college students, was tested for confirmatory factor analysis and criterion validity. The criterion validity was tested using the Negative Automatic Thoughts questionnaire (ATQ) and Dysfunctional Attitudes Scale (DAS). Test-retest reliability was evaluated in 40 college students from sample 1 with  4 weeks interval. RESULTS The corrected item-total correction (ITC) ranged from 0.675 (emotional reasoning) to 0.829 (unfair comparison). Exploratory factor analysis revealed the variance of the CD-Quest items was unidimensional, and it explained 55.261% of the data variance. Confirmatory factor analysis indicated all regression coefficients were higher than 0.4. The criterion validity was excellent, as shown by the relationships among CD-Quest, DAS, and ATQ (r=0.447, 0.566, respectively). Cronbach's alpha coefficient was 0.941 and the test-retest reliability was 0.928. CONCLUSIONS The Chinese version of CD-Quest had good reliability and validity, suggesting it is a reliable tool to evaluate cognitive distortion of Chinese college students.

Evaluation of an optimized method to directly identify bacteria from positive blood cultures using MALDI-TOF mass spectrometry.

BACKGROUND: Although various methods have been developed to directly identify bacteria from positive blood cultures by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), the necessity of using commercial kits still leads to a high cost and long assay time. Moreover, few evaluations of these methods have been conducted. This study aimed to evaluate the feasibility of an optimized MALDI-TOF MS method for direct identification of bacteria in positive blood cultures. METHODS: A total of 829 non-repeated positive cultures were collected from July 2018 to August 2019, and direct identification was performed by an optimized MALDI-TOF MS method. The same positive blood cultures were sub-cultivated to obtain a single bacterial colony and identified by classical biochemical BD testing, which is the gold standard to compare the accuracy of direct identification of positive blood cultures by MALDI-TOF MS. RESULTS: After excluding 7 false-positive samples from the 829 positive blood cultures, the most accurate rate of direct identification by this optimized MALDI-TOF MS method was for gram-negative bacteria (91.5%), followed by gram-positive bacteria (88.3%), fungi (84.8%), anaerobic bacteria (80%), and other rare bacteria (66.67%). CONCLUSION: Common bacteria in positive blood cultures can be identified directly within 1 hour by MALDI-TOF MS, and thus, this optimized method can be used as a primary identification method by clinicians. Routine implementation of this method may significantly increase the optimal utilization rate of antibiotics and decrease mortality in bacteremia patients.

Co-carrying of KPC-2, NDM-5, CTX-M-3 and CTX-M-65 in three plasmids with serotype O89: H10 Escherichia coli strain belonging to the ST2 clone in China.

Carbapenem-resistant Enterobacteriaceae strains as a new serious threat for the public health have been increasingly reported worldwide. In this study, one multi-resistant Escherichia coli strain ZSH6 which co-carried blaKPC-2, blaNDM-5 and blaCTX-M, was isolated from human blood sample. By using plasmid conjugation experiments, ZSH6 was found to harbor three plasmids carrying the blaNDM-5 gene, the blaKPC-2 and blaCTX-M gene, respectively. Whole-genome sequencing of ZSH6 yielded 122 scaffolds of chromosomal DNA and three circular plasmids including pZSH6-blaKPC-2 (46,319 bp), pZSH6-blaNDM-5 (46,161bp) and pZSH6-blaCTX-M (184,723). The isolate was classified to Sequence Type 2 and to the O89: H10 serotype. The results of genome analyses revealed that ZSH6 carried three virulence factors (capU, gad and iss) and twenty resistance genes [blaKPC-2blaNDM-5, blaCTX-M-3, blaCTX-M-65, blaTEM-1, floR, tet(A), tet(B), dfrA17, aadA5, sul1, mdf(A), mph(A), erm(B), aph(3')-Ia, aph(3')-Ib, aph(4)-Ia, aph(6)-Id, aac(3)-Iva, aac(3)-IId]. Therefore, the co-existence of such a large number of resistance genes in multiple plasmids making ZSH6 highly resistant to almost all kinds of commonly used antibiotics, and brings a serious challenge for resistance control and clinical treatment of infections caused by this bacterium.

Is a positive Christie-Atkinson-Munch-Peterson (CAMP) test sensitive enough for the identification of Streptococcus agalactiae?

BACKGROUND: For a long time, the Christie-Atkinson-Munch-Peterson (CAMP) test has been a standard test for the identification of Streptococcus agalactiae, and a positive result for S.agalactiae has been considered sensitive enough. METHODS: To confirm whether a positive CAMP test is a requirement for the identification of S.agalactiae, five suspected CAMP-negative S.agalactiae isolates from two hospitals, confirmed as Gram-positive and catalase-negative streptococci, were verified by the CAMP test in three batches of plates from two manufacturers and identified by the Phoenix system, MALDI-TOF MS, the PCR assay and the 16S rDNA gene sequencing. RESULTS: All five suspected strains were S.agalactiae, four of which were CAMP-negative and one of which was not S.agalactiae by the PCR assay. CONCLUSIONS: A positive CAMP test was lacking sensitivity for the identification of S.agalactiae, and the question of whether the cfb gene is worthy of targeting should be further studied.

Co-location of the blaKPC-2, blaCTX-M-65, rmtB and virulence relevant factors in an IncFII plasmid from a hypermucoviscous Klebsiella pneumoniae isolate.

Hypervirulent variants of klebsiella pneumoniae (hvKP), which cause serious infections not only healthy individuals, but also the immunocompromised patients, have been increasingly reported recently. One conjugation of a hypermucoviscous strian SWU01 co-carried the resistance gene blaKPC-2 and virulence gene iroN by the PCR detection from three carbapenem-resistance hvKP. To know the genetic context of this plasmid. The whole genome of this strain was sequenced. We got a 162,552-bp plasmid (pSWU01) which co-carried the resistance gene blaKPC-2 and virulence gene iroN. It is composed of a typical IncFII-type backbone, five resistance genes including blaCTX-M-65, blaKPC-2, blaSHV-12, blaTEM-1 and rmtB, and several virulence relevant factors including iroN, traT and toxin-antitoxin systems. The plasmid pSWU01 co-carrying the multidrug resistance determinants and virulence relevant factors from the hypermucoviscous K. pneumoniae represents a novel therapeutic challenge.

Clinical Characteristics of Nosocomial Bloodstream Infections in Neonates in Two Hospitals, China.

BACKGROUND: The improvement of medical condition requires prolonged hospital stays, which increase the risk of nosocomial bloodstream infections (BSIs). METHODS: All nosocomial BSI newborns in two hospitals were included, and the demographic and clinical characteristics of bacteremia patients were obtained from the information systems. Isolates were identified by biochemical assays. Antimicrobial susceptibility was determined using disk diffusion method. RESULTS: Except for three same risk factors, intubation with mechanical ventilation was a risk factor in Chongqing, while low birth weight was a risk factor in Henan. Klebsiella pneumoniae was the predominant strain in Chongqing, and Escherichia coli was the most prevalent strain in Henan. The resistance rate of gram-negative bacteria in Henan was higher than that of strains in Chongqing. CONCLUSIONS: The risk factors and resistance rate of pathogens were different in different areas. Therefore, treatment protocols should be established based on the trends of drug resistance and bacterial spectrum.

Genome organisation of the Acinetobacter lytic phage ZZ1 and comparison with other T4-like Acinetobacter phages.

BACKGROUND: Phage ZZ1, which efficiently infects pathogenic Acinetobacter baumannii strains, is the fifth completely sequenced T4-like Acinetobacter phage to date. To gain a better understanding of the genetic characteristics of ZZ1, bioinformatics and comparative genomic analyses of the T4 phages were performed. RESULTS: The 166,687-bp double-stranded DNA genome of ZZ1 has the lowest GC content (34.4%) of the sequenced T4-like Acinetobacter phages. A total of 256 protein-coding genes and 8 tRNA genes were predicted. Forty-three percent of the predicted ZZ1 proteins share up to 73% amino acid identity with T4 proteins, and the homologous genes generally retained the same order and transcriptional direction. Beyond the conserved structural and DNA replication modules, T4 and ZZ1 have diverged substantially by the acquisition and deletion of large blocks of unrelated genes, especially in the first halves of their genomes. In addition, ZZ1 and the four other T4-like Acinetobacter phage genomes (Acj9, Acj61, 133, and Ac42) share a well-organised and highly conserved core genome, particularly in the regions encoding DNA replication and virion structural proteins. Of the ZZ1 proteins, 70, 64, 61, and 56% share up to 86, 85, 81, and 83% amino acid identity with Acj9, Acj61, 133, and Ac42 proteins, respectively. ZZ1 has a different number and types of tRNAs than the other 4 Acinetobacter phages, although some of the ZZ1-encoded tRNAs share high sequence similarity with the tRNAs from these phages. Over half of ZZ1-encoded tRNAs (5 out of 8) are related to optimal codon usage for ZZ1 proteins. However, this correlation was not present in any of the other 4 Acinetobacter phages. CONCLUSIONS: The comparative genomic analysis of these phages provided some new insights into the evolution and diversity of Acinetobacter phages, which might elucidate the evolutionary origin and host-specific adaptation of these phages.

Causal relationship between type 1 diabetes mellitus and mycoses: a Mendelian randomization study.

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.

Rapid inference of antibiotic resistance and susceptibility for Klebsiella pneumoniae by clinical shotgun metagenomic sequencing.

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.

In vitro repolarized tumor macrophages inhibit gastric tumor growth.

Gastric cancer is the second most frequent cause of cancer-related death worldwide. Combined surgery and chemo/radiotherapy give only a limited 5-year survival rate. Alternative therapeutic strategies such as immunotherapy are needed to improve this survival rate. Macrophages are functionally plastic cells. Type 1 macrophages (M1) inhibit, whereas type 2 macrophages (M2) promote, tumor growth. In this study, we examined the effects of in vitro repolarized tumor macrophages on gastric tumor growth in vivo. We demonstrated that peritoneal macrophages isolated from mouse forestomach carcinoma (MFC) tumor-bearing mice (TPM) displayed a M2 functional phenotype as indicated by a characteristic cytokine production profile and expression pattern of inducible nitric oxide synthase (iNOS) and arginase (Arg) of M2 macrophages. Treatment of TPM with type 1 cytokine IL-12 and IFN-gamma repolarized TPM toward the M1 phenotype as confirmed by a cytokine production profile and expression pattern of iNOS and Arg of typical M1 macrophages. Repolarized TPM significantly inhibits the growth of MFC tumors implanted subcutaneously compared to peritoneal macrophage (PM) isolated from normal animals, TPM, or M2 macrophages. Our study supports in vitro repolarization of macrophages as a potential immunotherapeutic strategy for gastric cancer.

Rapid screening for Chlamydia trachomatis infection by detecting α-mannosidase activity in urogenital tract specimens.

BACKGROUND: Chlamydia trachomatis may cause multiple different urogenital tract disorders, but current non-culture assays for rapid screening of C. trachomatis typically use immunochromatography-based methods. We established another new rapid non-culture method for detection of C. trachomatis based on the measurement of α-mannosidase enzymatic activity in urogenital tract specimens. METHOD: To evaluate the performance of this method, α-mannosidase activities of C. trachomatis serotype D strain 、 and 29 standard strains related to clinical urogenital pathogens were investigated. Furthermore, 553 urogenital tract specimens were used for clinical assays via cell culture method and ligase chain reaction method (LCR), adopting an expanded gold standard. RESULTS: Only C. trachomatis was positive for α-mannosidase activity among different types of microbes tested in the research. When prostate fluid specimens, which have some interfering activity, were excluded, the sensitivity and specificity of the enzymatic method were 91.8% (78/85) and 98.3% (409/416), respectively. There were no significant differences (P > 0.05). CONCLUSIONS: These results showed that α-mannosidase activity could be utilised as a screening marker of C. trachomatis infection.

Pachymic Acid Protects Against Bleomycin-Induced Pulmonary Fibrosis by Suppressing Fibrotic, Inflammatory, and Oxidative Stress Pathways in Mice.

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.

Microbiological Analysis and Mortality Risk Factors in Patients with Polymicrobial Bloodstream Infections.

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.

Genomic Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae in ICU Inpatients in Henan Province, China: a Multicenter Cross-Sectional Study.

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.