Curing of common plasmids in gram-negative bacteria using a Cas9-based conjugative vector.

We report the creation of 17 Escherichia coli strains harboring the conjugative plasmid pLCasCureT with a CRISPR-Cas9 system to surgically "cure" the most common plasmids among Enterobacterales species. This approach can create isogenic pairs of strains to study host-plasmid interactions, correlate plasmid genotype and phenotype, and create plasmid-free cloning strains.

Tracking emergence and outbreak of Klebsiella pneumoniae co-producing NDM-1 and KPC-2 after sulfamethoxazole-trimethoprim treatment: Insights from genetic analysis.

The co-production of KPC and NDM carbapenemases in carbapenem-resistant Klebsiella pneumoniae (CRKP) complicates clinical treatment and increases mortality rates. The emergence of KPC-NDM CRKP is believed to result from the acquisition of an NDM plasmid by KPC CRKP, especially under the selective pressure of ceftazidime-avibactam (CZA). In this study, a CRKP-producing KPC-2 (JNP990) was isolated from a patient at a tertiary hospital in Shandong Province, China.

Characterization of nontyphoidal strains from a tertiary hospital in China: serotype diversity, multidrug resistance, and genetic insights.

Objective: Nontyphoidal is a significant public health concern due to its ability to cause foodborne illnesses worldwide. This study aims to characterize the nontyphoidal strains isolated from patients in China.

Methods: A total of 19 nontyphoidal strains were characterized through serovar identification, antimicrobial susceptibility testing (AST), biofilm formation assessment.

The first report of Apiotrichum mycotoxinivorans isolation from human cerebrospinal fluid.

Fungal infections due to Apiotrichum mycotoxinivorans are clinically rare. Here, we report a case of invasive blood and cerebrospinal fluid infection by Apiotrichum mycotoxinivorans in a girl with B-cell acute lymphoblastic leukemia. This is the first report of the isolation of Apiotrichum mycotoxinivorans from human cerebrospinal fluid.

Epidemiology and antifungal susceptibility of fungal infections from 2018 to 2021 in Shandong, eastern China: A report from the SPARSS program.

Purpose: We analyzed the pathogenic fungal epidemiology and antifungal susceptibility from 2018 to 2021 in Shandong Province, China, to provide the basis for empiric antifungal therapy.

Methods: Fungal isolates were collected from 54 hospitals in Shandong province from 2018 to 2021 through the Shandong Province Pediatric bacterial & fungal Antimicrobial Resistance Surveillance System (SPARSS), WHONET v5.6 and SPSS software v20.

Interaction of multidrug-resistant hypervirulent with components of human innate host defense.

strains with a combination of multidrug resistance and hypervirulence genotypes (MDR hvKp) have emerged as a cause of human infections. The ability of these microbes to avoid killing by the innate immune system remains to be tested fully. To that end, we compared the ability of a global collection of hvKp and MDR hvKp clinical isolates to survive in human blood and resist phagocytic killing by human neutrophils.

Genetic and enzymatic characterization of two novel bla variants in Escherichia coli strains.

The widespread of different NDM variants in clinical Enterobacterales isolates poses a serious public health concern, which requires continuous monitoring. In this study, three E. coli strains carrying two novel bla variants of bla were identified from a patient with refractory urinary tract infection (UTI) in China.

Meta-analysis of the efficacy of glycyrrhizin for postoperative liver preservation in patients with liver cancer.

Objective: This meta-analysis comprehensively summarizes the current clinical research on compound glycyrrhizin (CG) treatment for liver cancer and protecting liver function to guide clinical treatment.

Methods: Eighteen English-language articles were retrieved from PubMed, SinoMed, Cochrane, Embase, Web of Science, and three Chinese databases: The Wan Fang database, China National Knowledge Infrastructure (CNKI), and the VIP database.

Results: CG treatment improved the patient's alanine aminotransferase (ALT) level (in the metastatic liver cancer group: mean deviation (MD) = -13.

Characterization of IncHI1B Plasmids Encoding Efflux Pump in Carbapenem-Resistant , , and Strains.

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, , and its variants, and , encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three -harboring species strains, collected from two teaching tertiary hospitals in China, including one , one , and one .

Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains.

Background: Recent studies indicated that the monosubstituted deoxystreptamine aminoglycoside apramycin is a potent antibiotic against a wide range of MDR Gram-negative pathogens.

Objectives: To evaluate the in vitro activity of apramycin against carbapenem-resistant Klebsiella pneumoniae (CRKp) isolates from New York and New Jersey, and to explore mechanisms of apramycin resistance.

Methods: Apramycin MICs were determined by broth microdilution for 155 CRKp bloodstream isolates collected from 2013 to 2018.

Clinical laboratory evaluation of COVID-19.

COVID-19, caused by SARS-CoV-2, is a highly infectious disease, and clinical laboratory detection has played important roles in its diagnosis and in evaluating progression of the disease. Nucleic acid amplification testing or gene sequencing can serve as pathogenic evidence of COVID-19 diagnosing for clinically suspected cases, and dynamic monitoring of specific antibodies (IgM, IgA, and IgG) is an effective complement for false-negative detection of SARS-CoV-2 nucleic acid. Antigen tests to identify SARS-CoV-2 are recommended in the first week of infection, which is associated with high viral loads.

Comparative genome analysis of multidrug-resistant Pseudomonas aeruginosa JNQH-PA57, a clinically isolated mucoid strain with comprehensive carbapenem resistance mechanisms.

Background: The prevalence of clinical multidrug-resistant (MDR) Pseudomonas aeruginosa has been increasing rapidly worldwide over the years and responsible for a wide range of acute and chronic infections with high mortalities. Although hundreds of complete genomes of clinical P. aeruginosa isolates have been sequenced, only a few complete genomes of mucoid strains are available, limiting a comprehensive understanding of this important group of opportunistic pathogens.

TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis.

Background: To investigate the roles of the transcription factors twist family bHLH transcription factor 1 (TWIST1), twist family bHLH transcription factor 2 (TWIST2), and peroxisome proliferator activated receptor gamma (PPARγ) in the progression of nonalcoholic steatohepatitis.

Methods: The protein levels of TWIST1, TWIST2 and PPARγ were determined in the serum of nonalcoholic fatty liver disease (NAFLD) patients and healthy controls by enzyme-linked immunosorbent assay (ELISA). An in vivo model for fatty liver was established by feeding C57BL/6 J mice a high-fat diet (HFD).

CRISPR-Cas9-Mediated Carbapenemase Gene and Plasmid Curing in Carbapenem-Resistant .

Combating plasmid-mediated carbapenem resistance is essential to control and prevent the dissemination of carbapenem-resistant (CRE). Here, we conducted a proof-of-concept study to demonstrate that CRISPR-Cas9-mediated resistance gene and plasmid curing can effectively resensitize CRE to carbapenems. A novel CRISPR-Cas9-mediated plasmid-curing system (pCasCure) was developed and electrotransferred into various clinical CRE isolates.

Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Isolates.

Objective: The emergence of carbapenem-resistant and hypervirulent (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates.

Unique properties of IgG4 antibody and its clinical application in autoimmune pancreatitis.

Background: Autoimmune pancreatitis (AIP) is defined as a unique form of chronic pancreatitis characterized by clinical presentation with obstructive jaundice, a dense lymphoplasmacytic infiltrate and fibrosis histologically, and a dramatic response to steroids therapeutically. The possible role of IgG4 in driving the pathology of AIP is a controversial subject that has not been addressed satisfactorily.  Objective: The purpose of this review is to discuss the unique biology of IgG4 that are important for its role and the clinical applications for serologic detection.

The reliable assurance of detecting somatic mutations in cancer-related genes by next-generation sequencing: the results of external quality assessment in China.

To evaluate the proficiencies of laboratories utilizing next-generation sequencing (NGS) to detect somatic mutations in cancer-related genes, an external quality assessment (EQA) was implemented by the National Center for Clinical Laboratories of China in 2015. We prepared a panel of samples that comprised eight samples made by mixing synthetic mutated DNA fragments with normal human genomic DNA and one reference sample containing only genomic DNA. We validated our sample panel, and then distributed it to laboratories across China.

Evaluation of serum immunoglobulins concentrations and distributions in vitiligo patients.

Vitiligo is a dermatological disorder with an autoimmune mechanism characterized by production of a variety of autoantibodies. Different levels of immunoglobulins can indicate the presence and the stage of some autoimmune diseases. We aimed to investigate serum IgA, IgM and IgG subclass levels and melanocyte-reactive antibodies in 65 vitiligo patients by the immunonephelometric assay (35 healthy people as controls).

Hybrid kappa\lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer.

The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid κ\λ antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid κ\λ antibodies in human sera.

Diagnostic Value of Serum IgG4 for IgG4-Related Disease: A PRISMA-compliant Systematic Review and Meta-analysis.

Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them.The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA.