Uses of a real-time automatic nosocomial infection surveillance system to support prevention and control of hospital-acquired infections in the ICU.

Introduction: The intensive care unit (ICU) caters to patients with severe illnesses or injuries who require constant medical attention. These patients are susceptible to infections due to their weak immune systems and prolonged hospital stays. This makes the ICU the specialty with the highest hospital-acquired infection (HAI) cases. The core dimension of infection prevention and control for ICUs is infection surveillance, which analyses the risk factors of HAI and implements comprehensive interventions for HAI prevention and control. Hence, this study aimed to investigate the potential risk factors for developing HAI in the ICU using real-time automatic nosocomial infection surveillance systems (RT-NISS) to surveil, and analyze the effectiveness of RT-NISS coupled with comprehensive interventions on HAI prevention and control in the ICU. Methods: A retrospective analysis was conducted using data from an RT-NISS for all inpatients in the ICU from January 2021 to December 2022. Univariate and multivariate logistic regression analyses were performed to analyse potential risk factors for HAI in the ICU. Surveillance of the prevalence proportion of HAI, the prevalence proportion of site-specific HAI, the proportion of ICU patients receiving antibiotics, the proportion of ICU patients receiving key antimicrobial combination, the proportion of HAI patients with pathogen detection, the proportion of patients with pathogen detection before antimicrobial treatment and the proportion of patients before receiving key antimicrobial combination, the utilization rate of devices and the rate of device-associated HAIs were monitored monthly by the RT-NISS. Comprehensive interventions were implemented in 2022, and we compared the results of HAIs between 2021 and 2022 to evaluate the effect of the RT-NISS application combined with comprehensive interventions on HAI prevention and control. Results: The relative risk factors, observed as being a significantly higher risk of developing HAI, were hospitalization over 2 weeks, chronic lung diseases, chronic heart diseases, chronic renal diseases, current malignancy, hypohepatia, stroke, cerebrovascular accident, severe trauma, tracheal intubation and tracheostomy and urinary catheter. By implementing comprehensive interventions depending on infection surveillance by the RT-NISS in 2022, the prevalence proportion of HAI was reduced from 12.67% in 2021 to 9.05% in 2022 (χ2 = 15.465, p < 0.001). The prevalence proportion of hospital-acquired multidrug-resistant organisms was reduced from 5.78% in 2021 to 3.21% in 2022 (χ2 = 19.085, p < 0.001). The prevalence proportion of HAI in four sites, including respiratory tract infection, gastrointestinal tract infection, surgical site infection, and bloodstream infection, was also significantly reduced from 2021 to 2022 (both p < 0.05). The incidence of ventilator-associated pneumonia in 2022 was lower than that in 2021 (15.02% vs. 9.19%, χ2 = 17.627, p < 0.001). Conclusion: The adoption of an RT-NISS can adequately and accurately collect HAI case information to analyse the relative high-risk factors for developing HAIs in the ICU. Furthermore, implementing comprehensive interventions derived from real-time automation surveillance of the RT-NISS will reduce the risk and prevalence proportions of HAIs in the ICU.

Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis. OBJECTIVES: To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis. METHODS: The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments. RESULTS: We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation. CONCLUSION: Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.

Bacteroides ovatus-mediated CD27- MAIT cell activation is associated with obesity-related T2D progression.

Type 2 diabetes (T2D) is highly associated with obesity. However, the factors that drive the transition from excessive weight gain to glucose metabolism disruption are still uncertain and seem to revolve around systemic immune disorder. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial metabolites, have been reported to be altered in obese people and to lead to metabolic dysfunction during obesity. By studying the immunophenotypes of blood MAIT cells from a cross-sectional cohort of obese participants with/without T2D, we found an elevation in CD27-negative (CD27-) MAIT cells producing a high level of IL-17 under T2D obese conditions, which could be positively correlated with impaired glucose metabolism in obese people. We further explored microbial translocation caused by gut barrier dysfunction in obese people as a triggering factor of MAIT cell abnormalities. Specifically, accumulation of the bacterial strain Bacteroides ovatus in the peripheral blood drove IL-17-producing CD27- MAIT cell expansion and could be associated with T2D risk in obese individuals. Overall, these results suggest that an aberrant gut microbiota-immune axis in obese people may drive or exacerbate T2D. Importantly, CD27- MAIT cell subsets and Bacteroides ovatus could represent targets for novel interventional strategies. Our findings extend current knowledge regarding the clinical relevance of body mass index (BMI)-associated variation in circulating MAIT cells to reveal the role of these cells in obesity-related T2D progression and the underlying cellular mechanisms.

Induced regulatory T cells suppress Tc1 cells through TGF-ß signaling to ameliorate STZ-induced type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic ß cells. In addition to well-established pathogenic effector T cells, regulatory T cells (Tregs) have also been shown to be defective in T1D. Thus, an increasing number of therapeutic approaches are being developed to target Tregs. However, the role and mechanisms of TGF-ß-induced Tregs (iTregs) in T1D remain poorly understood. Here, using a streptozotocin (STZ)-induced preclinical T1D mouse model, we found that iTregs could ameliorate the development of T1D and preserve ß cell function. The preventive effect was associated with the inhibition of type 1 cytotoxic T (Tc1) cell function and rebalancing the Treg/Tc1 cell ratio in recipients. Furthermore, we showed that the underlying mechanisms were due to the TGF-ß-mediated combinatorial actions of mTOR and TCF1. In addition to the preventive role, the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic (NOD) mouse models were tested, which revealed improved ß cell function. Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.

Rapid and Reliable Detection of Nonsyndromic Hearing Loss Mutations by Multicolor Melting Curve Analysis.

Hearing loss is a common birth defect worldwide. The GJB2, SLC26A4, MT-RNR1 and MT-TS1 genes have been reported as major pathogenic genes in nonsyndromic hearing loss. Early genetic screening is recommended to minimize the incidence of hearing loss. We hereby described a multicolor melting curve analysis (MMCA)-based assay for simultaneous detection of 12 prevalent nonsyndromic hearing loss-related mutations. The three-reaction assay could process 30 samples within 2.5 h in a single run on a 96-well thermocycler. Allelic types of each mutation could be reproducibly obtained from 10 pg ~100 ng genomic DNA per reaction. For the mitochondrial mutations, 10% ~ 20% heteroplasmic mutations could be detected. A comparison study using 501 clinical samples showed that the MMCA assay had 100% concordance with both SNaPshot minisequencing and Sanger sequencing. We concluded that the MMCA assay is a rapid, convenient and cost-effective method for detecting the common mutations, and can be expectedly a reliable tool in preliminary screening of nonsyndromic hearing loss in the Chinese Han population.