Prevalence and risk factors of carbapenem-resistant Enterobacterales positivity by active screening in intensive care units in the Henan Province of China: A multi-center cross-sectional study.

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.

Long-term results of surgical treatment of aortic and mitral regurgitation with enlarged left ventricle.

Mitral valve and aortic valve regurgitation associated with enlarged left ventricle remains difficult to manage and the long-term results following surgical treatment is uncertain. Between April 1988 and September 2000, 82 patients with aortic and mitral regurgitation associated with enlarged left ventricle underwent valve replacement at Anzhen Hospital. The valve disease was rheumatic in origin in 75 patients (91.5%) and congenital in 7 (8.5%). Twenty-eight patients were in New York heart Association Functional (NYHA) class II and 39 in class III and 15 in class IV. Echocardiogram showed severe aortic insufficiency associated with mild to moderate mitral regurgitation in 66 patients and severe mitral regurgitation associated with mild to moderate AI in 16 patients. The mean left ventricular diastole diameter (LVDD) was 77.8 ± 5.2 mm. Valve replacement was performed under hypothermic cardiopulmonary bypass (CPB). Early hospital mortality was 7.3%. Two weeks after surgery the echocardiogram showed a reduction of LVDD. Follow up was completed in 69 patients with mean of 13.5 years. 20 patients were in NYHA class I; 26 in Class II and 3 in Class III and 2 in class IV. The follow-up survival rate was 73.9%, and follow-up mortality was 26.1%. LVDD reduced from 77.8 ± 5.2 mm to 58.3 ± 4.5 mm (P < 0.001). In 24 patients, the LVDD was less than 50 mm. Double valve replacement and/or repair carried out an acceptable early and Long-term clinical outcomes in patients with MR and AI with associated LV great enlargement. Both LVDD and NYHA improved following surgical treatment in survival patients.

Radioprotective effect on HepG2 cells of low concentrations of cobalt chloride: induction of hypoxia-inducible factor-1 alpha and clearance of reactive oxygen species.

It has been found that low doses of certain toxicants might generate a protective response to cellular damage. Previous data have shown that elevated doses of cobalt (Co) induce injury to cells and organisms or result in radiological combined toxicity. Whether low doses of Co generate a protective effect or not, however, remains controversial. In this study, we investigated the effect and mechanism of action of low dose cobalt chloride (CoCl2, 100 µM) on the viability of irradiated cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay was used to observe the radio-sensitivity of HepG2 cells under different pretreatments. The alteration of intracellular DNA damage was further measured using micronucleus (MN) assay. Levels of hypoxia inducible factor-1α (HIF-1α) expression and its target gene, EPO, were monitored by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively, and intracellular reactive oxygen species (ROS) content was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe staining. Our results show that low dose CoCl2does not influence HepG2 cell viability, but induces the expression of HIF-1α, followed by increased radio-resistance. Additionally, cells treated with HIF-1α siRNA retained a partial refractory response to irradiation concomitant with a marked reduction in intracellular ROS. The change of MN further indicated that the reduction of DNA damage was confirmed with the alteration of ROS. Our results demonstrate that low dose CoCl2may protect cells against irradiative harm by two mechanisms, namely HIF-1α expression and ROS clearance.

Regulation of hypoxia inducible factor-1α expression by the alteration of redox status in HepG2 cells.

Hypoxia inducible factor-1 (HIF-1) has been considered as a critical transcriptional factor in response to hypoxia. It can increase P-glycoprotein (P-Gp) thus generating the resistant effect to chemotherapy. At present, the mechanism regulating HIF-1α is still not fully clear in hypoxic tumor cells. Intracellular redox status is closely correlated with hypoxic micro-environment, so we investigate whether alterations in the cellular redox status lead to the changes of HIF-1α expression. HepG2 cells were exposed to Buthionine sulphoximine (BSO) for 12 h prior to hypoxia treatment. The level of HIF-1α expression was measured by Western blot and immunocytochemistry assays. Reduce glutathione (GSH) concentrations in hypoxic cells were determined using glutathione reductase/5,5'-dithiobis-(2-nitrob-enzoic acid) (DTNB) recycling assay. To further confirm the effect of intracellular redox status on HIF-1α expression, N-acetylcysteine (NAC) was added to culture cells for 8 h before the hypoxia treatment. The levels of multidrug resistance gene-1 (MDR-1) and erythropoietin (EPO) mRNA targeted by HIF-1α in hypoxic cells were further determined with RT-PCR, and then the expression of P-Gp protein was observed by Western blotting. The results showed that BSO pretreatment down-regulated HIF-1α and the effect was concentration-dependent, on the other hand, the increases of intracellular GSH contents by NAC could partly elevate the levels of HIF-1α expression. The levels of P-Gp (MDR-1) and EPO were concomitant with the trend of HIF-1α expression. Therefore, our data indicate that the changes of redox status in hypoxic cells may regulate HIF-1α expression and provide valuable information on tumor chemotherapy.