Analysis of distribution and antibiotic resistance of Gram-positive bacteria isolated from a tertiary-care hospital in southern China: an 8-year retrospective study.

Objective: Due to the severe drug resistance situation of Gram-negative bacteria, especially Gram-negative enterobacter, relatively little attention has been paid to the changes in Gram-positive bacteria species and drug resistance. Therefore, this study analyzed the prevalence and drug resistance of Gram-positive bacteria in a general tertiary-care hospital from 2014 to 2021, in order to discover the changes in Gram-positive bacteria distribution and drug resistance that cannot be easily identified, inform clinicians in their respective regions when selecting antimicrobial agents, and to provide the basis for the diagnosis of Gram-positive bacterial infection, and for the comprehensive and multi-pronged prevention and control of drug-resistant bacteria. Methods: A retrospective study was conducted on Gram-positive bacteria isolated from patients presented to a general tertiary-care hospital from January 2014 to December 2021. A total of 15,217 Gram-positive strains were analyzed. Results: During the 8-year period, the total number and the species of Gram-positive bacteria isolated from clinic increased continuously. The seven most common species were Streptococcus pneumoniae (21.2%), Staphylococcus aureus (15.9%), Enterococcus faecium (20.6%), Enterococcus faecalis (14.0%), and Staphylococcus epidermidis (7.8%), Staphylococcus haemolyticus (4.8%), Streptococcus agalactiae (3.6%). The isolation rates of Staphylococcus aureus and Streptococcus agalactiae increased, and the isolation rate of Enterococcus faecium decreased. The resistance rates of Staphylococcus aureus to erythromycin, clindamycin, tetracycline, rifampicin and furantoin decreased obviously. The resistance rates of Streptococcus pneumoniae to cefepime (non-meningitis) and ceftriaxone (meningitis) decreased significantly. The resistance rates of Enterococcus faecium to penicillin, ampicillin, erythromycin, levofloxacin, ciprofloxacin and furantoin rose rapidly from 50.3, 47.6, 71.5, 44.9, 52.3, and 37.5% in 2014 to 93.1, 91.6, 84.9, 86.8, 86.8, and 60.0% in 2021, respectively. Conclusion: The total number and the species of Gram-positive bacteria isolated during the 8-year period increased continuously. Streptococcus pneumoniae and Staphylococcus aureus are the main causes of positive bacterial infections in this hospital. The resistance rates of Enterococcus faecium to a variety of commonly used antibiotics increased significantly. Therefore, it is very important to monitor the distribution of bacteria and their resistance to antibiotics to timely evaluate and identify changes in drug resistance that are not easily detected.

Nomogram for predicting coronary artery lesions in patients with Kawasaki disease.

BACKGROUND: Coronary artery lesions are the most important complications of Kawasaki disease. Approximately 25-30% of untreated patients develop coronary artery disease, which can lead to long-term cardiovascular sequelae. AIM: The aim of this study is to evaluate the risk factors for coronary artery lesions in Kawasaki disease and to construct a nomogram for predicting the likelihood of developing such lesions. METHODS: Data from 599 patients between January 2012 and June 2020 were reviewed retrospectively. Patients were randomly assigned to the training set (n = 450) and the validation set (n = 149). A comparison of clinical features and laboratory data was performed, followed by multivariate logistic regression analysis to identify independent risk factors and develop the nomogram. The predictive efficiency of the nomogram was evaluated using the calibration curve, area under the receiver operating characteristic curve (AUC), C-index, and decision curve analysis (DCA). RESULTS: Intravenous immunoglobulin (IVIG) resistance, delayed IVIG treatment, C-reactive protein, and neutrophil/lymphocyte ratio were identified as independent risk factors for the development of coronary artery lesions. The nomogram was constructed based on these four variables. The calibration curve of the nomogram showed a high degree of agreement between the predicted probability and the actual probability. The AUC of the nomogram in the training and validation set was 0.790 and 0.711, respectively. In addition, DCA revealed that the nomogram provided a significant net benefit, further supporting its clinical utility. CONCLUSIONS: The constructed nomogram demonstrates a strong and reliable performance in predicting coronary artery lesions, which enables clinicians to make timely and tailored clinical decisions.

An N6-methyladenosine regulation- and mRNAsi-related prognostic index reveals the distinct immune microenvironment and immunotherapy responses in lower-grade glioma.

BACKGROUND: N6-methyladenosine (m6A) modification is involved in tumorigenesis and progression as well as closely correlated with stem cell differentiation and pluripotency. Moreover, tumor progression includes the acquisition of stemness characteristics and accumulating loss of differentiation phenotype. Therefore, we integrated m6A modification and stemness indicator mRNAsi to classify patients and predict prognosis for LGG. METHODS: We performed consensus clustering, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator Cox regression analysis to identify an m6A regulation- and mRNAsi-related prognostic index (MRMRPI). Based on this prognostic index, we also explored the differences in immune microenvironments between high- and low-risk populations. Next, immunotherapy responses were also predicted. Moreover, single-cell RNA sequencing data was further used to verify the expression of these genes in MRMRPI. At last, the tumor-promoting and tumor-associated macrophage polarization roles of TIMP1 in LGG were validated by in vitro experiments. RESULTS: Ten genes (DGCR10, CYP2E1, CSMD3, HOXB3, CABP4, AVIL, PTCRA, TIMP1, CLEC18A, and SAMD9) were identified to construct the MRMRPI, which was able to successfully classify patients into high- and low-risk group. Significant differences in prognosis, immune microenvironment, and immunotherapy responses were found between distinct groups. A nomogram integrating the MRMRPI and other prognostic factors were also developed to accurately predict prognosis. Moreover, in vitro experiments illustrated that inhibition of TIMP1 could inhibit the proliferation, migration, and invasion of LGG cells and also inhibit the polarization of tumor-associated macrophages. CONCLUSION: These findings provide novel insights into understanding the interactions of m6A methylation regulation and tumor stemness on LGG development and contribute to guiding more precise immunotherapy strategies.

Clinical Diagnostic Value of Quantitative Hepatitis B Virus Core Antibody Test in Chronic Viral Hepatitis B.

The level of CHB virus (HBV) core antibody (HBcAb) is different in four stages of chronic HBV infection and may be used for differential diagnosis of the natural history of chronic HBV infection. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose different stages of chronic HBV infection. The quantitative detection of HBcAb, hepatitis B surface antigen (HBsAg), HBV DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count (PLT) were determined in the serum of 73 cases of low-replicative phase (LR), 46 cases of immune-tolerant phase (IT), 44 cases of immune clearance phase (IC), and 57 cases of HBeAg-negative hepatitis (ENH). Differentiating performance of these serum protein levels was analyzed by receiver operating characteristic (ROC) curve analysis. Our results showed that the levels of HBcAb, ALT, and AST levels were significantly higher in IC and ENH than those in LR and IT (both P ≤ 0.001). The levels of HBV DNA and HBsAg were higher in IC and IT than those in LR and ENH (both P ≤ 0.001). Logistic regression models showed that HBcAb, HBsAg, HBV DNA, ALT, and AST were the independent variables, respectively, and when combined, they provided high diagnostic accuracy for the staging of CHB. To sum up, HBcAb quantification is a new index, which can reflect whether the liver is in the immune activation state of HBV infection, and is related to the inflammatory state of the host liver. The combined detection of HBcAb quantification and other indicators has showed promising efficiency for staging of IC and ENH and can assist the diagnosis and treatment of CHB.

In vitro investigation of protective mechanisms of triptolide against coronary heart disease by regulating miR-24-3p-BCL2L11 axis and PPARs-PGC1α pathway.

Coronary heart disease (CHD) is a fatal disease associated with coronary atherosclerosis. Although triptolide (TTL) has been reported to protect against CHD, the mechanism has not yet been determined. This study intended to explore its molecular regulation mechanism in CHD. It is shown in this study that TTL contributed to the proliferation and migration of in vitro cell models of CHD (endothelial cells) and the inhibition of apoptosis, and had an improvement effect on apoptosis factors and endoplasmic reticulum stress (ERS). From its mechanisms, TTL evidently downregulates miR-24-3p which is elevated in CHD, and evidently upregulates BCL2-like 11 (BCL2L11) which is suppressed in CHD, as well as affects the activation of peroxisome proliferator-activated receptors (PPARs)-Peroxisome proliferator activated receptor-γ co-activator-1α (PGC-1α) pathway of nuclear receptor transcription factors. In addition, miR-24-3p-BCL2L11-PPARs-PGC1α axis regulates protective effects of TTL against CHD.

Ultrasensitive mushroom-like electrochemical immunosensor for probing the activity of histone acetyltransferase.

A novel mushroom-like electrochemical immunoassay for the ultrasensitive detection of histone acetyltransferase activity (HAT p300) has been established on account of the new composite graphene oxide (GO) nanolayer. The immunoassay involves immobilization of substrate peptide onto Au electrode, acetylation in lysine of substrate peptide, and the interaction between acetyl group of lysine and acetyl-antibody (AbAc) of the GO nanolayer. The GO nanolayer comprises large amounts of methylene blue molecules (MB), giving rise to large signal amplification. Only in the presence of HAT p300, an obvious electrochemical signal appears and the peak linear current is proportion to the HAT p300 concentrations ranging from 0.01 to 150 nM with a detection limit of 0.0036 nM. The great enhancement on sensitivity of the proposed mushroom-like immunosensor derives from both the constructed Faraday cage and the extended outer Helmholtz plane (OHP). Further, the immunosensor with excellent sensitivity and selectivity can be applied for the HAT p300 activity detection in Hela cell lysates, serum and urine, hinting an improved and splendid analytical performance. Briefly, this stable, simple and ultrasensitive electrochemical immunoassay has considerable promise for further applications in the HATs-interrelated epigenetic studies and drug development.

The association between CD69 and EGR1 levels, and CHD patients without reflow after PCI.

Association between CD69 and EGR1 levels and coronary heart disease (CHD) patients without reflow after percutaneous coronary intervention (PCI) was investigated. Data of 156 patients undergoing PCI from September 2014 to December 2016 in People's Hospital of Hunan Province were analyzed, and they were divided into 72 cases in reflow group (group A) and 84 cases in no-reflow group (group B) according to the patient's postoperative blood flow. Another 70 volunteers undergoing normal physical examination in the same period were selected as control group (group C). The venous blood was extracted from patients before operation, at 5 min, 2 h and 6 months after operation, the serum CD69 and EGR1 levels were detected with flow cytometry and RT-qPCR methods, and association between CD69 and EGR1 levels and postoperative blood flow recovery was analyzed. CD69 expression before and 2 h after operation in group A was significant (P<0.05), and a difference in patients at 6 months after operation between group A, B and group C (P<0.05). The CD69 expression in group A was significantly lower than that in group B (P<0.05), but in group B was significantly higher than that in group C (P<0.05). The EGR1 expression in group A was significantly higher than that in group B (P<0.05), but in group B was significantly lower than that in group C (P<0.05). Multivariate logistic regression analysis revealed that CD69 (OR=6.424, P=0.025) and EGR1 (OR=3.684, P=0.013) were independent risk factors for patients without reflow after undergoing PCI. After undergoing PCI in CHD patients, if there was an increase in CD69 level and a significant decrease in EGR1 level in the early postoperative period, the patient may be suspected of having no-reflow and checked in time to improve the patient's therapeutic effect.

Value analysis of CD69 combined with EGR1 in the diagnosis of coronary heart disease.

Expression and clinical significance of CD69 and early growth response (EGR1) in plasma of patients with coronary heart disease (CHD) were investigated. A total of 194 patients with CHD and 130 healthy subjects, respectively, were selected as CHD and control group, clinical data were collected and coronary angiography was performed. RT-qPCR was used to detect the expression of EGR1. Flow cytometry was used to detect the expression level of CD69 and the receiver operating characteristic curve was used to analyze the values of relative expression of CD69 and EGR1. The relative expression of CD69 in plasma of patients with CHD was higher than that in control group, while the relative expression of EGR1 was lower than that in control group. The relative expression of EGR1 in plasma of patients with CHD was negatively correlated with lipoprotein a [Lp(a)] and high sensitive C-reactive protein (hs-CRP) (r=-0.394 and -0.524, P<0.05), and the relative expression of CD69 in peripheral blood was positively correlated with [Lp(a)] and hs-CRP (r=0.352 and 0.402, P<0.05). The area under curve (AUC) of the relative expression of CD69 in peripheral blood of patients with CHD in evaluating the course of the disease of patients was 0.889 (95% CI: 0.822-0.958). The AUC of the relative expression of EGR1 in plasma in evaluating the course of the disease of patients was 0.933 (95% CI: 0.867-0.978). By the combined detection of CD69 and EGR1, it was found that the AUC was 0.954 (95% CI: 0.887-0.982). The expression level of EGR1 in plasma of patients with CHD decreased, while the expression level of CD69 increased, and both of them were related to the severity of the disease of patients, which could be used as an indicator to evaluate the progression of the patients' conditions.

[Predictive value of immature granulocytes for persistent systemic inflammatory response syndrome in patients with acute pancreatitis: analysis of 1 973 cases].

OBJECTIVE: To analyze the clinical value of immature granulocytes in peripheral blood for prediction of persistent systemic inflammatory response syndrome (SIRS) in patients with acute pancreatitis (AP). METHODS: 1 973 patients with AP in Hunan People's Hospital from 2012 to 2017 were retrospectively enrolled and divided by SIRS duration into the persistent SIRS group, temporary SIRS group and non-SIRS group. The independent risk factor for persistent SIRS in AP patients was evaluated by Logistic regression analysis, and predictive value of immature granulocytes for persistent SIRS in AP patients was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: These 1 973 AP patients (1 165 males, 59.0%) with an average age of 49 (40, 60) years old, including 288 persistent SIRS, 189 temporary SIRS and 1 496 non-SIRS cases. There was no significant difference in gender, age and etiology among three groups. Compared with non-SIRS group, more severe symptoms were observed in the temporary and persistent SIRS groups. Moreover, The acute physiology and chronic health evaluation II (APACHE II), CT severity index (CTSI), multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS) incidence, mortality and C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT) and immature granulocytes in persistent SIRS group were further higher than those in the temporary SIRS group [APACHE II: 9 (6, 12) vs. 5 (3, 7), CTSI: 6 (4, 6) vs. 4 (3, 6), MOF incidence: 92.0% vs. 32.8%, ARDS incidence: 39.9% vs. 10.1%, morbidity: 11.1% vs. 4.2%, CRP (mg/L): 25.00 (0.80, 212.25) vs. 0.80 (0.80, 123.50), WBC (×109/L): 15.17±6.78 vs. 14.84±5.86, PCT (g/L): 0.23 (0.10, 1.76) vs. 0.10 (0.10, 0.31), immature granulocytes: 1.95 (0.90, 4.95) % vs. 0.80 (0.40, 2.10) %, all P < 0.05]. Logistic regression analysis showed that besides pancreatic necrosis, WBC and CRP, immature granulocyte was an independent risk factor for persistent SIRS associated with AP [odds ratio (OR) = 1.844, 95% confidence interval (95%CI) = 1.372-2.220]. ROC curve showed that immature granulocytes had better predictive value for persistent SIRS, the area under the curve (AUC) was 0.806, which was significantly higher than the APACHE II (AUC = 0.783), CTSI (AUC = 0.752), PCT (AUC = 0.676), CRP (AUC = 0.677), WBC (AUC = 0.644). The cut-off value of immature granulocyte was 0.65%, the sensitivity was 84.0%, the specificity was 66.3%, the positive predictive value was 62.4%, and the negative predictive value was 76.3%. CONCLUSIONS: Immature granulocyte in peripheral blood is a potential indicator for persistent SIRS in AP patients.