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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Tan, Ouyang, Ma, Peng, Shi and Xie.)