Infective Endocarditis Due to High-Level Gentamicin-Resistant Enterococcus faecalis Complicated Multisystemic Complications in an Elderly Patient.

The escalating incidence of infective endocarditis (IE) caused by aminoglycoside-resistant Enterococcus is a growing concern for clinicians. This issue is particularly pronounced in elderly patients, who face an elevated risk of renal damage during antibiotic treatment, thereby limiting available pharmacological options. Furthermore, elderly patients often present with multiple comorbidities, leading to heightened mortality rates. In this article, we present a case involving an elderly male patient who sought medical attention on two separate occasions due to inflammation of the lower extremities and lumbosacral pain. Subsequent diagnosis revealed infective endocarditis (IE) caused by high-level gentamicin-resistant Enterococcus faecalis through blood culture and echocardiography. The patient also experienced peripheral and cerebral arterial embolism, secondary spine infection, and subsequent heart failure, highlighting the severity of the clinical situation. Following an initial 10-day course of vancomycin and ceftriaxone therapy, the patient developed renal impairment, necessitating a switch to bactericidal therapy with ampicillin in combination with ceftriaxone. Additionally, aortic valve replacement was performed during this period. Ultimately, the patient achieved clinical remission. This case underscores the critical importance of prompt and accurate diagnosis, appropriate antibiotic selection, and timely surgical intervention in enhancing the prognosis of elderly patients with IE.

Effects of first-line nucleot(s)ide analogues on lipid profiles in patients with chronic hepatitis B: a network meta-analysis.

INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.

LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is known to progress due to the impact of long non-coding RNAs (lncRNAs), which have been linked to autophagy, pyroptosis, and fibrosis in NASH cells. However, the exact mechanisms underpinning these processes remain unclear. This study focuses on the role of lncRNA MIR22HG (MIR22HG) in NASH. METHODS: The expression of differentially expressed lncRNA was analyzed by RNA sequencing. Mouse models of NASH induced by MCD and HFD were validated. The expression of MIR22HG in HFD and MCD mouse liver tissue samples, FFA cells constructed with HepG2 and Huh7, and human liver tissue samples were detected by QRT-PCR. In addition, We used RNA immunoprecipitation, luciferase reporting, miRNA transfection, plasmid construction, immunofluorescence, Western blot, qRT-PCR, ELISA, and hybridization techniques to elucidate the relationship between MIR22HG, microRNA-9-3p (miR-9-3p), and IGF1. In addition, the mechanism of MIR22HG and PTEN/AKT was explored by Western blot analysis. RESULTS: RNA-seq found that 3751 mRNAs and 23 lncRNAs were differentially expressed, which constituted a lncRNA-miRNA-mRNA regulatory network. Studies demonstrated the downregulation of MIR22HG in HFD and MCD mouse liver tissue samples (p = 1.00E-04 and p = 4.6E-03). Our results showed that overexpression of MIR22HG promoted autophagy and inhibited pyroptosis and fibrosis through the miR-9-3p/IGF1 pathway, thus slowing the occurrence and development of NASH. Further, we observed a low expression of MIR22HG and IGF1, but a high expression of miR-9-3p in NASH patients, a finding in alignment with our in vivo and in vitro results. CONCLUSION: Using MIR22HG as a biomarker and therapeutic target for NASH patients, we found that it plays a pivotal role in detecting autophagy, pyroptosis, and fibrosis through the ceRNA pathway.

Probable targets and mechanism of ginsenoside Rg1 for non-alcoholic fatty liver disease: a study integrating network pharmacology, molecular docking, and molecular dynamics simulation.

Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.

Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior.

Thorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. In this study, we generated conditional knockout mice (cKO) with Thorase deletion in Purkinje cells. Thorase cKO mice exhibited cerebellar degenerative diseases-like behavior and significant impairment in motor coordination. Thorase deletion resulted in more Purkinje neuron apoptosis, leading to Purkinje cell loss in the cerebellum of Thorase cKO mice. We also found enhanced expression of the inflammatory protein ASC, IL-1ß, IL-6 and TNF-α in the Thorase cKO cerebellum, which contributed to the pathogenesis of cerebellar degenerative disease. Our findings provide a better understanding of the role of Thorase in the cerebellum, which is a theoretical basis for Thorase as a therapeutic drug target for neurodegenerative diseases.

Epidemiology and prediction model of patients with carcinosarcoma in the United States.

Background: Carcinosarcoma is a rare biphasic tumor composed of both carcinoma and sarcoma elements, which occurs at various sites. Most studies are case reports or small population-based studies for a single disease site, so comprehensive evaluations of epidemiology and prognostic factors for carcinosarcoma are needed. Methods: Surveillance, Epidemiology, and End Results (SEER)-8 (1975-2019) provided data for the epidemiological analysis. SEER-17 (2000-2019) provided data on the primary tumor sites, initial treatment, construction, and validation of the nomogram. Results: The age-adjusted incidence per 100,000 persons of carcinosarcoma increased significantly from 0.46 to 0.91 [1975-2019; average annual percent change (AAPC): 1.3%, P = 0.006], with localized stage increasing from 0.14 to 0.26 [2005-2015; annual percent change (APC): 4.2%]. The 20-year limited-duration prevalence per 100,000 increased from 0.47 to 3.36 (1999-2018). The mortality per 100,000 increased significantly from 0.16 to 0.51 (1975-2019; AAPC: 1.9%, P < 0.001). The 5-year relative survival was 32.8%. The greatest number of carcinosarcomas were from the uterus (68.7%), ovary (17.8%), lung and bronchus (2.3%). The main treatment is comprehensive treatment based on surgery; however, surgery alone is preferred in older patients. In multivariate analysis (N = 11,424), age, sex, race, year of diagnosis, disease stage, tumor site, and treatment were associated with survival. A nomogram was established to predict 1-, 3-, and 5-year survival, and the C-indexes were 0.732 and 0.748 for the training and testing sets, respectively. The receiver operating characteristic curve demonstrated that the nomogram provided a comprehensive and accurate prediction [1-year area under the curve (AUC): 0.782 vs. 0.796; 3-year AUC: 0.771 vs. 0.798; 5-year AUC: 0.777 vs. 0.810]. Conclusions: In this study, the incidence, prevalence, and mortality of carcinosarcoma have increased over the past decades. There was a rapid rise in the incidence of localized stage in recent years, which reflected improved early detection. The prognosis of carcinosarcoma remains poor, signifying the urgency of exploring targeted cancer control treatments. Explicating distribution and gender disparities of carcinosarcoma may facilitate disease screening and medical surveillance. The nomogram demonstrated good predictive capacity and facilitated clinical decision-making.

TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis.

Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aß1-40 and Aß1-42 peptides and more Aß plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aß peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1ß) in response to Aß peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aß pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.