Incidence of low-level viremia and its impact on virologic failure among people living with HIV who started an integrase strand transfer inhibitors: a longitudinal cohort study.

BACKGROUND: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. METHODS: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50-999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. RESULTS: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137-0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. CONCLUSION: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies.

Association of ACP5 with the tumor immune microenvironment and its role in cell proliferation and metastasis in pancreatic cancer.

BACKGROUND: Tartrate-resistant acid phosphatase (ACP5) has been implicated in the progression of most malignant tumors, but its role in pancreatic cancer (PC) remained unclear. Thus, this study aimed to elucidate the role and function of ACP5 in PC progression. METHODS: The expression of ACP5 in PC samples was assessed via R programming, TNM plot, and Gene Expression Profiling Interactive Analysis (GEPIA). Western blotting and immunohistochemistry (IHC) were performed to detect ACP5 expression in cells and tissues. The correlation between ACP5 and methylation was analyzed using the University of ALabama at Birmingham Cancer data analysis Portal (UALCAN) and cBio Cancer Genomics Portal (cBioPortal). The Database for Annotation, Visualization and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were used for the enrichment of ACP5 in PC. Subsequently, Cell Counting Kit-8 (CCK8), clonogenic, and wound healing assays were used to investigate the role of ACP5 in PC. Finally, Tumor Immune Estimation Resource (TIMER) and R programming was utilized in evaluating the association between ACP5 and immune cell infiltration in PC. RESULTS: The analyses confirmed that ACP5 was highly expressed in PC samples. According to UALCAN and cBioPortal analysis, ACP5 expression, and methylation levels were negatively correlated in PC. The enrichment analysis also revealed that ACP5 was enriched in the proliferation and migration pathways. Meanwhile, ACP5 knockout reduced PC cell proliferation and migration and impaired the cells' independent viability. This gene also positively correlated with immune cell infiltration in PC, particularly regulatory T cells (Tregs). CONCLUSION: ACP5 is crucial for proliferation, migration, and immune cell infiltration in PC. Therefore, ACP5 may be a valuable target for future PC treatment.

GLUT5: structure, functions, diseases and potential applications.

Glucose transporter 5 (GLUT5) is a membrane transporter that specifically transports fructose and plays a key role in dietary fructose uptake and metabolism. In recent years, a high fructose diet has occupied an important position in the daily intake of human beings, resulting in a significant increase in the incidence of obesity and metabolic diseases worldwide. Over the past few decades, GLUT5 has been well understood to play a significant role in the pathogenesis of human digestive diseases. Recently, the role of GLUT5 in human cancer has received widespread attention, and a large number of studies have focused on exploring the effects of changes in GLUT5 expression levels on cancer cell survival, metabolism and metastasis. However, due to various difficulties and shortcomings, the molecular structure and mechanism of GLUT5 have not been fully elucidated, which to some extent prevents us from revealing the relationship between GLUT5 expression and cell carcinogenesis at the protein molecular level. In this review, we summarize the current understanding of the structure and function of mammalian GLUT5 and its relationship to intestinal diseases and cancer and suggest that GLUT5 may be an important target for cancer therapy.

Development of a prognostic signature based on anoikis-related genes in hepatocellular carcinoma with the utilization of LASSO-cox method.

To develop a signature based on anoikis-related genes (ARGs) for predicting the prognosis of patients with hepatocellular carcinoma (HCC), and to elucidate the molecular mechanisms involved. In this study, bioinformatic algorithms were applied to integrate and analyze 777 HCC RNA-seq samples from the cancer genome atlas and international cancer genome consortium repositories. A prognostic signature was developed via the least absolute shrinkage and selection operator-cox regression method. To evaluate the accuracy of the signature in predicting events, multi-type technical means, such as Kaplan-Meier plots, receiver operating characteristic curve analysis, nomogram construction, and univariate and multivariate Cox regression studies were performed. We investigated the underlying molecular biological mechanisms and immune mechanisms of the signature using gene set enrichment analysis and the CIBERSORT R package, respectively. Meanwhile, immunohistochemical staining acquired from the human protein atlas was used to confirm the differential expression levels of hub genes involved in the prognostic signature. We developed an HCC prognostic signature with a collection of 5 ARGs, and the prognostic value was successfully assessed and verified in both the test and validation cohorts. The risk scores calculated by the prognostic signature were proved to be an independent negative prognostic factor for overall survival. A set of nomograms based on risk scores was established and found to be effective in predicting OS. Further investigation of the underlying molecular biological mechanisms and immune mechanisms indicated that the signature may be relevant to metabolic dysregulation and infiltration of gamma delta T cells in the tumor. The survival prognosis of HCC patients can be predicted by the anoikis-related prognostic signature, and it serves as a valuable reference for individualized HCC therapy.