Analysis of ART effects and drug resistance in adult HIV/AIDS patients in Meigu County, Liangshan Prefecture, China.

BACKGROUND OBJECTIVE: This study aimed to understand the basic situation of adults with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) in Meigu County, Liangshan Yi Autonomous Prefecture. The information of patients who had been on ART for more than 6 months, the effect of ART, the possible reasons for ART failure, knowledge of drug resistance among patients with ART failure and the possible reasons for the emergence of drug resistance were analyzed. METHODS: A total of 2753 people living with HIV (PLWH) were collected for HIV-1 RNA virus nucleic acid testing. Plasma specimens with HIV-1 RNA ≥ 1000 copies/mL were sent to the laboratory for nucleic acid extraction, PCR, electrophoresis and sequencing, and the sequencing results were submitted to the HIV drug resistance database of Stanford University for subtyping to determine the drug resistance mutation sites and drug sensitivity levels. RESULTS: A total of 2753 patients were enrolled in this study. Antiviral therapy failed in 288 patients and was successfully amplified in 245, of which 111 had resistance genes. The resistance rate to failure of viral suppression was 45.3% (111/245). The highest rates of resistance to NNRTIs were found for efavirenz (EFV) and nevirapine (NVP) (42.9%), and the highest rates of resistance to NRTIs were found for 3TC and emtricitabine (FTC) (15.9%). The most common NNRTI resistance mutation site was K103N (20.8%), followed by V179D (9.4%) and V106M (7.8%); the most common NRTI resistance mutation site was M184V/I/MV (14.3%), followed by K65R (6.9%); three PI-associated resistance mutation sites were identified. The subtype of the resistant strain was CRF07-BC in almost all patients (98.9%). CONCLUSIONS: Compared with the previous low ART efficacy in the county, this study showed that the overall virological failure (VF) resistance rate in the county is still low, dominated by resistance to EFV, NVP, 3TC, FTC, and didanosine (DDI). Due to economic constraints, the core regimen is still 3TC + TDF, but before initiating ART, testing for HIV-1 subtypes and resistance should be conducted to avoid resistance that can lead to VF, especially for patients with high risk factors for resistance as shown by epidemiologic investigations.

Expression Profile of Pyroptosis-Related Genes and the Associated Regulatory Axis in Primary Gout Patients.

Purpose: Analyzed the expression characteristics of pyroptosis-related genes (PRGs) in peripheral blood mononuclear cells (PBMCs) of gout patients by microarray, and constructed ceRNA network to explore the molecular mechanism of RNA-mediated pyroptosis regulation. Patients and Methods: Human mRNA, lncRNA, circRNA microarray data were used to identify differentially expressed in PBMCs from patients with primary gout and healthy controls. Differential PRGs in PBMCs of gout patients identified by Genecard database and mRNA microarray data. GO and KEGG enrichment analyses of these genes were then conducted. Protein-protein interaction networks and cytoHubba were used to identify hub genes. Combining the lncRNA and circRNA microarray data, a ceRNA network was constructed by Cytoscape to screen out key non-coding RNA molecules that can regulate target PRGs. Finally, the relative expression levels of target miRNA and circRNA in 60 gout patients and 40 healthy subjects were detected by qRT-PCR. Results: The results revealed 30 differentially expressed PRGs. GO and KEGG analysis of these genes were mainly concentrated in the production and regulation of cytokines, NOD-like receptor signaling pathway and so on. Nine hub genes were screened by PPI network, including IL1B, DDX3X, NLRP3, NLRP9, AIM2, CASP8, P2XR7, CARD8 and IFI16. The has_circRNA_102906\hsa_circRNA_102910\hsa_circRNA_102911-hsa-miR-129-5p-DDX3X\NLRP3\NLRP9 regulatory network was constructed. The expression of has_circRNA_102906, hsa_circRNA_102910, hsa_circRNA_102911 were up-regulated and hsa-miR-129-5p down-regulated in PBMCs of gout patients. The relative expression of hsa_circRNA_102911 was positively correlated with clinical inflammatory indicators associated with gout, and the area under the curve of hsa_circRNA_102911 for gout diagnosis was 0.85 (95% CI: 0.775-0.925; p < 0.001). Conclusion: There are several differentially expressed PRGs in PBMCs of gout patients, which are involved in the regulation of gout inflammation through multiple pathways. hsa_circRNA_102911-hsa-miR-129-5p-DDX3X\NLRP3\NLRP9 may be the key regulatory pathway for pyroptosis to regulate gout inflammation, and hsa_circRNA_102911 may be a potential biomarker for the diagnosis of primary gout.

Establishment and Validation of Predictive Model of Tophus in Gout Patients.

(1) Background: A tophus is a clinical manifestation of advanced gout, and in some patients could lead to joint deformities, fractures, and even serious complications in unusual sites. Therefore, to explore the factors related to the occurrence of tophi and establish a prediction model is clinically significant. (2) Objective: to study the occurrence of tophi in patients with gout and to construct a predictive model to evaluate its predictive efficacy. (3) Methods: The clinical data of 702 gout patients were analyzed by using cross-sectional data of North Sichuan Medical College. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze predictors. Multiple machine learning (ML) classification models are integrated to analyze and identify the optimal model, and Shapley Additive exPlanations (SHAP) interpretation was developed for personalized risk assessment. (4) Results: Compliance of urate-lowering therapy (ULT), Body Mass Index (BMI), course of disease, annual attack frequency, polyjoint involvement, history of drinking, family history of gout, estimated glomerular filtration rate (eGFR), and erythrocyte sedimentation rate (ESR) were the predictors of the occurrence of tophi. Logistic classification model was the optimal model, test set area under curve (AUC) (95% confidence interval, CI): 0.888 (0.839-0.937), accuracy: 0.763, sensitivity: 0.852, and specificity: 0.803. (5) Conclusions: We constructed a logistic regression model and explained it with the SHAP method, providing evidence for preventing tophus and guidance for individual treatment of different patients.

Altered Cerebral Blood Flow is Linked to Disease Duration in Patients with Generalized tonic‒clonic Seizures.

Purpose: To investigate cerebral blood flow (CBF) characteristics in individuals with generalized tonic‒clonic seizures (GTCS) during the interictal phase using voxel-based analysis of 3D pseudocontinuous arterial spin labeling (PCASL). Patients and Methods: Patients with GTCS (GTCS group) (during the interictal period) and healthy volunteers (control group) underwent head MR imaging with a 3.0T MR scanner with a 3D PCASL sequence. CBF was compared between the two groups. Spearman correlations of CBF in regions of interest (ROIs) in GTCS patients with the duration of disease and age of onset were analyzed and corrected using the false discovery rate (FDR). Results: Twenty patients with GTCS (GTCS group) and twenty healthy volunteers (control group) were recruited for this study. On 3D PCASL, (1) GTCS patients had lower CBF in the brainstem, right cerebellum, right inferior temporal gyrus, parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, triangular part of inferior frontal gyrus, left temporal pole of superior temporal gyrus and thalamus and had higher CBF in the bilateral superior parietal gyri, precuneus, precentral gyri, postcentral gyri, and left dorsolateral superior frontal gyrus than controls. (2) The CBF of the right temporal pole of the middle temporal gyrus was negatively correlated with the duration of disease (PFDRcorrected<0.05), with a correlation coefficient r of -0.7333 and a PFDRcorrected value of 0.04. Conclusion: Voxel-based analysis of 3D PCASL imaging can be used to sensitively detect brain perfusion differences in GTCS patients. The decrease in CBF in the right temporal pole of the middle temporal gyrus may be associated with disease onset. These findings may offer new perspectives on the pathogenesis of GTCS and the underlying pathophysiological changes associated with perfusion.

The whole genome analysis for the first human infection with H10N3 influenza virus in China.

A strain of H10N3 influenza virus, A/Jiangsu/428/2021/H10N3, was isolated from patient in Jiangsu province, eastern China. Phylogenetic analysis illustrated this human H10N3 virus was a low pathogenic avian-origin recombinant virus with HA and NA genes from H10N3 viruses and the other six internal genes from H9N2 viruses. To date, this is the first report of interspecies transmission of an avian H10N3 influenza virus to human.