BackgroundThe aim of this study was to identify independent risk factors for the time to hyperuricemia (HUA) in PLWH and develop an HUA risk model based on a retrospective study in Hangzhou, China.MethodsPLWH treated at Hangzhou Xixi Hospital between July 2016 and December 2024 were randomly assigned to training and validation cohorts in a 7:3 ratio. Independent risk factors associated with the occurrence of HUA were identified using multivariable Cox regression analysis. Characteristic variables for constructing the HUA risk prediction model were selected through the least absolute shrinkage and selection operator (LASSO) method, and the model was visualized using a nomogram. The model’s performance was assessed through time-independent receiver operating characteristic (ROC) curve, calibration curve, concordance index (C-index), and decision curve analysis (DCA) to evaluate its discriminatory ability, calibration, and clinical applicability. A generalized linear mixed model (GLMM) was used to investigate the effects of different ART regimens on the SUA levels over time among PLWH.ResultsA total of 631 participants were included in this study, with 439 assigned to the training set and 192 to the validation set. The final model for predicting HUA risk in PLWH incorporated two factors: baseline serum uric acid (SUA) levels and baseline CD4+ T-cell count. The area under the ROC curve (AUC) values for 1-, 3-, and 5-year HUA risks were 0.72, 0.74, and 0.75 in the training set, and 0.66, 0.67, and 0.70 in the internal validation sample, respectively. The calibration curve demonstrated strong agreement between predicted and observed outcomes. Both the C-index and DCA confirmed the nomogram’s superior predictive performance. Furthermore, the prevalence of hypercholesterolemia and abnormal eGFR differed significantly between the defined high- and low-risk groups. Comparing with PLWH receiving the B/F/TAF regimens, there was a significant decrease in SUA values over time in PLWH receiving EFV-containing ART regimens.ConclusionsWe established and validated a HUA-specific nomogram for predicting the risk of HUA in PLWH. This model provides clinicians with a practical tool for the early-stage identification of PLWH at high risk of HUA, a capability that is highly significant for guiding clinical treatment.

Abstract Immune non-responders (INRs), a subset of people living with HIV (PLWH), fail to achieve full immune reconstitution and remain at increased risk of morbidity, mortality, and non-AIDS-related illnesses. As the mechanisms underlying this impaired immune recovery remain poorly understood, we performed single-cell multi-omics profiling on peripheral blood mononuclear cells from 43 INRs, 47 immune responders and 53 healthy donors. Our dataset comprises 2,744,009 transcriptomes and 1,226,658 chromatin-accessibility profiles across 58 identified immune cell types. INRs exhibited markedly elevated inflammatory signaling, increased apoptotic activity, and dysregulation of immune-activating ligand-receptor interactions. Additionally, we identified 2,996 interaction cis -eGenes and 5,938 cis -caPeaks, and validated key cell type-specific cis -xQTL effects associated with immune reconstitution failure. Furthermore, we identified 3,551 sc-eQTLs and 872 cell-state interaction eQTLs (ieQTLs) in CD4 + T cells. A genotype-specific upregulation of OAS3 in INRs, likely regulated by STAT1, was identified based on these results. We developed scPRISM (single cell Predictive Reconstitution Immune Status Model), a multi-modal framework that integrates scRNA-seq and scATAC-seq data to perform the dual tasks of differentiating disease states and predicting gene expression from chromatin accessibility, thereby deciphering the cell type-specific cis -regulatory basis of the disease. Our study delineates the transcriptional and epigenomic landscape of immune dysregulation in INRs and provides new genetic insights into HIV-associated immune reconstitution failure. These findings offer a foundation for developing biomarkers and precision therapies to restore immune function in PLWH.

To achieve covalent CDK7 inhibitors with superior antiproliferative activity and enhanced selectivity, we designed and synthesized a series of covalent CDK7 inhibitors bearing diverse warheads based on the THZ1 scaffold. Experimental validation confirmed that 2-chloroacrylamide-based covalent inhibitors possess potent CDK7 kinase inhibitory activity. HRMS results revealed that the interaction between these compounds and the cysteine residue of CDK7 extends beyond a simple Michael addition, potentially involving nucleophilic substitution at the covalent warhead. Among them, compound B19 exhibited potent CDK7 kinase inhibition with an IC50 value of 0.370 ± 0.0200 nM, as well as strong anti-proliferative activity against MV-4-11 (IC50 = 0.820 ± 0.0500 nM), Molm-13 (IC50 = 1.14 ± 0.0900 nM) and MDA-MB-231 (IC50 = 20.2 ± 1.34 nM) cells. Furthermore, B19 strongly suppressed CDK7-mediated downstream signaling and induced apoptosis and G0/G1 phase arrest in MV-4-11 cells, supporting its potent antitumor effects. Wash-out assays indicated that compound B19 possesses a prolonged activity profile compared with THZ1. Additionally, B19 displayed favorable selectivity across a panel of other kinases. Collectively, these results identify B19 as a promising lead compound for targeting CDK7.

BackgroundHepatitis B e antigen (HBeAg) loss with anti-HBe appearance marks the first durable immunological milestone during nucleos(t)ide analogues (NAs) therapy, yet static baseline or single time-point biomarkers anticipate this event poorly. We hypothesized that early dynamic parameters reflecting viral, antigenic and hepatic function during the first 12 weeks of therapy contain richer prognostic information than baseline values alone.AimsThis study aimed to construct a model that fuses week-12 changes in serum biochemical and virological parameters and tested its performance in predicting week-60 HBeAg seroconversion (SR).MethodsSerum biochemical and virological parameters of HBeAg-positive patients receiving NAs treatment between January and December 2023 were collected. Difference, ratio and absolute week-12 values of variables were derived. After ten-fold cross-validation, a multi-variable signature was selected to build a least absolute shrinkage and selection operator (LASSO) logistic regression model.ResultsOverall, 38.24% (26/68) of patients achieved HBeAg SR. Using LASSO regression with ten-fold cross-validation, an eight-variable signature related to the dynamic changes of HBeAg, hepatitis B surface antigen (HBsAg), gamma-glutamyl transferase (GGT), and albumin (ALB) were selected. In the training cohort (n=68), the multi- variable model demonstrated an area under the curve (AUC) of 0.975 (sensitivity, 96.2%; specificity, 95.2%), significantly outperforming single-variable models. In the test cohort (n=34), the model achieved an AUC of 0.721 with maintained high specificity (95%) and positive predictive value (PPV, 90%).ConclusionsEarly on-treatment integrated dynamics of HBeAg, HBsAg, GGT and ALB showed predictive value for subsequent HBeAg SR. The eight-variable model may assist monitoring or alternative strategies in patients receiving treatment.

Background Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome involving dysfunction of multiple immune cell types.Objective This study aimed to comprehensively depict the dynamic trajectory of immune responses throughout the disease course of HBV-related ACLF (HBV-ACLF).Design Single-cell RNA sequencing and single-cell proteomics were performed on the peripheral blood mononuclear cells of 45 samples from 17 patients who were hospitalised (progressive/stable/recovering course of HBV-ACLF, 6/5/6) and 15 control subjects (liver cirrhosis, chronic hepatitis B and healthy controls, 5/5/5). Functional and mechanistic experiments were validated in vivo and in vitro.Results Single-cell multiomics analysis revealed specific changes in the peripheral immune response in ACLF. VCAN+CD14+-monocytes with activated interferon-stimulated genes and enhanced inflammatory functions, stimulated by HBV relapse and expanded in ACLF-1, fuelling early inflammatory storm. The subsequent apoptotic hepatocytes predominantly induce hyperinflammatory C-X-C motif chemokine receptor 2 (CXCR2)+-neutrophils and CD163+-monocytes, enriching in patients with progressive ACLF and serving as significant markers of disease deterioration. Cytotoxic T-cells were functionally impaired and significantly decreased in progressive patients. CXCR2+-neutrophils exhibited immunosuppressive activity and induced the exhaustion of cytotoxic T-cells. Pharmacological inhibition of CXCR2 significantly reduced neutrophils infiltration, restored cytotoxic T-cells and showed therapeutic effect in ACLF mice. Six immune cellular modules (CMs) were identified for patient stratification, with CM2 and CM6 showing strong predictive value for disease outcomes, and CM3 indicating a potential early therapeutic window.Conclusion Our longitudinal multiomics study revealed the dynamic evolution of the immune response in HBV-ACLF and characterised diverse immune patterns for the future precise management and therapeutic intervention.

BackgroundNeurosyphilis has resurged globally, presenting a significant public health threat, yet challenges in early diagnosis persist. This study aims to evaluate the diagnostic value of C-X-C motif chemokine ligand 1 (CXCL1), C-X-C motif chemokine ligand 5(CXCL5), and C-X-C motif chemokine ligand 8 (CXCL8) in cerebrospinal fluid (CSF) for neurosyphilis.MethodsA total of 126 patients were included in this study, comprising 44 syphilis patients and 82 diagnosed with neurosyphilis (28 asymptomatic and 54 symptomatic). We assessed CSF chemokines, CSF parameters, and lymphocyte subpopulations. Univariate and multivariate logistic regression analyses were conducted to identify predictors of neurosyphilis. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic value of individual and combined biomarkers for this condition.ResultsCSF CXCL1 and CSF CXCL8 levels were significantly elevated in the neurosyphilis group compared to the syphilis group (P < 0.05). Additionally, CSF white cell count (CSF WBC) and CSF total protein (CSF TP) levels were increased, while CD4 levels were decreased. Binary logistic regression analysis identified CSF CXCL8 and CSF TP as independent predictors of neurosyphilis. ROC curve analysis revealed areas under the curve (AUC) for CSF CXCL8 and CSF TP distinguishing neurosyphilis from syphilis of 0.766 and 0.830, respectively. The combined assessment of CSF CXCL8 and CSF TP further improved diagnostic accuracy, with an AUC of 0.865.ConclusionsThe levels of CSF CXCL1 and CSF CXCL8 are valuable for diagnosing neurosyphilis and assessing treatment efficacy. The combined detection of CSF CXCL8 and CSF TP enhances diagnostic precision.

Hepatocellular carcinoma (HCC) is widely recognized as one of the three leading causes of cancer-related death worldwide. Glycyrrhetinic acid (GA) exhibits potent anti-HCC activity, but its poor aqueous solubility limits its clinical application. At high concentrations, nitric oxide (NO) exerts cytotoxic effects on tumor cells. In this study, an ultrasound-assisted albumin nanoparticle system co-loaded with GA and NO (SNO-HSA-GA) was developed for synergistic HCC therapy. The optimized formulation exhibited an average particle size of 232.4 ± 6.2 nm, a zeta potential of -31.2 ± 1.5 mV, and a GA loading of 11.86 ± 1.05

BACKGROUND:This study investigated dyslipidemia and its relative factors among Chinese healthcare workers from 2019 to 2022. METHOD:This retrospective cohort study was conducted from 2019 to 2022. The endpoints were dyslipidemia or the end of follow-up. Univariate Cox proportional hazard regression and LASSO regression models were used to select variables, and a multivariate Cox proportional hazard regression model was constructed to explore factors associated with dyslipidemia. RESULTS:67 (9.2%) medical staff members were diagnosed with dyslipidemia, 106 (14.5%) resigned from the hospital, and 558 (76.3%) kept normal lipid files. Compared with healthcare workers with previous working time <10 years, the hazard ratios (HRs) of those with 10-20 years and ≥ 20 years of working experience were 0.34 (0.18-0.64) (P = 0.001) and 0.47 (0.26-0.85) (P = 0.01); compared with 0-day frontline working time, the HR of those with ≥ 30 days frontline working time was 0.38 (0.19-0.75) (P = 0.005). The HRs of TG, HDL, LDL, TBIL and HB were 3.14 (1.65-6.01) (P < 0.001), 0.20 (0.06-0.65) (P = 0.008), 2.93 (1.70-5.05) (P < 0.001), 1.06 (1.02-1.10) (P = 0.002) and 0.98 (0.97-0.99) (P = 0.04), respectively. CONCLUSION:Healthcare workers with high frontline working time and longer previous working time were less likely to have dyslipidemia, while healthcare workers with high levels of TG, LDL, HB, TBIL, and low levels of HDL were more likely to have dyslipidemia. Supporting healthcare workers should be a priority for policymakers and hospital administrators.

Background/Aims Glycyrrhizic acid (GA) has demonstrated promising efficacy in patients with mild COVID-19, however, its applicability in severe and critical patients needs more substantial evidence. This study aimed to evaluate the effectiveness of GA in this patient population and to explore whether an extended treatment course could provide additional clinical benefits. Methods This retrospective study enrolled 73 patients with severe or critical COVID-19. Based on their receipt of GA therapy, patients were divided into an observation group (received GA therapy) and a control group (did not receive GA therapy). The primary outcome was in-hospital all-cause mortality. The mortality between the two groups was compared using survival analysis, and a multivariate logistic regression model was further employed to identify independent predictors of mortality. Results The all-cause mortality during hospitalization was significantly lower in the observation group than in the control group (P = 0.005). Furthermore, survival curves demonstrated a significantly lower mortality rate in the observation group (P = 0.039). Patients in the observation group also had significantly shorter durations of corticosteroid use and median hospital stays among survivors. By hospital day 14 or at discharge, the observation group exhibited more pronounced improvements in inflammatory markers and a higher rate of improvement on lung CT imaging. In a subgroup analysis of patients who received GA therapy, the long-course group showed lower mortality than the short-course group (10.71% vs. 27.78%), although this difference did not reach statistical significance (P = 0.059). However, the difference in survival curves between these two subgroups reached borderline statistical significance (P = 0.051). Multivariate regression analysis identified non-receipt of GA therapy as an independent risk factor for mortality. Conclusion GA therapy may confer benefits in delaying disease progression and reducing mortality among patients with severe or critical COVID-19. Furthermore, increasing the dosage or extending the treatment course represent viable strategies to potentially enhance its clinical efficacy.

The persistence of covalently closed circular DNA (cccDNA) in hepatitis B virus (HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment. Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies. In this study, we investigated the role of RNA binding motif protein 25 (RBM25) in HBV replication, focusing on its interaction with cccDNA and its regulation of host transcription factors. The results demonstrated that RBM25 knockdown markedly inhibited HBV replication, reducing levels of HBV DNA, hepatitis B e antigen (HBeAg), hepatitis B surface antigen (HBsAg), HBV RNA, and L-HBs in HBV-replicating and infected cell models. Consistent results were observed in a mouse model hydrodynamically injected with 1.2 ​× ​HBV plasmid. Conversely, RBM25 overexpression significantly enhanced HBV replication. Mechanistically, RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains. This effect was mediated by increased Yin Yang 1 (YY1) expression, which enhanced acetylation of cccDNA-bound histones, promoting HBV transcription. Furthermore, RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation, while overexpression of RBM25 promoted core protein degradation. In conclusion, this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA. It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25, which helps sustain HBV replication.

Chronic hepatitis B (CHB), a chronic liver infectious disease, results from persistent hepatitis B virus (HBV) infection lasting over 6 months. It has become a substantial global public health burden. CHB is often manifested by concomitant hepatic biochemical abnormalities, and/or notable inflammatory necrosis, and/or liver histological fibrosis. If left uncontrolled, CHB can progress to severe liver diseases and may even lead to death. Although currently approved therapeutic agents can effectively suppress viral replication and, to a certain extent, reduce related complications, their ineffectiveness in targeting covalently closed circular DNA (cccDNA) fundamentally restricts their potential to achieve a clinical cure. In recent years, research focused on attaining a functional cure for CHB has been on the rise. Drugs with different targeting mechanisms and diverse therapeutic strategies have rendered a clinical cure for CHB a possibility. Among these, emerging small nucleic acid drugs show great promise, exhibiting high potential for achieving a sustained functional cure. In this review, we systematically investigate the unique structure of the HBV genome. Moreover, we delve into the classification, mechanisms of action, and pathways for small nucleic acid drugs used in CHB treatment to achieve a functional cure. Additionally, we analyze some challenges encountered in the development of these drugs and propose corresponding solutions. Furthermore, we discuss current clinical studies and combination therapies involving small nucleic acid drugs for CHB treatment.

Liver fibrosis is a key intermediate stage in the progression of chronic liver disease to end-stage liver cirrhosis. Mortality rises expo nentially once it reaches decompensated liver disease. In a healthy liver microenvironment, hepatocytes, Kupffer cells, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells, and other cells interact with extracellular matrix (ECM) to maintain cell stability and liver function. Different types of liver injury (such as viral hepatitis and alcoholic liver injury) can cause liver fibrosis. Liver injury signals acti vate Kupffer cells and recruit immune cells, leading to liver inflammation. This inflammation, together with liver injury, stimulates the activation of HSCs. Activated HSCs migrate to injury sites and secrete ECM. The ECM increase and stiffening contribute to fibrosis. Microenvironment changes alter cell phenotypes, perpetuating HSC activation. This article explores liver fibrosis mechanisms, reviews cellular and microenvironmental changes, summarizes fibrosis characteristics, and provides insights for clinical treatment. Cite this article as: Zou X, Ke Y, Shao Y, Liu S, Shi T. Liver fibrosis: interactions between cells and microenvironments. Turk J Gastroenterol. 2025;36(11):711-722.

The quinazoline scaffold serves as a fundamental framework, demonstrating potent anti-tumor activity. Employing the pharmacophore-based scaffold hopping principle, we successfully synthesized a series of FAK/PLK1 inhibitors incorporating the quinazoline scaffold. The synthesized compounds were characterized using 1H NMR, 13C NMR, and HRMS techniques. Through computer-assisted screening and antitumor activity tests, the majority of the compounds demonstrated significant inhibitory effects against various cancer cell lines. Notably, compound 3m exhibited remarkable anticancer activity by inducing G2/M phase cell cycle arrest, apoptosis, as confirmed by western blot assay, cellular fluorescence staining, and transcriptomics testing. Docking simulation was performed to determine the probable binding conformation of compound 3m within the active sites of FAK and PLK1. This compound emerged as a highly promising lead compound during our screening process, displaying high efficiency. Quinazoline-based compound in L-shape anchors amino acids for potent anti-tumor action as FAK/PLK1 dual inhibitor.

Background:The correlation between hepatitis B virus (HBV) RNA, HBV DNA and hepatitis B surface antigen (HBsAg) during antiviral treatment and the clinical value of HBV RNA for virological response and drug discontinuance, are still unknown. This study was to investigate the clinical significance and predicting ability of HBV RNA for hepatitis B e antigen (HBeAg) seroconversion (SR) in chronic hepatitis B (CHB) patients receiving antiviral therapy. Methods:A total of 138 patients with CHB who were newly diagnosed from January 2023 to December 2023 were enrolled in this study. Patients were divided into the SR group and the non-seroconversion (NSR) group according to HBeAg SR in baseline to the 60th week. The dynamic changes and correlations between HBV RNA, HBV DNA, HBsAg and HBeAg was analyzed between the two groups and the predictive values of them for HBeAg SR were calculated. Results:The 60th week HBeAg SR rate was 23.9% (33/138), patients treated with tenofovir alafenamide fumarate (TAF) had higher SR rate than others (P < 0.001). After antiviral therapy, the serum HBV RNA levels of SR group decreased significantly than in the NSR group. Baseline HBV RNA levels were significantly correlated with HBV DNA, HBsAg and HBeAg in both groups, but weakened after antiviral therapy. Univariate and multivariate regression analysis showed that the serum HBV RNA levels at the 12th week was an independent predictor of HBeAg SR. The area under the receiver operating characteristic curve (AUROC) of the serum HBV RNA levels at the 12th week had a higher value (AUROC = 0.8039, 95% CI [0.691-0.917]). The cut off value of HBV RNA level with 5.68 lg copies/ml at the 12th week had a sensitivity of 76.47% and a specificity of 72.55% for predicting HBeAg SR. Conclusions:Baseline HBV RNA levels in CHB patients exhibited a significantly positive correlation with HBV DNA and HBsAg levels, this correlation weakened after antiviral therapy. The serum HBV RNA level at the 12th week could serve as an early predictor for the HBeAg SR in patients with CHB. The CHB patients treated with antiviral drug TAF showed a higher HBeAg SR rate compared to ETV and TDF.

OBJECTIVES:Indicators that predict the severity and outcomes of COVID-19 are essential to guide medical decision-making. This retrospective study explored whether the combined levels of serum amyloid A (SAA) and heparin-binding protein (HBP) in elderly COVID-19 patients are useful in this context. PATIENTS:This retrospective study included COVID-19 patients aged ≥ 60 years admitted to a designated hospital in Hangzhou, China between December 2022 and March 2023. The clinical, epidemiological, radiological, and laboratory parameters of the patients were analyzed. RESULTS:Compared with COVID-19 survivors, the levels of HBP, procalcitonin, SAA, C-reactive protein, D-dimer, and interleukin-6, as well as the white blood cell and neutrophil counts, were significantly elevated in non-survivors, whereas the total protein and lymphocyte count were lower. The admission SAA and HBP levels were significantly elevated in COVID-19 patients compared with reference values and increased with disease severity. Receiver operating characteristic curves were used to evaluate the diagnostic utility of SAA plus HBP levels for predicting COVID-19-associated mortality. An SAA level cut-off of 348.73 mg/L combined with HBP level cut-off of 42.75 ng/mL showed a sensitivity, specificity, and area under the curve of 96.7%, 85.7%, and 0.96, respectively. An admission SAA level ≥ 348.73 mg/L and HBP level ≥ 42.75 ng/mL increased the risk of unfavorable outcomes in elderly COVID-19 patients. CONCLUSION:Combined admission levels of SAA and HBP reliably predicted COVID-19 severity and prognosis in patients aged ≥ 60 years. Elderly patients with elevated SAA and HBP levels at admission should receive aggressive and timely treatment.

A novel polymeric nanosensor (named PEINAC) based on polyethyleneimine (PEI), was designed for the selective fluorescence detection of l-lysine (L-Lys) in aqueous solutions. The sensor was synthesized through a one-step, three-component reaction involving orthophthalaldehyde (OPA), PEI, and acetylcysteine. This reaction simultaneously facilitated the creation of an isoindole fluorophore, which was chemically attached to the PEI backbone. The structural properties, size, and morphology of PEINAC were thoroughly analyzed using various characterization techniques. When introduced into a buffered solution at pH 7.0, PEINAC demonstrated high specificity for L-Lys, inducing a marked fluorescence enhancement at 450 nm upon excitation at 367 nm. The fluorescence intensity exhibited a linear relationship with L-Lys concentration, ranging from 1 μM to 1000 μM, with a detection limit of 0.13 μM. Notably, the sensor exhibited excellent selectivity, showing no significant interference from other biomolecules and common transition metal ions and anions. This sensor was successfully applied for L-Lys quantification in blood and urine samples and for cellular L-Lys imaging, demonstrating its potential in various analytical and biomedical applications.

Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China. Methods:We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected. Results:A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001). Conclusions:The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.

OBJECTIVE:To investigate chemiluminescence immunoassay (CLIA) in detecting anti-centromere antibodies (ACA) in primary biliary cholangitis (PBC) patients. METHODS:In this retrospective study, 165 patients diagnosed with PBC at Hangzhou Xixi Hospital between December 2020 and January 2023 were enrolled. ACA positivity was assessed using three methods: indirect immunofluorescence (IIF), line immunoassay (LIA), and CLIA. The agreement among the methods was evaluated using kappa statistics and correlation analysis. Logistic regression was used to assess the association between ACA positivity and portal hypertension. Receiver operating characteristic (ROC) curve analysis was performed to compare the predictive performance of CLIA and LIA for portal hypertension. RESULTS:Among the 165 PBC patients, 69 (41.8%), 68 (41.2%), and 66 (40.0%) were ACA-positive by IIF, LIA, and CLIA, respectively. CLIA showed excellent agreement with IIF (κ = 0.962) and LIA (κ = 0.975), and a strong correlation with LIA in quantitative detection (R = 0.893, p < 0.001). Logistic regression confirmed that ACA positivity was significantly associated with portal hypertension (OR = 2.726, 95% CI: 1.437-5.169, p = 0.002). CLIA demonstrated superior predictive performance over LIA for portal hypertension (AUC: 0.705 vs. 0.638, p = 0.001). CONCLUSION:CLIA exhibits excellent concordance with conventional methods for detecting ACA and provides a broader linear range for quantitative assessment. ACA positivity was significantly associated with portal hypertension in PBC patients. The main advantage of CLIA lies in its precise quantification of ACA and prognostic value, highlighting its potential role in risk stratification and disease monitoring in PBC patients.

To characterise T-cell immunity and inflammatory profiles in HIV patients with mycobacterial co-infections. This study enrolled 41 HIV patients co-infected with Mycobacterium tuberculosis (HIV-TB, n  = 27) or non-tuberculous mycobacteria (HIV-NTM, n  = 14), along with 30 controls (20 HIV-monoinfected, 10 post-treatment) from a single centre. Flow cytometry quantified T-cell subsets (CD3 + CD4+, CD3 + CD8+, CD28+ subsets), mitochondrial parameters (mass [MM], low membrane potential [MMP-low%]) and cytokines (IFN-γ, IL-2/4/6/10/17A, TNF-α). Co-infected groups showed reduced T-cell counts versus HIV-monoinfected controls ( p  < 0.05). Elevated MMP-low% in CD3 + CD4+/CD28+ T cells indicated mitochondrial dysfunction in co-infected patients ( p  < 0.05). HIV-TB patients exhibited higher CD3 + CD4+/CD28+/CD8+ T-cell MM than HIV-NTM ( p  < 0.05), while HIV-NTM demonstrated greater MMP-low% ( p  < 0.05). Proinflammatory cytokines (IFN-γ, IL-6, IL-17A) inversely correlated with CD4+ counts and MM, but positively with CD8 + CD28+ MMP-low%. MMP-low% in CD3 + CD4 + CD28+ T cells and IL-2 differentiated IRIS/non-IRIS cases ( p  < 0.05), with combined AUC = 0.834 for IRIS prediction ( p  = 0.001). HIV/mycobacterial co-infection exacerbates T-cell depletion and mitochondrial dysfunction, with HIV-NTM showing more severe impairment. MMP-low% and IL-2 may serve as biomarkers for IRIS risk stratification.