Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multifactorial disorder driven by complex interactions among genetic, epigenetic, transcriptional, proteomic, metabolic, and microbiome factors. Single-omics technologies have provided valuable insights into disease mechanisms, yet each layer captures only a partial view of MAFLD pathogenesis. Recent advances in multi-omics integration allow systematic dissection of molecular networks, cell differentiation trajectories, intercellular communication, and spatial organization, revealing causal links between molecular alterations and tissue phenotypes. Horizontal integration connects different omic layers within the same biological state, while longitudinal integration captures dynamic changes across disease stages. Emerging spatial transcriptomics, proteomics, and metabolomics techniques further enable in situ mapping of cellular and molecular heterogeneity, uncovering spatially defined pathogenic niches and regulatory hubs. Collectively, these integrated approaches offer a multidimensional framework for understanding MAFLD progression, identifying potential biomarkers, and guiding precision therapeutic strategies. Future efforts should focus on standardized multi-omics pipelines, interdisciplinary collaboration, and functional validation to translate these insights into clinical applications.

Bilateral above-knee amputation stump ulcers with poor arterial inflow, multidrug-resistant infection, and bone involvement are rare and difficult to manage. We report a 52-year-old man who developed nonhealing bilateral stump ulcers more than one month after emergency bilateral amputation for extensive aortoiliac and lower-extremity arterial thrombosis. On admission on January 6, 2026, the right stump wound measured approximately 16.0 × 13.0 cm, with exposed femoral bone, purulent medullary drainage, and necrotic tissue; the left measured 18.0 × 12.0 cm, with slough and persistent exudation. Wound culture yielded carbapenem-resistant Klebsiella pneumoniae, and right femoral bone pathology supported chronic necrotizing osteomyelitis. Because immediate revascularization was not feasible, we used a staged debridement strategy—repeated selective debridement preserving viable tissue, with negative pressure wound therapy (NPWT) as a bridge between operations—combined with delayed stump repair, culture-guided antimicrobial therapy, anticoagulation, analgesia, vascular protection, and nutritional support. NPWT was applied in seven cycles over approximately 54 days. The wounds achieved complete closure by discharge on March 16, 2026. At follow-up on March 30, 2026, there was no exudation, sinus tract, recurrent dehiscence, exposed bone, recurrent infection, or significant stump pain, although prosthetic fitting was not yet possible. This case suggests that NPWT combined with serial staged debridement may offer short-term salvage for selected complex infected amputation stumps when arterial inflow is poor and one-stage closure is unsafe; however, durability and generalizability remain uncertain.

The clinical spectrum from cirrhosis to hepatocellular carcinoma (HCC) reflects interactions among hepatic dysfunction, systemic inflammation, and tumor burden. Whether circulating biomarkers add value beyond clinical parameters remains uncertain. This study aimed to evaluate an exploratory Model for End-Stage Liver Disease (MELD)–neutrophil-to-lymphocyte ratio (NLR)-based clinical–inflammatory phenotyping framework for discriminating advanced HCC features and to determine whether circulating hsa_circ_101555 provides incremental discriminatory value beyond this framework.

This single-center cross-sectional study included 92 consecutive patients (30 with cirrhosis without HCC and 62 with HCC). Patients were classified into three exploratory clinical–inflammatory phenotypes using a hierarchical MELD–NLR algorithm (Phenotype I, n = 25; II, n = 33; III, n = 34). Circulating hsa_circ_101555 was quantified by reverse transcription quantitative polymerase chain reaction. Receiver operating characteristic analysis evaluated Barcelona Clinic Liver Cancer stage C among patients with HCC (n = 62; events = 28). Internal validation used bootstrap resampling.

Higher-risk phenotypes included progressively larger proportions of patients with HCC and greater frequencies of advanced tumor characteristics. The combined MELD–NLR model showed the highest discrimination (the area under the receiver operating characteristic curve (AUC) 0.90; 95% confidence interval 0.82–0.97), with 85.7% sensitivity, 82.4% specificity, and 83.9% accuracy. This performance exceeded that of NLR alone (AUC, 0.80) and MELD alone (AUC, 0.77). Circulating hsa_circ_101555 was associated with smaller tumors and an earlier Barcelona Clinic Liver Cancer stage but showed modest discrimination (AUC, 0.69) and did not improve the MELD–NLR model (ΔAUC = 0.002; DeLong P = 0.79).

The exploratory MELD–NLR-based clinical–inflammatory framework identifies patient groups with differing frequencies of advanced HCC features. Circulating hsa_circ_101555 provides no incremental discriminatory value beyond routinely available clinical–inflammatory parameters and requires external validation before clinical use.

Anti-anxiety medications may cause adverse effects and can be associated with long-term health risks. Rooibos tea (Aspalathus linearis) contains polyphenolic compounds that may confer health benefits. This study aims to investigate the effects of green rooibos extract supplementation on anxiety levels in adults with mild-to-moderate anxiety.

This double-blind, placebo-controlled, randomized controlled trial will enroll 60 adults aged 18-65 years with mild-to-moderate anxiety. Participants will receive either green rooibos extract (19.25 mg aspalathin per capsule; n = 30) or placebo (n = 30). They will take one capsule each morning during the first week and two capsules each morning during the subsequent 7 weeks. The anxiety subscale of the 21-item Depression, Anxiety and Stress Scale will be the primary outcome and will be assessed from baseline to post-intervention. Secondary outcomes will include salivary biomarkers, heart rate variability, sleep quality, and dietary intake. Measurements will be collected at baseline, mid-intervention, and post-intervention.

The findings may help determine whether green rooibos extract supplementation is associated with reduced anxiety and improvements in related health markers in adults with mild-to-moderate anxiety.

Although hepatitis B surface antigen (HBsAg)-specific B cells have been partially characterized in chronic hepatitis B (CHB), the role of naïve B cells and their potential relevance to functional cure remain insufficiently explored. Here, we aimed to characterize the naïve B-cell subsets in functionally cured and uncured patients with CHB.

In this retrospective study, we applied single-cell RNA sequencing to compare peripheral B-cell profiles in functionally cured and uncured CHB patients. Key findings were validated by flow cytometry in an independent cohort and further supported in a nucleos(t)ide analog monotherapy cohort stratified by HBsAg levels.

Single-cell RNA sequencing characterized two naïve B-cell subsets, designated IL-4R+SELL+ and IL-4R−SELL− naïve B cells, which were differentially distributed between functionally cured and uncured patients. Functionally cured patients showed higher frequencies of total B cells and IL-4R+SELL+ naïve B cells than uncured patients. In contrast, functionally uncured patients exhibited persistent hyperactivation of type I interferon signaling in both naïve and memory B cells. The IL-4R+SELL+ subset showed a transcriptional signature associated with germinal center biology and exhibited stronger ligand–receptor interactions with CD40LG+CD4+ T cells. Notably, the frequency of the IL-4R+SELL+ subset was inversely correlated with HBsAg levels. Consistently, patients with lower HBsAg levels also exhibited significantly higher frequencies of IL-4R+SELL+ naïve B cells compared with those with high HBsAg levels.

Collectively, these findings indicate that the IL-4R+SELL+ naïve B-cell subset is characterized by germinal center-related responses and enhanced T-cell-mediated help and may serve as an immunological component associated with functional cure in CHB.

The selectivity of chemotherapy remains limited by systemic toxicity. pH-sensitive polymeric nanocarriers exploit the acidic extracellular environment of solid tumors as a drug-release trigger, but they respond passively to a pre-existing pH gradient that is modest and heterogeneous. We hypothesize that controlled glucose priming, temporally coordinated with nanocarrier administration, may transiently widen the tumor-to-normal extracellular pH differential sufficiently to trigger release from a sharply tuned ultra-pH-sensitive (UPS) carrier in responsive tumor regions. Historical animal studies and limited human observations report tumor-associated extracellular pH decreases of approximately 0.17–0.20 units under selected conditions, while UPS micelles can dissociate cooperatively across a window narrower than 0.25 units and have tunable transition pH thresholds (pHt). The carrier would be tuned below the baseline extracellular pH (pHe) of the target tumor (with a pHt of approximately 6.5–6.6), remaining assembled where local pHe remains above pHt until a priming-induced pH excursion crosses the threshold. The central uncertainty is the accompanying effect on tumor perfusion and carrier delivery: tumor blood flow was unchanged at 1 g/kg in one animal study and reduced by 31% at 4 g/kg, while perfusion at 2 g/kg and the net effect across the proposed 1–2 g/kg testing range remain insufficiently characterized. Human evidence is limited and heterogeneous. Recent intracellular pH imaging associated glucose-induced pH changes with the lactate-to-pyruvate ratio but not with fluorodeoxyglucose standardized uptake value; fluorodeoxyglucose positron emission tomography avidity is therefore retained only as an exploratory candidate biomarker. A previous pH-low insertion peptide (pHLIP)-modified liposomal study supports the general principle of glucose-enhanced pH-responsive delivery but uses a mechanistically distinct carrier. The present work formulates a class-level, falsifiable framework for conformational UPS polymers. The essential next step is simultaneous measurement of tumor extracellular pH, perfusion, nanocarrier accumulation, and cargo release across glucose doses and administration sequences in tumor-bearing animals. Until those variables are measured together, the strategy should be regarded as a falsifiable preclinical proposal rather than a clinically feasible protocol.

Upper gastrointestinal precancerous lesions are important targets for cancer screening and prevention. This study evaluated the diagnostic accuracy of artificial intelligence (AI)-assisted endoscopy for upper gastrointestinal precancerous lesions.

PubMed, Embase, MEDLINE, Cochrane Library, and IEEE Xplore were searched from inception to March 31, 2026. Studies reporting sensitivity and specificity, or sufficient data for their calculation, were included. Two reviewers independently extracted data. Pooled sensitivity, specificity, and the area under the receiver operating characteristic curve were estimated using a bivariate random-effects model.

Fifteen studies comprising 24 datasets and 19,578 records were included. Pooled sensitivity and specificity were 0.930 (95% confidence interval (CI): 0.886–0.958) and 0.944 (95% CI: 0.906–0.967), respectively; the diagnostic odds ratio was 223.79 (95% CI: 92.24–542.94), and the area under the receiver operating characteristic curve was 0.9661. Substantial heterogeneity was observed (bivariate I² = 73%). Among the variables formally evaluated by meta-regression, imaging modality was associated with heterogeneity (global test P = 0.005); image-enhanced endoscopy had higher sensitivity than white-light endoscopy (0.960 vs. 0.875). No significant publication bias was detected by Egger’s test (P = 0.833), Begg’s test (P = 0.641), or Deeks’ funnel plot asymmetry test (P = 0.053).

AI-assisted endoscopy shows high diagnostic accuracy for upper gastrointestinal precancerous lesions. Multicenter prospective studies are needed for validation.