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.

Biliary atresia (BA) is the leading cause of pediatric obstructive cholestasis and a major indication for liver transplantation in infants. Organoid models are increasingly used to investigate BA pathogenesis and therapeutic responses, but incomplete methodological and clinical reporting may limit cross-study comparison and translational interpretation. This study aimed to map the landscape of BA-related organoid research, identify major reporting gaps, and propose Biliary Atresia Minimum Reporting Standard (BA-MRS) as a preliminary framework for improving reporting completeness.

PubMed, Scopus, and Web of Science Core Collection were searched on March 8, 2026, in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) and the 2024 Joanna Briggs Institute (JBI) Manual for Evidence Synthesis. Reporting completeness was assessed using a 36-item BA-MRS across six domains, scored as fully reported, partially reported, not reported, or not applicable.

Twenty-six studies published between 2020 and 2026 were included. Fibrosis and epithelial–mesenchymal transition were the most frequently studied themes, whereas only one study linked organoid findings to post-Kasai outcomes. BA case/model definition, ethics approval, and differentiation protocols were fully reported in all applicable studies (100%). In contrast, contamination monitoring (3.8%), core biliary function assays (34.6%), and clinical outcome linkage (26.3%) were poorly reported. Culture System and Sample Acquisition showed the lowest domain-level fully reported rates (58.1% and 63.2%, respectively).

BA organoid research has progressed beyond early model development, but reporting remains insufficient for robust comparison, reproducibility, and clinically meaningful interpretation. BA-MRS may serve as a preliminary framework for improving standardized reporting in future studies.

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 between cured and uncured patients with CHB.

In this retrospective study, we applied single-cell RNA sequencing to compare peripheral B-cell profiles between 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. Cured patients showed higher frequencies of total B cells and IL-4R+SELL+ Naïve B cells than uncured patients. In contrast, 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.

Hepatitis B virus (HBV) vertical transmission remains a major health challenge, and the characteristics of the placental immune microenvironment in chronic infection remain unclear. This study aimed to use mass cytometry to comprehensively analyze phenotypic changes in placental immune cell subsets.

We collected placental tissues from 20 pregnant women (6 healthy controls and 14 with chronic HBV infection). CD45+ leukocytes were detected using a 35-marker antibody panel. Unsupervised clustering identified 14 clusters, of which 13 immune clusters were analyzed.

HBV mainly caused functional remodeling of placental immune cells rather than changes in cell composition (P > 0.05 for all subsets). In natural killer (NK) cells, CD38 (P = 0.015) and CD16 (P = 0.0020) were notably upregulated and strongly correlated (ρ = 0.872, P < 0.001), suggesting potentially enhanced ADCC function. T cells showed upregulation of CD27, CD38, and CXCR5. Basophils exhibited the most pronounced changes: 9 differential markers (including chemokine receptors CCR4 and CCR7) were consistently downregulated. Classical monocytes showed an M1 polarization tendency (CD38↑, CD163↓). All P-values were raw; no markers remained significant after false discovery rate correction at an FDR threshold of < 0.1, indicating nominal significance. In addition, the coordinated expression patterns of markers within multiple cell subsets were weakened after infection.

These exploratory findings suggest that HBV may reshape placental immunity through enhanced NK cell activation, broad basophil suppression, and disrupted marker coordination. The sample size was limited (n = 20), so the results need to be validated in larger cohorts. These findings provide new perspectives for understanding the mechanisms of mother-to-child transmission.

Ferroptosis, an iron-dependent form of regulated cell death, serves as an important mechanism associated with cancer progression. Natural compounds, particularly alkaloids, have emerged as attractive candidates for regulating ferroptotic cell death, thereby providing a promising anticancer strategy. However, the molecular mechanisms underlying their antitumor effects remain poorly understood. In this study, we aimed to investigate the antitumor effects and underlying mechanisms of natural alkaloids against HCC.

An alkaloid library was used to screen alkaloids with anti-hepatocellular carcinoma (HCC) activity. A combination of proteomic profiling, in vitro functional assays, and in vivo animal experiments was performed to explore the biological roles and molecular mechanisms of the lead compound.

Through high-throughput screening of an alkaloid library, we identified palmatine (PAL), an active component isolated from Fibraurea recisa Pierre, as a potential ferroptosis sensitizer in HCC cells. PAL treatment triggered typical ferroptotic features in HCC cells, including elevated ferrous iron, reactive oxygen species, and lipid peroxidation, along with decreased glutathione levels. Importantly, the pro-ferroptotic effect of PAL was significantly abolished by two ferroptosis inhibitors, ferrostatin-1 and deferoxamine. Mechanistically, PAL directly interacted with troponin T1 (TNNT1) to trigger its K48-linked polyubiquitination and subsequent protein degradation. Ectopic TNNT1 overexpression significantly rescued PAL-mediated ferroptosis and abrogated its tumor-suppressive effects. In vivo animal models further confirmed that PAL suppressed tumor growth by downregulating TNNT1, with a favorable safety profile.

Therefore, this study reveals a previously unrecognized role of PAL as a ferroptosis sensitizer and highlights its translational potential for anti-HCC therapy.

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.