Development of mixed histiocytosis (Langerhans cell histiocytosis (LCH))/Erdheim–Chester disease (ECD)) after treatment in patients with an initial skull LCH lesion has not been well recognized. An elderly woman initially developed LCH at the left temporal bone, preceded by polyuria and polydipsia five years earlier; the lesion was surgically removed. Two years thereafter, she experienced her first LCH relapse with a right parietal skull lesion, in which a BRAF V600E mutation was confirmed, and chemotherapy was initiated. After a second LCH relapse involving the left parietal bone, the patient presented with a third relapse at the L2 vertebra. This lesion was pathologically diagnosed as mixed histiocytosis (LCH/ECD), resulting in refractoriness to conventional chemotherapy, and was successfully treated with targeted therapy using BRAF and MEK inhibitors. Spinal mixed histiocytosis (LCH/ECD) may develop following relapses of skull LCH after chemotherapy, for which targeted therapy could be effective.

Pancreatic fibrosis, a major pathological feature of chronic pancreatitis, is primarily driven by the abnormal activation of pancreatic stellate cells (PSCs) and excessive deposition of extracellular matrix. Traditional Chinese medicine (TCM) offers a holistic and synergistic approach to preventing and treating pancreatic fibrosis through multi-target regulation of PSC activation. This review systematically elucidates the mechanisms by which TCM—encompassing both bioactive monomers and compound formulations—modulates key signaling pathways involved in PSC activation, including the mitogen-activated protein kinase, transforming growth factor-β/Smad, platelet-derived growth factor, nuclear factor kappa B, and Wingless/β-catenin pathways. By simultaneously targeting these interconnected signaling networks, TCM strategies effectively inhibit PSC activation, attenuate inflammatory responses, and reduce extracellular matrix deposition. In contrast to single-target pharmacological inhibitors, TCM embodies a “multi-component, multi-pathway” therapeutic paradigm that aligns with the complex pathophysiology of pancreatic fibrosis. This review also draws comparative insights from liver fibrosis, highlighting conserved pathways and organ-specific regulatory contexts. Ultimately, TCM represents a promising integrative avenue for the prevention and treatment of pancreatic fibrosis, supported by growing preclinical evidence and aligned with the principles of holistic intervention.

Steatotic donor livers are highly susceptible to post-transplant dysfunction; however, the underlying mechanisms remain incompletely understood. This study aimed to investigate the role of galectin-3 (LGALS3)-mediated pyroptosis in steatotic liver graft injury and explore its therapeutic potential.

A mouse model of steatotic liver transplantation was established. Graft tissues were subjected to RNA sequencing to identify key regulators. In vitro, LGALS3 was modulated in steatotic hepatocytes under ischemia/reperfusion stress to assess its impact on the NLRP3 inflammasome and pyroptosis. The regulatory mechanism by which LGALS3 modulates NLRP3 ubiquitination was further examined. Finally, the therapeutic efficacy of LGALS3 inhibition was evaluated in an orthotopic liver transplantation model.

Transcriptomic analysis identified LGALS3 as a key upregulated molecule in steatotic grafts, associated with pyroptosis pathways. In vitro, LGALS3 overexpression enhanced NLRP3 inflammasome activation and pyroptotic cell death, whereas LGALS3 knockdown exerted protective effects. Mechanistically, LGALS3 modulated NLRP3 inflammasome activity by regulating its ubiquitination. In vivo, pharmacological inhibition of LGALS3 significantly improved graft function, reduced histological injury, suppressed pyroptosis, and prolonged recipient survival.

This study demonstrates that LGALS3 drives steatotic graft injury by promoting NLRP3-mediated pyroptosis through the regulation of ubiquitination. These findings identify LGALS3 as a promising therapeutic target for improving the outcomes of liver transplantation using steatotic donor organs.

Hashimoto’s thyroiditis (HT), an autoimmune disease with a prevalence 2–7 times higher in women than in men, is associated with daytime sleepiness. The present study aimed to test the hypothesis that thyroid function is associated with chronotype and daytime sleepiness in women with HT.

This retrospective cross-sectional study included women with confirmed HT. Demographic, clinical and laboratory data were collected. The reduced Morningness-Eveningness Questionnaire (rMEQ) and the Epworth Sleepiness Scale (ESS) were used to assess chronotype and daytime sleepiness, respectively. Based on rMEQ, women were categorized as having a morning (≥18), intermediate (12–17) or evening (≤11) chronotype. Based on ESS, women were categorized as having normal or increased daytime sleepiness.

Overall, 106 women, aged 43 ± 12 years, were included. Most had normal daytime sleepiness (68.9%), and the majority had an intermediate chronotype (61.3%), while only one had a morning chronotype (0.9%). Age was significantly associated with chronotype (P = 0.026). There was a significant association between chronotype and thyroglobulin antibodies (TgAb, P = 0.012). Free triiodothyronine (fT3) levels were significantly higher in women with an evening chronotype than in those with an intermediate chronotype (P = 0.045; OR = 0.500; 95% CI 0.25–0.98). Daytime sleepiness was significantly associated with TgAb (P = 0.016) and thyroid-stimulating hormone (TSH, P = 0.040). TgAb levels were significantly higher in women with increased daytime sleepiness (P = 0.049, OR = 1.003, 95% CI 1.00–1.01) than in those with normal daytime sleepiness.

Approximately one-third of women have an evening chronotype, and approximately one-third had increased daytime sleepiness. TgAb, fT3, and TSH are associated with daytime sleepiness or chronotype in women with HT. Further investigation is required for the underlying mechanisms.

Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF.

Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and in vitro assays examined NETs distribution and endothelial interactions.

NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity in vitro. Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation.

NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.

Chronic stress-induced hypercortisolism causes diminished ovarian reserve (DOR), contributing to infertility and miscarriage. Androgen supplementation is an emerging therapeutic approach for DOR. The traditional Chinese herbal decoction modified Gengnianchun formula (MGNC) has shown clinical efficacy in treating DOR. This study aimed to compare the effectiveness of MGNC with that of androgens in a stress-induced DOR mouse model.

Sexually mature female C57 mice aged six weeks were randomly assigned to six groups (n = 10 per group, with 3 independent replicates per group), including the control, model, low-dose testosterone (LT), medium-dose testosterone (MT), high-dose testosterone (HT), and MGNC groups. This sample size and study design were determined based on preliminary experimental data. Chronic stress was induced in mice, except for the control group, by daily glucocorticoid injection, and the mice in the LT, MT, HT, and MGNC groups were treated at the same time with testosterone (low, medium, or high dose) or MGNC for six weeks. Body weight, estrous cycles, ovarian follicle counts, hormone profiles, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and testosterone, and in vitro preantral follicle growth rates (via MGNC-enriched or androgen-treated serum) were assessed.

All groups presented stable body weights. MGNC ameliorated estrous cycle irregularities caused by stress, while testosterone exacerbated the abnormality. Moreover, MGNC outperformed LT in improving primordial/primary/antral follicle counts and corpus luteum formation, while MT and HT did not improve ovarian follicle reserve. LT was associated with the highest serum estradiol level, but none of the testosterone doses reduced FSH levels or the FSH/LH ratio, whereas MGNC lowered FSH and the FSH/LH ratio. Additionally, MGNC-enriched serum significantly enhanced the in vitro follicular growth rate in corticosterone-supplemented culture medium, and this effect was superior to that observed with testosterone-pretreated serum.

MGNC demonstrates superior efficacy over androgen therapy in treating chronic stress-induced DOR in mice, supporting further investigations into its clinical potential and mechanisms.

The immunosuppressive tumor microenvironment (TME) limits immunotherapy efficacy in intrahepatic cholangiocarcinoma (ICC). Understanding the molecular drivers of this TME is essential for developing new therapies. This study aimed to identify novel oncogenes that modulate the immune landscape of ICC using a multi-omics approach.

We integrated transcriptomic and proteomic data from our ICC cohorts with public datasets (TCGA-CHOL, GSE107943, OEP002768) to identify genes co-upregulated with PD-L1 (CD274). Single-cell RNA sequencing (scRNA-seq) was used to analyze cell-type-specific expression and intercellular communication. Clinical significance was validated through tissue microarrays and multiplex immunofluorescence in an independent ICC cohort.

Multi-omics screening identified TACC3 as a key candidate in ICC. Elevated TACC3 expression in ICC tissues correlated with poor prognosis and promoted tumor cell proliferation and migration. TACC3 activated the STAT3 pathway, increasing PD-L1 transcription. scRNA-seq showed TACC3/PD-L1 interaction in malignant epithelial cells, with PD-L1 co-expressed with FOXP3 in regulatory T cells (Tregs). Cell–cell communication analysis predicted strong interactions between malignant cells and Tregs. TACC3 knockdown reduced PD-L1 expression and inhibited STAT3 and AKT phosphorylation. Clinical validation confirmed co-expression of TACC3, PD-L1, and FOXP3, with high TACC3 levels linked to worse clinicopathological features and shorter progression-free survival.

Our study defines a TACC3-STAT3-PD-L1 axis driving immunosuppression in ICC. TACC3 fosters an immunosuppressive TME by upregulating PD-L1 and is associated with a Treg-rich contexture, suggesting that TACC3 may serve as a potential therapeutic target to overcome ICC immunosuppression.

Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a predominant cause of chronic liver disease, underscoring the demand for accessible, non-invasive diagnostic tools. Tongue diagnosis in Traditional Chinese Medicine provides a distinctive perspective on systemic health, though it remains largely subjective. This study aimed to develop an interpretable multimodal deep learning model for MAFLD screening by integrating quantitative tongue image features with routine clinical data.

From 904 screened candidates, 477 subjects (157 healthy, 320 MAFLD) were included and randomly allocated to training, validation, and test sets in an 8:1:1 ratio. All participants underwent standardized tongue imaging (International Commission on Illumination L*a*b color features) and comprehensive clinical evaluation. We constructed a dual-stream deep learning model, combining a ConvNeXt-Tiny network for tongue images and a multilayer perceptron for clinical variables. Feature fusion was achieved via a Dynamic Affine Feature Transformation module, and the model was trained using weighted cross-entropy loss.

MAFLD patients showed significant metabolic abnormalities compared to healthy controls. A progressive decrease in tongue yellowness (b* value) was observed with advancing fibrosis. On an independent test set (n = 48), the multimodal model achieved 97.92% accuracy, Quadratic Weighted Kappa of 0.9538, and 96.88% sensitivity, and 100% specificity, outperforming single-modality and serological models. Interpretability analyses confirmed the model’s focus on clinically relevant tongue regions and key metabolic drivers.

We developed an accurate and interpretable multimodal model that synergizes tongue image features with metabolic indicators for MAFLD screening. This approach presents a promising, low-cost tool potentially well-suited for resource-limited settings.