Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA). However, clinical evidence for its use in AA is limited. Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA. Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12). Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug’s effects on inflammatory pathways. Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively). Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common. In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege. Conclusion Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies. Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.

Purpose: Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model. Materials and Methods: A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88). Results: The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. Conclusion Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.