Interleukin-7 (IL-7) is an essential cytokine for T-cell homeostatic proliferation and maintenance. Clinical studies have shown the potential benefits of IL-7 therapy in various diseases associated with lymphopenia. However, the kinetics of the T-cell response to a single administration of IL-7 in humans have not been fully elucidated. Here, we investigated the effects of Fc-fused long-acting recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa) on lymphocytes in healthy adults after a single subcutaneous or intramuscular administration. Administration of hIL-7-hyFc increased the CD8+ and CD4+ T-cell numbers up to 2.5-fold, with corresponding upregulation of Ki-67 and Bcl-2 expression, peaking at day 3 or 7. Regulatory T cells (Tregs) did not expand. Among CD8+ and CD4+ T cells, all T-cell subsets (TN, TEM, TCM, TEMRA, and TSCM) increased for 56 days. The T-cell receptor repertoire diversity of naive CD8+ and CD4+ T cells was increased by hIL-7-hyFc, whereas the memory T-cell subsets did not differ between day 56 and day 0. Transcriptomic analysis revealed that hIL-7-hyFc induced robust T-cell expansion without changes in gene expression profiles associated with T-cell functions or genes related to T-cell exhaustion, senescence, and anergy. The effector functions of antigen-specific CD8+ T cells were preserved after hIL-7-hyFc administration. Our results suggest that hIL-7-hyFc administration induced a sustained increase in the numbers of CD8+ and CD4+ T cells, but not Tregs, without qualitative changes. These results support the potential of hIL-7-hyFc as a treatment for patients with compromised T-cell immunity or as a vaccine adjuvant.

Summary: Background: 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), which is an enzyme that converts cortisone to cortisol, plays a role in the regulation of glucose metabolism and inflammation. J2H‐1702 is a novel 11β‐HSD1 inhibitor, and the inhibition of 11β‐HSD1 has been shown to improve insulin sensitivity, reduce inflammation, and prevent the development of nonalcoholic steatohepatitis (NASH) in preclinical models.Aims: We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of J2H‐1702 after a single‐dose oral administration.Methods: A randomised, double‐blinded, placebo‐controlled, single‐dose, dose‐escalation study was conducted on 50 healthy volunteers. Blood and urine samples were collected to assess the PK and PD of J2H‐1702.Results: The peak plasma concentration of J2H‐1702 was observed at 2–2.9 h after a single‐dose oral administration. J2H‐1702 reduced 11β‐HSD1 activity compared to the placebo at all dose levels. The drug reached its maximal inhibitory effect within 12–24 h post‐dose administration, and the inhibitory effect was maintained till 1 day after administration of the study drug. The drug showed typical first‐order elimination kinetics, with a mean elimination half‐life of 9.8–14.7 h. Systemic exposure to J2H‐1702 increased in a dose‐dependent manner. J2H‐1702 was well tolerated after a single oral administration of up to 300 mg. A total of 11 treatment‐emergent adverse events (TEAEs) occurred in seven (14%) participants, all of which were mild and resolved spontaneously. The most common TEAE was diarrhoea (8%), followed by dizziness (4%).Conclusions: The results of this study suggest that J2H‐1702 could be developed as an effective therapeutic option for NASH.

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) oversee pharmaceutical regulations, including orphan drugs targeting rare diseases with limited patient populations. Post‐marketing studies are crucial for monitoring safety and efficacy, with post‐marketing requirements (PMRs) mandated by the regulatory agencies to ensure compliance. This study aims to compare PMR statuses, objectives, and pivotal trial characteristics of orphan drugs approved by the FDA (n = 154) and EMA (n = 79) from 2008 to 2018, shedding light on regulatory differences and their impact on drug development. Contrary to expectations, our analysis found no significant disparity in the proportion of orphan drugs with and without PMRs approved by both the FDA (48.1%) and EMA (55.7%). Safety concerns surrounding orphan drugs post‐approval, attributed partly to pivotal trial design, underscore the need for robust post‐marketing surveillance. While the FDA primarily focuses on post‐marketing safety (36.1%), the EMA places a higher emphasis on both efficacy and safety (47.1%), reflecting distinct approaches to PMR management between the two regulatory bodies. The observed trend of delayed PMRs at the EMA (47.1%) highlights the importance of effective cooperation between regulators and pharmaceutical companies to ensure the timely completion of PMRs and enhance drug safety.

Purpose: This study aims to analyze global and regional (China, Japan, and South Korea) research on virtual reality (VR) in the field of pain medicine over the past 30 years. Specifically, we quantify VR-related publications, examine the distribution of research topics on chronic and acute pain, and identify trends and future directions. Methods: The Web of Science Core Collection (WoSCC) database was used for bibliometric analysis. This study included articles written in English between 1993 and 2022. The search strategy used predefined terms related to VR and pain. Based on the articles’ titles and abstracts, two pain physicians independently reviewed and classified them as acute or chronic pain. Quantitative data on countries, institutions, journals, and research categories were analyzed. VOSviewer software was used for keyword mapping and clustering. Results: We analyzed 808 VR-related articles on pain medicine. Over the past three decades, the number of publications in this field has increased steadily. The United States of America (n = 259) had the highest number of publications. Moreover, China (n = 42), Japan (n = 18), and South Korea (n = 24) also contributed continuously. Acute and chronic pain research accounted for 44.2% and 37.9% of the articles, respectively. The most common acute pain topic was procedure-related (n = 129, 16.0%), whereas the most common chronic pain topic was neuropathic (n = 104, 12.9%). Keywords clustered around neuroscience, pediatric pain management, and chronic pain management. Conclusion: Our study revealed academic achievements and growing interest in VR-related research in pain medicine. Researchers worldwide have shown balanced interest in applying VR technology to acute and chronic pain, with specific contributions from China, Japan, and South Korea. Harnessing VR technology is promising for improving pain management and enhancing patients’ quality of life in the field of pain medicine.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and sarcopenia share underlying pathophysiological mechanisms and can bidirectionally influence the development and progression of each other. Diagnosing sarcopenia in individuals with MASLD is challenging due to overlapping symptoms and the frequent requirement for expensive, specialized equipment for muscle mass assessment. Therefore, accessible screening methods are crucial. Serum indices based on creatinine (Cr) and cystatin C (CysC), including Calculated Body Muscle Mass (CBMM), Sarcopenia Index (SI), and estimated glomerular filtration rate (eGFR) ratio, have emerged as potential biomarkers for sarcopenia. This study aimed to compare the performance of these serum indices in screening for low skeletal muscle index (SMI) among patients with MASLD.Methods: This prospective observational study enrolled 146 participants with MASLD. Anthropometric and laboratory data were collected. The CBMM, SI, and eGFR ratios were calculated using serum Cr and CysC levels. Low SMI was determined using Bioelectrical Impedance Analysis (BIA) according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Linear regression analysis was used to assess the correlations between serum indices and SMI. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the discriminative ability of these serum indices for detecting low SMI. Furthermore, machine learning models (Linear Regression, Random Forest, and XGBoost), coupled with SHapley Additive exPlanations (SHAP) analysis, were employed to evaluate the importance of these indices in predicting low SMI.Results: Patients with higher fibrosis-4 (FIB-4) scores (≥2.67) had a significantly higher prevalence of low SMI. CBMM demonstrated the strongest correlation with SMI (R² = 0.4306, p < 0.0001) and the best discriminative ability for low SMI (Area under ROC: 0.9149 for males and 0.9444 for females) compared with SI and eGFR ratio. Machine learning models consistently identified CBMM as the most important feature for predicting SMI based on the SHAP analysis.Conclusion: These findings suggest that CBMM, derived from readily available serum markers, could serve as a valuable initial screening tool for identifying MASLD patients at risk of sarcopenia who may benefit from further assessment and early interventions.