Ultrasound is among the most widely used imaging modalities in clinical trials, and yet its dependence on operator skill and equipment settings has historically limited the reproducibility of ultrasound-based endpoints in multi-center studies. Artificial intelligence (AI) now addresses this limitation across two complementary dimensions: automated measurement algorithms that quantify cardiac function, organ volume, and vascular parameters with reproducibility approaching or, in select settings, exceeding that of trained human readers and real-time acquisition guidance systems that enable clinicians with no formal sonography training to perform diagnostic-level examinations, making remote and decentralized assessment increasingly feasible. This narrative review synthesizes current evidence and regulatory developments across three interconnected domains. First, use of automated ultrasound to ascertain endpoints has advanced from single-institution validation to prospective and randomized evidence, with deep learning measurement of the left ventricular ejection fraction demonstrating formal equivalence to expert readers across multiple echocardiographic parameters and AI-first workflows shortening the time to diagnosis in a blinded non-inferiority trial. Second, AI-guided ultrasound acquisition by nurses and other non-expert operators has achieved a high rate of diagnostic acceptability in cardiac and pulmonary ultrasound, laying the groundwork for use of ultrasound-based endpoints in decentralized clinical trial designs, as reflected in Food and Drug Administration (FDA) guidance on decentralized trial elements. Third, the regulatory frameworks governing AI-enabled medical devices - including the U.S. FDA's Predetermined Change Control Plan guidance, the EU Artificial Intelligence Act, and internationally harmonized good machine learning practice relevant to Japan and other jurisdictions - increasingly emphasize overlapping principles such as specification of prospective performance, post-marketing oversight, and transparent reporting. Addressing remaining challenges in domain generalization across vendors, subgroup fairness, and algorithm change management during ongoing trials will be essential for AI-assisted ultrasound to fulfill its potential as a robust, scalable endpoint in clinical research worldwide.

Inflammatory bowel disease (IBD) is a digestive system disorder characterized by chronic recurrent inflammation, primarily including ulcerative colitis (UC) and Crohn's disease (CD). Although modern precision medicine therapies, represented by biologics and small-molecule drugs, have reshaped the IBD treatment landscape, clinical practice still faces challenges such as primary non-response, secondary loss of response, risks of severe opportunistic infections, and an increasingly heavy health-economic burden. Traditional Chinese Medicine (TCM), as a unique medical system with millennia of clinical experience and guided by its distinct theoretical framework of "holistic concept" and "treatment based on syndrome differentiation," shows great potential in IBD management. In recent years, advances in evidence-based medicine and modern biotechnology have propelled TCM research in IBD from empirical treatment toward precision medicine. TCM exerts its effects through multi-target and multi-pathway mechanisms, demonstrating unique advantages particularly in immunomodulation, intestinal barrier repair, and gut microbiota regulation. Furthermore, modern research, from holistic perspectives such as the "gut-lung axis" and "gut-brain axis," scientifically interprets the modern biological connotations of traditional TCM theories, providing new understanding for TCM's application in IBD. Concurrently, this article discusses the revolutionary progress of nanodrug delivery systems and multi-omics technologies in enhancing the bioavailability of TCM components, reducing toxicity, and elucidating complex mechanisms. It aims to construct a modern scientific framework for TCM in treating IBD through the dual macroscopic and microscopic perspectives of systems biology and translational medicine, offering insights for achieving precision therapy, whole-life-cycle management of IBD, and complementary integration of Chinese and Western medicine.

The modernization of traditional medicine follows diverse pathways. This paper aims to provide a narrative review of the manufacturing processes, research on active ingredients, and models for the clinical use of formulated granules of traditional Chinese medicines (TCM) and Japanese Kampo medicines in the context of their modernization by comparing advances in research on the two and their challenges. By searching databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), this review included relevant literature published up to 2026. After screening, a total of 48 relevant articles were included in the review. In TCM, formulated granules evolved from the need to modernize herbal medicines through multi-stage extraction and granulation. This enhances convenience while preserving medicinal properties. TCM enables flexible syndrome differentiation and it is working to industrially produce and standardize herbal medicines while refining quality standards. Japanese Kampo, based on fixed classical formulations and covered by National Health Insurance, has developed a highly standardized, evidence-based model. Research in China broadly investigates numerous formulations using omics technologies to explore their material basis and network pharmacology. Research in Japan focuses on in-depth analysis of "pathways to efficacious formulations" for select classic formulations. Faced with the challenge of providing modern evidence, granules can produce real-world data on TCM. This comparative analysis offers insights into the development of quality granules and their use internationally and it explores prospects for Sino-Japanese collaboration in complementary manufacturing processes and fundamental research.

Chronic constipation is one of the most common gastrointestinal disorders worldwide. It has an impact on daily life and poses a considerable economic burden. Tongfu Powder originated from the Xiaochengqi Decoction with the intent of promoting defecation. Acupoint application of Tongfu Powder has exhibited potentially beneficial effects in the treatment of constipation. However, the potential mechanisms by which acupoint application of Tongfu Powder regulates gastrointestinal motility and gut microbiota are still unclear. The current study sought to investigate the effects and underlying mechanisms of acupoint application of Tongfu Powder on loperamide-induced constipation in mice. The results demonstrated that acupoint application of Tongfu Powder significantly improved the overall defecation of constipated mice, including an increase in the number of fecal pellets, fecal weight, and water content, a decrease in gastric residual volume, and an increase in the intestinal propulsion rate. It also alleviated loperamide-induced colonic histopathological deterioration such as cellular infiltration and thinning of the muscular and mucosal layers in constipated mice. Acupoint application of Tongfu Powder significantly up-regulated the levels of interstitial cells of Cajal (ICC) markers (c-Kit and SCF) and it increased synthesis of intestinal 5-hydroxytryptamine (5-HT) and related proteins (TPH1, HTR4 and SERT). Acupoint application of Tongfu Powder promoted intestinal mucin-2 (MUC2) secretion and increased the expression of tight junction proteins (claudin-1 and occludin). 16S rRNA gene sequencing revealed that acupoint application of Tongfu Powder significantly increased the abundance of Akkermansia muciniphila, a bacterium known to be involved in regulating gut motility and intestinal barrier function, thereby alleviating intestinal dysfunction. In addition, it is worth noting that the therapeutic effect of Tongfu Powder acupoint application combined with lactulose is superior to that of either treatment alone. In conclusion, results revealed that acupoint application of Tongfu Powder might alleviate loperamide-induced constipation by regulating the intestinal barrier and gut microbiota.

Tuberculosis (TB) remains a significant global health issue. Early diagnosis is crucial, yet current diagnostic technologies are limited by suboptimal sensitivity. Thus, we developed a novel tuberculosis metabolic labeling probe (single cell metabolic labeling probe for tuberculosis, SCMLP-TB) and evaluated its diagnostic performance. In this retrospective study of 70 suspected TB patients, we calculated the sensitivity and specificity of SCMLP-TB and compared it with culture and Xpert MTB/RIF (Xpert) using the final clinical diagnosis as reference standard. Eligible participants were classified as confirmed TB (CT), clinically diagnosed TB (CDxT), or non-TB cases based on the diagnosis criteria for pulmonary tuberculosis (WS 288-2017). Of the 70 participants, 40 (57.0%) were diagnosed with TB, including 30 CT cases and 10 CDxT cases. The overall diagnostic sensitivity and specificity of SCMLP-TB were 97.5% and 96.7%, respectively. Notably, SCMLP-TB identified 10 CDxT cases missed by both culture and Xpert. The overall diagnostic sensitivity of culture and Xpert was 62.5% and 72.5%, respectively, while both showed a specificity of 100.0%, demonstrating that SCMLP-TB was more sensitive than culture and Xpert. Besides, the fluorescence intensity from TB patients was significantly higher than non-TB patients. The fluorescence intensity showed a significant negative correlation with the time to positivity (TTP) of culture, which suggested that SCMLP-TB could also serve as an indicator of bacterial loads in patients' samples. Consequently, SCMLP-TB demonstrated a promising tool for the sensitive and ultra-fast diagnosis of pulmonary TB suspects, particularly for paucibacillary pulmonary TB.

The treatment strategies and outcomes for advanced intrahepatic cholangiocarcinoma (ICC) are restricted. The treatment modalities and effectiveness of local interventional chemotherapy and systemic chemotherapy remain indeterminate. The objective of this study is to explore and assess the influence of different chemotherapy methods on the prognosis of patients with advanced ICC. A retrospective investigation was carried out at two research centers. The recruited patients were divided into the systemic chemotherapy cohort and the local chemotherapy cohort (Transarterial Chemoembolization, TACE). The primary endpoint of this study was overall survival (OS), while the secondary endpoints encompassed progression free survival (PFS), response rate (RR), and adverse events (AE). From January 2014 to January 2024, a total of 124 patients were included. Systemic/local chemotherapy combined with targeted therapy exhibited superior survival performance compared to chemotherapy alone. Additionally, patients with lesions confined to the liver and large tumors (> 6 cm) obtained better survival benefits from systemic chemotherapy. There was no significant disparity in grade 3 or more severe adverse events between the two groups. Whether it is systemic chemotherapy or TACE, combining them with targeted therapy can confer significant therapeutic advantages to patients with advanced ICC. ICC patients with a higher tumor burden may attain better therapeutic outcomes by selecting systemic chemotherapy.

Nursing and healthcare-associated pneumonia (NHCAP) pose significant challenges in older populations, yet factors predicting antibiotic treatment failure remain elusive. This exploratory secondary analysis of a multicenter phase IV trial aimed to identify the clinical and microbiome predictors of treatment failure in patients with NHCAP treated with lascufloxacin. Among the 56 evaluable patients (median age 86 years; cured n = 44, not cured n = 12), paired sputum and tongue samples were analyzed using 16S ribosomal RNA gene clone library sequencing. Alpha diversity was assessed using the Shannon index, Simpson index, observed richness, and Pielou's evenness, whereas beta diversity was calculated using Bray-Curtis dissimilarity and visualized by principal coordinate analysis. Serum albumin was significantly lower in not cured patients (3.0 vs. 3.5 g/dL, p = 0.0497) and emerged as the strongest predictor of treatment failure in univariate logistic regression (odds ratio 0.18, 95% confidence interval 0.05–0.73, p = 0.016). Sputum Pielou's evenness showed a comparable predictive ability (odds ratio 0.010, p = 0.047). The overall microbiome community composition did not differ according to the outcome. Notably, patients with hypoalbuminemia (< 2.85 g/dL) exhibited significantly reduced sputum alpha diversity (Shannon p = 0.034, Simpson p = 0.025, Pielou's evenness p = 0.010). A simple risk stratification combining hypoalbuminemia and denture use identified a high-risk subgroup with markedly elevated treatment failure rates (75.0% vs. 12.5%, p = 0.001). These findings suggest an interconnected pathophysiology linking nutritional status and respiratory microbiome stability in patients with NHCAP. Nutritional status and oral health may be modifiable targets for improving treatment outcomes in high-risk patients.

Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors are therapeutic options for patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs); however, no randomized controlled trial has compared their efficacy and safety. Since both act through the JAK–signal transducer and activator of transcription pathway, a comparative evaluation is warranted. We conducted a prospective, randomized, open-label trial at 55 centers in Japan, randomizing patients with active RA despite csDMARD therapy in a 1:1 ratio to receive 200 mg/day filgotinib or subcutaneous tocilizumab as monotherapy; the primary endpoint was American College of Rheumatology (ACR) 50 at week 12, and secondary endpoints included clinical disease activity indices, musculoskeletal ultrasonography scores, patient-reported outcomes, and serum biomarkers through 52 weeks. Twenty-six patients were enrolled (13 per group) before study termination due to insufficient recruitment, and descriptive analyses were performed. At week 12, ACR50 was achieved in 38.5% (5/13) patients in the filgotinib group and 46.2% (6/13) in the tocilizumab group (risk difference: −7.69%; 95% confidence interval: −42.26 to 28.8). Both groups showed early and sustained improvements in disease activity from week 2. The improvement in patient global assessment scores was greater with filgotinib at week 2 but the difference diminished thereafter, and serum IL-6 level decreased with filgotinib but increased with tocilizumab. Four serious adverse events occurred with filgotinib, including infections and cardiac events. Because this study was underpowered and the analysis was descriptive, larger studies are needed to confirm these findings and define optimal use. (The study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) as jRCTs071200107 and in ClinicalTrials.gov as NCT05090410.)

Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disease characterized by systemic inflammation. Although IL-6 receptor blockade with tocilizumab is an established treatment, Janus kinase (JAK) inhibition may offer broader immunomodulation by targeting multiple cytokine signaling pathways. This comparative longitudinal study evaluated 41 serum cytokines/chemokines in 10 patients with plasma-cell-type iMCD (five treated with filgotinib (JAK1 preferential inhibitor) for 52 weeks and five treated with tocilizumab for a median of 28 months) to compare the cytokine/chemokine suppression profiles between these two mechanistically distinct therapies. Patient values were normalized to those of healthy controls (n = 101) using Z-scores. At baseline, both groups exhibited marked elevations in cytokines, including IL-12p70, IL-22, IFN-γ, and IL-6. Both treatments resulted in significant changes in multiple cytokines, with 12 cytokines showing significant changes in each group. Between-group comparison revealed only three cytokines with differential responses: IL-6 (receptor blockade artifact), IL-15 (greater suppression with filgotinib), and PDGF-AA (greater suppression with tocilizumab). Overall, cytokine suppression was equivalent between the treatments (median ΔZ-score: −0.32 (filgotinib) vs. −0.27 (tocilizumab), p = 0.74). Principal component analysis demonstrated parallel treatment trajectories toward normalization. These exploratory findings from this small-sample study suggest that JAK inhibition and IL-6 receptor blockade may achieve comparable broad-spectrum cytokine/chemokine suppression in iMCD, despite the different mechanisms of action. However, the discordance between cytokine suppression and clinical improvement with filgotinib suggests that complete IL-6 pathway blockade remains critical for the clinical response in iMCD, highlighting the need to identify additional pathogenic drivers beyond the measured cytokine network.

Constipation is a common gastrointestinal disorder that markedly affects health and quality of life. In Japan, magnesium-based and contact laxatives have long been widely prescribed. Since the launch of lubiprostone in November 2012, several new agents with novel mechanisms have been introduced, and their use has increased. However, to our knowledge, no nationwide study has examined their use. This study aimed to analyze nationwide trends and regional differences in the prescription of medications for constipation. We used data from the Japanese National Health Insurance Claims and Specific Health Checkup Database Open Data from fiscal years (FYs) 2019 to 2023, covering the period when all currently available constipation medications were on the market in Japan, and prior to the inclusion of the drug selection flowchart in the Evidence-Based Clinical Guidelines for Chronic Constipation 2023. Prescription trends were evaluated using defined daily doses per 1,000 inhabitants per day (DID), and regional variations were assessed using standardized claim ratios (SCRs). The DID for contact laxatives decreased during the study period, whereas the DID for other constipation medications increased. Magnesium oxide showed the smallest regional variation, whereas polyethylene glycol and linaclotide showed the largest variations in FY 2019 and FY 2023, respectively. Throughout the 5-year period, the highest SCRs for contact laxatives were observed in Akita, Iwate, and Aomori prefectures. Our findings provide a comprehensive nationwide picture of evolving constipation treatment patterns and regional variations in Japan, establishing baseline data for evaluating the impact of guideline dissemination and evidence accumulation on clinical practice.