The Japanese Orthopaedic Association (JOA), founded in 1926, celebrates its centennial in 2026 as one of the world's largest national orthopaedic societies. This article reviews the historical development of the JOA during its first century and highlights major scientific, clinical, educational, and public health achievements of Japanese orthopaedics. The JOA has played a central role in the development of Japanese orthopaedics through specialist education, clinical practice guidelines, nationwide registries, and the promotion of basic and clinical research. Japanese orthopaedic surgeons have contributed to modern orthopaedics through pioneering surgical techniques, technological innovations, and international academic exchange. These developments have expanded the role of orthopaedics beyond the treatment of musculoskeletal disorders to encompass broader public health challenges associated with population aging and the maintenance of mobility and quality of life. Over the past century, Japanese orthopaedics has evolved from a small academic discipline into an internationally recognized field, alongside profound demographic and epidemiological changes, particularly the emergence of a super-aged society.
Individuals differ in their understanding of the causes of illnesses or problems and the appropriate methods for addressing them. Mental disorders can be interpreted from multiple perspectives shaped by cultural backgrounds and personal experiences. The conceptual framework through which individuals recognize and interpret illnesses or problems is referred to as an explanatory model. This study aimed to develop the Explanatory Model Scale for Mental Disorders (EMS-MD), based on Haslam's (2003) explanatory styles-"Medicalizing," "Moralizing," and "Psychologizing"-with the addition of "Socializing" and "Spiritualizing," and to examine its reliability and validity among Japanese adults. An online survey was administered to 928 Japanese adults aged 18 years and older using five mental disorder vignettes (depression, schizophrenia, alcohol use disorder, anorexia nervosa, and social anxiety disorder). A split-sample approach was used to conduct exploratory and confirmatory factor analyses. Internal consistency, test-retest reliability, convergent and discriminant validity, and measurement invariance across gender and vignette contexts were also examined. The analyses suggested a 24-item, 6-factor structure comprising "Socializing," "Spiritualizing," "Biologizing," "Medicalizing," "Moralizing," and "Psychologizing." Notably, "Biologizing" and "Medicalizing" emerged as distinct factors, although this distinction was exploratory because both had originally been conceptualized as part of a broader "Medicalizing" category. Most subscales demonstrated adequate internal consistency, and all exhibited good test-retest reliability. However, "Psychologizing" showed low internal consistency, indicating that this subscale should be interpreted cautiously and requires further item refinement of its item pool. Correlations with measures of the Attribution of Responsibility Process and the Japanese Health Locus of Control subscales were generally consistent with predictions, providing preliminary evidence for convergent validity. The Fornell-Larcker criterion provided preliminary evidence for discriminant validity. Multigroup analyses indicated that the measurement structure was generally stable across gender; however, measurement invariance across vignette contexts was limited. Overall, the EMS-MD shows promise as a preliminary measure of explanatory styles for mental disorders among Japanese adults. Nevertheless, limitations related to model fit, the internal consistency of "Psychologizing," and measurement equivalence across vignettes highlight the need for further item refinement and validation in other cultural contexts.
Habitual diet and the gut microbiota each influence frailty in older adults, but whether they contribute jointly and whether the fiber-frailty association is statistically mediated by gut microbial composition remain poorly characterized in Asian populations. To quantify the joint contribution of dietary patterns and gut microbial clusters to frailty and to test whether a butyrate-producer-rich microbial axis statistically mediates the cross-sectional fiber-frailty association in older Japanese adults. In 785 community-dwelling participants aged ≥65 years from Kyotango, a Japanese longevity area, BDHQ-derived intakes (27 food groups) and 16S rRNA gene amplicon sequencing of fecal samples (47 CLR-Z genus-level taxa) were each summarized by Varimax-rotated PCA and k-means clustering, yielding four dietary patterns and four microbial clusters. A 32-item deficit-accumulation frailty index (FI; frail = FI ≥ 0.21) was the outcome. Regression models adjusted for age, sex and energy intake; a pre-specified mediation model tested whether Microbe PC2 - a butyrate-producer-rich axis dominated by Faecalibacterium, Fusicatenibacter and Eubacterium eligens - statistically mediated the fiber-FI association; indirect effects used 5,000-bootstrap percentile 95% CIs. Frail prevalence was 15.2% overall but varied nine-fold across the 16 diet × microbiota cells, from 4.0% (Pattern 1 [Vegetable, soy and dairy] × Ruminococcus-Faecalibacterium cluster) to 36.4% (Pattern 3 [Seafood and washoku] × Lachnoclostridium-Ruminococcus gnavus cluster). Total fiber intake was inversely associated with FI (β = -0.142, p < 0.0001), and Microbe PC2 statistically mediated this cross-sectional association (indirect β = -0.016, 95% CI -0.031 to -0.005; Sobel p = 0.009; proportion mediated 11.4%). Dietary patterns and gut microbial clusters jointly stratify frailty in older Japanese adults, with a small but consistent statistical mediation of the fiber-frailty association via a butyrate-producer-rich microbial axis. Combined dietary-microbial profiling may refine frailty risk assessment.
This paper systematically reviewed the evolvement and development of pulse diagnosis illustrations in the annotated versions of Nan Jing in both Chinese and Japanese editions. It compared and analysed the content and characteristics of the three pulse diagram systems - the Ding, the Hua and the Zhang in China with that in the annotated edition of Nan Jing in the Japanese edition in the Edo period of Japan. The paper demonstrated the core function of pulse diagrams in interpreting the theories of pulse in Nan Jing. It was found that the pulse diagram illustrations evolved through multiple dynasties and came to the Ding system which focused on the pulse patterns corresponded to 'heaven and humans', the Hua which integrated multi-dimensional factors and the Zhang which fully differentiated diagrams clinically. By comparison the annotated Japanese version of Nan Jing,based on the three pulse diagram systems above in China, featured with localisation evolution, such as disassembled diagram illustrations, metric refinement, and functional differentiation. It was also found that Nan Jing in China as well as in Japan both undertook holistic insights and dialectical thinking, presented different interpretation for the diverse medical practice and cultural context differentiation, providing academic references for the visualized evolvement and cross-cultural communication in terms of traditional Chinese pulse theory. 系统梳理中日《难经》注本中脉诊图释的传承与发展脉络，通过对比分析中国丁氏、滑氏、张氏三大脉图体系与日本江户时期主要注本脉图的内容与特征，揭示了脉图在阐释《难经》脉理中的核心作用。研究发现，中国脉图历经多个朝代的演进，形成了丁氏侧重脉理与天人对应、滑氏整合多元素及张氏实用化全难图解的差异化体系；日本注本在承袭中国三大脉图体系基础上，通过图文拆解、度量细化、功能分化等本土化演进，形成兼具传承性与独特性的脉图系统。通过中日《难经》脉诊图释图像化表达特点进一步探微一难独取寸口、二难尺寸阴阳、三难关格覆溢及十八难五行相生等核心脉理，可见中日脉图既共同承载了《难经》脉学的整体观与辨证思维，又因医学实践与文化语境差异呈现出不同的阐释路径，为中医脉学理论的可视化传承与跨文化传播研究提供了重要学术依据。.
To evaluate the clinical outcomes following bilateral TECNIS Odyssey implantation in patients who self-identify as Japanese. This was a retrospective, single-site, single arm, observational study of clinical outcomes following bilateral TECNIS Odyssey implantation in patients who self-identify as Japanese. Outcome measures were monocular and binocular uncorrected and distance corrected visual acuities at distance (UDVA, CDVA) and near (UNVA, DCNVA; 40cm), refraction, and patient self-reported spectacle independence. Data from a total of 30 patients were included. The percentages of patients with postoperative binocular visual acuity 20/20 or better were 100% (30/30) for UDVA, 100% (30/30) for CDVA, 93% (28/30) for UNVA, and 93% (28/30) for DCNVA. In addition, 100% (60/60) of eyes had ≤ 0.5 D of residual astigmatism, and 100% (60/60) of eyes had postoperative manifest refraction spherical equivalent (MRSE) of ≤ 0.5 D. Finally, 3% (1/30) of subjects reported using glasses for near and 3% (1/30) of subjects reported mild halos. The results of this study suggest good visual outcomes at distance and near, high spectacle independence, and low reports of halos following bilateral implantation with the Odyssey IOL in patients who self-identify as Japanese.
The Japanese General Rules of Clinical and Pathological Reporting of Cancers (Kiyaku) are unique standardized systems for cancer handling and documentation used by professionals involved in cancer care in Japan. The Japanese Society of Pathology (JSP) conducted a questionnaire survey among practicing pathologists regarding the utilization and awareness of Kiyaku. We analyzed 1083 valid responses, representing 22.4% of the JSP members and 33.8% of the board-certified pathologists. Kiyaku, with > 90% latest-edition ownership, covered approximately 90% of all cancers in Japan. The timing of the implementation of the new editions varied not only across institutions but also among individuals in each institution. Among department directors, 46.1% reported implementing new editions at their discretion without prior notice. Item-level responses were collected for the stomach, lung, and breast as representative Kiyaku; histological classification and descriptive symbols were widely considered useful and frequently used across the three cancers, whereas biopsy-related items in the lung and breast were used less frequently. In conclusion, Kiyaku is broadly embedded in daily practice and facilitates standardized cancer documentation in Japan, although several challenges remain. The JSP should clearly articulate the purpose of Kiyaku and promote coordinated adoption to standardize its use in pathology practice.
Genetic improvement of growth traits is a key objective in aquaculture breeding. In this study, we performed whole-genome resequencing of 282 Japanese flounder individuals from a single farmed cohort and obtained approximately 6.67 million high-quality SNPs. Single-trait and multi-trait GWAS were conducted for 11 growth traits: body weight (BW), total length (TL), body length (BL), body depth (BD), trunk length (TUL), head length (HL), snout length (SnL), caudal peduncle depth (CPD), eye diameter (ED), postorbital head length (PoL), and interorbital width (IW). Heritability estimates ranged from 0.172 (IW) to 0.487 (HL). Head length showed the highest heritability, followed by PoL (0.328), ED (0.323), BD (0.300), and CPD (0.291). Genetic correlation analysis revealed that BW was strongly positively correlated with most body size traits (rg > 0.9), indicating that simultaneous improvement of these traits is feasible. Single-trait GWAS identified a total of 55 suggestive associated loci (top five SNPs per trait, combined across all 11 traits, at p < 1 × 10-5). Notably, we observed pronounced pleiotropic effects, where a single SNP or gene influences multiple growth traits. For example, multiple SNPs on chromosome 14 were associated with more than five traits (TL, BL, BD, TUL, BW), and the fras1 gene affected both head length and post-orbital head length, demonstrating a genetic basis of pleiotropy. Additionally, fras1 was associated with head length, and nkd1 with interorbital width. Multi-trait GWAS uncovered 12 novel loci not detected in single-trait analyses, with candidate gene annotation pointing to pathways such as ECM-receptor interaction (e.g., fras1, lamb4) and Wnt signaling (e.g., nkd1), suggesting that these biological processes may underlie the observed associations. These findings are preliminary and require validation in larger independent cohorts. KEGG enrichment analysis showed significant enrichment in ECM-receptor interaction and non-homologous end-joining pathways (corrected p < 0.05). Our results provide a genetic basis for growth trait improvement and candidate markers for breeding programs in Japanese flounder.
This substudy of the OPTIC-J trial analyzed magnetic resonance imaging (MRI) scans from a subset of Japanese patients to examine changes in orbital tissues after teprotumumab treatment vs placebo for active thyroid eye disease (TED). Post hoc exploratory. Volumes and inflammation/edema of extraocular muscles (EOMs) and orbital fat were measured before and after 24 weeks of teprotumumab treatment or placebo using MRI in patients enrolled at four of the 16 trial sites. Inflammation/edema in EOM and orbital fat were evaluated using the signal intensity ratio, based on T2 intensity in the cerebral white matter, and an ordinal grading scale (0-3), respectively. Key clinical outcomes included proptosis, diplopia, and clinical activity score (CAS). Mean (%) changes in total EOM and orbital fat volumes in study eyes treated with teprotumumab (n = 6) and placebo (n = 8) were -1,022 mm3 (-31%; P = 0.007) and -348 mm3 (-11%; P = 0.039), and -771 mm3 (-6%; P = 0.120) and 418 mm3 (4%; P = 0.084), respectively. Reductions were significantly greater with teprotumumab vs placebo (EOM, P = 0.021; fat, P = 0.016). Mean (%) changes in total EOM and orbital fat inflammation/edema grading of study eyes treated with teprotumumab were -1.82 (-31%; P = 0.005) and -1 (P = 0.031), respectively. Patients administered teprotumumab exhibited improvements in proptosis (83%), diplopia (67%), and resolution of activity determined by CAS (50%). In this OPTIC-J trial substudy, reductions in orbital soft tissue volumes and inflammation/edema were observed with MRI after teprotumumab treatment vs placebo; corresponding improvements in TED clinical outcomes were also observed.
NLRC5 is a known activator of MHC class I genes and a regulator of type I interferon activity. Although its expression increases in brains infected with Japanese encephalitis virus (JEV), its specific contribution to JEV pathogenesis and neuroinflammation remains unclear. We utilised in vitro cell cultures, in silico modelling, and in vivo mouse knockdown models of NLRC5 to investigate its impact on JEV replication, antiviral immune responses, central nervous system (CNS) inflammation, and overall disease progression. JEV infection upregulated NLRC5 expression in the brain, microglia, and non-neuronal cells, but not in neuronal cells. However, NLRC5 expression could be induced in neuroblastoma cells via IFN-γ treatment. Experimental modulation demonstrated that the typical antiviral restriction of JEV replication by IFN-γ is lost in NLRC5-deficient cells. Evaluation of stable cell lines expressing different NLRC5 variants showed that cytoplasmic retention and NLRC5 leucine-rich repeats (LRRs) are essential for viral restriction. Mechanistically, in silico modelling, co-immunoprecipitation, and immunofluorescence confirmed that NLRC5 binds directly to the viral NS3 protein in an LRR-dependent manner. In mouse models, in vivo knockdown of NLRC5 in the brain significantly accelerated clinical disease progression, heightened mortality, and triggered uncontrolled viral replication, indicated by elevated viral titers and NS3/NS1 expression. This viral surge induced severe neuroinflammation, as evidenced by significantly elevated levels of ASC and cleaved caspase-3 in NLRC5-deficient brains. These findings demonstrate that NLRC5 functions as a cell-type-specific antiviral regulator during JEV infection. It suppresses viral replication by directly binding to and degrading the viral NS3 protein. Loss of NLRC5 impairs IFN-γ-mediated antiviral restriction, leading to enhanced viral replication, severe neuroinflammation, and accelerated disease progression in vivo.
Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.
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Chronic inflammation and cyclooxygenase (COX)-2-mediated prostanoid signaling contribute to melanoma progression, yet their modulation by natural products remains poorly defined. We examined the effects of dogwood fruit extracts-Japanese cornel (Cornus officinalis) and two European cultivars ('Uholok', 'Yantarnyi')-on temporal prostanoid dynamics in A375 (primary tumor-derived) and MeWo (metastasis-derived) mela-noma cells. Dynamic changes rather than static levels were modeled using GAMLSS or zero-inflated Gamma models to assess time, cell line, cornel type, and dose effects. Untreated A375 cells showed time-dependent increases in PGE2, PGF2α, thromboxane B2, and 13,14-dihydro-PGE1, consistent with inducible COX-2 activation, whereas MeWo cells maintained consistently high prostanoid levels, reflecting constitutive COX-2 expression. Cornus extracts modulated these trajectories in a cell- and dose-dependent manner. In A375, low concentrations allowed prostanoid accumulation, while higher doses flattened or reversed these increases; Japanese cornel produced the strongest inhibition, whereas European cultivars showed weaker or cultivar-specific effects. MeWo cells were less responsive, with significant changes emerging only at higher doses. PGD2 and 6-keto-PGF1α remained largely unchanged, indicating selective targeting of COX-2-dependent prostanoids. Extracts also reduced accumulation of downstream prostanoids, including 15-deoxy-Δ12,14-PGJ2 and 13,14-dihydro-PGE1, particularly in A375 cells. These differences highlight a stronger susceptibility of early-stage melanoma to phytochemical intervention and support cultivar-dependent bioactivity linked to phytochemical composition. In summary, Cornus extracts selectively attenuate time-dependent trajectories of tumor-promoting prostanoids-most effectively with Japanese cornel-while sparing homeostatic mediators, warranting further investigation on their potential for melanoma chemoprevention or adjunctive therapy.
In this study, Klobuchar coefficients optimized for the Japanese region, referred to as the Klobuchar Regional (KR) model, were estimated using the International GNSS Service (IGS) Global Ionosphere Map (GIM) and evaluated against the Klobuchar GPS (KG) and Klobuchar QZSS (KQ) models. The grid points were defined based on ionospheric pierce points (IPPs) derived from Japanese GNSS stations, and the coefficients were estimated via a nonlinear least-squares approach using the vertical total electron content (VTEC) within the defined region (12.5-52.5° N, 115-170° E) under both solar minimum (2019) and solar maximum (2024) conditions. During the solar minimum, the number of distinct KG correction coefficient values was limited to fewer than 16, and intermodel correlations were found to vary with solar activity level, with the KQ-KR pair exhibiting the highest correlation for α0 (r = 0.85). Vertical Total Electron Contents (VTEC) root mean square error (RMSE) analysis indicated that KR achieved an approximately 50% improvement in accuracy relative to both KG and KQ. Furthermore, standard point positioning (SPP) results at three Japanese stations demonstrated that KR and KQ exhibited comparable performance within 0.1 m during the solar minimum, whereas KR generally outperformed KQ during the solar maximum, with the standard deviation of KR approximately half that of KQ, confirming superior stability and reliability in positioning performance.
BackgroundLactococcus cremoris YRC3780 (previously Lactococcus lactis subsp. cremoris YRC3780), isolated from kefir, has been suggested to improve sleep quality by acting on intestinal immune cells and promoting cytokine production and has been shown to improve subjective sleep quality in healthy young men without sleep problems.AimWe examined the effects of YRC3780 in subjects dissatisfied with their sleep.MethodsWe investigated the effects of daily YRC3780 intake for 8 weeks on sleep in a randomized, placebo-controlled, double-blind, parallel-group study involving 105 healthy Japanese adults with baseline Athens Insomnia Scale (AIS) scores of ≥6.SummaryAfter 8 weeks, the AIS score and the change from baseline score were significantly better in the YRC3780 group than in the placebo group. The YRC3780 group showed significant improvements compared with the placebo group in the scores for the individual AIS items related to "sleep induction" at 4 weeks and in those for "functioning capacity during the day" at 8 weeks. The percentage changes from baseline at 4 weeks for the Oguri-Shirakawa-Azumi Sleep Inventory Middle-aged and Aged version question "fell asleep quickly" and for the Japanese version of the Epworth Sleepiness Scale question about sleepiness while watching TV were significantly better in the YRC3780 group than in the placebo group. In conclusion, daily YRC3780 intake significantly improved sleep quality and alleviated daytime sleepiness and difficulty falling asleep in healthy Japanese adults with sleep complaints (UMIN-CTR, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000060004, UMIN000052586).
Pediatric intensive care units (PICUs) are well developed in Western countries and have been linked to improved survival. However, evidence comparing the outcomes between PICUs and general intensive care units (GICUs) remains inconsistent. In Japan, limited PICU capacity raises concerns that many children receive critical care in GICUs. This study compared the clinical outcomes between these settings using a national inpatient database and propensity score overlap weighting analyses. We conducted a retrospective cohort study using a national Japanese inpatient database from July 2010 to March 2022. We included mechanically ventilated children aged ≤14 years admitted to ICUs and compared patient characteristics between those treated in PICUs and GICUs. In-hospital mortality was evaluated using overlap weighting analyses. Of the 48,106 eligible patients, 36% received care in PICUs. After overlap weighting analyses, PICU care was associated with a significantly lower in-hospital mortality than GICU care (mean 2.73% vs. 3.42%; odds ratio, 0.79; 95% CI, 0.69-0.91; p = 0.001). PICU care was associated with longer overall hospital stays (mean 22.74 vs. 22.13 days; difference, +0.61 days; 95% CI, 0.30-0.93; p < 0.001) and longer ICU stays (mean 6.37 vs. 5.42 days; difference, +0.95 days; 95% CI, 0.82-1.09; p < 0.001). Most mechanically ventilated children in Japanese ICUs were treated in GICUs. Pediatric patient care in GICUs was associated with higher mortality relative to that in PICUs, underscoring the need for further centralization.
Esomeprazole, a proton pump inhibitor (PPI), is widely approved for gastroesophageal reflux disease (GERD) in adults and pediatrics globally, but prior to December 2022, its oral tablets (20 and 40 mg) were approved only for adults in China. To address unmet needs in Chinese adolescents aged 12-17 years, physiologically based pharmacokinetic (PBPK) modeling was employed to extrapolate data and support label extension, leveraging similarities in GERD pathophysiology and PK/PD relationships across ages and ethnicities. A PBPK model was developed for esomeprazole to capture the enteric-coated formulation's pharmacokinetics. The model was validated against clinical PK studies in Caucasian, Japanese, and Chinese adults and/or adolescents, demonstrating good predictions of concentration-time profiles and area under the curve (AUC) for CYP2C19-specific genotypes as well as overall populations across these ethnic groups. All predicted-to-observed ratios for AUC fell within 0.5- to 2.0-fold, with 14 out of 18 predictions within the 0.67- to 1.5-fold. This robust validation enabled the model's application to predict PK in Chinese adolescents. PBPK predictions for Chinese adolescents indicated that steady-state AUC for 20- and 40-mg doses was comparable to that in Japanese adolescents and slightly higher than in Caucasian adolescents. By integrating an established PK/PD relationship between AUC and the percentage of time with intragastric pH >4, once-daily doses of 20 or 40 mg were justified, achieving adequate acid suppression with a favorable safety profile. This PBPK-informed extrapolation was accepted by China's National Medical Products Administration (NMPA), enabling GERD indication extension to adolescents.