Helicobacter pylori East Asian type CagA hijacks more SHIP2 by its EPIYA-D motif to potentiate the oncogenicity.

CagA is a significant oncogenic factor injected into host cells by Helicobacter pylori, which is divided into two subtypes: East Asian type (CagAE), characterized by the EPIYA-D motif, and western type (CagAW), harboring the EPIYA-C motif. CagAE has been reported to have higher carcinogenicity than CagAW, although the underlying reason is not fully understood. SHIP2 is an intracellular phosphatase that can be recruited by CagA to perturb the homeostasis of intracellular signaling pathways. In this study, we found that SHIP2 contributes to the higher oncogenicity of CagAE. Co-Immunoprecipitation and Pull-down assays showed that CagAE bind more SHIP2 than CagAW. Immunofluorescence staining showed that a higher amount of SHIP2 recruited by CagAE to the plasma membrane catalyzes the conversion of PI(3,4,5)P3 into PI(3,4)P2. This alteration causes higher activation of Akt signaling, which results in enhanced IL-8 secretion, migration, and invasion of the infected cells. SPR analysis showed that this stronger interaction between CagAE and SHIP2 stems from the higher affinity between the EPIYA-D motif of CagAE and the SH2 domain of SHIP2. Structural analysis revealed the crucial role of the Phe residue at the Y + 5 position in EPIYA-D. After mutating Phe of CagAE into Asp (the corresponding residue in the EPIYA-C motif) or Ala, the activation of downstream Akt signaling was reduced and the malignant transformation of infected cells was alleviated. These findings revealed that CagAE hijacks SHIP2 through its EPIYA-D motif to enhance its carcinogenicity, which provides a better understanding of the higher oncogenic risk of H. pylori CagAE.

Study of sex-biased differences in genomic profiles in East Asian hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients' prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK-STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient's age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331-32.677, P < 0.001; Hazard ratio = 2.547, 95% CI 1.195-5.432, P = 0.016, respectively). In summary, this study provides valuable insights into understanding sex disparity in HCC in the East Asian population. Validation through larger cohorts and extensive sequencing efforts is warranted.

Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.

PURPOSE: Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility. METHODS: In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan. RESULTS: The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 - 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population. CONCLUSION: This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

T2DM may exert a protective effect against digestive system tumors in East Asian populations: a Mendelian randomization analysis.

Introduction: Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included. Methods: Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively. Results: T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044). Conclusion: T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.

Delineation of the phenotypes and genotypes of PIK3CA-related overgrowth spectrum in East asians.

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term to describe a diverse range of developmental disorders. Research to date has predominantly emerged from Europe and North America, resulting in a notable scarcity of studies focusing on East Asian populations. Currently, the prevalence and distribution of PIK3CA variants across various genetic loci and their correlation with distinct phenotypes in East Asian populations remain unclear. This study aims to elucidate the phenotype-genotype correlations of PROS in East Asian populations. We presented the phenotypes and genotypes of 82 Chinese patients. Among our cohort, 67 individuals carried PIK3CA variants, including missense, frameshift, and splice variants. Six patients presented with both PIK3CA and an additional variant. Seven PIK3CA-negative patients exhibited overlapping PROS manifestations with variants in GNAQ, AKT1, PTEN, MAP3K3, GNA11, or KRAS. An integrative review of the literature pertaining to East Asian populations revealed that specific variants are uniquely associated with certain PROS phenotypes. Some rare variants were exclusively identified in cases of megalencephaly and diffuse capillary malformation with overgrowth. Non-hotspot variants with undefined oncogenicity were more common in CNS phenotypes. Diseases with vascular malformation were more likely to have variants in the helical domain, whereas phenotypes involving adipose/muscle overgrowth without vascular abnormalities predominantly presented variants in the C2 domain. Our findings underscore the unique phenotype-genotype patterns within the East Asian PROS population, highlighting the necessity for an expanded cohort to further elucidate these correlations. Such endeavors would significantly facilitate the development of PI3Kα selective inhibitors tailored for the East Asian population in the future.

Adaptive evolution of two distinct adaptive haplotypes of Neanderthal origin at the immunoglobulin heavy-chain locus in East Asian and European populations.

Immunoglobulins have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations.

Association between Subjective Cognitive Complaints and Sleep Disturbance among Community-Dwelling Elderly Individuals in Japan.

Subjective cognitive complaints (SCCs) are a crucial modifiable risk factor for dementia. There is increasing interest in the association between SCC and sleep disturbance; however, the effects of sleep disturbance on SCC development among community-dwelling elderly individuals in Japan remain unclear. We aimed to cross-sectionally investigate the association between SCC and sleep disturbance, with adjustment for multiple factors related to cognitive decline, among 241 community-dwelling elderly persons without cognitive impairment. The measures were SCCs (Kihon Checklist-Cognitive Function, KCL-CF), sleep disturbance (Japanese version of the Athens Insomnia Scale, AIS-J), general cognitive function (Mini-Mental State Examination), and depressive symptoms (five-item version of the Geriatric Depression Scale [GDS-5]). The following data were collected: sex, age, educational history, whether the participants had visited a medical institution for diseases (hypertension, diabetes, hyperlipidemia, heart disease), and the presence/absence of established risk factors (hearing loss, history of head injury, drinking habits, smoking habits, social isolation, and physical inactivity and activity). Based on the KCL-CF, 96 and 145 participants were considered to have and lack SCCs, respectively. On logistic regression analysis, the AIS-J score and smoking history were significantly associated with SCCs. Our findings suggest that sleep disturbance is associated with SCC development among community-dwelling elderly people in Japan. Evaluating and managing sleep disturbances can be important in preventing SCCs and dementia.

Impacts of demographic factors and the COVID-19 pandemic on job stress in Japanese childcare workers.

BACKGROUND: Japan has a shortage of childcare personnel, and the high levels of stress causing turnover in childcare workers must be urgently resolved. However, there is a lack of knowledge regarding the characteristics and influencing factors of job stress in Japanese childcare workers. OBJECTIVE: This study aimed to evaluate the job stress of childcare workers and explore the influence of demographic factors and the COVID-19 pandemic on such stress. METHODS: The data were collected through an Internet survey from 2,472 respondents. A 23-item version of the Brief Job Stress Questionnaire was used to measure occupational stress in childcare workers. The instrument is recommended in the stress-check program implemented as a mental health measure in workplaces in Japan. RESULTS: The percentage of childcare workers with high stress exceeded that of general workers. Multiple regression analyses showed that the only factor affecting all job stressors and social support was the fear of contracting COVID-19. Job stressors and the COVID-19 pandemic had a significant large effect on stress responses. Additionally, being married and having children moderated childcare workers' stress. CONCLUSIONS: This study provided basic data regarding job stress in Japanese childcare workers and compared them with those of other professionals. In the future, it will be necessary to clarify how stress is related to turnover intention and turnover in Japanese childcare workers to promote their career continuity.

Prevalence of Antibiotic Resistance and Virulence Genes in Escherichia coli Carried by Migratory Birds on the Inner Mongolia Plateau of Northern China from 2018 to 2023.

(1) Background: Antibiotic resistance in bacteria is an urgent global threat to public health. Migratory birds can acquire antibiotic-resistant and pathogenic bacteria from the environment or through contact with each other and spread them over long distances. The objectives of this study were to explore the relationship between migratory birds and the transmission of drug-resistant pathogenic Escherichia coli. (2) Methods: Faeces and swab samples from migratory birds were collected for isolating E. coli on the Inner Mongolia Plateau of northern China from 2018 to 2023. The resistant phenotypes and spectra of isolates were determined using a BD Phoenix 100 System. Conjugation assays were performed on extended-spectrum ß-lactamase (ESBL)-producing strains, and the genomes of multidrug-resistant (MDR) and ESBL-producing isolates were sequenced and analysed. (3) Results: Overall, 179 isolates were antibiotic-resistant, with 49.7% MDR and 14.0% ESBL. Plasmids were successfully transferred from 32% of ESBL-producing strains. Genome sequencing analysis of 91 MDR E. coli strains identified 57 acquired resistance genes of 13 classes, and extraintestinal pathogenic E. coli and avian pathogenic E. coli accounted for 26.4% and 9.9%, respectively. There were 52 serotypes and 54 sequence types (STs), including ST48 (4.4%), ST69 (4.4%), ST131 (2.2%) and ST10 (2.2%). The international high-risk clonal strains ST131 and ST10 primarily carried blaCTX-M-27 and blaTEM-176. (4) Conclusions: There is a high prevalence of multidrug-resistant virulent E. coli in migratory birds on the Inner Mongolian Plateau. This indicates a risk of intercontinental transmission from migratory birds to livestock and humans.

Cone-beam CT evaluation of post-extraction alveolar bone changes at the maxillary incisor sites in an East Asian population: A cross-sectional study.

Objective: Understanding the characteristics of alveolar bone resorption in an East Asian population after maxillary incisor extraction and providing a reference for implant treatment plans. Study design: Cone-beam computerized tomography (CBCT) data of 125 East Asian patients with unilateral extraction of maxillary incisors for 3 months were collected. The alveolar bone width and height in the extraction sites were measured and compared with the corresponding contralateral sites. Results: The differences in alveolar bone width between the extraction site and contralateral site were as follows: 4.11 mm, 2.68 mm, and 2.09 mm (3 mm, 5 mm, 7 mm apical from CEJ of the contralateral tooth). Data are expressed as the median. The horizontal resorption ratio of alveolar bone was 49.94 %, 31.5 %, and 24.46 %. The difference in alveolar bone height was 0.78 mm. The vertical resorption ratio was 7.78 %. The resorption did not differ significantly between sexes and was not significantly affected by tooth positions. Conclusions: In the studied East Asian population, significant horizontal and vertical alveolar bone resorption occurs after natural healing of maxillary incisor extraction for 3 months. The closer to the alveolar ridge crest, the more significant the horizontal resorption, resulting in an "inverted triangle" shape residual alveolar bone.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

BACKGROUND: Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. METHODS: SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. RESULTS: Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p = 0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p = 0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p = 0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p = 0.974), showed no significant correlation with facial aging. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.

Agreements for conserving migratory shorebirds in the Asia-Pacific are better fit for addressing habitat loss than hunting.

A full-life cycle approach is a tenet of migratory species conservation, yet the degree to which this is achieved remains largely unassessed. This knowledge gap can be addressed using the concept of social-ecological fit, understood as the match between governance and ecological dimensions. Here, we assess the social-ecological fit for conserving migratory shorebirds in the Asia-Pacific, focusing on habitat loss and hunting. We identify the governance architectures for addressing these two threats and then assess the coordinating capacity of each architecture, measure institutional coverage for each species across their range, and determine the degree of institutional connectivity along their migratory network. We find that social-ecological fit is higher for the governance of habitat designation than for hunting management, with implications for governance practice. Analyses of social-ecological fit thus provide critical insights on the potential effectiveness of governance and therefore are a useful first step for migratory species conservation.

Evolutionary profiles and complex admixture landscape in East Asia: New insights from modern and ancient Y chromosome variation perspectives.

Human Y-chromosomes are characterized by nonrecombination and uniparental inheritance, carrying traces of human history evolution and admixture. Large-scale population-specific genomic sources based on advanced sequencing technologies have revolutionized our understanding of human Y chromosome diversity and its anthropological and forensic applications. Here, we reviewed and meta-analyzed the Y chromosome genetic diversity of modern and ancient people from China and summarized the patterns of founding lineages of spatiotemporally different populations associated with their origin, expansion, and admixture. We emphasized the strong association between our identified founding lineages and language-related human dispersal events correlated with the Sino-Tibetan, Altaic, and southern Chinese multiple-language families related to the Hmong-Mien, Tai-Kadai, Austronesian, and Austro-Asiatic languages. We subsequently summarize the recent advances in translational applications in forensic and anthropological science, including paternal biogeographical ancestry inference (PBGAI), surname investigation, and paternal history reconstruction. Whole-Y sequencing or high-resolution panels with high coverage of terminal Y chromosome lineages are essential for capturing the genomic diversity of ethnolinguistically diverse East Asians. Generally, we emphasized the importance of including more ethnolinguistically diverse, underrepresented modern and spatiotemporally different ancient East Asians in human genetic research for a comprehensive understanding of the paternal genetic landscape of East Asians with a detailed time series and for the reconstruction of a reference database in the PBGAI, even including new technology innovations of Telomere-to-Telomere (T2T) for new genetic variation discovery.

Investigation of the myopic outcomes of the newer intraocular lens power calculation formulas in Korean patients with long eyes.

This study investigated the underlying causes of the myopic outcomes of the optic-based newer formulas (Barrett Universal II, EVO 2.0, Kane, Hoffer-QST and PEARL-DGS) in long Korean eyes with Alcon TFNT intraocular lens (IOL) implantation. Postoperative data from 3100 randomly selected eyes of 3100 patients were analyzed to compare the reference back-calculated effective lens positions (ELPs) based on the Haigis formula using conventional axial length (AL) and Cooke-modified AL (CMAL) with the predicted ELP of each single- and triple-optimized Haigis formula applied to AL- and CMAL. Contrary to the AL-applied Haigis formula, the predicted ELP curve of the CMAL-applied, single-optimized Haigis formula, simulating the methods of the newer formulas, exhibited a significant upward deviation from the back-calculated ELP in long eyes. The relationship between the AL and anterior chamber depth in our long-eyed population differed from that in the base population of the PEARL-DGS formula. The myopic outcomes in long eyes appeared to stem from the substantial overestimation of the postoperative IOL position with AL modification, leading to the implantation of inappropriately higher-powered IOLs. This discrepancy may be attributed to the ethnic differences in ocular biometrics, particularly the relatively smaller anterior segment in East Asian patients with long AL.

Longitudinal analysis of epigenome-wide DNA methylation reveals novel loci associated with BMI change in East Asians.

BACKGROUND: Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations. METHODS: This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years. RESULTS: We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change. CONCLUSION: This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

The impact of eco-preneurship and green technology on greenhouse gas emissions - An analysis of East Asian economies.

The pressing need to address the effects of rising greenhouse gas emissions on the environment has become a global concern. Policymakers, governments, and stakeholders advocate a sustainable clean environment. Therefore, green technology and eco-entrepreneurship initiatives are being implemented to reduce these emissions. Despite their efforts in sustainable environments, there is insufficient research on how these initiatives impact economies. This study explores the impact of eco-entrepreneurship and green technology on reducing greenhouse gas emissions in East Asia. Using China and Japan, ranked the first and fifth highest greenhouse gas emitters globally, as case studies, the study employed ARDL and NARDL models for empirical analysis. The findings show that short-run linear estimates of eco-entrepreneurship are significant only in China, while nonlinear short-run estimates are significant for both China and Japan. Comparably, short-run linear estimates of green technology are significant for both China and Japan, while nonlinear coefficient estimates are significant only in Japan. The linear estimate of eco-entrepreneurship was significant and negative in both countries. The coefficient estimates for green technology are significant and negative for both countries. In the nonlinear model, the positive shock coefficient estimates for eco-entrepreneurship are negative and significant in China and Japan. These initiatives are vital for reducing greenhouse gas emissions and improving East Asian economies.

Anti-Inflammatory, Analgesic, Functional Improvement, and Chondroprotective Effects of Erigeron breviscapus (Vant.) Hand.-Mazz. Extract in Osteoarthritis: An In Vivo and In Vitro Study.

Osteoarthritis (OA) is a degenerative bone disease characterized by inflammation as a primary pathology and currently lacks therapeutic interventions to impede its progression. Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) is an east Asian herbal medicine with a long history of use and a wide range of confirmed efficacy against cardiovascular and central nervous system diseases. The purpose of this study is to evaluate whether EB is worthy of further investigation as a treatment for OA based on anti-inflammatory activity. This study aims to assess the potential of EB as a treatment for OA, focusing on its anti-inflammatory properties. Analgesic effects, functional improvements, and inhibition of cartilage destruction induced by EB were evaluated in acetic acid-induced peripheral pain mice and monosodium iodoacetate-induced OA rat models. Additionally, the anti-inflammatory effect of EB was assessed in serum and cartilage tissue in vivo, as well as in lipopolysaccharide-induced RAW 264.7 cells. EB demonstrated a significant alleviation of pain, functional impairment, and cartilage degradation in OA along with a notable inhibition of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, matrix metalloproteinases 13, and nitric oxide synthase 2, both in vitro and in vivo, in a dose-dependent manner compared to the active control. Accordingly, EB merits further exploration as a potential disease-modifying drug for OA, capable of mitigating the multifaceted pathology of osteoarthritis through its anti-inflammatory properties. Nonetheless, additional validation through a broader experimental design is essential to substantiate the findings of this study.

Climate, diseases and medicine: the welfare of soldiers during the East Asian War of 1592-1598.

This article examines the care provided for the welfare of soldiers by the three combatant countries - China, Korea and Japan - during the East Asian War of 1592-8. Also known as the Imjin War, this large-scale military conflict can also be understood as an encounter between different state cultures and strategies of military medicine. This study focuses on cold-induced injuries, epidemic outbreaks and external wounds suffered during the war. I illuminate provision of prophylactic measures against cold by the Ming state, as well as attempts by the Sino-Choson medical alliance to manage epidemics and treat wounded soldiers. I contrast these measures with the lack of similar centralised support for the Japanese forces, and examine the effect these differences had upon on military outcomes during the war. The difference in the amount of time, efforts and resources that the three combatant states devoted to sick and injured soldiers has implications not only for our understanding of the war but also for illuminating the early modern history of military medicine in East Asia. By exploring East Asian military medicine during and after the Imjin War, this article responds to recent calls for more detailed examination of histories of military medicine in premodern periods and non-European regions.