Using oral molecular hydrogen supplements to combat microinflammation in humans: a pilot observational study.

Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH2) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH2, OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs.

Enhancing the Central Venous Catheterization Competency of Medical Students through a Specialized Team and an Interactive Response System: A pre-post study.

Background: Central venous catheterization (CVC) is a critical clinical procedure. To avoid complications, possessing good knowledge regarding the CVC care bundle and skills for the proper insertion and maintenance of CVC are important. Objectives: To evaluate the effectiveness of an educational intervention and the use of an interactive response system in enhancing the CVC bundle care and insertion skills of medical students undergoing critical care medicine training. Materials and Methods: Sixth-year medical students (equivalent to fourth-year students in the United States) engaged in didactic lessons, interactive demonstrations, and simulator training facilitated by a CVC team comprising three thoracic and two vascular surgeons (all with a minimum 5 years of experience in central venous access) during their intensive care unit (ICU) rotation. Self-reported knowledge and confidence levels were assessed using pre-and posttests administered through the Zuvio App, an interactive response system. Results: A total of 60 students underwent the educational intervention, of which 54 completed the pretest and 40 completed the posttest. In the posttest, significant improvement was found in the CVC bundle care competency and understanding (P = 0.002), preprocedural preparation (P = 0.002), insertion procedures (P = 0.004), complications (P = 0.003), and insertion depth decisions (P = 0.001). Staff and students reported that assessment and interaction via the Zuvio App were valuable, practical, and feasible in a clinical setting, providing trainees with an individual competency portfolio of receiving precise medical education. Conclusions: Integrating the training provided by a specialized team with an interactive response system enhanced the knowledge and competency level in CVC insertion among medical students in this study.

Molecular Hydrogen as a Promising Therapy Could Be Linked With Increased Resting Treg Cells or Decreased Fas+ T Cell Subsets in a IgG4-PF-ILD Patient: A Case Report.

BACKGROUND/AIM: Progressive fibrosing interstitial lung disease (PF-ILD) refers to a group of chronic lung conditions commonly associated with immunoglobulin G4-related disorders. It is characterized by progressive scarring (fibrosis) within the pulmonary interstitium, resulting in respiratory failure and early mortality. Some patients do not respond to standard therapeutic interventions. Numerous studies have confirmed the anti-inflammatory and antioxidant properties of molecular hydrogen in various disease models. CASE REPORT: In this report, we present a case study of an 85-year-old female diagnosed with suspected IgG4-related PF-ILD complicated by hospital-acquired pneumonia. On the fourth day of hydrogen-assisted therapy, a noticeable improvement in lung infiltrations was observed in chest X-rays as the patient gradually progressed towards weaning off mechanical ventilation. To assess treatment responses, we compared immune phenotypes before and after hydrogen treatment. A marked increase was observed in resting regulatory T cell levels after treatment, accompanied by a notable decrease in Fas+ helper T cell and cytotoxic T cell subtypes. CONCLUSION: This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future.

Immunomodulatory and anti-angiogenesis effects of excavatolide B and its derivatives in alleviating atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 µM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.

IVIG as a Promising Therapy for Methotrexate-induced Life-threatening Neutropenic Enterocolitis in an Elderly Patient With Rheumatoid Arthritis: A Case Report and Literature Review.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with the functional impairment of multiple joints and the destruction of bone and cartilage. Methotrexate (MTX) is a first-line drug commonly used to treat RA; however, even low doses of MTX can potentially cause rare but severe adverse reactions, such as neutropenic enterocolitis (NE), a life-threatening disease characterized by intestinal mucosal damage and immunodeficiency. CASE REPORT: Here, we report on an 82-year-old RA patient who developed life-threatening NE after ten years of low-dose MTX treatment. The condition of the patient rapidly worsened, requiring emergency electrical cardioversion and intravenous treatment with immunoglobulin (IVIG). Immunophenotypic responses were analyzed before and after treatment to evaluate therapeutic efficacy. CONCLUSION: This case highlights the importance of monitoring elderly patients with RA receiving low-dose MTX treatment for the potential accumulation of MTX toxicity. Our findings also illustrate the importance of providing timely IVIG therapy for MTX-induced NE.

Health Care Trainees' and Professionals' Perceptions of ChatGPT in Improving Medical Knowledge Training: Rapid Survey Study.

BACKGROUND: ChatGPT is a powerful pretrained large language model. It has both demonstrated potential and raised concerns related to knowledge translation and knowledge transfer. To apply and improve knowledge transfer in the real world, it is essential to assess the perceptions and acceptance of the users of ChatGPT-assisted training. OBJECTIVE: We aimed to investigate the perceptions of health care trainees and professionals on ChatGPT-assisted training, using biomedical informatics as an example. METHODS: We used purposeful sampling to include all health care undergraduate trainees and graduate professionals (n=195) from January to May 2023 in the School of Public Health at the National Defense Medical Center in Taiwan. Subjects were asked to watch a 2-minute video introducing 5 scenarios about ChatGPT-assisted training in biomedical informatics and then answer a self-designed online (web- and mobile-based) questionnaire according to the Kirkpatrick model. The survey responses were used to develop 4 constructs: "perceived knowledge acquisition," "perceived training motivation," "perceived training satisfaction," and "perceived training effectiveness." The study used structural equation modeling (SEM) to evaluate and test the structural model and hypotheses. RESULTS: The online questionnaire response rate was 152 of 195 (78%); 88 of 152 participants (58%) were undergraduate trainees and 90 of 152 participants (59%) were women. The ages ranged from 18 to 53 years (mean 23.3, SD 6.0 years). There was no statistical difference in perceptions of training evaluation between men and women. Most participants were enthusiastic about the ChatGPT-assisted training, while the graduate professionals were more enthusiastic than undergraduate trainees. Nevertheless, some concerns were raised about potential cheating on training assessment. The average scores for knowledge acquisition, training motivation, training satisfaction, and training effectiveness were 3.84 (SD 0.80), 3.76 (SD 0.93), 3.75 (SD 0.87), and 3.72 (SD 0.91), respectively (Likert scale 1-5: strongly disagree to strongly agree). Knowledge acquisition had the highest score and training effectiveness the lowest. In the SEM results, training effectiveness was influenced predominantly by knowledge acquisition and partially met the hypotheses in the research framework. Knowledge acquisition had a direct effect on training effectiveness, training satisfaction, and training motivation, with ß coefficients of .80, .87, and .97, respectively (all P<.001). CONCLUSIONS: Most health care trainees and professionals perceived ChatGPT-assisted training as an aid in knowledge transfer. However, to improve training effectiveness, it should be combined with empirical experts for proper guidance and dual interaction. In a future study, we recommend using a larger sample size for evaluation of internet-connected large language models in medical knowledge transfer.

Functional implications of rs9373441 with FOXP3+Treg and Tr1 for the clinical effectiveness of csDMARDs in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis. Particularly, individuals with the TT allele at rs9373441 exhibited a more favorable response, characterized by a significant increase in FOXP3 + Treg and Type 1 regulatory T cells (Tr1) (p = 0.04, 0.02) and a decrease in Effector T helper cells (Effector Th) (p = 0.03). The GATA3-GCM2-PTH and GATA3-FOXO1-FOXP3 pathways were implicated. RNA-sequencing (RNA-seq) analysis revealed increased expression levels of UTRN, PTH2R, FOXO1, and FOXO3 in good and moderate responders (p = 0.01, 0.03, 0.0005, and 0.02). Notably, the change in FOXP3 + Treg and Tr1 was positively correlated with UTRN expression (both p = 0.03). These findings underscore the critical link between rs9373441 and the response to csDMARDs, empowering clinicians to tailor treatments for enhanced outcomes in patients with RA.

Therapeutic Effects of Treating COVID-19 Vaccine-Induced Anti-TIF1-γ-Positive Dermatomyositis.

An increase in skin-related autoimmune disorders has been reported as an adverse effect of coronavirus disease 2019 (COVID-19) vaccines. We present the case of a 90-year-old Taiwanese female who was newly diagnosed with anti-transcription intermediary factor 1-gamma (anti-TIF1-γ)-positive dermatomyositis (DM) after receiving a second dose of the AstraZeneca COVID-19 vaccine. Under treatment with prednisolone and monoclonal antibody therapy of abatacept, her skin lesions improved, and her muscle power increased. The serum creatinine phosphokinase level decreased from 4858 to 220 U/L, and the anti-TIF1-γ antibody titer decreased from 202 to 99. Flow cytometry data showed an increase in T cells, while NK cells, B cells (CD19), and plasma blasts all decreased. These findings suggest that standard DM treatment might be beneficial to patients with COVID-19 vaccine-induced DM.

Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis.

BACKGROUND/AIM: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. MATERIALS AND METHODS: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. RESULTS: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). CONCLUSION: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.

Predicting the clinical efficacy of JAK inhibitor treatment for patients with rheumatoid arthritis based on Fas+ T cell subsets.

Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28-ESR. Overall, 16 cell subsets presented significant differences between the non-response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28-ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi.

Evaluation of the safety and potential lipid-lowering effects of oral hydrogen-rich coral calcium (HRCC) capsules in patients with metabolic syndrome: a prospective case series study.

Background: Metabolic syndrome is characterized by a cluster-like occurrence of conditions such as hypertension, hyperglycaemia, elevated low-density lipoprotein (LDL) cholesterol or triglycerides (TG) and high visceral fat. Metabolic syndrome is linked to the build-up of plaque within the artery, which leads to disorders of the circulatory, nervous and immune systems. A variety of treatments target the regulation of these conditions; nevertheless, they remain dominant risk factors for the development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), which affect 26.9% of the US population. Management and intervention strategies for improving cholesterol and/or TG are worthwhile, and recent studies on hydrogen treatment are promising, particularly as molecular hydrogen is easily ingested. This study aimed to investigate the lipid-lowering effects and quality of life (QOL) improvement of hydrogen-rich coral calcium (HRCC) in patients with metabolic syndrome. Methods: The patients, all Taiwanese, were randomly assigned to 3 different doses (low, medium, and high) of HRCC capsules. The primary outcome was the adverse effects/symptoms during this 4-week use of HRCC capsules. The secondary outcome was lipid profile changes. Complete blood count, inflammatory biomarkers, and QOL were also measured before and after the course of HRCC. Results: Sixteen patients with metabolic syndrome completed this study (7 males, 9 females; mean age: 62 years; range: 32-80). No obvious adverse effects were recorded. Only changes in blood TG reached significance. The baseline TG value was 193.19 µL (SD = 107.44), which decreased to 151.75 µL (SD = 45.27) after 4 weeks of HRCC (p = 0.04). QOL showed no significant changes. Conclusion: This study is the first human clinical trial evaluating HRCC capsules in patients with metabolic syndrome. Based on the safety and potential TG-lowering effects of short-term HRCC, further long-term investigations of HRCC are warranted. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05196295].

Interleukin 26 Induces Macrophage IL-9 Expression in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease with chronic inflammation, bone erosion, and joint deformation. Synovial tissue in RA patients is full of proinflammatory cytokines and infiltrated immune cells, such as T help (Th) 9, Th17, macrophages, and osteoclasts. Recent reports emphasized a new member of the interleukin (IL)-10 family, IL-26, an inducer of IL-17A that is overexpressed in RA patients. Our previous works found that IL-26 inhibits osteoclastogenesis and conducts monocyte differentiation toward M1 macrophages. In this study, we aimed to clarify the effect of IL-26 on macrophages linking to Th9 and Th17 in IL-9 and IL-17 expression and downstream signal transduction. Murine and human macrophage cell lines and primary culture cells were used and stimulated by IL26. Cytokines expressions were evaluated by flow cytometry. Signal transduction and transcription factors expression were detected by Western blot and real time-PCR. Our results show that IL-26 and IL-9 colocalized in macrophage in RA synovium. IL-26 directly induces macrophage inflammatory cytokines IL-9 and IL-17A expression. IL-26 increases the IL-9 and IL-17A upstream mechanisms IRF4 and RelB expression. Moreover, the AKT-FoxO1 pathway is also activated by IL-26 in IL-9 and IL-17A expressing macrophage. Blockage of AKT phosphorylation enhances IL-26 stimulating IL-9-producing macrophage cells. In conclusion, our results support that IL-26 promotes IL-9- and IL-17-expressing macrophage and might initiate IL-9- and IL-17-related adaptive immunity in rheumatoid arthritis. Targeting IL-26 may a potential therapeutic strategy for rheumatoid arthritis or other IL-9 plus IL-17 dominant diseases.

2023 Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) Joint Consensus on Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.

Applying the Student Response System in the Online Dermatologic Video Curriculum on Medical Students' Interaction and Learning Outcomes during the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted medical education worldwide. Online lecture is increasingly prevalent in higher education, but students' completion rate is quite low. Aims: This study aimed to determine the effectiveness of the student response system (SRS) in the online dermatologic video curriculum on medical students. Methods: A prospective study was conducted on 176 undergraduate fourth-year medical students. The online video lecture was integrated with SRS. Results: A total of 173 students completed the pre-test, and the attendance rate (pre-test/total) was 98.3%. A total of 142 students completed the post-test, and the completion rate (post-test/pre-test) was 82.8%. The post-test score (83.69 ± 4.34) was found to be significantly higher than that of the pre-test (62.69 ± 6.08, P =0.0002). A total of 138 students completed the questionnaire, and 92% of students opined that SRS was easy to operate. 86% of students agreed with the fact that the use of SRS could increase their learning performance by interacting with teachers. In the open-ended question, students stated that SRS offered opportunities for student-faculty interaction, allowed them to get immediate feedback, and promote active participation. Conclusions: These results highlight that the integration of SRS in the online video curriculum increases students' completion rates and learning outcomes. Moreover, the SRS is easy to operate for the students and enhances student-faculty interaction. The SRS may be adopted in online learning during this challenging time.

KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case-Control Study.

Objective: Krebs von den Lungen-6 (KL-6) is expressed on regenerating type II pneumocytes and has been recognized as biomarkers in interstitial lung disease (ILD). We aim to identify the role of the serum KL-6 level in patients with newly diagnosed Sjögren syndrome (SS), as well as the correlation between the immunoassays. Methods: Patients with newly diagnosed SS and receiving HRCT for clinical reason during follow-up were included. Baseline KL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced turbidimetric immunoassay (LETIA). Results: Of the 39 patients, 21 (53.85%) developed interstitial lung disease (ILD) by the conclusion of the follow-up period. The median time to diagnosis of ILD was 2.24 years (IQR 1.15-4.34) in the ILD group. The median serum KL-6 level, measured using ELISA, was 1232 U/mL (IQR 937-2242) and 764.5 U/mL (IQR 503.25-1035.75) in the ILD group and the non-ILD group, respectively (p = 0.001). The median LETIA for serum KL-6 was 329 U/mL (IQR 235-619) and 245 U/mL (IQR 215.25-291) in the ILD group and the non-ILD group, respectively (p = 0.074). Conclusion: Serum KL-6 levels were higher in newly diagnosed SS patients with ILD diagnosis during follow-up. Thus, the serum KL-6 level can serve as a valuable biomarker to identify hidden ILD in patients with newly diagnosed SS patients. However, the immunoassay procedure may influence the efficacy of the prediction and its clinical association.

Association between Clinical Use of Colchicine and Risk of Type 2 Diabetes Mellitus among Gouty Patients: A Nationwide Cohort Study.

BACKGROUND: Gout is the most common form of inflammatory arthritis in adults. Even though a link between gouty arthritis and type 2 diabetes mellitus (T2DM) has been reported, there is a limited understanding of the association between the anti-inflammatory agent colchicine and the risk of T2DM. This aim of this study was to assess the association between the use of colchicine and the risk of T2DM in an Asian cohort. METHODS: A retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan from 2000 to 2013. The study cohorts comprised 3841 gouty patients using colchicine (the exposed cohort) and 7682 gouty patients not using colchicine (the unexposed -cohort). The primary outcome was incident DM. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from a Cox proportional regression model were used to assess the association between colchicine use and the risk of diabetes. RESULTS: The cumulative incidence of T2DM was significantly lower in the exposed cohort (18.8%) than in the unexposed cohort (25.0%). The risk of T2DM was significantly lower in colchicine users than in non-users (adjusted HR, 0.74; 95% CI, 0.36-0.87). The inverse relationship between colchicine use and diabetes risk remained consistent across sex and age groups. CONCLUSIONS: This cohort study provides longitudinal evidence that the use of colchicine is associated with a reduced risk of T2DM. This conclusion, however, needs to be interpreted cautiously given the lack of body mass index data in the NHIRD. Further studies are needed to determine the clinical implications of this study.

Anticancer Activities of 9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c] quinolin-11-one (SJ10) in Glioblastoma Multiforme (GBM) Chemoradioresistant Cell Cycle-Related Oncogenic Signatures.

Current anticancer treatments are inefficient against glioblastoma multiforme (GBM), which remains one of the most aggressive and lethal cancers. Evidence has shown the presence of glioblastoma stem cells (GSCs), which are chemoradioresistant and associated with high invasive capabilities in normal brain tissues. Moreover, accumulating studies have indicated that radiotherapy contributes to abnormalities in cell cycle checkpoints, including the G1/S and S phases, which may potentially lead to resistance to radiation. Through computational simulations using bioinformatics, we identified several GBM oncogenes that are involved in regulating the cell cycle. Cyclin B1 (CCNB1) is one of the cell cycle-related genes that was found to be upregulated in GBM. Overexpression of CCNB1 was demonstrated to be associated with higher grades, proliferation, and metastasis of GBM. Additionally, increased expression levels of CCNB1 were reported to regulate activation of mitogen-activated protein kinase 7 (MAPK7) in the G2/M phase, which consequently modulates mitosis; additionally, in clinical settings, MAPK7 was demonstrated to promote resistance to temozolomide (TMZ) and poor patient survival. Therefore, MAPK7 is a potential novel drug target due to its dysregulation and association with TMZ resistance in GBM. Herein, we identified MAPK7/extracellular regulated kinase 5 (ERK5) genes as being overexpressed in GBM tumors compared to normal tissues. Moreover, our analysis revealed increased levels of the cell division control protein homolog (CDC42), a protein which is also involved in regulating the cell cycle through the G1 phase in GBM tissues. This therefore suggests crosstalk among CCNB1/CDC42/MAPK7/cluster of differentiation 44 (CD44) oncogenic signatures in GBM through the cell cycle. We further evaluated a newly synthesized small molecule, SJ10, as a potential target agent of the CCNB1/CDC42/MAPK7/CD44 genes through target prediction tools and found that SJ10 was indeed a target compound for the above-mentioned genes; in addition, it displayed inhibitory activities against these oncogenes as observed from molecular docking analysis.