Two-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration with 'observe before treat-and-extend' method.

Purpose: To evaluate two-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with 'observe before treat-and-extend' (O-TAE) strategy in the real-world setting. Methods: This retrospective study included treatment-naïve nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after 3 monthly loading injections. In case of recurrence, treatment was resumed using the treat-and-extend (TAE) regimen starting from the 4th injection. In case of non-recurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following 3 loadings were analyzed. Results: 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logMAR improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the 1st year (p = 0.01), and 0.25 ± 0.22 in the 2nd year (p = 0.054). CMT decreased significantly from 357.4 ± 74.5 at baseline to 269.6 ± 48.1 in the 1st year (p < 0.001), and 279.1 ± 54.6 in the 2nd year (p < 0.001). Numbers of injections were 5.1 ± 1.7 in the first year and 3.8 ± 2.4 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after 3 loadings, 28 eyes (78%) recurred, and the average period of recurrence was 6.5 months. The remaining 8 eyes (22%) had no recurrence during the mean follow-up period of 29.7 months. Conclusion: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

RAFT Dispersion PISA with Poly(methyl methacrylate) as Stabilizer Block in Alcohol/Water: Unconventional PISA Morphology Transitions.

Reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization-induced self-assembly (PISA) was conducted in the presence of poly(methyl methacrylate) (PMMA) stabilizer in ethanol/water mixture (80/20 by volume). Two different systems were explored by utilizing (i) 2-ethylhexyl methacrylate (EHMA) and (ii) n-butyl methacrylate (BMA). The morphology transitions of these systems were investigated by varying the polymerization conditions, i.e., the presence of the solvophilic comonomer MMA, the solids content, and the target degree of polymerization (DP). As observed in conventional PISA, the presence of solvophilic comonomer, increase in solids content and target DP promoted the formation of high-order morphology. However, unusual morphology transitions were observed whereby the morphology transformed from high-order morphologies to a mixture of spherical nanoparticles, worms, and vesicles and finally to vesicles with increasing target DP. This unusual evolution may be attributed to the limited solubility of PMMA in the ethanol/water solvent mixture, whereby PMMA is soluble at the polymerization temperature but insoluble at lower temperatures.

Association between Liver Function Markers and Menstrual Cycle Irregularity in Korean Female Population.

Background: The liver plays an important role in gonadal steroid hormone metabolism, which can affect reproductive health, including the menstrual cycle. However, evidence from large population-based studies is limited. Therefore, this study aimed to investigate the association between liver function markers and menstrual cycle irregularities in premenopausal Korean women using nationwide data. Methods: This study analyzed Data from the Korea National Health and Nutrition Examination Survey 2010-2011. We investigated 3,045 premenopausal women aged 19-59 years. Liver function markers including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, and fatty liver index were analyzed. Multivariable logistic regression analysis was performed to investigate the association between liver function markers and menstrual cycle irregularity while adjusting for confounding factors. Values were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analysis was also performed. Results: Baseline characteristic analysis showed that approximately 14.4% of the study population experienced menstrual cycle irregularity. The mean age was 34.5±0.7 years. The highest quartile of serum ALT and AST levels showed significantly higher ORs for menstrual cycle irregularity (adjusted OR, 1.83; 95% CI, 1.26-2.64 and adjusted OR, 1.67; 95% CI, 1.17-2.39, respectively). A similar result was observed in the subgroup analysis. Conclusion: Liver function markers were positively associated with menstrual cycle irregularities. In clinical settings, women of reproductive age with relatively decreased liver function should be considered for regular followup of their reproductive health status.

Clinical Applicability and Safety of Conventional Frame-Based Stereotactic Techniques for Stereoelectroencephalography.

Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

Right Ventricular Subclinical Dysfunction as a Predictor of Postoperative Adverse Clinical Outcomes in Patients with Femoral Fracture.

BACKGROUND: Femoral fractures often lead to complications such as altered pulmonary hemodynamics. Right ventricular global longitudinal strain (RV GLS), which correlates with pulmonary hemodynamics, indicates the subclinical function of the right ventricle (RV). This study aimed to investigate the predictive value of RV GLS for the risk of adverse clinical composite outcomes in patients with femoral fractures. METHODS: Data were obtained from a prospective single-center cohort of patients hospitalized for femoral fractures and followed up for at least 1 year between March 2021 and October 2022. The primary outcome was the development of an adverse composite clinical event, which included pneumonia, pulmonary oedema or effusion, pulmonary thromboembolism, and all-cause mortality within the 1-year period following surgery. RESULTS: Among the 163 patients, 36 (22.09%) experienced adverse composite clinical events during 1-year follow-up. The adverse outcome group demonstrated poorer RV GLS and RV free wall strain values than the non-adverse outcome group. The optimal cut-off value of RV GLS for predicting composite adverse clinical events was -12.55%. The cumulative composite event-free survival rate was significantly lower in the RV GLS ≥ -12.55% group (log-rank p-value = 0.003). After adjusting for confounding factors, multivariate Cox proportional hazards regression analyses showed that RV GLS ≥ -12.55% independently increased the risk of composite adverse clinical events by 2.65-fold. CONCLUSIONS: Poor RV GLS is a significant predictor of adverse clinical outcomes in patients with femoral fractures. Specifically, an RV GLS value of ≥ -12.55% indicated a substantially increased risk of adverse events.

Effect of low blood pressure on prognosis of acute heart failure.

Low blood pressure (BP) is associated with poor outcomes in patients with heart failure (HF). We investigated the influence of initial BP on the prognosis of HF patients at admission, and prescribing patterns of HF medications, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB). Data were sourced from a multicentre cohort of patients admitted for acute HF. Patients were grouped into heart failure reduced ejection fraction (HFrEF) and HF mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) groups. Initial systolic and diastolic BPs were categorized into specific ranges. Among 2778 patients, those with HFrEF were prescribed ACEi, ARB, or BB at discharge, regardless of their initial BP. However, medication use in HFmrEF/HFpEF patients tended to decrease as BP decreased. Lower initial BP in HFrEF patients correlated with an increased incidence of all-cause death and composite clinical events, including HF readmission or all-cause death. However, no significant differences in clinical outcomes were observed in HFmrEF/HFpEF patients according to BP. Initial systolic (< 120 mmHg) and diastolic (< 80 mmHg) BPs were independently associated with a 1.81-fold (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.349-2.417, p < 0.001) and 2.24-fold (OR 2.24, 95% CI 1.645-3.053, p < 0.001) increased risk of long-term mortality in HFrEF patients, respectively. In conclusion, low initial BP in HFrEF patients correlated with adverse clinical outcomes, and BP < 120/80 mmHg independently increased mortality. However, this relationship was not observed in HFmrEF/HFpEF patients.

Respiratory Viruses Co-detection on a Multiplex RT-PCR Panel: a Comparative Clinical Study.

BACKGROUND: The FilmArray Respiratory Panel RP 2.1 plus (FilmArray RP) is a point-of-care syndromic panel for respiratory pathogens. Although highly valuable in the clinical settings, the co-detection of pathogens in FilmArray RP may confound result interpretation. METHODS: Nasopharyngeal swab specimens collected from patients with respiratory symptoms were analyzed by comparing co-detection results from FilmArray RP with those of Allplex Respiratory Panels (Allplex RP: Power-Chek for SARS-CoV-2). RESULTS: Out of 765 FilmArray RP tests, 143 (18.7%) showed co-detections (two: 122 (85.3%), three: 18 (12.6%), four: 2 (1.4%), and five viruses: 1 (0.7%). The most frequent co-detection was human rhinovirus/enterovirus (HRV/HEV) with respiratory syncytial virus (RSV) (22.3%, 32/143). The overall discordance rate between Film-Array RP and other tests was 32.9%. Notably, discordance in detecting adenovirus (AdV) was significant, with cases detected by FilmArray often not appearing in Allplex RP. CONCLUSIONS: Discordances were varied by virus combination. It is advisable to perform additional confirmatory testing based on clinical relevance.

Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta.

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Estimated pulse wave velocity as a forefront indicator of developing metabolic syndrome in Korean adults.

BACKGROUND/AIMS: The predictive value of the estimated pulse wave velocity (ePWV) for the development of metabolic syndrome has not yet been extensively explored. This study aimed to fill this gap by evaluating ePWV as a potential predictor of metabolic syndrome development in middle-aged Korean adults. METHODS: Using prospective data obtained from the Ansan-Ansung cohort database, participants without metabolic syndrome at baseline were studied. ePWV was calculated using specific equations based on age and blood pressure. The primary outcome was the incidence of metabolic syndrome during a median follow-up period of 187 months. RESULTS: Among the 6,186 participants, 2,726 (44.1%) developed metabolic syndrome during the follow-up period. ePWV methvalues were categorized into tertiles to assess their predictive value for the development of metabolic syndrome. An ePWV cut-off of 7.407 m/s was identified as a predictor of metabolic syndrome development, with a sensitivity of 0.743 and a specificity of 0.464. Participants exceeding this cut-off, especially those in the third tertile (8.77-14.63 m/s), had a notably higher risk of developing metabolic syndrome. Specifically, the third tertile exhibited a 52.8% cumulative incidence compared with 30.8% in the first tertile. After adjustments, those in the third tertile faced a 1.530-fold increased risk of metabolic syndrome (95% confidence interval, 1.330-1.761). CONCLUSION: ePWV is a significant predictor of the development of metabolic syndrome. This finding underscores the potential of ePWV as a cardiometabolic risk assessment tool and can thus provide useful information for primary prevention strategies.

Comparing blood pressure measurements between sitting in chairs and sitting on the floor.

BACKGROUND: The current standard approach to measuring home blood pressure (BP) involves taking measurements while sitting in a chair. In cultures where floor sitting is common, including Korea, assessing BP while sitting on the floor would be more feasible. However, there is still a lack of research investigating whether BP measurements obtained while seated in a chair and while sitting on the floor can be regarded as interchangeable. The aim of the study was to evaluate whether there is a difference between BP measurements taken while sitting in a chair and while sitting on the floor in a Korean adult. METHODS: Among the participants who visited for evaluation of pulse wave velocity, a total of 116 participants who agreed to participate in the study were randomly selected. All subjects rested for 5 min, and BP measurements were taken at 1-min intervals according to a randomly assigned order of standard method (chair-sitting) and BP in a seated on the floor (floor-sitting). RESULTS: Of the 116 participants, the median age was 68 (with an interquartile range of 59 to 75), and 82% were men. There were no significant differences in systolic BP (SBP, 129.1 ± 17.8 mmHg in chair-sitting and 130.1 ± 18.9 mmHg in floor-sitting, P = 0.228) and diastolic BP (DBP, 73.9 ± 11.4 mmHg in chair-sitting and 73.7 ± 11.4 mmHg in floor-sitting, P = 0.839) between the two positions. In addition, there was a high level of agreement between BP measurements taken in the two positions (intraclass correlation coefficients: 0.882 for SBP and 0.890 for DBP). CONCLUSION: These findings provide important insights into securing the reliability of home BP measurements through the commonly practiced floor-sitting posture in cultures where floor sitting is common. Furthermore, this could serve as substantial evidence for providing specific home BP measurement guidelines to patients who adhere to a floor-sitting lifestyle.

Microbiome dynamics in immune checkpoint blockade.

Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome. In this review, we describe recent findings from clinical trials, observational studies of human patients, and animal studies on the impact of the microbiome on the efficacy of ICB, highlighting the role of the intestinal and tumor microbiomes and the contribution of methodological advances in their study.

Facial Trauma Affects the Radiological Diagnosis of Nasal Bone Fractures.

OBJECTIVES: Timely and accurate diagnosis of nasal bone fractures (NBFs) is crucial for preserving the cosmetic and functional aspects of the nose. This study aims to identify factors influencing radiographic and computed tomography (CT) diagnosis of NBF in patients with nasal trauma. METHODS: Two hundred six patients with acute nasal trauma underwent both conventional radiography and facial bone CT. An experienced otorhinolaryngologist independently interpreted images. Results were categorized into "Concordance" or "Discrepancy" groups, with demographic and clinical data compared. RESULTS: The study classified 167 patients into "Concordance" and 39 into "Discrepancy" groups based on radiography and CT interpretations. The "discrepancy group" showed higher rates of previous nasal bone fractures (P=0.044), rhinoplasty history (P=0.044), and concomitant facial bone fractures (P=0.001). Adjusted odds ratios revealed significant associations between discrepancies and a history of nasal bone fracture (OR=5.197, 95% CI 1.165-23.171), rhinoplasty (OR=6.114, 95% CI 1.393-26.847), and concomitant facial bone fractures (OR=3.765, 95% CI 1.663-8.523). CONCLUSION: This study highlights the impact of facial trauma, including rhinoplasty, on the radiological diagnosis of NBF. Consequently, in the presence of signs of concurrent facial trauma, previous nasal trauma, or rhinoplasty history, a prompt CT scan and comprehensive evaluation are recommended for accurate diagnosis and timely treatment, ultimately improving the patient's prognosis.

Comparison of the Effects of Pilates and Yoga Exercise on the Dynamic Balancing Ability and Functional Movement of Fencers.

This study was conducted to compare and analyze whether Pilates exercise and yoga exercise help improve the performance of female fencers and prevent injury, and the dynamic balance test (LQ-YBT) and functional movement screening (FMS) test score of the elite adult female fencers were compared and analyzed as evaluation indicators. Participants were randomly classified into Pilates (n = 10) and yoga groups (n = 10), members of which took part in 50 min of exercise (5 min of warm-up, 40 min of main exercise, and 5 min of cool-down) twice weekly for eight weeks. The results obtained from this study were analyzed via independent t-test and 2-way ANOVA. The results were as follows: LQ-YBT measures (reaching distance) increased significantly for both groups, as did FMS scores (deep squat, hurdle step, inline lunge, shoulder mobility, active straight-leg raise, trunk-stability push-up, and rotary stability). These results suggest that Pilates exercise and yoga exercise might be likely effective in improving the performance of adult female fencers and injury prevention by increasing their dynamic balance ability and functional movement.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Data Resource Profile: The Cancer Public Library Database in South Korea.

This paper provides a comprehensive overview of the Cancer Public Library Database (CPLD), established under the Korean Clinical Data Utilization for Research Excellence project (K-CURE). The CPLD links data from four major population-based public sources: the Korea National Cancer Incidence Database in the Korea Central Cancer Registry, cause-of-death data in Statistics Korea, the National Health Information Database in the National Health Insurance Service, and the National Health Insurance Research Database in the Health Insurance Review & Assessment Service. These databases are linked using an encrypted resident registration number. The CPLD, established in 2022 and updated annually, comprises 1,983,499 men and women newly diagnosed with cancer between 2012 and 2019. It contains data on cancer registration and death, demographics, medical claims, general health checkups, and national cancer screening. The most common cancers among men in the CPLD were stomach (16.1%), lung (14.0%), colorectal (13.3%), prostate (9.6%), and liver (9.3%) cancers. The most common cancers among women were thyroid (20.4%), breast (16.6%), colorectal (9.0%), stomach (7.8%), and lung (6.2%) cancers. Among them, 571,285 died between 2012 and 2020 owing to cancer (89.2%) or other causes (10.8%). Upon approval, the CPLD is accessible to researchers through the K-CURE portal. The CPLD is a unique resource for diverse cancer research to investigate medical use before a cancer diagnosis, during initial diagnosis and treatment, and long-term follow-up. This offers expanded insight into healthcare delivery across the cancer continuum, from screening to end-of-life care.

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.

Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial.

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to ß-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers. Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication. Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339). Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.