Purpose: This study focused on analyzing the contact pressure and area on different patellar component designs in total knee arthroplasty (TKA) to evaluate biomechanics related to the patellofemoral (PF) joint. Materials and Methods: The patellar components studied included the dome design, modified dome design, and anatomical design implants. Using finite element analysis and mechanical testing, the pressure and area were evaluated. The first loading condition was simulated at flexion angles of 0°, 15°, 45°, 90°, 120°, and 150°. The second loading condition was simulated for a clinically relevant scenario, involving a 2-mm medial shift at a flexion angle of 45°. Results: For both the modified dome and anatomical designs, the contact area and pressure increased with the flexion angle. The dome design reached its maximum contact area at a flexion angle of 120°. Among the designs, the anatomical design had the largest contact area and a lower contact pressure compared to the dome and modified dome designs. However, when a medial shift of 2 mm was simulated at a 45° flexion angle, which can occur clinically, the anatomical design showed edge contact, leading to higher contact pressure and reduced contact area. In contrast, the modified dome design demonstrated the lowest contact pressure and the greatest contact area under the same shifted conditions. Conclusion These findings suggest that the design of the patellar component significantly affects patellar biomechanics and stability. Specifically, the modified dome design showed improved biomechanical effects in clinically relevant scenarios. Therefore, patellar components with a modified dome design are expected to better manage PF joint pain and reduce complications in TKA.

Objectives: Excessive sedentary behavior in youth is a major global issue, contributing to the rise in childhood obesity and metabolic diseases. International public health authorities have issued guidelines recommending that children and adolescents limit their daily sedentary time, including screen time. However, to date, no studies have explored the relationship between sedentary behavior as an exposure factor and skeletal muscle strength and mass as outcomes in this population. The present study investigated the association of sedentary behavior with handgrip strength (HGS) and appendicular lean mass (ALM) among United States adolescents. Methods: A total of 1449 adolescent participants from the National Health and Nutrition Examination Survey (2011-2014) were included. Information on sedentary behavior, specifically daily sedentary time, was obtained through a self-reported questionnaire. Muscular parameters, including HGS and ALM, were measured. To adjust for differences in body size, these parameters were divided by body mass index (BMI) and weight. Linear regression analyses were performed to evaluate the associations between daily sedentary time and each muscular parameter, adjusting for age, sex, ethnicity, annual family income, and moderate-to-vigorous physical activity (MVPA). Results: The linear regression analyses revealed negative associations between daily sedentary time and all muscular parameters, apart from absolute ALM. These included HGS (β, -0.265; standard error [SE], 0.074; p=0.001), HGS/BMI (β, -0.021; SE, 0.004; p<0.001), HGS/weight (β, -0.008; SE, 0.002; p<0.001), ALM/BMI (β, -0.008; SE, 0.003; p=0.010), and ALM/weight (β, -0.003; SE, 0.001; p=0.005). Conclusions After adjusting for MVPA, daily sedentary time was inversely associated with HGS, HGS/BMI, HGS/weight, ALM/BMI, and ALM/weight in United States adolescents.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.

Connecting peptide (C-peptide), a byproduct of insulin biosynthesis, has diverse cellular and biological functions. Particulate mat-ter 2.5 (PM2.5 ) adversely affects human skin, leading to skin thickening, wrinkle formation, skin aging, and inflammation. This study aimed to investigate the protective effects of C-peptide against PM2.5 -induced damage to skin cells, focusing on oxidative stressas a key mechanism. C-peptide mitigated NADPH oxidation and intracellular reactive oxygen species (ROS) production inducedby PM2.5 . It also suppressed PM2.5 -induced NADPH oxidase (NOX) activity and alleviated PM2.5 -induced NOX1 and NOX4 expression. C-peptide protected against PM2.5 -induced DNA damage, lipid peroxidation, and protein carbonylation. Additionally, C-peptide mitigated PM2.5 -induced apoptosis by inhibiting intracellular ROS production. In summary, our findings suggest that C-peptide mitigates PM2.5 -induced apoptosis in human HaCaT keratinocytes by inhibiting intracellular ROS production and NOX activity.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.