Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.

Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions. Conclusions Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL–COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL–COL ball. CONCLUSION Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Background: Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. Results: PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. Conclusions In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.