Background/Aims: Blocking the complement system is a promising strategy to impede the progression of metabolic dysfunction–associated steatotic liver disease (MASLD). However, the interplay between complement and MASLD remains to be elucidated. This comprehensive approach aimed to investigate the potential association between complement dysregulation and the histological severity of MASLD. Methods: Liver biopsy specimens were procured from a cohort comprising 106 Korean individuals, which included 31 controls, 17 with isolated steatosis, and 58 with metabolic dysfunction–associated steatohepatitis (MASH). Utilizing the Infinium Methylation EPIC array, thorough analysis of methylation alterations in 61 complement genes was conducted. The expression and methylation of nine complement genes in a murine MASH model were examined using quantitative RT-PCR and pyrosequencing. Results: Methylome and transcriptome analyses of liver biopsies revealed significant (p<0.05) hypermethylation and downregulation of C1R, C1S, C3, C6, C4BPA<, and SERPING1, as well as hypomethylation (p<0.0005) and upregulation (p<0.05) of C5AR1, C7, and CD59, in association with the histological severity of MASLD. Furthermore, DNA methylation and the relative expression of nine complement genes in a MASH diet mouse model aligned with human data. Conclusions Our research provides compelling evidence that epigenetic alterations in complement genes correlate with MASLD severity, offering valuable insights into the mechanisms driving MASLD progression, and suggests that inhibiting the function of certain complement proteins may be a promising strategy for managing MASLD.

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis.Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

Purpose: Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model. Materials and Methods: A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88). Results: The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort. Conclusion Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

Background/Aims: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. Methods: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. Results: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. Conclusions We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. in vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.

Objective: Endoscopic hemostasis is a key treatment for variceal upper gastrointestinal bleeding. However, the effects of early endoscopy in variceal upper gastrointestinal bleeding have not been sufficiently studied. This study investigated the effects of the use of the critical pathway (CP) for upper gastrointestinal bleeding. Methods: The study was designed as a ‘before and after’ study. A group of patients diagnosed with variceal upper gastrointestinal bleeding from January 1, 2011, to December 31, 2014, and CP activated patients from January 1, 2015, to December 31, 2018, were reviewed retrospectively. The study endpoints included an analysis of the following in the two groups: time from emergency department (ED) arrival to endoscopy, number of blood transfusions, hospitalization period, intensive care unit (ICU) admission, 30-day mortality. Results: From January 1, 2011, to December 31, 2018, 207 patients were admitted with variceal upper gastrointestinal bleeding, and 137 patients with a Blatchford score of 7 or higher were included in the study. Of these, 88 patients visited before the implementation of CP and 49 patients visited thereafter. The time from ED arrival to endoscopy was 218.1±201.7 minutes in the CP activated group, which was about 200 minutes shorter (P=0.046) than the non-CP group. There was no statistical difference in 30-day mortality, transfusion, emergency room hospitalization time, number of ICU admissions, and hospitalization days (P=0.348, P=0.394, P=0.651, P=0.164, and P=0.069). Conclusion After CP, the time to endoscopy was significantly shortened, but it did not reduce mortality.

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. in vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.

PURPOSE: In order to prevent tuberculosis transmission early, it is important to diagnose and treat tuberculosis infection by investigating people who have contact with patients with active tuberculosis. METHODS: From July 2014 to June 2017, the intrafamilial childhood contacts of the patients who were diagnosed with active tuberculosis at Chungnam National University Hospital were investigated for the presence of tuberculosis infection. We also retrospectively analyzed the treatment status of children treated with latent tuberculosis infection (LTBI) during the same period. RESULTS: Among the 269 children who had intrafamilial contact with active tuberculosis patient, 20 (7.4%) did not receive any screening. At the first screening, one (0.4%) was diagnosed with pulmonary tuberculosis, seven (2.8%) had a previous history of tuberculosis infection, and 42 patients (16.9%) were diagnosed with LTBI. At the second screening, 29 patients (11.6%) were diagnosed with LTBI, and 61 patients did not finish the investigation. Only 188 (69.9%) out of 269 patients completed the investigation. Ninety patients received treatment for LTBI and 83 patients (92.2%) completed the treatment, of which 18 patients had side effects such as rash, fatigue, and gastrointestinal symptoms. However, there were no serious side effects requiring treatment discontinuation. CONCLUSIONS: The completion rate of childhood tuberculosis contact investigation was low, but the completion rate of LTBI treatment was high in children without serious side effects. In order to prevent and manage the spread of tuberculosis, active private-public partnership efforts and education of the patient and guardian are needed.
Child ; Chungcheongnam-do ; Disease Transmission, Infectious ; Education ; Exanthema ; Fatigue ; Humans ; Latent Tuberculosis ; Mass Screening ; Retrospective Studies ; Tuberculosis ; Tuberculosis, Pulmonary

PURPOSE: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. RESULTS: Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). CONCLUSION: Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.
Antiemetics ; Dexamethasone ; Drug Therapy* ; Humans ; Nausea* ; Quality of Life ; Vomiting*