Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background: Distal nerve block approaches have been explored to reduce hemidiaphragmatic paresis (HDP) more effectively than interscalene block (ISB). However, these approaches are associated with a high incidence of HDP. The costoclavicular block (CCB) provides effective analgesia while reducing HDP. Here, we hypothesized that CCB would decrease the incidence of HDP compared to ISB while still providing effective pain relief after surgery. Methods: Seventy patients who underwent arthroscopic rotator cuff repair were randomly allocated to receive either ultrasound-guided CCB (n = 35) or ISB (n = 35). Each group received 0.2% ropivacaine (20 ml CCB, 10 ml ISB). The primary outcome was the incidence of HDP, as measured using M-mode ultrasound. Diaphragmatic excursion, pulmonary function test results, opioid consumption, and pain scores were evaluated. Results: Sixty-six patients were included. CCB group had a significantly lower incidence of HDP than those in the ISB group (5.9% vs. 84.4%, P < 0.001). The diaphragmatic excursion reduction was significantly more in the ISB (3.87 cm) group than in the CCB (0.25 cm) group (P < 0.001). The decrease in forced vital capacity and forced expiratory volume in 1 s from baseline was significantly greater in the ISB. There was no significant difference in opioid consumption between the two groups during the entire postoperative period. Conclusions Compared with ISB, CCB significantly reduced the incidence of HDP while maintaining effective analgesia and causing less pulmonary function impairment. CCB may be a viable option for diaphragmatic-sparing analgesia after shoulder surgery.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Purpose: This study aimed to characterize the clinical patterns and severity of brain injury in neonates who survived extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory failure during the neonatal period, to evaluate their short-term neurodevelopmental outcomes, and to identify the factors associated with these outcomes. Methods: We retrospectively reviewed the medical records of neonates who survived ECMO between 2018 and 2024. Based on brain magnetic resonance imaging (MRI) findings, the patients were classified into two groups: no/mild and moderate/severe brain injury. Neurodevelopmental outcomes were assessed at 12–40 months of age using the Bayley Scale of Infant Development II/III and/or the Korean Developmental Screening Test. Results: Among the 19 neonates included in the study, 18 (94.7%) showed varying degrees of brain injury on MRI (mild: 12, moderate: 1, severe: 5). Neonates with moderate/severe brain injury had significantly longer durations of ECMO support and extended durations of mechanical ventilation and were more likely to receive continuous renal replacement therapy than those with no or mild injury. Developmental delay was identified in 36.8% of survivors and was significantly associated with prolonged mechanical ventilation, longer neonatal intensive care unit stays, and a higher incidence of seizures. Conclusion Brain injury is frequently observed on MRI in neonates treated with ECMO. However, its direct association with adverse neurodevelopmental outcomes is not definitive. Since MRI findings alone cannot predict developmental outcomes, clinical and environmental factors should be integrated into prognostic assessments.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by alveolar destruction and increased inflammation, leading to respiratory symptoms. This study aimed to identify the traits for COPD progression from mild to severe stages. Additionally, we explored the correlation between coronavirus disease-2019 (COVID-19) and COPD to uncover overlapping respiratory patterns. Materials and Methods: Bulk RNA sequencing was conducted on data from 43 healthy individuals and 39 COPD patients across one dataset (GSE239897) to distinguish COPD characteristics. Single-cell RNA analysis was then performed on samples from seven mild patients, seven moderate patients, and three severe patients from three datasets (GSE167295, GSE173896, and GSE227691) to analyze disease progression. Finally, single-nuclei RNA analysis was applied to data from seven healthy individuals and 20 COVID-19 patients from one dataset (GSE171524) to compare the two conditions. Results: Bulk RNA sequencing revealed enhanced inflammatory pathways in COPD patients, indicating increased inflammation.Single-cell RNA sequencing showed a stronger inflammatory response from mild to moderate COPD with a decrease from moderate to severe stages. COVID-19 displayed similar biological patterns to moderate COPD, suggesting that stage-specific COPD analysis could enhance COVID-19 management. Conclusion The analysis found that immune responses increased from mild to moderate stages but declined in severe cases, marked by reduced pulmonary T cell activation. The overlap between moderate COPD and COVID-19 suggests shared therapeutic strategies, warranting further investigation.

Overactive bladder (OAB) and detrusor underactivity (DUA) are representative voiding dysfunctions with a chronic nature and limited treatment modalities, and are ideal targets for stem cell therapy. In the present study, we investigated the therapeutic efficacy of human mesenchymal stem cells (MSCs) with a high antioxidant capacity generated by the Primed Fresh OCT4 (PFO) procedure in chronic bladder ischemia (CBI)-induced OAB and DUA rat models. Sixteen-week-old male Sprague-Dawley rats were divided into three groups (sham, OAB or DUA, and stem cell groups; n=10, respectively).CBI was induced by bilateral iliac arterial injury (OAB, 10 times; DUA, 30 times) followed by a 1.25% cholesterol diet for 8 weeks. Seven weeks after injury, rats in the stem cell and other groups were injected with 1×10 6 PFO-MSCs and phosphate buffer, respectively. One week later, bladder function was analyzed by awake cystometry and bladders were harvested for histological analysis. CBI with a high-fat diet resulted in atrophy of smooth muscle and increased collagen deposits correlating with reduced detrusor contractility in both rat models. Arterial injury 10 and 30 times induced OAB (increased number of non-voiding contractions and shortened micturition interval) and DUA (prolonged micturition interval and increased residual volume), respectively. Injection of PFO-MSCs with the enhanced glutathione dynamics reversed both functional and histological changes; it restored the contractility, micturition interval, residual volume, and muscle layer, with reduced fibrosis. CBI followed by a high-fat diet with varying degrees of arterial injury induced OAB and DUA in rats. In addition, PFO-MSCs alleviated functional and histological changes in both rat models.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.