Purpose: Anorectal fistulas present a treatment challenge, with conventional surgical methods potentially resulting in complications such as fecal incontinence. To improve patient outcomes, more effective and minimally invasive therapies are critically needed. In this study, an optimal porcine model for the creation of anorectal fistulas was developed and used to evaluate the efficacy of radiofrequency ablation (RFA) therapy. Methods: Two distinct but related experiments were conducted. In the first experiment, a reliable and standardized porcine anorectal fistula model was developed. In the second, the healing process was assessed, and outcomes were compared between the RFA-treated group and the control group using the established porcine model. Results: The results indicated that a 3.5-cm fistula tract length and a 14-day evaluation period following seton removal are optimal for the porcine anorectal fistula model. In the second experiment, the RFA group tended to exhibit better outcomes regarding fistula closure, although the differences were not statistically significant. Histopathologically, no significant difference in inflammation grade was observed between groups; however, scar tissue was more predominant in the RFA group. Conclusion The findings suggest that RFA therapy may offer potential benefits in the treatment of anorectal fistulas, as demonstrated using a porcine model. To validate these results and explore the mechanisms of action underlying RFA therapy for anorectal fistulas, further research involving larger sample sizes and a more robust study design is required.

Background: A nationwide Rehabilitation at Home Care Pilot Program for patients undergoing lower extremity orthopedic surgeries has been ongoing since 2020. The program was designed to improve clinical outcomes through early mobilization and rehabilitation after discharge. This study aimed to analyze the interim data to assess its effectiveness and suggest improvements, particularly for older patients who are more vulnerable compared to younger patients. Methods: We analyzed the data of 872 patients from seven hospitals. Patients were divided into an older-age group (OG; ≥60 years) and younger-age group (YG; <60 years). The Berg Balance Scale (BBS) and Numeric Rating Scale (NRS) scores for pain were the main outcomes. Results: Participants were categorized into OG (n=801) and YG (n=71). The most common surgeries were knee joint replacement (63.7%) in OG and hip joint replacement in YG (77.5%). It took more days to enroll in the pilot program in OG (4.4 days) than YG (3.2 days). OG showed less improvement in BBS than YG for all surgeries (23.3 vs. 31.9) and hip joint surgery (19.8 vs. 33.5). In patients with hip joint replacement in OG, those with a higher number of comorbidities (≥3) showed less BBS improvement than those with fewer comorbidities (<3). In the pain domain, NRS scores decreased in both groups. Conclusion The postoperative rehabilitation education program appeared to be effective in improving physical function and reducing pain severity, though the improvement was less obvious in older patients who may require a more comprehensive approach compared to younger patients.

Purpose: The results of the TAILORx trial have shown that premenopausal patients with intermediate Oncotype Dx (ODx) recurrence score of 16–25 may benefit from adjuvant chemotherapy. In addition, the clinicopathological features showed the information complementary to ODx results. However, the characteristics may vary depending on menopausal status even in the same score. This study aimed to analyze the differences in the clinical characteristics by menopausal status. Methods: This study conducted a retrospective analysis of 756 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-negative breast cancer who underwent the ODx test from July 2013 to December 2020 at the Severance Hospital. Results: Of the 756 patients, 261 patients were postmenopausal, and 495 were premenopausal. The premenopausal patients with a midrange ODx had similar clinicopathological features as compared to those with a high ODx. Conversely, the postmenopausal patients with a midrange ODx did not show significantly different clinicopathological features from those with a low ODx, whereas a difference was seen as compared to those with a high ODx. Conclusion In this study, unlike the postmenopausal patients, some of the clinicopathological characteristics of the premenopausal patients with a midrange ODx were closer to those with a high ODx than those with a low ODx. In the premenopausal patients with a midrange ODx, considering the baseline characteristic itself, there was a significant difference between those with a low ODx when compared with postmenopausal patients. Therefore, more aggressive treatment decisions may be helpful in premenopausal patients with a midrange ODx.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

Purpose: Regenerative medicine is expected to offer an alternative to liver transplantation for treating liver diseases in the future, with one significant challenge being the establishment of an effective stem cell administration route. This study assessed the antifibrogenic effects of adipose-derived stem cells (ASCs) in a liver fibrosis mouse model, focusing on 2 methods of delivery: intravenous injection and scaffold implantation. Methods: An extracellular matrix mimic scaffold was utilized for culturing peroxisome proliferator-activated receptor gamma coactivator 1-alpha–overexpressing ASCs (tASCs). These scaffolds, laden with tASCs, were then implanted subcutaneously in mice exhibiting liver fibrosis. In contrast, the Cell groups received biweekly intravenous injections of tASCs for 4 weeks. After 4 weeks, tissue samples were harvested from the euthanized mice for subsequent analysis. Results: Real-time PCR and Western blot analyses on liver tissues, focusing on markers like alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2, and transforming growth factor-beta 1 (TGF-β1), showed that both delivery routes substantially lowered fibrotic and inflammatory markers compared to controls (P < 0.05), with no significant differences between the routes. Histological examinations, along with immunohistochemical analysis of α-SMA, collagen type I alpha, and TGF-β1, revealed that the scaffold implantation approach resulted in a greater reduction in fibrosis and lower immunoreactivity for fibrotic markers than intravenous delivery (P < 0.05). Conclusion These findings indicate that delivering tASCs via a scaffold could be more effective, or at least similarly effective, in treating liver fibrosis compared to intravenous delivery. Scaffold implantation could offer a beneficial alternative to frequent intravenous treatments, suggesting its potential utility in clinical applications for liver disease treatment.

Hangovers from alcohol consumption cause symptoms like headaches, nausea, and fatigue, disrupting daily activities and overall well-being. Over time, they can also lead to inflammation and oxidative stress. Effective hangover relief alleviates symptoms, prevents dehydration, and replenishes energy needed for daily tasks. Natural foods considered high in antioxidants and antiinflammatory properties may aid in the hepatic breakdown of alcohol. The study aims to investigate the impact of glutathione or its enriched yeast extract, which is recognized for its antioxidant characteristics, on alcohol metabolism and alleviating hangovers in a rat model exposed to binge drinking. In this study, glutathione and its enriched yeast extract controlled hangover behaviour patterns, including locomotor activity. Additionally, it enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) following ethanol ingestion (3 g/kg). Further, the incorporation of glutathione led to an increase in the expression of antioxidant enzymes, such as SOD and catalase, by activating the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway.This activation reduced the excessive production of reactive oxygen species (ROS) and malondialdehyde. Next, glutathione modulated the activity of cytochrome P450 2E1 (CYP2E1) and the protein expressions of Bax and Bcl2. Besides, in vitro and in vivo investigations with glutathione demonstrated a regulating effect on the pan-s-glutathionylation and its associated protein expression, glutaredoxin 1 (Grx1), glutathione-S-transferase Pi (GST-π), and glutathione reductase (GR). Together, these findings suggest that glutathione or its enriched yeast extract as a beneficial dietary supplement for alleviating hangover symptoms by enhancing alcohol metabolism and its associated Nrf2/Keap1 signalings.

Anticancer activities of Licochalcone D (LCD) in human colorectal cancer (CRC) cells HCT116 and oxaliplatin-resistant HCT116 (HCT116-OxR) were determined. Cell viability assay and soft agar assay were used to analyze antiproliferative activity of LCD.Flow cytometry was performed to determine effects of LCD on apoptosis, cell cycle distribution, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) dysfunction, and multi-caspase activity in CRC cells. Western blot analysis was used to monitor levels of proteins involved in cell cycle and apoptosis signaling pathways. LCD suppressed the growth and anchorageindependent colony formation of both HCT116 and HCT116-OxR cells. Cell cycle analysis by flow cytometry indicated that LCD induced cell cycle arrest and increased cells in sub-G1 phase. In parallel with the antiproliferative effect of LCD, LCD up-regulated levels of p21 and p27 while downregulating cyclin B1 and cdc2. In addition, phosphorylation levels of JNK and p38 mitogen-activated protein kinase (MAPK) were increased by LCD. Inhibition of these kinases somehow prevented the antiproliferative effect of LCD. Moreover, LCD increased ROS and deregulated mitochondrial membrane potential, leading to the activation of multiple caspases. An ROS scavenger N-acetyl-cysteine (NAC) or pan-caspase inhibitor Z-VAD-FMK prevented the antiproliferative effect of LCD, supporting that ROS generation and caspase activation mediated LCD-induced apoptosis in CRC cells. In conclusion, LCD exerted antitumor activity in CRC cells by inducing ROS generation and phosphorylation of JNK and p38 MAPK. These results support that LCD could be further developed as a chemotherapeutic agent for treating CRC.

Although histone deacetylase 6 (HDAC6) is considered a therapeutic target for Alzheimer’s disease (AD), its role in cholinergic dysfunction in AD patients remains unclear. This study investigated the effects of (E)-3-(2-(4-fluorostyryl)thiazol-4-yl)-N-hydroxypropanamide (4-FHA), a new synthetic HDAC6 inhibitor, on cognitive and memory impairments in a scopolamine-induced-AD mouse model. Behaviorally, 4-FHA improved scopolamine-induced memory impairments in the Y-maze, passive avoidance, and Morris water maze tests. In addition, 4-FHA ameliorated scopolamine-induced cognitive impairments in the novel object recognition and place recognition tests. Furthermore, 4-FHA increased acetylation of α-tubulin (a major HDAC6 substrate); the expression of BDNF; and the phosphorylation of ERK 1/2, CREB, and ChAT in the hippocampus of scopolamine-treated mice. In summary, according to our data 4-FHA, an HDAC6 inhibitor, improved the cognitive and memory deficits of the AD mouse model by normalizing BDNF signaling and synaptic transmission, suggesting that 4-FHA might be a potential therapeutic candidate for AD.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.