Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Purpose: Obesity and metabolic syndrome are acknowledged as key factors contributing to the development of non-alcoholic fatty liver disease (NAFLD). Vitamin D (VitD) is a multifaceted secosteroid hormone known for its anti-fibrotic and anti-inflammatory properties, with its deficiency often linked to obesity. Our study aimed to investigate whether VitD supplementation could mitigate the liver pathology associated with NAFLD. Materials and Methods: The NAFLD model was developed by subjecting male C57BL/6 mice to a high-fat diet (HFD) for 14 weeks.These mice were supplemented with VitD through intraperitoneal injection at a dosage of 7 μg/kg, administered three times per week for 7 weeks. Results: HFD resulted in VitD deficiency, insulin resistance, and increased liver weight. It elevated serum levels of liver aminotransferases and triglyceride, ultimately leading to steatohepatitis with fibrosis. This model exhibited increased levels of transforming growth factor (TGF)-β1, pro-inflammatory cytokines, HNF4α transcription factors, reactive oxygen species (ROS), renin-angiotensin system activity, and epithelial-mesenchymal transitions (EMT) within the liver. Supplementation with VitD resulted in the recovery of liver weight, improvement in histologic features associated with steatohepatitis, and reduction in alanine aminotransferases and triglyceride levels induced by the HFD. Additionally, it mitigated the HFD-induced over-expressions of TGF-β1 and fibrosis-related genes, along with pro-inflammatory cytokines and ROS. Notably, no adverse effect was found due to VitD supplementation in this model. Conclusion VitD ameliorates steatohepatitis within obesity-induced NAFLD through its multifaceted pathways. VitD supplementation emerges as a potentially safe, cost-effective, and direct treatment approach for NAFLD patients dealing with obesity or metabolic dysfunction.

Purpose: To develop a machine learning (ML) classifier for predicting post-induction hypotension (PIH) in non-cardiac surgeries. Materials and Methods: Preoperative data and early vital signs were obtained from 3669 cases in the VitalDB database, an opensource registry. PIH was defined as sustained mean arterial pressure (MAP) <65 mm Hg within 20 minutes since induction or from induction to incision. Six different ML algorithms were used to create binary classifiers to predict PIH. The primary outcome was the area under the receiver operating characteristic curve (AUROC) of ML classifiers. Results: A total of 2321 (63.3%) cases exhibited PIH. Among ML classifiers, the random forest regressor and extremely gradient boosting regressor showed the highest AUROC, both recording a value of 0.772. Excluding these models, the light gradient boosting machine regressor showed the second highest AUROC [0.769; 95% confidence interval (CI), 0.767–0.771], followed by the gradient boosting regressor (0.768; 95% CI, 0.763–0.772), AdaBoost regressor (0.752; 95% CI, 0.743–0.761), and automatic relevance determination regression (0.685; 95% CI, 0.669–0.701). The top three important features were mean diastolic blood pressure (DBP), minimum MAP, and minimum DBP from anesthetic induction to tracheal intubation, and these features were lower in cases with PIH (all p<0.001). Conclusion ML classifiers exhibited moderate performance in predicting PIH, and have the potential for real-time prediction.

Purpose: Hair disorders, which are often attributed to conditions associated with a shortened anagen growth phase, oxidative stress, and hormonal dysregulation, especially during aging, have profound psychological implications. Currently, only minoxidil has been approved as a topical hair growth solution; thus, alternative therapies for treating hair loss and promoting hair health are urgently needed. Herein, we aimed to develop and assess a novel method to promote hair growth and health using mastic (Pistacia lentiscus) gum and peppermint (Mentha piperita L.) extracts. Materials and Methods: After determining the optimal ratio of mastic gum and peppermint extracts, we performed in vitro and in vivo experiments to verify the efficacy of the 7:3 mastic gum-peppermint mixture (MP73; FHH-MG) for enhancing hair growth and health. Results: Mastic gum significantly promoted cell proliferation and demonstrated synergistic benefits when combined with peppermint extract. In vitro, FHH-MG increased human dermal follicle papilla cell proliferation and demonstrated anti-inflammatory and antioxidant effects. In vivo, treatment with FHH-MG dose-dependently enhanced hair growth and gloss and increased the expression of vascular endothelial growth factor, epidermal growth factor, β-catenin, and insulin-like growth factor-1 in C57BL/6 mice compared to the negative control. Conclusion The novel mixture exhibited hair growth-promoting effects in C57BL/6 mice; thus, FHH-MG may serve as a botanical alternative for hair growth and health promotion.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: s/Aims: Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. Methods: Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. Results: The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.

Background: Although the presence of both obesity and reduced muscle mass presents a dual metabolic burden and additively has a negative effect on a variety of cardiometabolic parameters, data regarding the associations between their combined effects and left ventricular diastolic function are limited. This study investigated the association between the ratio of skeletal muscle mass to visceral fat area (SVR) and left ventricular diastolic dysfunction (LVDD) in patients with preserved ejection fraction using random forest machine learning. Methods: In total, 1,070 participants with preserved left ventricular ejection fraction who underwent comprehensive health examinations, including transthoracic echocardiography and bioimpedance body composition analysis, were enrolled. SVR was calculated as an index of sarcopenic obesity by dividing the appendicular skeletal muscle mass by the visceral fat area. Results: In the random forest model, age and SVR were the most powerful predictors of LVDD. Multivariate logistic regression analysis demonstrated that older age (adjusted odds ratio [OR], 1.11; 95% confidence interval [CI], 1.07 to 1.15) and lower SVR (adjusted OR, 0.08; 95% CI, 0.01 to 0.57) were independent risk factors for LVDD.SVR showed a significant improvement in predictive performance and fair predictability for LVDD, with the highest area under the curve noted in both men and women, with statistical significance. In non-obese and metabolically healthy individuals, the lowest SVR tertile was associated with a greater risk of LVDD compared to the highest SVR tertile. Conclusion Decreased muscle mass and increased visceral fat were significantly associated with LVDD compared to obesity, body fat composition, and body muscle composition indices.

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.