Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-ß-Mediated JAK/STAT1 Pathway in vitro.

Interferon (IFN)-ß and/or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) secreted by adipose tissue-derived mesenchymal stem cells (ASCs) have been proposed as key mechanistic factors in anti-cancer efficacy in lung cancer and breast cancer cells, where they act through paracrine signaling. We hypothesized that IFN-ß and TRAIL produced by ASCs suppress proliferation of hepatocellular carcinoma cells (HCCs). The present study evaluated the anti-cancer effects of ASCs on HCCs in vitro. We found that indirect co-culture with ASCs diminished growth of Huh7 hepatocellular carcinoma cells with increased protein levels of p53/p21 and phosphorylated STAT1 (pSTAT1), without apoptosis. Treatment with ASC-conditioned medium (ASC-CM) also decreased growth of Huh7 cells through elevated p53/p21 and pSTAT1 signaling. ASC-CM-mediated inhibition of cell growth was neutralized in Huh7 cells treated with anti-IFN-ß antibody compared to that in ASC-CM-treated Huh7 cells incubated with an anti-TRAIL antibody. Treatment with JAK1/JAK2 inhibitors recovered inhibition of growth in Huh7 cells incubated in ASC-CM or IFN-ß via down-regulation of pSTAT1/p53/p21. However, treatment of IFN-ß resulted in no alterations in resistance of Huh7 cells to TRAIL. Our findings suggest that ASCs decrease growth through activated STAT1-mediated p53/p21 by IFN-ß, but not TRAIL, in Huh7 cells.

Association of Gout with Head and Neck Cancer: Longitudinal Follow-Up Studies Using a National Health Insurance Database in South Korea.

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04-1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16-1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01-1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06-1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72-0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83-0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81-0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC.

Substantiation and Effectiveness of Remote Monitoring System Based on IoMT Using Portable ECG Device.

Cardiovascular disease is a major global health concern, with early detection being critical. This study assesses the effectiveness of a portable ECG device, based on Internet of Medical Things (IoMT) technology, for remote cardiovascular monitoring during daily activities. We conducted a clinical trial involving 2000 participants who wore the HiCardi device while engaging in hiking activities. The device monitored their ECG, heart rate, respiration, and body temperature in real-time. If an abnormal signal was detected while a physician was remotely monitoring the ECG at the IoMT monitoring center, he notified the clinical research coordinator (CRC) at the empirical research site, and the CRC advised the participant to visit a hospital. Follow-up calls were made to determine compliance and outcomes. Of the 2000 participants, 318 showed abnormal signals, and 182 were advised to visit a hospital. The follow-up revealed that 139 (76.37%) responded, and 30 (21.58% of those who responded) sought further medical examination. Most visits (80.00%) occurred within one month. Diagnostic approaches included ECG (56.67%), ECG and ultrasound (20.00%), ultrasound alone (16.67%), ECG and X-ray (3.33%), and general treatment (3.33%). Seven participants (23.33% of those who visited) were diagnosed with cardiovascular disease, including conditions such as arrhythmia, atrial fibrillation, and stent requirements. The portable ECG device using the patch-type electrocardiograph detected abnormal cardiovascular signals, leading to timely diagnoses and interventions, demonstrating its potential for broad applications in preventative healthcare.

Associations between Peritonsillar Abscess and Deep Neck Infection in Chronic Periodontitis Patients: Two Nested Case-Control Studies Using a National Health Screening Cohort.

Background/Introduction: Odontogenic infection is one of the main etiologies of deep neck infection (DNI). However, the relationship between chronic periodontitis (CP) and the incidence of DNI has not been examined. This study aimed to evaluate the incidence of DNI and peritonsillar abscess (PTA) after CP. Methods: The Korean National Health Insurance Service-National Sample Cohort 2002-2019 was used. In Study I, 4585 PTA patients were matched with 19,340 control I participants. A previous history of CP for 1 year was collected, and the odds ratios (ORs) of CP for PTA were analyzed using conditional logistic regression. In Study II, 46,293 DNI patients and 185,172 control II participants were matched. A previous history of CP for 1 year was collected, and conditional logistic regression was conducted for the ORs of CP for DNI. Secondary analyses were conducted in demographic, socioeconomic, and comorbidity subgroups. Results: In Study I, a history of CP was not related to the incidence of PTA (adjusted OR = 1.28, 95% confidence interval [CI] = 0.91-1.81). In Study II, the incidence of DNI was greater in participants with a history of CP (adjusted OR = 1.55, 95% CI = 1.41-1.71). The relationship between CP history and DNI was greater in groups with young, male, low-income, and rural residents. Conclusions: A prior history of CP was associated with a high incidence of DNI in the general population of Korea. Patients with CP need to be managed for the potential risk of DNI.

Occult Pneumothorax in Blunt Thoracic Trauma: Clinical Characteristics and Results of Delayed Tube Thoracostomy in a Level 1 Trauma Center.

Occult pneumothorax in blunt trauma patients is often diagnosed only after computed tomography because supine chest X-ray (CXR) is preferred as an initial evaluation. However, improperly managed preexisting occult pneumothorax could threaten the vitality of patients. Therefore, this study aimed to evaluate the incidence, characteristics, risk factors, and outcomes of occult pneumothorax in a single trauma center. From 2020 to 2022, patients who were admitted to the level 1 trauma center were retrospectively investigated. Inclusion criteria focused on blunt chest trauma. Variables including demographic factors, image findings, injury-related factors, tube thoracostomy timing, and treatment results were evaluated. Of the 1621 patients, 187 who met the criteria were enrolled in the study: 32 with overt pneumothorax and 81 with occult pneumothorax. Among all of the pneumothorax cases, the proportion of occult pneumothorax was 71.7% (81/113), and its incidence in all admitted trauma victims was 5.0% (81/1621). Subcutaneous emphysema and rib fractures on supine CXR were risk factors for occult pneumothorax. Six patients underwent delayed tube thoracostomy; however, none had serious complications. Given that occult pneumothorax is common in patients with blunt chest trauma, treatment plans should be established that consider the possibility of pneumothorax. However, the prognosis is generally good, and follow-up is an alternative.

Association of Chest Anteroposterior Radiography with Computed Tomography in Patients with Blunt Chest Trauma.

Background: In cases of chest trauma, computed tomography (CT) can be used alongside chest anteroposterior (AP) radiography and physical examination during initial evaluation. Performing a CT scan may be difficult if a patient has unstable vital signs. In contrast, radiography may not always reliably diagnose nonmarked pneumothorax or extensive subcutaneous emphysema. Objectives: This study aimed to determine the agreement between chest radiography and CT findings in patients with blunt chest trauma. The study also aimed to determine the occurrence of occult pneumothorax and clarify the proportion of subcutaneous emphysema and pneumothorax detected through radiography and CT, respectively. Methods: We included patients (n = 1284) with chest trauma who were admitted to the emergency room of a tertiary hospital between January 2015 and June 2022. We excluded patients aged <18 years, those with stab injury, those without radiography and CT findings, and patients who required iatrogenic intervention, such as chest tube insertion, before imaging. We recorded age, sex, trauma mechanism, and Abbreviated Injury Scale score for each patient. From radiography and CT scans, we recorded the presence of rib fracture, subcutaneous emphysema, lung contusion, pneumothorax, and pneumomediastinum. The accuracy, sensitivity, specificity, and positive and negative predictive values were calculated to assess the reliability of radiography as a predictor of CT-based diagnosis. Results: Radiography exhibited a specificity of nearly 100% for all items. In most cases, findings that could not be confirmed by CT were not evident on radiographs. The incidence of occult pneumothorax was 87.3%. When subcutaneous emphysema was observed on radiography, CT findings indicated pneumothorax in 96.7% of cases. Conclusions: In situations where the patient's vital signs are unstable and performing a CT scan is not feasible, the presence of subcutaneous emphysema on radiography may indicate the need for chest decompression, even if pneumothorax is not observed.

Occult pneumothorax in patients with blunt chest trauma: key findings on supine chest radiography.

Background: In patients with multiple trauma, a supine chest radiography [chest X-ray (CXR)] is preferred over a erect CXR. However, this method has limitations in detecting post-traumatic pneumothorax. The use of chest computed tomography (CT) to detect traumatic pneumothorax is well known. However, pneumothorax that is not detected before a chest CT scan is known as an occult pneumothorax (OP), and it can cause serious complications in the patient. This study sought to evaluate the frequency and risk factors for OP in trauma patients. Methods: Patients who suffered thoracic trauma at the Level 1 Regional Trauma Center of Wonju Severance Christian Hospital between 2015 and 2022 were included in this study. All patients were at least 18 years old. The study reviewed all patients' supine CXR and chest CT images and classified them into five radiographic diagnoses: pneumothorax, rib fracture, subcutaneous emphysema, lung contusion, and pneumomediastinum. Results: The study included 1,284 patients, all with diagnoses of pneumothorax, rib fracture, subcutaneous emphysema, lung contusion, and pneumomediastinum following supine CXR and chest CT. The patient's average age was 58.3±15.2 years. Pneumothorax diagnosis on supine CXR had the lowest accuracy, at 46.7%, and the lowest sensitivity, at 12.7%. In univariate analysis, rib fracture, lung contusion, and subcutaneous emphysema on supine CXR were all found to be statistically significant regarding traumatic OP. In multivariate analysis, the risk factors for OP were lung contusion [odds ratio (OR), 1.440; 95% confidence interval (CI): 1.115-1.860; P=0.005] and subcutaneous emphysema (OR, 25.883; 95% CI: 13.155-50.928; P<0.001) on supine CXR. Conclusions: The lung contusion and subcutaneous emphysema in supine CXR of trauma patients indicate the presence of OP. Therefore, if chest CT cannot be performed immediately due to unstable vital signs or other circumstances, recognizing the above radiological findings of traumatic pneumothorax may be necessary.

12-O-tetradecanoylphorbol-13-acetate Reduces Activation of Hepatic Stellate Cells by Inhibiting the Hippo Pathway Transcriptional Coactivator YAP.

Although protein kinase C (PKC) regulates various biological activities, including cell proliferation, differentiation, migration, tissue remodeling, gene expression, and cell death, the antifibrotic effect of PKC in myofibroblasts is not fully understood. We investigated whether 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, reduced the activation of hepatic stellate cells (HSCs) and explored the involvement of the Hippo pathway transcriptional coactivator YAP. We analyzed the effect of TPA on the proliferation and expression of α-smooth muscle actin (SMA) in the LX-2 HSC line. We also analyzed the phosphorylation of the Hippo pathway molecules YAP and LATS1 and investigated YAP nuclear translocation. We examined whether Gö 6983, a pan-PKC inhibitor, restored the TPA-inhibited activities of HSCs. Administration of TPA decreased the growth rate of LX-2 cells and inhibited the expression of α-SMA and collagen type I alpha 1 (COL1A1). In addition, TPA induced phosphorylation of PKCδ, LATS1, and YAP and inhibited the nuclear translocation of YAP compared with the control. These TPA-induced phenomena were mostly ameliorated by Gö 6983. Our results indicate that PKCδ exerts an antifibrotic effect by inhibiting the Hippo pathway in HSCs. Therefore, PKCδ and YAP can be used as therapeutic targets for the treatment of fibrotic diseases.

Characteristics of pediatric thoracic trauma: in view of before and after the establishment of a regional trauma center.

PURPOSE: Pediatric thoracic trauma differs from those of adult in terms of the small anatomy and rapid tissue recovery. Therefore, it is important to know the characteristics of the pediatric thoracic trauma to improve treatment results. In addition, this study examined the changes in pediatric thoracic trauma features and results from the establishment of a level 1 regional trauma center. METHODS: Data of 168 patients' ≤ 15 years old diagnosed with thoracic trauma between 2008 and 2019 were retrospectively analyzed. RESULTS: Pedestrian traffic accidents were the most common cause of chest injury. The average injury severity score was 17.1 ± 12.4 and the average pediatric trauma score was 5.6 ± 4.1. Lung contusion was the most common in 134 cases. There were 48 cases of closed thoracostomy. There was one thoracotomy for cardiac laceration, one case for extracorporeal membranous oxygenation, and six cases for embolization. Of all, 25 patients died, providing a mortality rate of 14.9%. In addition, independent risk factors of in-hospital mortality were hemopneumothorax and cardiac contusion. Since 2014, when the level 1 regional trauma center was established, more severely injured thoracic trauma patients came. However, the mortality was similar in the two periods. CONCLUSIONS: Understanding the clinical features of pediatric thoracic trauma patients can help in efficient treatment. In addition, as the severity of pediatric thoracic trauma patients has increased due to the establishment of the regional trauma center, so pediatric trauma center should be organized in regional trauma center to improve the outcomes of pediatric thoracic trauma.

Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS).

Background and Objectives: Currently, safety pharmacological tests for the central nervous system depend on animal behavioral analysis. However, due to the subjectivity of behavioral analysis and differences between species, there is a limit to appropriate nervous system toxicity assessment, therefore a new neurotoxicity assessment that can simulate the human central nervous system is required. Methods and Results: In our study, we developed an in vitro neurotoxicity assessment focusing on neuronal function. To minimize the differences between species and fast screening, hiPSC-derived neurons and a microelectrode array (MEA) that could simultaneously measure the action potentials of the neuronal networks were used. After analyzing the molecular and electrophysiological characters of our neuronal network, we conducted a neurotoxicity assessment on neurotransmitters, neurotoxicants, illicit drugs, and new psychoactive substances (NPS). We found that most substances used in our experiments responded more sensitively to our MEA-based neurotoxicity assessment than to the conventional neurotoxicity assessment. Also, this is the first paper that evaluates various illicit drugs and NPS using MEA-based neurotoxicity assessment using hiPSC-derived neurons. Conclusions: Our study expanded the scope of application of neurotoxicity assessment using hiPSC-derived neurons to NPS, and accumulated evaluation data of various toxic substances for hiPSC-derived neurons.