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Objective: The relationship between impaired fasting glucose (IFG) and risk of cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely according to sex and ethnicity. We evaluated the relationship between IFG and CVD or IHD among Korean men and women.Research Design and Methods: A total of 408,022 individuals who underwent voluntary private health examinations in 17 centers in South Korea were followed for 10 years. Data regarding CVD or IHD events were obtained from the Korean National Health Insurance database. IFG was categorized as grade 1 (fasting glucose 100-109 mg/dL) or grade 2 (110-125 mg/dL).Results: Incidence rates of CVD (per 100,000 person-years) were 2,203 for diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13-1.20) for grade 1 IFG, 1.30 (1.24-1.35) for grade 2 IFG, and 1.81 (1.75-1.86) for diabetes. The increased risk for women was similar to that of men. Age-adjusted HRs for IHD and ischemic stroke were also significantly increased for men and women with IFG and diabetes. After multivariate adjustment of conventional risk factors (hypertension, dyslipidemia, smoking, obesity, and family history of CVD), the overall risk of CVD was greatly attenuated in all categories. However, the HRs for IHD and ischemic stroke remained significantly increased in men for grade 2 IFG but not in women.Conclusions: In Korea, grade 2 IFG is associated with increased risk of IHD and ischemic stroke, independent of other conventional risk factors, in men but not in women. [ABSTRACT FROM AUTHOR]

Objective: Ectrodactyly is a rare malformation with various presentations. The current report describes a case of ectrodactyly detected using 2-dimensional (2D) and 3-dimensional (3D) ultrasonography at 16 weeks' gestation. Methods and Results: The 2D ultrasonographic findings were ectrodactyly in the right hand and monodactyly in the left hand, and these results were confirmed and further clarified using 3D imaging. The postmortem X-ray findings were consistent with the ultrasonography. Conclusion: We conclude that 3D ultrasonography can assist in clarifying 2D ultrasonography findings of hand malformations during the second trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a β-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of β-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of transcripts from the β-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and β-catenin. This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anticancer activity of capsaicin in human colorectal cancer cells. [ABSTRACT FROM AUTHOR]

It has been reported that the proinflammatory cytokine interleukin-1beta (IL-1beta) induces mucus hypersecretion in normal human nasal epithelial (NHNE) cells and that the MAP kinase pathway may be an important signal pathway in IL-1beta-induced MUC5AC gene expression. Green tea (Camellia sinensis) polyphenols are potent anti-inflammatory agents and have been shown to inhibit inflammation in tumor cell lines and cultured respiratory epithelial cells. In this study, we examined the effect of (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, on IL-1beta-induced MUC5AC gene expression and secretion in NHNE cells. After cells had been treated with IL-1beta (10 ng/ml) and pretreated with EGCG (10, 50 and 100 microM), mRNA expression of MUC5AC was determined by real-time polymerase chain reaction. The suppression of each signal pathway protein was determined by Western blot analysis after treatment with IL-1beta and EGCG, respectively. IL-1beta increased MUC5AC gene expression and MUC5AC secretion. EGCG markedly suppressed IL-1beta-induced MUC5AC gene expression and MUC5AC secretion via suppression of the phosphorylation of ERK MAP kinase, MSK1, and transcription factor, cAMP response element-binding protein. IL-1beta increased the number of cells staining positive with MUC5AC antibodies, and EGCG treatment decreased this number. Our data suggest that EGCG may be an effective inhibitor of IL-1beta-induced mucus hypersecretion. [ABSTRACT FROM AUTHOR]

In recent studies, green tea components have been shown to induce cell growth arrest and apoptosis in head and neck squamous cell carcinoma (HNSCC) cells. In this report, we have investigated the effects of epicatechin gallate (ECG), one of the catechins in green tea, on anti-cancer activity in vitro. We found that cyclin D1 was highly expressed in HNSCC cells, and ECG suppressed 90% of cyclin D1 expression in SCC7 cells. We have also evaluated the effect of ECG on cell growth and apoptosis, showing that ECG (50 microM) exhibited a significant inhibition (50%) on the growth of SCC7 cells via G1 cell cycle arrest. ECG suppressed cyclin D1 in SCC7 cells in a dose- and time-dependent manner, and the suppression of the beta-catenin pathway by ECG is one of the mechanism to facilitate ECG-induced cell growth arrest. These results suggest that ECG has a potential usage as a chemopreventive agent in HNSCC. [ABSTRACT FROM AUTHOR]

Advancements in nanotechnology led to significant improvements in synthesizing plasmon-enhanced nanoarchitectures for biosensor applications, and high-yield productivity at low cost is vital to step further into medical commerce. Metal nanoframes via wet chemistry are gaining attention for their homogeneous structure and outstanding catalytic and optical properties. However, nanoframe morphology should be considered delicately when brought to biosensors to utilize its superior characteristics thoroughly, and the need to prove its clinical applicability still remains. Herein, we controlled the frameworks of double-walled nanoframes (DWFs) precisely via wet chemistry to construct a homogeneous plasmon-enhanced nanotransducer for localized surface plasmon resonance biosensors. By tuning the physical properties considering the finite-difference time-domain simulation results, biomolecular interactions were feasible in the electromagnetic field-enhanced nanospace. As a result, DWF 10 exhibited a 10-fold lower detection limit of 2.21 fM compared to DWF 14 for tau detection. Further application into blood-based clinical and Alzheimer's disease (AD) diagnostics, notable improvement in classifying mild cognitive impairment patients against healthy controls and AD patients, was demonstrated along with impressive AUC values. Thus, in response to diverse detection methods, optimizing nanoframe dimensions such as nanogap and frame thickness to maximize sensor performance is critical to realize future POCT diagnosis.

Image 1., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Breast cancer is a prevalent malignancy affecting women globally, necessitating effective treatment strategies. This study explores the potential of ergosterol, a bioactive compound found in edible mushrooms, as a candidate for breast cancer treatment. Breast cancer cell lines (MCF-7 and MDA-MB-231) were treated with ergosterol, revealing its ability to inhibit cell viability, induce cell cycle arrest, and suppress spheroid formation. Mechanistically, ergosterol demonstrated significant inhibitory effects on the Wnt/beta-catenin signaling pathway, a critical regulator of cancer progression, by attenuating beta-catenin translocation in the nucleus. This suppression was attributed to the inhibition of AKT/GSK-3beta phosphorylation, leading to decreased beta-catenin stability and activity. Additionally, ergosterol treatment impacted protein synthesis and ubiquitination, potentially contributing to its anti-cancer effects. Moreover, the study revealed alterations in metabolic pathways upon ergosterol treatment, indicating its influence on metabolic processes critical for cancer development. This research sheds light on the multifaceted mechanisms through which ergosterol exerts anti-tumor effects, mainly focusing on Wnt/beta-catenin pathway modulation and metabolic pathway disruption. These findings provide valuable insights into the potential of ergosterol as a therapeutic candidate for breast cancer treatment, warranting further investigation and clinical application., (© 2024. The Author(s).)

Artificial Intelligence (AI) is transforming healthcare, notably in ophthalmology, where its ability to interpret images and data can significantly enhance disease diagnosis and patient care. Recent developments in oculomics, the integration of ophthalmic features to develop biomarkers for systemic diseases, have demonstrated the potential for providing rapid, non-invasive methods of screening leading to enhance in early detection and improve healthcare quality, particularly in underserved areas. However, the widespread adoption of such AI-based technologies faces challenges primarily related to the trustworthiness of the system. We demonstrate the potential and considerations needed to develop trustworthy AI in oculomics through a pilot study for HbA1c assessment using an AI-based approach. We then discuss various challenges, considerations, and solutions that have been developed for powerful AI technologies in the past in healthcare and subsequently apply these considerations to the oculomics pilot study. Building upon the observations in the study we highlight the challenges and opportunities for advancing trustworthy AI in oculomics. Ultimately, oculomics presents as a powerful and emerging technology in ophthalmology and understanding how to optimize transparency prior to clinical adoption is of utmost importance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate functional outcomes, radiologic results, and complications after hybrid total hip arthroplasty (THA) in patients with subchondral insufficiency fractures (SIFs) of the femoral head., Methods: From June 2009 to December 2020, among 985 patients who underwent hybrid THA at our hospital, 19 patients diagnosed with SIF through a retrospective chart review were included. Those under 50 years of age, with radiographic findings of osteonecrosis on the contralateral side of surgery, a history of organ transplantation, and alcohol abuse, were excluded. Functional evaluation was performed using a modified Harris Hip Score (HHS). After surgery, inclination and anteversion of the acetabular cup and version of the femoral system were measured using postoperative x-ray. The outpatient follow-up was performed at 6 weeks, 3 months, 9 months, and 12 months after surgery and every year thereafter. Complications including dislocation, implant loosening, stem subsidence, and periprosthetic infection were observed on follow-up radiographs., Results: The average follow-up time was 29.3 ± 9.1 months (range, 24-64 months) with no loss to follow-up. The mean modified HHS was 83.4 ± 9.6 (range, 65-100) at the last outpatient clinic follow-up. The average inclination of the acetabular cup was 41.9° ± 3.4° (range, 37°-48°), and the anteversion was 27.5° ± 6.7° (range, 18°-39°). The version of the femoral stem was 19° ± 5.7° (range, 12°-29°). There was no case of intraoperative fracture. There were no cases of dislocation, loosening of the cup, subsidence of the femoral stem, intraoperative or periprosthetic fracture, or periprosthetic infection on the follow-up radiographs., Conclusions: In our study, hybrid THA showed favorable outcomes in patients diagnosed with SIF, and there were no further special considerations as for THA performed due to other diseases or fractures., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Background: To ensure effective patient engagement, patients' efforts, partnerships with healthcare professionals, and the organisation's role in providing safe healthcare settings must be emphasised. Perception gaps regarding patient engagement between the public and healthcare professionals could prevent healthy partnerships from forming and hinder patient engagement activities. This study examined healthcare professionals' perception of patient engagement and compared the findings with that determined for the public in a previous study., Methods: An anonymous online survey was conducted in February 2020 among 1,007 healthcare professionals (physicians, nurses). The questionnaire comprised five parts regarding the perception of patient engagement. Descriptive analysis and Chi-squared/Fisher's exact tests determined the frequency and significant differences among the public from previous study and healthcare professionals in this study., Results: The perception of the importance of patient safety was high among healthcare professionals and the public. However, statistically significant differences in perceptions were observed among the public and healthcare professionals in all categories. The perception gaps were substantial between the groups in sub-categories of engagement for patient safety during medical treatment; 86% of physicians and 90% of nurses agreed that patients participate in the decision-making for the treatment process. Conversely, 58% of the public agreed. Only 22% of the public agreed with confirming healthcare professionals' hand washing to prevent infection, versus 57% of physicians and 65% of nurses. More than 89% of healthcare professionals positively perceived medical dispute mediation versus only half of the public. In certain areas such as "medical dispute mediation and arbitration programs", "fall prevention", and "infection prevention", there was a statistically significant difference in the perception of patient involvement among healthcare professionals, with nurses' perception being particularly more positive than that of physicians., Conclusions: The healthcare professionals' perception of patient engagement was more positive than that of the public. To narrow the perception gaps and enhance the public's perception, strategies involving changes in healthcare systems, promotional efforts, and educational initiatives should be developed. Additionally, strategies should be formulated for healthcare professionals to better engage as partners in patient care.

Neurodegenerative diseases, characterized by progressive neuronal dysfunction and loss, pose significant health challenges. Glutamate accumulation contributes to neuronal cell death in diseases such as Alzheimer's disease. This study investigates the neuroprotective potential of Albizia lebbeck leaf extract and its major constituent, luteolin, against glutamate-induced hippocampal neuronal cell death. Glutamate-treated HT-22 cells exhibited reduced viability, altered morphology, increased ROS, and apoptosis, which were attenuated by pre-treatment with A. lebbeck extract and luteolin. Luteolin also restored mitochondrial function, decreased mitochondrial superoxide, and preserved mitochondrial morphology. Notably, we first found that luteolin inhibited the excessive process of mitophagy via the inactivation of BNIP3L/NIX and inhibited lysosomal activity. Our study suggests that glutamate-induced autophagy-mediated cell death is attenuated by luteolin via activation of mTORC1. These findings highlight the potential of A. lebbeck as a neuroprotective agent, with luteolin inhibiting glutamate-induced neurotoxicity by regulating autophagy and mitochondrial dynamics., (© 2024. The Author(s).)

Background: Obesity is characterized by an imbalance between energy intake and expenditure, leading to the excessive accumulation of triglycerides in adipose tissue., Objective: This study investigated the potential of Oxylia to prevent obesity in mice fed with a high-fat diet (HFD)., Design: C57BL/6J mice were fed with one of the following five diets - AIN93G normal diet (normal control), 60% (HFD; control), HFD containing metformin at 40 mg/kg body weight (b.w.) (Met; positive control), HFD containing Oxylia at 30 mg/kg b.w. (O30), or HFD containing Oxylia at 60 mg/kg b.w. (O60) - for 15 weeks., Results: Mice under an HFD supplemented with Oxylia had decreased body weight gain, adipose tissue weight, and adipose tissue mass. In addition, triglyceride (TG), total cholesterol, and VLDL/LDL cholesterol levels were lower in the O60 groups than in the HFD-fed control group. Moreover, Oxylia supplementation decreased the expression of adipogenesis-related mRNAs and lipogenesis-related proteins while increasing the expression of lipolysis-related proteins in white adipose tissue and thermogenesis-related proteins in brown adipose tissue., Conclusions: These findings suggest that Oxylia has potential as a functional food ingredient for the prevention and treatment of obesity and related metabolic disorders., Competing Interests: The authors declare no conflict of interest. No funding was received., (© 2024 Seong-Hoo Park et al.)

Introduction: In 2022 chatGPT™ (OpenAI, San Francisco) was introduced to the public. The complex reasoning and the natural language processing (NLP) ability of the AI platform has generated much excitement about the potential applications. This study conducted a preliminary analysis of the chatGPT™'s ability to formulate a management plan in accordance with oncological principles for patients with colorectal cancer., Methodology: Colorectal cancer cases discussed in the multidisciplinary tumor (MDT) board at a single tertiary institution between September 2022 and January 2023 were prospectively collected. The treatment recommendations made by the chatGPT™ for Stage IV, recurrent, synchronous colorectal cancer were analysed for adherence to oncological principles. The recommendations by chatGPT™ were compared with the decision plans made by the MDT., Results: In all cases, the chatGPT™ was able to adhere to oncological principles. The recommendations in all 30 cases factored in the patient's overall health and functional status. The oncological management recommendation concordance rate between chatGPT™ and the MDT was 86.7%., Conclusions: This study shows a high concordance rate of the chatGPT™'s recommendations with that given by the MDT in the management of complex colorectal patients. This will need to be verified in a larger prospective study., (© 2023 Royal Australasian College of Surgeons.)

Image 1., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to significant global casualties. This study examines the postoperative impact of COVID-19 on patients who underwent gastrointestinal surgery, considering their heightened vulnerability to infections and increased morbidity and mortality risk., Methods: This retrospective observational study was conducted at a tertiary center and patients who underwent gastrointestinal surgery between January 2022 and February 2023 were included. Postoperative COVID-19 infection was defined as the detection of severe acute respiratory syndrome coronavirus 2 RNA by RT-PCR within 14 days after surgery. Propensity score matching was performed including age, sex, American Society of Anesthesiology physical status classification, and emergency operation between the COVID-19-negative (-) and -positive (+) groups., Results: Following 1:2 propensity score matching, 21 COVID-19(+) and 42 COVID-19(-) patients were included in the study. In the COVID-19(+) group, the postoperative complication rate was significantly higher (52.4% vs. 23.8%, P = 0.023). Mechanical ventilator requirement, intensive care unit (ICU) admission, and readmission rate did not significantly differ between the 2 groups. The median length of ICU (19 days vs. 4 days, P < 0.001) and hospital stay (18 vs. 8 days, P = 0.015) were significantly longer in the COVID-19(+) group. Patients with COVID-19 had a 2.4 times higher relative risk (RR) of major complications than patients without COVID-19 (RR, 2.37; 95% confidence interval, 1.254-4.467; P = 0.015)., Conclusion: COVID-19 infection during the postoperative period in gastrointestinal surgery may have adverse outcomes which may increase the risk of major complications. Preoperative COVID-19 screening and protocols for COVID-19 prevention in surgical patients should be maintained., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

(1) Introduction : The laparoscopic approach to low pelvic tumors is challenging and hindered by suboptimal tumor visualization and dissection, with possible oncological failure. Stereotactic navigation provides real-time image guidance that may optimize safety, accuracy, and precision when dissecting challenging low pelvic tumors. (2) Methods: Preoperative CT images were acquired with eight skin-fixed fiducials and loaded into a navigation system. A patient tracker was mounted on the bed side. Patient-to-image paired point registration was performed, and an instrument tracker was mounted on a laparoscopic instrument and calibrated for instrument tracking. Surgical operations were performed with real-time stereotactic navigation assistance. (3) Results : Three patients underwent stereotactic navigation surgery. Fiducial registration errors were good to optimal (±1.9, ±3.4, and ±3.4 mm). Lesions were easily identified and targeted with real-time navigation. Surgeries were uneventful. Histopathology examinations identified one retro-rectal schwannoma, one lateral pelvic recurrence from rectal adenocarcinoma, and one advanced anal canal carcinoma. No navigation-related complications, readmissions, or postoperative mortalities were observed. (4) Conclusions: The application of laparoscopic stereotactic navigation surgery to complex low pelvic tumors is feasible and could impact oncological surgical quality by enabling tumor targeting and ensuring resection margins. Further wider series are needed to confirm stereotactic navigation's impact on challenging low pelvic tumors.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Background: Cerebral amyloid angiopathy (CAA) pathology is becoming increasingly important in Alzheimer's disease (AD) because of its potential link to amyloid-related imaging abnormalities, a critical side effect observed during AD immunotherapy. Identification of CAA without typical magnetic resonance imaging (MRI) markers (MRI-negative CAA) is challenging, and novel detection biomarkers are needed., Methods: We included 69 participants with high neuritic plaques (NP) burden, with and without CAA pathology (NP with CAA vs. NP without CAA) based on autopsy data from the Alzheimer's Disease Neuroimaging Initiative. Two participants with hemorrhagic CAA markers based on MRI were excluded and the final analysis involved 36 NP without CAA and 31 NP with CAA. A logistic regression model was used to compare the cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), phosphorylated tau181, and total tau levels, the amyloid positron emission tomography (PET) standardized uptake ratio (SUVR), and cognitive profiles between NP with and without CAA. Regression models for CSF and PET were adjusted for age at death, sex, and the last assessed clinical dementia rating sum of boxes score. Models for cognitive performances was adjusted for age at death, sex, and education level., Results: NP with CAA had significantly lower CSF Aβ42 levels when compared with those without CAA (110.5 pg/mL vs. 134.5 pg/mL, p-value = 0.002). Logistic regression analysis revealed that low CSF Aβ42 levels were significantly associated with NP with CAA (odds ratio [OR]: 0.957, 95% confidence interval [CI]: 0.928, 0.987, p-value = 0.005). However, amyloid PET SUVR did not differ between NP with CAA and those without CAA (1.39 vs. 1.48, p-value = 0.666). Logistic regression model analysis did not reveal an association between amyloid PET SUVR and NP with CAA (OR: 0.360, 95% CI: 0.007, 1.741, p-value = 0.606)., Conclusions: CSF Aβ42 is more sensitive to predict MRI-negative CAA in high NP burden than amyloid PET., Competing Interests: There is nothing to declare.

This study aimed to assess recurrence patterns and related risk factors following curative resection of colorectal cancer (CRC). This retrospective observational study was conducted at a tertiary care center, including 2622 patients with stage I-III CRC who underwent curative resection between 2008 and 2018. Hazard rates of recurrence were calculated using a hazard function. The primary outcome was the peak recurrence time after curative resection and secondary outcomes were prognostic factors associated with recurrence. Over a median follow-up period of 53 months, the overall, locoregional and systemic recurrence rates were 8.9%, 0.7%, and 8.5%, respectively. Recurrence rates were significantly higher for rectal cancer (14.9% overall, 4.4% locoregionally, and 12.3% systemically) than for colon cancer (all p < 0.001). The peak recurrence time was 11 months, with variations in hazard rates and curves depending on the tumor location, stage, and risk factors. Patients with AL or CRM involvement exhibited a distinct pattern, with a high hazard rate in the early postoperative period. Understanding these recurrence patterns and risk factors is crucial for establishing effective postoperative surveillance strategies. Our findings suggested that short-interval surveillance should be considered during the first 2 years post-surgery, particularly for high-risk patients who should receive early attention.

The purpose of this study was to identify differences in temporal parameters correlating to the presence of aspiration and the severity of penetration-aspiration scale (PAS) in patients with dysphagia after stroke. We also investigated whether there was a significant difference in temporal parameters based on the location of the stroke lesion. A total of 91 patient videofluoroscopic swallowing study (VFSS) videos of stroke patients with dysphagia were retrospectively analyzed. Various temporal parameters including oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration, upper esophageal sphincter opening duration and upper esophageal sphincter reaction time were measured. Subjects were grouped by the presence of aspiration, PAS score, and location of the stroke lesion. Pharyngeal response time, laryngeal vestibule closure duration, and upper esophageal sphincter opening duration were significantly prolonged in the aspiration group. These three factors showed positive correlation with PAS. In terms of stroke lesion, oral phase duration was significantly prolonged in the supratentorial lesion group, while upper esophageal sphincter opening duration was significantly prolonged in the infratentorial lesion group. We have demonstrated that quantitative temporal analysis of VFSS can be a clinically valuable tool identifying dysphagia pattern associated with stroke lesion or aspiration risk., (© 2023. The Author(s).)

Several diseases are associated with improper regulation of the Hippo pathway, which plays an important role in cell proliferation and cancer metastasis. Overactivation of the YAP and TAZ proteins accelerates cell proliferation, invasion, and migration during tumorigenesis. Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug (NSAID) that exhibits activity against various types of cancer. In this study, we observed that TA decreased YAP and TAZ protein levels in cancer cells. TA increased the phosphorylation of YAP and TAZ, leading to the degradation of YAP and TAZ in the cytoplasm and nucleus. TA predominantly affected multiple phosphodegron sites in the YAP and TAZ and lowered 14-3-3β protein expression, causing YAP and TAZ to enter the ubiquitination pathway. Proteins that affect YAP and TAZ regulation, such as NAG-1 and several YAP/TAZ E3 ligases, were not involved in TA-mediated YAP/TAZ degradation. In summary, our results indicate that TA affects phosphodegron sites on YAP/TAZ, demonstrating a novel effect of TA in tumorigenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT)., Methods: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness., Discussion: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness., Trial Registration: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023., (© 2023. The Author(s).)

Temporal parameters during swallowing are analyzed for objective and quantitative evaluation of videofluoroscopic swallowing studies (VFSS). Manual analysis by clinicians is time-consuming, complicated and prone to human error during interpretation; therefore, automated analysis using deep learning has been attempted. We aimed to develop a model for the automatic measurement of various temporal parameters of swallowing using deep learning. Overall, 547 VFSS video clips were included. Seven temporal parameters were manually measured by two physiatrists as ground-truth data: oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration, and upper esophageal sphincter opening duration. ResNet3D was selected as the base model for the deep learning of temporal parameters. The performances of ResNet3D variants were compared with those of the VGG and I3D models used previously. The average accuracy of the proposed ResNet3D variants was from 0.901 to 0.981. The F1 scores and average precision were 0.794 to 0.941 and 0.714 to 0.899, respectively. Compared to the VGG and I3D models, our model achieved the best results in terms of accuracy, F1 score, and average precision values. Through the clinical application of this automatic model, temporal analysis of VFSS will be easier and more accurate., (© 2023. Springer Nature Limited.)

Raman spectroscopy is widely used for its exceptional identification capabilities in various fields. Traditional methods for target identification using Raman spectroscopy rely on signal correlation with moving windows, requiring data preprocessing that can significantly impact identification performance. In recent years, deep-learning approaches have been proposed to leverage data augmentation techniques, such as baseline and additive noise addition, in order to overcome data scarcity. However, these deep-learning methods are limited to the spectra encountered during training and struggle to handle unseen spectra. To address these limitations, we propose a multi-input hybrid deep-learning model trained with simulated spectral data. By employing simulated spectra, our method tackles the challenges of data scarcity and the handling of unseen spectra encountered in traditional and deep-learning methods. Experimental results demonstrate that our proposed method achieves outstanding identification performance and effectively handles spectra obtained from different Raman spectroscopy systems., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Natural products have successfully treated several diseases using a multi-component, multi-target mechanism. However, a precise mechanism of action (MOA) has not been identified. Systems pharmacology methods have been used to overcome these challenges. However, there is a limitation as those similar mechanisms of similar components cannot be identified. In this study, comparisons of physicochemical descriptors, molecular docking analysis and RNA-seq analysis were performed to compare the MOA of similar compounds and to confirm the changes observed when similar compounds were mixed and used. Various analyses have confirmed that compounds with similar structures share similar MOA. We propose an advanced method for in silico experiments in herbal medicine research based on the results. Our study has three novel findings. First, an advanced network pharmacology research method was suggested by partially presenting a solution to the difficulty in identifying multi-component mechanisms. Second, a new natural product analysis method was proposed using large-scale molecular docking analysis. Finally, various biological data and analysis methods were used, such as in silico system pharmacology, docking analysis and drug response RNA-seq. The results of this study are meaningful in that they suggest an analysis strategy that can improve existing systems pharmacology research analysis methods by showing that natural product-derived compounds with the same scaffold have the same mechanism., (© The Author(s) 2023. Published by Oxford University Press.)

Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1), also known as growth differentiation factor-15 (GDF-15), is associated with cancer, diabetes, and inflammation, while there is limited understanding of the role of NAG-1 in nociception. Here, we examined the nociceptive behaviors of NAG-1 transgenic (TG) mice and wild-type (WT) littermates. Mechanical sensitivity was evaluated by using the von Frey filament test, and thermal sensitivity was assessed by the hot-plate, Hargreaves, and acetone tests. c-Fos, glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule-1 (Iba-1) immunoreactivity was examined in the spinal cord following observation of the formalin-induced nociceptive behaviors. There was no difference in mechanical or thermal sensitivity for NAG-1 TG and WT mice. Intraplantar formalin injection induced nociceptive behaviors in both male and female NAG-1 TG and WT mice. The peak period in the second phase was delayed in NAG-1 TG female mice compared with that of WT female mice, while there was no difference in the cumulative time of nociceptive behaviors between the two groups of mice. Formalin increased spinal c-Fos immunoreactivity in both TG and WT female mice. Neither GFAP nor Iba-1 immunoreactivity was increased in the spinal cord of TG and WT female mice. These findings indicate that NAG-1 TG mice have comparable baseline sensitivity to mechanical and thermal stimulation as WT mice and that NAG-1 in female mice may have an inhibitory effect on the second phase of inflammatory pain. Therefore, it could be a novel target to inhibit central nervous system response in pain.

Background: Herbal medicines traditionally target organs for treatment based on medicinal properties, and this theory is widely used for prescriptions. However, the scientific evidence explaining how herbs act on specific organs by biological methods has been still limited. This study used bioinformatic tools to identify the target organ locations of Radix Achyranthis Bidentatae (RAB), a blood-activating herb that nourishes the liver and kidney, strengthens bones, and directs prescription to the lower body. Methods: RAB's active compounds and targets were collected and predicted using databases such as TCMSP, HIT2.0, and BATMAN-TCM. Next, the RAB's target list was analyzed based on two approaches to obtain target organ locations. DAVID and Gene ORGANizer enrichment-based approaches were used to enrich an entire gene list, and the BioGPS and HPA gene expression-based approaches were used to analyze the expression of core genes. Results: RAB's targets were found to be involved in whole blood, blood components, and lymphatic organs across all four tools. Each tool indicated a particular aspect of RAB's target organ locations: DAVID-enriched genes showed a predominance in blood, liver, and kidneys; Gene ORGANizer showed the effect on low body parts as well as bones and joints; BioGPS and HPA showed high gene expression in bone marrow, lymphoid tissue, and smooth muscle. Conclusion: Our bioinformatics-based target organ location prediction can serve as a modern interpretation tool for the target organ location theory of traditional medicine. Future studies should predict therapeutic target organ locations in complex prescriptions rather than single herbs and conduct experiments to verify predictions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tran, Baek, Jun and Lee.)

Background: Serum carcinoembryonic antigen (CEA) increase in patients with colorectal cancer (CRC) recurrence was observed to vary depending on their initial values. This study aimed to evaluate the diagnostic accuracy of CEA for detecting CRC recurrence in patients with normal and elevated initial CEA levels., Methods: A total of 261 CRC recurrence patients who underwent curative resection were included and divided into two groups, normal and elevated initial CEA. Analysis was performed comparing patient, tumor, and recurrence characteristics retrospectively., Results: There were 192 patients with normal and 69 with high initial CEA levels. Patient and tumor characteristics were similar. Eighty-six patients had elevated CEA at the time of recurrence, and the overall sensitivity of CEA for recurrence was 33.0%. In the high initial CEA group, 59.4% exhibited increased CEA level at recurrence, whereas in patients with normal initial CEA levels, only 23.4% showed elevated levels (p < 0.001). Patients with both high CEA preoperatively and at recurrence had more local recurrence, but there was no statistical significance (p = 0.053), and the rate of lung metastasis was higher in patients whose CEA remained normal at recurrence (38.3% vs. 24.4%, p = 0.026). The overall survival of patients with elevated CEA at recurrence was worse than those with normal CEA levels (56.9% vs. 42.4%, p = 0.003)., Conclusion: The diagnostic accuracy of CEA for detecting recurrence depends on initial CEA level. Regardless of the initial CEA level, elevation at recurrence was significantly associated with overall survival in patients with recurrent CRC., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background: Cold atmospheric plasma is a novel innovative approach for wound care, and it is currently underrepresented in veterinary medicine., Objectives: To investigate the efficacy and safety of using cold atmospheric microwave plasma (CAMP) as an adjunct therapy for wound healing in dogs and cats., Methods: Wound healing outcomes were retrospectively analyzed using clinical records of client-owned dogs and cats who were first managed through standard wound care alone (pre-CAMP period) and subsequently via CAMP therapy (CAMP period). The degree of wound healing was estimated based on wound size and a modified wound scoring system., Results: Of the 27 acute and chronic wounds included in the analysis, 81.48% showed complete healing after the administration of CAMP as an adjunct therapy to standard care. Most wounds achieved complete healing in < 5 weeks. Compared with the pre-CAMP period, the rate of wound healing significantly increased every week in the CAMP period in terms of in wound size (first week, p < 0.001; second week, p = 0.012; third week, p < 0.001) and wound score (first week, p < 0.001; second week, p < 0.001; third week, p = 0.001). No adverse events were noted except for mild discomfort and transient erythema., Conclusions: CAMP is a well-tolerated therapeutic option with immense potential to support the treatment of wounds of diverse etiology in small animal practice. Further research is warranted to establish specific criteria for CAMP treatment according to wound characteristics., Competing Interests: Cheol-Yong Hwang is a founder and chief clinical officer, and Seung Joon Baek is a founder and chief medical officer at IonMedical. IonMedical was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (© 2023 The Korean Society of Veterinary Science.)

Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1-splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed that TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type, as identified in vivo and in vitro. These activities of TSP1V are caused by inhibiting phospho-Smad and phospho-focal adhesion kinase. Reverse transcription polymerase chain reaction and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs enhanced IR. We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment. Additionally, sulindac sulfide reduced phospho-RBM5 levels in a time-dependent manner. Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In cell-based regenerative medicine, induced pluripotent stem cells (iPSCs) generated from reprogrammed adult somatic cells have emerged as a useful cell source due to the lack of ethical concerns and the low risk of immune rejection. To address the risk of teratoma formation, which is a safety issue in iPSC-based cell therapy, it is essential to selectively remove undifferentiated iPSCs remaining in the iPSC-derived differentiated cell product prior to in vivo transplantation. In this study, we explored whether an ethanol extract of coptidis rhizoma (ECR) exhibited anti-teratoma activity and identified the active components involved in the selective elimination of undifferentiated iPSCs. Transcriptome analysis of iPSCs confirmed that cell death-related pathways were significantly altered by ECR treatment. Our results demonstrate that ECR effectively induced apoptotic cell death and DNA damage in iPSCs, and that reactive oxygen species generation, mitochondrial damage, caspase activation, and p53 activation were involved in ECR-mediated iPSC death. However, in iPSC-derived differentiated cells (iPSC-Diff), reduced cell viability and the DNA damage response were not observed after ECR treatment. We co-cultured iPSCs and iPSC-Diff and found that ECR treatment selectively removed iPSCs, whereas iPSC-Diff remained intact. Prior to in ovo implantation, ECR treatment of a mixed cell culture of iPSCs and iPSC-Diff significantly suppressed iPSC-derived teratoma formation. Among the main components of the ECR, berberine and coptisine showed selective cytotoxicity to iPSCs but not to iPSC-Diff. Together, these results indicate the usefulness of ECRs in preparing safe and effective iPSC-based therapeutic cell products with no risk of teratoma formation.

Background: Glutamate, an excitatory neurotransmitter, was elevated in the brain of neurodegenerative disease (ND) patients. The excessive glutamate induces Ca 2+ influx and reactive oxygen species (ROS) production which exacerbates mitochondrial function, leading to mitophagy aberration, and hyperactivates Cdk5/p35/p25 signaling leading to neurotoxicity in ND. Stigmasterol, a phytosterol, has been reported for its neuroprotective effects; however, the underlying mechanism of stigmasterol on restoring glutamate-induced neurotoxicity is not fully investigated., Purpose: We investigated the effect of stigmasterol, a compound isolated from Azadirachta indica (AI) flowers, on ameliorating glutamate-induced neuronal apoptosis in the HT-22 cells., Study Design: To further understand the underlying molecular mechanisms of stigmasterol, we investigated the effect of stigmasterol on Cdk5 expression, which was aberrantly expressed in glutamate-treated cells. Cell viability, Western blot analysis, and immunofluorescence are employed., Results: Stigmasterol significantly inhibited glutamate-induced neuronal cell death via attenuating ROS production, recovering mitochondrial membrane depolarization, and ameliorating mitophagy aberration by decreasing mitochondria/lysosome fusion and the ratio of LC3-II/LC3-I. In addition, stigmasterol treatment downregulated glutamate-induced Cdk5, p35, and p25 expression via enhancement of Cdk5 degradation and Akt phosphorylation. Although stigmasterol demonstrated neuroprotective effects on inhibiting glutamate-induced neurotoxicity, the efficiency of stigmasterol is limited due to its poor water solubility. We conjugated stigmasterol to soluble soybean polysaccharides with chitosan nanoparticles to overcome the limitations. We found that the encapsulated stigmasterol increased water solubility and enhanced the protective effect on attenuating the Cdk5/p35/p25 signaling pathway compared with free stigmasterol., Conclusion: Our findings illustrate the neuroprotective effect and the improved utility of stigmasterol in inhibiting glutamate-induced neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The reaching performance scale for stroke evaluates reach-to grasp movement of the upper extremity and compensatory movements. The objective of the study was to translate and cross-culturally adapt the reaching performance scale for stroke into Korean and assess its reliability and validity. An expert committee supervised the forward and backward translation and the final translated Korean version of reaching performance scale for stroke (K-RPSS). Ninety-eight individuals (mean age 63.63 ± 13.13 years), with hemiplegia after stroke (97.82 ± 191.50 weeks) were evaluated independently by physiatrist and occupational therapist using K-RPSS. Degree of the motor impairment and functional status of patients were evaluated with the Fugl-Meyer assessment for upper limb and manual function test. The K-RPSS demonstrated excellent intra-rater (intraclass correlation coefficient = 0.9865), inter-rater (intraclass correlation coefficient 0.9866) reliability, and internal consistency (Cronbach α = 0.977 for total score). The validity of K-RPSS was confirmed with strong correlation with Fugl-Meyer assessment and manual function test. The K-RPSS had ceiling effect and the 3 points is the score change needed to indicate a change in a patient. K-RPSS has been shown to be a reliable and valid tool for assessing the compensation and movement quality of the upper limb and trunk when performing a reach-to grasp task. The K-RPSS is expected to be used widely by Korean speaking clinicians and researchers., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Korean diesel particulate matter 20 (KDP20) is a pollutant comprising a complex mixture of carbon and chemical irritants. Although particulate matter and nasal inflammation are strongly associated, the underlying molecular mechanism based on systematic transcriptome analysis remains unknown. In this study, genome-wide gene expression profiles of mouse nasal tissues were determined following exposure to KDP20 for 5 and 10 days and compared with those of the control (n = 4/group). We identified 758 significant differentially expressed genes (DEGs) and classified them as 5-day-specific, 10-day-specific, and common among groups based on their expression patterns. The terms "regulation of alpha-beta T cell differentiation," "macrophage differentiation," and "cell adhesion mediated by integrin" were significantly enriched in each group. Receiver operating characteristic analysis revealed six genes as potential predictive biomarkers. The differential expression of these six genes was validated using quantitative RT-PCR (n = 3/group). Furthermore, a possible mechanism for nasal inflammation was suggested through the binding analysis between metal ions and genes. The genes identified in this study may play important roles in regulating the mechanism of nasal inflammation induced by diesel particles, especially immune cell regulation, and may function as markers for diesel particle-induced nasal inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The applicability of laparoscopic D3 oncological resection for splenic flexure cancer (SFC) surgery has not been fully explored due to technical difficulties and variations in surgical procedure. The aim of this work is to describe the feasibility of performing laparoscopic D3 resection in SFC and its impact on long-term survival., Method: A retrospective study on 47 out of 52 consecutive patients who underwent elective laparoscopic colectomy for SFC from December 2006 until December 2019 at Korea University Anam Hospital was performed. Data on patients' demographic and clinical features, surgical procedures, intraoperative and postoperative complications, pathological features and follow-up were collected. Categorical data are expressed as frequencies (n) and percentages (%). Continuous data are expressed as mean ± standard deviation and median (range). The Kaplan-Meier test was used to determine the overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS)., Results: The median age of patients was 67.0 years (range 27-87 years) and 72.3% were men. Ten (21.3%) patients presented with an obstructing tumour and underwent an elective laparoscopic colectomy, while 68.1% of patients presented with Stage II and III disease. The conversion rate was 4.3% and the morbidity rate was 31.9%. There was one postoperative death secondary to splenic infarction and anastomotic leak leading to multi-organ failure. Four deaths occurred due to disease progression during a median follow-up of 63.8 months. The rate of recurrence was 20%, the 5-year OS was 89.6% and the 5-year PFS was 72.9%. After R0 resection, the 5-year OS was 91.5% and the 5-year DFS was 74.5%., Conclusion: Laparoscopic D3 colectomy for SFC is feasible, with an acceptable morbidity and long-term oncological outcome when performed by highly skilled laparoscopic colorectal surgeons with knowledge of the complex anatomy around the splenic flexure. Further randomized trials should be performed to determine the advantage of laparoscopic D3 colectomy over conventional colectomy for SFC., (© 2022 Association of Coloproctology of Great Britain and Ireland.)

Hair loss or alopecia is an unpleasant symptom that exacerbates an individual's self-esteem and requires appropriate treatment. The Wnt/β-catenin signaling is a central pathway that promotes dermal papilla induction and keratinocyte proliferation during hair follicle renewal. GSK-3β inactivated by its upstream Akt and ubiquitin-specific protease 47 (USP47) has been shown to inhibit β-catenin degradation. The cold atmospheric microwave plasma (CAMP) is microwave energy enriched with mixtures of radicals. CAMP has been reported to have antibacterial and antifungal activities with wound healing activity against skin infection; however, the effect of CAMP on hair loss treatment has not been reported. We aimed to investigate the effect of CAMP on promoting hair renewal in vitro and to elucidate the molecular mechanism, targeting β-catenin signaling and YAP/TAZ, the co-activators in the Hippo pathway, in human dermal papilla cells (hDPCs). We also evaluated plasma effects on the interaction between hDPCs and HaCaT keratinocytes. The hDPCs were treated with plasma-activating media (PAM) or gas-activating media (GAM). The biological outcomes were determined by MTT assay, qRT-PCR, western blot analysis, immunoprecipitation, and immunofluorescence. We found that β-catenin signaling and YAP/TAZ were significantly increased in PAM-treated hDPCs. PAM treatment also induced β-catenin translocation and inhibited β-catenin ubiquitination by activating Akt/GSK-3β signaling and upregulating USP47 expression. In addition, hDPCs were more aggregated with keratinocytes in PAM-treated cells compared with control. HaCaT cells cultured in a conditioned medium derived from PAM-treated hDPCs exhibited an enhancing effect on activating YAP/TAZ and β-catenin signaling. These findings suggested that CAMP may be a new therapeutic alternative for alopecic treatment., (© 2023. The Author(s).)

Purpose: To investigate oncologic outcomes including overall survival and disease-free survival depending on the extent of lymphadenectomy (D3 versus D2) by comparing D3 and D2 lymphadenectomy in patients with clinical stage 2/3 right colon cancer., Methods: Consecutive series of patients who underwent radical resection for right colon cancer at our three hospitals between January 2015 and June 2018 were retrospectively analyzed. Study cohorts were divided into two groups: D3 group and D2 group. Oncologic, pathologic, and perioperative outcomes of the two groups were compared., Results: A total of 295 patients (167 in the D2 group and 128 in the D3 group) were included in this study. Patients' characteristics showed no significant difference between the two groups. The median number of harvested lymph nodes was significantly higher in the D3 group than in the D2 group. The rate of complications was not significantly different between the two groups except for chyle leakage, which was more frequent in the D3 group. Five-year disease-free survival was 90.2% (95% CI: 84.8-95.9%) in the D3 group, which was significantly (p = 0.028) higher than that (80.5%, 95% CI: 74-87.5%) in the D2 group. There was no significant difference in overall survival between the two groups., Conclusion: Our results indicate that D3 lymphadenectomy is associated with more favorable 5-year disease-free survival than D2 lymphadenectomy for patients with stage 2/3 right-sided colon cancer. D3 lymphadenectomy might improve oncologic outcomes in consideration of the recurrence rate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lateral pelvic lymph node dissection has been performed selectively in rectal cancer cases; however, it involves highly skilled techniques because of the complex adjacent anatomical structures., Materials and Methods: Laparoscopic EP-LPND was performed in Korea University Anam Hospital from June 2018, and short-term surgical outcomes were analyzed from June to December 2018. Among the patients with histologically diagnosed rectal adenocarcinoma, patients who were suspected Lateral pelvic lymph node metastasis at magnetic resonance imaging were selected for this procedure ., Results: Seven patients underwent laparoscopic extraperitoneal approach for lateral pelvic lymph node dissection in the study period. The mean number of retrieved lymph node was 4.57, and metastatic lymph nodes were identified in 3 patients (42.8%). All of the lymph nodes with suspected metastasis preoperatively were removed in postoperative images. There was no immediate postoperative complication beyond the moderate grade associated with lateral pelvic lymph node dissection. The median follow-up was 9 months, and there were no local recurrence nor complications related to sexual and voiding functions., Conclusions: The laparoscopic extraperitoneal approach might be an efficient way to perform lateral pelvic lymph node dissection using the same principles as the conventional method without violation of the peritoneum.

Cutaneous wound healing is a biological process that occurs upon skin injury and involves different mechanisms to repair tissue damage. Improper healing or prolonged curation period of wound lesions may induce unpleasant complications. Cold atmospheric microwave plasma (CAMP) is an upcoming medical therapeutic option for skin infection and wound treatment. However, the molecular mechanisms of CAMP-mediated canine wound healing are not well characterized. Wound-healing activity was examined to elucidate the biological effects and molecular mechanisms of CAMP. Canine keratinocytes (CPEKs) were treated using CAMP, and their wound-healing activities were evaluated. The molecular mechanisms of that effect were examined, based on RNA-Seq analysis data, and verified using immunoblotting and polymerase chain reaction. It was found that the CAMP-treated cells exhibited a significant increase in cell migration evaluated by scratch assay in human keratinocytes (HaCaT) and canine keratinocytes (CPEK). Additionally, CAMP-treated CPEK cells showed a significant positive effect on cell invasion. The RNA-Seq data revealed that CAMP alters different genes and pathways in CPEK cells. Gene expression involved in the cell cycle, cell proliferation, angiogenesis, cell adhesion, and wound healing was upregulated in CAMP-treated cells compared with gas-activated media used as a control. The Hippo pathway was also analyzed, and the protein and mRNA levels of YAP were significantly increased in CAMP-treated cells. CAMP-treated CPEK cells indicated the downregulation of E-cadherin and upregulation of vimentin, Snail, and Slug at transcription and translation levels, contributing to a favorable effect on cell migration. Our findings suggested that CAMP treatment provided beneficial effects on the curative wound process through the induction of genes involved in wound healing, promotion of EMT, and increase in the molecular targets in the Hippo signaling pathway., Competing Interests: C-YH and SJB are cofounders of Ion Medical Inc. None of the other authors of this manuscript have a financial or non-financial interest related to this work. Ion Medical Inc. was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lertpatipanpong, Sillapachaiyaporn, Oh, Kang, Hwang and Baek.)

The stem bark of Holoptelea integrifolia (Roxb.) Planch. has been applied for the treatment of human cutaneous diseases as well as canine demodicosis in several countries. However, no detailed mechanistic studies have been reported to support their use. In this study, thin-layer chromatography and gas chromatography were used to screen phytochemicals from the fresh stem bark extract of H. integrifolia . We found the two major bioactive compounds, friedelin and lupeol, and their activity on wound healing was further investigated in keratinocytes. Both bioactive compounds significantly reduced wound area and increased keratinocyte migration by increasing matrix metalloproteinases-9 production. Subsequently, we found that the mRNA gene expressions of cadherin 1 and desmoglobin 1 significantly decreased, whereas the gene expression involved in keratinocyte proliferation and homeostasis (keratin-17) increased in compound-treated human immortalized keratinocytes cells. The expression of inflammatory genes (cyclooxygenase-2 and inducible nitric oxide synthase) and pro-inflammatory cytokine genes (tumor necrosis factor-alpha and interleukin-6) was reduced by treatment with n -hexane extract of H. integrifolia and its bioactive compounds. Our results revealed that H. integrifolia extract and its bioactive compounds, friedelin and lupeol, exhibit wound-healing activity with anti-inflammatory properties, mediated by regulating the gene expression involved in skin re-epithelialization.