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AIM OF THE STUDY: Gomisin A (GA) is a small molecular weight lignan contained in Fructus Schisandrae, the dried seed of Schisandra chinensis which is widely used as a tonic in traditional Korean medicine. We previously demonstrated that GA induces endothelium-dependent and -independent relaxation in rat thoracic aorta, however the signaling pathways involved was not clarified. In this study, we examined whether GA could actually induce nitric oxide (NO) production and clarified the mechanism in cultured human coronary artery endothelial cells (HCAEC). RESULTS: Treatment of HCAEC with GA induced NO production in a time- and concentration-dependent manner in association with an enhanced endothelial NO synthase (eNOS) activity with an increased cytosolic translocation of eNOS. Both GA-induced NO production and eNOS activation were attenuated by pretreatment of the cells with EGTA, an extracellular Ca(2+) chelator, and BAPTA-AM, an intracellular Ca(2+) chelator, but not by LY 294002, a PI3-kinase/Akt inhibitor, suggesting involvement of Ca(2+). Furthermore, GA rapidly increased the intracellular Ca(2+) concentration, which was abolished in Ca(2+) free media. CONCLUSION: Taken together, our results suggest that GA induces Ca(2+)-dependent activation and translocation of eNOS in HCAEC, events linked to NO production and thereby endothelial-dependent vasorelaxation. [ABSTRACT FROM AUTHOR]

Background Osteoarthritis (OA) is a prevalent and exhausting condition often requiring long-term management. While there is a steady growth in the use of collagen-based treatment for OA, there is a lack of studies assessing the safety and efficacy of repeated administration of injectable atelocollagen for OA. Objective This study aims to evaluate the clinical efficacy and safety of repeated administration of injectable atelocollagen in reducing knee pain for patients with knee OA. Methods Clinical records of 91 patients from five hospitals were reviewed for this retrospective study. All 91 patients had received repeated administration of injectable atelocollagen (CartiPRO ® , Dalim Tissen Co., Ltd., South Korea) as a treatment for knee OA for seven months. The efficacy of injectable atelocollagen was evaluated by physicians at least 30 days after the last administration, with outcomes categorized as "effective", "moderately effective", or "not effective". For analysis purposes, both "effective" and "moderately effective" were grouped as "effective" while "not effective" was classified as "ineffective". Safety was assessed by monitoring the incidence of adverse events (AEs) reported within six months following the re-administration of atelocollagen. Results Among the 91 patients, 96.7% (88 patients) experienced effective pain relief following the re-administration of CartiPRO ® , with 3.3% (three patients) reporting ineffectiveness. In terms of safety assessment, 35 patients reported AEs, totaling up to 44 events, with no serious or unexpected device-related AEs. Conclusion The repeated use of atelocollagen was found to be both safe and effective in managing knee pain for patients with knee OA. These findings support the repeated use of injectable atelocollagen as a reliable treatment option for managing knee OA pain in clinical practice., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Park et al.)

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia's role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang's potential to enhance ischemic outcomes by targeting microglia. Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48 h, and examined the changes in microglial morphology through skeleton analysis. Results: Weisheng-tang (300 mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor-ticagrelor-eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage. Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke., 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 © 2024 Kim, Lee, Ryu, Lee, Choi, Yun and Shin.)

Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), which is related to anti-apoptosis, cellular proliferation, invasion and migration of tumours, has prognostic significance in malignant tumours in humans as well as in canine melanoma. However, the significance of pSTAT3 in canine liver tissues has not yet been evaluated. This study's objective was to compare its expression in canine normal, non-neoplastic hepatic disease and hepatocellular carcinoma (HCC) tissues by immunohistochemical analysis. Furthermore, the association between pSTAT3 immunostaining and clinicopathological factors was investigated. Overall, 68 canine liver tissues, including 10 normal liver tissues, 30 non-neoplastic hepatic disease tissues and 28 HCC tissues were examined, revealing distinct differences in pSTAT3 immunostaining among the groups. (p < 0.001). Additionally, high pSTAT3 immunostaining was significantly associated with increased tumour size (5 > cm) (p = 0.041), and metastasis (p = 0.046). Furthermore, Kaplan-Meier survival curve analysis revealed a correlation between high pSTAT3 immunostaining and poor disease-free survival (p = 0.013) and overall survival (p = 0.011). These findings suggest that overactivation of STAT3 is associated with poor prognosis in canine HCC. Therefore, pSTAT3 is considered a potential prognostic marker and therapeutic target for canine HCC., (© 2024 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Cheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects., Aim of the Study: The purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study., Materials and Methods: A single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors., Results: CWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca 2+ /calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction., Conclusions: CWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this study to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The digital transformation of healthcare in South Korea, accelerated by COVID-19, has led to increased focus on critically ill patients in large hospitals. To address this, a monitoring system was developed to ensure safe inpatient treatment and improve staff efficiency. This aligns with the Medical Data-Centric Hospitals initiative, which leverages data for healthcare innovation. The case study highlights the implementation of a ward critical care monitoring system, which has improved patient safety, work efficiency, and expanded patient monitoring scope. Key lessons include the importance of addressing technical and user challenges, aligning innovations with national policies, and the potential of data-driven solutions to tackle healthcare challenges.

Although anterior cervical discectomy and fusion (ACDF) is one of the most frequently performed spinal surgeries, there is no consensus regarding the necessity of prescribing a cervical brace after surgery. This study aimed to investigate any difference in radiological and clinical outcomes when wearing or not wearing cervical braces after single- or double-level ACDF. We examined 2 cohorts of patients who underwent single- or double-level ACDF surgery with and without a cervical brace: patients who underwent ACDF between March 2018 and December 2019 received a cervical brace, while patients who underwent ACDF between January 2020 and May 2021 did not. Each patient was evaluated radiologically and functionally using plain X-ray, modified Japanese Orthopedic Association score, and visual analog scale for neck and arm until 12 months after surgery. Fusion rate, subsidence, and postoperative complications were also evaluated. Eighty-three patients were included in the analysis: 38 were braced and 45 were not. The demographic characteristics and baseline outcome measures of both groups were similar. There was no statistically significant difference in any of the clinical measures at baseline. The modified Japanese Orthopedic Association score and visual analog scale for neck and arm were similar in both groups at all time intervals and showed statistically significant improvement when compared with preoperative scores. In addition, fusion rate, subsidence, and postoperative complications were similar in both groups. Our results suggest that the use of cervical braces does not improve the clinical outcomes of individuals undergoing single- or double-level ACDF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models., Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR., Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9 , Pcp2 , Ccl11 , and Cxcl13 , in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models., Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines., Competing Interests: CONFLICTS OF INTEREST Hwa Kyoung Shin has been an editorial board member of Journal of Pharmacopuncture since 2022 but has no role in the decision to publish this article. No other potential conflicts of interest relevant to this aricle were reported., (© 2024 Korean Pharmacopuncture Institute.)

Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function., Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum 's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum 's effects on cognitive decline and AD., Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis., Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum . We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders., Competing Interests: CONFLICTS OF INTEREST Hwa Kyoung Shin has been an editorial board member of Journal of Pharmacopuncture since 2022 but has no role in the decision to publish this article. No other potential conflicts of interest relevant to this aricle were reported., (© 2024 Korean Pharmacopuncture Institute.)

Purpose: Recently, many studies revealed that frailty affects unfavorably on postoperative outcomes in lumbar spinal diseases. This study aimed to investigate the relationship between frailty and clinical outcomes while identifying risk factors associated with worse clinical outcomes following lumbar spinal surgery., Methods: From March 2019 to February 2021, we prospectively enrolled eligible patients with degenerative lumbar spinal diseases requiring surgery. Frailty was assessed preoperatively. To identify the impact of frailty on lumbar spinal diseases, clinical outcomes, which were measured with patient-reported outcomes (PROs) and postoperative complications, were compared according to the frailty. PROs were assessed preoperatively and one year postoperatively. In addition, risk factors for preoperative and postoperative worse clinical outcomes were investigated., Results: PROs were constantly lower in the frail group than in the non-frail group before and after surgery, and the change of PROs between before and after surgery and postoperative complications were not different between the groups. In addition, frailty was a persistent risk factor for postoperative worse clinical outcome before and after surgery in lumbar spinal surgery., Conclusion: Frailty persistently affects the clinical outcome negatively before and after surgery in lumbar spinal surgery. However, as the change of the clinical outcome is not different between the frail group and the non-frail group, it is difficult to interpret whether the frail patients are vulnerable to the surgery. In conclusion, frailty is not an independent risk factor for worse clinical outcome in lumbar spinal surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We propose that cervical intrafacetal fusion (cIFF) using bone chip insertion into the facetal joint space additional to minimal PLF is a supplementary fusion method to conventional posterolateral fusion (PLF)., Methods: Patients who underwent posterior cervical fixation accompanied by cIFF with minimal PLF or conventional PLF for cervical myelopathy from 2012 to 2023 were investigated retrospectively. Radiological parameters including Cobb angle and C2-7 sagittal vertical axis (SVA) were compared between the 2 groups. In cIFF with minimal PLF group, cIFF location and PLF location were carefully divided, and the fusion rates of each location were analyzed by computed tomography scan., Results: Among enrolled 46 patients, 31 patients were in cIFF group, 15 in PLF group. The postoperative change of Cobb angle in 1-year follow-up in cIFF with minimal PLF group and conventional PLF group were 0.1° ± 4.0° and -9.7° ± 8.4° respectively which was statistically lower in cIFF with minimal PLF group (p = 0.022). Regarding the fusion rate in cIFF with minimal PLF group in postoperative 6 months, the rates was achieved in 267 facets (98.1%) in cIFF location, and 244 facets (89.7%) in PLF location (p < 0.001)., Conclusion: Postoperative sagittal alignment was more preserved in cIFF with minimal PLF group compared with conventional PLF group. Additionally, in cIFF with minimal PLF group, the bone fusion rate of cIFF location was higher than PLF location. Considering the concerns of bone chip migration onto the spinal cord and relatively low fusion rate in PLF method, applying cIFF method using minimized PLF might be a beneficial alternative for posterior cervical decompression and fixation.

Objective: Stereotactic radiosurgery (SRS) has been performed for spinal tumors. However, the quantitative effect of SRS on postoperative residual cervical dumbbell tumors remains unknown. This study aimed to quantitatively evaluate the efficacy of SRS for treating postoperative residual cervical dumbbell tumors., Methods: We retrospectively reviewed cases of postoperative residual cervical dumbbell tumors from 1995 to 2020 in 2 tertiary institutions. Residual tumors underwent SRS (SRS group) or were observed with clinical and magnetic resonance imaging (MRI) follow-up (observation group). Tumor regrowth rates were compared between the SRS and observation groups. Additionally, risk factors for tumor regrowth were analyzed., Results: A total of 28 cervical dumbbell tumors were incompletely resected. Eight patients were in the SRS group, and 20 in the observation group. The mean regrowth rate was not significantly lower (p = 0.784) in the SRS group (0.18 ± 0.29 mm/mo) than in the observation group (0.33 ± 0.40 mm/mo). In the multivariable Cox regression analysis, SRS was not a significant variable (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.18-1.79; p = 0.336)., Conclusion: SRS did not significantly decrease the tumor regrowth rate in our study. We believe that achieving maximal resection during the initial operation is more important than postoperative adjuvant SRS.

Objectives: To compare facial growth prediction models based on the partial least squares and artificial intelligence (AI)., Materials and Methods: Serial longitudinal lateral cephalograms from 410 patients who had not undergone orthodontic treatment but had taken serial cephalograms were collected from January 2002 to December 2022. On every image, 46 skeletal and 32 soft-tissue landmarks were identified manually. Growth prediction models were constructed using multivariate partial least squares regression (PLS) and a deep learning method based on the TabNet deep neural network incorporating 161 predictor, and 156 response, variables. The prediction accuracy between the two methods was compared., Results: On average, AI showed less prediction error by 2.11 mm than PLS. Among the 78 landmarks, AI was more accurate in 63 landmarks, whereas PLS was more accurate in nine landmarks, including cranial base landmarks. The remaining six landmarks showed no statistical difference between the two methods. Overall, soft-tissue landmarks, landmarks in the mandible, and growth in the vertical direction showed greater prediction errors than hard-tissue landmarks, landmarks in the maxilla, and growth changes in the horizontal direction, respectively., Conclusions: PLS and AI methods seemed to be valuable tools for predicting growth. PLS accurately predicted landmarks with low variability in the cranial base. In general, however, AI outperformed, particularly for those landmarks in the maxilla and mandible. Applying AI for growth prediction might be more advantageous when uncertainty is considerable., (© 2024 by The EH Angle Education and Research Foundation, Inc.)

Background: This study aimed to evaluate the efficacy of unilateral pediculectomy and reduction with short-segment pedicle screw fixation for thoracolumbar burst fracture., Methods: We retrospectively reviewed patients who underwent a unilateral pediculectomy and reduction with short-segment fixation and interbody fusion for thoracolumbar burst fracture. The unilateral pediculectomy created sufficient space to approach the ventral side of the spinal cord for removing bone fragments and insertion of an interbody cage to correct kyphosis. Lumbar lordosis (LL), pelvic incidence (PI) minus LL, and segmental Cobb angle were measured at 3 time points: preoperatively, postoperatively, and final follow-up. Furthermore, sagittal vertical axis (SVA) was measured to assess global sagittal balance at the final follow-up., Results: A total of 10 patients, with a mean age of 39.8 ± 21.0, underwent the surgical procedure. All patients had a thoracolumbar injury classification and severity score > 5. The mean follow-up period was 15.8 ± 13.9 months. The mean postoperative LL (46.0 ± 5.8) was significantly higher (P = 0.008) than the preoperative measurement (32.8 ± 8.2). The mean postoperative PI minus LL (2.2 ± 8.4) was not significantly lower (P = 0.051) than preoperative measurement (15.4 ± 12.6). The mean postoperative segmental Cobb angle (11.4 ± 8.4) was significantly higher (P < 0.001) than the preoperative measurement (-11.6 ± 10.9). At the final follow-up, the mean sagittal vertical axiswas 10.0 ± 28.8 mm., Conclusions: Unilateral pediculectomy and reduction with short-segment fixation and interbody fusion served as an efficient surgical method for thoracolumbar burst fracture., (Copyright © 2023. Published by Elsevier Inc.)

Gamisoyo-san is an herbal formula widely used to treat psychological issues, menopausal symptoms, and dysmenorrhea. However, there is insufficient information on its safety profile. This study aimed to confirm the genotoxic and acute toxic potential of Gamisoyo-san . We performed a battery of tests, which included a bacterial reverse mutation test (Ames test) using five bacterial strains, an in vitro chromosomal aberration test using Chinese hamster lung (CHL) cells, an in vivo micronucleus test in mice, and human Cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) assays. In the acute toxicity study, male and female rats were orally administered Gamisoyo-san 1000, 2000, or 5000 mg/kg and observed for 14 days. The activities of human CYP450s and UGTs were evaluated using recombinant baculosomes. Gamisoyo-san showed no signs of genotoxicity in the five bacterial strains, CHL cells, or mouse bone marrow cells. The acute toxicity test showed that the median lethal dose (LD 50 ) of Gamisoyo-san was greater than 5000 mg/kg in rats. Gamisoyo-san inhibited the activities of CYP1A2, CYP2C19, and UGT1A1. In conclusion, Gamisoyo-san may not exert severe toxicological events or genotoxic effects at doses up to 5000 mg/kg in rats.

Rationale: Non-invasive transcranial direct current stimulation (tDCS), a promising stimulation tool to modulate a wide range of brain disorders, has major limitations, such as poor cortical stimulation intensity and focality. We designed a novel electrode for tDCS by conjugating a needle to a conventional ring-based high-definition (HD) electrode to enhance cortical stimulation efficacy. Method: HD-tDCS (43 µA/mm 2 , charge density 51.6 kC/m 2 , 20 min) was administered to male C57BL/6J mice subjected to early-stage ischemic stroke. Behavioral tests were employed to determine the therapeutic effects, and the underlying mechanisms of HD-tDCS were determined by performing RNA sequencing and other biomedical analyses. Results: The new HD-tDCS application, showing a higher electric potential and spatial focality based on computational modeling, demonstrated better therapeutic effects than conventional HD-tDCS in alleviating motor and cognitive deficits, with a decrease in infarct volume and inflammatory response. We assessed different electrode configurations in the new HD electrode; the configurations variously showed potent therapeutic effects, ameliorating neuronal death in the peri-infarct region via N-methyl-D-aspartate-dependent sterol regulatory element-binding protein 1 signaling and related inflammatory factors, further alleviating motor and cognitive deficits in stroke. Conclusion: This new HD-tDCS application showed better therapeutic effects than those with conventional HD-tDCS in early-stage stroke via the amelioration of neuronal death in the penumbra. It may be applied in the early stages of stroke to alleviate neurological impairment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This study was conducted to assess the effect of Evodiae Fructus 70% ethanol extract (EFE) on the pathology of atopic dermatitis using in vitro and in vivo models. The major compounds in EFE were identified by ultra-performance liquid chromatography with tandem mass spectrometry as rutaecarpine, evodiamine, evodol, dehydroevodiamine, limonin, synephrine, evocarpine, dihydroevocarpine, and hydroxyevodiamine. EFE significantly decreased chemokine levels in tumor necrosis factor-α/interferon-γ-stimulated HaCaT cells. In house dust mite-treated NC/Nga mice, topical application of EFE significantly decreased the dermatitis score, epidermal hyperplasia and thickening, mast cell infiltration, and plasma levels of histamine and corticosterone. Thymic stromal lymphopoietin, CD4 + T cells, interleukin-4, and intercellular adhesion molecule-1 expression in the lesioned skin was reduced in the treated mice. The mechanism of EFE was elucidated using transcriptome analysis, followed by experimental validation using Western blotting in HaCaT cells. EFE down-regulated the activation of Janus kinase (JAK)-signal transducers and activators of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in HaCaT cells. EFE improves atopic dermatitis-like symptoms by suppressing inflammatory mediators, cytokines, and chemokines by regulating the JAK-STAT and MAPK signaling pathways, suggesting its use as a potential agent for the treatment of atopic dermatitis., (© 2024. The Author(s).)

Rationale: Promotion of mitophagy is considered a promising strategy for the treatment of neurodegenerative diseases including Alzheimer's disease (AD). The development of mitophagy-specific inducers with low toxicity and defined molecular mechanisms is essential for the clinical application of mitophagy-based therapy. The aim of this study was to investigate the potential of a novel small-molecule mitophagy inducer, ALT001, as a treatment for AD. Methods: ALT001 was developed through chemical optimization of an isoquinolium scaffold, which was identified from a chemical library screening using a mitophagy reporter system. In vitro and in vivo experiments were conducted to evaluate the potential of ALT001 as a mitophagy-targeting therapeutic agent and to investigate the molecular mechanisms underlying ALT001-induced mitophagy. The therapeutic effect of ALT001 was assessed in SH-SY5Y cells expressing mutant APP and mouse models of AD (5×FAD and PS2APP) by analyzing mitochondrial dysfunction and cognitive defects. Results: ALT001 specifically induces mitophagy both in vitro and in vivo but is nontoxic to mitochondria. Interestingly, we found that ALT001 induces mitophagy through the ULK1-Rab9-dependent alternative mitophagy pathway independent of canonical mitophagy pathway regulators such as ATG7 and PINK1. Importantly, ALT001 reverses mitochondrial dysfunction in SH-SY5Y cells expressing mutant APP in a mitophagy-dependent manner. ALT001 induces alternative mitophagy in mice and restores the decreased mitophagy level in a 5×FAD AD model mouse. In addition, ALT001 reverses mitochondrial dysfunction and cognitive defects in the PS2APP and 5×FAD AD mouse models. AAV-mediated silencing of Rab9 in the hippocampus further confirmed that ALT001 exerts its therapeutic effect through alternative mitophagy. Conclusion: Our results highlight the therapeutic potential of ALT001 for AD via alleviation of mitochondrial dysfunction and indicate the usefulness of the ULK1-Rab9 alternative mitophagy pathway as a therapeutic target., Competing Interests: Competing Interests: J.H. Um, D. J. Shin, S. Choi, Y.Y. Kim, J.J. Cho, and J. Yun have filed a patent about the treatment of AD using a mitophagy inducer. E. Yoo, J.J. Cho, and J. Yun are co-founders of Altmedical co. J.H. Jeong and E. Yoo are employees of Altmedical co. The other authors declare no competing interests., (© The author(s).)

Aim: To compare the clinical and radiological results of patients who underwent multilevel posterior cervical fusion (PCF) with different end levels (C6 or C7)., Material and Methods: We collected radiographs and clinical results of all subjects who underwent 3 level or more PCF for degenerative disease from May 2012 to December 2020. Based on the location of the end of fusion during surgery, patients were divided into C6 (group 1) and C7 patients (group 2). The clinical and radiological results of both groups were compared over two years., Results: A total of 52 patients met the inclusion criteria of this study (21 in group 1 and 31 in group 2). The clinical results demonstrated a statistically significant difference with respect to a lower neck visual analog scale score in group 1 than in group 2 at the last follow-up (p=0.03). With regard to the radiological results, the C2-C7 sagittal vertical axis showed significantly greater values in group 2 than in group 1 at the final follow-up (p=0.02). For thoracic kyphosis (TK), group 2 had lower TK values than group 1 (p=0.03), and the T9 spinopelvic inclination was significantly greater in group 2 than in group 1 (p=0.01)., Conclusion: In this study, aggravation of cervical kyphosis and neck pain was observed when C7 was included in multilevel PCF surgery. The inclusion of C7 also affected the thoracolumbar parameters and global spine alignment.

Objectives: Since stroke is a serious health issue, novel therapeutic strategies are required. In a mouse model of ischemic stroke, this study analyzed the potential of electroacupuncture (EA) and tenuigenin (TE) to improve the efficacy of human mesenchymal stem cell (hMSC) transplantation., Methods: Middle cerebral artery occlusion (MCAO) with reperfusion was used to generate ischemic stroke. Forty-eight male C57BL/6 mice were randomly divided into five groups control, MCAO-operated, MCAO-EA, MCAO-TE, or MCAO + EA + TE. Subsequently, hMSCs were transplanted into the ischemic region and EA, TE, or the combination was administered. Behavior assessments and immunohistochemistry were conducted to evaluate motor and cognitive recovery and hMSCs survival, migration, and differentiation., Results: The combined treatment of EA and TE exhibited enhanced hMSCs survival, migration and differentiation into neural cell lineages while suppressing astrocyte formation. Immunohistochemistry demonstrated increased neurogenesis through hMSCs transplantation in the ischemic brain. Immediate behavioral improvements were not significantly different between groups, but there was a gradual recovery in motor and cognitive function over time., Conclusion: These findings highlight the potential of EA and TE co-treatment as a therapeutic strategy for ischemic stroke, opening avenues for further research to optimize treatment protocols and elucidate underlying mechanisms., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest., (© 2023 Korean Pharmacopuncture Institute.)

Objective: Cerebrospinal fluid (CSF) leakage is a major concern related to anterior cervical decompression and fusion for ossification of the posterior longitudinal ligament (OPLL). We propose a management algorithm for CSF leakage following anterior cervical decompression and fusion for OPLL involving the use of pump-regulated volumetric continuous lumbar drainage., Methods: We retrospectively reviewed patients who underwent anterior cervical decompression and fusion for OPLL and were managed with the proposed algorithm between March 2018 and July 2022. The proposed management algorithm for CSF leakage by pump-regulated volumetric continuous lumbar drainage was as follows. On exposure of the arachnoid membrane with or without CSF leakage, a dural sealant patch was applied to manage the dural defect. In case of persistent CSF leakage despite application of the dural sealant patch, patients underwent pump-regulated volumetric continuous lumbar drainage., Results: Fifty-one patients were included in the study. CSF leakage occurred in 14 patients. Of these 14 patients, 9 patients underwent lumbar drain insertion according to the proposed management algorithm. Successful resolution of CSF leakage was observed in 8 of the 9 patients who underwent lumbar drainage. All patients were encouraged to ambulate without concern of CSF overdrainage due to gravity, because it could be avoided with pump-regulated volumetric continuous CSF drainage. Therefore, complications associated with absolute bed rest or CSF overdrainage were not observed., Conclusion: The proposed management algorithm with pump-regulated volumetric continuous lumbar drainage showed safety and efficacy for management of CSF leakage following anterior decompression and fusion for OPLL.

Objective: Two commonly used techniques for spinopelvic fixation in adult deformity surgery are iliac screw (IS) and sacral 2 alar-iliac screw (S2AI) fixations. In this article, we systematically meta-analyzed the complications of sacropelvic fixation for adult deformity surgery comparing IS and S2AI., Methods: The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched until March 29, 2023. The proportion of postoperative complications, including implant failure, revision, screw prominence, and wound complications after sacropelvic fixation, were pooled with a random-effects model. Subgroup analyses for the method of sacropelvic fixation were conducted., Results: Ten studies with a total of 1,931 patients (IS, 925 patients; S2AI, 1,006 patients) were included. The pooled proportion of implant failure was not statistically different between the IS and S2AI groups (21.9% and 18.9%, respectively) (p = 0.59). However, revision was higher in the IS group (21.0%) than that in the S2AI group (8.5%) (p = 0.02). Additionally, screw prominence was higher in the IS group (9.6%) than that in the S2AI group (0.0%) (p < 0.01), and wound complication was also higher in the IS group (31.7%) than that in the S2AI group (3.9%) (p < 0.01)., Conclusion: IS and S2AI fixations showed that both techniques had similar outcomes in terms of implant failure. However, S2AI was revealed to have better outcomes than IS in terms of revision, screw prominence, and wound complications.

Objective: Romosozumab is increasingly employed to manage osteoporosis. However, no studies have analyzed its effects on recent osteoporotic vertebral compression fractures (OVCFs). Therefore, this study aimed to evaluate the efficacy of romosozumab compared with teriparatide in managing OVCFs., Methods: The electronic medical records of postmenopausal patients with recent OVCFs who were administered romosozumab or teriparatide for one year from March 2018 to August 2022 were retrospectively reviewed. We compared the 2 groups for demographics, radiological outcomes (compression ratio, Cobb angle, and bone mineral density [BMD]), and clinical outcomes (Numerical Rating Scale [NRS] for back pain)., Results: Fifty-five patients with OVCFs, 32 patients treated with romosozumab and 23 with teriparatide, were included in this study. The change of BMD (g/cm2) values was significantly higher (p = 0.016) in the romosozumab (0.04 ± 0.06) than in the teriparatide group (0.00 ± 0.08) in the femur total. Furthermore, in subgroup analysis, the change of BMD (g/cm2) values in the lumbar spine was significantly higher (p = 0.016) in the romosozumab (0.12 ± 0.06) than in the teriparatide group (0.07 ± 0.06) in the lumbar spine. The decrease in NRS was significantly higher (p = 0.013) in the romosozumab (6.6 ± 2.0) than in the teriparatide group (5.5 ± 2.1). However, there was no significant difference in radiologic outcomes between the 2 groups., Conclusion: Our findings suggest that romosozumab may be more effective than teriparatide in treating OVCFs in postmenopausal females, particularly in improving BMD and reducing back pain as measured by NRS.

Waste wood, which has a large amount of cellulose fibers, should be transformed into useful materials for addressing environmental and resource problems. Thus, this study analyzed the application of waste wood as supercapacitor electrode material. First, cellulose fibers were extracted from waste wood and mixed with different contents of graphene nanoplatelets (GnPs) in water. Using a facile filtration method, cellulose papers with GnPs were prepared and converted into carbon papers through carbonization and then to porous activated carbon papers containing GnPs (ACP-GnP) through chemical activation processes. For the morphology of ACP-GnP, activated carbon fibers with abundant pores were formed. The increase in the amount of GnPs attached to the fiber surfaces decreased the number of pores. The Brunauer-Emmett-Teller surface areas and specific capacitance of the ACP-GnP electrodes decreased with an increase in the GnP content. However, the galvanostatic charge-discharge curves of ACPs with higher GnP contents gradually changed into triangular and linear shapes, which are associated with the capacitive performance. For example, ACP with 15 wt% GnP had a low mass transfer resistance and high charge delivery of ions, resulting in the specific capacitance value of 267 Fg -1 owing to micropore and mesopore formation during the activation of carbon paper.

Daeshiho-tang (DSHT), a traditional herbal formula with diverse pharmacological effects, has shown promise in medicine owing to its anti-hypertensive, anti-diabetic, and anti-inflammatory properties. However, the precise molecular mechanism underlying these effects remains unclear. Thus, we investigated the effect of DSHT on inflammatory response and oxidative stress to understand its molecular mechanism using lipopolysaccharide (LPS)-induced macrophage (RAW 264.7) cells. DSHT decreased the contents of nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) through downregulating inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. DSHT suppressed the LPS-induced TLR4 as well as MyD88, subsequently suppressing the NF-κB activation and the phosphorylation of MAPK (p38, ERK, and JNK). Radical scavenging activity results revealed a dose-dependent response of DSHT with diminished ABTS activity, a hallmark of oxidative stress potential. Furthermore, DSHT enhanced Nrf2 and HO-1 expression in response to LPS. Collectively, our findings indicated that DSHT exert anti-inflammatory effect and regulating oxidative stress by modulating TLR4/MyD88, NF-κB, MAPK, and Nrf2/HO-1 pathways, consequently can provide potential therapeutic strategy for the prevention and treatment of inflammation and oxidative stress-related diseases., (© 2023. The Author(s).)

Study Design: Histologic analysis of the ligamentum flavum (LF) in the lumbar spine., Objective: The objective of this study is to investigate the levels of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the LF tissue of patients with lumbar spinal stenosis (LSS)., Summary of Background Data: The hypertrophy of the LF is the primary cause of the progression of LSS. Recently, Wnt signaling has been proposed as one of the molecular processes contributing to LF hypertrophy. GSK-3β and β-catenin are recognized to play a crucial part in the control of this signaling pathway., Materials and Methods: From May 2020 to July 2022, LF from 51 LSS patients (LSS group) and 18 lumbar disc herniation patients (control group) were prospectively collected during surgery. Histologic analysis was investigated to confirm the progression of LF fibrosis. The levels of α-smooth muscle actin, phosphorylation of GSK-3β (p-GSK-3β; inactive form), and β-catenin were analyzed in LF with Western blot analysis to reveal the GSK-3β/β-catenin signaling pathway. Continuous variables are expressed as mean±SD and compared using the student t test. Categorical variables are compared using the χ 2 test or Fisher exact test, as appropriate. To determine the association between p-GSK-3β and LF thickness, the Pearson correlation coefficient was calculated based on the results of Western blot analysis., Results: The LSS group was older and had thicker LF than the controls. The LSS group showed increased collagen fiber and cellularity than the controls. The levels of α-smooth muscle actin, p-GSK-3β, and β-catenin in the LF of the LSS group were significantly higher than that of the control group. There was a strong positive correlation between p-GSK-3β (Ser9) level and LF thickness in LSS patients ( r =0.69, P =0.01)., Conclusion: This research proposes a molecular mechanism for the pathogenesis of LF hypertrophy in LSS. Specifically, GSK-3β/β-catenin signaling appears to be related to LF hypertrophy in LSS and a positive correlation exists between p-GSK-3β level and LF thickness., Level of Evidence: Level 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The association between skeletal muscle mass and diabetes incidence/insulin resistance/glycated hemoglobin (HbA1C) is unknown. The aim of this study was to investigate such association in clinically apparently healthy males and females., Methods: A cross-sectional study of 372,399 Korean males and females who completed bioelectrical impedance analysis (BIA) in a health-screening programme was performed. Skeletal muscle index was used as an indicator of skeletal muscle mass. Skeletal muscle index (%) [appendicular skeletal muscle mass (kg)/body weight (kg)X100] was estimated using BIA. The study outcomes were diabetes incidence, homoeostasis model assessment of insulin resistance (HOMA-IR), and HbA1C., Results: The mean age of study participants was 38.92 ± 8.54 years. Multiple logistic regression analysis revealed a significant negative association between Skeletal muscle index and diabetes incidence/HOMA-IR/HbA1C after adjusting for various confounding factors. Odds ratios (95% confidence interval (CI)) of diabetes incidence in Q2, Q3, and Q4 compared to the lowest quantile (Q1) were 0.95 (0.85-1.05), 0.88 (0.78-0.99), and 0.79 (0.69-0.9), respectively. Beta coefficients (95% CI) of HOMA-IR in Q2, Q3, and Q3 with Q1 were 0.05 (0.03-0.07), -0.06 (-0.09∼-0.04), and -0.19 (-0.22∼-0.16), respectively. Beta coefficients (95% CI) of HbA1C in Q2, Q3, and Q4 with Q1 were 0.02 (0.01-0.03), -0.001 (-0.01∼0.01), and -0.02 (-0.03∼-0.01), respectively., Conclusions: This study demonstrated negative associations of skeletal muscle mass with diabetes incidence, insulin resistance, and HbA1C levels in healthy adults., (© 2023 John Wiley & Sons Ltd.)

New approach methods (NAMs) have been developed to predict a wide range of toxicities through innovative technologies. Liver injury is one of the most extensively studied endpoints due to its severity and frequency, occurring among populations that consume drugs or dietary supplements. In this review, we focus on recent developments of in silico modeling for liver injury prediction using deep learning and in vitro data based on adverse outcome pathways (AOPs). Despite these models being mainly developed using datasets generated from drug-like molecules, they were also applied to the prediction of hepatotoxicity caused by herbal products. As deep learning has achieved great success in many different fields, advanced machine learning algorithms have been actively applied to improve the accuracy of in silico models. Additionally, the development of liver AOPs, combined with big data in toxicology, has been valuable in developing in silico models with enhanced predictive performance and interpretability. Specifically, one approach involves developing structure-based models for predicting molecular initiating events of liver AOPs, while others use in vitro data with structure information as model inputs for making predictions. Even though liver injury remains a difficult endpoint to predict, advancements in machine learning algorithms and the expansion of in vitro databases with relevant biological knowledge have made a huge impact on improving in silico modeling for drug-induced liver injury prediction., Competing Interests: Declaration of competing interest None conflicted interest needs to be declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Selectively excited o -toluidine and α-methylbenzylamine have been studied with quasi-classical trajectory procedures to determine the extent and timescales of intramolecular energy flow. The initial excitation is in the stretching mode of the para -CH bond, and its flow is initiated by interaction with an argon atom. Energy flow to the NH stretching mode is the dominant relaxation pathway, and its effectiveness is enhanced strongly by the methyl-NH interaction. Energy flow characteristics in both molecules are similar, but the flow is more effective in o -toluidine than in α-methylbenzylamine because the methyl group bonded to the benzene ring exerts stronger perturbation on the energy-flow pathway than the group bonded to the side chain. The relaxation of the initially excited CH completes on a timescale of several picoseconds, but the main part of energy flow to the NH occurs on a subpicosecond scale. In o -toluidine, carbon-carbon overtone modes lead to ring-CC bonds gaining and transporting more energy than high-frequency CH bonds, but they all gain far less energy than the NH stretching mode.

Background: In multilevel posterior lumbar interbody fusion (PLIF) with posterior screw fixation, obtaining sufficient lumbar lordosis (LL) is difficult, especially in patients with osteoporosis. We performed intraoperative table modification (TM) using gravitational dropping of the patient's lumbar spine, to improve restoration of LL., Methods: We retrospectively reviewed the medical records of patients who underwent three- or four-level PLIF between 2005 and 2019. One hundred eleven patients were enrolled, with 96 patients receiving non-TM-PLIF and 15 patients receiving TM-PLIF. Radiological parameters, including segmental lordosis (SL), LL, sacral slope (SS), pelvic incidence, and pelvic tilt, were measured. Clinical outcomes were measured using a visual analogue scale (VAS) for the back and leg preoperatively and at the last follow-up. Additionally, the correlation between the bone mineral density (BMD) and the radiological parameters was calculated for TM-PLIF. We performed propensity score matching between the groups to control the baseline difference., Results: We found a statistically better correction between immediate and last follow-up postoperative SL (p = 0.04), as well as between preoperative and last follow-up SL (p < 0.01) in the TM-PLIF group compared to that in the non-TM-PLIF group. VAS for the back and leg were not significantly different between the two groups. Additionally, the efficacy of lordosis correction in the TM-PLIF group showed a statistically significant negative correlation between BMD and the SS change both before and after the surgery (rho = -0.60, p = 0.02)., Conclusion: Whilst further study is required to conclusively establish its efficacy, TM-PLIF (table modification using gravitational dropping) shows potential advantages for restoring and maintaining LL in multilevel lumbar fusion, particularly in cases with low BMD.

The indoor environment has been recognized as a crucial factor that can influence health and wellbeing of occupants. This is particularly true in hospital settings, where various environmental attributes can significantly affect patients' recovery and staff members' productivity. The present study aimed to investigate how occupants in hospitals perceived indoor environment, focusing specifically on COVID-19 hospitals across Republic of Korea. The study recruited two groups of participants: patients ( n = 100) who had been hospitalized in COVID-19 hospitals and staff members ( n = 103) who worked in COVID-19 hospitals. The data collected from the participants were analyzed using multiple regression models to determine which environmental attributes significantly affected their perception of the indoor environment. The study revealed that satisfaction with indoor acoustic environment and odor were significant predictors for how patients perceived the indoor environment as helpful for their recovery from COVID-19. On the other hand, odor was also the significant factor affecting staff members' perceived helpfulness for work. The results suggested that different environmental attributes can have a significant impact on the perception of the indoor environment, depending on the characteristics of occupancy. The study's findings provided insights into the certain environmental factors that COVID-19 hospitals can prioritize. These insights can help policymakers and hospital administrators to develop strategies to create hospital environments that meet the needs of both groups. The study also suggested that further research is needed to investigate additional factors affecting occupants' perception of the indoor environment in hospital settings., 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 Park, Shin and Kim.)

The coronavirus disease 2019 (COVID-19) pandemic has had a major influence on working patterns worldwide, given the various lockdown periods and the shift to remote working. As people's noise perception is known to be closely linked with their work performance and job satisfaction, investigating the noise perception in indoor spaces, especially in situations where people work from home, is crucial; however, studies on this aspect are limited. Thus, here, this study aimed to investigate the relationship between indoor noise perception and remote work during the pandemic. The study assessed how people who worked from home perceived indoor noise, and how it related with their work performance and job satisfaction. A social survey was conducted with respondents who worked from home during the pandemic in South Korea. A total of 1,093 valid responses were used for data analysis. Structural equation modeling was used as a multivariate data analysis method to simultaneously estimate multiple and interrelated relationships. The results showed that indoor noise disturbance significantly affected annoyance and work performance. Annoyance with indoor noise affected job satisfaction. Job satisfaction was found to have a significant impact on work performance, particularly on two dimensions of the work performance that are crucial for achieving organizations' goals. Moreover, one dimension of the work performance had a significant impact on annoyance. The study proposed that reducing negative perception of indoor noise and improvement of job satisfaction can lead to the maximization of one's work performance when working from home., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)