Deferoxamine preconditioning of canine stem cell derived extracellular vesicles alleviates inflammation in an EAE mouse model through STAT3 regulation.

Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs), specifically those preconditioned with deferoxamine (DFO) in canine adipose tissue-derived MSCs (cAT-MSCs), were explored for treating autoimmune diseases. This study assessed the effects of DFO-preconditioned EVs (EVDFO) in an experimental autoimmune encephalomyelitis (EAE) mouse model. cAT-MSCs were treated with DFO for 48 h, after which EVs were isolated. EAE mice received intranasal EV or EVDFO treatments and were euthanized following histopathologic analysis; RNA and protein expression levels were measured. Histologically, EV and EVDFO groups showed a significant reduction in inflammatory cell infiltration and demyelination. Immunofluorescence revealed increased CD206 and Foxp3 expression, indicating elevated M2 macrophages and regulatory T (Treg) cells, particularly in the EVDFO group. Treg cells also notably increased in the spleen of EVDFO -treated mice. STAT3 and pSTAT3 proteins were upregulated in the EAE groups compared to the naïve group. However, following EV treatment, STAT3 expression decreased compared to the EAE group, whereas pSTAT3 expression was similar in both the EV and EAE groups. In conclusion, EVDFO treatment resulted in reduced STAT3 expression, suggesting its role in T cell regulation and the potential of EVDFO in modulating the STAT3 pathway for reducing inflammation more effectively than non-preconditioned EVs.

Effects of high tibial osteotomy on the coronal, sagittal, and axial alignments of the ankle joint.

BACKGROUND: No comprehensive study has been conducted on the effects of high tibial osteotomy (HTO) on the coronal, sagittal, and axial alignments of the ankle joint. Therefore, this study aimed to investigate the multiplane changes in the ankle joint following HTO using the EOS biplanar X-ray imaging system. METHODS: The medical records of 43 patients who underwent HTO for the treatment of medial knee osteoarthritis were retrospectively reviewed. Preoperative and postoperative EOS images and lower-extremity scanograms were evaluated; the correlations between the outcomes were evaluated. RESULTS: After HTO, the ankle joint axis point on the weight-bearing line showed significant lateralization (p < .001). The knee lateral ankle surface angle increased significantly in the sagittal alignment (p < .001). The distal tibia showed a significant internal rotation in the axial plane (p = .022). Tibial rotation showed no significant relationship with the other parameters. CONCLUSIONS: HTO induced lateralization of the ankle joint axis (coronal), increased the posterior tibial slope (sagittal), and caused the internal rotation of the distal tibia (axial). Axial changes in the distal tibia showed no significant relationship with other coronal and sagittal parameters of the ankle joint. We suggest that surgeons should consider, during HTO, that the ankle joint axis shifts laterally and distal tibia has tendency to rotate internally after HTO.

Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

INTRODUCTION: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. RESULTS: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. CONCLUSION: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

Multifunctional Nanomesh Enables Cellular-Resolution, Elastic Neuroelectronics.

Silicone-based devices have the potential to achieve an ideal interface with nervous tissue but suffer from scalability, primarily due to the mechanical mismatch between established electronic materials and soft elastomer substrates. This study presents a novel approach using conventional electrode materials through multifunctional nanomesh to achieve reliable elastic microelectrodes directly on polydimethylsiloxane (PDMS) silicone with an unprecedented cellular resolution. This engineered nanomesh features an in-plane nanoscale mesh pattern, physically embodied by a stack of three thin-film materials by design, namely Parylene-C for mechanical buffering, gold (Au) for electrical conduction, and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) for improved electrochemical interfacing. Nanomesh elastic neuroelectronics are validated using single-unit recording from the small and curvilinear epidural surface of mouse dorsal root ganglia (DRG) with device self-conformed and superior recording quality compared to plastic control devices requiring manual pressing is demonstrated. Electrode scaling studies from in vivo epidural recording further revealed the need for cellular resolution for high-fidelity recording of single-unit activities and compound action potentials. In addition to creating a minimally invasive device to effectively interface with DRG sensory afferents at a single-cell resolution, this study establishes nanomeshing as a practical pathway to leverage traditional electrode materials for a new class of elastic neuroelectronics.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

A Comparative Study of Postoperative Complications Associated with Distal Gastrectomy and Pylorus-Preserving Gastrectomy among Gastric Cancer Patients Based on Nationwide Survey Data and Propensity Score Weighting.

BACKGROUND/OBJECTIVE: This study aimed to compare complication rates between pylorus-preserving gastrectomy (PPG) and distal gastrectomy (DG) using Korean nationwide survey data and propensity score weighting (PSW). PPG preserves gastric function but may lead to more postoperative complications than DG. METHODS AND RESULTS: We analyzed 9424 gastric cancer patients who underwent either DG (n = 9183) or PPG (n = 241). PSW balanced variables such as age, sex, TNM stage, comorbidities, ASA score, and surgical approach. Before PSW, 87.8% of DG patients and 87.1% of PPG patients had no complications (p = 0.053). Severe complications (Clavien-Dindo IIIa or higher) were more frequent in PPG (6.6%) than in DG (3.8%) (p = 0.039). After PSW, overall complication rates (p = 0.960) and severe complication rates (p = 0.574) were similar between groups. Incidence rates of anastomotic stricture and leakage were higher in PPG (2.9% and 1.7%) compared to DG (0.6% and 0.5%) (p = 0.001 and 0.036) before PSW, but these differences were not significant after PSW (p = 0.999 and 0.123). CONCLUSION: The PSW-adjusted analysis indicates no significant difference in overall and severe complication rates between PPG and DG in gastric cancer patients.

Improved Diagnostic Accuracy of Thyroid Fine-Needle Aspiration Cytology with Artificial Intelligence Technology.

Background: Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. Methods: We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. Results: A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. Conclusions: These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Immunoglobulin G4-related disease mimicking an appendiceal neoplasm: a case report.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.

Sialyllactose preserves residual hearing after cochlear implantation.

In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.

Neuroprotective and immunomodulatory effects of superoxide dismutase on SH-SY5Y neuroblastoma cells and RAW264.7 macrophages.

Superoxide dismutase (SOD) is an antioxidant enzyme that protects the body from free radicals. It has both antioxidant and immunomodulatory properties, inducing macrophage polarization from M1 to M2. Macrophages, key mediators of the innate immune response, are divided into the M1 (pro-inflammatory) and M2 (anti-inflammatory) subtypes. In this study, we aimed to assess the antioxidant and neuroprotective effects of SOD on nerve cells and its immunomodulatory effects on macrophages. We observed that SOD inhibited the accumulation of reactive oxygen species and enhanced the viability of H2O2-treated nerve cells. Furthermore, SOD reduced the degree of necrosis in nerve cells treated with the conditioned medium from macrophages, which induced inflammation. In addition, SOD promoted the M1 to M2 transition of macrophages. Our findings suggest that SOD protects nerve cells and regulates immune responses.

Estimation of patient-reported outcome measures based on features of knee joint muscle co-activation in advanced knee osteoarthritis.

Electromyography (EMG) is considered a potential predictive tool for the severity of knee osteoarthritis (OA) symptoms and functional outcomes. Patient-reported outcome measures (PROMs), such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS), are used to determine the severity of knee OA. We aim to investigate muscle activation and co-contraction patterns through EMG from the lower extremity muscles of patients with advanced knee OA patients and evaluate the effectiveness of an interpretable machine-learning model to estimate the severity of knee OA according to the WOMAC (pain, stiffness, and physical function) and VAS using EMG gait features. To explore neuromuscular gait patterns with knee OA severity, EMG from rectus femoris, medial hamstring, tibialis anterior, and gastrocnemius muscles were recorded from 84 patients diagnosed with advanced knee OA during ground walking. Muscle activation patterns and co-activation indices were calculated over the gait cycle for pairs of medial and lateral muscles. We utilized machine-learning regression models to estimate the severity of knee OA symptoms according to the PROMs using muscle activity and co-contraction features. Additionally, we utilized the Shapley Additive Explanations (SHAP) to interpret the contribution of the EMG features to the regression model for estimation of knee OA severity according to WOMAC and VAS. Muscle activity and co-contraction patterns varied according to the functional limitations associated with knee OA severity according to VAS and WOMAC. The coefficient of determination of the cross-validated regression model is 0.85 for estimating WOMAC, 0.82 for pain, 0.85 for stiffness, and 0.85 for physical function, as well as VAS scores, utilizing the gait features. SHAP explanation revealed that greater co-contraction of lower extremity muscles during the weight acceptance and swing phases indicated more severe knee OA. The identified muscle co-activation patterns may be utilized as objective candidate outcomes to better understand the severity of knee OA.

Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

Long-Term Outcomes of High-Flexion Design Total Knee Arthroplasty with a Short Posterior Flange.

Background: The purpose of this study was to evaluate the clinical and radiological outcomes of high-flexion total knee arthroplasty (TKA) using Vega Knee System (B. Braun, Aesculap) at a long-term follow-up and to analyze the implant survivorship. Methods: We enrolled 165 patients (232 knees) with a minimum 7-year follow-up after TKA (VEGA Knee System). For clinical assessment, range of motion (ROM), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used. For radiologic assessment, hip-knee-ankle angle, component position, and the existence of radiolucent lines and loosening were used. Survival analysis was conducted using the Kaplan-Meier method. Results: The mean follow-up period was 9.8 years. The mean ROM increased from 124.4° to 131.4° at the final follow-up. The WOMAC score decreased from 38.5 to 17.4 at the final follow-up (p < 0.001). All 5 subscales of the KOOS improved at the final follow-up (all subscales, p < 0.001). Revision TKA was performed in 10 cases (4.3%), which included 9 cases of aseptic loosing and 1 case of periprostatic joint infection. Of the 9 aseptic loosening cases (3.9%), 8 cases (3.4%) were loosening of the femoral component and 1 case (0.4%) was loosening of the tibial component. When revision for any reason was considered an endpoint, the 10-year survivorship was 96.2% (95% confidence interval [CI], 93.9%-98.5%). On the other hand, when revision for aseptic loosening was considered the endpoint, the 10-year survivorship was 96.6% (95% CI, 94.4%-98.8%). Conclusions: The Vega Knee System provided good clinical results in the long-term follow-up period. Although the VEGA Knee System showed acceptable implant survivorship, loosening of the femoral component occurred in about 3.4% of the patients. For more accurate evaluation of the survivorship of high-flexion design TKA with a short posterior flange, it is necessary to conduct more long-term follow-up studies targeting diverse races, especially Asians who frequently perform high-flexion activities.

Poly (Adp-Ribose) Polymerase-1 (PARP-1) Is a Good Prognostic Marker for Pancreatic/Periampullary Cancers.

BACKGROUND: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well. MATERIALS AND METHODS: We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray. RESULTS: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers. CONCLUSIONS: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

Artificial-Intelligence-Assisted Detection of Metastatic Colorectal Cancer Cells in Ascitic Fluid.

Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.

TRPM7 Mediates Neuropathic Pain by Activating mTOR Signaling in Astrocytes after Spinal Cord Injury in Rats.

In this study, we investigated whether transient receptor melastatin 7 (TRPM7), known as a non-selective cation channel, inhibits neuropathic pain after spinal cord injury (SCI) and how TRPM7 regulates neuropathic pain. Neuropathic pain was developed 4 weeks after moderate contusive SCI and TRPM7 was markedly upregulated in astrocytes in the lamina I and II of L4-L5 dorsal horn. In addition, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by a TRPM7 inhibitor, carvacrol. In particular, carvacrol treatment inhibited mechanistic target of rapamycin (mTOR) signaling, which was activated in astrocytes. When rats were treated with rapamycin, an inhibitor of mTOR signaling, neuropathic pain was significantly inhibited. Furthermore, blocking TRPM7 and mTOR signaling by carvacrol and rapamycin inhibited astrocyte activation in lamina I and II of dorsal spinal cord and reduced the level of p-JNK and p-c-Jun, which are known to be activated in astrocytes. Finally, inhibiting TRPM7/mTOR signaling also downregulated the production of pain-related factors such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, chemokine (C-C motif) ligand (CCL) 2, CCL-3, CCL-4, CCL-20, chemokine C-X-C motif ligand 1, and matrix metalloproteinase 9 which are known to be involved in the induction and/or maintenance of neuropathic pain after SCI. These results suggest an important role of TRPM7-mediated mTOR signaling in astrocyte activation and thereby induction and/or maintenance of neuropathic pain after SCI.

Post-COVID-19 Vaccination Myocarditis: A Histopathologic Study on a Monocentric Series of Six Cases.

Many reports on the development of myocarditis following coronavirus disease 2019 (COVID-19) vaccination (PCVM) have emerged. However, only a few case studies have investigated endomyocardial biopsy (EMB) results. This study describes the clinicopathologic features of PCVM. We surveyed all hospitalized patients in a single university hospital in Korea and identified six cases of PCVM. All six patients underwent EMB, five of whom were men aged 15-85 years. All patients developed cardiac dysfunction. Among these patients, two had mild disease without sequelae, whereas the other four had dilated cardiomyopathy with depressed cardiac function. All six cases demonstrated lymphohistiocytic myocarditis. Two of our cases fulfilled the criterion of CD3+ T lymphocytes > 7 cells/mm2 (Case nos. 3 and 6), while the remaining four cases did not fulfill the Dallas criteria. In conclusion, most PCVM cases showed mild degree inflammation histopathologically, and some cases could not fulfill the Dallas criteria and were classified as borderline myocarditis.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

TRPM7 Mediates BSCB Disruption After Spinal Cord Injury by Regulating the mTOR/JMJD3 Axis in Rats.

After spinal cord injury (SCI), secondary injuries including blood cells infiltration followed by the production of inflammatory mediators are led by blood-spinal cord barrier (BSCB) breakdown. Therefore, preventing BSCB damage could alleviate the secondary injury progresses after SCI. Recently, we reported that transient receptor potential melastatin 7 channel (TRPM7) expression is increased in vascular endothelial cells after injury and thereby mediates BSCB disruption. However, the mechanism by which TRPM7 regulates BSCB disruption has not been examined yet. In current research, we show that TRPM7 mediates BSCB disruption via mammalian target of rapamycin (mTOR) pathway after SCI in rats. After contusion injury at T9 level of spinal cord, mTOR pathway was activated in the endothelial cells of blood vessels and TRPM7 was involved in the activation of mTOR pathway. BSCB disruption, MMP-2/9 activation, and blood cell infiltration after injury were alleviated by rapamycin, a mTOR signaling inhibitor. Rapamycin also conserved the level of tight junction proteins, which were decreased after SCI. Furthermore, mTOR pathway regulated the expression and activation of histone H3K27 demethylase JMJD3, known as a key epigenetic regulator mediating BSCB damage after SCI. In addition, rapamycin inhibited JMJD3 expression, the loss of tight junction molecules, and MMP-2/9 expression in bEnd.3, a brain endothelial cell line, after oxygen-glucose deprivation/reoxygenation. Thus, our results suggest that TRPM7 contributes to the BSCB disruption by regulating JMJD3 expression through the mTOR pathway after SCI.