A rare case of a large solid pseudopapillary neoplasm with extensive liver metastasis.

Solid pseudopapillary neoplasms (SPNs) are uncommon pancreatic tumors that primarily affect young females. We report a case of a 24-year-old female diagnosed with SPN and liver metastasis during a routine examination. Imaging revealed an 8-cm pancreatic mass with multiple liver metastases. Histopathology confirmed SPN. Subsequent next-generation sequencing revealed a CTNNB1 mutation. The patient underwent a total pancreatectomy with splenectomy, right hemihepatectomy, and intraoperative radiofrequency ablation. Two years after the surgery, she remained complication-free. She is under regular surveillance. This case underscores the importance of early detection and comprehensive management of SPN.

Mesenchymal Stem Cell-Derived Exosomes Attenuate Hepatic Steatosis and Insulin Resistance in Diet-Induced Obese Mice by Activating the FGF21-Adiponectin Axis.

Exosomes derived from mesenchymal stem cells have shown promise in treating metabolic disorders, yet their specific mechanisms remain largely unclear. This study investigates the protective effects of exosomes from human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) against adiposity and insulin resistance in high-fat diet (HFD)-induced obese mice. HFD-fed mice treated with hWJMSC-derived exosomes demonstrated improved gut barrier integrity, which restored immune balance in the liver and adipose tissues by reducing macrophage infiltration and pro-inflammatory cytokine expression. Furthermore, these exosomes normalized lipid metabolism including lipid oxidation and lipogenesis, which alleviate lipotoxicity-induced endoplasmic reticulum (ER) stress, thereby decreasing fat accumulation and chronic tissue inflammation in hepatic and adipose tissues. Notably, hWJMSC-derived exosomes also promoted browning and thermogenic capacity of adipose tissues, which was linked to reduced fibroblast growth factor 21 (FGF21) resistance and increased adiponectin production. This process activated the AMPK-SIRT1-PGC-1α pathway, highlighting the role of the FGF21-adiponectin axis. Our findings elucidate the molecular mechanisms through which hWJMSC-derived exosomes counteract HFD-induced metabolic dysfunctions, supporting their potential as therapeutic agents for metabolic disorders.

Deep Learning Segmentation of Ascites on Abdominal CT Scans for Automatic Volume Quantification.

Purpose: To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods: This retrospective study included contrast-enhanced and non-contrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years ± 11 [s.d.]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results: On NIH-LC (25 patients; mean age, 59 years ± 14 [s.d.]; 14 male) and NIH-OV (166 patients; mean age, 65 years ± 9 [s.d.]; all female), the model achieved Dice scores of 0.855±0.061 (CI: 0.831-0.878) and 0.826±0.153 (CI: 0.764-0.887), with median volume estimation errors of 19.6% (IQR: 13.2-29.0) and 5.3% (IQR: 2.4-9.7) respectively. On UofW-LC (124 patients; mean age, 46 years ± 12 [s.d.]; 73 female), the model had a Dice score of 0.830±0.107 (CI: 0.798-0.863) and median volume estimation error of 9.7% (IQR: 4.5-15.1). The model showed strong agreement with expert assessments, with r 2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion: The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments.

Clinical effect of prophylactic pegfilgrastim in patients with newly diagnosed acute lymphoblastic leukemia who receive intensive chemotherapy.

BACKGROUND: Using granulocyte colony-stimulating factor (G-CSF) after completing chemotherapy reduces the duration of neutropenia and infections. However, the efficacy and safety of prophylactic pegfilgrastim in acute lymphoblastic leukemia (ALL) patients have not yet been evaluated after intensive cytotoxic chemotherapy compared to the daily G-CSF. This study aimed to evaluate the efficacy of pegfilgrastim for ALL patients who received intensive chemotherapy compared with a short-acting G-CSF. PATIENTS AND METHODS: Clinical data of 145 patients treated with hyper-CVAD, modified VPDL/VPD, or KALLA 1406/1407 regimen were retrospectively evaluated. Pegfilgrastim or the short-acting G-CSF was selected according to the clinician's discretion. Patients not receiving pegfilgrastim were treated with the short-acting G-CSF. RESULTS: The median age of enrolled patients was 45 years. Sixty newly diagnosed ALL patients were treated with hyper-CVAD regimen, while KALLA and VPDL regimens were administered to 39 and 46 patients, respectively. Among the 60 patients treated with hyper-CVAD, 20 patients received pegfilgrastim. Patients who received pegfilgrastim had a significantly shorter duration of neutropenia and hospitalization and reduced incidence of severe infections compared to patients receiving the short-acting G-CSF. Consistent results were also confirmed in an analysis targeting only patients who achieved remission during hyper-CVAD induction therapy. There was no significant difference in neutrophil recovery ability and hospitalization duration when the daily short-acting G-CSF was used prophylactically after completing hyper-CVAD, KALLA, and VPDL regimens as induction therapy. CONCLUSION: Using pegfilgrastim after hyper-CVAD therapy was more effective than the short-acting G-CSF in terms of infection, neutropenia recovery, and hospitalization in patients with newly diagnosed ALL.

Indocyanine Green Angiography-Assisted Pure Hemi-Periareolar Incision Nipple-Sparing Mastectomy and Direct-to-Implant Breast Reconstruction.

BACKGROUND: Although pure hemi-periareolar incisions for mastectomy can prevent visible scarring, nipple-areolar complex (NAC) necrosis is a potential risk. Superficial-arterial inflow of the NAC can be evaluated by indocyanine green angiography (ICG-A). OBJECTIVES: This study evaluated the impact of ICG-A assisted periareolar incision on NAC necrosis during nipple-sparing mastectomy (NSM) and direct-to-implant (DTI) breast reconstruction. METHODS: Between December 2018 and November 2021, lateral hemi-periareolar incisions for NSM were routine. After that time, ICG-A-assisted hemi-periareolar incisions were performed between December 2021 and Sept. 2023. The location of the main arterial inflow was evaluated during preoperative ICG-A and the periareolar incision was planned to avoid disruption. NAC necrosis in the ICG-A-assisted and blind-incision groups was compared using univariate and multivariate analyses. RESULTS: A total of 202 breasts were analyzed including 80 breasts from 75 patients in the ICG-A-assisted group and 122 breasts from 115 patients in the blind-incision group. On preoperative ICG-A, superficial-arterial inflow was observed in 67 of 80 (83.75%) breasts. Perfusion of the nipple without superficial-arterial inflow (base-perfusion pattern) was observed in 13 breasts (16.25%). The main arterial inflow was most common in the upper-medial direction at the areolar margins (65.67%). The full-thickness NAC necrosis rate in the ICG-A-assisted incision group was significantly lower than that in the blind-incision group (2.5% vs. 13.1%, p = 0.010). Multivariate analysis demonstrated that ICG-A-assisted incisions significantly reduced the risk of NAC necrosis (odds 0.155, p = 0.030). CONCLUSIONS: ICG-A-assisted pure hemi-periareolar incisions reduced NAC necrosis in DTI breast reconstructions.

Impact of Covert Brain Infarction Following Coronary Angiography on Coronary Artery Bypass Surgery Outcomes.

OBJECTIVE: To determine the association between preoperative covert brain infarction following coronary angiography (CAG) and major adverse cardiac and cerebrovascular events (MACCEs) after coronary artery bypass grafting (CABG). DESIGN: A cohort study was conducted between January 2006 and December 2019, with the follow-up period concluding at either 5 years after surgery, the date of death, or April 27, 2023. SETTING: A single tertiary center in Korea. PARTICIPANTS: Patients who underwent preoperative CAG and subsequent brain magnetic resonance imaging (MRI) before elective CABG. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of MACCEs within 30 days of CABG. MACCEs included operative death (all-cause death within 30 days of surgery or before discharge), myocardial infarction, mechanical circulatory support, circulatory arrest, and stroke. Secondary outcomes included each component of MACCEs and all-cause mortality at 5 years after surgery. Of the 2,476 study patients (median [interquartile range] age: 65 [58-71] years; 24.7% were female), 212 (8.6%) had covert cerebral infarction on brain MRI after CAG but before CABG, and 353 (14.3%) patients experienced MACCEs after CABG. After performing 1:4 propensity-score matching, 1,057 patients were included in the final outcome analysis (212 with covert brain infarction and 845 without). The incidence of MACCEs within 30 days was not significantly different between patients with covert brain infarction and those without (15.1% [32/212] v 15.6% [132/845]; risk difference: -0.5, 95% confidence interval: -5.6 to 4.4; risk ratio: 0.97, 95% confidence interval: 0.66 to 1.32, p = 0.85). There were also no significant differences in each component of MACCEs within 30 days. There was no significant difference between the two groups regarding all-cause mortality at 5 years (18.7% v 17.0%, respectively, p for stratified log-rank test = 0.33). CONCLUSIONS: Among patients undergoing elective CABG, there was no significant association between covert brain infarction following CAG and the occurrence of MACCEs within 30 days or long-term mortality after CABG.

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

PURPOSE: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725). CONCLUSION: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Variability in Breast Density Estimation and Its Impact on Breast Cancer Risk Assessment.

Breast density is an independent risk factor for breast cancer, although variability exists in measurements. This study sought to evaluate the agreement between radiologists and automated breast density assessment software and assess the impact of breast density measures on breast cancer risk estimates using the Breast Cancer Surveillance Consortium (BCSC) model (v.2). A retrospective database search identified women who had undergone mammography between December 2021 and June 2022. The Breast Imaging Reporting and Data System (BI-RADS) breast composition index assigned by a radiologist (R) was recorded and analyzed using three commercially available software programs (S1, S2, and S3). The agreement rate and Cohen's kappa (κ) were used to evaluate inter-rater agreements concerning breast density measures. The 5-year risk of invasive breast cancer in women was calculated using the BCSC model (v.2) with breast density inputs from various density estimation methods. Absolute differences in risk between various density measurements were evaluated. Overall, 1,949 women (mean age, 53.2 years) were included. The inter-rater agreement between R, S1, and S2 was 75.0-75.6%, while that between S3 and the others was 60.2%-63.3%. Kappa was substantial between R, S1, and S2 (0.66-0.68), and moderate (0.49-0.50) between S3 and the others. S3 placed fewer women in mammographic density d (14.9%) than R, S1, and S2 (40.5%-44.0%). In BCSC risk assessment (v.2), S3 assessed fewer women with a high 5-year risk of invasive breast cancer than the other methods, resulting in an absolute difference of 0% between R, S1, and S2 in 75.0%-75.6% of cases, whereas the difference between S3 and the other methods occurs in 60.2%-63.3% of cases. Breast density assessment using various methods showed moderate-to-substantial agreement, potentially affecting risk assessments. Precise and consistent breast density measurements may lead to personalized and effective strategies for breast cancer prevention.

Optimal measurement method for anterior instability on stress radiographs in anterior cruciate ligament tear: Considering the effect of static anterior tibial subluxation.

INTRODUCTION: Accurate assessment of anterior cruciate ligament (ACL) function is vital for guiding treatment. Nevertheless, the presence of tibial subluxation in the neutral position of a patient with an ACL injury may potentially introduce a confounding factor. This study aims to investigate whether tibial subluxation in the neutral position affects the diagnosis of anterior instability in patients with ACL injuries, potentially impacting the reliability and diagnostic accuracy of stress radiography. METHODS: This study included 88 patients: 30 with acute complete ACL tears (acute group), 28 with chronic complete ACL tears (chronic group), and 30 patients who underwent knee arthroscopic surgery other than ACL reconstruction (control group). Side-to-side differences (SSD) in stress radiography were measured using the Telos load status and the SSD of the gap between the Telos load and unload statuses. Diagnostic accuracy of the two methods was assessed using areas under the receiver operating characteristic curves (AUCs). RESULTS: The load SSD (5.92 ± 5.28 mm) was higher than the load-unload SSD (4.27 ± 5.99 mm) in the chronic group (P = 0.017). The load SSD demonstrated a significantly higher diagnostic value than that of the load-unload SSD in the combined group (AUC = 0.920 vs. 0.830; P = 0.012) and chronic group (AUC = 0.913 vs. 0.754; P = 0.002). After adjusting the symptoms for radiographic duration from 6 to 3 months in the chronic group, the load SSD exhibited a significantly higher diagnostic value (AUC = 0.902) than that of the load-unload SSD (AUC = 0.740; P < 0.001). CONCLUSION: The load SSD provides superior diagnostic accuracy compared to the load-unload SSD in ACL tear cases, where static anterior tibial subluxation may result in false negatives. Although load-unload SSD may have diagnostic value within the first 3 months post-injury, the load SSD method provides a reliable assessment of ACL function for patients beyond this timeframe.

Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.

BACKGROUND: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics. METHODS: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort. RESULTS: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799). CONCLUSIONS: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.

Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Genetic profiling and diagnostic strategies for patients with ectodermal dysplasias in Korea.

BACKGROUND: Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer. RESULTS: In this study, we analyzed the genetic profiles of 27 Korean patients with ED. Whole exome sequencing (WES) was performed on 23 patients, and targeted panel sequencing was conducted on the remaining 4 patients. Among the patients in the cohort, 74.1% (20/27) tested positive for ED. Of these positive cases, EDA and EDAR mutations were found in 80% (16/20). Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations. Among the 23 patients who underwent WES, we conducted a virtual panel analysis of eight well-known genes, resulting in diagnoses for 56.5% (13/23) of the cases. Additionally, further analysis of approximately 5,000 OMIM genes identified four more cases, increasing the overall positivity rate by approximately 17%. These findings underscore the potential of WES for improving the diagnostic yield of ED. Remarkably, 94.1% of the patients manifesting the complete triad of ED symptoms (hair/skin/dental) displayed detectable EDA/EDAR mutations. In contrast, none of the 7 patients without these three symptoms exhibited EDA/EDAR mutations. CONCLUSIONS: When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent.

Two families with spondylo-epi-metaphyseal dysplasia due to compound heterozygocity in the vWFA domain of MATN3.

Heterozygous variants of MATN3 is one of the common causes of multiple epiphyseal dysplasia (MED). Here we report three individuals from two unrelated families who harbor compound heterozygous variants in MATN3 (p.Arg121Trp and p.Val220Ala). Contrary to the MED phenotype, these individuals exhibit spondyloepimetaphyseal dysplasia (SEMD) resembling the phenotypes caused by homozygous MATN3 variants. Clinical manifestations included short stature, aggravating genu varum, joint laxity, and spinal abnormalities. Radiographic findings were distinct from typical MED. These compound heterozygous variants in the von Willebrand factor A domain of MATN3 expand the phenotypic spectrum associated with MATN3, and suggest that extreme MATN3 dysfunction resulting from dual variants can lead to a specific pattern of SEMD.

The Modified S-GRAS Scoring System for Prognosis in Korean with Adrenocortical Carcinoma.

Background: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0-1, 2-3, 4-5, and 6-9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell's concordance index (C-index), and the Kaplan-Meier method. Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13). Conclusion: mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Zinc-Alpha-2-Glycoprotein Peptide Downregulates Type I and III Collagen Expression via Suppression of TGF-ß and p-Smad 2/3 Pathway in Keloid Fibroblasts and Rat Incisional Model.

BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.

A Comparison of the Effectiveness of the McCoy Laryngoscope and the C-MAC D-Blade Video Laryngoscope in Obese Patients.

Background and Objective: Obesity is associated with difficult or failed intubation attempts, making general anesthesia challenging for anesthesiologists to perform. The purpose of this study was to evaluate and compare the efficacy of a McCoy laryngoscope and a C-MAC D-blade video laryngoscope for intubation in obese patients with a body mass index (BMI) ≥ 35 kg/m2. Methods: In total, 104 patients were randomly assigned to be intubated with a McCoy (McCoy group) or C-MAC D-blade video laryngoscope (C-MAC group). The primary outcome was intubation time. The secondary outcomes were vocal cord exposure time, vocal cord passage time, proportion of successful intubation, mask ventilation scale, intubation difficulty scale (IDS), percentage of glottis opening (POGO) score, and hemodynamic variables. Results: Although the intubation time did not significantly differ, the C-MAC group showed shorter vocal cord exposure times and a higher rate of successful vocal cord exposure within 5 s. The IDS value was significantly lower in the C-MAC group than in the McCoy group. The proportion of patients who required an increase in lifting force during laryngoscopy was higher in the McCoy group than in the C-MAC group, which may explain the difference in MAP between the groups. Conclusions: Both the McCoy laryngoscope and the C-MAC D-blade video laryngoscope were useful during the intubation of obese patients. The C-MAC D-blade video laryngoscope might be more useful for obese patients in terms of hemodynamic stability.

Challenges in endoscopic third ventriculostomy for patients with achondroplasia: a focus on third ventricle floor anatomy.

OBJECTIVE: Hydrocephalus is one of the neurological risks occurring in patients with achondroplasia. Ventriculoperitoneal shunt (VPS) insertion is the most common treatment. However, reports of successful endoscopic third ventriculostomy (ETV) suggest that ETV may be a good alternative to VPS insertion in achondroplasia. However, it has been stated that ETV in achondroplasia patients is technically demanding to perform. The current study examined the anatomical variations of the third ventricle and the brainstem in achondroplasia patients and correlated the findings with the difficulty of performing ETV. METHODS: A retrospective analysis of 51 patients with achondroplasia and 138 hydrocephalus patients without achondroplasia (48 patients had tumor-related hydrocephalus and 90 patients had hydrocephalus of nontumorous origin) who have visited the authors' institution since 2012 was performed. Preoperative T2-weighted sagittal MR images were used to measure α (steepness of the third ventricle floor), ß (endoscopic angle of incidence), d1 (vertical distance between the dorsum sellae and basilar bifurcation), and d2 (horizontal distance between the dorsum sellae and basilar artery). Each value was compared using the Tukey multicomparison test. RESULTS: Achondroplasia patients showed significantly smaller α (p < 0.001) and ß (p < 0.001) angles, while there were no significant differences between the control groups (p = 0.947 for α, p = 0.836 for ß). The d1 value was significantly larger in achondroplasia patients (p < 0.001), and d2 was smaller (p < 0.001). The control groups showed similar d1 and d2 values (p = 0.415 for d1, p = 0.154 for d2). Smaller α and ß values meant that in achondroplasia patients the third ventricle floor stood more vertically than in other patients with hydrocephalus, and the endoscopic contact angles were small, increasing the risk of ventriculostomy devices slipping down into the infundibular recess. Additionally, a large d1 meant that the basilar artery was shifted upward and a small d2 indicated that the basilar artery was located closer to the dorsum sellae, potentially increasing the risk of basilar artery damage. CONCLUSIONS: Achondroplasia patients' skull and brain anatomies were significantly different from those of other hydrocephalus patients, with steeper third ventricle floors and basilar arteries closer to the dorsum sellae. Because these anatomical differences lead to difficulties in performing ETVs in achondroplasia patients, such differences should be considered when ETV is planned for the patients.

Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.

BACKGROUND: Transposable elements (TEs) are known to be inserted into genome to create transcript isoforms or to generate long non-coding RNA (lncRNA) sequences. The insertion of TEs generates a gene protein sequence within the genome, but also provides a microRNA (miRNA) regulatory region. OBJECTIVE: To determine the effect of gene sequence changes caused by TE insertion on miRNA binding and to investigate the formation of an overlapping lncRNA that represses it. METHODS: The distribution of overlapping regions between exons and TE regions with lncRNA was examined using the Bedtools. miRNAs that can bind to those overlapping regions were identified through the miRDB web program. For TE-lncRNA overlapping genes, bioinformatic analysis was conducted using DAVID web database. Differential expression analysis was conducted using data from the GEO dataset and TCGA. RESULTS: Most TEs were distributed more frequently in untranslated regions than open reading frames. There were 30 annotated TE-lncRNA overlapping genes with same strand that could bind to the same miRNA. As a result of identifying the association between these 30 genes and diseases, TGFB2, FCGR2A, DCTN5, and IFI6 were associated with breast cancer, and HMGCS1, FRMD4A, EDNRB, and SNCA were associated with Alzheimer's disease. Analysis of the GEO and TCGA data showed that the relevant expression of miR-891a and miR-28, which bind to the TE overlapping region of DCTN5 and HMGCS1, decreased. CONCLUSION: This study indicates that the interaction between TE-lncRNA overlapping genes and miRNAs can affect disease progression.

Irisin promotes hair growth and hair cycle transition by activating the GSK-3ß/ß-catenin pathway.

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF-1, FGF and irisin are reprehensive myokines. Although VEGF, IGF-1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/ß-catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF-1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/ß-catenin signalling inhibitor, suppressed the irisin-mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/ß-catenin pathway and highlight its therapeutic potential in hair loss treatment.