Extracranial carotid artery aneurysms (ECAAs) are rare, and the optimal therapeutic modality for these lesions remains controversial. Surgical resection and covered stents may be limited to selected cases. While the concept of using flow diversion is appealing for large aneurysms, the application of flow diverters in extracranial carotid lesions may face restrictions due to off-label use, reimbursement challenges, and factors related to the devices themselves. We report our experience with multiple overlapping Low-profile Visualized Intraluminal Support (LVIS) stents as a reconstructive option for selected ECAAs. Five patients with large ECAAs were treated with multiple overlapping LVIS stents. The primary goal was parent-artery reconstruction and reduction of intra-aneurysmal flow reduction by increasing local metal coverage across the neck of the aneurysm. Double overlapping LVIS stents were used in 3 cases, whereas triple or more extensive overlapping constructs were used in 2 cases. During a mean radiologic follow-up of 24 months, complete occlusion in 2 cases, partial occlusion in 3 cases, and adjunctive procedures in 3 cases were required, and no major thromboembolic or hemorrhagic complications were documented. Adjunctive or staged treatment was required in 3 cases, including balloon angioplasty, additional LVIS stenting, flow-diverter placement, stent-graft placement, or coil embolization. Multiple overlapping LVIS stenting is a feasible and relatively safe reconstructive option for selected large or clinically significant ECAAs, particularly when primary flow-diverter treatment is constrained by off-label indication or reimbursement issues. However, they have limited standalone efficacy, particularly in large or complex aneurysms, often requiring adjunctive or staged treatment.

BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Background: Seborrheic dermatitis (SD) is a chronic inflammatory scalp disorder associated with Malassezia dysbiosis and increased sebum production. AMPamide has been suggested to have anti-inflammatory and sebum-regulating effects, but its clinical efficacy and microbiome-modulating effects in SD remain unclear. Objective: To evaluate the clinical efficacy and scalp microbiome changes following 4 weeks of use of an AMPamide-containing shampoo in patients with SD. Methods: In this observational study, 30 patients with SD applied an AMPamide-containing shampoo for 4 consecutive weeks. Clinical outcomes, including sebum levels and overall severity scores, were assessed. Scalp bacterial and fungal communities were analyzed to evaluate α- and β-diversity and changes in Malassezia composition. Results: Treatment resulted in significant reductions in sebum levels and clinical severity scores, particularly in erythema, dandruff, and pruritus. Bacterial community composition remained largely stable, while fungal α-diversity increased, and β-diversity analysis revealed a decrease in the ratio of Malassezia restricta to Malassezia globosa. Conclusion AMPamide-containing shampoo was associated with improved clinical symptoms and a shift toward a more balanced fungal community composition in patients with SD, supporting its potential as a non-steroidal therapeutic option for SD.

The da Vinci single-port (SP) platform (Intuitive Surgical, Inc.) has catalyzed a new phase of remote-access breast surgery by delivering multi-jointed, wristed instrumentation and stable 3-dimensional optics through a single trocar. This narrative review synthesizes contemporary evidence and practice patterns for SP-assisted procedures, drawing on a recent series of robotic nipple-sparing mastectomies (NSMs). Indications parallel conventional NSM with patient selection favoring small-to-moderate breasts and tumors distant from the nipple–areolar complex; formal contraindications largely mirror those of open techniques. SP kinematic features, such as cobra wrist configurations, diminish the blind spots typical of multiport approaches, and the SP system’s combined multi-image display supports real-time imaging overlays that help maintain uniform flap thickness. Across comparative cohorts, overall postoperative complication rates with robotic approaches do not differ significantly from conventional NSM. Oncologic follow-up remains limited, underscoring the need for longer surveillance to establish non-inferiority. Cosmesis and patient satisfaction are consistently superior due to hidden incisions and improved contour. Unique risks demand caution, notably skin-flap ischemiaecrosis, as well as the opposite risk of residual tissue when flaps are made too thick. Safe adoption depends on structured training that includes device familiarization, team-based drills, high-fidelity simulation, and staged proctoring. Recognition of a learning curve characterized by substantial reductions in operative time was found across initial cases. Critical priorities are prospective, controlled trials of oncologic outcomes, standardized frameworks for credentialing and competency, and comprehensive cost-effectiveness evaluations. With disciplined case selection, standardized flap assessment, and team-based training, SP robotic breast surgery achieves concealed-scar cosmesis while maintaining core oncologic principles.

Purpose: Atherosclerotic plaques in peripheral arterial disease (PAD) include fatty, mixed, and calcified types. Plaque burden is significantly associated with restenosis, reintervention, and amputation-free survival. Rotational and aspirational atherectomy (RAA) may effectively remove such plaques. This study aimed to evaluate long-term outcomes of RAA for infrainguinal PAD. Methods: Patients with infrainguinal lesions underwent revascularization using the Jetstream Atherectomy System (Boston Scientific). This 60-month extension assessed primary patency rate (PPR) and clinically driven target lesion revascularization (CD-TLR). Kaplan-Meier curves were used for survival analysis; P < 0.05 was considered statistically significant. Results: A total of 150 patients (mean age, 70.9 years; male, 86.0%; 65.4% with diabetes) were enrolled. The mean lesion length was 15.8 cm, with 74.0% occlusions and 47.3% severe calcification. Lesions were sclerotic (72.4%), thrombosclerotic (13.4%), thrombotic (9.4%), or in-stent (4.7%). A drug-coated balloon (DCB) was used in 85.5% of cases. PPR at 1, 3, and 5 years was 84.1%, 68.1%, and 58.5%, respectively. CD-TLR rates were 93.0%, 81.5%, and 67.4%, respectively. The benefit of DCB was sustained through 3 years but attenuated thereafter, highlighting the need for extended follow-up in infrainguinal interventions. Conclusion RAA demonstrated durable 5-year patency and safety outcomes. Device type, DCB use, lesion morphology, and calcium grade did not significantly influence long-term results. Lesion complexity remains the primary predictor of clinical outcome. Despite the complexity of infrainguinal lesions, the use of RAA demonstrated sustained patency through 3 years, with lesion complexity (particularly TASC classification) emerging as the most critical predictor of long-term success.

Purpose: Drainage fluid may serve as a biologically informative indicator of immune and infectious status during postsurgical recovery after trauma. However, microbiome shifts in drainage fluid associated with clinical resilience have not yet been characterized. This study aimed to investigate microbial dynamics in drainage fluid across the intensive care unit (ICU) and ward recovery phases in Korean trauma patients. Methods: A total of 25 drainage and 10 stool samples were collected from 10 trauma patients who underwent abdominal surgery at a regional trauma center. Microbial composition was analyzed using 16S ribosomal RNA amplicon sequencing.Alpha and beta diversity were compared between sample types and recovery stages. Linear mixed-effects models were used to identify recovery-associated taxa while adjusting for clinical variables, and predicted metabolic pathways were assessed using PICRUSt2. Results: Drainage fluid harbored distinct microbial communities independent of the intestinal microbiota. Shared taxa between drainage and stool increased significantly in patients with bowel injury, suggesting microbial translocation.Seven genera and 5 species showed significantly decreased abundance during the ward stage, with Modestobacter and Blastococcus tunisiensis demonstrating the highest discriminative ability between recovery stages (area under the curve = 0.721). Predicted metabolic pathways related to fatty acid degradation, amino acid degradation, and pro-inflammatory processes were more active during the ICU stage. Conclusion These findings provide preliminary evidence that drainage fluid microbiome profiles may reflect recovery dynamics following trauma, supporting its potential utility for microbiome-based monitoring and biomarker discovery in trauma surgery.

Skeletal muscle atrophy is a major complication associated with aging, chronic disease, and chemotherapy. Doxorubicin (Dox), a widely used anticancer agent, accelerates muscle wasting; however, the underlying cellular mechanisms remain poorly understood. In this study, we examined the effects of Dox on myogenic differentiation, senescence, and lipid metabolism using C2C12 myoblasts. Dox exposure impaired myotube formation without causing overt cytotoxicity. Mechanistically, Dox disrupted myogenic differentiation by inhibiting protein kinase B/mammalian target of rapamycin (AKT/mTOR) signaling, thereby de-repressing forkhead box O1/3 (FOXO1/3) and upregulating the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1), which promote proteolysis. Dox also decreased glycogen synthase kinase 3β (GSK3β) phosphorylation while paradoxically increasing total and phosphorylated β-catenin, indicating dysregulated Wnt/β-catenin signaling. These alterations were accompanied by a senescence-like phenotype, characterized by elevated senescence-associated β-galactosidase (SA-β-gal) activity, increased phosphorylated histone variant γH2AX, and activation of the p53–p21 axis. Notably, cellular senescence coincided with excessive lipid accumulation in myotubes. Dox reduced phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) while enhancing expression of key lipogenic regulators, thereby creating a metabolic environment favoring lipid storage. Collectively, these findings demonstrate that Dox not only suppresses myogenic differentiation but also induces premature senescence and metabolic reprogramming toward lipid accumulation. Targeting these pathways through AMPK activation, FOXO inhibition, or senolytic interventions may offer therapeutic strategies to preserve skeletal muscle integrity in patients undergoing chemotherapy.

Chrysoeriol, a flavonoid naturally found in several plants, including Danggui Susan, a traditional herbal medicine, exhibits promising anti-inflammatory and antioxidant properties. Its potential to prevent cardiovascular diseases, primarily through inhibiting platelet activation and aggregation, has attracted significant interest. This study aimed to investigate the molecular mechanisms underlying the antiplatelet effects of chrysoeriol. The compound effectively suppressed collagen-induced platelet aggregation without inducing cytotoxicity. Chrysoeriol elevated intracellular levels of cyclic AMP (cAMP) and cyclic GMP (cGMP), enhanced inositol 1,4,5-trisphosphate receptor (IP 3R) phosphorylation, and reduced cytosolic calcium (Ca2+ ) mobilization, all of which contributed to its antiplatelet action. Furthermore, chrysoeriol inhibited the phosphorylation of PI3K, Akt, JNK, and p38 MAPK, pathways involved in the activation of cytosolic phospholipase A2 (cPLA 2) and thromboxane A2 (TXA2) production. These effects were accompanied by reduced TXA2 production and secretion of dense granules (ATP and serotonin). Chrysoeriol also impaired thrombin-induced clot retraction, further suggesting its capacity to regulate platelet responses and cytoskeletal rearrangements. These findings highlight chrysoeriol’s multi-target mechanisms, including modulation of cyclic nucleotides, kinase pathways, and platelet function, offering potential as a therapeutic agent to prevent thrombotic cardiovascular events.

This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Mutations in p53 have been implicated in poor prognosis and reduced sensitivity to 5-fluorouracil (5-FU) treatment in colon cancer.While p53-dependent mechanisms have been widely studies, less is known about how p53 deficiency reshapes cellular signaling and contributes to 5-FU resistance. In this study, we aimed to profile proteomic alterations associated with p53 loss by comparing colon cancer cells with and without p53 expression. Differentially expressed proteins (DEPs) related to cell cycle regulation were of particular interest, as 5-FU treatment induced G1 phase arrest in HCT116 p53 wild-type (WT) cells, whereas p53 knockout (KO) cells predominantly showed S phase arrest. We identified several DEPs in p53 deficient cells following 5-FU treatment. Notably, F3 expression was increased, while aldehyde dehydrogenase family 1 member A4 (ALDH1A3), histone deacetylase 2 (HDAC2), and protein S100-A4 (S100A4) were decreased. The expression levels of these genes were associated with overall survival in patients with colon cancer. These findings highlight proteomic alterations linked to p53 deficiency and support a proposed model in which differential regulation of specific proteins may be associated with reduced sensitivity to 5-FU, providing a basis for future mechanistic and functional studies.