Long-Term Outcome of Anterior Chest Keloid Excision Using Intercostal Artery Perforator Propeller Flaps.

Background: The chest, with its high skin tension, is prone to keloids and has a high relapse rate. Surgical excision of keloids combined with radiation therapy significantly reduces the recurrence rate. For larger chest keloids (3-10 cm), intercostal artery perforator propeller flap can be used to reduce tension.

Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.

Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins.

A suprapubic refractory skin ulcer following keloid radiotherapy: from hyper-proliferation to hypo-proliferation.

Radiation-induced skin ulcer following cancer and/or tumour is well-documented in the literature. However, radiation-induced skin ulcer following the excision of keloid is yet to be reported. Here, we report the case of a 33-year-old female patient with a suprapubic skin ulcer of five months' duration following keloid treatment with electron beam therapy at recommended dosage.

A Three-Step Approach (MUC) for Umbilicoplasty: Creating a Deep Umbilical Depression in Lipoabdominoplasty.

Background: Various methods of umbilicoplasty have been proposed to create an aesthetically pleasing umbilicus. However, following conventional lipoabdominoplasty, some patients, particularly those with a thin layer of abdominal fat, may exhibit a shallow navel.

Methods: A modified umbilicoplasty with a three-step approach was performed between Jan 2019 and Mar 2023.

Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively.

A Randomized, Double-Blind, Parallel-Group Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of CMAB015, a Candidate Secukinumab Biosimilar, with Its Reference Product Cosentyx in Healthy Chinese Male Subjects.

Purpose: Secukinumab, a monoclonal antibody targeting interleukin (IL)-17A, is approved for the treatment of psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa. This study compared the pharmacokinetics (PK), safety, and immunogenicity of CMAB015, a candidate secukinumab biosimilar, with the reference product secukinumab (Cosentyx) in healthy Chinese male subjects.

Patients And Methods: This double-blind, parallel-group study randomized healthy Chinese male subjects (N=130) to receive either a single dose of 150 mg CMAB015 or secukinumab subcutaneously.

NS8593 inhibits chondrocyte ferroptosis and alleviates cartilage injury in rat adjuvant arthritis through TRPM7 / HO-1 pathway.

Ferroptosis is an emerging target in rheumatoid arthritis (RA). We previously reported that transient receptor potential melastatin 7 (TRPM7) expression is correlated with RA cartilage destruction and demonstrated that TRPM7 mediates ferroptosis in chondrocytes. Here, we further determined the role and mechanism of (R)-N-(Benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphthylamine (NS8593), a TRPM7 inhibitor, in chondrocyte ferroptosis of RA.

Efferocytosis: Unveiling its potential in autoimmune disease and treatment strategies.

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance.

NS8593 inhibits sodium nitroprusside-induced chondrocyte apoptosis by mediating the STING signaling pathway.

Articular cartilage damage and chondrocyte apoptosis are among the distinguishing features of osteoarthritis. (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) is a transient receptor potential cation channel subfamily M member 7 (TRPM7) channel inhibitor and was initially considered a potent inhibitor of small-conductance Ca-activated K channels(SK1-3 or KCa2.1-2.

A 16-Year-Old Girl with Sinonasal Cutaneous Fistula Following Excision and Radiotherapy for Rhabdomyosarcoma Requiring Reconstructive Surgery Using an Expanded Forehead Flap.

BACKGROUND Sinonasal rhabdomyosarcoma (RMS) is a rare malignancy in children and adolescents. It is aggressive and locally invasive, and can require local postoperative radiotherapy. This report presents the case of a 16-year-old girl with a sinonasal-cutaneous fistula following excision and radiotherapy for rhabdomyosarcoma, which required reconstructive surgery using an expanded forehead flap.

Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects.

Background: SHEN26, an oral broad-spectrum antiviral drug, possesses potent preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a favorable safety profile.

Methods: We report safety, tolerability, and pharmacokinetic data from a randomized, double-blind, placebo-controlled phase I study of SHEN26. Eighty-six healthy subjects were enrolled in the three studies: a single ascending-dose study (SAD), a multiple ascending-dose study (MAD), and a food-effect study (FE).

ASH2L Mediates Epidermal Differentiation and Hair Follicle Morphogenesis through H3K4me3 Modification.

The processes of epidermal development in mammals are regulated by complex molecular mechanisms, such as histone modifications. Histone H3 lysine K4 methylation mediated by COMPASS (complex of proteins associated with Set1) methyltransferase is associated with gene activation, but its effect on epidermal lineage development remains unclear. Therefore, we constructed a mouse model of specific ASH2L (COMPASS methyltransferase core subunit) deletion in epidermal progenitor cells and investigated its effect on the development of mouse epidermal lineage.

TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis.

Transient receptor potential melastatin 7 (TRPM7) is a cation channel that plays a role in the progression of rheumatoid arthritis (RA), yet its involvement in synovial hyperplasia and inflammation has not been determined. We previously reported that TRPM7 affects the destruction of articular cartilage in RA. Herein, we further confirmed the involvement of TRPM7 in fibroblast-like synoviocyte (FLS) proliferation, metastasis and inflammation.

KIF4A functions as a diagnostic and prognostic biomarker and regulates tumor immune microenvironment in skin cutaneous melanoma.

Background: KIF4A is upregulated in various malignancies and serves as an independent risk factor. However, its function in skin cutaneous melanoma (SKCM) and the regulation of the immunological environment remains unknown.

Methods: We first explored the mRNA and protein levels of KIF4A in SKCM through public databases.

Extracellular CIRP induces abnormal activation of fibroblast-like synoviocytes from patients with RA via the TLR4-mediated HDAC3 pathways.

The development of rheumatoid arthritis (RA) is closely related to the excessive activation of fibroblast-like synoviocytes (FLSs), which are regulated by a variety of endogenous proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (CIRP), as a novel endogenous proinflammatory molecule, plays an important role in inflammatory diseases. More importantly, the synovial concentration of CIRP in patients with RA was significantly higher than that in patients with osteoarthritis (OA).

IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity.

Safety and Pharmacokinetics of HRS-2261, a P2X3 Receptor Antagonist, in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study.

Background: P2X3 receptor antagonists hold promising potential as a therapeutic option for patients with refractory or unexplained chronic cough, a condition lacking approved therapies. This study assessed the safety, tolerability, and pharmacokinetics (PK) of HRS-2261, a novel selective P2X3 receptor antagonist, in healthy subjects.

Methods: This randomized, double-blinded, placebo-controlled phase 1 trial of HRS-2261 consisted of three phases: the single ascending dose (SAD) study phase, the food-effect study phase, and the multiple ascending dose (MAD) study phase.

Shear Wave Elastography for Assessment of Changes in Abdominal Soft Tissues after Lipoabdominoplasty.

Background: The changes in the elasticity of the abdominal skin, subcutaneous tissues and muscles after lipoabdominoplasty are still unknown. The aim of this study was to provide an objective assessment of tissue elasticity after lipoabdominoplasty using ultrasound elastography.

Methods: A total of 21 female patients (31-41 years old) who underwent lipoabdominoplasty from Oct 2019 to Mar 2022 were included in this retrospective study.

IOX1 epigenetically enhanced photothermal therapy of 3D-printing silicene scaffolds against osteosarcoma with favorable bone regeneration.

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions.

Safety, pharmacokinetics and pharmacodynamics of HRS-7535, a novel oral small molecule glucagon-like peptide-1 receptor agonist, in healthy participants: A phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose, and food effect trial.

Aim: To assess the safety, tolerability, pharmacokinetics (PKs) and pharmacodynamics of HRS-7535, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), in healthy participants.

Materials And Methods: This phase 1 trial consisted of single-ascending dose (SAD), food effect (FE) and multiple-ascending dose (MAD) parts. In the SAD part, participants were randomized (6:2) to receive HRS-7535 (at doses of 15, 60 and 120 mg; administered orally once daily) or placebo.

Rh(III)-Catalyzed -Amino-Directed C-H Coupling with 3-Methyleneoxetan-2-ones for 1,2-Dihydroquinoline-3-carboxylic Acid Synthesis.

Dynamic polarity analysis is proposed herein as a general tool for investigating static polarity and transient polarity and revealing expanded reactivity patterns. Through this analysis formalism, polarity matching has been established for Rh(III)-catalyzed -amino-directed C-H coupling with 3-methyleneoxetan-2-ones, providing efficient access to 1,2-dihydroquinoline-3-carboxylic acids. The identified reaction, by virtue of the internal oxidative mechanism, showcases mild reaction conditions (room temperature), a short reaction time (2 h), and a generally high product yield.