课程文献中心 更多>>

关键词： lower extremity flap   locoregional flap   microsurgery   National Surgical Quality Improvement Project (NSQIP)   plastic surgery   chirurgie plastique   lambeau locor & eacute   gional   lambeau sur les membres inf & eacute   rieurs   microchirurgie   NSQIP  

摘要： Introduction: Soft tissue flaps are an integral and versatile tool to help manage soft tissue defects of varying severities. These complex procedures can be done by a variety of specialties and can lead to a variety of postoperative complications. Locoregional flaps are the middle rung of the reconstructive ladder and can be performed by surgeons of various training pathways. The profile of patients and their complications when stratified by surgical specialty is unknown. The purpose of this study was to compare short-term postoperative outcomes between surgical subspecialists performing a locoregional flap of the lower extremity to determine factors influencing complication rates. Methods: The National Surgical Quality Improvement Project (NSQIP) database was queried using Current Procedural Terminology code 15,738 to identify adult patients undergoing a muscle, myocutaneous, or fasciocutaneous lower extremity flap procedure from 2016 to 2019. We examined the primary outcome of a pooled wound complication rate with secondary outcomes including the individual NSQIP wound- and nonwound complications. Results: A total of 1324 patients were identified. Plastic surgeons performed 926 (70%) procedures, general surgeons performed 243 (18%) procedures, orthopedic surgeons performed 89 (7%) procedures, and vascular surgeons performed 66 (5%) procedures. On multivariate analysis, surgical subspecialty was not associated with the primary outcome, but malignancy-related operations and nonelective status were considered significant. Conclusions: Patient characteristics, but not surgeon subspecialty, account for the variation in patient outcomes in lower extremity flap reconstruction. Larger, prospective studies examining these outcomes are needed to further characterize complication risk factors in this patient population. Introduction : Les lambeaux de tissus mous sont un outil essentiel et polyvalent pour g & eacute;rer les anomalies des tissus mous de diverses gravit & eacut

关键词： Pain   Extracellular vesicle   MSC   Neuron   MicroRNA  

摘要： Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) has shown promise for pain relief, but its efficacy is limited. Preconditioning MSC with tumor necrosis factor-alpha (TNF-alpha) may enhance their therapeutic potential;however, the impact on analgesia and underlying mechanisms remains unclear. Here, we investigated the analgesic effects of EV from TNF-alpha-preconditioned MSC (T-EV) in a chronic constriction injury (CCI) mouse model and examined the molecular mechanisms involved. Following intrathecal injection, T-EV produced greater improvements in mechanical and thermal pain thresholds than control MSC-EV (C-EV), achieving enhanced pain relief for two weeks. Whole-cell patch-clamp recordings revealed that T-EV markedly decreased both the firing rate and action potential amplitude of dorsal root ganglion (DRG) neurons. RNA sequencing revealed that T-EV was enriched in miR-101b-3p. Silencing miR-101b-3p in T-EV abolished their enhanced analgesic effects and reversed DRG hyperexcitability. Moreover, miR-101b-3p was shown by luciferase assays to bind directly to the 3 ' UTR of Nav1.6, suppressing its expression. Engineered MSC-derived nanovesicle overexpressing miR-101b-3p replicated the increased pain relief observed with T-EV. These findings demonstrate that TNF-alpha preconditioning improves the analgesic potency of MSC-EV by delivering miR-101b-3p, which downregulates Nav1.6 and decreases DRG hyperexcitability. This study supports the therapeutic potential of miR101b-3p-enriched vesicle as a novel strategy for treating neuropathic pain.

关键词： Signal transduction  

摘要： Sendai virus, belonging to the Respirovirus genus in the Paramyxoviridae family, possesses C protein to escape from host innate immunity by inhibiting the IFN-α/β–induced STAT1:STAT2 pathway and the interferon (IFN)-γ–induced STAT1 pathway via binding to the N-terminal domain of STAT1 (STAT1ND). In this study, a yeast two-hybrid analysis revealed that C protein also binds directly to the N-terminal domain of STAT3 (STAT3ND). The C-terminal region of C protein (named Y3) was sufficient for binding to STAT3ND, similar to STAT1ND binding. However, the affinity of Y3 for STAT3ND was significantly weaker than that for STAT1ND. Transfection experiments using 293T cells demonstrated that the introduction of C protein significantly stimulated the IFN-γ–induced phosphorylation of STAT3. Considering the results of stoichiometric and confocal analyses together, C protein likely plays a role in stabilizing the dimeric structure formed by STAT3ND, stimulating the recruitment of dimeric STAT3 to the plasma membrane. Reporter assay demonstrated the persistent activation of the STAT3 pathway in the presence of C protein after IFN-γ stimulation. The STAT1 homodimer, bound to two molecules of C protein, cannot take an active form to promote the transcription of target genes. In contrast, STAT3 can take an active form even in the presence of C protein, probably because the complex formed between them is fragile. © 2025 The Authors

关键词： Allogeneic   Major histocompatibility complex   Immune evasion   Alginate scaffolds   Gene expression   Histology  

摘要： The allogeneic administration of equine mesenchymal stem/stromal cells (MSCs) has numerous advantages over autologous therapy, but their interactions with the patient's immune system need to be further elucidated. These interactions can be influenced by factors such as the compatibility between donor-receptor for the major histocompatibility complex (MHC) and by the MHC expression levels, which can change under different conditions like inflammatory exposure and chondrogeneic differentiation. In this study, we evaluated the local immune response induced by chondrogeneically differentiated (MSC-chondro), pro-inflammatory primed (MSC-primed) and basal (MSC-na & iuml;ve) MSCs, and how this response changes the immunomodulatory and immunogenic profiles of MSCs in vivo. Equine MSCs were embedded in alginate scaffolds and subcutaneously implanted into autologous, MHC-matched and MHC-mismatched horses. Scaffolds were recovered at different time-points for histologic and gene expression analyses, and the procedure was repeated to assess the effect of a second administration. Our results suggest that MHC-compatibility may play a key role in attenuating the local immune response induced by MSCs, which may be related to the upregulation of immunomodulatory genes in the three MSC types in vivo. In contrast, when MSCs were administered into MHC-mismatched horses, expression of immunogenic genes was higher across all MSC conditions. Therefore, the conditions in which MSCs are administered may not affect the long-term local immune response, but MHC-matched administration would favour the immune evasion of MSCs, thus being advisable especially when repeated MSC administrations are required. Comprehensively investigating the in vivo immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.

关键词： IL-6   Pulmonary fibrosis   Fibroblast-to-Myofibroblast transition   STAT3   PD-L1  

摘要： Pulmonary fibrosis is a fatal lung disease. Owing to its unknown pathogenesis, treatment options are limited. Interleukin (IL)-6, a multifunctional cytokine, is overexpressed in pulmonary fibrosis and may contribute to its development through multiple pathways, mainly the signal transduction and transcriptional activator 3 (STAT3) signaling pathway. Moreover, programmed cell death ligand 1 (PD-L1), an immune checkpoint molecule, is crucial in immune regulation and also shows abnormal expression in pulmonary fibrosis, potentially involved in fibrogenesis. PD-L1 may be regulated by IL-6 in pulmonary disorders. Given the pivotal role of IL-6 and PD-L1 in the pathogenesis of pulmonary fibrosis, this study aimed to explore the effect and mechanism of blocking IL-6 on PD-L1 expression and pulmonary fibrosis. We established the pulmonary fibrosis model by instilling bleomycin (BLM) intratracheally into mice and stimulating human fetal lung fibroblasts 1 (HFL1s) with transforming growth factor-beta 1 (TGF-(31). Upon inhibition of IL-6 signaling or reduction of PD-L1 expression, we analyzed the tissue morphology, protein expression and function. We observed elevated expression of IL-6 and PD-L1 in pulmonary fibrosis models. Blocking IL-6 relieved BLM-induced lung tissue destruction, diminished collagen production and deposition and inhibited the expression of alpha smooth muscle actin (alpha-SMA), Vimentin, and Collagen I. Blocking IL-6 could reverse fibroblast-to-myofibroblast transformation induced by TGF-(31 in HFL1s via inhibiting the STAT3 signaling pathway. Interestingly, targeting IL-6/STAT3 signaling could also downregulate PD-L1 expression. Inhibiting PD-L1 could mitigate pulmonary fibrosis. Our findings provide new molecular targets for exploring the pathogenesis and treatment of pulmonary fibrosis.

关键词： Artificial tears   dry eye disease   lifestyle advice   management   therapy   treatment   medication   pharmacological   CMC   Carboxymethylcellulose   CsA   Cyclosporine A   DED   Dry Eye Disease   DEWS   Dry Eye Workshops   FDA   Food and Drug Administration   HP-guar   Hydroxypropyl guar   HA   Hyaluronic acid   IL   Interleukin   IPL   Intense pulsed light   LASIK   Laser-assisted in situ keratomileusis   LLT   Lipid layer thickness   LLLT   Low-level light therapy   MGD   Meibomian gland dysfunction   MMP   Matrix metalloproteinase   NGF   Nerve growth factor   NIBUT   Noninvasive tear breakup time   NF-kB   Nuclear factor kappa-light-chain-enhancer of activated B cells   OSDI   Ocular Surface Disease Index   PEG   Polyethylene glycol   PRGF   Plasma rich in growth factors   PRP   Platelet-rich plasma   PUFA   Polyunsaturated fatty acids   RCT   Randomized controlled trial   rhPRG4   Recombinant human proteoglycan 4   ROS   Reactive oxygen species   SANDE   Symptom Assessment iN Dry Eye (questionnaire)   SDP-4   Silk-derived protein   SPEED   Standard Patient Evaluation of Eye Dryness (questionnaire)   TBUT   fluorescein tear breakup time   TFOS   Tear Film & Ocular Surface Society   TMH   Tear meniscus height   TRPM8   Transient Receptor Potential cation channel subfamily M member 8   TTO   Tea tree oil   UCS   Umbilical cord serum  

摘要： This report provides an evidence-based review of current strategies to manage dry eye disease (DED). First-line management focuses on methods to replenish, conserve, and stimulate the tear film, with an emphasis on ocular supplements, which remain the cornerstone of DED treatment. Meibomian gland dysfunction, a primary contributor to DED, is typically treated with warm compresses and a wide variety of in-office treatments, including device-driven technologies to warm the eyelids, intense pulsed light therapy, low-level light therapy, and other new and emerging technologies. Lid hygiene treatments include lid wipes, anti-Demodex therapies, blepharoexfoliation, and topical antibiotics. DED caused by certain etiological drivers can benefit from anti-inflammatory therapies, including topical and oral corticosteroids, T-cell immunomodulatory drugs, and a wide variety of pharmacological agents, in addition to biologic tear substitutes such as autologous serum and platelet-rich plasma. Emerging therapies, such as neuromodulation via nasal neurostimulation and novel pharmacological treatments, offer potential future options. Advanced options, including amniotic membrane grafts and complex surgical methods, provide options for severe or refractory cases. Lifestyle modifications, including optimized blinking, dietary supplementation, and environmental adjustments, play a crucial role in long-term management. Patient education and adherence to treatment regimens remain essential for sustained symptom relief. The TFOS DEWS III prescribing algorithm provides an evidence-based framework to offer guidance to clinicians in selecting relevant interventions based on disease etiology that aim to provide targeted management of the relevant DED subtype(s) that an individual is experiencing. (Am J Ophthalmol 2025;279: 289-386. (c) 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://***/licenses/by/4.0/))

关键词： Upper lid blepharoplasty   Cooling   Ecchymosi   Edema  

摘要： Purpose. - To determine the efficacy of eyelid cooling before upper lid blepharoplasty in terms of pain, edema, erythema, and hematoma and report the results for the first time in the literature. Methods. - Forty-two patients who were scheduled to undergo upper lid blepharoplasty were enrolled in this study. One eyelid (right eye) was chosen to be cooled, and the other eyelid was left uncooled before the surgery. Pain scores were reported by the patients using a Visual Analog Scale (0 to 10), and photographs were obtained by the same ophthalmologist 1 hour, 1 day, and 1 week after surgery. The ecchymosis and edema of the eyelids were evaluated and classified according to these photographs using respective graded scales. Results. - Compared with the uncooled lids, less edema was observed on postoperative day 1 in the eyelids treated by cooling (P < 0.01). The degree of eyelid ecchymosis did not differ between the two groups (P > 0.05). Pain in the cooled eyelids was significantly less 1 hour and 1 day after surgery (P < 0.01), but did not differ 1 week after surgery. Conclusions. - We recommend the use of cooling before, not after, blepharoplasty, as it reduces pain and edema and eliminates patient compliance. (c) 2025 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

摘要： [This retracts the article DOI: 10.3892/ol.2018.7914.].

关键词： Lumpy skin disease virus   ORF142   cGAS/STING   Autophagy   Immune evasion  

摘要： Lumpy skin disease (LSD), caused by the Lumpy skin disease virus (LSDV), poses a significant threat to the global cattle farming industry. Viral proteins evolved the ability to escape host immune responses. Here, we demonstrate that LSDV infection inhibits interferon-(3 (IFN-(3) production in Madin-Darby bovine kidney (MDBK) cells, even in the presence of Sendai virus (SEV) inducers. Through further investigation, we identify multiple genes at both ends of the LSDV genome that strongly inhibit IFN-(3 or NF-kappa B activation of the promoter. Notably, ORF142 selectively inhibits IFN-(3 promoter activity but fails to inhibit NF-kappa B promoter activity. Subsequently, we reveal that ORF142 negatively regulate the cGAS/STING-mediated IFN-I production. Overexpression of ORF142 suppresses IFN-(3 and interferon-stimulated response element (ISRE) activity, while the absence of ORF142 upregulates the transcription levels of IFN-(3 and interferon-stimulated genes (ISGs) in MDBK cells. Mechanistically, ORF142 interacts with STING to facilitate autophagy-lysosomal degradation by recruiting NBR1, thereby impeding the activation of downstream signaling molecules, such as IRF3, and inhibiting IFN-I production. In conclusion, our findings elucidate the immune evasion mechanism of ORF142 encoded by LSDV, offering insights for the development of antiviral drugs or attenuated live vaccines to mitigate LSD.

关键词： IL-32   Mycobacterium tuberculosis   Macrophage   RNA-Seq   TNF pathway   AEBP1  

摘要： Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, survives in host macrophages, the primary effector and antigen-presenting cells involved in the host immune response. We previously showed that Interleukin-32 (IL-32) is significantly increased in the peripheral blood plasma of tuberculosis patients, can act as an anti-MTB agent. However, the underlying molecular mechanism for its effect remains unknown. Here, we showed that inhibiting IL-32 with monoclonal antibody increases MTB loads that was positively correlated with higher antibody concentrations and longer exposure times. RNA-Sequencing result indicated that 3797 genes were shown to be up-regulated in response to IL-32 inhibition, while 1365 genes were down-regulated. GO and KEGG analysis indicated that classical signaling pathways, including TNF, cell cycle, and Wnt were significantly enriched. Consistent expression trends were observed in NF-kappa B pathway-related antibacterial factors that are functionally capable of inhibiting MTB. Using differentially expressed gene and protein-protein interaction analysis, AEBP1 was the gene with the most significant difference in expression and regulated by IL-32. These findings suggest a dynamic molecular and cellular mechanism by which IL-32 positively regulates the AEBP1I kappa B alpha-NF-kappa B-TNF-alpha axis to inhibit MTB infection in human macrophages.