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Abstract Background Neuropathic pain (NP) is a debilitating condition caused by lesion or dysfunction in the somatosensory nervous system. Accumulation of advanced oxidation protein products (AOPPs) is implicated in mechanical hyperalgesia. However, the effects of AOPPs on NP remain unclear. Methods A rat model of NP was established by chronic constriction injury (CCI) and employed to evaluate the changes of mechanical withdrawal threshold, thermal and cold withdrawal latency, as well as AOPPs levels. The effects of AOPPs on the activation of satellite glial cells (SGCs) in the dorsal root ganglion (DRG), receptor for advanced glycation end-products (RAGE) expression, and NF-κB signaling pathway activation were also investigated using western blotting, immunofluorescence, and the Fluo4-AM fluorescence probe for calcium signaling. Additionally, oxidative stress levels and inflammatory cytokine production in SGCs, triggered by AOPPs exposure, were measured through the DCFH-DA probe for ROS detection and ELISA kits for cytokine quantification. Results CCI significantly elevated the AOPPs levels in the plasma and sciatic nerve and caused AOPPs accumulation in the DRG. Exogenous AOPPs activated SGCs, increased reactive oxygen species and inflammatory response, upregulated the RAGE, and activated NF-κB signaling. The RAGE inhibitor FPS-ZM1 effectively inhibited AOPPs-induced SGC activation. Additionally, AOPPs intervention worsened CCI-induced hyperalgesia and neuroinflammation in vivo. Conclusion These results indicate that AOPPs exacerbate the SGC activation and NP following nerve injury, and AOPPs accumulation might play an important role in the pathogenesis of NP.

Abstract The fibrogenic conversion of satellite cells contributes to the atrophy and fibrosis of skeletal muscle, playing a significant role in the pathogenesis of age-related sarcopenia. Melatonin, a hormone secreted by the pineal gland, exhibits anti-aging and anti-fibrotic effects in various conditions. However, the effect of melatonin on satellite cell fate and age-related sarcopenia remains under-explored. Here, we report that melatonin treatment mitigated the loss of muscle mass and strength in aged mice, replenished the satellite cell pool and curtailed muscle fibrosis. When primary SCs were cultured in vitro and subjected to aging induction via d-galactose, they exhibited a diminished myogenic potential and a conversion from myogenic to fibrogenic lineage. Notably, melatonin treatment effectively restored the myogenic potential and inhibited this lineage conversion. Furthermore, melatonin attenuated the expression of the fibrogenic cytokine, transforming growth factor-β1, and reduced the phosphorylation of its downstream targets Smad2/3 both in vivo and in vitro. In summary, our findings show melatonin's capacity to counteract muscle decline and inhibit fibrogenic conversion in aging SCs and highlight its potential therapeutic value for age-related sarcopenia. Graphical Abstract

Objective To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. Methods Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep‐tissue injury of the soft‐tissue defects. The skin flap and muscle flap were fanned out on the wound, and single‐ or two‐staged split‐thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post‐operationally. Complications at both recipient site and donor site were carefully recorded. Results The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post‐traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6–8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12–36 months post‐operational follow‐up. Conclusion The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.

Abstract Background Deep dead space may be thought as an independent risk factor of the poor infection control after flap reconstruction in complex limb wounds. But it can be easily neglected. The conventional skin flap and musculocutaneous flap are difficult to obliterate the deep dead space in irregular shape effectively. It was investigated that the clinical application of chimeric anterolateral thigh perforator flap in the treatment of complex wounds complicated with deep dead space of the extremities in the paper. Methods Fifty-six cases complicated with deep dead space wounds were registered in group. Following thorough debridement and treatment with VSD, the granulation tissues grew with well-controlled infection. And then the chimeric anterolateral thigh perforator flap was used to obliterate the deep dead space and repair the wounds. The postoperative flap survival and infection conditions were evaluated. Results Overall, the infection was effectively controlled, without persistent exudation or sinus tract formation after wound healing. While 5 cases lost to follow-up, the remaining 51 cases were followed up until 15 months on average. Generally, the affected extremities recovered satisfactorily with normal appearances and texture of the flaps, along with normal functions. Importantly, no recurrence of infection was observed. Conclusion During the grafting of chimeric perforator flap pedicled with lateral thigh muscle flap, the muscle flap is recommended to obliterate the deep dead space while the skin flap is being used to cover the wound. The combination of these two technologies performed well in the repair and reconstruction of the complex wounds of the extremities, possessing potential for broader clinical application.