Hypoxic mesenchymal stem cell-derived exosomes promote the survival of skin flaps after ischaemia-reperfusion injury via mTOR/ULK1/FUNDC1 pathways.

Flap necrosis, the most prevalent postoperative complication of reconstructive surgery, is significantly associated with ischaemia-reperfusion injury. Recent research indicates that exosomes derived from bone marrow mesenchymal stem cells (BMSCs) hold potential therapeutic applications in several diseases. Traditionally, BMSCs are cultured under normoxic conditions, a setting that diverges from their physiological hypoxic environment in vivo. Consequently, we propose a method involving the hypoxic preconditioning of BMSCs, aimed at exploring the function and the specific mechanisms of their exosomes in ischaemia-reperfusion skin flaps. This study constructed a 3 × 6 cm2 caudal superficial epigastric skin flap model and subjected it to ischaemic conditions for 6 h. Our findings reveal that exosomes from hypoxia-pretreated BMSCs significantly promoted flap survival, decrease MCP-1, IL-1ß, and IL-6 levels in ischaemia-reperfusion injured flap, and reduce oxidative stress injury and apoptosis. Moreover, results indicated that Hypo-Exo provides protection to vascular endothelial cells from ischaemia-reperfusion injury both in vivo and in vitro. Through high-throughput sequencing and bioinformatics analysis, we further compared the differential miRNA expression profiles between Hypo-Exo and normoxic exosomes. Results display the enrichment of several pathways, including autophagy and mTOR. We have also elucidated a mechanism wherein Hypo-Exo promotes the survival of ischaemia-reperfusion injured flaps. This mechanism involves carrying large amounts of miR-421-3p, which target and regulate mTOR, thereby upregulating the expression of phosphorylated ULK1 and FUNDC1, and subsequently further activating autophagy. In summary, hypoxic preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of BMSC-derived exosomes in the treatment of flap ischaemia-reperfusion injury.

The rare complication of vascular malformations of the limb after sclerotherapy: a report of 3 cases and brief literature review.

BACKGROUND: Vascular malformations are common but complicated types of disease in infants, with unclear causes and lack of effective prevention. The symptoms usually do not disappear and tend to progress without medical intervention. It is extremely necessary to choose correct treatment options for different types of vascular malformations. A large number of studies have confirmed that sclerotherapy has a tendency to become the first-line treatment in near future, but it is also associated with mild or severe complications. Furthermore, to our knowledge, the serious adverse event of progressive limb necrosis has not been systematically analyzed and reported in the literature. CASE PRESENTATION: Three cases (two females and one male) were presented who were all diagnosed as vascular malformations and were treated by several sessions of interventional sclerotherapy. Their previous medical records showed the use of several sclerosants in different sessions including Polidocanol and Bleomycin. The sign of limb necrosis did not occur during the first sclerotherapy, but after the second and third sessions. Furthermore, the short-term symptomatic treatment could improve the necrosis syndrome, but could not change the outcome of amputation. CONCLUSION: Sclerotherapy undoubtedly tends to be the first-line treatment in near future, but the adverse reactions still remain major challenges. Awareness of progressive limb necrosis after sclerotherapy and timely management by experts in centers of experience of this complication can avoid amputation.

Clinical application of magnetic resonance lymphangiography in the vascularized omental lymph nodes transfer with or without lymphaticovenous anastomosis for cancer-related lower extremity lymphedema.

Background: The recent increase in the number of patients with lower extremities lymphedema and the development of microsurgery techniques have led to a rise in lymphedema treatment. Vascularized omental lymph node transfer (VOLT), an emerging treatment modality for extremity lymphedema, has shown its unique advantages in reconstructing lymphatic circulation and absorbing exudated lymphatic fluid. Patients who underwent radical tumor resection with/without radiation therapy treatment often present with impairment or degeneration of the inguinal lymph nodes. For such cases, VOLT could provide adequate lymph nodes and tissue to absorb edema fluid in these areas. Therefore, we analyzed the operative outcomes of VOLT under the guidance of magnetic resonance lymphangiography (MRL) in this study, as this individualized and precise surgical procedure could benefit patients and improve their quality of life. Methods: From November 2021 to September 2022, a total of 14 patients' 19 legs with extremity lymphedema underwent a VOLT with or without lymphaticovenous anastomosis (LVA). Outcomes, including circumference reduction rates, preoperative and postoperative MRL results, and other complications, were analyzed. Results: The mean follow-up period was 8.86±1.41 months (range, 7-11 months). The mean circumference reduction rates {circumference reduction rate (%) = [1 - (postoperative affected limb - healthy limb)/(preoperative affected limb - healthy limb)] × 100%} of different planes (i.e., ankle, 10 cm above the knee, 10 cm below the knee, 10 cm above the ankle, and 20 cm above the knee) were 15.64%±40.08%, 11.79%±30.69%, 20.25%±24.94%, 7.73%±30.05%, -1.517%±16.75%. Notably, one patient had multi-drug-resistant gram-negative infections, which resulted in the loss of three flaps. The postoperative MRL showed improved lymphatic drainage and lower extremity volume in the remaining 13 cases. Conclusions: The precision evaluation of inguinal lymph nodes and lower extremities lymphatic system through MRL using VOLT can provide surgeons with a comprehensive understanding and reliable evidence for the treatment of cancer-related lower extremity lymphedema.