BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Objective:To evaluate the relationship between prognostic nutritional index (PNI) and risk of functional dependence in patients receiving maintenance hemodialysis (MHD).Methods:It was a cross-sectional survey study. The clinical data of MHD patients in the Second Affiliated Hospital of Soochow University from June to December 2023 were collected. The Katz and Lawton-Brody questionnaires were used to assess the functional status. The patients were divided into normal functional status group and functional dependence group, and the differences of the clinical data between the two groups were compared. Serum albumin and lymphocytes were used to determine PNI, and the patients were divided into four subgroups: Q1 group (PNI≤44.3), Q2 group (44.349.8) according to the quartile of PNI. Logistic regression analysis method was used to analyze the relationship between PNI and risk of functional dependence in MHD patients, and subgroup analysis was conducted. The receiver-operating characteristic (ROC) curve was used to assess the efficacy of PNI, serum albumin, and lymphocytes in predicting the risk of functional dependence in MHD patients.Results:A total of 206 MHD patients were included in this study, with age of (58.35±0.98) years old, and 132 (64.1%) males. There were 58 (28.2%) patients with diabetes, 179 (86.9%) patients with hypertension, and 36 (17.5%) patients with cardiovascular diseases. There were 95 (46.1%) patients developing functional dependence. Compared with normal functional status group, functional dependence group had higher age ( t=-6.87, P<0.001), proportion of diabetes ( χ2=6.58, P=0.010), and pulse pressure ( t=-3.17, P=0.002), and lower diastolic pressure ( t=3.88, P<0.001), serum creatinine ( t=3.44, P=0.001), serum albumin ( t=4.09, P<0.001) and PNI ( t=3.92, P<0.001). The incidence of functional dependence in PNI Q1 group (69.2%, 36/52) was significantly higher than those in Q2 group (49.0%, 25/51), Q3 group (34.0%, 18/53) and Q4 group (32.0%, 16/50), and the differences among groups were statistically significant (all P<0.05). Logistic regression analysis showed that after adjusting for confounding factors: age, diabetes, pulse pressure, and serum creatinine, the risk of functional dependence of PNI Q1 group was 3.217 folds higher than that in Q4 group ( OR=3.217, 95% CI 1.229-8.422, P=0.017). The risk probability model of PNI predicting the occurrence of functional dependence in MHD patients: logit (odds)=5.854-0.128 3×PNI. The area under the ROC curve ( AUC) for PNI predicting the risk of functional dependence in MHD patients was 0.66 (95% CI 0.58-0.73, P<0.001), slightly higher than that of serum albumin ( AUC=0.64, 95% CI 0.54-0.73, P<0.001). The optimal cutoff value of PNI predicting the occurrence of functional dependence was 46.15, with sensitivity of 72.07% and specificity of 57.89%. Conclusion:Low PNI is associated with high risk of functional dependence in MHD patients.

Flap surgery is a complex surgical procedure that has become an effective method for the treatment of many diseases and traumas. Flap survival is closely related to a variety of factors including cellular autophagy, oxidative stress, inflammatory response, mesenchymal stem cells (MSCs) function, and vascular regeneration. Cellular autophagy maintains intracellular homeostasis and plays a key role in reducing oxidative stress and inflammation and promoting injury repair. Excessive oxidative stress and inflammatory responses pose a threat to flaps, affecting their survival and successful transplantation. Endothelial cells are involved in vascular regeneration through proliferation, migration, and production of angiogenic factors, and vascular endothelial growth factor directly promotes blood vessel formation and maintains endothelial cell function.MSCs play an important role in promoting flap survival and tissue repair due to their unique biological properties and multiple mechanisms of action. The multiple roles played by cellular autophagy, oxidative stress, inflammatory response, MSCs function, and vascular regeneration in influencing postoperative flap survival are hereby elaborated. The aim is to provide a basis for the clinical application of regulating the above factors to improve postoperative flap survival, improve the success rate of flap surgery, reduce complications, and bring more hope for the recovery and quality of life of patients.

Objective:To investigate the attributes and influencing factors of care needs for maternal after perinatal loss, and to provide a reference for promoting maternal physical and mental health and improving the quality of care.Methods:From February to June of 2023, a cross-sectional study was used, 222 maternal after perinatal loss were selected by the convenience sampling method and completed a battery of questionnaires, including a general information questionnaire, the Distress Thermometer (DT), the Perceived Social Support Scale (PSSS), the Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF) and Kano Model-based Questionnaire on Care Needs for Maternal after Perinatal Loss.Results:A total of 207 maternal after perinatal loss were included in the complete data, (31.12±4.55) years old, (68.64 ± 10.70) of PSSS, (16.10 ± 3.43) of ATSPPH-SF. The care needs for maternal after perinatal loss included 4 must-be quality, 8 one-dimensional quality and 13 attractive quality. Multiple linear regression analysis showed that education level ( t=2.28), the PSSS score ( t=2.15) and the ATSPPH-SF score ( t=3.94) were the main influencing factors of care needs for maternal after perinatal loss (all P<0.05). Conclusions:Health care professionals should gradually improve the nursing service system according to the priority division of care needs attributes of maternal after perinatal loss, and develop personalized care according to different influencing factors.

Objective To explore the application value of polidocanol foam combined with absolute ethanol in the treatment of lower extremity venous malformation(VM)in children.Methods The clinical data of 20 children with lower extremity VM were analyzed retrospectively.All of these children were diagnosed with VM of lower extremity by MRI and were treated with digital subtraction angiography(DSA)guided percutaneous sclerotherapy.Different hardening agents were selected according to the classification,the size of the lesion range and the flow rate during the operation.The VM with small lesions range,shallow location and slower velocity were treated with polidocanol foam only,while the VM with larger lesion range and faster velocity were combined treated with abso-lute ethanol.Clinical symptoms and MRI were used to evaluate the curative effect one month after operation.Results Twenty chil-dren received sclerotherapy.After the treatment,15 cases were cured,3 cases showed significantly effective,and 2 cases were effec-tive.Some of the children had pain and swelling of different degrees within 48 hours after operation,who were given symptomatic treatment,and the symptoms disappeared in the short time.The skin of the lesion ulcerated in one case and the ulceration healed after treatment.Conclusion Polidocanol foam combined with absolute ethanol is safe and effective in the treatment of lower extremity VM in children,and the combination can improve the curative effect and reduce the occurrence of postoperative complications.

Objective To explore the clinical application value of interventional embolization in the treatment of giant infant parotid hemangioma.Methods The clinical data of 17 cases of giant infant parotid hemangioma were analyzed retrospectively.All childrens were performed relevant preoperative examination and CT enhancement examination,with no absolute contraindications for the treat-ment.Interventional embolization was performed under static aspiration compound anesthesia,propranolol was given orally on the same postoperative day.One month after surgery,the clinical effect was evaluated according to the clinical symptoms and ultrasound examination.Results A total of 18 interventional embolization were performed on 17 childrens,who were followed up for 6 months after surgery.The tumor body shrank by more than 80％,after treatment,the child had a symmetrical facial face,no soft tissue rupture,and normal skin color with no impairment of the parotid gland and facial nerve function.Conclusion Interventional embolization is safe and effective in the treatment of giant infant parotid hemangioma,and can become one of the preferred treatment methods for giant infant parotid hemangioma.