ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

OBJECTIVE: To investigate the effectiveness of posterior lateral perforator flap in lower limb combined with free fibula for maxillary tissue defect repair. METHODS: Between December 2018 and December 2023, 16 patients with the maxillary malignant tumors were admitted. There were 10 males and 6 females, with an average age of 64.3 years (range, 54-75 years). There were 7 cases of maxillary gingival cancer, 5 cases of hard palate cancer, and 4 cases of maxillary sinus cancer. According to the 2017 American Joint Committee on Cancer (AJCC) TNM stage, there were 8 cases of stage Ⅲ, 6 cases of stage Ⅳa, and 2 cases of stage Ⅳb. After resection of the lesion, the remaining maxillary defects were classified into class Ⅱa in 3 cases, class Ⅱb in 5 cases, and class Ⅲb in 8 cases according to Brown's classification. The size of soft tissue defects ranged from 4 cm×3 cm to 8 cm×6 cm. The posterior lateral perforator flap in lower limb in size of 5 cm×4 cm-9 cm×7 cm were harvested to repair soft tissue defects, and free fibula in length of 6-11 cm were used to repair bone defects. The donor sites of the lower limb were sutured directly (6 cases) or repaired with free skin grafting (10 cases). Six patients with positive lymph node pathology were treated with radiotherapy after operation. At 6 and 12 months after operation, the self-assessment was performed by the University of Washington Quality of Survival Questionnaire Form (QUW-4) in five dimensions (facial appearance, swallowing function, chewing function, speech function, and mouth opening), and swallowing function was evaluated by using the Kubota water swallowing test. RESULTS: Postoperative pathological examination showed that all patients were squamous cell carcinoma. One patient who was treated with radiotherapy developed osteomyelitis and 1 patient developed venous crisis of skin flap. The rest of the flaps and all skin grafts survived, and the wounds healed by first intention. All patients were followed up 1-5 years (mean, 2.8 years). Two patients died of local recurrence of the tumor at the 4th and 5th years after operation, respectively. Except for the chewing function score and total score at 6 months after operation, which showed significant differences compared to preoperative scores ( P<0.05), there was no significant difference in other QUW-4 scale scores between different time points ( P>0.05). The patients' swallowing function evaluated by Kubota water swallowing test reached normal in 4 cases, suspicious in 9 cases, and abnormal in 3 cases at 6 months after operation, and 10, 6, and 0 cases at 12 months after operation, respectively. The swallowing function at 12 months was significantly better than that at 6 months ( Z=-2.382, P=0.017). CONCLUSION The posterior lateral perforator flap in the lower limb combined with free fibula to repair maxillary tissue defects can repair soft and hard tissue defects at the same time, so that the patient's facial appearance, swallowing function, chewing function, speech function, and mouth opening are satisfactorily restored and the mid-term effectiveness is good.
Humans ; Middle Aged ; Male ; Female ; Fibula/surgery* ; Aged ; Perforator Flap ; Plastic Surgery Procedures/methods* ; Maxilla/surgery* ; Maxillary Neoplasms/surgery* ; Free Tissue Flaps/transplantation* ; Lower Extremity/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

OBJECTIVE: To summarize the clinical characteristics of foot and ankle deformities combined with knee and lower limb deformities and evaluate the advantages, clinical outcomes, and considerations of QIN Sihe's surgical strategy for treating such complex deformities. METHODS: Between January 2022 and December 2024, 32 patients with foot and ankle deformities combined with knee and lower limb deformities were enrolled. The cohort included 23 males and 9 females, aged 10-67 years (mean, 41.1 years). The main etiologies included post-polio sequelae (20 cases) and congenital limb deformities (3 cases). Deformities were categorized as follows: equinovarus foot (12 cases), equinus foot (2 cases), equinovalgus foot (3 cases), equinus foot with swan-neck deformity (2 cases), calcaneus foot (5 cases), foot valgus (2 cases), knee flexion deformity (14 cases), genu recurvatum (4 cases), genu varum (3 cases), genu valgum (3 cases), lower limb shortening (3 cases), and lower limb external rotation (6 cases). QIN Sihe's surgical strategies included osteotomies, tendon releases, and tendon transfers for deformity correction, followed by external fixation for residual deformity adjustment and stabilization. Outcomes were assessed using QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction. RESULTS: All patients were followed up 8-32 months (mean, 16.5 months). Complications included pin tract infection (1 case, 1 site), ankle pain (2 cases), delayed healing at the proximal tibial osteotomy site (1 case), and anterior talar dislocation (1 case). At last follow-up, insufficient correction of foot deformity was observed in 1 case; both knee and lower limb deformities were corrected, with only mild recurrence of knee flexion deformity in 1 case. The foot/ankle and knee joint function improved. Based on QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction, outcomes were rated as excellent in 30 cases and good in 2 cases, with an excellent-good rate of 100%. CONCLUSION Foot and ankle deformities combined with knee and lower limb deformities are complex, QIN Sihe's surgical strategy can achieve satisfactory clinical outcomes for simultaneous correction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Child ; Adolescent ; Aged ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Lower Extremity Deformities, Congenital/surgery* ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery* ; Ankle Joint/surgery* ; Knee Joint/surgery* ; Foot Deformities/surgery*

Objective To investigate the effect of Scutellarin(Scu)regulating miR-26a-3p/Survivin molecular axis on myocardial ischemia/reperfusion injury(MIRI)in rats and its mechanism.Methods Fifty SD rats were randomly divided into sham group,model group,scutellarin group(Scu),miR-26a-3p agomir group(agomir)and scutellarin+miR-26a-3p agomir group(Scu+agomir)with 10 rats in each group.The animal model of MIRI was established by ligating the anterior descending coronary artery.The rats in each group were given 20 mg/kg Scu or 10 nmol agomir before and during operation,respectively,and the rats in sham group and model group were given the same amount of solvent.At 48 h after operation,the cardiac function of rats was examined by echocardiography.The pathological changes of myocardial tissue were detected by HE staining.The levels of myocardial injury markers creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH)and cardiac troponin I(cTnI)in serum and the contents of oxidative markers Malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in myocardial tissue were detected by biochemical kit.The apoptosis of rat cardiomyocytes was detected by TUNEL staining.The mRNA expression levels of miR-26a-3p and Survivin in rat myocardium were detected by qRT-PCR.Expression levels of Survivin,cyclin-dependent kinase inhibitor(p21)and cleaved-caspase 3 were detected by Western blot.Results Compared with sham group,the pathological damage of myocardial tissue in the model group was serious,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly increased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly decreased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly increased(P<0.01),while the SOD and GSH-Px levels significantly decreased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly increased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly decreased(P<0.01).Compared with model group,the pathological injury of myocardium in Scu group was significantly improved,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly decreased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly increased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly decreased(P<0.01),while the SOD and GSH-Px levels significantly increased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly decreased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly increased(P<0.01).However,intervention with miR-26a-3p agomir could significantly reverse the improvement effect of Scu on MIRI in rats.Conclusion Scu can improve cardiac function and myocardial injury and inhibit myocardial cell apoptosis in MIRI rats,and its mechanism may be related to the regulation of miR-26a-3p/Survivin molecular axis.

Objective:To evaluate lung ultrasound (LUS) for assessing lung aeration heterogeneity in neonatal respiratory distress syndrome (NRDS) across gestational ages and analyze its correlation with oxygenation.Methods:This retrospective cohort study enrolled 125 ventilated NRDS neonates from the neonatal intensive care unit of Hebei Children's Hospital (from March 2023 to May 2024), who were stratified as <32 gestational weeks ( n=47) and ≥32 gestational weeks ( n=78). All underwent LUS, chest X-ray, and blood gas analysis within 2 h of admission. The lung ultrasound score (LUSsc) quantified impaired lung volume percentage (graded: A=normal, B=coalescent B-lines, C=dense B-lines/focal consolidation, D=lobar consolidation). Aeration heterogeneity was measured by coefficient of variation (CV, within-patient) and Gini-Simpson index (between-patients), while oxygenation was assessed by arterial oxygen partial pressure/inhaled oxygen concentration (P/F). Group comparisons, including basic information, lung aeration, and lung aeration heterogeneity, used two independent sample t-tests, Mann-Whitney U tests, Chi square tests, or Wilcoxon tests; partial correlation analyzed aeration-oxygenation relationships. Results:(1) Analysis of impaired lung volume percentage revealed similar distribution patterns between groups, with the <32-week cohort ( n=47, 564 lung segments) showing proportions of 15.6% (88/564), 14.9% (84/564), 35.5% (200/564), and 34.0% (192/564) for graded patterns A through D, respectively, while the ≥32-week cohort ( n=78, 936 segments) demonstrated corresponding proportions of 15.7% (147/936), 16.3% (153/936), 31.7% (297/936), and 36.2% (339/936), with no statistically significant difference between groups ( Z=－0.24, P=0.812). (2) Within-patient heterogeneity analysis revealed no significant CV difference between <32-week group and ≥32-week group [0.33 (0.20-0.84) vs. 0.43 (0.21-0.73), Z=－0.99, P=0.321]. (3) Between-patient heterogeneity was significantly higher in the ≥32-week group, as reflected by the Gini-Simpson index [0.12 (0.09-0.14) vs. 0.09 (0.06-0.14), Z=－1.99, P=0.046], with heterogeneous aeration predominantly located in non-gravity-dependent regions—specifically the left upper lung in the <32-week group and anterior lungs in the ≥32-week group. (4) Correlation analyses demonstrated significantly inverse relationships between CV and LUSsc in <32-week and ≥32-week groups ( r=－0.912, P<0.001; r=－0.886, P<0.001), while the ≥32-week group additionally showed positive CV-P/F correlation ( r=0.373, P=0.001) and inverse LUSsc-P/F association ( r=－0.287, P=0.013). Conclusions:LUS effectively evaluates aeration and its heterogeneity in early NRDS. Infants ≥32 weeks exhibit greater between-patient heterogeneity, with ventilation parameters correlating significantly with oxygenation status.

Objective To investigate the expression and clinical significance of serum cystatin SA(Cystatin SA)and long non-coding RNA(lncRNA)promoter of CDKN1A antisense DNA damage activated RNA(PANDAR)in patients with type 2 dia-betic kidney disease(T2DN).Method A total of 142 patients with type 2 diabetes mellitus(T2DM)admitted to Shanghai Jiao Tong University School of Medicine Suzhou Jiulong Hospital from February 2021 to October 2023 were selected.According to whether they had nephropathy,they were divided into T2DN group(n=82)and non-T2DN group(n=60).60 healthy people who underwent physical examination during the same period were used as the control group.Serum Cystatin SA levels were detected by enzyme-linked immunosorbent assay(ELISA).Serum lncRNA PANDAR level was detected by real-time fluorescence quanti-tative PCR.Pearson correlation analysis was used to analyze the correlation between serum Cystatin SA,lncRNA PANDAR and clinical parameters in T2DN patients.Logistic regression analysis was used to analyze the influencing factors of T2 DN.The re-ceiver operating characteristic(ROC)curve was used to analyze the value of serum Cystatin SA and lncRNA PANDAR in the evaluation of T2DN.Results Serum Cystatin SA(236.28±44.63 ng/L)and serum lncRNA PANDAR(3.21±0.34)in the T2DM group were higher than those in the control group(91.25±22.33 ng/L,1.06±0.23),and the differences were statistically significant(t=23.127,42.379,all P<0.001).Serum Cystatin SA(275.08±46.83 ng/L)and lncRNA PANDAR(3.64±0.38)in T2DN group were higher than those in non-T2DN group(183.25±40.88 ng/L,2.62±0.30),and the differences were statistically significant(t=12.169,17.226,all P<0.001).Serum Cystatin SA and lncRNA PANDAR in T2DN patients were positively correlat-ed with diabetes duration,serum creatinine(sCr),blood urea nitrogen(BUN)and UACR(r=0.562～0.750,all P<0.001),and neg-atively correlated with eGFR(r=-0.656,-0.634,all P<0.001).Serum Cystatin SA,lncRNA PANDAR,duration of diabetes,UACR,sCr were risk factors for T2DN,eGFR was a protective factor(Wald χ2=4.257～12.360,all P<0.001).The area under the curve(AUC)of serum Cystatin SA combined with lncRNA PANDAR in predicting T2DN was 0.920(0.899～0.960),which was greater than that of single index[0.847(0.791～0.887),0.851(0.803～0.896)],and the differences were statistically significant(Z=4.522,4.319,all P<0.05).Conclusion Serum Cystatin SA and lncRNA PANDAR are elevated in patients with T2DN,which are related to renal function indexes and are risk factors affecting the occurrence of T2DN.The combination of the two can effec-tively evaluate the occurrence of T2DN.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.