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.

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 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.

Glaesserella parasuis is the causative agent of Gl?sser's disease in pigs.However,the pathogenic mechanisms underlying its virulence is not yet fully understood.The RuvB protein,a member of the AAA+superfamily,is implicated in various cellular processes,yet its specific role in the virulence of Glaesserella parasuis has not been fully characterized.In this study,we con-structed a RuvB gene deletion mutant,designated ΔRuvB,using the serotype 13 Glaesserella pa-rasuis strain ZJ1208 and a suicide plasmid-mediated natural transformation approach.To elucidate the functional role of the RuvB gene,we comprehensively evaluated the biological characteristics of the ΔRuvB strain through a series of assays,including growth kinetics,colony morphology,bac-terial staining,transmission electron microscopy(TEM),osmotic stress tolerance,high-tempera-ture tolerance,heat shock resistance,UV resistance,capsular polysaccharide quantification,serum bactericidal assays,and murine virulence experiments.Our findings revealed that the growth rate of ΔRuvB showed no significant difference compared to the parental strain.TEM revealed a notable increase in bacterial cell length;however,the number of outer membrane vesicles(OMVs)on the surface of ΔRuvB did not significantly increase.Notably,the ΔRuvB strain displayed a significant reduction in capsular polysaccharide production and serum resistance,as well as diminished toler-ance to UV radiation and high temperatures.Significant alterations were observed in its resistance to osmotic stress or oxidative stress.In the mouse toxicity challenge experiment,in com-parison with the parental strain ZJ1208,the mortality rate dropped by 20 percentage points,suggesting that the virulence of ΔRuvB has been weakened to some extent.Collectively,these results underscore the critical role of the RuvB gene in enhancing the environmental adaptability of Glaesserella parasuis.

Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

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 observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.