An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Objective:To investigate the effect of dihydroartemisinin (DHA) and gasdermin E(GSDME) on the proliferation, metastasis and pyroptosis of laryngeal cancer cells as well as its related mechanisms.Methods:Human laryngeal squamous cell cancer Hep-2 cells were taken and divided into 4 groups: the blank group (untreated Hep-2 cells), DHA group (Hep-2 cells treated with 50 μmol/L DHA), GSDME-siRNA group (Hep-2 cells transfected with GSDME-siRNA), and DHA+GSDME-siRNA group (Hep-2 cells treated with 50 μmol/L DHA and transfected with GSDME-siRNA). Methyl thiazolyl tetrazolium (MTT) method was used to detect the effect of DHA on the proliferation ability of Hep-2 cells, and the cell proliferation inhibition rate and half inhibitory concentration ( IC50) were calculated. Flow cytometry was used to detect the pyroptosis rate, Transwell assay was used to detect cell invasion ability and Western blot was used to detect the relative expression levels of GSDME, caspase-3, hexokinase Ⅱ (HK-Ⅱ), cyclophilin D, and voltage-dependent anion channel (VDAC) proteins. Results:The cell proliferation inhibition rates of Hep-2 cells treated with 10, 20, 40, 80, 160 μmol/L DHA for 48 h were higher than those treated with the corresponding concentration for 24 h (all P < 0.05). The IC50 values of Hep-2 cells treated by DHA for 24 h and 48 h were 57.20 μmol/L and 43.50 μmol/L, respectively, and thus 50 μmol/L DHA was selected for subsequent experiments. The pyroptosis rate was (6.5±0.8)%, (22.7±2.5)%, (3.1±0.6)% and (7.0±1.0)%, respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 221.20, P < 0.05). The number of invasive cells was (153±14), (95±10), (205±16), and (148±16), respectively in the blank group, DHA group, GSDME-siRNA group, and DHA+GSDME-siRNA group, and the difference was statistically significant ( F = 56.89, P < 0.05). The results of Western blot showed that the relative expression levels of GSDME and caspase-3 in DHA group were higher than those in the blank group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in GSDME-siRNA group were lower than those in DHA group (both P < 0.05); the relative expression levels of GSDME and caspase-3 in DHA+GSDME-siRNA group were higher than those in GSDME-siRNA group (both P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA group were lower than those in the blank group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in GSDME-siRNA group were higher than those in DHA group (all P < 0.05); the relative expression levels of HK-Ⅱ, cyclophilin D, and VDAC in DHA+GSDME-siRNA group were lower than those in GSDME-siRNA group (all P < 0.05). Conclusions:Dihydroartemisinin can increase the pyroptosis of laryngeal cancer cells and reduce cell proliferation and metastasis ability. The mechanism may be related to the inhibition of mitochondrial HK-Ⅱ expression.

Objective:To explore the clinical efficacy of disease-modifying drug nusinersen on children with spinal muscular atrophy.Methods:The baseline and longitudinal clinical data of 15 children who were treated with nusinersen in the Children′s Hospital, Zhejiang University School of Medicine from October 2019 to October 2021 were retrospectively collected. The general data (gender, age, genotype, and clinical classification, etc.), motor function, nutritional status, scoliosis and respiratory function were analyzed. Wilcoxon rank-sum test was used for comparing multi-system conditions before and after treatment.Results:The age of 15 cases (7 males, 8 females) was 6.8 (2.8, 8.3) years, with 2 cases of type 1, 6 cases of type 2, and 7 cases of type 3 respectively, and the course of disease was 55.0 (21.0, 69.0) months. After 9.0 (9.0, 24.0) months of treatment, the motor function scale evaluations of the Hammersmith neurological examination section 2 (13.0 (7.0, 23.0) vs. 18.0 (10.0, 25.0) scores, Z=-2.67, P=0.018) of 15 children, the Hammersmith functional motor scale expanded (38.0 (18.5, 45.5) vs. 42.0 (23.0, 51.0) scores, Z=-2.38, P=0.018), and the revised upper limb module (27.0 (19.5, 32.0) vs. 33.0 (22.5, 35.5) scores, Z=-2.52, P=0.012) of children with type 2 and 3 had significantly improved. Thirteen patients achieved clinically significant motor function improvement, and 2 of them had kept stable scale scores. Subjective reports also indicated that the muscle strength and daily exercise ability of these children improved after treatment, and no serious adverse reactions were reported. Supplemented by the multi-disciplinary team management, the levels of some indicators such as Cobbs angle of scoliosis and forced vital capacity all had significantly improved (all P<0.05). Conclusions:Nusinersen can improve the motor function of patients with 5q spinal muscular atrophy, which is also proved safe to be used in children. The drug treatment supplemented by the multi-disciplinary team management is helpful to improve the multi-system function of the children with spinal muscular atrophy.

To evaluate the effectiveness and safety of self-prepared absorbable hemostatic fibrils.A kind of absorbable hemostatic fibrils were prepared by self-developed patent technique. The physical form and molecular structure of the fibrils and a marketed product Surgicel were characterized by general observation and infrared spectroscopy; the carboxyl content, pH value and relative molecular mass of fibrils were determined by potentiometric titration method, pH meter and copper ethylenediamine method, respectively. The behavior of the fibrils and Surgicel in contact with blood was observed by inverted microscope, the cytotoxicity was evaluated by agarose diffusion cell assay . The external iliac artery hemorrhage model and the back muscle infiltration model in rats were established. The hemostatic effectiveness of the fibrils was investigated by hemostasis time and blood weight, and the degradation and biosafety of fibrils were investigated by observation photography, immune organ weighing, hematology and coagulation index measuring, and histopathological examination. The fibrils and Surgicel had similar molecular structures. Compared with the raw material regenerated cellulose, the typical carboxyl stretching vibration absorption peak of -COOH appeared near in both fibrils and Surgicel. The carboxyl content of the two materials was about 20%, and the pH value was about 3. The relative molecular mass of the fibers after oxidation was 4466±79, which was close to that of Surgicel(>0.05). After contacting with blood, the volume of fibrils and Surgicel expanded, and absorbed blood of dozens of times as their own weight. The results of agar diffusion test showed that the fibrils had no cytotoxicity. The results of animal experiments showed that the hemostasis completed within and there was no significant difference in blood weight and speed of hemostasis between two products (both >0.05). The fibrils could be degraded 1 week after being implanted to the bleeding sites of the muscle. There were no pathological effects on the appearance, body weight, food intake, immunological tissue thymus, spleen, lymph nodes, hematology and coagulation indexes of the rats, and no obvious abnormality found in the histopathological examination. The prepared absorbable hemostatic fibrils have excellent biological safety and effectiveness.
Animals ; Cellulose/pharmacology* ; Hemostasis ; Hemostatics/pharmacology* ; Rats ; Spleen

Objective:To investigate the clinical effect on ultrasound-guided vascular access-interventional therapy of hemodialysis in day surgery mode.Methods:Hemodialysis patients with vascular access dysfunction who underwent ultrasound-guided interventional therapy in the First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2018 to October 31, 2020 were retrospectively analyzed. Demographic and clinical data were collected by electronic medical record system and telephone follow-up. Kaplan-Meier method was used to analyze the patency rate of vascular access.Results:A total of 421 cases of ultrasound-guided vascular access intervention were performed in 269 patients. The technical success rates of stenosis, chronic occlusion and acute occlusion lesion were 98.8%, 90.6% and 86.4%, respectively, and 406 cases (96.4%) of 246 patients were clinically successful. The postoperative brachial artery blood flow was 821(627, 1 029) ml/min, which was significantly higher than 309(202, 453) ml/min before the operation ( Z=-13.547, P<0.001). No serious complications occurred during and after the operation. At 6, 12, 18 and 24 months after operation, the primary patency rate was 74%, 59%, 48% and 45%, respectively, the assisted primary patency rate was 94%, 91%, 88% and 82%, and the secondary patency rate was 96%, 93%, 91% and 86%. Compared with the conventional inpatient surgery mode, the total cost of the day surgery mode was significantly reduced [12 067(10 051, 13 198) yuan vs 14 986(12 411, 20 643) yuan, Z=-13.185, P<0.001], and the hospital stay was significantly shortened [5.1(3.5, 6.9) h vs 73.4(31.6, 146.6) h, Z=-13.348, P<0.001]. Conclusion:It is safe and effective to perform interventional therapy for vascular access malfunction under ultrasound in day surgery mode, which can save cost and time of hospitalization, and can be carried out in hospitals with relevant conditions.

Objective By detecting vascular cysteine-rich 61(Cyr61) related factor,connective tissue growth factor (CTGF),vascular endothelial growth factor (VEGF) and CD105 markers of microvascular density (MVD) of muscle tissue in patients with PM/DM,the role and significance of the expression of Cyr61,CTGF,VEGF and CD105 in the process of vascular lesions of dermatomyosits (DM) and polymyosits (PM) were discussed.Methods The expression of Cyr61,CTGF,VEGF and CD105 markers of micro vascular density (MVD) were detected in 10 cases of DM,10 cases of PM and 20 controls by using immunohistochemical Envision two step method.Data were analyzed using Statistical Product and Service Solutions (SPSS) statistical software.Fisher's exact probability analysis and Spearman correlation analysis were conducted.Results Compared with the control group,Cyr61,CTGF,VEGF positive expression rate in muscle tissue of patients with DM and PM group were significantly different (P＜0.01),the positive expression rates of Cyr61,CTGF,VEGF in DM group and PM group were 90％,70％,90％,80％,80％,70％,and the control group (5％,10％,5％) respectively.In the muscle tissue of patients with DM and PM group,CD105 markers of capillaries could be seen,and MVD in DM and PM group were higher than that in the control group,the difference was statistically significant (F=8.103,P=0.001).Cyr61,CTGF and VEGF protein expression levels in muscle tissueof patients with DM and PM were positively correlated with MVD.Conclusion The muscle tissue of PM/DMpatients may have new blood vessels formation.Cyr61,CTGF,VEGF may be involved in the formation of newblood vessels in the PM/DM muscle tissue.The results of this study suggest that microvascular lesion plays animportant role in the immune pathogenesis of inflammatory myopathy such as PM/DM.