BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

OBJECTIVE: To prepare decellularized nerve grafts from alpha-1, 3-galactosyltransferase (GGTA1) gene-edited pigs and explore their biocompatibility for xenotransplantation. METHODS: The sciatic nerves from wild-type pigs and GGTA1 gene-edited pigs were obtained and underwent decellularization. The alpha-galactosidase (α-gal) content in the sciatic nerves of GGTA1 gene-edited pigs was detected by using IB4 fluorescence staining and ELISA method to verify the knockout status of the GGTA1 gene, and using human sciatic nerve as a control. HE staining and scanning electron microscopy observation were used to observe the structure of the nerve samples. Immunofluorescence staining and DNA content determination were used to evaluate the degree of decellularization of the nerve samples. Fourteen nude mice were taken, and subcutaneous capsules were prepared on both sides of the spine. Decellularized nerve samples of wild-type pigs ( n=7) and GGTA1 gene-edited pigs ( n=7) were randomly implanted in the subcutaneous capsules. Blood was drawn at 1, 3, 5, and 7 days after implantation to detect neutrophil counting. RESULTS: IB4 fluorescence staining and ELISA detection showed that GGTA1 gene was successfully knocked out in the nerves of GGTA1 gene-edited pigs. HE staining showed that the structure of the decellularized nerve from GGTA1 gene-edited pigs was well preserved; the nerve basement membrane tube structure was visible under scanning electron microscopy; no cell nuclei was observed, and the extracellular matrix components was retained in the nerve grafts by immunofluorescence staining; and the DNA content was significantly reduced when compared with the normal nerves ( P<0.05). In vivo experiments showed that the number of neutrophils in the two groups were similar at 1, 3, and 7 days after implantation, with no significant difference ( P>0.05); only at 5 days, the number of neutrophils was significantly lower in the GGTA1 gene-edited pigs than in the wild-type pigs ( P<0.05). CONCLUSION The decellularized nerve grafts from GGTA1 gene-edited pigs have well-preserved nerve structure, complete decellularization, retain the natural nerve basement membrane tube structure and components, and low immune response after xenotransplantation through in vitro experiments.
Animals ; Transplantation, Heterologous ; Galactosyltransferases/genetics* ; Sciatic Nerve/immunology* ; Swine ; Tissue Engineering/methods* ; Humans ; Graft Rejection/prevention & control* ; Gene Editing ; Mice ; Mice, Nude ; Heterografts/immunology* ; Animals, Genetically Modified ; Tissue Scaffolds ; Decellularized Extracellular Matrix

Objective:To design a management system of internet of things(IoT)smart operation room based on business process reconstruction theory,and explore the application effect of that in improving management effectiveness for operation room.Methods:Aimed at the existing problems of key points in the management for operation room,the process was reconstructed on the basis of the original information system,relevant systems,workflows and standards of operation room of Fuwai Hospital of Medical Sciences and Peking Union Medical College.Then,a management system of IoT smart operation room based on business process reconstruction theory was designed.The surgical data of 13159 patients who underwent relevant operation of cardiovascular surgery from January to December 2022 were selected,and they were divided into"before-application"group(6 483 cases)and"after-application"group(6 676 cases)according to the point before and after the system was applied.Some indicators'data,which included scheduling management situation of picking up and dropping off patients by medical auxiliaries,duration of preparing anesthesia,duration of preoperative waiting,interval duration of continuous surgery and usage amount of surgical gowns under same amount of surgery,between two groups were compared.Results:The transportation efficiency of patients who underwent surgery after system was applied was(1.38±0.09)surgeries/h,which was higher than(0.99±0.09)surgeries/h before it was applied,and the difference was statistically significant(t=6.604,P<0.001).The satisfaction score of medical auxiliaries increased from 3.83(3.33,4.5)before application to 4.50(4.33,4.83)after application,and the difference was significant(Z=2.02,P<0.05).The duration of preparing anesthesia and duration of preoperative waiting after the system was applied were respectively(62.04±2.29)and(8.09±2.46)min,both of which were less than those before the system was applied,and the differences of them between two groups were statistically significant(t=2.309,2.280,P<0.05).The usage amount of surgical gowns under same amount of surgery after the system was applied was(4.11±0.57)gowns/surgery,which was less than(5.81±0.29)gowns/surgery before the system was applied,and the difference was statistically significant(t=6.489,P<0.05).Conclusion:The application of the management system of IoT smart operation room based on business process reconstruction theory can provide more safely,high-qualitatively and efficiently medical services for patients,and improve work efficiency and management effectiveness for operation room,and reduce resource consumption and operating cost.

Objective:To study and explore the hemostatic effect and safety of new type of absorbable bone wax and conventional non-absorbable bone wax in surgery.Methods:A total of 141 patients from orthopedic department and cardiac surgery department,who underwent surgery at Beijing Jishuitan Hospital,and Fuwai Hospital of the Chinese Academy of Medical Sciences from July 2022 to October 2023,were selected.Patients were allocated via block randomization into the absorbable bone wax group(70 cases)and the non-absorbable bone wax group(71 cases).The success rates of hemostasis(within 3min),postoperative wound healing conditions,evaluation of using apparatuses(satisfaction and adhesion),incidence of postoperative complication and the severe adverse events of two groups were compared.Results:The success rates of hemostasis(within 3 minutes)of the absorbable bone wax group and the non-absorbable bone wax group were respectively 98.57%(69/70)and 100.00%(71/71),and the difference was not statistically significant(P>0.05).The differences of wound healing conditions before discharge,at 1st month and 3rd month after surgery between two groups were not significant(P>0.05).In the evaluation of using apparatuses,the satisfaction evaluation of 66 cases(94.29%)of 70 patients in the absorbable bone wax group was superior grade,and the adhesion of 57 cases(81.43%)was superior grade.The satisfaction evaluation of 62 cases(87.32%)of 71 patients in the non-absorbable bone wax group was superior grade,and the adhesion of 48 cases(67.61%)was superior grade.The differences of them between two groups were not statistically significant(P>0.05).There was no significant in the postoperative complication between two groups(P>0.05).The incidence of severe adverse events was 2.86%in the absorbable bone wax group,and it was 4.23%in the non-absorbable bone wax group,there was no statistically significant difference in that between two groups(P>0.05).Conclusion:The absorbable bone wax has the same hemostatic effect and safety with conventional non-absorbable bone wax,and the absorbable bone wax group has better evaluation for using apparatuses.

Objective: To explore the influence of social support and school connectedness on the developmental trajectory of self efficacy in adolescents and analyze its subgroup effects, so as to provide a basis for enhancing adolescents self-efficacy. Methods: Using a cluster random sampling method, 930 first year middle school students from four schools in Xiangxi Autonomous Prefecture, Hunan Province, were selected for three longitudinal surveys in October 2023 (T1), April 2024 (T2), and October 2024 (T3). The General Self-efficacy Scale (GSES), Social Support Scale (SSS), and School Connectedness Scale (SCS) were administered. Latent growth mixture modeling (LGMM) was used to identify different developmental trajectories of self-efficacy in early adolescence. Multivariate Logistic regression was employed to examine the associations of self-efficacy trajectories with social support and school connectedness in adolescents. Results: The developmental trajectory of self-efficacy in adolescents was classified into three categories:category 1 was low efficacy-rapid growth group (53 students, 6.6%), category 2 was moderate efficacy-stable growth group (793 students, 84.1%), and category 3 was high efficacy-rapid decline group (84 students, 9.3%). Using the low efficacy- rapid growth group as the reference, students with higher social support were more likely to belong to the moderate efficacy- stable growth group ( OR=1.06, 95%CI =1.03-1.08) and the high efficacy-rapid decline group ( OR=1.06, 95%CI = 1.03 -1.09), students with higher school connectedness were more likely to belong to the high efficacy-rapid decline group ( OR= 1.10 , 95%CI =1.03-1.18) (all P <0.05). Subgroup analysis revealed significant effects for boarding status (low efficacy-rapid growth group at T1, t =2.10; high efficacy-rapid decline group in social support, t =-2.15) and only child status (moderate efficacy-stable growth group at T2, t =2.05) (all P <0.05). Conclusions The developmental trajectory of self-efficacy in adolescents exhibits group heterogeneity, with boarding status and only child status showing subgroup effects. Enhancing social support and school connectedness can help improve self-efficacy in adolescents.

ObjectiveTo explore the mechanism of action of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in the treatment of recurrent spontaneous abortion （RSA） through network pharmacology， molecular docking， and cell experiment verification. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and UniPort databases were used to screen and organize the active ingredients and corresponding targets of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma. The potential therapeutic targets of RSA were screened in Online Mendelian Inheritance in Man （OMIM）， GeneCards database， DrugBank database， DisGeNET database， and Therapeutic Target Database （TTD）. The potential core targets of Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma for treating RSA were further screened by constructing a protein-protein interaction （PPI） network and topological analysis. Meanwhile， the Database for Annotation， Visualization and Integrated Discovery （DAVID） was chosen to perform enrichment analysis on intersection targets. On this basis， AutoDock software was used for molecular docking， and the data were imported into PyMOL software for visualization and composition. Finally， the cell counting kit-8 （CCK-8） experiment， Transwell cell invasion assay， and Western blot were used to detect the effects of serum containing Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma on HTR-8/SVneo cells and observe the effects on the interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway and related proteins. ResultsThrough network pharmacology analysis， a total of 69 active ingredients， 73 potential therapeutic targets， and 17 core targets， including IL-6， IL-10， and STAT3， were collected. The 73 common targets were enriched in 614 Gene Ontology （GO） entries and 57 Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. The molecular docking results indicated that IL-6 and STAT3 had good binding ability with the main active ingredients， including matrine， cryptotanshinone， and tanshinone Ⅱ_A. The cell experiment results showed that， compared with those of the control group， after 24 hours of treatment with the drug-containing serum， the survival and invasion rates of HTR-8/SVneo cells were significantly increased （P<0.05）， and the expression of IL-6/STAT3 signaling pathway and related proteins IL-10 and c-Myc was significantly elevated （P<0.05）. Moreover， the trend of action in the drug-containing serum group was consistent with that of pathway agonists. ConclusionCuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma may enhance the survival rate and invasive activity of HTR-8/SVneo cells to further prevent and treat RSA by activating the IL-6/STAT3 signaling pathway and upregulating the expression of downstream factors IL-10 and c-Myc in the pathway.

Objective: To explore the dynamic relationship between depressive symptom and non-suicidal self-injury(NSSI) behavior among rural left behind junior high school students, as well as the mediating role of social support, so as to provide a reference for preventing the occurrence of behaviors that endanger the physical and mental health of rural adolescents. Methods: In October 2023, 828 rural left behind junior high school students from four counties and cities in Xiangxi Autonomous Prefecture, namely Luxi County, Huayuan County, Baojing County and Longshan County, were selected by cluster random sampling for a one year follow up investigation (T1:October 2023,T2:April 2024,T3:October 2024). Depressive symptom, NSSI behavior and social support of junior high school students were evaluated by using the Patient Health Questionnaire-9(PHQ-9),Adolescent Non suicidal Self injury Assessment Questionnaire (ANSAQ), and Social Support Scale for University Students(SSSUS). A cross lag panel model was constructed to analyze the dynamic relationship between depression symptom and NSSI behavior, as well as the longitudinal mediating role of social support. Results: The levels of depressive symptoms(T1-T3:150.00±5.88，14.29±7.52，13.97±6.70) and NSSI behavior (T1-T3:6.91±4.65，6.10±3.92，4.79±3.51) of rural left behind junior high school students both showed downward trends ( F =13.41, η 2=0.02; F =50.49, η 2=0.06), the level of social support (59.17±14.68，62.27±15.36，61.82±15.90) showed an upward trend ( F =20.94, η 2=0.03), and the depressive symptom and NSSI behavior of girls were higher than those of boys ( F =19.91, η 2=0.02; F =4.57, η 2=0.01)(all P <0.05). The positive predictive relationships between depressive symptom and NSSI behavior among rural left behind junior high school students [depressive symptom of T1 positively predicted NSSI behavior of T2 and T3 ( β =0.10, 0.16); depressive symptom of T2 positively predicted NSSI behavior of T3 ( β =0.14), all P <0.01]. Social support during the T2 period played a partial mediating role between depressive symptom in T1 and NSSI in T3, with a mediating effect of 0.02 (95% CI =0.01-0.17, P <0.05). Conclusions Depressive symptom positively predict the occurrence of NSSI behavior among rural left behind junior high school students. Social support is an important mediating factor in alleviating the influence of depressive symptoms on the occurrence of NSSI behavior. It should prevent and reduce the occurrence of depression symptoms and NSSI behavior by improving the social support level of rural left behind junior high school students.