Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective To establish a three-dimensional finite element model of knee joint in patients with mild knee osteoarthritis in the absence of CT and MRI with thin layer thickness,and to analyze the stress distributions of the tibial plateau.Methods A female patient with mild knee osteoarthritis was selected as the study object,and received serial CT scan from pelvis to distal tibia of fibula.The obtained files in DICOM format were imported into Mimics software for extracting the bony structures of knee joint through threshold segmentation,and then optimizing the extracted structures with Edit Masks,Cavity Fill and Region Grow.The generated model of bony structures was imported into 3-matic for smoothing and wrapping,and Geomagic Wrap was used for bony structure processing with mesh doctor inspection,surface defect repair and surface fitting.The cartilages,meniscus and ligaments were established by contour extension,and assembled with bony structures in SolidWorks in the way of origin coincidence.After defining material properties and contact relationships,meshing,and setting constraints and loads in ANSYS software,the stress distributions of the tibial plateau when standing with both legs were analyzed.Results A complete knee joint model including bony structure,cartilage and ligament was successfully established.When standing with two legs,the peak value of contact stress was about 1.21 MPa,and the maximum stress was 0.72 MPa at the medial middle of tibial plateau and lateral tibial plateau.The 62.7%and 37.3%of the total load were borne by the inner and outer compartments.Conclusion The model of the total knee joint is established with CT extraction and software rendering,and the finite element analysis results meet clinical expectations,indicating that the model established by the proposed method is reliable and can be used for follow-up research.

Objective To construct a curriculum system for higher vocational education in speech-language-hearing rehabilitation based on the World Health Organization rehabilitation competency framework(RCF),to align with international standards. Methods Based on RCF,curriculum theory and principles of vocational education psychology,a curriculum system and its content for higher vocational education in speech-language-hearing rehabilitation were developed.The curric-ulum content and core competencies were analyzed in detail across four levels:basic courses,specialized basic courses,specialized core courses and practical training courses. Results From the perspective of the seven competency domains of RCF,the theoretical and practical significance of con-structing a speech-language-hearing higher vocational education curriculum system based on RCF was systemati-cally elaborated.The study emphasized the importance of establishing competency-oriented higher vocational re-habilitation education for developing students'professional competence,adapting to job requirements,and pro-moting career development.A curriculum content system for speech-language-hearing rehabilitation higher voca-tional education based on RCF was systematically constructed,encompassing basic courses,professional cours-es,and practical training courses.The course names,main content and competency objectives at each level were analyzed in detail. Conclusion It is important to develop the course system of higher vocational education of speech-language-hearing reha-bilitation based on RCF.By comparing with international standards,the curriculum is optimized,focusing on im-proving students'vocational competence and promoting the international development.The curriculum system covers key areas such as core values,beliefs,practice and professionalism,integrates basic,core and practical training courses to achieve a competence-oriented curriculum system for higher vocational speech-language-hear-ing rehabilitation education.

Objective:This study aims to investigate the anxiety-like behavior induced by cystitis and its neurobio-logical mechanisms in the anterior cingulate cortex(ACC)by constructing a mouse model of cystitis.Methods:A cys-titis model was established using lipopolysaccharide(LPS).Anxiety-like behavior in mice was explored through the open field test,and single-nucleus RNA sequencing was used to analyze changes in gene expression of neurons in the ACC.Results:HE staining results indicated significant inflammatory responses in the bladders of LPS-treated mice,including extensive infiltration of inflammatory cells,tissue edema,and bladder epithelial shedding.The open field test showed that the time and distance of mice moving in the central area of the open field were significantly reduced,indica-ting obvious anxiety-like behavior.Quality control of single-nucleus sequencing data suggested good data quality.Di-mensionality reduction clustering of the top 2000 highly variable genes revealed seven different cell subpopulations in the ACC.Five major cell types were identified in the ACC,and neurons were further clustered into five different subpopula-tions,identifying two main cell types.Differential gene analysis indicated significant changes in gene expression in neu-rons,with functional enrichment in pathways related to synaptic dysfunction.Conclusion:Cystitis can induce changes in gene expression in specific cell subpopulations in the ACC,suggesting that neurons may play an important role in the anxiety-like behavior induced by cystitis.This provides a new perspective for understanding the relationship between cystitis and anxiety behavior and offers important experimental evidence for future exploration of the brain regions and molecular mechanisms underlying cystitis-induced anxiety behavior.

Objective To compare the stability of multi-rod structures with double-headed screws and traditional connectors in posterior three-column osteotomy of the spine using finite element analysis.Methods A finite element model of the T3-L4 thoracolumbar spine was constructed based on postoperative computed tomography(CT)data of patients with severe kyphosis.Based on the patient's standard two-rod model(2R),a double-headed screw multi-rod structure model(4R-DHS)and a traditional connector multi-rod structure model(4R-TC)were constructed.The two models were evaluated under 300 N follower load and 7.5 N-m moment load,and the stability,maximum von Mises stresses on the main rods,and stress distributions of the two multi-rod structures were analyzed.Results There was little difference in the stability between the two multi-rod structures.Compared with 4R-TC,4R-DHS showed a decrease in the maximum von Mises stresses on the main rods during all motions(the stress decreased by 7.2％,8.8％,8.7％,18.5％,and 16.9％during flexion,left lateral bending,right lateral bending,left axial rotation,and right axial rotation,respectively)and more uniform stress distribution,except for a slight increase in the maximum von Mises stresses on the main rods during post-extension.Conclusions The double-headed screw multi-rod structure can reduce the maximum stress on the main rod compared with the traditional connector multi-rod structure,and there is no problem with stress concentration on the main rod near the connector,which can more effectively reduce the risk of internal fixation failure.

Objective    To establish the gene-based esophageal cancer (ESCA) risk score prediction models via whole transcriptome analysis to provide ideas and basis for improving ESCA treatment strategies and patient prognosis. Methods    RNA sequencing data of esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC) and adjacent tissues were obtained from The Cancer Genome Atlas database. The edgeR method was used to screen out the differential genes between ESCA tissue and normal tissue, and the key genes affecting the survival status of ESCC and EAC patients were initially identified through univariate Cox regression analysis. The least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to further screen genes and establish ESCC and EAC risk score prediction models. Results    The risk score prediction models were the independent prognostic factors for ESCA, and the risk score was significantly related to the survival status of patients. In ESCC, the risk score was related to T stage. In EAC, the risk score was related to lymph node metastasis, distant metastasis and clinical stage. The constructed nomogram based on risk score showed good predictive ability. In ESCC, the risk score was related to tumor immune cell infiltration and the expression of immune checkpoint genes. However, this feature was not obvious in EAC. Conclusion 聽 聽The ESCC and EAC risk score prediction models have shown good predictive capabilities, which provide certain inspiration and basis for optimizing the management of ESCA and improving the prognosis of patients.

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

OBJECTIVE: The current fertilization methods for Chinese yam are uneconomic and unfriend to environment. A rational one is very important to achieve desired balance of high yield of Chinese yam, economic and friend to environment. Here, we studied the effects of nitrogen (N), phosphorus (P), and potassium (K) fertilizers on the yield of 'Qinfeng' Chinese yam in shallow-groove directional cultivation. METHODS: The experiments were conducted in Dehua County, Fujian Province, China using a "3414" optimal design. Overall, three fertilizer factors (N, P, and K) were evaluated at the following four levels: 0, no fertilizer; 1, 0.5-fold the typical rate; 2, typical fertilization rate; and 3, 1.5-fold the typical rate. There were 14 different fertilization treatments. RESULTS: Treatment 6 (N₂P₂K₂) produced the longest (75.6 cm) and thickest tubers (4.9 cm) with the highest tuber fresh weight (1311.9 g) and yield (41 015.9 kg/hm²), whereas, treatment 1 produced the shortest (65.6 cm) and thinnest tubers (3.9 cm) with the lowest fresh weight (953.4 g) and yield (28 532.8 kg/hm²) among the 14 fertilizer combinations. The experimental data could be fitted to single-variable quadratic and binary quadratic models but not to a ternary quadratic polynomial model. Appropriate N, P, and K fertilizer application rates increased Chinese yam yield. However, excessive fertilization lowered the yield. Chinese yam yield was significantly and strongly correlated with the amounts of N, P, and K fertilizer applied. CONCLUSION Based on the single variable quadratic and binary quadratic models, we propose that the quantities of N, P, and K fertilizer used to grow 1 hm² 'Qinfeng' Chinese yam should be 360-388.3, 90-100.95, and 416.3-675 kg, respectively.

Objective:To explore the effect of pre-hospital health education based on "Internet +" on self-management efficacy, anxiety and depression of patients undergoing pulmonary tumor surgery, and provide reference for pre-hospital nursing care of this group.Methods:It was a randomized controlled trial. A total of 100 outpatients in Department of Pulmonary Oncology, Tumor Hospital of Tianjin Medical University to be hospitalized for surgery during November 2021 to March 2022, were divided into experimental group ( n=50) and control group ( n=50) by random number method according to the order of outpatient visits. Patients in control group received routine thoracic surgery nursing and health education after admission. Those in experimental group received "Internet +" pre-hospital health education during patients waiting for hospital beds for surgery, nursing care after admission was the same as that of the control group. The scores of Strategies Used by People to Promote Health (SUPPH) and Hospital Anxiety and Depression Score (HADS) were compared between the two groups 1 day before discharge. Results:At the time of outpatient visit, there was no statistically significant difference between the two groups in the comparison of all dimensions and total scores of SUPPH and the score of HADS ( P>0.05). Total SUPPH score, and self-decompression, self-decision and positive attitude score of experimental group were (110.62 ± 17.73) points, (38.74 ± 6.56) points, (11.98 ± 2.20) points, (59.90 ± 10.18) points, respectively, while in the control group, the scores were (92.86 ± 18.91) points, (32.46 ± 7.39) points, (9.76 ± 2.00) points and (50.64 ± 11.50) points, respectively, with statistically significant differences ( t values were -5.29--4.27, all P<0.01). Besides, the anxiety and depression scores of HADS in experimental group were (3.92 ± 2.25) points and (3.36 ± 2.38) points, respectively, while those in control group were (7.12 ± 3.49) points and (7.00 ± 3.53) points, respectively, and the differences were statistically significant ( t=5.45, 6.04, both P<0.01). Conclusions:The "Internet +" pre-hospital health education model can promote the self-management efficacy of patients undergoing pulmonary tumor surgery, and improve their psychological state during treatment. The study provided reference for promoting diversified extended nursing services in clinical practice.

Objective: To investigate the current situation of using virtual simulation technology in undergraduate schools of stomatology in China, analyze the problems and put forward corresponding improvement suggestions. Methods: A questionnaire survey was conducted among 672 teachers and 3 849 students in undergraduate schools of stomatology in China. Results : 25.81% of all participants had took part in dental virtual simulation courses, and 37.80% of the participants from “Double First-Class” universities had participated in dental virtual simulation courses. 92.12% of the virtual simulation courses were established for undergraduates. "Traditional course + virtual simulation model demonstration" is the main teaching form of virtual simulation courses. Most of the participants were satisfied with the virtual simulation courses offered by their schools. At present, there are also some deficiencies in the virtual simulation courses, such as lack of teaching resources, insufficient interaction and simulation. Conclusion There is difference in the application of virtual simulation technology in undergraduate schools of stomatology in China. The virtual simulation technology is more widely used in "Double First-Class" universities than in ordinary universities. Undergraduates are the main teaching objects of virtual simulation courses. Stomatological schools in China should pay attention to the development and utilization of virtual simulation curriculum resources by cooperation, enrich the form of virtual simulation courses and strengthen the promotion and application of virtual simulation technology in stomatological education.