Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.

Objective To develop a portable three-dimensional foot motion analysis system based on low-cost inertial measurement units(IMU)and force sensing resistor(FSR),and to explore the feasibility of assessing three-dimensional motion of internal small joints of foot in barefoot and shod conditions. Methods The system consisted of data sampling,data transmitting and data processing parts.IMUs were employed for data acquisition of small foot joints,and FSRs were utilized to detect heel strike and toe off.All the data were transmitted via wireless local area network.Data processing was accomplished by a self-programmed Excel mac-ro.From January to July,2024,two healthy female subjects wearing the device walked in the corridor at self-se-lected pace,for ten meters.Gait analysis was used to conduct consistency test on subject 2.Dorsiflexion-plan-tarflexion,adduction-abduction and internal rotation-external rotation of the 1st metatarsal relative to the phalan-geal(Met-Ph),the midfoot relative to the 1st metatarsal(Mid-Met)were recorded and analyzed on subject 1 in consecutive barefoot walking and two types of nurse footwear walking conditions. Results The system showed good consistency between tests.Dorsiflexion-plantarflexion,adduction-abduction and inter-nal rotation-external rotation ranges of motion were reduced in both Met-Ph and Mid-Met with shoes compared with those of bare foot,they were the least in arch support. Conclusion A low-cost,portable three-dimensional foot motion analysis system has been developed,which could be used to measure barefoot motion and shod foot motion in consecutive walking.

Objective To investigate the influence of different cell structures on the static and dynamic mechanical performance of porous titanium alloy scaffolds,and to provide a theoretical mechanical basis for the application of scaffolds in the repair of mandibular bone defects.Methods Porous titanium alloy scaffolds with diamond,cubic,and cross-sectional cubic cell structures were manufactured using three-dimensional printing technology.Uniaxial compression tests and ratcheting fatigue with compression load tests were conducted to analyze the static and dynamic mechanical performances of scaffolds with different cell structures.Results The elastic moduli of the diamond cell,cross-sectional cubic cell,and cubic cell scaffolds were 1.17,0.566,and 0.322 GPa,respectively,and the yield strengths were 71.8,65.1,and 31.8 MPa,respectively.After reaching the stable stage,the ratcheting strains of the cross-sectional cubic,diamond,and cubic cell scaffolds were 3.3%,4.0%,and 4.5%,respectively.The ratcheting strain increased with increasing average stress,stress amplitude,and peak holding time,and decreased with increasing loading rate.Conclusions The evaluation results of the static mechanical performance showed that the diamond cell scaffold was the best,followed by the cross-sectional cubic cell scaffold and the cubic cell scaffold.The evaluation results of the dynamic mechanical performance showed that the cross-sectional cubic cell scaffold performed the best,followed by the diamond cell scaffold,whereas the cubic cell scaffold performed the worst.The fatigue performance of the scaffold is affected by the loading conditions.These results provide new insights for scaffold construction for the repair of mandibular bone defects and provide an experimental basis for further clinical applications of this scaffold technology.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective To study stress relaxation behaviors of cartilage scaffolds under different degradation cycles by using finite element analysis combined with theoretical models. Methods Based on the established degradation theoretical model, the elastic modulus of the scaffold was calculated under different degradation cycles. The finite element model of cartilage scaffolds was established and stress relaxation simulation was performed to analyze the variation of scaffold relaxation stress with time. The stress relaxation constitutive model was established to predict mechanical properties of the scaffold. Results The elastic modulus of cartilage scaffolds at 14 th, 28th, 42nd, 56th day after degradation was 32. 35, 31. 12, 29. 91, 28. 74 kPa, respectively. The upper layer for cartilage scaffolds was the largest. The overall relaxation stress of the scaffold decreased rapidly with time and then tended to be stable. At 8th week after degradation, the stress which the scaffold couldwithstand was still within the physiological load range of the cartilage. The predicted results of the stress relaxation constitutive model were in good agreement with the finite element simulation results. Conclusions The elastic modulus of the scaffold gradually decreases with the increase of degradation time. The longer the degradation period is, the less stress the scaffold can withstand. At the same degradation period, the larger the applied compressive strain, the larger the stress on the scaffold. Both the finite element simulation and stress relaxation constitutive model can effectively predict stress variations of cartilage scaffolds under degradation

Gas therapy has been proven to be a promising and advantageous treatment option for cancers. Studies have shown that nitric oxide (NO) is one of the smallest structurally significant gas molecules with great potential to suppress cancer. However, there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor. Therefore, the anti-cancer mechanism of NO is the key to cancer treatment, and rationally designed NO delivery systems are crucial to the success of NO biomedical applications. This review summarizes the endogenous production of NO, its physiological mechanisms of action, the application of NO in cancer treatment, and nano-delivery systems for delivering NO donors. Moreover, it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies. The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Objective To study the effect of irrigation mechanical stimulation on scaffold degradation by numerical simulation, so as to predict its degradation degree. MethodsBased on perfusion experimental data, the fluid-solid coupling model was established by Comsol. The finite element model of scaffold was established by ABAQUS. Based on the models, the degradation performance of scaffold was simulated and predicted. Results The fluid-solid coupling simulation showed that the initial pressure at the speed of 15.79 mL/min was two-fold of that at 7.89 mL/min. Along the thickness of scaffold from the surface to the bottom, the pressures between the two velocities were decreased and gradually close to each other. The degradation of scaffold structure could be simulated dynamically by combining the degradation constitutive model with the finite element model. The obtained degradation data were consistent with the experimental data, and the residual molecular weight reached 0.643 on the 56th day. Compared with the experimental data, the simulation accuracy was higher than 98%. Conclusions The larger the perfusion velocity is, the greater the pressure on scaffold will be. Under the same perfusion velocity, the maximum force occurs on the surface of scaffold. The degradation pattern of scaffold can be predicted by applying the degradation constitutive model and the finite element model.

The small molecule nutrients and cell growth factors required for the normal metabolism of chondrocyte mainly transport into the cartilage through free diffusion. However, the specific mass transfer law in the cartilage remains to be studied. In this study, using small molecule rhodamine B as tracer, the mass transfer models of cartilage were built under different pathways including surface pathway, lateral pathway and composite pathway. Sections of cartilage at different mass transfer times were observed by using laser confocal microscopy and the transport law of small molecules within different layers of cartilage was studied. The results showed that rhodamine B diffused into the whole cartilage layer through surface pathway within 2 h. The fluorescence intensity in the whole cartilage layer increased with the increase of mass transfer time. Compared to mass transfer of 2 h, the mean fluorescence intensity in the superficial, middle, and deep layers of cartilage increased by 1.83, 1.95, and 3.64 times, respectively, after 24 h of mass transfer. Under lateral path condition, rhodamine B was transported along the cartilage width, and the molecular transport distance increased with increasing mass transfer time. It is noted that rhodamine B could be transported to 2 mm away from cartilage side after 24 h of mass transfer. The effect of mass transfer under the composite path was better than those under the surface path and the lateral path, and especially the mass transfer in the deep layer of cartilage was improved. This study may provide a reference for the treatment and repair of cartilage injury.
Cartilage, Articular ; Rhodamines/pharmacology* ; Chondrocytes

Objective:To explore the effect of online and offline blended scenario simulation teaching in the practice of nursing undergraduates.Methods:From August 2020 to May 2021, convenience sampling was used to select 76 nursing undergraduates in the class of 2017 who practiced in the Cardiology Department of the Second Affiliated Hospital of Harbin Medical University as the research object. The undergraduates were randomly divided into the experimental group and the control group, 38 in each group. The control group received the traditional graduation practice training, and the experimental group received online and offline blended scenario simulation teaching on this basis. After the practice, the clinical thinking ability of the two groups of students was evaluated by the Clinical Thinking Ability Evaluation Scale, the clinical practice ability of the two groups of students was evaluated by the Objective Structured Clinical Examination (OSCE) , and a teaching satisfaction survey was conducted.Results:The total score of clinical thinking ability, critical thinking ability, systematic thinking ability, evidence-based thinking ability, OSCE total score of the students in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . The students in the experimental group thought that the teaching method was helpful for in-depth understanding and application of theoretical knowledge, improving nursing assessment skills, clinical coping skills and communication skills, and at the same time helping to cultivate critical thinking and teamwork awareness, and arouse learning enthusiasm, and the differences were statistically significant (all P<0.05) . Conclusions:The online and offline blended scenario simulation teaching can effectively improve the clinical thinking ability, clinical practice ability and teaching satisfaction of nursing undergraduates, and it has good effect in the graduation practice of undergraduate nursing students.

BACKGROUND: Children and adolescents are in the growth and development stage, so the use of the same reconstruction methods as adults is easy to induce complications including limb length differences, high graft failure rate and re-surgical intervention. Simultaneously, the occurrence of osteoarthritis will also be advanced. OBJECTIVE: To explore the anatomical characteristics of the anterior cruciate ligament between children, adolescents and adults on MRI, and to provide an anatomical basis for the reconstruction of the anterior cruciate ligament in children and adolescents. METHODS: A retrospective analysis of patients undergoing knee MRI examination in Qingdao Municipal Hospital from October 2016 to October 2018 was conducted. These patients were divided into child and adolescent group and adult group (n=48 per group). The angle between the anterior cruciate ligament and the tibia and femur on the sagittal plane and the position of the anterior cruciate ligament tibial insertion, the angle between the anterior cruciate ligament and the tibia on the coronal plane, the tibial insertion of the anterior cruciate ligament and femur, and the position of the femur stop point on the axial position were measured in both groups. The data obtained from the measurement of the anterior cruciate ligament of children and adolescents were processed. The growth curves of the shape and position of the anterior cruciate ligament of children and adolescents were drawn, and the law of its growth changes was analyzed. RESULTS AND CONCLUSION: (1) The angle between the sagittal plane of the anterior cruciate ligament and the femur (t=﹣2.906, P<0.05), the angle between the sagittal plane of the anterior cruciate ligament and the tibia (t=﹣10.280, P < 0.05), the anterior cruciate ligament angle between the coronal plane and the tibia (t=﹣5.714, P<0.05) were smaller in the child and adolescent group than those of the adult group, and the difference was significant. (2) The ratio of the tibia coronal plane of the anterior cruciate ligament (t=﹣7.263, P < 0.05) and the ratio of the anterior cruciate ligament and femur axial plane (t=﹣7.378, P < 0.05) were lower in the child and adolescent group than those of the adult group, and the difference was significant. (3) There was no significant difference in the anterior cruciate ligament and tibia sagittal plane ratio (t=﹣1.588, P>0.05) and anterior cruciate ligament and femoral coronal surface ratio (t=﹣1.647, P>0.05) between the child and adolescent group and the adult group. (4) The growth curve results showed that during the growth and development, the angle between the anterior cruciate ligament and the femur and tibia on the sagittal plane and the angle with the tibia on the coronal plane changed from small to large (P<0.05). The relative position of the tibial insertion in the coronal position changed from small to large, which indicates that during the growth and development, the tibial insertion moved from inside to outside relative to the inside of the tibial plateau on the coronal plane (P < 0.05). (5) The relative position of femoral insertion in the axial position changed from small to large, suggesting that during the growth and development, the femoral insertion moved from the outside to the inside relative to the lateral femoral condyle (P<0.05). (6) There was no significant difference in the tibial insertion and the femoral insertion between the child and adolescent group and adult group (P>0.05).