BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L^-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L^-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L^-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L^-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L^-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L^-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC₅₀） of ACHN cells of 70.42 μmol·L^-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.

Objective:To observe any effect of combining low-frequency transcranial magnetic stimulation (rTMS) with interactive virtual scenario training on the recovery of upper limb motor function after a stroke.Methods:Ninety stroke survivors were randomly divided into a pseudo-rTMS group, an rTMS group and a combination group, each of 30. In addition to basic medication, conventional rehabilitation and nursing care, the pseudo-rTMS, rTMS and combination groups received either sham rTMS treatment, 1Hz rTMS or virtual situational interaction along with 1Hz rTMS 5 days a week for 4 weeks. Before and after the 4 weeks their motor evoked potentials, cortical latency and central motor conduction time were measured, and surface electromyography was applied to the affected biceps brachii and triceps brachii. Meanwhile, the National Institutes of Health Stroke Scale, the Fugl-Meyer upper extremity assessment and the modified Barthel index were employed to assess the degree of neurological deficit, upper extremity motor function and ability in the activities of daily living (ADL).Results:After the 4-week intervention, a significant improvement was observed in all of the outcome measurements with all three groups. At that time the average scores of the rTMS group were significantly better than the pseudo-rTMS group′s averages but the average scores of the combination group were significantly better than those of either of the other two groups.Conclusion:Repeated application of low-frequency transcranial magnetic stimulation combined with virtual scenario interactive training can effectively improve the upper limb motor function and ADL performance of stroke survivors, and relieve the symptoms of neurological deficit. The combined therapy is worthy of application in clinical practice.

Objective:Hepatocellular carcinoma(HCC)patients at the same stage exhibit different prognosis,and the underlying molecular mechanism remains unclear.This study aims to identify the key genes impacting the prognosis of HCC patients. Methods:Differentially expressed gene analyses were performed between HCC samples and normal ones,and between patients with long overall survival(OS)and those with short OS,in TCGA-LIHC and GSE14520 datasets.The Kaplan-Meier method with log-rank test was used to evaluate the role of secreted phosphoprotein 2(SPP2)in the prognosis of HCC patients.Gene set enrichment analysis(GSEA)was used to understand the difference of enriched signaling pathways between SPP2-stratified HCC subgroups.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to predict the potential functional pathways in which SPP2 might participate. Results:SPP2 was significantly down-regulated in tumors when compared with normal tissues,or in tumor samples with short OS when compared with those with long OS[fold change(FC)>2 and false discovery rate(FDR)<0.05].Low expression of SPP2 was associated with worse clinicopathological features like vascular invasion(P=1.6e-05),poor cancer status(with tumor,P=0.021),advanced T stage(T3 or T4,P=4.5e-04),advanced TNM stage(stage Ⅲ or Ⅳ,P=3.1e-04),and with unfavorable prognosis(shorter OS,P= 0.002).Gene enrichment analyses revealed that SPP2 might involve in the metabolic homeostasis of HCC and in the development of liver fibrosis and cirrhosis. Conclusion:SPP2 might inhibit the development of liver fibrosis and cirrhosis and the tumorigenesis of HCC,and analogs of SPP2 might be potential drugs in the prevention of these diseases.

Objective    To study the clinical characteristics of patients with partial and transitional atrioventricular septal defects (P/TAVSDs) in our hospital, and to evaluate the early follow-up outcomes from a real-world research perspective. Methods    The clinical data of all patients diagnosed with P/TAVSDs from January 1, 2018 to July 12, 2020, in our hospital were collected, and all patients' examination results were used as the real-world follow-up data, univariable Cox risk proportional model was used to analyze the outcomes. A total of 93 patients were finally included in the analysis, 72 with partial and 21 with transitional AVSD. There were 38 males and 55 females at age of 182.0 months (20.0 d to 779.5 months). Results    Univariable Cox proportional risk model suggested that at least one cardiac malformation (HR=15.00, 95%CI 3.00 to 75.00, P=0.001), preoperative moderate or greater mitral regurgitation (HR=6.60, 95%CI 1.70 to 26.00, P=0.007), and preoperative moderate or greater tricuspid regurgitation (HR=13.00, 95%CI 3.10 to 51.00, P<0.000 1) were  risk factors for moderate or greater postoperative atrioventricular valve regurgitation. Conclusion    Children with coarctation of the aorta or partial pulmonary vein connection, moderate or greater preoperative mitral regurgitation, and moderate or greater preoperative tricuspid regurgitation need to be alerted to the risk of moderate or greater postoperative atrioventricular valve regurgitation. Real-world data, with relaxed statistical P values and combined expertise, can suggest clinical conclusions that are close to those of high-quality retrospective studies.

Intelligent medical image segmentation methods have been rapidly developed and applied, while a significant challenge is domain shift. That is, the segmentation performance degrades due to distribution differences between the source domain and the target domain. This paper proposed an unsupervised end-to-end domain adaptation medical image segmentation method based on the generative adversarial network (GAN). A network training and adjustment model was designed, including segmentation and discriminant networks. In the segmentation network, the residual module was used as the basic module to increase feature reusability and reduce model optimization difficulty. Further, it learned cross-domain features at the image feature level with the help of the discriminant network and a combination of segmentation loss with adversarial loss. The discriminant network took the convolutional neural network and used the labels from the source domain, to distinguish whether the segmentation result of the generated network is from the source domain or the target domain. The whole training process was unsupervised. The proposed method was tested with experiments on a public dataset of knee magnetic resonance (MR) images and the clinical dataset from our cooperative hospital. With our method, the mean Dice similarity coefficient (DSC) of segmentation results increased by 2.52% and 6.10% to the classical feature level and image level domain adaptive method. The proposed method effectively improves the domain adaptive ability of the segmentation method, significantly improves the segmentation accuracy of the tibia and femur, and can better solve the domain transfer problem in MR image segmentation.
Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Magnetic Resonance Imaging ; Knee ; Knee Joint

ObjectiveTo study the inhibitory effect of Celastrus orbiculatus extract （COE） on gastric cancer cells， to clarify the specific mechanism of COE promoting the apoptosis of gastric cancer cells by affecting the mitochondrial structure and function， and to provide an experimental basis for the further development and clinical application of C. orbiculatus. MethodBrdu staining combined with flow cytometry and Annexin V-fluorescein isothiocyanate （AnnexinV-FITC） staining combined with flow cytometry were employed to detect the effects of COE （20， 40， 80 mg·L^-1） on the proliferation and apoptosis of gastric cancer cells， respectively. The changes in mitochondrial membrane potential were detected with JC-1 mitochondrial membrane potential assay kit. The expression of apoptosis-associated proteins including B-cell lymphoma-2 （Bcl-2）， B-cell lymphoma-xL （Bcl-xL）， Bcl-2-associated X （Bax）， and cysteine aspartutespecific protease-3 （Caspase-3） in gastric cancer cells was determined by Western blot. Transmission electron microscopy was employed to detect changes in the mitochondrial microstructure of gastric cancer cells exposed to COE. Western blot was employed to measure the expression of mitochondrial marker proteins ［superoxide dismutase 1 （SOD1）， voltage-dependent anion channel （VDAC）， prohibitin 1 （PHB1）， and heat shock protein 60 （HSP60）］ in gastric cancer cells. ResultCompared with the control group， COE （40， 80 mg·L^-1） inhibited the proliferation and promoted the apoptosis of gastric cancer cells （P<0.05）. Furthermore， COE reduced the mitochondrial membrane potential of gastric cancer cells. Compared with the control group， COE （20， 40， 80 mg·L^-1） up-regulated the expression of Bax and Caspase-3 which promoted apoptosis of gastric cells （P<0.05， P<0.01）， and COE at 40 and 80 mg·L^-1 down-regulated the expression of Bcl-2 and Bcl-xL which inhibited the apoptosis of gastric cancer cells （P<0.01）. The results of transmission electron microscopy showed that COE changed the microstructure of gastric cancer cells， which led to the appearance of vacuoles in the cell membrane and mitochondria and damaged the mitochondrial structure. Compared with the control group， COE （20， 40， 80 mg·L^-1） changed the expression of mitochondrial marker proteins. Specifically， it up-regulated the expression of SOD1 involved in stress response （P<0.05， P<0.01） and down-regulated that of VDAC， PHB1， and HSP60 associated with mitochondrial stability and permeability （P<0.01）. ConclusionCOE can significantly inhibit the proliferation and promote the apoptosis of gastric cancer cells. It may activate the mitochondrial apoptosis pathway by destroying the mitochondrial structure and function of gastric cancer cells.