OBJECTIVE To investigate the effects of galangin （GLA） on autophagy and apoptosis of chondrocytes in knee osteoarthritis （KOA） rats by regulating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/UNC-51-like kinase 1 （ULK1） signaling pathway. METHODS KOA rat model was constructed and separated into model group， L-GLA， M-GLA， H-GLA groups [subcutaneous injection of 100， 200， 400 μg/kg GLA]， GLA+Compound C group [subcutaneous injection of 400 μg/kg GLA+0.2 mg/kg AMPK inhibitor Compound C]， with 10 rats in each group. Additionally， 10 normally fed rats were selected as the sham operation group. After the last medication， the degree of knee joint swelling of rats in each group was detected； the pathology of knee joints in KOA rats was observed. The serum expressions of matrix metalloproteinase 13 （MMP-13） and interleukin-1β （IL-1β） in KOA rats were detected； the autophagy of chondrocytes in KOA rats was observed； the chondrocyte apoptosis in KOA rats was detected； the phosphorylation of AMPK/mTOR/ULK1 pathway-related proteins in cartilage tissue of knee joint were detected in rats. RESULTS Compared with the sham operation group， the arrangement of articular chondrocytes in the model group was disordered， with nuclear pyknosis and severe fibrosis of the articular cartilage layer， accompanied by a large amount of inflammatory cell infiltration； the degree of joint swelling， the number of autophagic vacuoles and apoptosis rate of chondrocytes， serum levels of MMP-13 and IL-1β， and the phosphorylation of mTOR protein in cartilage tissue of knee joint were all increased significantly （P＜0.05）， while the phosphorylation of AMPK and ULK1 protein were all decreased significantly in cartilage tissue of knee joint （P＜0.05）. Compared with the model group， L- GLA， M-GLA， H-GLA groups showed significant improvement in joint cartilage injury and reduced infiltration of inflammatory cells in rats. The above quantitative indicators were significantly reversed in a dose-dependent manner，except the number of autophagic vacuoles increased significantly （P＜0.05）. Compared with the H-GLA group， the GLA+ Compound C group showed aggravated cartilage tissue of joint cartilage injury and inflammatory cell infiltration in rats， and the above quantitative indicators were reversed significantly （P＜0.05）. CONCLUSIONS GLA can promote autophagy and inhibit apoptosis of chondrocytes in KOA rats， the mechanism of which may be associated with activating AMPK/mTOR/ULK1 signaling pathway.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

ObjectiveTo explore the effects of the Tibetan medicine Sanwei Doukoutang （SWDK） on cognitive dysfunction in mice suffering from Alzheimer's disease （AD） and its related mechanism. MethodsFifty SPF 5 × FAD mice were randomly divided into model group， total ginsenoside group（0.04 g·kg^-1）， high-， medium-， and low-dose groups of SWDK （32.60， 16.30， 8.15 g·kg^-1）， with 10 mice in each group， and ten wild-type mice of the same age were used as the normal group， male and female in 1∶1. Gavage administration was performed once daily for 8 weeks. The Morris water maze test and contextual fear memory experiment were used to observe learning and memory function. Hematoxylin-eosin （HE） staining was utilized to observe the changes in the pathomorphology of brain tissue in mice. The levels of synaptophysin （SYP） and postsynaptic dense substance 95 （PSD95） in mice serum were detected by enzyme-linked immunosorbent assay （ELISA）. The positive expression of brain-derived neurotrophic factor（BDNF） in the dentate gyrus （DG） region of mouse brain tissue was observed by immunohistochemistry （IHC）. The protein levels of BDNF， Wnt family member 3A（Wnt3a）， and β-catenin were detected in the hippocampus of mice by Western blot. ResultsCompared with the normal group of mice， the model group of mice had significantly more complex swimming routes and lower swimming speed （P<0.01）， significantly lower percentage of time spent in the target quadrant （P<0.01）， and a significantly lower percentage of freezing time （P<0.05）. The number of neurons in the hippocampal region of mice was obviously reduced and unevenly arranged. The levels of SYP and PSD95（P<0.01） in the serum of mice were reduced， and the positive expression of BDNF in the DG region of the brain tissue of mice was reduced. The levels of hippocampal BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice were obviously reduced （P<0.05， P<0.01）. Compared with the model group， the mice in the SWDK group and the total ginsenoside group had significantly shorter swimming routes， the high- and medium- dose SWDK groups significantly higher swimming speeds （P<0.01）， significantly higher percentage of time spent in the target quadrant （P<0.01）， obviously higher percentage of Freezing time （P<0.05）， and obviously more neurons in the hippocampal region of the mice with tighter arrangement. The mice had elevated levels of serum SYP （P<0.05， P<0.01）， PSD95 （P<0.01）， increased BDNF-positive cells in the DG region of brain tissue， and obviously elevated levels of BDNF， Wnt3a， and β-catenin proteins in the hippocampus of mice （P<0.05， P<0.01）. ConclusionSWDK can significantly improve the cognitive dysfunction of AD mice， and its mechanism may be related to regulating the Wnt/β-catenin signaling pathway， which promotes BDNF expression and thereby enhances synaptic plasticity， allowing neuronal signaling to be restored.

OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway. METHODS Human glioma T98G cells were cultured in vitro， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF- κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （P＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （P＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （P＜0.05）； above indexes were reversed significantly by pathway activator （P＜0.05）. CONCLUSIONS Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.

Background and objective Lung cancer is a common malignant tumor of the lung.To explore the molecular mechanism of the occurrence and development of lung cancer is a hot topic in current research.Cyclic RNA D1(CircCCND1)is highly expressed in lung cancer and may be a potential target for the treatment of lung cancer.The aim of this study was to investigate the effect of CircCCND1 on the malignant biological behaviors of lung cancer cells by regulat-ing the miR-340-5p/transforming growth factor β-induced factor homeobox 1(TGIF1)axis.Methods The expression of CircCCND1,miR-340-5p,and TGIF1 mRNA in human normal lung epithelial cells BEAS-2B and human lung cancer H446 cells were detected.H446 cells cultured in vitro were randomly divided into control group,CircCCND1 siRNA group,miR-340-5p mimics group,negative control group,and CircCCND1 siRNA+miR-340-5p inhibitor group.Cell proliferation,mito-chondrial membrane potential,apoptosis,migration,and invasion were detected,and the expressions of CircCCND1,miR-340-5p,TGIF1 mRNA,BCL2-associated X protein(Bax),cleaved Caspase-3,N-cadherin,E-cadherin,and TGIF1 proteins in each group were detected.The targeting relationship of miR-340-5p with CircCCND1 and TGIF1 was verified.Results Compared with BEAS-2B cells,CircCCND1 and TGIF1 mRNA were increased in H446 cells,and miR-340-5p expression was decreased(P＜0.05).Knocking down CircCCND1 or up-regulating the expression of miR-340-5p inhibited the proliferation,migration and invasion of H446 cells,decreased the expression of TGIF1 mRNA and TGIF 1 protein,and promoted cell apop-tosis.Down-regulation of miR-340-5p could antagonize the inhibitory effect of CircCCND1 knockdown on the malignant bio-logical behavior of H446 lung cancer cells.CircCCND1 may target the down-regulation of miR-340-5p,and miR-340-5p may target the down-regulation of TGIF 1.Conclusion Knocking down CircCCND1 can inhibit the malignant behaviors of lung cancer H446 cells,which may be achieved through the regulation of miR-340-5p/TGIF1 axis.

Objective:To investigate the clinical characteristics and potential predisposing factors of the external cervical resorption(ECR).Methods:22 ECR cases with 38 affected teeth from 2016 to 2022 were retrospectively reviwed.Descriptive analysis combined with single factor analysis was used to study the clinical characteristics and influencing factors of ECR.Results:Maxillary anterior teeth(34.2％)were the most affected by ECR.Univariate analysis showed that ECR was more commonly noted in teeth without percussion pain and palpation pain,the probing depth of the periodontal pocket was greater than 3mm,with pulp activity reaction,without forma-tion of abscess and/or sinus tract,and without periapical lesions.There were statistically significant differences in percussion tender-ness,palpation tenderness and probing depth among the different Heithersary stages(P＜0.05).In the advanced cases,deep periodon-tal pockets and abscess formation were observed.The most common related dental factors of ECR were orthodontic treatment(15.87％)and dental traumatic injury(28.57％).Conclusion:ECR affected teeth often lack of clinical signs and symptoms.Radiology is the key to early diagnosis.

By combining the ability of SMOTE data augmentation method to process complex audio data with the accurate prediction ability of GA-SVM,a GA-SVM model based on SMOTE data augmentation algorithm is proposed and applied to the diagnosis of thyroid diseases.The results demonstrate the excellent performance of the proposed method in the classification and diagnosis of thyroid diseases.Compared with other methods,the proposed method has better diagnostic efficacy and higher applicability in the classification and diagnosis of thyroid diseases.

Objective To explore the correlations between self-esteem,social support and mental health status of patients with deep bums at special sites at different stages of the disease course.Methods A total of 36 inpatients who were admitted to Department of Burn Surgery of The First Affiliated Hospital of Naval Medical University(Second Military Medical University)between Jan.2020 and Sep.2023 were enrolled.The patients were assessed with self-rating anxiety scale(SAS),self-rating depression scale(SDS),post-traumatic stress disorder(PTSD)checklist-civilian version(PCL-C),Rosenberg self-esteem scale(RSES),and perceived social support scale(PSSS)within 7 d of burns(early stage of disease),at wound closure(early rehabilitation stage),and 3 months after wound closure(late rehabilitation stage).The data were collected and invalid data were excluded for statistical analysis.Results A total of 36 patients effectively completed all the scales.There were anxiety,depression and PTSD in patients with deep bums at special sites at different stages of the disease course,and the number of burn patients with anxiety,depression and PTSD showed a downward trend with the course of disease.The RSES score at the early rehabilitation stage was positively correlated with SAS score(rs=0.412,P=0.013),SDS score(rs=0.347,P=0.038)and PCL-C score(rs=0.447,P=0.006)at the early stage of disease,but not with SAS,SDS,or PCL-C scores at the early and late rehabilitation stages(all P＞0.05).There were no correlations between PSSS score at the early rehabilitation stage and SAS,SDS,or PCL-C scores at the early stage of disease or SAS or PCL-C scores at the early stage of rehabilitation(all P＞0.05),but there were negative correlations between PSSS score at the early rehabilitation stage and SDS score at the early stage of rehabilitation(r=-0.430,P=0.009)and SAS score(r=-0.467,P=0.004),SDS score(r=-0.483,P=0.003),and PCL-C score(rs=-0.351,P=0.036)at the late stage of rehabilitation.Conclusion Anxiety,depression,and PTSD are observed in patients with deep burns in special areas at different stages of the disease.A high level of self-esteem is associated with an increased risk of mental problems at early stage of burns.Conversely,a high level of social support is associated with a reduced likelihood of mental problems at late stage of rehabilitation.

Objective The aim of this study was to investigate the molecular regulatory mechanism of cancer susceptibility candidate 15(CASC15),a long-stranded non-coding RNA(lncRNA),in hepatocellular carcinoma(HCC).Methods Bioinformat-ics methods were used to predict the expression of target genes and analyze the relationship between the expression of target genes and the survival time of patients;Hepatocellular carcinoma tissues and adjacent tissues from patients with HCC were collected;CCK-8,Tr-answell,and flow cytometry experiments were used to detect proliferation,invasion,migration and apoptosis of SMMC7721 cells and Huh-7 cells;The dual-luciferase assay was used to detect the targeting relationship between miR-144-3p and CASC15,as well as leucine rich repeat containing protein 1(LRRC1);RT-qPCR and Western blot were used to detect mRNA and protein expression of target genes;Immunofluorescence was used for protein localization of target genes;Replicate experiment was performed to verify the effect of CASC15/miR-144-3p/LRRC1 on the progression of HCC.In vivo experiment was performed to verify the effect of CASC15 on HCC progression.Results TCGA database and RT-qPCR assay showed high expression of CASC15,low expression of miR-144-3p,and high expression of LRRC1 in HCC tissues and cells(P<0.05).The results of cell function experiments on proliferation,inva-sion and migration showed that CASC15 and LRRC1 played a promoting role in tumor development,while miR-144-3p had an inhibi-tory effect,consistent with the results of apoptosis experiments(P<0.05).Cell function experiments showed that CASC15 inhibited miR-144-3p function,miR-144-3p inhibited LRRC1,and CASC15 bound to miR-144-3p,leading to the upregulation of LRRC1.The replicate experimental results indicated that CASC15 promoted LRRC1 expression through inhibiting miR-144-3p,thereby pro-moting HCC cell proliferation,invasion and migration,and inhibiting apoptosis.Conclusion CASC15 may promote HCC progression by regulating the miR-144-3p/LRRC1 axis.

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.