BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

【Objective】 To construct a prognostic model of clear cell renal cell carcinoma (ccRCC) based on endoplasmic reticulum stress (ERS)-related long non-coding ribonucleotides (lncRNA),so as to explore the correlation between immune cell infiltration and prognosis of ccRCC patients,and to search for new drugs for the treatment of ccRCC. 【Methods】 The transcriptome and clinical data of cancerous and paracancerous tissues of ccRCC were obtained from the TCGA database.The ERS-associated gene set was obtained from the MSigDB database.ERS co-expressed lncRNAs were screened with Pearson correlation analysis.ERS-related lncRNA (ERSRL) with prognostic significance were screened with Lasso regression,univariate and multivariate Cox regression analyses,and a prognostic model was constructed.The risk value of each sample was calculated according to the prognostic model formula.The patients were divided into high- risk and low- risk groups for survival difference analysis.The predictive performance of the prognostic model was evaluated with survival curve,receiver operating characteristic (ROC) curve and calibration curve.The infiltration of immune cells in high-and low-risk groups was analyzed with CIBERSORT database.The relationship between ERSRL and drug sensitivity was analyzed with GDSC database to identify drugs with potential efficacy against ccRCC. 【Results】 A total of 9 lncRNAs with independent prognostic significance were screened to construct the prognostic model.Kaplan-Meier analysis showed significant survival differences between the high- and low-risk groups.Univariate and multivariate Cox regression analyses showed that age,grade,stage and risk score could be used as independent prognostic factors.The area under the ROC curve (AUC) of the 1-,3-,and 5-year survival rates of the training set were 0.754 (95%CI:0.659-0.848),0.744 (95%CI:0.667-0.815),and 0.759 (95%CI:0.662-0.820),respectively,and the C-index was 0.777 (95%CI:0.759-0.796).Immune infiltration results showed that plasma cells,activated memory CD4⁺T cells,regulatory T cells,M0 macrophages,and activated mast cell infiltration levels were higher in the high-risk group than those in the low-risk group.Drug susceptibility analysis identified 12 drugs with potential curative effects on ccRCC,including AZD8055. 【Conclusion】 Based on 9 ERSRLs,a prognostic model for ccRCC patients was constructed,and 12 drugs with potential therapeutic effects were screened,including AZD8055.

ObjectiveTo investigate the mechanism of Ershiwuwei Guijiu pill in preventing and treating postmenopausal osteoporosis （PMOP） by activating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway and inhibiting excessive autophagy. MethodFemale SD rats were ovariectomized and randomly divided into the sham operation group （Sham）， the operation group （OVX）， the Ershiwuwei Guijiu pill （GJ） group， and the raloxifene hydrochloride （RLX） group， with 10 rats in each group. Enzyme-linked immunosorbent assay （ELISA） and colorimetric methods were used to detect the levels of estrogen， bone metabolism markers in serum， and total superoxide dismutase （T-SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in tibial tissue. Flow cytometry was used to detect reactive oxygen species （ROS） levels in bone marrow mesenchymal stem cells. Masson staining was used to observe pathological changes in the proximal tibia， and micro-computed tomography （Micro-CT） was used to observe changes in tibial microstructural parameters. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of autophagy-related proteins Beclin1， microtubule-associated protein 1A/1B-light chain 3 （LC3）， autophagy-related 5 （Atg5）， as well as PI3K， Akt， and mTOR in tibial tissue. ResultCompared with the Sham group， the OVX group showed a significant decrease in serum levels of estradiol （E₂） and calcium ion （Ca²⁺）， and T-SOD， GSH-Px， PI3K， Akt， and mTOR mRNA levels in bone tissue （P<0.05， P<0.01）， significantly reduced bone mineral density （BMD）， bone surface/bone volume （BS/BV）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular connectivity （Con） in the tibia （P<0.05， P<0.01）， thinner epiphyseal growth plate， and the bone marrow cavity filled with fat vacuoles. Moreover， the levels of phosphorus （P）， MDA， ROS， and mRNA and protein expression of Beclin1， LC3， and Atg5， as well as trabecular separation （Tb.Sp） were significantly elevated （P<0.05， P<0.01）. Compared with the OVX group， the GJ and RLX groups showed significant increases in serum E₂ and Ca²⁺， and bone tissue levels of SOD， GSH-Px， and the mRNA levels of PI3K， Akt， and mTOR （P<0.05， P<0.01）， significantly increased BMD， BS/BV， Tb.Th， Tb.N， and Con in the tibia， thickened epiphyseal growth plate， and significantly reduced fat vacuoles in the bone marrow cavity （P<0.05， P<0.01）. Additionally， the levels of P， MDA， ROS， Beclin1， LC3， Atg5 mRNA and proteins， and Tb.Sp were significantly decreased （P<0.05， P<0.01）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR， which were significantly reduced in the OVX group （P<0.01）， were significantly increased in the GJ and RLX groups （P<0.01）. ConclusionThe Ershiwuwei Guijiu pill reduces oxidative stress and inhibits autophagy， thereby preventing and treating postmenopausal osteoporosis. Its mechanism may be related to the activation of the PI3K/Akt/mTOR signaling pathway， which inhibits autophagy.

Purpose/Significance To expound the content features of online medical reviews and its impact on the utilization of pa-tients'online consultation services,and to provide references for the information management of online medical platforms.Method/Process The LDA topic model based on TF-IDF is constructed,the semantic analysis method based on sentiment dictionary is adopted to mine the content features of online medical reviews,and the principal component analysis(PC A)is applied to classify and explore them,and the regression analysis is carried out by binary logistic.Result/Conclusion The content features of online medical reviews are divided into 3 categories,including 9 indicators.Among them,the attributes of reviewers,timeliness,consultation process,service atti-tude and platform feedback have a significant impact on the utilization of efficient online consultation services by patients.It is suggested to improve the utilization level of online consultation services by optimizing related services of online medical platform review section.

Objective:To identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA by using bioinformatics analysis and explore the effects of DMARDs such as methotrexate, tocilizumab and rituximab on the DEGs in RA synovium.Methods:RA expression profile microarray data GSE7307、GSE12021、GSE55457、GSE55235、GSE77298、GSE89408 were acquired from the public gene chip database (GEO), including 113 synovial tissue samples from RA and 70 healthy controls (HC). At the same time, synovial expression microarrays GSE45867, GSE24742 and GSE97165 after DMARDs treatment were obtained. These data included 8 samples treated with methotrexate, 12 treated with tocilizumab, 12 treated with rituximab and 19 treated with combined tDMARDs. R software was used to screen DEGs and Venn plots using gene ontology function enrichment and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Hub genes were selected by STRING online analysis tool and Cytoscape software.Results:Compared with HC, 797 DEGs were up-regulated and 434 DEGs were down-regulated in the synovial tissue of RA. These DEGs were mainly enriched in T cell activation, immune response-activating cell surface receptor signaling pathway. Using Cytoscape and cytoHubba to obtain 5 sets of DEGs based on the STRING database model, the degree algorithm screened out 10 hub genes: LCK, SYK, PTPRC, HLA-DRA, LYN, NCAPG, TOP2A, JUN, CXCR4, CCNB1. Methotrexate treatment significantly up-regulated 20 DEGs and down-regulated 30 DEGs. Rituximab treatment up-regulated 100 DEGs and down-regulated 55 DEGs. Tocilizumab treatment up-regulated 91 DEGs and down-regulated 317 DEGs. These altered DEGs were enriched in regulating cell adhesion, leukocyte-cell adhesion, leukocyte transfer, and insulin-like growth factor receptor signaling pathways. It was worth noting that after treatment, a total of 306 high-expressing DEGs were down-regulated, and 36 low-expressing DEGs were up-regulated.Conclusion:LCK, insulin-like growth factor receptor signaling pathway, etc. are the responsible molecular mechanisms and key pivot genes for the occurrence and development of RA, and the treatment of DMARDs, which are closely related to the response of RA to the treatment of DMARDs.

Purpose/Significance To explore the characteristics and clinical significance of differentially expressed genes closely re-lated to HPV E6/E7 by using bioinformatics.Method/Process The cervical tissue and clinical information of cervical cancer in TCGA and GTEx of UCSC are used as the training set.The expression profile chip GSE63514 related to cervical cancer in GEO is used as the validation set.Firstly,the limma package of R software is used to screen DEGs of tumor and normal samples,and Venn map of genes re-lated to E6/E7 protein in MigDB is made.Survival analysis is performed by survival kit and verified by ROC and protein expression lev-els.Secondly,key genes are obtained by copy number variation and methylation correlation.Finally,the specific co-expression network is constructed and enrichment analysis and immune infiltration analysis are performed.Result/Conclusion There are 101 differentially expressed genes related to HPV E6/E7 protein,and three genes are found to have significance after screening,namely E2F1,MCM4 and PCNA.At the same time,it is found that the genes in the specific coexpression network are significantly enriched in the DNA replication and chromosome organization pathways.Immune correlation analysis shows that key genes are significantly associated with CD4 T cells,B cells and neutrophils.DNA replication,chromosome organization,etc.,are the molecular mechanisms and key genes significantly related to the development of cervical squamous cell carcinoma and HPV E6/E7 encoded proteins.

ObjectiveTo explore the mechanism of Tibetan medicine Ershiwuwei Guijiuwan against osteoporosis in ovariectomized rats through the classical Wnt/β-catenin signaling pathway. MethodForty-eight 3-month-old SD female rats were randomized into model group （equivalent volume of normal saline）， sham operation group （equivalent volume of normal saline）， estradiol group （0.1 mg·kg^-1 estradiol valerate）， and high-， medium-， low-dose Ershiwuwei Guijiuwan groups （800， 400， 200 mg·kg^-1， respectively）. For the modeling， some adipose tissue near the ovaries was removed in the sham operation group， and ovaries were excised in other groups. Administration （ig， once a day） started two weeks after the operation and lasted 12 weeks. After sampling， based on hematoxylin and eosin （HE） staining， the morphological changes of the right femur and lumbar spine of the rats were observed. The enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum levels of rat tartrate-resistant acid phosphatase 5b （TRAP5b）， collagen type Ⅰ C-terminal peptide （CTX-Ⅰ）， bone alkaline phosphatase （BALP）， amino-terminal propeptide of type Ⅰ procollagen （PINP）， and bone Gla-protein （BGP）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to examine the mRNA expression of β-catenin and Runt-related transcription factor 2 （Runx2） in femur， and Western blot to detect the protein expression of β-catenin， Runx2， and low-density lipoprotein receptor-related protein-5 （Lrp-5）. ResultCompared with the sham operation group， the model group showed disordered and sparse bone trabecula with fewer connections， decrease in serum levels of BALP， BGP， and PINP （P<0.01）， increase in levels of CTX-Ⅰ and TRAP5b （P<0.01）， reduction in mRNA expression of β-catenin and Runx2 in femoral tissue （P<0.01） and protein expression of Lrp-5， β-catenin， and Runx2 （P<0.01）. Compared with the model group， estradiol and each dose of Ershiwuwei Guijiuwan increased the volume of bone trabecula， made thebone trabecula closely arranged， reduced the loss of the trabecular meshwork， raised the serum levels of BALP and BGP （P<0.01）， and lowered TRAP5b level （P<0.01）. PINP level was significantly increased in the high-dose Ershiwuwei Guijiuwan group and estradiol group （P<0.01） and CTX-Ⅰ level was significantly decreased in the high-dose Erwenwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. The mRNA expression of β-catenin in femoral tissue and protein expression of Lrp-5 and β-catenin in estradiol group and three Ershiwuwei Guijiuwan groups were significantly increased （P<0.05， P<0.01）， and the levels of Runx2 mRNA and protein were significantly increased in the high-dose Ershiwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. ConclusionTibetan medicine Ershiwuwei Guijiuwan is effective for the osteoporosis in ovariectomized rats， which may be related to the classic Wnt/β-catenin signaling pathway. It affects bone metabolism by up-regulating the expression of osteogenesis-related genes in the signaling pathway.

Objective:To statistically analyze SCI paper output and research hotspots of Chinese stomatology research institutes from 2011 to 2020.Methods:The papers of Chinese stomatology research institutions in the Web of Science database were searched and analyzed by bibliometric methods in various dimensions including publication time, institutional and journal distribution, international (regional) cooperation, and research hotspots.Results:The number and quality of publications in Chinese dental research institutions have increased significantly in the past decade, and the top four institutions in terms of publication number were Sichuan University, Peking University, Shanghai Jiaotong University, and Air Force Military Medical University. The distribution of the journals to which the articles belong was relatively scattered, and the research hotspots mainly focused on squamous cell carcinoma, periodontitis, bone regeneration, and materials science.Conclusions:The output of SCI papers and the number of high-quality papers in Chinese stomatology research institutions increased year by year during 2011-2020, and the scientific research strength continued to increase.

OBJECTIVE： To systematically review the efficacy and safety of colesevelam hydrochloride combined with other hypoglycemic drugs in the treatment of T2DM， and to provide evidence-based reference for clinical treatment of T2DM. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane Library， CJFD， VIP and Wanfang database during database establishement-Jul. 2019， randomized controlled trials （RCT） about the efficacy and safety of colesevelam hydrochloride combined with other hypoglycemic drugs （trial group） vs. placebo or other hypoglycemic drugs （control group） in the treatment of T2DM were collected. After extracting data from clinical studies that met the inclusion criteria， the quality of the studies was evaluated by Cochrane System Evaluator Manual 5.1.0. Meta-analysis was conducted by using Rev Man 5.3 statistical software in respects of the levels HbA1c， FPG， LDL-C， the incidence of total ADR， incidence of hypoglycemia and incidence of gastrointestinal ADR. RESULTS： A total of 11 RCTs were included， involving 2 625 patients. Results of Meta-analysis showed that HbA1c levels [MD＝－0.37， 95％CI（－0.51， －0.22），P＜0.001]， FPG level [MD＝－0.47， 95％CI（－0.88， －0.07）， P＝0.02] and LDL-C level [MD＝－0.38， 95％CI（－0.49， －0.28）， P＜0.001] in trial group were significantly lower than control group， with statistical significance. In terms of safety， the incidence of total ADR [OR＝1.24， 95％CI（1.06， 1.45）， P＝0.007] and gastrointestinal ADR [OR＝1.78，95％CI（1.05， 3.02），P＝0.03] in trial group were significantly higher than control group， with statistical significance. There was no significant difference in the incidence of hypoglycemia [OR＝1.03， 95％CI（0.62，1.72），P＝0.90]. CONCLUSIONS： Colesevelam hydrochloride combined with other hypoglycemic drugs can effectively reduce the levels of HbA1c， FPG and LDL-C in T2DM patients， but attention should be paid to the occurrence of gastrointestinal ADR.

Objective To research the effects of hyperbaric oxygen (HBO) on the ultrastructure of heart,brain and lung in rats with plateau deacclimatization.Methods Forty-mine SD rats were selected.Fortyfour SD rats were routinely fed in a hypobaric hypoxia chamber at the simulated altitude of 5 000 m for 3 months.Nine rats died in the hypobaric hypoxia chamber.After coming out from the chamber,35 survival rats were randomly divided into the high altitude control group (instantly after out of the hypobaric hypoxia chamber),HBO group Ⅰ,Ⅱ and Ⅲ (7 days,1 months and 2 months after HBO treatment) and control groups Ⅰ,Ⅱ and Ⅲ according to the body mass,5 cases in each group;the HBO groups were treated by HBO for 7 d.The control group Ⅰ,Ⅱ and Ⅲ were synchronously fed in normal pressure and oxygen environment after HBO treatment.The rats in all groups were synchnonously sacrificed,the other 5 SD rats as the plain control group were fed in hormal pressure oxygen environment.The frontal cortex,heart and lung tissues were taken out for observing the ultrastructure changes by optical microscopy and electron microscopy.Results Hypoxia induced mitochondria swelling and ridge breakage in cranial nerves cells,swelling of mitochondria and peripheral structures,myocardial cells cloudy swelling,vacuolar degeneration,muscle fibers irregular arrangement,inflammatory cell infiltration and vasodilatation.The alveolar septm was broadened,blood capillaries were dilated and congestive,alveolar space was filled with pink transudation,inflammatory cells were infiltrated,and alveolar wall was incrassated.After HBO treatment,the tissue ultrastructure injurys were significantly improved compared with the control group,the recovery in the HBO group Ⅱ was significantly better than that in the HBO group Ⅰ,and the HBO group Ⅲ was significantly better than the HBO group Ⅱ,which recovered to plain level after 2 months.Conclusion HBO treatment has the effects for improving cranial nerves injury in hypoxia rat,promotes cellular function recovery,decreases hypoxia induced pulmonary hypertension,and has the protective effect on ischemic myocardium.