Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

The primary cause of injury and death in the elderly has been reflected in fall the elderly, so the application of reasonable and effective prevention strategies has great significance in reducing the risk of fall in the elderly. The research progress of virtual reality technology applied in preventing fall in the elderly at home and abroad over the years was systematically reviewed in this study. The mechanism of the technology in preventing fall in the elderly was mainly elaborated from five aspects of improving balance ability, gait disturbance, cognitive impairment, muscle strength and the fear psychology of falling. The purpose of this thesis is to broaden the research ideas of medical personnel on the prevention of fall of the elderly, provide more effective clinical practice plans, reduce the occurrence of fall, and guarantee the safety of the elderly.
Aged ; Humans ; Gait ; Muscle Strength ; Technology ; Virtual Reality

Objective To investigate the differences of the characteristic and syndrome of patients with alcoholic cirrhosis(AC) and viral cirrhosis(VC).Methods Seventy patients with AC and 300 patients with VC in the Binzhou People's Hospital were selected as our subjects.The information including gender,age,disease history,chnical syndrome were collected.Meanwhile,the levels of Aspartate aminotransferase/alanine aminotransferase (AST/ALT),γ-glutamyl transferase (γ-GT),alkaline phosphatase (ALP) and total bilirubin (TBil) in serum were measured.Results The proportion of males in the AC group was 91.43％ (64/70),significantly higher than that of VC group(64％ (192/300),x2 =15.76,P =0.003)).The age,disease periods in AC group were (50.13 ± 12.35) years old and (2.09 ± 0.67) years,lower than the VC group ((58.66 ± 7.45) yearsold,t =3.97,P =0.042 ; (4.56 ± 1.14) years,t =5.22,P =0.034).There was no significant difference regarding of liver function index (P ＞ 0.05).The rate of nasal carp (18.57％),gum bleeding (27.14％),liver palms(64.29％),spider(45.71％) in the AC group were significantly higher than the VC group (6.33％,15.00％,47.00％,29.67％ respectively,P =0.017,0.036,0.025,0.016 respectively).The ratio of splenomegaly and esophageal varices were (81.43％) and (65.71％) in AC group,significantly lower than VC group (90.33％,86.00％ respectively,P =0.037,0.011 respectively).The cirrhosis laboratory parameters results showed AST/ALT ratio (1.97 ± 0.45),gamma-GT ((152.33 ± 23.41) U/L),ALP indicators ((232.46 ±35.16) U/L in AC group patients,which were significantly higher in the VC group(1.00± 0.22,(45.89 ± 11.23) U/L and (102.23 ± 21.78) U/L,P =0.035,0.011,0.007 respectively).Conclusion There are difference in term of characteristic,manifestations and the testing laboratory indicators between alcoholic cirrhosis and viral cirrhosis.

Objective To discuss the efficacy and security of entecavir and interferon sequential combination therapy on chronic hepatitis B.Methods 108 patients with chronic hepatitis B were randomly divided into the sequential combination therapy group,the entecavir group and the interferon group.Each group had 36 cases.The efficacy and security of different therapy were observed.Results The HBV DNA negative rate of the sequential combination therapy group was 77.78％,and the ALT normalization rate was 91.67％,which were both higher than those of the entecavir group and the interferon group(x2 =14.40,22.12,20.07,18.47,all P ＜ 0.05).The total effective rate of the sequential combination therapy group was 91.67％,which was obviously higher than that of entecavir group and the interferon group(x2 =12.09,6.82,all P ＜ 0.05).The entecavir and interferon sequential combination therapy had a good security.Conclusion Entecavir combined with interferon sequential therapy in the treatment of chronic hepatitis B had a significant clinical efficacy and deserved promotion.

To screen antitumor active compounds, drug-like or leading compounds from Chinese traditional and herbal drugs.

One major problem to successful treatment of cancer is the development of resistance by tumor cells to multiple chemotherapeutic drugs, a phenomenon named multidrug resistance (MDR). Searching for the novel chemotherapeutical agents is one of the important strategies for overcoming MDR. By using a cytotoxicity assay, flow cytometry analysis, Western-blotting and RT-PCR, a drug (Taxol, TAX) resistant human nasopharyngeal carcinoma KB cell line (KB/TAX) was established by addition of the drug to the cell cultures gradually, then a novel N-sugar substituted thalidomide analogue (STA-35) was investigated for its reversal effect on MDR of KB/TAX cells and possible mechanism. The results showed that KB/TAX cells were resistant to several chemotherapeutical agents, and the relative resistance to TAX was 73.1. Compared with parental KB cells, the function and protein expression of P-glycoprotein (P-gp), as well as mdr1 gene in the KB/TAX cells were remarkable reduced. Moreover, both KB and KB/TAX cells were sensitive to STA-35, the relative resistance to TAX on KB/TAX cells was decreased by the addition of STA-35. Furthermore, STA-35 (5 ～20 ?mol/L)was capable to reduced the activity of P-gp by increasing the accumulation of rhodamine 123, decreasing P-gp expression in KB/TAX cells in a dose dependent manner , but had no effect on the mdr1 gene expression. These results suggest a potential action of STA-35 as MDR reversing agent, and one of the possible mechanisms could be the suppression of P-gp function and protein expression.

OBJECTIVE To investigate the prevalence of DHA AmpC ?-lactamases mediated by plasmid in Klebsiella pneumoniae in China.METHODS Antimicrobial susceptibility test was conducted by the methods of double agar dilution and ESBLs confirmatory in K-B method according to the criteria of guidelines of CLSI.AmpC ?-lactamases were detected on the basis that AmpC ?-lactamases could be inhibited by 3-aminophenylboronic acid(APB).Gene chip technology and PCR were used to detect ESBLs and AmpC gene.RESULTS Among total 34 isolates of K.pneumoniae 32(94.1%) produced AmpC ?-lactamases and ESBLs.The most common(38.3%) were types DHA and TEM and SHV.MIC50 and MIC90 of all strains to all tested antimicrobial agents were lower than 34 strains tested 0.25?g/ml and 0.5?g/ml.Fourteen strains AmpC and ESBLs were conjugated successfully.CONCLUSIONS DHA AmpC ?-lactamases mediated by plasmid are the most common in K.pneumoniae in General Hospital of PLA of China.The most common(38.3%) are types DHA and TEM and SHV.Fourteen(41.2%) strains can be spreaded by plasmid.

It has been well known that apoptosis induction and cell cycle arrest are typical biological effects observed in cancer cells after proteasome inhibition. TH2 is a new natural xanthone analogue isolated from the resin of Garcinia hurburyi tree. Here, the cell growth inhibition of TH2 on human hepatocellular carcinoma cell line (Bel-7402) was evaluated in vitro using SRB assay. The treatment of 10 ?mol/L TH2 reduced the surviving fraction from 86% (12 h) to 17.2% (48 h). To assess whether TH2 induce apoptosis, the appearance of sub-G1 peak, a specific fraction for apoptosis was detected by flow cytometry analysis. Progressive increase in the percentage of apoptotic population was observed in a dose-and time-dependent manner. Furthermore, a cleavage of poly (ADP-ribose) polymerase (PARP), a marker of early apoptosis, was observed clearly when the cells exposed to 10 ?mol/L of TH2 for 24 h by immunoblotting analysis. In vitro activities of 20 S proteasome purified from human erythrocytes on fluorogenic peptide substrates revealed that TH2 inhibited the trypsin-like, chymotrypsin-like and peptidylglutamyl peptide hydrolyzing activities in dose-dependent manner. Moreover, the turnover of tumor suppressor p53, a sign of deregulation of cell cycle progression and apoptosis induction by classical proteasome inhibitors, was disrupted in Bel-7402 cells. All these data indicate that TH2 had inhibitory effect on the proliferation of Bel-7402 cells and induction of apoptosis, which might be related to its inhibition of proteasome.

Objective To investigate the protective effects of 1-hydroxy-2, 3, 5-trimethoxyxanthone (QGS) on acute lung injury of mice induced by ip lipopolysaccharide (LPS). Methods Mice were pretreated with QGS for 7 d. Murine models of acute lung injury were duplicated by injection of LPS 20 mg/kg intraperitoneally. In 12 h, the lung weight index was observed and the NO level in the bronchoalveolar lavage fluid (BALF) was measured with kits. The lung was also assessd for the expression of I-?B, inducible nitric oxide synthase (iNOS), and cyclooxygenase-Ⅱ (COX-2) using Western blotting analysis. Lung pathological changes were also observed by HE in each group. Results The lung weight index of injury lung in mice induced by LPS was decreased in 500 mg/kg QGS group (P