Objective: To systematically elucidate the molecular mechanisms and core targets underlying the anti-hepatocellular carcinoma (HCC) effects of icariin through integrated network pharmacology and experimental validation. Methods: Potential targets of icariin were screened using the PubChem database and SwissTargetPrediction platform, followed by intersection analysis with HCC-related genes from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to characterize the biological functions of candidate targets. Key genes were identified using the random survival forest algorithm, and their associations with the tumor microenvironment were evaluated through immune infiltration analysis. Molecular docking was employed to predict the binding affinity between icariin and its core targets, which was subsequently validated by in vitro enzyme inhibition assays. Functional targets were determined through overexpression experiments in HepG2 cells, and mechanistic investigations were conducted using Western blot and co-immunoprecipitation techniques. In vivo anti-tumor efficacy was evaluated using a subcutaneous HepG2 xenograft mouse model by monitoring tumor volume progression and endpoint tumor weight, and the impact of polo-like kinase 1 (PLK1) overexpression on icariin-mediated tumor growth inhibition was assessed. Results: Network pharmacology analysis identified 36 common targets between icariin and HCC, which were primarily enriched in hypoxia-inducible factor-1 (HIF-1), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and forkhead box O (FoxO) signaling pathways. Among these, PLK1, ATP binding cassette subfamily C member 1 (ABCC1), and matrix metallopeptidase 3 (MMP3) were identified as key genes, with their high expression significantly associated with poor patient prognosis (P < 0.0001, P = 0.004, and P = 0.03, respectively). Immune infiltration analysis revealed significant correlations between these three genes and various immune cell types, suggesting their involvement in modulating the tumor immune microenvironment. Molecular docking predicted stable binding between icariin and these targets, and in vitro enzymatic assays confirmed that icariin (20 µmol/L) exhibited the highest inhibitory rate against PLK1 (49.67% ± 4.19%), significantly greater than that against ABCC1 (24.33% ± 3.40%) and MMP3 (38.00% ± 3.06%). Functional validation demonstrated that PLK1 overexpression reversed icariin-mediated inhibition of HepG2 cell proliferation (P < 0.05), whereas ABCC1 or MMP3 overexpression showed no such effect, indicating PLK1 as the primary functional target of icariin. Mechanistic studies revealed that icariin specifically reduced PLK1 phosphorylation levels and disrupted its interaction with forkhead box M1 (FoxM1). In vivo experiments confirmed that PLK1 overexpression significantly attenuated icariin-induced suppression of tumor growth in xenograft mice (P < 0.001). Conclusion PLK1 is a critical target mediating the anti-HCC effects of icariin through inhibition of the PLK1-FoxM1 axis, providing a mechanistic basis for the clinical development of icariin as an HCC therapeutic agent.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

To establish a rapid Akabane virus(AKAV)antibody detection method in animals,the re-combination AKAV N protein was expressed by the expression system of Escherichia coli,puri-fied from the supernatant,and used to immunized New Zealand White rabbits.The polyclonal anti-body against AKAV N protein had a titer of 1∶8.192×107 and showed good reactivity.After opti-mizing the reaction conditions,an AKAV double antigen sandwich ELISA antibody detection method was established.This method can detect AKAV antibody in a variety of animals including cattles,sheep and goats.The method had no cross-reactivity with the positive serum of BTV,EHDV,BEV and PRV with the intra-and inter-batch coefficients of variation less than 10％.Com-pared with the AKAV blocking ELISA kit,the sensibility of the method was increased by 8-16 folds with a compliance rate of 93.33％and the κ value of 0.864.These results showed that the double antigen sandwich ELISA displayed strong specificity,high sensitivity and repeatability,which could provide technical suport for detection,the prevention and control of AKAV.

Objective: In order to evaluate the therapeutic effects and safety of denosumab and bisphosphonates in glucocorticoid induced osteoporosis patients. Methods: Standard studies were obtained by searching CNKI, CBM, VIP, Wanfang, Pubmed, Embase and Cochrane databases. Results: Three RCTs with 869 patients were included in this study. It showed that the mean changes of lumbar spine, total hip and femoral neck bone mineral density (BMD) for patients in denosumab group were increased by 2.47%, 1.43% and 1.07% respectively compared to those of bisphosphonates group.There was no statistically significant difference between patients receiving denosumab and those receiving bisphosphonate in terms of adverse events and serious adverse events. Conclusions Denosumab has an effective increase for lumbar spine, total hip and femoral neck bone mineral density, and the safety of both is similar.

Objective To analyze the expression of interleukin 16 (IL-16) in atherosclerosis (AS) patients, and to study the roles of IL-16in the pathogenesis of AS.Methods Thirty AS patients in Affiliated Hospital of Jining Medical College from August 2015to August 2016were randomly selected as the case group and twenty-nine healthy subjects were selected as the healthy control group.Peripheral blood of the subjects were collected.IL-16levels were determined with enzyme-linked immunosorbent assay (ELISA).Reverse transcriptase-polymerase chain reaction was applied to analyze IL-16mRNA level.IL-16expression in the atherosclerotic plaque samples was detected with immunohistochemical analysis.IL-16expression in aortic atherosclerotic plaque of AS patients and atherosclerotic ApoE-/-mice were analyzed by immunohistochemical staining.The aortic plaque changes of AS mice injected intraperitoneally with recombinant IL-16were detected.Results Both IL-16protein levels and IL-16mRNA levels were higher in case group than those of healthy control group, the difference was statistically significant (P＜0.05).The IL-16mRNA was highly expressed in the atherosclerotic plaque.The aortic plaque area of the mice underwent IL-16intraperitoneal injection were decreased while the plaque stability increased.Conclusion IL-16levels elevated in both AS patients and AS mice, which suggested that IL-16might play aprotective role against AS.

Objective To investigate the clinical features and related risk factors of osteoporosis and osteoporotic fracture (OPF) in patients with rheumatic diseases (RD),and the fracture predictive values of fracture risk assessment tool fracture risk assessment (FRAX(R))for Han patients.Methods A total of 313 untreated RD patients were included.Each individual BMD was measured at lumbar spine and femoral neck with Dual-energy X-ray absorptionary.Ten-year probability of fracture (％) was calculated by fracture risk assessment tool FRAX(R) of Chinese model.Each individual previous fracture was confirmed by X-ray or CT examination.The associations between BMD,FRAX),previous fracture and age,bone mass index,nationality,erythrocyte sedimentation rate (ESR) and RD types were analyzed.T test or Wilcoxon test was used to compare the difference between groups for statistical analysis.Pearson/Spearman rank order and binary regression were used to analyze the correlations between variables of normal/non-normal and two classification distribution.Results ① The BMD of patients with untreated RD was significantly lower than that of control group (P=0.000).Individuals diagnosed with "osteopenia" in the RD group and control group were accounted for 39.3％ (123/313) and 15.8％ (47/296) respectively.Individuals diagnosed with "osteoporosis" in RD group and control group were accounted for 11.5％ (36/313) and 5.4％ (16/296) respectively.② The next 10-year probability of the hip (Z=-2.28,P=0.02) and major osteoporotic fracture (Z=-1.98,P=0.03) were higher than those of the control group,as well as the actual incidence of OPF (x2=25.11,P=0.00),the difference was statistically significant.③ 27.3％(18/66) and 55.0％(11/20) of the previous OPF patients in RD group and control group achieved the diagnostic criteria of "high risk" of hip fracture.And 12.1％ (8/66) and 35.0％ (7/20) achieved the "high risk" of major osteoporotic fracture.④ Patients with RA,SLE and pSS had significantly increased risk of fracture.Ten-year fracture risks were negatively related to advanced age,female gender and ESR.Conclusion Bone loss and increased fracture risk are prevalent in the early stage of untreated rheumatism patients.RA,SLE plays an important role in low bone mass.The FRAX China model may underestimate 10-year fracture probability of RD patients and controls.Further explore should be done to predict the FRAX China model on different areas and different RDs.

Theories of classified management which are based on risk governance are introduced into the newly revised , but the punishments on the manufacturers of unconformity products are not classified based on the severity and risks caused by the test items. This article analysed the disadvantages of current punishment measures on the manufacturers of unconformity products and the theoretical basis of classified punishments. The feasibility of classified punishments had also been studied and some basis of discretionary punishments was provided under the current regulations.
Equipment Failure ; Equipment and Supplies ; standards ; Punishment

Objective To detect the change of exoression level of plasma microRNA‐21(miR‐21) and TGF‐β1 in cardiac remode‐lin affer acute myocardial infarction(AMI) of the pateins .Methods 200 pateints with AMI and 100 normal controls(age ,sex matched) were enrolled .Blood samples were obtained from the normal controls and patients with AMI on the 3 days ,7 days and 14 days .Real‐time PCR was developed to detect the expression of miR‐21 and TGF‐β1 in plasma .Results The expression of miR‐21 was significantly up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .74 ± 0 .21 vs .2 .62 ± 0 .23 , vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 up‐regulation in the 3 days ,7 days and 14 days in MI group than that cntrol group ,0 .98 ± 0 .18 vs .2 .35 ± 0 .24 ,vs .3 .67 ± 0 .25 ,vs .4 .13 ± 0 .27 ,P<0 .05 ,respectively .The expression of miR‐21 and TGF‐β1 were up‐regulation with the change of cardiac function .Positive relationship between miRNA‐21 expression and LVDd (r=0 .757 ,P<0 .05);Positive relationship between TGF‐β1 mRNA expression and LVDd(r=0 .701 ,P<0 .05) .Conclusion The expression of miR‐21 and TGF‐β1 were up‐regulation in cardiac remodelin affer AMI of the pateins ,which involved in regulation in cardiac remodelin affer AMI .

UNLABELLEDBackround N-terminal pro-brain natriuretic peptide (NT-proBNP) is a reliable predictor in acute coronary artery disease (CAD). Little is known about patients with stable CAD, especially Chinese patients with CAD. The aim of the present study was to investigate the association of NT-proBNP levels with the severity of CAD in patients with normal left ventricular ejection fraction.

METHODSA total of 658 consecutive patients were divided into two groups based on angiograms: CAD group (n = 484) and angiographic normal control group (n = 174). The severity of CAD was evaluated by modified Gensini score, and its relationship with NT-proBNP was analyzed.

RESULTSThe prevalence of risk factors such as age, male gender, diabetes mellitus (DM), dyslipidemia, smoking, and family history of CAD in the CAD group were higher than that in the control group. In multivariate regression model analysis, age, gender, and DM were determinants of the presence of CAD. NT-pro BNP was found to be an independent predictor for CAD (OR:1.66 (95% CI: 1.06-2.61), P < 0.05). In a receiver operating characteristic (ROC) curve analysis, an NT-proBNP value of 641.15 pmol/L was identified as a cut-off value in the diagnosis or exclusion of CAD (area under curve (AUC) = 0.56, 95% CI: 0.51-0.61). Furthermore, NT-proBNP was positively correlated with Gensini score (r = 0.14, P < 0.001) in patients with CAD.

CONCLUSIONNT-proBNP was an independent predictor for Chinese patients with CAD, suggesting that the NT-proBNP level might be associated with the presence and the severity of CAD.

Coronary Disease ; blood ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Prospective Studies ; Risk Factors ; Severity of Illness Index ; Stroke Volume

Medical education should combine clinical professional skills with humanities skills,integrate humanities knowledge into vocational education.Taking 2008 grade seven-year program clinical medicine students in the 2nd affiliated hospital of Harbin Medical University as fostering object,we made researches into students' understanding of doctor-patient relationship before practice and their mastering of skills.Through conducting questionnaire,we got to know the effect of humanities practice skill training for seven-year program clinical medicine students.Meanwhile,we compared students' self evaluation results before and after training,discussed on how to improve medical students' communication skills,cultural skills and the reform direction in an aim to guide students to transit from students to clinical doctor.