Protein is involved in a variety of biological activities and associated with disease development,such as cancer.With the development of mass spectrometry-based proteomic technologies,qualitative and quantitative analysis of protein in clinical specimen using mass spectrometry is rapidly progressing in cancer biomarker study.Novel cancer biomarker for early diagnosis and prognosis evaluation is the key to reducing death rate and improving survival rate.This review summarizes mass spectrometry technologies and proteomic studies for cancer biomarker discovery.

Aim To establish a rat aortic calcification sub-chronic model induced by vitamin D3 and nicotine.Methods The vascular calcification model was produced by vitamin D3(300 kIU?kg-1,im) plus nicotine(25 mg?kg-1,5 ml?kg-1,po).Rat body weight and blood pressure were monitored on a regular basis.Ratio of heart to body weight,plasma calcium,plasma phosphate content,vascular calcium content,Von Kossa staining,activity of alkaline phosphatase(ALP) and 45Ca deposition in aorta were measured as the index of calcification at the 8th and the 16th week.Results Compared with control group,the VDN group rats showed higher values of blood pressure from the 3rd week(all P

Objective To discuss the relationship between diabetic macular edema(DME) and visual field defects and evaluatethe therapeutic effect of micro-pulse laser.Methods A total of 117 patients (149 eyes) with diabetic retinopathy(DR) were enrolled in this study and divided into two groups according to early treatment diabetic retinopathy study(ETDRS) DME diagnostic criteria:DME group(n=50,70 eyes) and N-DME group(n=67,79 eyes).Healthy subjects(n=40,80 eyes)were selected as NC group in thisstudy.The clinical data and biochemical index were collectedand visual fields were examined in all the subjects.Then the DME group was further divided into two subgroups:micro-pulse laser subgroup(35 eyes) and conventional laser subgroup(35 eyes).The vision recovery after treatment was evaluated on different time points.Results Diabetes duration,FPG,HbA1c and HOMA-IR were significantly higher in DME group than in N-DME group (P<0.05).RF value was less than 15% in each group,suggestingreliable test results.The levels of MD index[(7.81±0.75) vs (4.32±0.67) vs (1.14±0.22) dB],LV[(20.17±4.85) vs (15.34±3.19) vs (4.72±1.11) dB] and sLV[(10.71±1.37) vs (7.22±1.12) vs (2.35±0.41) dB] were significantly higher in DME group and N-DME group than in NC group,and those in DME group were higher than in N-DME group(P<0.01).After three month's treatment,the levels of MD index,LV and sLV were lower in micro-pulse laser subgroup than in conventional laser subgroup(P<0.05).There were no statistically significant difference in MD index,LV and sLV in conventional laser subgroup on different time points(P>0.05).Multiple logistic regression analysis showed that DM duration,FPG,HbA1c and HOMA-IR were riskfactors for DME(all P<0.01).Conclusion Patients with DME have severe vision loss.Micro-pulse laser therapy is helpful invision recovery,while conventional laser therapy have no obvious effect on it.Longer duration of DM,higher level of FPG,HbA1c,and IR severity may increase the risk of DME.

Objective To explore the ability of advanced oxidation protein products (AOPP)in predicting the progression of diabetic retinopathy (DR)in patients with type 2 diabetes mellitus (T2DM). Methods 363 T2DM patients were enrolled in this prospective cohort study. According to the quartile points of baseline AOPP level,patients were divided into four groups (Q1,Q2,Q3 and Q4 ). The progression rate of DR was calculated according to the changes of non-mydriatic fundus photography after a 5-year follow-up. Results With the increase of baseline AOPP level,the rate of progression of DR increased (19.51% vs 28.42% vs 37.36% vs 47.37%,P <0.01). Logistic regression analysis showed that baseline level of AOPP was an independent risk factor for the progression of DR (OR=1.833,95%CI:1.573~1.982,P<0.05).Area under the curve of AOPP in predicting DR is 0.883 (95% CI:0.842~0.924)with the sensitivity 86.1% and specificity 91.9%. Conclusion AOPP may be one of the biomarkers for the prediction of type 2 diabetic retinopathy progression.

Objective To explore the risk factors of vascular cognitive impairment (VCI)among Chinese population, and to clarify the scientific evidences for further prevention and treatment.Methods PubMed,CNKI,CBM,VIP and Wangfang databases (from 2002.1 to 2013.1)were searched to collect case-control studies or cohort studies studying risk factors of VCI among Chinese population. Meta-analysis was performed to calculate combined odds ratio (OR)or mean difference (MD)and its 95% confidence interval (95%CI).Results A total of 42 proper papers involving 3 282 cases and 7 815 controls were included in the review.For categorical variables,pooled OR and its 95% CI were as follows:hypertension 2.56 (2.03 - 3.21 ), hyperlipidemia1.79 (1.39 - 2.30 ), hyperglycemia 2.46 (1.90-3.19),Leukoaraiosis 5.46 (2.60-11.46),cerebral infraction multiple foci 4.39 (2.61-7.38),stroke history3.79(2.35-6.11),left hemisphere lesions 2.13(1.42-3.20),smoking 1.51 (1.08-2.11),drinking 0.99(0.73-1.36),basal ganglia lesions 2.15(1.55-2.99),thalamus lesions 2.34(1.57-3.47);for continuous variables,MD and its 95%CI were as follows:level of TG 0.35(0.15-0.55),level of TC 0.44(-0.16-1.04),level of folic acid -4.10(-5.50- -2.69),vitamin B12 -130.44(-225.46--35.41).Conclusion Except for drinking and level of TC, hypertension, hyperlipidemia, hyperglycemia, leukoaraiosis,cerebral infraction multiple foci,stroke history,left hemisphere lesions,smoking,basal ganglia lesions,thalamus lesions,high level of TG,low level of folic acid and vitamin B12 might be the risk factors of VCI among Chinese population.

Abstract Ischemic stroke is characterized by high morbidity, disability and mortality. At present, there is a lack of effective treatment for ischemic stroke, so it is of great significance to reduce the incidence risk of ischemic stroke. Studies show that vitamin C can prevent atherosclerosis, thus reduce the incidence risk of ischemic stroke. However, this point is controversial due to the differences of study population, inconsistent evaluation methods of vitamin C content and the influence of various confounding factors. This paper reviews the related animal experiments, clinical trials and cohort studies, in order to provide reference for subsequent studies on reducing the incidence risk of ischemic stroke.

Objective To analyse a novel splice mutation in EXT1 gene of hereditary multiple osteochondroma, and study its pathogenic mechanism.Methods In April of 2013, the proband was hospitalized from the outpatient department with multiple joint deformity for more than 20 years, peripheral blood of the proband and his parents were collected and genomic DNA was extracted .Coding regions and adjacent intron sequences of EXT1/EXT2 genes in genomic DNA of the family members were amplified and sequenced.Bioinformatics was used to analyze the mutation from sequencing .cDNA from peripheral blood of the proband ,the mother and normal control was made respectively as a template for amplifying coding regions of EXT1 gene, and the product was T-A cloned and sequenced.The abnormal transcripts of each group were counted and analyzed using chi square test to study the pathogenic mechanism of the mutation .Results Sequencing results of family members revealed that there was a heterozygous deletion mutation ( c.1284 +2del) in the 5′splice site of intron 4 in EXT1 gene of the proband and his mother .Bioinformatics predicted that exon 4 of EXT1 gene was skipping or spliced aberrantly due to the mutation .T-A clone and sequencing results as well as the statistical analysis suggested that there was a significantly higher proportion of transcripts with skipping exon 4 in the proband and his mother compared with the normal control (P=0.000, P<0.01).Conclusions c.1284+2del in EXT1 gene is reported for the first time internationally , which results in a considerable number of abnormal transcripts with skipping exon 4 in EXT1 gene, thereby influences the normal transcription and translation of EXT1 gene.

Objective To investigate the effects of a miRNA family member, let-7e, and a combi-nation of miR-106b and miR-20a on the expression of cytokines by THP-1 cells with Luminex xMAP technol-ogy.Methods The efficiency of transfection was evaluated by immunofluorescence assay after transfecting THP-1 cells with micrONTM mimic negative control (Cy3) for 24 h, 36 h and 48 h.The three miRNA mim-ics (let-7e, miR-106b and miR-20a) were respectively used to transfect the THP-1 cells for 24 h, 36 h and 48 h and the expression of each miRNA was analyzed by qRT-PCR analysis for screening out the optimal transfection time.The transfected THP-1 cells were stimulated with1 mg/L of LPS for 1 h.The Luminex xMAP technology was used to detect the expression of IL-8, interferon-inducible protein-10 (IP-10), mono-cyte chemotactic protein 1 (MCP-1), IL-1α, IL-6, IL-10, TNF-α, IFN-αand IFN-βin the supernatants of cell culture.A statistical analysis was performed to analyze the data obtained by using SPSS16.0 software. Results More than 90% of the transfected THP-1 cells were labeled with red fluorescence.The optimal transfection times for let-7e mimic and miR-106b/miR-20a mimics were 48 h and 24 h, respectively.Com-pared with the corresponding negative control (NC), the expression of IL-8, IP-10 and MCP-1 by THP-1 cells were enhanced after the transfection with let-7e mimic, but were inhibited after the co-transfection with miR-106b and miR-20a mimics.Conclusion The expression of IL-8, IP-10 and MCP-1 were enhanced in let-7e transfected THP-1 cells, but were inhibited in miR-106b and miR-20a co-transfected THP-1 cells.

Objective To analyze the policy support of rural doctors for the essential medicine system,and explore the main influence factors and mechanism affecting the support degree.Methods 621 rural doctors from five cities in Shandong province were subject to a stratified random sampling for a quantitative questionnaire,to build a hypothesis model of policy support of rural doctors,which is verified using factor analysis and path analysis.Results 59.1% of rural doctors support the essential drugs policy.It was found that the essential medicine factor,the factor to influence the practitioner,and the supporting policy factor had a direct impact on policy support of rural doctors,with the effect of 0.305, 0.1 59 and 0.135 respectively;Essential medicine factor and the supporting policy factor indirectly influence the policy support of rural doctors through the factor to influence practitioners,with the effect of 0.065 and 0.032 respectively.Conclusion The essential medicine system needs to emphasize such rationality as the quality,list and pricing of essential medicines;it is imperative for the government to better oversee the purchase and supply of essential drugs,to cater to the interests of rural doctors,to encourage the enforcement of the system,and promote the development of village clinics.

OBJECTIVE:To learn the application and tendency of hepatoprotective drugs in a third grade class A hospital dur-ing 2011-2014,and to provide reference for rational drug use. METHODS:DDDs analysis and consumption ordering method were adopted to analyze the change of DDDs,DDC and other index of hepatoprotective drugs in this hospital from 2011 to 2014. RE-SULTS:2011-2014,the amount and DDDs of Hepatoprotective injection in this hospital increased year by year,while oral dosage form decreased year by year. DDC order of each drug kept stable during 2011-2014;DDC and DDDs of drugs for promoting ener-gy metabolism were all in high level,and ornithine aspartate and ademetionine always took up the first 2 places in 4 years. Polyene phosphatidylcholine and Reduced glutathione injection were cheap,but had higher DDDs. Except Glutathione tablet,DUI of other hepatoprotective drugs had no great difference in 3 years,and fluctuated in 2014;hepatoprotective drugs with DUI>1 and DUI<1 occupied a large proportion. From 2010 to 2014,compared with previous year,the drugs with consumption sum/DDDs ratio num-ber close to 1 reduced significantly in the next year,decreasing year by year. CONCLUSIONS:In this hospital,injections are used too frequently,and overuse of drugs for promoting energy metabolism exist. Polyene phosphatidylcholine and Reduced glutathione injection can be used as a valuable drug in the clinic,and their cost are more acceptable,but not in excess.