Objective To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. Methods In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown.Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis.Results As compared to the younger age group (≥42,＜61 years), the risk of colorectal cancer in older age group (≥61 years) increased significantly ( OR = 2.04,95% CI: 1.49-2.80). Similar result was observed in the family cancer history ( OR = 1.51, 95% CI : 1.05-2.17 ). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0. 616, P=0.011 ). Using a logistic regression model, the"high-risk"individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model ( OR = 2.72,95% CI : 1.66-4.47 ). Conclusion The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.

AIM:To investigate the effects of proteasome inhibitor MG 132 on the expression of SnoN in renal tubule epithelial cells incubated in high glucose , and to explore the possible mechanism and function that MG 132 reduces or slows down renal tubular interstitial injury after incubated in high glucose .METHODS:The NRK-52E cells were divid-ed into normal control group (NG), high glucose group (HG) and high glucose plus pretreatment with different doses of MG132 group (HG+MG132).The immunofluorescence staining was used to detect the protein expression of E-cadherin and α-smooth muscle actin (α-SMA) in NRK-52E cells under different conditions .The relative protein expression levels of SnoN, Smad ubiquitination regulatory factor 2 (Smurf2), Arkadia, E-cadherin, α-SMA and collagen type Ⅰ(Col-Ⅰ) were detected by Western blotting .RESULTS:Compared with NG group , the expression of E-cadherin and SnoN was de-creased (P<0.05), while the expression of α-SMA, Col-Ⅰ, Smurf2 and Arkadia was increased (P<0.05).Compared with HG group, the protein expression of SnoN and E-cadherin was significantly up-regulated in HG+MG132 group ( P<0.05 ) , and the protein expression of α-SMA and Col-Ⅰwas significantly down-regulated in a dose-depended manner ( P<0.05).However, no effect on the protein expression of Smurf2 and Arkadia was observed.CONCLUSION: MG132 in-hibits the degradation of SnoN protein induced by high glucose , thus reducing the renal fibrosis .

Objective To evaluate the value of CT guided percutaneous transthoracic needle biopsy (PTNB) for the diagnosis of lung ground‐glass opacity (GGO) with a Meta‐analysis .Methods Relevant English and Chinese language studies were searched on the PubMed ,EMBASE ,EBSCO ,OVID ,CNKI ,CBM ,VIP and WANFANG databases ,respectively .Data were calculated with software of Stata 12 .0 and Meta‐Disc 1 .4 .Results 6 of 82 retrieved studies were included (n=341) .The pooled sensitivity ,specifici‐ty ,LR+ ,LR- ,DOR ,AUC and 95% CI were 0 .92(0 .86-0 .95) ,0 .98(0 .85-1 .00) ,49 .03(5 .72-420 .18) ,0 .08(0 .05-0 .15) , 586 .24(65 .18-5 272 .83) and 0 .99(0 .98-1 .00) ,respectively .Conclusion CT guided PTNB can be used as one of the primary examination modalities for lung GGO with moderate sensitivity and specificity .

Xanthium strumarium is a common Chinese medicine used for the treatment of "Bi Yuan",it mainly contains water-soluble glycosides,sesquiterpene lactones,essential oils,fatty oils,phenolic acids and other compounds,its pharmacology contains hypoglycemic,antianaphylaxis,anti-microbial,anti-inflammatory,analgesia and anti-tumor.This article summarized the chemical composition and pharmacological effects of Xanthium strumarium in order to provide reference for later study.

AIM:To study the influence of bone marrow mesenchymol stem cell-drived exosomes(BMSC-exo-somes)on hindlimb activity,and the numbers of reactive astrocytes and residual neurons in spinal cord injury(SCI)rats. METHODS:BMSCs were cultured using the whole bone marrow adherent culture method and surface markers CD 90 and CD34 were verified by flow cytometry.Exosomes were isolated by ultracentrifugation and the morphology of exosomes was observed under transmission electron microscope.The protein markers CD63 and CD9 were verified by Western blot.After exosomes were applied to SCI rats,the Basso,Beattie and Bresnahan locomotor rating scale score,the Nissl staining of the lesion site,and the numbers of reactive astrocytes and residual neurons were assessed at various time points.RESULTS:Transmission electron microscopic observation revealed the presence of saucer -shaped vesicles.BMSC-exosomes were found to express high levels of CD63 and CD9.Compared with injury group,significant improvement of hindlimb activity scores from day 14 after injury in treatment group was observed(P<0.05),and less reactive astrocytes and more residual neu-rons from day 7 after injury were also observed(P<0.05).CONCLUSION:BMSC-exosomes inhibit reactive astrocytes and death of neurons,and improve hindlimb activity in the rats after SCI.

AIM:To investigate the change of late sodium current (INaL) and the effect of Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) inhibitor KN-93 on INaLin the cardiomyocytes after isoproterenol-induced heart fai-lure (HF) in rabbits. METHODS:The rabbit model of HF was induced by injecting isoproterenol (300 μg·kg-1· d-1) for 15 d. One month later, all rabbits received by echocardiography and HE staining to observe the morphological changes of myocardium for evaluating the HF model. The protein expression of NaV1.5, CaMKⅡδ and phosphorylated CaMKⅡδ was determined by Western blot. The ventricular myocytes were isolated from the rabbits of normal saline(NS) group and HF group by Langendorff perfusion, and the whole-cell patch-clamp technique was used to record INaL. RE-SULTS:Compared with NS group,the heart rate in HF group was increased (P<0.01), the ventricular cavity was en-larged (P<0.05),and the cardiac function was decreased(P<0.01). Compared with NS group,the cardiomyocytes in HF group arranged in disorder, vacuolar degeneration and myocardial interstitial edema were observed, and fibrous tissue increased. The protein levels of NaV1.5,CaMKⅡδ and phosphorylated CaMKⅡδ in HF group were higher than those in NS group(P<0.01). INaLin HF group significantly increased compared with NS group (P<0.01). After adding sea anemone toxin Ⅱ (ATXⅡ), the density of INaLin HF group and NS group was significantly increased, but that in HF group increased more obviously than that in NS group (P<0.01). After ATXⅡ had induced stable current, we added KN-93 into NS group and HF group,and we found that the ATXⅡ-increased INaLin NS group and HF group was signifi-cantly decreased(P<0.05).CONCLUSION:CaMKⅡinhibitor KN-93 inhibits the increase in INaLin HF rabbits,which may be related to the activity of CaMKⅡδ and the regulation of CaMKⅡ δ on INaL.

OBJECTIVETo study the effect of rifampin (RFP) on the metabonomic profile of rat urine and its relationship with traditional toxicity evaluation of blood biochemical indicators and histopathology.

METHODSThirty-six male Wistar rats were randomly divided into control group, 50 mg/kg RFP group, and 100 mg/kg RFP group, with 12 rats in each group. Rats in each group were given intragastric infusion with a daily dose of 0, 50 mg/kg RFP, and 100 mg/kg RFP for 3, 7, and 14 days, respectively. Then 4 rats in each group were killed on the next day of administration to collect blood samples and liver sample for the determination of blood biochemical indicators and for the pathological analysis of the liver. The urine specimens over 24 hours of each rat were collected before and after each treatment until the rat was killed. 1H nuclear magnetic resonance (1H NMR) spectra of these urine specimens were acquired and subjected to data preprocess and principal component analyses (PCA).

RESULTSThe level of serum total bilirubin of the rat administrated with 100 mg/(kg x d) RFP for 7 days was significantly higher than that of control group (P < 0.05). Mild hepatotoxicity to the rat, treated with RFP of higher dosage (100 mg/kg) and longer duration (14 days), was revealed by the traditional histopathological method. The metabonomic spectra of rat urine in different groups differed from each other; a trajectory bias in determination of rat urine by 1H NMR occurred depending on the administration duration. As demonstrated by 1H NMR spectra of urine in rats treated with RFP, the concentration of urinary citrate and 2-oxoglutarate decreased, along with the remarkable increase of the concentrations of urinary taurine and glucose (compared with those of the control group).

CONCLUSIONSBeing consistent with the results of traditional toxicity evaluation measurements, metabonomic method is more sensitive. The 1H-NMR metabonomic profile of the rat urine is closely related with the duration of RFP. The hepatic toxicity induced by RFP is related to the reduction of energy metabolism in tricarboxylic acid cycle and the perturbation of glucose and lipid metabolism.

Animals ; Antibiotics, Antitubercular ; administration & dosage ; toxicity ; Blood Chemical Analysis ; Drug-Related Side Effects and Adverse Reactions ; Infusions, Parenteral ; Liver ; drug effects ; pathology ; Male ; Metabolomics ; Models, Animal ; Random Allocation ; Rats ; Rats, Wistar ; Rifampin ; administration & dosage ; toxicity ; Urine ; chemistry

BACKGROUNDType 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.

METHODSThis cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.

RESULTSIn patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37-4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47-38.03), dyslipidemia (OR 2.65, CI 1.54-4.56), diastolic blood pressure (OR 1.02, CI 1.00-1.04), and body mass index (OR 0.95, CI 0.92-0.99) are independent factors for early-onset T2DM.

CONCLUSIONSWe observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.

Adult ; Blood Glucose ; analysis ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; etiology ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Male ; Risk Factors ; Waist-Hip Ratio

The present study aimed to investigate the effects of ursolic acid on the chloride channels and cell volume in nasopharyngeal carcinoma cells (CNE-2Z). The whole-cell patch clamp technique was used to detect the current, and cell imaging technique was applied to measure cell volume. The properties of the currents induced by ursolic acid were investigated by changing the extracellular osmotic pressure, replacing the extracellular anions and applying chloride channel blockers. The results showed that, under isotonic conditions, the background current was weak and stable. When perfusing the cells with ursolic acid (100 nmol/L), a large current (-59.86 pA/pF ± 4.86 pA/pF at -80 mV, 78.92 pA/pF ± 6.39 pA/pF at +80 mV) was induced. The chloride current showed outward rectification and negligible time- and voltage-dependent inactivation. The reversal potential (-4.83 mV ± 0.30 mV) of the current was close to the calculated equilibrium potential for Cl⁻ (-0.9 mV). The permeabilities of the channel to different anions were ranked in order as follows: Cl⁻ = I⁻ > Br⁻ > gluconate. Hypertonic solutions inhibited the current induced by ursolic acid. The chloride channel blockers, tamoxifen (20 μmol/L) and 5-nitro-2-(3-phenylpro-pylamino) benzoic acid (NPPB, 100 μmol/L), suppressed the current. Furthermore, ursolic acid decreased the cell volume by (11.78 ± 1.20)% in 1 h, and the effect was inhibited by NPPB. These results suggest that ursolic acid can activate chloride channels, resulting in outflow of Cl⁻ and decrease of cell volume in nasopharyngeal carcinoma cells.
Carcinoma ; Cell Differentiation ; Cell Line, Tumor ; Cell Size ; Chloride Channels ; antagonists & inhibitors ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; Patch-Clamp Techniques ; Tamoxifen ; pharmacology ; Triterpenes ; pharmacology

Animals ; Borrelia burgdorferi ; genetics ; China ; DNA, Bacterial ; genetics ; isolation & purification ; Rodentia ; microbiology ; Sequence Analysis, DNA