Objective To observe the neuroprotective effect of celecoxib against degeneration of dopaminergic neurons caused by lipopolysaccharide in vivo.Methods The rat model of Parkinson disease(PD)was established by intranigral injection of lipopolysaccharide.Sprague-Dawley rats were randomly divided into control group,PD group,and celecoxib group.Behavioural changes were recorded,and the expressions of tyrosine hydroxylase(TH)and cyclooxygenase-2(COX-2)were determined by immunohistochmistry and Western blot.Results No behavioral change was found in control group.There was significant difference in the number of circling behavior between PD and celecoxib groups(196.90±9.52 vs 109.30±9.38,P＜0.01).The number of TH-positive cells and the expression of TH protein in rat substantia nigra were significantly higher in celecoxib group than in PD group(P＜0.01).Compared with PD group,the number of COX-2positive cells and the expression of COX-2 protein were significant lower in celecoxib group(P＜0.01).Conclusion Celecoxib has neuroprotective effect on the degeneration of dopaminergic neurons caused by lipopolysaccharide in vivo.

Background and purpose:miRNA plays important roles in tumorigenesis. It has been reported that many kinds of serum miRNA serve as markers for tumor diagnosis and screening. This study aimed to detect the expression of serum miRNA-31 (miR-31) in colorectal cancer patients and to explore the effect of miR-31 on cell proliferation, apoptosis and cell cycle distribution. Methods: The expressions of miR-31 in 40 cases of colorectal cancer serum and 35 cases of the healthy control were examined by real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR). The correlation between miR-31 expression and clinicopathological features of colorectal cancer (including age, gender, depth of inifltration, lymph node metastasis, clinical stage) were further analyzed. The miR-31 mimics, inhibitor and miR-control (negative control) were transfected into HCT116 cells. The effect of miR-31 on cell proliferation was evaluated by CCK-8 method. Flow cytometry was used to examine the change of cell apoptosis and cell cycle. Results:Relative expression of serum miR-31 was signiifcantly increased in cancer patients compared with healthy controls (P<0.01). Expression of serum miR-31 was higher in poorly differentiated carcinoma than that in well or moderately differentiated carcinoma (P<0.05). No correlation was found between serum miR-31 expression and other clinicopathological variables. CCK-8 assay showed that after transfection with miR-31 mimics, the cell proliferation was increased, compared with miR-31 inhibitor and negative control group. Meantime, the apoptotic cell number was signiifcantly decreased, particularly in late apoptosis. The cell number of G1 stage was remarkably increased in miR-31 inhibitor group, compared with miR-31mimics and negative control group. Conclusion:The expression of serum miR-31 is higher in colorectal cancer. miR-31 can promote cell proliferation and inhibit the apoptosis of HCT116 cells. It might be a potential biomarker for colorectal cancer.

OBJECTIVE To investigate the mechanism of nicotinamide mononucleotide (NMN) on inflammation and fibrosis between endogenous nicotinamide phosphoribosyltransferase (NAMPT) and bone morphogenetic protein 7 (BMP-7) in diabetic glomerular cells.METHODS ① In vivo,spontaneous diabetic C57/BL6 mice and wild C57/BL6 mice were divided into two groups.When blood glucose was above (34.2±1.9) mmol· L-1,renal histology of diabetic mice became obvious.The protein expressions of Nampt and nuclear transcription factors-kappa B p65 (NF-κB p65),silent mating type information regulation 2 homolog 1 (SIRT1) and BMP7 were analyzed by lengths of immunofluorescence.② In vitro,rats' glomerular cells HBZY-1 were incubated with glucose 200 mmol· L-1 for different lengths of time (0,24,48 and 72 h) and at different concentrations of NMN (0,50,100 and 200 iμmol· L-1).The protein levels of Nampt and BMP7 were detected by Western blotting and the protein expressions of NF-κB p65 and α-SMA were measured by immunofluorescence assay.The protein levels of Nampt,BMP7 and NF-κB p65 were detected by Western blotting after HBZY-1 cells were treated with NMN 100 μmol· L-1 and FK866 10 μmol· L-1 for 24 h.RESULTS ① In vivo,the glomeruli of diabetic C57/BL6 mice showed obvious atrophy.Fluorescence intensity of Nampt was increased (P＜0.05),but that of BMP7 and SIRT1 in renal glomeruli cells was decreased compared with the wild type (P＜0.01).② In vitro,HBZY-1 cells were cultured in glucose 200 mmol· L-1 for 48 and 72 h.The protein expression of NAMPT was increased,but that of BMP7 was decreased (P＜0.05,P＜0.01).Expressions of NF-κB p65 and α-SMA were increased (P＜0.01) by immunofluorescence.The expression of BMP7 was increased after treatment with glucose 200 mmol· L-1,followed by NMN 50,100 and 200 μmol · L-1 for 24 h (P＜0.01).The expressions of NAMPT and NF-κB p65 were decreased (P＜0.01).The expressions of Nampt and NF-κB p65 in glucose 5.6 mmol· L1 +FK866 and glucose 5.6 mmol· L-1+ NMN groups were increased (P＜0.01),but the expression of BMP7 did not change.CONCLUSION Upregulation of endogenous Nampt obviously intervenes in BMP7 expression in the process of glomerular inflammatory fibrosis in severe diabetes.NMN can affect the protein expression of BMP7 via a special Nampt signaling pathway.

Objective]To compare the efficacy and safety of retroperitoneal laparoscopic intrasinusal pyelolithotomy (RLIP) and percutaneous nephrolithotomy(PCNL)in the treatment of solitary renal pelvic stone.[Methods]From March 2012 to September 2016,101 patients with solitary renal pelvic stone,divided into RLIP group(n=46)and PCNL group(n=55),were retrospectively analyzed to compare the difference between the two groups in clinical curative effect.[Results]There was no difference between the two groups regarding age,sex,stone side and stone size. Although the operative time was significantly longer,the stone-free rate in the RLIP group was significantly higher than that in the PCNL(P < 0.05). The postoperative complication of urinary tract infection was lower in the RLIP group (P < 0.05),however ,no significant difference was found in postoperative discharge time ,fever (>38.5℃)and the decrease values of hemoglobin and glomerular filtration rate.[Conclusion]Compared to PCNL,RLIP was more efficient and slight safer in the management of solitary renal pelvic stone ,and had a certain value for generalization in clinic.

Objective To explore the effect of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism,environmental factor and their interactions on antidepressant treatment.Methods 340 patients of major depressive disorder (MDD) who met the diagnosis criteria of MDD ( DSM-Ⅳ Axis Ⅰ) were recruited.280 patients of them were finished 12 weeks antidepressant treatment.The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS) before and after 12 weeks antidepressant treatment.Childhood Trauma Questionnaire,28-item Short Form (CTQ-SF) and Life Events Scale (LES) were used to evaluate childhood adverse and life stress before onset.Genotyping of BDNF Val66Met polymorphism was detected by Illumina GoldenGate assays.Results Male patients proportion were significantly higher in non-remitters than remitters (P =0.008 ).After adjusting by gender, the frequencies of genotype and allele for the BDNF Val66Met polymorphism were no significant difference between remitters (AA: AG: GG = 28: 79: 40, A:G = 135:159 ) and non-remitters (AA: AG: GG = 29:81:23 ,A: G = 139:127 ) (P ＞0.05 ).There was no significant difference of CTQ scores and LES scores between the two groups (P＞0.05 ).The regression analysis showed that social intercourse problem and age were the risk factor for the severity of depression.The gender, HDRS baseline scores and mental disorder family history were associated with the efficacy of 12 weeks antidepressant.However,there was no significantly relationship between the interaction of BDNF Val66Met polymorphism and environment with the antidepressant treatment.Conclusion The older men with the mental disorder family history, severe depression symptom would be less-response to antidepressant treatment.However, BDNF Val66Met polymorphism, childhood trauma, life events stress and the interaction of BDNF Val66Met polymorphism and environment have no significantly effect on the 12 weeks antidepressant treatment.

BACKGROUND:Bone defects are the leading cause of nonunion after firearm injury. Firearm injury is relatively special. Autograft and alograft al have big drawbacks, which cannot meet the requirements of basic-level hospitals. Using tissue-engineered bone with good blood vessels and osteogenic capability in repair of firearm bone defect wil be an ideal and feasible restoration method. OBJECTIVE: To explore the application of human vascular endothelial growth factor 121 gene-modified materials in the repair of firearm-induced radial injury in rabbits. METHODS: A total of 128 rabbits were randomly divided into surgical injury group and firearm injury group (n=64 per group). In the firearm injury group, 0.25 g steel bal was launched using 56-style musket to establish a firearm radial injury model; in the surgical injury group, surgical methods were used to produce a 1.2 cm radial injury model. Human vascular endothelial growth factor 121 gene-modified materials were used. The related histocytes from rabbits were harvested to obtain bone marrow stromal cels for culture. A porous scaffold material was prepared. The obtained materials were respectively implanted into radial defect sites in the surgical injury and firearm injury groups. The application of human vascular endothelial growth factor 121 gene-modified materials in rabbit radial defect repair was analyzed. RESULTS AND CONCLUSION: Compared with the surgical injury group, at 8, 12 and 16 weeks after repair, the gray level ratio of bone defect site and the anti-compression mechanical ratio at the healthy and repairing sides of the radius in the firearm injury group were decreased (P < 0.05), and the new bone area increased (P < 0.05). At 2 and 4 weeks after repair, the local blood flow at the repair area was significantly increased (P < 0.05). These results suggest that compared with the surgical injury group, the curative effect of human vascular endothelial growth factor 121 gene is more ideal in the firearm injury group because of the emergence of local ischemia and hypoxia in the process of radial defect repair. Human vascular endothelial growth factor 121-modified material can repair bone marrow stromal cels. The application of human vascular endothelial growth factor 121 in firearm burns can enhance the synthesis and secretion of angiogenic factors, improve the local blood flow, reduce anti-compression mechanical ratio, and increase the new bone area.

Objective To explore distribution characteristics and risk factors of cerebral microbleeds (CMBs),and the correlation between CMBs and white matter lesions (WML) in patients with ischemic cerebrovascular disease(ICVD).Methods 180 patients with ICVD in neurology department of Hebei General Hospital from February 2015 to January 2017 were recruited.Those patients were underwent brain magnetic resonance imaging (MRI),and magnetic susceptibility weighted imaging (SWI).Recorded the baseline data and risk factors of high blood pressure,diabetes,hyperlipidemia,and high homocysteine were recorded.Patients with CMBs were counted and graded to understand the characteristics of CMBs distribution.Logisitic regression analysis was used to analyze the influencing factors.ICVD patients were divided into CMBs group and non CMBs group.CMBs group was further divided into 4 groups according to the severity,which was divided into level 1-3.The correlation between CMBs influencing factors and classification was further studied.Then patients with ICVD were divided into WML group and non WML group.WML group scored each region with age-related white matter changes rating scale (ARWMCrs).The correlation between WML and CMBs classification was further studied.Results (1) The overall prevalence of CMBs in patients with ICVD was 61.7％ (111/180).The most common location of CMBs in patients with ICVD was the cortical and subcortical regions (80/111,72.1％),followed by the basal ganglia and thalamus regions (61/111,55.0％),and the infratentorial regions(38/111,34.2％).The difference between them were significant (x2 =32.061,P=0.000).In cortical and subcortical regions of CMBs,temporal lobe was the most common (61.3％).(2) Age(B=0.046,Or=1.047,95％CI =1.017～ 1.077,P=0.002) and the high homocysteine (B =1.458,Or=4.299,95％ CI =2.114 ～ 8.744,P＜0.001) were the risk factors for CMBs.(3) Four classification of CMBs was positively correlated with and WML total score (r=0.393,P=0.393).Conclusion The temporal lobe was the most common region for CMBs in patients with ICVD.Age and high homocysteine were risk factors for CMBs.With the increase of WML total score,severity of CMBs was also increased.

Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.