BACKGROUNDCerebral arteriovenous malformation (cAVM) is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage.

METHODSImmunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM-1), and endothelial nitric oxide synthase (eNOS). Western blotting and real-time fluorescent quantitative polymerase chain reaction (PCR) were performed to determine protein and mRNA expression levels. Student's t-test was used for statistical analysis.

RESULTSVEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels of VEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant (P < 0.05).

CONCLUSIONSVEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.

OBJECTIVETo investigate the application and effect of minimally invasive percutaneous anterior pelvic pubic ramus screw fixation in Tile B fractures.

METHODSA retrospective review was conducted on 56 patients with posterior pelvic ring injury combined with fractures of anterior pubic and ischiadic ramus treated between May 2010 and August 2015, including 31 males and 25 females with an average age of 36.8 years old ranging from 35 to 65 years old. Based on the Tile classification, there were 13 cases of Tile B1 type, 28 cases of Tile B2 type and 15 cases of Tile B3 type. Among them, 26 patients were treated with sacroiliac screws combined with external fixation (external fixator group) and the other 30 patients underwent sacroiliac screw fixation combined with anterior screw fixation (pubic ramus screw group). Postoperative complications, postoperative ambulation time, fracture healing, blood loss, Majeed pelvic function score and visual analogue scale(VAS) were compared between two groups.

RESULTSFifty-four patients were followed up from 3 to 24 months with a mean of 12 months. There were no significant difference in the peri-operative bleeding and operation time between two groups(>0.05). The postoperative activity time and fracture healing time of pubic ramus screw group were shorter than those of the external fixator group, the differences were statistically significant(<0.05). The Majeed score, VAS score of pubic ramus screw group were higher than those of the external fixator group, the differences were statistically significant(<0.05). The incidence of postoperative complications of pubic ramus screw was lower than that of the external fixator group, the difference was statistically significant (<0.05).

CONCLUSIONSPercutaneous iliosacral screws fixation combined with the pubic ramus screw is an effective and safty treatment method to the Tile B pelvic fracture. It has advantages of early ambulation, relief of the pain and few complications.

OBJECTIVETo understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors.

METHODSWe recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model.

RESULTSIn individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = -0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = -0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = -0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI: 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes (P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke (OR = 2.64, 95% CI: 1.58-4.40, P < 0.001).

CONCLUSIONCDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke.

Adiponectin ; blood ; Aged ; Brain Ischemia ; blood ; genetics ; Cadherins ; genetics ; China ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Stroke ; blood ; genetics

OBJECTIVETo study the efficacy and safety of voluntary rehabilitation exercise in the treatment of knee osteoarthritis, based on the traditional Chinese medicine theory of "treating muscle for bone".

METHODSNinety participants with early knee osteoarthritis were randomly divided into experimental group (=45) and control group (=45). Patients in experimental group were treated with voluntary rehabilitation exercise combined with isometric extension of quadriceps femoris. Patients in control group were treated with apparatus training combined with isometric extension of quadriceps femoris. The treatment course lasted for two weeks. Visual analogue scale (VAS), Lysholm score and total therapeutic effect were evaluated before and after treatments.

RESULTSAfter two weeks of treatment, cure-remarkable-effective rate in experimental group (86.67%) was higher than that in control group (71.11%). The VAS scores and Lysholm scores were significantly improved in both two groups (<0.05). The results were significantly better in experimental group those in control group (<0.05). There were no serious adverse events.

CONCLUSIONSVoluntary rehabilitation exercise combined with isometric extension of quadriceps femoris was effective and safe in the treatment of early knee osteoarthritis.

OBJECTIVETo determine the regulatory effects of the circadian clock gene Per1 on cell cycle-related genes and its influence on the proliferation, apoptosis, cycle, and tumorigenicity in vivo of human oral squamous cell carcinoma SCC15 cells.

METHODSThree groups of the short hairpin RNA (shRNA) of lentivirus recombinant plasmids were designed against the RNA of Per1 and then transfected to the SCC15 cells. The optimum interference group was screened through Western blot and quantitative real-time PCR (qRT-PCR) and assigned as the experimental group. The transfected lentivirus plasmid without an interference effect on any gene was set as the control group (Control-shRNA). Untreated SCC15 cells were set as the blank group. The mRNA expressions of cell cycle-related genes, namely, Per1, p53, Cyclin D1, Cyclin E, Cyclin A2, Cyclin B1, CDK1, CDK2, CDK4, CDK6, p16, p21, Wee1, cdc25, E2F, and Rbl1 in each group were detected through qRT-PCR. The cell proliferation, apoptosis, and cell cycle distribution in each group were evaluated through flow cytometry. The cells of the experimental group and the blank group were subcutaneously inoculated in nude mice to observe tumorigenesis.

RESULTSThree groups of Per1-shRNA lentivirus plasmids were constructed successfully. Among the groups, the Per1-shRNA- I group exhibited the highest interference effect, as indicated by qRT-PCR and Western blot analysis. As such, this group was set as the experimental group. The mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and Wee1 gene in the Per1-shRNA-I group were significantly higher than those in the Control-shRNA group and the SCC15 group (P < 0.05). By contrast, the mRNA expression levels of p53, Cyclin A2, p16, p21, and cdc25 in the Per1-shRNA-I group were significantly lower than those in the Control-shRNA group and the SCC15 group (P < 0.05). The mRNA expression levels of each gene between the Control-sLRNA group and the SCC15 group did not significantly differ (P > 0.05). The mRNA expression levels of CDK2, CDK4, CDK6, E2F, and Rb1 did not significantly differed in the three groups (P > 0.05). The proliferation index of the Perl-shRNA-I group was significantly higher than those of the Control-shRNA group and the SCC15 group (P < 0.05). The apoptosis index of the Per1-shRNA-I group was significantly lower than those of the Control-shRNA group and the SCC15 group (P < 0.05). The number of S-phase cells in the Per1-shRNA-I group was significantly lower than those of S-phase cells in the Control-shRNA group and the SCC15 group (P < 0.05). The number of G2/M-phase cells in the Per1-shRNA-I group was significantly higher than those of G2/M-phase cells in the Control-shRNA group and the SCC15 group (P < 0.05). Conversely, the proliferation index, apoptotic index, and cell cycle distribution of the cells in the Control-shRNA group did not significantly differ from those of the SCC15 group (P > 0.05). The tumorigenic ability in vivo was significantly enhanced in the Per1-shRNA-I group (P < 0.05).

CONCLUSIONPer1 is an important tumor suppressor gene. Per1 can regulate a large number of downstream cell cycle-related genes. The alteration of its expression can affect cell cycle progression, proliferation, apoptosis imbalance, and tumorigenic ability in vivo. Further studies on Per1 may elucidate cancer development and provide novel effective molecular targets for cancer treatment.

Animals ; Apoptosis ; Carcinoma, Squamous Cell ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Circadian Clocks ; genetics ; Cyclin D1 ; Humans ; Mice ; Mice, Nude ; Mouth Neoplasms ; Period Circadian Proteins ; genetics ; Plasmids ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Transfection

OBJECTIVETo explore the regulatory effect of GRK6 on the proliferation of multiple myeloma cells and its mechanism.

METHODSA lentivirus vector shRNA interfering in human GRK6 gene expression was constructed and trans-fected into multiple myeloma cells to obtain the cell line MM1R with stable down-regulation of GRK6 gene expression. The real-time quantitative PCR and Western blot were used to confirm the effectiveness of the GRK6 gene expression down-regulation mediated by lentivirus vector. The MM1R cells with most obvious down-regulation were selected to detect the effect of GRK6 gene on cell proliferation.

RESULTSThe lentivirus vector GRK6-shRNA interfering in human GRK6 gene was constructed succesufully and transfected into multiple myeloma cells, thereby the MM1R cell line with stable down-regulation of GRK6 gene was obtained. The CCK-8 assay showed that the proliferative viability of MM1R cells in experimental group was significantly lower than that in control group (P<0.05); the flow cytometry showed that cells in experimental group were arrested in G/Gphase(P<0.05); the Western blot detection showed that the Cyclin D1 and CDK4 levels in experiment group obviously decreased as compared with control group.

CONCLUSIONA lentivirus vector which can specifically interfere in GRK6 gene expression is constructed successfully, The MM1R cell line with stable down-regulation of GRK6 expression is obtained by transfection and screening. The down-regulation of GRK6 expression can arrest MM1R cells in G/Gphase, moreover inhibits the proliferation of MM1R cells by inhibition of Cyclin D1 and CDK4 levels.

OBJECTIVETo investigate the effect of ADAM10 inhibitor GI254023X on the proliferation and apoptosis of multiple myeloma H929 cell line and its mechanisms.

METHODSH929 cells were treated with different concentrations of GI254023X, the proliferation-inhibitive curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V/7-AAD double staining. The cleavage of Notch1 protein (cleaved notch1) was determined by Western blot. The transcripts of Notch1 target gene Hes-1 were detected by real-time PCR.

RESULTSThe GI254023X inhibited the proliferation of H929 cells in the time- and dose- dependent manners. As compared with the control group, the apoptosis of cells increased along with enhancement of GI254023X concentration; The expression of cleaved Notch1 was down-regulated after the treatment with GI254023X. The levels of Hes-1 mRNA transcripts in H929 cells was reduced in GI254023X treated group.

CONCLUSIONGI254023X can remarkably inhibit the proliferation and induce the apoptosis of H929 cells. Its mechanism may be associated with inbihition of Notch1 activation.

ADAM Proteins ; ADAM10 Protein ; Amyloid Precursor Protein Secretases ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Dipeptides ; Down-Regulation ; Humans ; Hydroxamic Acids ; Membrane Proteins ; Multiple Myeloma ; Receptor, Notch1

Acupuncture Therapy ; Adolescent ; Humans ; Male ; Superior Mesenteric Artery Syndrome ; therapy

OBJECTIVETo compare the long-term outcomes of patients receiving percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy for treatment of chronic total coronary occlusion (CTO).

METHODSThe patients with CTO were selected from a consecutive cohort of patients who underwent coronary angiography (CAG) between 2008 and 2009. The patients with multiple CAG were excluded. The patients received treatments with PCI, CABG, or conservative medication therapy and were followed for major adverse cardiovascular events (MACE) within 5 years.

RESULTSA total of 253 patients were enrolled in this study, including 192 receiving PCI, 48 receiving CABG, and 13 treated conservatively with medications. The baseline clinical characteristics were similar among the 3 groups except for increased low-density lipoprotein (LDL) and total cholesterol (TC) in the medication group, and increased Syndax score in CABG group. During the follow-up, the incidences of MACE, AMI, death, stroke or heart failure did not differ significantly among the 3 groups (P>0.05). However, CABG group showed a higher incidence of the stroke than the other two groups although this difference did not reach a statistically significantly level (P=0.06).

CONCLUSIONOur study did not demonstrate that recanalization offers greater long-term benefits than medications for treatment of CTO, and the patients receiving CABG appeared to have a higher incidence of stroke.

Chronic Disease ; Cohort Studies ; Coronary Angiography ; Coronary Artery Bypass ; Coronary Occlusion ; surgery ; therapy ; Humans ; Incidence ; Percutaneous Coronary Intervention ; Stroke ; epidemiology ; Treatment Outcome