Objective:To explore bromodomain and extra-terminal (BET) inhibition in the regulation of vascular endothelial cells activation and early atherosclerosis formation and its potential molecular mechanisms.Methods:1.Human umbilical vein endothelial cells (HUVEC) and mouse heart endothelial cells (MHEC) were isolated,and tumor necrosis factor α (TNFα) was used to activate in flammatory genes transcription in the presence or absence of JQ1,a specific BET inhibitor.The groups are as follows:(1)Normal control group;(2) TNFα(25 ng/mL)group;(3) TNFα+JQ 1 group.The gene mRNA and protein expression of inflammatory cytokines were measured by both real-time PCR and flow cytometry (FCM).2.LDL receptor-deficient (LDLR-/-) mice were randomly divided into 2 groups:JQ1 group (n=8,JQlintraperitoneal,50 mg/kg,daily) and control group (n=8,DMSO,daily).After 8 weeks feeding with high cholesterol diet,vascular cell adhesion molecule-1 (VCAM-1) expression in aortic arch was measured by immunohistochemistry.The activity of nuclear factor kappa B (NF-κB) signaling was monitored by 5XκB luciferase reporter assay in HEK293.Results:TNFα dramatically induced the mRNA and protein expression of inflammatory genes and JQ 1 significantly downregulated the induction of them (E-selectin,P-selectin,VCAM-1,IL-8)(P＜0.01).Immunohistochemistry detection indicated that JQ1 significantly downregulated the expression of VCAM-1 in aortic arch induced by 8 weeks high cholesterol diet feeding comparing to control group.In addition,BET bromodomain inhibition downregulated TNFα upregulated NF-κB transcriptional activity (P＜0.01).Conclusions:Our study demonstrated that BET bromodomain was involved in NF-κB mediated inflammatory genes expression;inhibition of BET bromodomain suppressed vascular endothelial activation in vitro,and attenuated early atherogenesis in vivo.

Objective To improve the establishment of rabbit model with VX2 liver tumor and assess sonographical value in monitoring the tumor growth.Methods Fifteen New Zealand white rabbits were implanted with VX2 tumor in two liver lobes under ultrasound guidance percutaneously.Ultrasound examinations were performed at twenty days and thirty-six days after implantation.At the same time exploratory laparotomy was performed.Results Among 30 implanted tumors of 15 rabbits,16(53%) tumors were successfully implanted with few complications.It took 15 to 40 minutes to implant tumors in one rabbit.Implantation rates of left lobe and right lobe were 53% and 50% respectively,and there was no significant difference.Ultrasound examination could monitor tumor growth well.Conclusions After the improvement,the establishment of model was easier,less time-consuming,minimally invasive and caused few complications than other implantation methods.Serial ultrasound examinations should be performed in monitoring the tumor growth.

Objective To investigate the expression levels of Interleukin(IL)?6 and matrix metalloproteinases(MMP)?13 in synovial fluid by in?vigorating kidney and activating blood formulae in treating rabbit knee osteoarthritis model. Methods A total of 30 New Zealand rabbit were ran?domly divided into blank group,model group,invigorating kidney group,activating blood group and invigorating kidney and activating blood group. Rabbits model with knee osteoarthritis were established by improved Hulth method. To give corresponding respectively the medicinal broth,model group was given saline,knee joint synovial fluid was collected after 4,8 and 12 weeks. Enzyme linked immunosorbent assay(ELISA)was used to measure the levels of IL?6 and MMP?13. Results The levels of IL?6 in rabbit knee osteoarthritis were obviously higher than that of normal control group at both 4 weeks and 8 weeks(P<0.001). But there was no statistical difference on the levels of IL?6 compared with controls in 12 weeks. In addition,the level of MMP?13 at 4 weeks,8 weeks and 12 weeks were significantly higher than the blank control group(P<0.001). After 8 weeks of Chinese medicine administration,the levels of IL?6 in synovial fluid were significantly decreased in invigorating kidney group,activating blood group and invigorating kidney and activating blood group(P<0.001),but there was no statistical difference among groups in 12 weeks. The MMP?13 levels of synovial fluid was significantly lower than the model group(P<0.001). Conclusion Our results indicate that IL?6 and MMP?13 par?ticipate in the pathological development of the rabbit knee osteoarthritis. Invigorating kidney and activating blood formulae could reduce the expres?sion of IL?6 and MMP?13 and alleviate osteoarthritis progression,and which is superior to the pure invigorating kidney formulae and activating blood formulae.

Objective To explore influences of the fistula's location on the procedure and outcome of a transvaginal vesicovaginal (VVF) repair.Methods The medical data of patients undertaken transvaginal VVF repairs in Peking University First Hospital between Janurary 2009 and Auguest 2016 were retrospectively collected,including age,past history,causes of the fistula,disease course,past treatment,outcomes of the cystoscopy and imaging test and surgical information.The follow-ups were performed.Patients who had incomplete clinical data and lost to follow-up were not included.The present study included 68 VVF subjects with the median age of 46 years (range:24-64 years).The univariate analysis was performed to figure out potential risk factors for the VVF repair outcome.The duration and blood loss of VVF repairs were compared among the subjects with the fistulae located at bladder neck,trigone and supra-trigone region.Results There were 5,23 and 40 cases having VVFs located at bladder neck,trigone and supratrigone region respectively.The overall repair success rate was 88.2％ (60/68).According to results of the univariate analysis,subjects with more past repair times had significantly lower success rates.There were no significant differences in success rates of surgical repairs for VVFs located at bladder neck (80.0％,4/5),trigone (91.3％,21/23) and supra-trigone region (87.5％,35/40).And the location of VVFs had no significant association with the duration and blood loss during the VVF repair.Conclusions The location of VVFs had no influences on the procedure and outcomes of the transvaginal repairs.The VVF repair approach may not be determined based on the fistula's location alone.

Objective To explore the clinical characteristics in twin premature infants in order to provide some guidance for clinical work in future.Methods The clinical data of 593 premature infants hospitalized in Department of Pediatrics,the Affiliated Hospital of Kunming Medical University were collected from June 2010 to June 2012,in terms of gestational age,birth weight and neonatal complications.A retrospective analysis was performed for the data.The premature infants were divided into 2 groups:study group of 131 twin premature infants and control group of 462 singleton premature infants.The 131 twin premature infants in study group were divided into large double group(n =64) and small double group(n =67) according to delivery time.The clinical data of premature infants in each group were statistically analyzed.Results The gestational age of study group was (34.23 ± 1.90) weeks,which in control group was (33.91 ± 1.82) weeks,and there was no significant difference between the 2 groups(t =1.689,P =0.092).The birth weight in study group [(1 921.64 ± 414.05)g] had statistically significant difference compared with control group [(2 164.98 ± 495.85) g] (t =-5.209,P =0.000).The study group of incidence of premature rupture of membranes was 16.79％ (22/131 cases)and which in the control group was 32.68％ (151/462 cases),and there was statistically significant difference between the 2 groups (x2 =12.472,P =0.000) ;the incidence of neonatal asphyxia of study group was 9.92％ (13/131 cases) and that of the control group was 17.10％ (79/462 cases),there was statistically significant difference between the 2 groups (x2 =4.010,P =0.045) ; the incidence of respiratory distress syndrome in study group was 6.87％ (9/131 cases) and that in the control group was 3.03 ％ (14/462 cases),the difference was statistically significant between the 2 groups (x2 =4.037,P =0.045) ; the incidence of apnea in study group was 4.58％ (6/131 cases) and that in the control group was 0.65％ (3/462 cases),the difference was statistically significant between the 2 groups(x2 =8.085,P =0.004) ; the incidence of meconium aspiration syndrome of study group was 0 and that of the control group was 3.90％ (18/462 cases),there was statistically significant difference (P =0.018) ;the incidence of neonatal hypoglycemia of study group was 27.48％ (36/131 cases) and that of the control group was 16.67％ (77/462 cases),the difference was statistically significant between the 2 groups (x2 =7.738,P =0.005) ;the incidence of sepsis of study group [16.79％ (22/131 cases)] was significantly higher than that of the control group [8.44％ (39/462 cases)],and the difference was statistically significant between the 2 groups (x2 =7.715,P =0.005) ;the incidence of extrauterine growth retardation of study group was 6.10％ (8/131 cases) and that of the control group was 2.38％ (11/462 cases),the difference was statistically significant between the both groups (x2 =4.568,P =0.033).In the study group,the incidence of neonatal sepsis in big double group was 29.68％ (19/64 cases),and that in small double was 14.93％ (10/67 cases),there was statistically significant difference between the 2 groups(x2 =4.138,P =0.042).The other complications between the big double group and small double group had no significant difference.Conclusions The incidence rates of acute respiratory distress syndrome,apnea,neonatal hypoglycemia,sepsis and extrauterine growth retardation of twin premature infants are higher than the singleton premature infants in the neonatal period.But the incidence rate of meconium aspiration syndrome is a higher in singleton premature infants.

Objective To investigate the impact of injection current (IC), injection voltage (IV), and pulse forming network (PFN) on energy (depth ratio D20/D10) and profiles of helical tomotherapy, and to improve the quality control for the stability of beam characteristics.Methods The energy and profiles were measured by ion chamber and TomoDose at different values of IC, IV, and PFN, the relationship between the energy and various parameters was evaluated by Pearson correlation analysis, and the changes in profiles were evaluated by comparative analysis.Results The energy had no correlation with IV and PFN values (P>0.05), but had a strong correlation with IC value (P=0.007), which showed a downward trend with the increase in IC.For the profiles in the x direction:(1) in the main beam region (-200 to 200 mm), the shoulder area of the profiles increased regularly with the increase in IC.There were no significant changes for the profiles when the IV values ranged from 6.42 V to 6.54 V, and the shoulder area of the profiles reached the highest point with IV=6.60 V, then decreased with further increase in IV.The shoulder area of the profiles decreased regularly with the increase in PFN.(2) In the penumbral region (±200 mm outside), all the three parameters had no effect on the profiles.For the profiles in the y direction:(1) in the main beam region (-20 to 20 mm), the profiles showed an upward trend in the area with an off-axis distance less than 16 mm when IC values were 5.40 V and 5.46 V, and showed an upward trend in the area with an off-axis distance less than 16 mm.But on the whole, the shoulder area of the profiles increased with the increase in IC, and was not affected by IV and PFN.(2) In the penumbral region (±20 mm outside), the profiles decreased regularly with the increase in IV, and was not affected by IC and PFN.IC had the highest influence on the profiles in the main beam region, followed by PFN and IV.Only IV had impact on the profiles in the penumbral region.Conclusions When the energy needs to be adjusted, the IC value should be given a priority, and PFN should be taken as a supplementary factor.When the profile needs to be adjusted, the IC value should be given a priority, and IV should be used as an auxiliary factor in the main beam region.But in the penumbral region, adjustment of parameters is only related to the profiles in y direction, so the IV value should be adjusted.This study has a guiding role in the quality control of energy and profiles, which can reduce the blindness of quality control, thus saving the time.

Cleidocranial Dysplasia ; pathology ; Diagnosis, Differential ; Dwarfism ; Humans ; Maxillofacial Abnormalities ; Osteosclerosis ; pathology ; Pycnodysostosis ; diagnostic imaging ; etiology ; pathology ; therapy ; Radiography ; Tooth Abnormalities

The mobilization efficiency of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to bone marrow mononuclear cells (MNCs) in mice was observed, and the changes of CXCL12/CXCR4 signal were detected in order to find out the mobilization mechanism of stem cells. Kunming mice were randomly divided into two groups. The mice in treatment group were subjected to subcutaneous injection of G-CSF at a dose of 100 mug/kg and SCF at a dose of 25 mug/kg every day for 5 days, and those in control group were given isodose physiological saline. The MNCs were separated, counted and cultured, and the colony-forming unit-fibroblast (CFU-F) was evaluated. CD34(+)CXCR4(+) MNCs were sorted by flow cytometry. The expression of CXCL12 protein in bone marrow extracellular fluid was detected by ELISA, and that of CXCL12 mRNA in bone marrow was measured by RT-PCR. The results showed that the counts of MNCs in peripheral blood and bone marrow were increased after administration of G-CSF/SCF (P<0.01). The factors had a dramatic effect on the expansion capability of CFU-F (P<0.05). Flow cytometric of bone marrow MNCs surface markers revealed that CD34(+)CXCR4(+) cells accounted for 44.6%+/-8.7% of the total CD34(+) MNCs. Moreover, G-CSF/SCF treatment induced a decrease in bone marrow CXCL12 mRNA that closely mirrored the fall in CXCL12 protein. In this study, it is evidenced that G-CSF/SCF can effectively induce MNCs mobilization by disrupting the balance of CXCL12/CXCR4 signaling pathway in the bone marrow and down-regulating the interaction of CXCL12/CXCR4.

This study examined endogenous cannabinoid (ECB)-anandamide (AEA) and its cannabinoid receptors (CBR) in mice liver with the development of schistosoma japonicum. Mice were infected with schistosoma by means of pasting the cercaria onto their abdomens. Liver fibrosis was pathologically confirmed nine weeks after the infection. High performance liquid chromatography (HPLC) was employed to determine the concentration of AEA in the plasma of mice. Immunofluorescence was used to detect the expression of CBR1 and CBR2 in liver tissue. Morphological examination showed typical pathological changes, with worm tubercles of schistosoma deposited in the liver tissue, fibrosis around the worm tubercles and infiltration or soakage of inflammatory cells. Also, CBR1 and CBR2 were present in hepatocytes and hepatic sinusoids of the two groups, but they were obviously enhanced in the schistosoma-infected mice. However, the average optical density of CBR1 in the negative control and fibrosis group was 13.28+/-7.32 and 30.55+/-7.78, and CBR2 were 28.13+/-6.42 and 52.29+/-4.24 (P<0.05). The levels of AEA in the fibrosis group were significantly increased as compared with those of the control group. The concentrations of AEA were (0.37+/-0.07) and (5.67+/-1.34) ng/mL (P<0.05). It is concluded that the expression of endocannabinoids AEA and its cannabinoid receptor CBR were significantly increased in schistosoma-infected mice. Endogenous endocannabinoids may be involved in the development of schistosoma-induced liver fibrosis.
Arachidonic Acids/*metabolism ; Endocannabinoids/*metabolism ; Liver Cirrhosis/etiology ; Liver Cirrhosis/*metabolism ; Liver Cirrhosis/parasitology ; Polyunsaturated Alkamides/*metabolism ; Random Allocation ; Receptor, Cannabinoid, CB1/*metabolism ; Receptor, Cannabinoid, CB2/*metabolism ; Schistosomiasis japonica/*complications ; Schistosomiasis japonica/metabolism

Objective To prospectively assess the predictive power of centralization phenomenon in the curative effect of automated PLD.Methods The survey population was consisted of 109 patients with inclusion heraiation demonstrated by CT/MRI,74 men and 35 women with average age of 43.1 years(17～75 years). All were complained of low back pain,with varying degrees of lower extremity pain and altered sensation, lasting for more than 2 months;including one symptomatic disc in 99 patients and two symptomatic discs in 10 patients.Patients were undergone dynamic mechanical spinal test and reported whether the test would aggravate their pain.The assessment included forward flexion,extension,rotation of the trunk to the right and left, rotation to the left with fight extension,rotation to the fight with left extension,and whether straight leg raising in the supine position would aggravate back pain or leg pain.Symptom resposes were categorized into three groups:centralization group(CG),partial-centralization group(PCG)and noncentralization group(NCG). Centralization of pain is the progressive retreat of the most distal extent of the referred or radicular pain toward or to the lumbar midline.Noncentralization of pain is the peripheralization of pain in one or more directions, and no change in the distal-most pain location or intensity.All patients received a single therapy with PLD. Results A follow-up of 109 patients for 3 to 6 months,including 46 cases with 24 as exellent and 22 as good reaching 100% of excellent good rate in CG by MacNab standards;43 cases with 5 as exellent,29 as good,9 as fair and poor,with total effective rate of 79.1% in PCG.Twenty cases of NCG symptoms showed no improvement and therefore surgery was considered.Conclusions Centralization phenomenon occurrence during initial mechanical evaluation is a very accurate predictor for successful PLD outcome.Nonoccurrence of centralization would accurately predict poor PLD outcome and thus helpful as early predictor of the need for surgical treatment.