Aim To evaluate the effects of aspirin on the expression of inflammatory proteins induced by oxidized low-density lipoprotein(ox-LDL) in human vascular endothelial cells (HUVECs). Methods HUVECs were stimulated with different concentrations of ox-LDL. The expression of inflammatory proteins was detected by Western blot.Intracellular ROS generation was measured by flow cytometry using perexide-sensitive flurscent probe 2′, 7′-dichrofluorescein diacetate(DCFH-DA).Results ① Aspirin inhibited COX-2 expression induced by ox-LDL. Cells were preincubated with 2.5 mmol?L-1, 5 mmol?L-1 of aspirin or without any treatment for 30 min and then stimulated by 0.3 g?L-1 ox-LDL for 16 h, COX-2 expression was reduced by treating of aspirin.COX-2 expression was enhanced after the stimulation with ox-LDL, and aspirin inhibited the increasing.② Aspirin suppressed ICAM-1 expression induced by ox-LDL in HUVECs. ICAM-1 expression was increased by ox-LDL stimulation for 16 h, and aspirin significantly down-regulated the expression. Similar results were obtained by immunofluorescence.③ Aspirin partially reduced ROS production induced by ox-LDL in HUVECs. After stimulation with 0.3 g?L-1 ox-LDL for 16 h, the intracellular level of ROS was increased, however, aspirin failed to fully inhibit the phenomenon.Conclusion Nonsteroidal anti-inflammatory drugs (NSAID) aspirin significantly down-regulated the expression of COX-2 and ICAM-1 induced by ox-LDL.The results suggested that aspirin could reduce the inflammation responses mediated by ox-LDL on HUVECs in atherosclerosis.

Objective To investigate the effect of indomethacin on prevention of heterotopic ossification (HO)after operative treatment of acetabular fractures.Methods Fifty patients with acetabular fractures received in our department operative treatment through Kocher-langenbeck(K-L)approach and oral administration of in- domethacin afer operation from February 2001 to August 2003.Forty-eight of them were successfully followed up for incidence of HO and their clinical functions were assessed.The results were compared with those of 40 patients who had been treated with the same operative procedures but without oral administration of indomethacin in our depart- ment from March 1993 to May 1998.The patients who could not tolerate the drug were not included.Results The follow-ups averaged 22.8 months(range,6 to 39 months).HO occurred in eight cases.The incidence of HO was 16.7%(8/48).According to Brooker evaluation of HO,five cases were rated as degreeⅠ,three as degreeⅡ, and none as degreeⅢorⅣ.The incidence of severe HO was 0.In the control group,the incidence of HO was 35.0%(14/40)and the incidence of severe HO was 10.0%(4/40).The differences were statistically significant (P＜0.05).Conclusion Oral administration of indomethacin after operative treatment of acetabular fractures can inhibit HO.

Objective To evaluate the operative treatment of nonunion of humeral shaft fracture with in- ternal plate fixation and autogenous cancellous hone graft.Methods Forty-one cases of nonunion of humeral shaft fracture operatively treated from February 2002 to December 2004 were analyzed retrospectively.There were 32 males and nine females.Their average age was 37.5 years(range,17 to 67 years).Sixteen nonunions were defined as hypertrophic and 25 as atrophic.We followed all the patients and obtained their complete medical information. Results Our average follow-up was 22.6 months(range,8 to 42 months).Forty fractures(97.6%)were united within an average of 5.8 months(range,3 to 12 months).Complications included iatrogenic radial nerve injury in three patients,wound infection in one patient and fracture nonunion in one patient.At the final follow-up,shou]der and elbow functions were found to be satisfactory.Conclusion Open reduction and plate internal fixation sup- plemented with autogenous cancellous bone graft is an effective treatment for nonunion of humeral shaft fracture.

BackgroundLaser peripheral iridotomy(LPI) can break the pupillary block,and is an effective method of treating acute primary angle closure (APAC).However,a part of APAC eyes may gradually develop a formation and extension of peripheral anterior synechia(PAS) and increased intraocular pressure(IOP) after LPI.ObjectiveTo investigate the relationship between appositional angle closure and darkroom provocative test(DRPT) in the fellow eyes with APAC after LPI.Methods Fellow eyes of APAC without PAS after LPI were studied.Ultrasounic biomicroscopy(UBM) were performed in darkness to observe whether appositional angle closure occurred and compare the relationship between the quadrants with appositional angle closure and the results of DRPT.Results Fifty-four patients were included in the study.Appositional angle closure was observed in at least one quadrant in 20(37.0％ ) of the 54 fellow eyes with APAC after LPI.Fifty-one patients were given DRPT and positive result in 9 patients( 17.6％ ).According to the quadrants with appositional angle closure,there were 5 patients with DRPT positive results in 46 patients with appositional angle closure 0 to 2 quadrants,and 4 patients with DRPT positive results in 5 patients with appositional angle closure 3 to 4 quadrants ( P =0.003 ).Bivariate correlation analysis indicated a positive correlation between the value of the increased IOP in DRPT and the number of quadrants with appositional angle closure in darkness( r =0.397,P =0.004).ConclusionsA certain proportional fellow eyes of APAC appeared appositional angle closure in darkness and DRPT positive result after LPI.The more the quadrants of appositional angle closure after LPI,the greater the likelihood of a positive DRPT.It suggests that the APAC fellow eyes and attack eyes with the same anatomical configuration still have the possibility of angle closure after LPI,and need follow-up and treatment for a long time.

Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.

Humans ; Infant ; Neuroaxonal Dystrophies ; diagnosis

BACKGROUNDTo characterize the intertype epitopes on human adenovirus (HAdV) hexon.

METHODSBased on computerized analysis on adenoviruses sequence of genomic alignment, antigenicity prediction and 3-D structure characteristics of hexon subunit, several peptides of hexon of adenoviruses were chosen to be synthesized or recombinant proteins of the hexon were expressed in E. coli by use of PGEX-5X. To identify the existence of intertype epitopes, the antisera raised with synthetic peptides or purified recombinant proteins were analyzed with Western blot and immunofluorescent assay.

RESULTSThe results of Western blot indicated that both peptide and recombinant antibodies showed specific reactivities with hexons of HADv-3, 4, 7 individually. Meanwhile, typical stain of immunofluorescence was found on HeLa cells infected with these HAdV by incubation with peptide as well as recombinant antibodies. Also, antibodies raised against peptide recognized the recombinant hexon protein in which a corresponding region of peptides was covered.

CONCLUSIONSMost of the predicted intertype epitopes of HAdV hexon wer e exclusively found in synthetic peptides and recombinant proteins. These intertype epitopes showed to be continuous and sequential which could be employed for development of antibodies of diagnostic use.

Adenoviruses, Human ; immunology ; Amino Acid Sequence ; Animals ; Capsid ; chemistry ; immunology ; Capsid Proteins ; immunology ; Epitopes ; immunology ; HeLa Cells ; Humans ; Mice ; Peptide Fragments ; immunology

Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the ex-pression of hypoxia inducible factor-1α(HIF-1α),Bax and Bcl-2, and the mechanism underlying the role of HIF-1αin he-patocyte apoptosis thereof. Methods Sixty rats were randomly divided into four groups: normal control group, rats were treated normally;IH group, rats were treated by 30 s nitrogen and then 90 s air, and rats were treated by from 9:00-17:00 daily;pulmonary emphysema group, rats were treated by smudging for half an hour, twice a day (8:00 and 18:00);IH with pul-monary emphysema group, rats were treated by 30 s nitrogen and then 90 s air from 9:00-17:00 daily. After exposure four-teen weeks, rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA and Bcl-2 mRNA in live tissues. Results The expressions of HIF-1αmRNA, Bax mRNA and Bax/Bcl-2 were significantly higher in IH with pulmonary emphysema group than those in control group,IH group and pulmonary emphysema group (P<0.05). The expression level of Bcl-2 mRNA was significantly lower in IH with pulmonary emphysema group than that of con-trol group and pulmonary emphysema group (P < 0.05), but no significant difference compared with that of IH group (P >0.05). The levels of HIF-1αand Bax were positively correlated with the level of Bax/Bcl-2 (r=0.732 and 0.699),but the lev-els of HIF-1αand Bax were negatively correlated with the level of Bcl-2 (r=-0.705). Conclusion The expression levels of HIF-1αmRNA, Bax mRNA and Bcl-2 mRNA were over-regulated in hepatocytes induced by intermittent hypoxia with pul-monary emphysema. The HIF-1αexpression was correlated with Bax and Bcl-2, suggesting that HIF-1αmay promote the hepatocyte apoptosis through transcriptional co-activators, Bax and Bcl-2.

Local focal adhesion kinase (FAK) is a non-receptor intracellular tyrosine kinase that plays an important role in tumor initiation, development, metastasis and invasion, and is considered to be an important target for the development of antineoplastic drugs. It has both kinase-dependent and non-kinase-dependent scaffolding functions. However, traditional small molecular inhibitors can only inhibit its kinase-dependent activity, so it is difficult to target the kinase-independent scaffolding function. Therefore, there is an urgent need for novel strategies to enhance FAK targeting to lay the foundation for determining the druggability and discovery of FAK inhibitors. Proteolysis targeting chimera (PROTAC) is a new drug development strategy that can recruit E3 ligase to specifically ubiquitinylate target proteins for degradation through the proteasome system. The unique mechanism of action of the PROTAC system could be used to target and degrade the FAK protein, thus eliminating the scaffolding function of FAK. In this review, FAK protein, the signaling pathway, and small molecule inhibitors are briefly described, and the latest research progress in targeting the degradation of FAK using PROTAC technology is summarized.

Objective To describe a new kind of Y-shaped metallic stent delivery system and evaluate its feasibility and preliminary effect for managing multiple airway stenoses involving the lower trachea and the tracheal carina.Methods The Y-shaped metallic stent delivery system consisted of three- tier structure.The inner-tier was composed of four parallel guiding tubes,which was used for two guidewires and two threads passing through,the middle-tier was delivery catheter,which contained the four guiding tubes,and the outer-tier was introducer sheath.Under the fluoroscopic guidance,15 patients with multiple stenoses involving the lower trachea and the tracheal carina were treated with the new covered self-expandable Y-shaped metallic stents.Results Stent placement in the tracheo-bronchial tree was technically successful in all patients with obliteration of the dyspnea immediately after stent placement,and SaO_2 was increased form preoperative 75%—89% to postoperative 96%—99%.During follow-up a period of 3—58 weeks (M 22 weeks),all stenosis were resolved without stent-related complications,and the general physical of all 15 patents was improved with no occurrence of obviously dyspnea and bleeding.Karnofsky performance status(KPS)was improved from preoperative 26%—45% to postoperative 72%—95%.Five patients died of the following causes unrelated to stent insertion:multiple organ failure(n=3),cachexia(n=1)and pulmonary infection caused by gastrobronchial fistula(n=1),and the remaining 10 patients were alive with no evidence.of dyspnea at the time of this report.Conclusion Deployment of the covered Y-shaped metallic stent with the use of Y metallic stent delivery system in the management of airway stenoses involving the lower trachea and the tracheal earina was a simple and safe procedure and with a good short-term clinical efficacy.