1.Doxazosin induces HeLa cell apoptosis via transcription factor activator protein-2?
Journal of Third Military Medical University 2003;0(24):-
Objective To investigate the pro-apoptotic effects of an ?1-adrenergic inhibitor,doxazosin,in HeLa cells and the role of transcription factor activator protein-2? (AP-2?) in the process.Methods The HeLa cells were treated with doxazosin (0,10,40 or 60 ?mol/L) for 16 h,and cell apoptosis was detected by flow cytometric analysis.After doxazosin (60 ?mol/L) treated the HaLa cells,the cells transfected with AP-2? overexpressing constructs or an antisense oligonucleotide against AP-2? for 16 h,the apoptosis was analyzed with FCM.The expression of AP-2? and caspase-3 in above 3 groups of cells was detected by relative quantitative RT-PCR and Western blot analysis,respectively.Results Doxazosin increased the apoptotic rate and total cell death rate of the HeLa cells,and upregulated the expressions of AP-2? and caspase-3 in a dose-dependent manner.Overexpressing AP-2? improved the increased apoptotic rate and total cell death rate induced by doxazosin,and enhanced the increased expression of caspase-3.Whereas doxazosin-induced apoptosis and the total cell death in HeLa cells were decreased by antisense AP-2?,and antisense AP-2? in part abolished the increased effects of doxazosin on caspase-3 expression.Conclusion Doxazosin induces apoptosis in HeLa cells in a dose-dependent manner,and transcription factor AP-2? is functionally involved in this process.
2.Diagnosis and treatment of post traumatic fat embolism syndrome
Hongsong FANG ; Zhenhua SONG ; Lu XIA
Journal of Clinical Surgery 2001;0(02):-
Objective To discuss diagnosis ant treatment of post traumatic fat embolism syndrome.Methods Since 1997,9 patients with FES have been treated in our hospital.These cases were analyzed on clinic features and results of treatment.Results According to Sevitt classification,there were 2 in fulminant,2 in typical,and 5 in subclinical.2 patients in fulminant died,7 patients were cured because of early diagnose and correct treatment.Conclusion Identify this disease,early and correct treatment help to improve the result.Post traumatic resuscitation is effecrive in decreasing the incidence of FES.
3.Preparation of rmOP-1 and its protective effect on renal ischemia reperfusion injury
Yanjiang LI ; Lijiang SUN ; Zhenhua LU ;
Chinese Journal of Organ Transplantation 2003;0(05):-
Objective To investigate the protective effect of recombinant mouse OP 1 (rmOP 1) on renal ischemia reperfusion injury. Methods The full length open reading frame of mouse OP 1 was cloned by RT PCR. The rmOP 1 was prepared and its osteogenesis was assayed in vitro. Thirty Wistar rat models of renal ischemia reperfusion were randomly divided into 3 groups: preventive group, therapeutic group and control group. The former two groups were administered with rmOP 1 (250 ?g/kg) via the superior mesenteric vein at different time points. The renal function and structure were assessed by serum BUN, Cr, histological findings and the modified Miller's scoring. Results rmOP 1 showed osteoinductive activities in vitro. The level of serum BUN, Cr and Miller's scoring were higher in control group than the others ( P 0.05 ). Histological finding showed that rmOP 1 minimized the cell necrosis. Conclusion rmOP 1 has an protective effect on renal function and structure.
4.Resveratrol ameliorates intestinal barrier injury in rats with hemorrhagic shock through superoxide dismutase 2 activation
Haihong FANG ; Siwei WEI ; Lulan LI ; Jiayin LU ; Zhenhua HU ; Wei XU ; Zhenhua ZENG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(2):184-187
Objective To explore the protective effect of resveratrol (RSV) on intestine barrier injury induced by hemorrhagic shock and its mechanism in rats.Methods According to random number table method,sixty-four SPF grade male Sprague-Dawley (SD) rats were divided into four groups:Sham operation group (only the catheters were indwelled in arterial and venous passages after anesthesia),hemorrhagic shock model group (model group,the catheters were indwelled in arterial and venous passages after anesthesia,and 0.3 mL solvent was administrated after hemorrhagic shock),RSV group (the catheters were indwelled in arterial and venous passages after anesthesia,15 mg/kg RSV was administered after hemorrhagic shock),superoxide dismutase 2 (SOD2) specific inhibitor,2-Methoxyoestradiol (2-ME) group (on the basic treatment of RSV group,0.1 mmol/L 2-ME was administered).The hemorrhagic shock model was reproduced by femoral artery bleeding.After drug administration,all rats were divided into two parts.One part was used for observations on 24-hour survival rate and survival time,while in the other part,2 hours after the hemorrhagic shock,the blood was collected for determination of the content of serum D-lactic acid,and afterward the rats were executed to obtain small intestine tissues for the examination of histopathological changes and Chiu's score.Moreover,differences of expression levels of tight junction proteins (Occludin,Claudin,ZO-1) of small intestine tissue and the oxidative stress related indexes SOD2 activity and reduced glutathione (GSH),oxidized glutathione (GSSH),malonaldehyde (MDA) contents were compared among the groups.Results Compared with the sham group,the model group demonstrated decreased survival rate,SOD2 activity,GSH content,GSH/GSSH ratio,reduced survival time,significantly increased serum D-lactic acid activity,Chiu's score and MDA content,and decreased expressions of tight junction proteins in small intestine tissue.Compared with model group,the RSV group showed significant increased survival rate [75.0% (6/8) vs.37.5% (3/8)] and prolonged survival time (hours:21.0±4.3 vs.10.4±5.8,P < 0.05),significantly decreased serum D-lactic acid (μg/L:380.18 ± 70.59 vs.500.88 ± 97.53) and Chiu's score (1.75 ± 0.71 vs.4.00± 0.53) in small intestine (both P < 0.05),obviously increased expressions of tight junction proteins,SOD2 activity,GSH and GSH/GSSG [Occludin (gray value):0.89 ± 0.10 vs.0.43 ± 0.77,Claudin (gray value):0.78±0.06 vs.0.33 ± 0.05,ZO-1 (gray value):0.83 ± 0.06 vs.0.34 ± 0.07,all P < 0.05],and the elevated SOD2 activity (kU/L:0.85 ± 0.12 vs.0.51 ± 0.11,P < 0.05],as well as increased GSH content and GSH/GSSG ratio [GSH (μmol/L):7.25±1.01 vs.3.86±0.54,GSH/GSSG:6.39± 1.14 vs.1.56±0.25,both P < 0.05] in the small intestine,and markedly reduced MDA content (ng/g:5.00± 1.31 vs.8.63±0.92,P < 0.05).Compared with RSV group,the 2-ME group demonstrated significantly decreased survival rate [50.0% (4/8) vs.75.0% (6/8)] and further shorter survival time (hours:12.2 ± 5.7 vs.21.0±4.3),increased serum D-lactic acid (μg/L:463.88 ± 60.16 vs.380.18 ± 70.59),obviously elevated Chiu's score (3.13 ± 0.99 vs.1.75±0.71,P < 0.05),decreased expressions of tight junction proteins [Occludin (gray value):0.55±0.04 vs.0.89±0.10,Claudin (gray value):0.38±0.05 vs.0.78±0.06,ZO-1 (gray value):0.41±0.04 vs.0.83±0.06,all P < 0.05];moreover,the activity of SOD2,GSH content,GSH/GSSG ratio were greatly reduced [SOD2 activity (kU/L):0.58 ± 0.13 vs.0.85 ± 0.12,GSH (μmol/L):4.49 ± 0.52 vs.7.25 ± 1.01,GSH/GSSG:1.57 ± 0.39 vs.6.39 ± 1.14,all P < 0.05],and increased MDA content (ng/g:6.25 ± 1.04 vs.5.00 ± 1.31,P < 0.05).The small intestine tissue was basically normal in Sham group,and no significant pathological changes were seen;in the model group,the small intestine epithelial mierovilli were collapsed and the mucosal barrier was destroyed obviously;in the RSV group the damages of small intestine microvilli and barrier were markedly alleviated;in 2-ME group the pathological changes were more evident compared with those in the RSV group.Conclusion RSV can improve intestinal barrier injury following hemorrhagic shock in rats;its mechanism may be related to SOD2 activation.
5.The effects of paired associative stimulation on motor cortex excitability and the recovery of motor function after stroke
Yanfang SUI ; Zhenhua SONG ; Liangqian TONG ; Lu YANG ; Tiecheng GUO
Chinese Journal of Physical Medicine and Rehabilitation 2013;35(9):703-707
Objective To investigate the effects of paired associative stimulation (PAS) on the recovery of upper limb motor function in stroke patients,and to analyze the relationship between the change of motor cortex excitability in the contralesional hemisphere and the recovery of motor function in the affected upper limb.Methods Thirty hemiplegic stroke patients were divided randomly into a treatment group and a control group.Both groups were given routine rehabilitation therapy,but the treatment group also received PAS consisting of transcranial magnetic stimulation (TMS) of the intact motor cortex and electrical stimulation (ES) of the median nerve at the wrist of the intact arm with an interval of 10 ms between the TMS and ES (PAS10).The PAS10 was delivered at a frequency of 0.05 Hz and an intensity of 120% the resting motor threshold (RMT),once daily for 30 minutes,five times a week for 4 weeks.Corticospinal excitability was measured using motor evoked potentials (MEP) and the RMT.The FuglMeyer upper limb assessment (FMA),Brunnstrom staging and the modified Barthel index (MBI) were also applied before and at the end of the 4 weeks of treatment.Correlation was sought between any changes in MEP amplitude,the RMT of the contralesional hemisphere and changes in the FMA results.Results Before the intervention there were no significant differences between the two groups in terms of any of the assessments.After 4 weeks of treatment,all the assessments had changed significantly compared to those before the treatment,but there were still no significant differences between the two groups in terms of any the assessments.After 4 weeks of treatment,the differences in MEP amplitude from the contra-lesional hemisphere and the differences in FMA scores were positively and significantly correlated with a correlation coefficient of r =0.431.The lesioned hemisphere was also positively correlated with the differences in FMA scores with a significant correlation coefficient of r =0.608.Conclusion PAS10 can facilitate the recovery of upper limb motor function.The change in motor cortex excitability of the contra-lesional hemisphere significantly correlates with functional recovery in the upper limb.
6.Genetic association between corneal curvature-related genes and high myopia in Chinese Han population
Zhenhua, DENG ; Zimeng, YE ; Bo, GONG ; Fang, LU
Chinese Journal of Experimental Ophthalmology 2017;35(8):716-720
Background High myopia is one of the primary factors of visual impairment,and its prevention and management are researching hot topics.Corneal curvature (CC) measures the steepness of the cornea which is an important parameter leading to myopia.Genome-wide association study (GWAS) showed that several genes are associated with CC in Asian populations.However,the association of corneal curvature-related genes with high myopia is unclear up to now.Objective This study was to investigate the association between single nucleotide polymorphism (SNP) in the rs74225573 (mechanistic target of rapamycin [MTOR]),rs60078183 (cytidine/uridine monophosphate kinase 1 [CMPK1]),rs1800813 (platelet derived growth factor receptor alpha [PDGFRA]),rs11204213 (retinol binding protein 3 [RBP3]) and high myopia in Chinese Han population.Methods A prospective cohort study was performed.Four hundreds and eighty-three patients with high myopia were collected in Sichuan Provincial People's Hospital from February 2012 to August 2013,with the diopter (-10.84±4.69)D in the right eyes and (-10.35±4.67)D in the left eyes or ocular axial length of (28.15±2.27)mm in the right eyes and (27.72±2.51)mm in the left eyes.Five hundreds and nineteen normal volunteers matched in age and gender were included in the same period as controls,and all the subjects were Chinese Han people without genetic relationship.The periphery blood of 4 ml was obtained for the DNA extraction from each subject under the written informed consent.The primers of rs74225573,rs60078183,rs1800813 and rs1 1204213 were designed based on the information of NCBI website.The four SNPs were amplified by real-time PCR and genotyped by SNaPshot method.Results All the genotype frequencies of these four SNPs were in Hardy-Weinberg equilibrium (HWE).There are no significant differences in minor allele frequency (MAF) distribution of rs74225573,rs60078183 and rs11204213 between high myopia group and normal control group (rs74225573:Pag-corrected =0.935,OR =0.98;rs60078183:Page-currected =0.782,OR =1.04;rs11204213:Page-currected =0.058,OR =1.66),and the M AF of rs1800813 was significantly higher in the high myopia group than that in the normal control group (Page-currected =0.001,OR =0.64).The genotype frequency of rs74225573,rs60078183 and rs11204213 was not evidently different in additive model 1 (AB vs.BB),additive model 2 (AA vs.BB),dominant model (AA+AB vs.BB) and recessive model (AA vs.AB+BB) (all at P>0.05),while significant differences were found in genotype frequency of rs1800813 both in additive model 1 and dominant model (additive model 1:P=0.002,OR=0.59;dominant model:P=0.001,OR=0.58).Conclusions The SNP of rs1800813 in the PDGFRA gene is associated with the pathogenesis of high myopia in the Chinese Han population,but the SNPs of rs74225573 (MTOR gene),rs60078183 (CMPK1 gene) and rs11204213 (RBP3 gene) appear to be not associated with high myopia.
7.Application of 3.0T magnetic resonance diffusion weighted imaging in evaluating the effect of advanced gastric cancerˊs neoadjuvant chemotherapy
Zengxin LU ; Zhenhua ZHAO ; Aijing SUN ; Feng TAO ; Jieqing LYU
Cancer Research and Clinic 2015;(7):453-457
Objective To evaluate the clinical value of 3.0T magnetic resonance imaging (MRI) diffusion weighted imaging (DWI) on evaluation effect of neoadjuvant chemotherapy in advanced gastric cancer. Methods 3.0 T MRI DWI examination was performed in 42 cases of advanced gastric cancer diagnosed by gastroscopy and pathology, including 32 patients were examined with DWI both before and after chemotherapy. Lymph nodes of gastric cancer lesions and display ability of stomach were measured, and the area of the apparent diffusion coefficient (ADC) values in normal stomach and tumors were compared. ADC values were compared in the same patients before and after neoadjuvant chemotherapy and analyzed along with postoperative pathological examinations. Results In a total of 40 patients who received 74 DWI examinations, ADC values in tumor and lymph nodes were significantly higher than those in normal tissue. The ADC value in tumors was (1.348 ±0.278) ×10-3 mm2/s, and in 12 cases of stomach lymph node enlargement was (1.329±0.188) ×10-3 mm2/s. However, the average ADC value of normal stomach was (2.081± 0.189) ×10-3 mm2/s with significantly lower DWI than that of the former (P< 0.001). After chemotherapy, the ADC value in tumors was increased, which was (1.572 ±0.261) ×10-3 mm2/s (P< 0.001). After neoadjuvant chemotherapy, 16 patients received gastric cancer radical prostatectomy, and postoperative pathological TRG ratings of tumor were decreased with different extent. Tumor cell density (TCD) before treatment with an average of 4.45 ×10-5 / px2, which was downgraduated to 2.48 ×10-5 / px2 after chemotherapy and surgery. Negatively correlation between TCD values and ADC values were observed. Conclusion MRI DWI examination can effectively detect advanced stomach cancer and the associated lymph node enlargement. Comparison of tumor morphology and ADC values in advanced gastric cancer before and after neoadjuvant chemotherapy has clinical value in prognosis.
8.Culprit vessel only versus“one-week”staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction
Lixiang MA ; Zhenhua LU ; Le WANG ; Xin DU ; Changsheng MA
Journal of Geriatric Cardiology 2015;(3):226-231
Objective To explore the impact of a“one-week”staged multivessel percutaneous coronary intervention (PCI) versus culprit-only PCI on deaths and major adverse cardiac events (MACE). Methods We retrospectively analyzed 447 patients with multivessel disease who experienced a ST-segment elevation myocardial infarction (STEMI) within 12 h before undergoing PCI between July 26, 2008 and Septem-ber 25, 2011. After completion of PCI in the infarct artery, 201 patients still in the hospital agreed to undergo PCI in non-infarct arteries with more than 70%stenosis for a“one-week”staged multivessel PCI. A total of 246 patients only received intervention for the culprit vessel. Follow-up ended on September 9, 2014. This study examined the differences in deaths from any cause (i.e., cardiac and noncardiac) and MACE between the two treatment groups. Results Compared to a culprit-only PCI treatment approach, the“one-week”staged multivessel PCI was strongly associated with greater benefits for 55-month all cause death [41 (16.7%) vs.13 (6.5%), P=0.004] and MACE [82 (33.3%) vs. 40 (19.9%), P=0.002] rates. In addition, there were significant differences in the number of myocardial infarctions [43 (17.5%) vs. 20 (10.0%), P=0.023], coronary-artery bypass grafting [CABG;20 (8.1%) vs. 6 (3.0%), P=0.021], and PCI [31 (12.6%) vs. 12 (6.0%), P=0.018]. Patients undergoing culprit-only PCI compared to“one-week”PCI had the same number of stent thrombosis events [7 (2.8%) vs. 3 (1.5%), P=0.522]. Conclusions Compared to a culprit-only PCI treatment approach,“one-week”staged multi-vessel PCI was a safe and effective selection for STEMI and multi-vessel PCI.
9.Literatures analysis of clinical significance of lymph node metastasis in gastrointestinal stromal tumor
Yanjun LU ; Xiaobo LIANG ; Liang YUE ; Xiaoyuan WANG ; Zhenhua WANG
Cancer Research and Clinic 2012;24(1):8-11
ObjectiveTo explore the clinical significance of lymph node metastasis in gastrointestinal stromal tumor (GIST).Methods A literature search to identify studies relating to GIST cases reported between January 1998 and December 2010 was conducted.The associations between lymph node metastasis and GIST clinicopathological features, gene expression, GIST stage, and GIST prognosis were evaluated.Results 6063 literatures were screened and only 16 GIST patients (median age of 49.25 years,10females) with lymph node metastasis were enrolled in this study.Among them,12 tumors were located in the stomach, 3 in the small intestine, and 1 in the esophagus.Morphologically, 13 specimens were mainly characterized by spindle cells.Gene analysis was examined in 7 cases.Conclusions Lymph node metastasis in GIST might more frequently found in the stomach, tumor stage of high grade, and cellular morphology of spindle-shaped.Gene mutation may have a relationship with lymph node metastasis.However, its clinical significance remains unclear.
10.A Meta-analysis of capecitalbine or 5-Fu combined with oxaliplatin therapy for metastatic colorectal cancer
Xiaoyuan WANG ; Xiaobo LIANG ; Yanjun LU ; Liang YUE ; Zhenhua WANG
Cancer Research and Clinic 2012;24(7):436-439
ObjectivesTo compare clinical outcomes and safety of 5-Fu or capecitabine combined with oxaliplatin therapy for metastatic colorectal cancer. MethodsLiterature search were performed by key words,such as metastatic colorectal cancer,capecitabine,oxaliplatin,5-Fu on all randomized controlled trails reported on 5-Fu or capecitabine combined with oxaliplatin therapy for metastatic colorectal cancer before Jun.2011.Two authors drew the details of trail design,characteristics of patients,outcomes and so on from the studies included. Data analysis was performed by RevMan 4.2. ResultsAccording to the same screening criteria,6 clinical studies were included in this Meta-analysis. Sample volume in this Meta-analysis was 2189 colorectal cancer cases.The baseline characteristics of 5-Fu group were similar to those of capecitabine group.The short-term outcome such as response rate,RR was 0.92 [95 %CI(0.82,1.02),P=0.12], and the long-term outcome such as median overall survival, median progression-free survival and the WMD was -0.19 [95 %CI(-0.73,0.35),P=0.49],-1.91 [95 %CI(-2.53,0.16),P=0.08],respectively,two groups weresimilar. In the comparison of Ⅲ-Ⅳ grade toxicity between the two groups, the incidences of neutropenic in 5-Fu group were higher than those in capecitabine group,and the RR was 0.24 [95 %CI(0.11,0.55), P=0.0007]. However, the incidence of wand-foot symptoms in 5-Fu group was lower than those in capecitabine group, the RR was 2.83 [95%CI (1.66,4.82), P=0.0001]. ConclusionBoth 5-Fu and capecitabine were similarly effective in the therapy of metastatic colorectal cancer. And the Ⅲ-Ⅳ grade toxicity such as neutropenic was easier to happen in 5-Fu group,while the incidence of hand-foot symptoms was on the other hand.