1.Effects of human annexin Ⅴ derivative on coagulation and thrombosis: Effective time and dosage
Junyou CUI ; Liansheng WANG ; Chengwei JU ; Xiang YANG ; Zichun HUA
Chinese Journal of Tissue Engineering Research 2005;9(27):192-194
BACKGROUND: As a common anticoagulant, heparin is widely used in clinic, but it has remarkable side effects such as severe bleeding and heparin-induced thrombocytopenia, and it cannot inactivate fibrin-bound thrombin. Annexin Ⅴ derivative (AND) is inosculated with C-terminal of hirudin and annexin Ⅴ, and its anticoagulation and anti-thrombosis effects are compared with those of heparin. OBJECTIVE: To investigate the relationship between quantitative effectiveness and time effectiveness of AND on coagulation and thrombosis, and study its reliability. DESIGN: Completely randomized grouping design and controlled study. SETTING: Cardiac Department of amunicipal hospital. MATERIALS: The experiment was conducted at the Animal Laboratory of Jiangsu Provincial People's Hospital from July 2000 to April 2001. Totally 32 male New Zealand white rabbits were randomly divided into 4groups, namely, high dosage AND group, low dosage AND group, common heparin group and saline group with 8 in each group. METHODS: Heparin and AND were diluted with saline.①High dosage AND group: 0.7 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.35mg/(kg ·h)for 2 hours.Low dosage AND group: 0.3 mg/kg AND was injected intravenously and followed by intravenous dripping of 0.15 mg/(kg·h) for 2 hours. Heparin group: 75 IU/kg heparin was injected intravenously and followed by intravenous dripping of 37.5 IU/(kg·h) for 2 hours. Saline group: The same volume of saline and medication were used as those in drug groups.② Blood sample was collected from the femoral vein before administration so as to test blood routine, activated partial thromboplastin time(APTT)and prothrombin time (PT) after 15-, 30- and 60-minute administration and 2-hour withdrawal.③Saccule was separated from endothelium of femoral artery to measure blood pressure of distal femoral artery at 15 minutes after administration.Time of pulse pressure equal to 0 mmHg was recorded when the vessel was occluded completely by a thrombus.Finally the injured femoral arteries whose vessel was stripped were collected to measure its length, wet weight and dry weight. ④Observation of AND toxicity and sideeffects:During the experiment,vital signs of the animals were measured,such as blood pressure,heart rate and breath;in addition,bowelhemorrhage was observed and the number of leucocytes was counted after dissection of some of the animals. MAIN OUTCOME MEASURES:①Effect of AND on blood coagulation system and arterial thrombosis.②AND toxicity and side effects. RESULTS: All the 32 white rabbits entered the final analysis. ① Anticoagulant effect: APTT: Fifteen minutes after administration, APTT in AND group was the longest,which was(136.86±39.46)s in high dosage AND group and (122.90±34.19) s in low dosage ANDgroup.Moreover, APTT was longer than that in saline group [(95.14±24.64) s], but shorter than that in common heparin group [(180.00±0.00) s, P < 0.05, 0.01]. At 30 minutes after administration,AND in high dosage group still had coagulation,and APTT was (124.61±40.19) s in high dosage group, which was longer than that in saline group [(85.57±27.67) s], but APTT was (112.94±43.17) sin low dosage group,which was shorter than that in common heparin group [(85.57±27.67)s,P < 0.05].APTT was shorter in high and low dosage groups than in common heparin group at 60 minutes after administration (P < 0.05),and longer than that in saline group 2 hours after drug withdrawal,but there was not significant difference(P > 0.05).PT:PT in common heparin group was longer than that in high and low dosage groups at 15,30 and 60 minutes after administration (P < 0.05).② Effect on arterial thrombosis:Wet weight of thrombus:It was lighter in AND group than in common heparin group(P < 0.05). Dry weight of thrombus:Thrombus was lighter in high and low dosage groups than in common heparin group, and was lighter in high dosage group than in low dosage group (P < 0.05).Thrombus length:It was shorter in low dosage group than in saline group (P < 0.05), and shorter in high dosage groupthan in common heparin group (P < 0.05). Time of complete occlusion: It was longer in high and low dosage groups than in saline group(P < 0.05).③ AND toxicity and side effects:The behavior of rabbits in high and low dosage groups was similar to that in other two groups. Obvious hemodynamic changes were not found, and bowel hemorrhage was not observed, either. CONCLUSION: AND is an effective anticoagulant and anti-thrombosis agent; the highest anticoagulation effect occurs at 15 minutes afteradminis tration. However, the anticoagulant effect is poor as compared to heparin.The effect is poorer after 60-minute administration. Effect of AND on thrombus is stronger than that of heparin,but the size of thrombus is smaller than that of heparin, and the dosage-dependence manner was found. In addition, the anti-thrombus effect of AND is stronger in high dosage group than in low dosage group.
2.Meta-Analysis of Risk Factors for Intracerebral Hemorrhage in General Population
Hong WANG ; Zhenzhong LI ; Baofeng FANG ; Zichun ZHAO ; Cuifang CAO
International Journal of Cerebrovascular Diseases 2008;16(10):771-778
To investigate the risk factors for intracerebral hemorrhage in general population.Methods:The related research was searched through English Medical Current Contents (EMCC),China Hospital Knowledge Database (CHKD),MEDLINE,and Chinese Biomedical Literature Database (CBM).The search terms were intracerebral hemorrhage,factor,and case-control study or cohort study.Results:There were 8 literatures with original data were in accordance with the inclusion criteria.All the data could not be combined because there were some differences in counting and metrology in the risk factors included in all the studies.Hypertension,family history of cerebrovascular disease,high salt diet,alcohol consumption,diabetes mellitus,high diastolic pressure,high systolic pressure,smoking,snoring disease,and increased weighted mean difference of body mass index (BMI) (95% confidence interval) were 5.71 (4.00-6.79),3.54 (2.44-5.14),2.58 (1.94-3.43),2.80 (2.29-3.43),2.78 (1.83-4.23,1.90 (1.35-2.70),17.76 (16.60-18.92),30.43 (28.61-32.25),5.42 (5.15-5.70),1.90 (1.34-2.69),6.88 (4.61-10.26,and 5.42 (5.15-5.70),respectively.There were significant differences between the patient groups and control groups among the above indexes (all P<0.000 01).Conclusions:The risk factors for intracerebral hemorrhage include hypertension,family history of cerebrovascular disease,high salt diet,smoking,alcohol consumption,snoring disease,diabetes mellitus,overweight,high diastolic blood pressure,high systolic blood pressure and increased BMI.
3.99Tcm-TP5-3 microSPECT/CT for the early evaluation of response in mice bearing MDA-MB-231 breast carcinoma after a single dose of paclitaxel chemotherapy
Rui LUO ; Feng WANG ; Yanjie HOU ; Tong FU ; Zichun HUA ; Jianping ZHANG ; Yingjian ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2014;34(4):312-316
Objective To synthesize 99Tcm-TP5-3 and evaluate its biodistribution and kinetics as a molecular probe for the detection of apoptosis,and evaluate tumor apoptosis after a single dose of paclitaxel chemotherapy in MDA-MB-231 breast tumor model.Methods TP5-3 was labeled with 99Tcm directly,and analyzed with HPLC.The radioactivity in tissues was measured and expressed as %ID/g and T/NT (tumor/muscle).The mice bearing MDA-MB-231 breast tumor were divided into two groups:the treatment group which was given a single dose of paclitaxel (40 mg· kg-1,via tail vein),and the control group which was injected with the same volume of normal saline.After therapy,99Tcm-TP5-3 was injected via tail vein in both groups (100 μ1 for each mouse).MicroSPECT/CT was performed at 3 h postinjection.Radioactivity in different tissues was determined after imaging.Apoptotic cells were measured with flow cytometry.The morphological changes of the apoptotic cells were observed by light microscopies.One-way analysis of variance,two-sample t test and linear correlation analysis were used to analyze the data.Results The radiolabeling efficiency was > 95% and the radiochemical purity of 99Tcm-TP5-3 was (96.0± 1.5)% at room temperature for 4 h.The predominant uptake was found in the kidneys at 30 min postinjection ((8.48± 1.07) %ID/g),with rapid tracer clearance from the circulation.By comparison with activity at 5 min postinjection ((13.74± 4.21) %ID/g),85% of the initial activity reduced in blood at 4 h ((2.07±0.35) %ID/g; F=11.310,P< 0.05).99Tcm-TP5-3 was mainly accumulated in the kidneys,liver and stomach,and excreted via the kidneys.T/NT in the treated group was 4.21±0.06,which was significantly higher than that of the control group (1.57±0.67; t =12.820,P<0.05).The radioactivity of tumor tissue in the treatment group was much higher than that in the control group (4.82±0.54) %ID/g vs (1.44±0.38) %ID/g,t=0.679,P<0.05).The tumor uptake of 99Tcm-TP5-3 in the treatment group positively correlated well with the apoptotic cells (r =0.985,P<0.05).Histopathology further confirmed that a large number of apoptosis had occurred in the tumor after paclitaxel treatment.Conclusion 99Tcm-TP5-3 appears to have potential to be a useful molecular probe for imaging tumor cell apoptosis.
4.Synergistic apoptotic effect of the combination of diosgenin and TRAIL on non-small-cell lung cancer cell line A549 evaluated with the Chou-Talalay method.
Yan HE ; Jishuang WANG ; Peng ZHANG ; Wenjing ZHANG ; Qilai HUANG ; Zichun HUA
Acta Pharmaceutica Sinica 2013;48(1):45-51
This study is to investigate the apoptotic induction effect of the combination of diosgenin and TNF-related apoptosis-inducing ligand (TRAIL) on non-small-cell lung cancer cell line A549 by using the Chou-Talalay method, and observe the mechanism of the combination. The apoptotic effect of diosgenin or TRAIL alone and their combination on A549 and normal cell line 293T proliferation was measured by MTT assay. Chou-Talalay method was used to evaluate the combination effect. Apoptosis was examined by Hoechst 33342 staining and flow cytometry assay. Western blotting detects the expression of apoptosis-associated proteins. Diosgenin or TRAIL alone can inhibit proliferation ofA549 in a concentration-dependent manner. According to the Chou-Talalay method, when f(a) = 0.1, CI > 1, when f(a) > 0.1, CI < 1. Combined with TRAIL, the IC50 of diosgenin decreases from 21.864 to 14.810 micromol x L(-1) (P < 0.05) on A549 cells. But for 293T cells, IC50 of diosgenin does not change significantly. As with Hoechst 33342 staining and flow cytometry assay, the apoptosis ratios also increased in the combination group. At protein expression level, combination-treated group displays increased Caspase-8, Caspase-9, Bid, Caspase-3 activation and PARP cleavage, significantly decreased Bcl-2 and increased Bax expression, and MAPK pathways were activated. The combination of diosgenin and TRAIL has synergistic effect on A549 cells.
5.Molecular Dynamics Simulation of Docking a Novel Hirudin-likeAnti-coagulant Protein to Thrombin
Yao FAN ; Jin WANG ; Shan YANG ; Xiang YANG ; Lina ZHANG ; Zichun HUA ; Dexu ZHU
Progress in Biochemistry and Biophysics 2001;28(1):86-89
Hirudin is one of the most potent anti-coagulant protein ever found, and its C-terminus is a key domain for inhibiting thrombin.In order to enhance its specificity,a novel anti-coagulant protein was constructed via fusing the C-terminus of hirudin to Annexin V, which was expected to sustain both anti coagulant activity and phorspholipid affinity. The structure of the designed protein was predicted with both molecular mechanics and dynamics. Molecular dynamics was adopted to simulate the docking interaction between the fusion protein and thrombin. The results showed the inhibitory activity of the fusion protein to thrombin.
6.Comparison of galE gene of Campylobacter jejuni strains associated Guillain-Barré syndrome
Xin LI ; Zhenzhong LI ; Xinli BAI ; Hui LIU ; Zichun ZHAO ; Weiwei LIU ; Baofeng FANG ; Hong WANG ; Yijie GUO ; Chunyan LI
Chinese Journal of Microbiology and Immunology 2009;29(6):555-558
Objective To investigate the Camtrylobacterjejuni's risk factors which were associated with the development of Guillain-Barre syndrome( GBS), the galE gene of C. jejuni strains were sequenced and the sequencing results were compared with other C. jejuni strains. Methods Selecting three GBS-asso-ciated C.jejuni strains isolated from stools of GBS patients who had been diagnosed as AMAN pattern by clin-ical and electrophysiological test from Hebei province, China. After sequencing galE gene, the results were spliced and assembled into a complete sequence by the terminals overlapped each other. The sequences of galE gene were compared with the corresponding sequences in GenBank to find the mutation and constructed the phylogenetic tree. Results The variation frequency of galE sequences of GBS-associated C. jejuni were higher than that of non-GBS-associated C. jejuni. The phylogenetic analysis demonstrated that each of the three C. jejuni strains was separately genetically closed to three strains which sequences have published in GenBank. The alignment with the related sequence of NCTC11168 shows that there are 4 same mutations in the galE gene of the three C. jejuni strains. The phylogenic tree reflected the regional feature of C. jejuni. Conclusion The probability of sequence variation of galE of GBS-associated C.jejuni is significantly higher than non-GBS-associated C. jejuni strains, the relation between the variation and GBS-pathogenesis remains to be further confirmed. The mutations found in the three C. jejuni strains established the foundation for ex-ploring the biologically characteristic of GBS-associated C. jejuni strains.
7. The application of superomedial pedicle combined with vertical incision for the treatment of female hypermastia with asymmetric
Zhengcai WANG ; Li CHEN ; Zichun GU ; Hua LI
Chinese Journal of Plastic Surgery 2019;35(3):232-236
Objective:
To evaluate the effect of vertical incision with superomedial pedicle for the treatment of female asymmetric hypermastia.
Methods:
The total of 31 patients with asymmetric breast hypertrophy were admitted from May 2012 to November 2018. All patients were female with an average age of 37.8 (28-55) years. Mammoplasty was performed by vertical incision with superomedial pedicle. According to the preoperative design, the epidermis of the pedicle, the excess skin and glandular tissue were removed. The superomedial pedicle was rotated upward and to be fixed on the major pectoralis fascia. After the fixation of the nipple areola, the incision was closed.
Results:
The mean follow up was (8.4±3.0) months, with a range from 6 to 18 months.One patient was unsatisfied with scar hyperplasia. One patient had slight mastoptosis 6 months after operation and received favorable outcome after revision. The rest of 29 patients had satisfactory results.
Conclusions
For patients with asymmetric breast hypertrophy, the new location of nipples on both sides should be determined by the degree of mastoptosis and hypermastia. So that, symmetry breast as well as smaller breast can be obtained.
8. Mechanism of promoted neovascularization by SVF after fat grafting
Zhengcai WANG ; Jingjing MA ; Zichun GU ; Wenjia SUN ; Li CHEN ; Hua LI
Chinese Journal of Plastic Surgery 2019;35(8):814-818
Stromal vascular fraction(SVF)are the remaining cells after removing mature fat cells in the adipose tissue. Containing a certain amount of adipose derived stem cells(ADSCs), SVF also includes many other cells, which may have the potential of promoting angiogenesis. In this review, the role of SVF in angiogenesis after fat transplantation was summarized by intensive reading relative literature in recent years. The result is that angiogenesis and fat graft revascularization are regulated by various factors: SVF promotes secretion of a diverse array of cytokines and growth which are capable of stabilizing endothelium vascular network. ADSCs have the potential of differentiating into smooth muscle cells and endothelial cells which can coroperate to form new blood vessels.
9.Clinical analysis of nonsyndromic oligodontia phenotypes
Lihong SHU ; Zichun TANG ; Haixia WANG ; Li CAO ; Hu LI
West China Journal of Stomatology 2024;42(1):89-96
Objective To provide references,this study investigated the clinical characteristics of patients with non-syndromic oligodontia.Methods The information of 178 patients with oligodontia was collected,including histories,oral examinations,and panoramic radiographs.Tooth agenesis characteristics were calculated and evaluated.All the data were statistically analyzed with SPSS 24.0 software.Results No significant difference in the number of missing teeth was found between sexes nor between the right and left sides,and congenitally missing teeth affected the maxillary arch(P<0.05).The highest prevalence of tooth agenesis was observed in the mandibular second premolars.In the maxillary arch,the most common pattern of tooth agenesis was agenesis of the bilateral first and second premolars.The agenesis of the bilateral second premolars was observed in the mandibular arch.The prevalence of a symmetric pattern between the right and left quadrants was significantly higher than that of matched patterns between the maxillary and mandibular an-tagonistic quadrants.Approximately 16.85%of patients with nonsyndromic oligodontia were affected by other tooth-re-lated anomalies.Conclusion The common patterns of tooth agenesis were successfully identified in patients with non-syndromic oligodontia.Dentists need to provide multidisciplinary treatments for patients with nonsyndromic oligodontia because of variations in occluding and full-mouth tooth agenesis patterns.
10.Diffusion kurtosis imaging in assessment of structural brain network topology alteration and microstructural damage in patients with multiple sclerosis
Zichun YAN ; Shuang DING ; Zhuowei SHI ; Qiyuan ZHU ; Feiyue YIN ; Xiaohua WANG ; Zeyun TAN ; Yongmei LI
Chinese Journal of Radiology 2023;57(11):1222-1230
Objective:To investigate the changes in structural brain network topology and microstructural damage in patients with multiple sclerosis (MS), and to analyze its correlation with cognitive function.Methods:Clinical and imaging data of 114 patients with MS (MS group) diagnosed in the First Affiliated Hospital of Chongqing Medical University from May 2021 to September 2022 were analyzed retrospectively. In addition, 71 volunteers were recruited as a healthy control group (HC group) during the same period. All subjects were performed on cognitive assessment and 3D-T 1 magnetization-prepared rapid gradient echo, 3D-fluid-attenuated inversion recovery, and diffusion kurtosis imaging (DKI) scans. GRETNA software was used to obtain network topology attributes, and global attributes included global efficiency, local efficiency, and small-world attributes [clustering coefficient(Cp), shortest path length(Lp), normalized Cp(γ), normalized Lp, and small-world index (σ)]. Local attributes included betweenness centrality (BC), degree centrality (DC), nodal clustering coefficient (NCp), nodal efficiency, nodal local efficiency (NLe) and nodal shortest path length. The DKI parameter map generated by the post-processing software was used to extract the DKI parameter values of the brain region with abnormal local topology of the brain structure network. The differences of global attributes, local attributes and DKI parameter values [kurtosis fractional anisotropy (KFA), mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) values] were analyzed by independent sample t-test or Mann-Whitney U test, and corrected by false discovery rate (FDR). Spearman or Pearson correlation analysis was used to evaluate the correlation between abnormal brain structure network topology attributes and cognitive scale scores in the MS group. Results:Both the MS group and the HC group structure network showed small-world attributes, and the γ and σ values of the MS group were significantly lower than those in the HC group (FDR correction, P<0.05). Compared with the HC group, BC, DC, NCp and NLe broadly reduced in the MS group, mainly involving in bilateral frontal, temporal, precuneus, amygdala, and thalamus (FDR correction, P<0.05). After FDR correction, compared with the HC group, the KFA, MK, RK and AK values of 23 brain regions with abnormal local attributes of the network in the MS group were significantly changed in several brain regions (FDR correction, P<0.05). The correlation analysis showed, after FDR correction, the DC value of the right putamen in MS patients was positively correlated with the digit span test (DST) scores ( r=0.318 ,P=0.001). Conclusion:There are extensive changes in the structural brain network of MS patients, accompanied by varying degrees of microstructural damage, and the reduction of degree centrality in the basal ganglia putamen region is associated with cognitive impairment.