1.Radiosensitization of C225 on human non-small cell lung cancer cell Hne H-520
Yingdong ZHANG ; Junjie WANG ; Feng LI ; Yong ZHAO
Chinese Journal of Radiation Oncology 2008;17(4):289-292
Objective To investigate the efficacy of C225(cetuximab),a chimeric human-mouse anti-epithelial growth factor receptor monoclonal antibody.combined with 60Co gamma irradiation against humall non-small cell lung cancer cell line H-520. Methods H-520 cells were treated either with different dose of 60Co irradiation(1,2,4,6,8 and 10 Gy)alone or together with C225(100 nmol/L).Colony forming capacity was determined to create the survival curve 10 days after the treatment.Cells in different groups were harvested 72 hours after irradiation for apoptosis analysis or 48 hours after irradiation for cell cycle analysis by flow cytometry assay. Results The clone number in combinational treatment group was less than that in irradiation only group,which suggested that the cell survival rate in the combinational treatment group was significantly decreased comparing with irradiation only group(F=6.36,P<0.05).The sensitizing enhance rate(SER)was 1.35.The percentage of apoptotic H-520 cells was 5.56%±0.62%,13.86%±0.80%,25.36%±1.02%and 29.89%±2.09%,respectively in 0,2,4 and 8 Gy irradiation alone groups,which were significantly lower than 13.75%±0.83%.25.12%±1.60%.46.12%±2.60%and 50.5l%±4.06%.respectively in irradiation combined with C225 treatment groups(F=4.72,P<0.05).The cellcycle analysis showed that cells arrested in G0+G1 phases for C225 treatment,in G2+M phases for 60Co irradiation,and in both G0+G1 and G2+M phases for C225 in combination with 60Co irradiation. Conclusions C225 has radiosensitizing effects on H-520 cells.which may through the enhancement of 60Co irradiation-induced cell death and cell cycle arrest.This study provides a supportive evidence for clinical treatment in non-small cell lung cancer.
2.The influence of CYP4F2(rs2108622)gene polymorphism on the warfarin dose in old patients
Mingjuan TAN ; Weiwei CUI ; Feng CHEN ; Yanping MEI ; Yingdong GAO
International Journal of Laboratory Medicine 2014;(11):1400-1401,1404
Objective To observe the effect of CYP4F2(rs2108622)polymorphism on the dose of warfarin in old patients(65 to 75 years old)who were treated with atrial fibrillation.Methods Sixty cases of old patients with atrial fibrillation were enrolled in the study.All the subjects had taken warfarin for 3 months,and the international normalized ratio(INR)maintained between 1.6 and 2.5.And the CYP4F2(rs2108622)variant were detected by PCR.Results The patients with CYP4F2(rs2108622)allele C/C scored significantly lower warfarin dose than patients with variant allele C/T and T/T (P < 0.05 ).Conclusion CYP4F2 (rs2108622)gene polymorphism have been related with warfarin dose in old patients.
3.Radiosensitization of recombinant human endostatin in human lung squamous cancer cells in vitro
Zhenyu YOU ; Junjie WANG ; Yong ZHAO ; Hongqing ZHUANG ; Feng LIU ; Yingdong ZHANG
Chinese Journal of Radiation Oncology 2009;18(4):326-329
Objective To investigate the radiosensitising effect of recombinant human endostatin (endostar) on human lung squamous cancer cell line H-520 in vitro and its mechanism. Methods H-520 cells in exponential growing phase were treated with endostar alone, irradiation alone, or endostar plus irra-diation. Colony-forming assay was used to investigate the cytotoxicity and radiosensitising effects of endostar. Cell survival fractions of all groups were calculated and cell survival curves were fitted by single-hit multi-tar-get model. Cell apoptosis, cell cycle distribution and activated Caspase expression level were investigated by flow cytometry. Results The D0, Dq, D10 and SF2 values of combined treatment group were much lower than those of irradiation alone group. The sensitization enhancement ratio (SER) was 1.50 (ratio of D0 values). Endnstar induced H-520 cell apoptosis in a dose dependant manner. After administration of endostar, H-520 cell proliferation was inhibited, and cell apoptosis rate and apoptotic bodies were increased. After irradiation of 0 Gy, 2 Gy, 4 Gy and 8 Gy, the apoptosis rate of H-520 cells was 4.27% ±0.29%, 14.3% ±1.15%, 28.49% ± 1.58% and 54.79% ± 1.89% in the radiotherapy alone group, and 22.38% ± 1.61%, 35.01% ±1.16%, 46.83%±2.06% and 64.08%±4.28% in the combined treatment group, respective-ly. The difference between the two groups was significant (t = 19.17, 17.79, 25.64 and 3.44,all P < 0.05 ). Flow cytometric analysis showed that cell cycle distribution changed and G0 + G1 phase arrest oc-curred after endostar treatment, while irradiation induced G2 + M arrest. The expression level of activated Caspase in combination group (62.7% ±1.9% ) was higher compared to the control group ( 12.1%± 0. 1% ) , endostar alone group ( 54.6% ±1.0% ) and irradiation alone group ( 34.1%±1.2% ) ( t = 46.69, 6.55 and 22.54 ; all P < 0.05 ). Conclusion Endostar can enhance the radiosensitivity of H-520 ceils by inhibiting cell proliferation, promoting cell apoptosis and facilitating cell cycle redistribution.
4.Effects of intensive blood pressure lowering on the early reperfusion and prognosis after intravenous thrombolysis in patients with acute ischemic stroke
Yuqiao ZHANG ; Junshan ZHOU ; Yingdong ZHANG ; Nihong CHEN ; Feng ZHOU ; Jie YANG ; Meng WANG ; Jiankang HOU
Chinese Journal of Neurology 2017;50(5):348-353
Objective To compare the effects of intensive blood pressure (BP) lowering and guideline-recommended standard BP lowering on the early reperfusion and prognosis after intravenous thrombolysis in patients with acute ischemic stroke. Methods This is a randomised controlled trial consisting of 118 consecutive patients who came from Department of Neurology, Nanjing First Hospital from July 2012 to April 2016, accepting intravenous recombinant tissue plasminogen activator thrombolysis with the systolic blood pressure (SBP) being 150-185 mmHg(1 mmHg=0.133 kPa). The patients with ischemic stroke were diagnosed by multi-mode MRI and confirmed to have ischemic penumbra. The SBP of patients randomly assigned to intensive BP lowering group and guideline BP lowering group was maintained in 140-150 mmHg or below 180 mmHg respectively for 72 h and all patients needed to reexamine multi-mode MRI at 24 h. The primary endpoints were the neurologic function at early stage, modified Rankin Scale (mRS) score and the mortality at 90 d;the secondary endpoints were the volume of infarction and hypoperfusion area, the rate of reperfusion, hemorrhagic transformation (HT) and syptomatic intracerebral hemorrhage (sICH). Results Forty-nine cases in intensive BP lowering group and 56 cases in guideline BP lowering group acquired the available images. The volume of infarction was increased both in these two groups, and there was no statistically significant difference in the increased values ((13.21±9.51) cm3 vs (12.95±9.68) cm3). There were no statistically significant differences in the volume of hypoperfusion, reperfusion rate, neurologic function at early stage, the mRS scores and mortality at 90 d, the incidence of sICH except the rate of HT (9.4%, 5/53 vs 23.1%, 15/65, χ2=3.860, P=0.049) between the two groups.Conclusion Early intensive BP-lowering treatment has no adverse effects on the transformation of ischemic penumbra and prognosis after intravenous thrombolysis in patients with acute ischemic stroke and may decrease the the rate of HT in some degree.
5.Anatomical study of plate invention for acetabular anterior column and baffle plate for acetabular quadrilateral body
Huiwen CHEN ; Zhengzhen ZHOU ; Chaojun WANG ; Rui ZUO ; Chunyun GUO ; Feng HUANG ; Yingdong FENG ; Bo WEI ; Zhen KONG ; Siling CHANG ; Yongjian SUN
Chinese Journal of Tissue Engineering Research 2017;21(11):1712-1717
BACKGROUND: It remains poorly understood whether anterior column quadrilateral wing plate exists to solve intraoperative multiple plastic and quadrilateral in vivo shift for treating acetabular anterior column and acetabular quadrilateral body fractures.OBJECTIVE: To figure out the promising application on measurement of anatomical character parameters when designing acetabular anterior column and acetabular quadrilateral body using Mimics software. METHODS: 60 pelvic CT scan data were collected and three-dimensionally reconstructed by Mimics software. The following anatomical character parameters were measured, including the angle between plane of arcuate line of true pelvis and plane of quadrilateral surface, the four boundary lines of quadrilateral body, and the thickness of substance of bone in quadrilateral region. The projection curve on quadrilateral surface of acetabular margin and dangerous zone for screw placement were both drew. Above all, the study attempted to find out the proper safe entry point of quadrilateral screw and to measure their leaning inside angles.RESULTS AND CONCLUSION: (1) The angle between plane of arcuate line of true pelvis and plane of quadrilateral surface was not significantly different between males and females. (2) The minimum thickness of quadrilateral body in males was larger than that in females. (3) The maximum leaning angle flapper plate screw P1 and P2 for quadrilateral body was significantly smaller in males than in females, but that of screw P3 was not significantly different between males and females. (4) The application of Mimics software made it easier, more intuitive and more practical for the design or development of new plate for acetabular anterior column and acetabular quadrilateral body. The common points and difference between acetabular anterior column and acetabular quadrilateral body could be specifically described by the new anatomical character parameters, which are defined by bone surface features of pelvis.
6. Clinical value of complements detection in pregnancy related thrombotic microangiopathy
Chinese Journal of Laboratory Medicine 2019;42(12):986-989
Thrombotic microangiopathy (TMA) is an acute clinico-pathological syndrome with varied reasons. Pregnancy related-TMA includes pregnancy associated thrombotic thrombocytopenic purpura (TTP), postpartum hemolytic-uremic syndrome (pHUS), severe preeclampsia (SPE) and Hemolysis, Elevated Liver enzymes and Low Platelet syndrome (HELLP syndrome) and the outcomes are severe. Aberrant activation of complement system plays an important role in the pathogenesis of these diseases. Although these diseases have similar clinical appearance, their pathogenesis, diagnostic and therapeutic methods are different. Precision diagnosis of these diseases to select targeted treatment will greatly improve the prognosis of these patients. Herein, the value of complement system components in the diagnosis and treatment of pregnancy-related TMA are introduced.
7.Effect of implantation pathological assessment on the early stage function of renal grafts from cardiac death donors
Lei LIU ; Xinlu PANG ; Wenjun SHANG ; Yingdong ZHAO ; Zhigang WANG ; Hongchang XIE ; Yonghua FENG ; Guiwen FENG
Chinese Journal of Organ Transplantation 2017;38(10):607-613
Objective To explore the morphological changes of renal grafts in implantation protocal biopsy,and early stage effect of lesions from donation after cardiac death (DCD) donors.Methods Preimplantation kidney biopsy from 48 cases of DCD donors from August 2016 to March 2017 was retrospectively reviewed.Protocal biopsy was performed on dual kidneys and evaluated according to Banff 2016 donor criteria before transplantation.The Banff score of kidneys was calculated and its effects on renal function were evaluated.Results There were 48 donors and 95 kidneys (there was one kidney with congenital renal indevelopment).In.one case,diffused thrombus in arteriae arcuata occurred on the left side (normal on the right side),and the left kidney was discarded.In one case,diffused arteriolar hyaline (ah3) occurred on the left side (normal on the right side),and the left kidney was discarded.Severe interstitial fibrosis (>70%) was seen in one pair of kidneys,and the kidneys were discarded.The proportion of glomerulosclerosis (GS) was >30% in one pair of kidneys,and the kidneys were discarded.There was no statistically significant difference in morphometric changes between left kidney group and right kidney group (P>0.05).Besides GS,the morbidity of interstitial fibrosis (ci) was 17%,that of tubular atrophy (ct) was 16%,that of interstitial inflammation (i) was 13%,that of fibrous intimal thickening (cv) was 19%,that of arteriolar hyaline changes (ah) was 28%,that of glomerolar thrombi (gt) was 0%,and that of acute kidney injury (AKI) was 81 %.Glomerular filtration rate (eGFR) estimated was compared between ah >2 group and ah≤2 group.eGFR in ah>2 group was significantly higher in 16 days,one month and three months,but not in 7 days.Terminal blood serum creatinine (t-Scr) in ah>2 group in three months was significantly higher than that in ah≤2 group (152.5 ± 47.38 vs.122.08 ± 36.57 μmol/L,P<0.05).The eGFR was compared between Banff score >3 group and Banff score ≤3 group.The eGFR in ah>2 group was significantly higher in one month and three months,but not in 7 days and 16 days.t-Scr in Banff score >3 group was higher significantly than in Banff score ≤3 group (146.18-± 44.55 vs.115.27 ± 30.67 μmol/L,P<0.05).Seven patients were diagnosed as having delayed graft function (DGF),there were 2 patients with ah>2 and Banff score>3,and 1 patient with primary non-function (PNF).Conclusion Vasculopathy and acute renal tubular injury were most common lesions in donor renal pathology.Kidneys with diffused arteriolar hyaline change (ah>2) or Banff score >3 have poor graft function at 3rd month.
8.Automated radiolabeling and in vivo evaluation of 18F-FDOPA
Zhenyu ZHAO ; Siwei ZHANG ; Pengjun ZHANG ; Zhiming JIN ; Yingdong ZHANG ; Feng WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(6):408-411
Objective To synthesize 18F-fluoro-L-3,4-dihydroxyphenylalanine (18 F-FDOPA) and evaluate its biodistribution and kinetics in mice,in order to explore its feasibility for insulinoma detection.Methods 18F-FDOPA was synthesized by a three-step nucleophilic reaction.Radiolabeling yield,radiochemical purity and stability in vitro were analyzed.Normal mice were scarified at 2,5,15,30,60 and 120 min postinjection to measure radioactive counts in main organs.Biodistribution and kinetics were evaluated by dynamic microPET in normal mice.The insulinoma tumor (INS-1) model was established and dynamic microPET was performed immediately after intravenous injection and stopped at 60 min.Region of interest (ROI) was drawn to access time-activity curve (TAC) in main organs and insulinoma.Results 18F-FDOPA was prepared with radiochemical yield of (11.0±0.4) %,radiochemical purity of (99.3±0.2)%.The radiochemical purity was still >99% after being stored for 120 min at room temperature.Predominant uptake of 18F-FDOPA was in the kidneys,and was cleared rapidly in blood.Pancreas showed stable uptake from 20 to 50 min,which was (5.98±0.71) percentage activity of injection dose per gram of tissue (% ID/g) at 20 min and (4.62±0.47) %ID/g at 50 min postinjection,respectively.18 F-FDOPA showed high affinity to tumor tissue of insulinoma ((11.42±0.70) %ID/g) at 2 min.Conclusions 18F-FDOPA could be easily synthesized in short total reaction time with high radiochemical purity and stability.Early phase imaging of 18F-FDOPA may be helpful for insulinoma detection.
9.The role of intravenous thrombolysis in the endovascular treatment of acute anterior circulation vascular occlusive stroke
Feng ZHOU ; Hongchao SHI ; Min LU ; Wei WANG ; Jiankang HOU ; Yukai LIU ; Yingdong ZHANG ; Junshan ZHOU
Chinese Journal of Neurology 2019;52(6):472-477
Objective To investigate the effect and safety of intravenous thrombolytic therapy in the endovascular treatment of acute anterior circulation vascular occlusive stroke.Methods The clinical data of 226 patients with acute anterior circulation vascular occlusive stroke who underwent endovascular treatment in Nanjing First Hospital,Nanjing Medical University from May 2015 to May 2018 were retrospectively collected.According to whether or not intravenous thrombolysis was performed,the patients were classified into simple thrombectomy group (n=112) and bridging treatment group (n=114).The modified Thrombolysis in Cerebral Infarction Score (mTICI) was used to evaluate the vascular opening effect,and the blood vessel recanalization time,mTICI,the symptomatic intracranial hemorrhage rate,and the modified Rankin Scale (mRS) score at 90 days after surgery were evaluated.Results There were no statistically significant differences in gender,age,past history and National Institute of Health Stroke Scale score between the two groups (P>0.05).There was no statistically significant difference in door-to-recanalization time between the two groups (P>0.05).Excluding the patients with post-wake stroke and unexplained onset time,the simple thrombectomy group (n=63) and the bridging treatment group (n=1 11) showed statistically significant differences in onset-to-door time ((235.04± 182.64) min vs (102.48±60.51) min,t=7.01,P<0.01)and onset-to-recanalization time ((405.31 ± 148.89) min vs (337.31 ± 117.65) min,t=3.32,P=0.01).The difference in number of thrombectomy between the simple thrombolysis group (2.55± 1.52) and the bridging treatment group (2.11± 1.48) was statistically significant (t=2.246,P=0.026).The total reperfusion (mTICI 2b/3) rate was 89.8% (203/226),88.4% (99/112) in the simple thrombectomy group and 91.2% (104/114) in the bridging treatment group,with no statistically significant difference between the two groups (P>0.05).The differences in symptomatic intracranial hemorrhage rate (8.93% (10/112) vs 11.4% (13/114)),mortality rate (12.5% (12/112) vs 16.7% (19/114)) and 90-day good functional outcome (mRS score 0-2;54.5% (61/112) vs 55.8% (63/114)) between the two groups were not statistically significant (P>0.05).Conclusions In patients with acute anterior circulation vascular occlusive stroke undergoing endovascular treatment,intravenous thrombolysis can reduce the number of thrombectomy,not increase the door-to-recanalization time,the risk of symptomatic intracranial hemorrhage and mortality,and has similar good functional outcome as the simple thrombeetomy group.Therefore,intravenous thrombolysis is safe and effective for endovascular treatment of acute anterior circulation large vessel occlusive stroke.
10.Effect of intensive blood pressure control after successful endovascular therapy on outcomes in patients with anterior circulation stroke: a multicentre, open-label, blinded-endpoint, randomized controlled trial
Chengfang LIU ; Qiwen DENG ; Hongchao SHI ; Feng ZHOU ; Yukai LIU ; Meng WANG ; Qiaoyu ZHANG ; Bingqi ZHANG ; Min LI ; Lei PING ; Tao WANG ; Haicun SHI ; Wei WANG ; Jiankang HOU ; Shi HUANG ; Jinfeng LYU ; Rui SHEN ; Yingdong ZHANG ; Junshan ZHOU
International Journal of Cerebrovascular Diseases 2023;31(6):401-408
Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.