1.Influence and interaction of genetic polymorphisms in norepinephrine transporter and enviroment on antidepressant drug response
Zhi XU ; Zhijun ZHANG ; Yonggui YUAN ; Lei LI ; Tianyu WANG
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(4):310-314
Objective To determine how genetic polymorphisms in norepinephrine transporter (NET) gene influence the response of antidepressant treatment and how they interact with childhood trauma and recent life stress in a Chinese depressive patients.Methods 281 Chinese Han depressive patients received single antidepressant drugs for 6 weeks.Hamilton Depression Scale-17 (HAMD-17),the Childhood Trauma Questionnaire short term (CTQ-SF) and the Life Events Scale (LES) were used to evaluate severity of depressive symptoms and the occurrence of stressful life events respectively.Three single nucleotide polymorphisms (SNPs) in norepinephrine transporter were genotyped.Associations of single locus and haplotypes with antidepressant treatment response were analyzed using UNPHASED 3.0.13.The interaction of gene and life stress was analyzed by SPSS13.0 software.Results One NET SNP rs2242446 was significantly associated with antidepressant response in this Chinese male sample(0.4118vs0.2375,x2=7.046,P=0.0079,OR=0.445,95% CI (0.243-0.815)),as was the haplotype CG(rs2242446 and rs5569;x2 =5.886,P=0.0153,OR=0.457,95% CI (0.198-1.054)) and another haplotype CG-G(rs2242446,rs1532701 and rs5569;x2=5.360,P=0.0206,OR=0.530,95% CI (0.202-1.386)) of NET in male samples.The NET SNPs rs5569 demonstrated interaction with childhood trauma to influence antidepressant response(β=-2.727,SE =1.195,P=0.023,OR=0.065,95% CI (0.006-0.681)).Conclusion Antidepressant drug response was influenced by not only NET genetic polymorphisms in norepinephrine transporter gene but also interaction between the NET genetic polymorphisms and early life stress.
2.Transfection of embryonic stem cells with green fluorescent protein gene and their differentiation into neural cells
Zhi-yan, SHAN ; Jing-ling, SHEN ; Lei, LEI ; Yan-ning, XU ; Lian-hong, JIN
Chinese Journal of Endemiology 2008;27(4):397-400
Objective To establish embryonic stem cells (ESC) that can express green fluorescent protein (CFP) and differentiate them into neurons. It would provide tagging neurons for clinical transplantation to cure neural system diseases. Methods ESC (R1) was transfeeted with a plasmid containing the GFP by electroporation. A transgeuic cell line was obtained after selection with G418. The ESCs were characterized by AKP staining. Monolayer differentiation method was used to induce neural differentiation derived from GFP-ESC and immunofluorescence method was used to identify Tuj1 positive cells. Results There was no significant difference(X2=3.14,P0.05) in transfect rates between liposome and electroporation (65% vs 79%). The AKP staining of GFP-ESC was positive. GFP-ESC could be differentiated into neural cells. Conclusions These results show that ESC expressing GFP has been estabhshed, which can be differemiated into neurons.
3.3D-CT guided percutaneous radiofrequency ablation against advanced lung cancer: short term effect assessment
Mu HU ; Xiuyi ZHI ; Baodong LIU ; Donghong CHEN ; Qingsheng XU ; Yi ZHANG ; Lei SU ; Ruotian WANG ; Lei LIU
Cancer Research and Clinic 2010;22(1):26-28
Objective Under the guidance of CT and three dimensional reconstruction, we made therapeutic plan for lung cancer by radiofrequency ablation (RFA) and observed its effect. Methods From February 2007 to January 2009, we used RITA radiofrequency therapeutic equipment to treat lung cancer under the guidance of 64-slice spiral CT (Siemens) and three dimensional reconstruction of the image. The target temperature is 90℃. Results We performed 29 RFA on 25 patients. In the follow-up, 10 of them showed tumor shrinkage by CT scan. 23 showed lack of tumor-uptake value by SPECT scan and 2 showed lower tumor-uptake value. Conclusion CT-guided percutaneous RFA is safe and practical for lung cancer. It has satisfactory short-term effect to reduce tumor burden.
4.Clinical research on chemotherapy of recurrent and refractory non-Hodgkin lymphoma directed by ATP bioluminescence chemosensitivity assay in vitro
Lei YANG ; Zhu-chen SONG ; Xiao-hong XU ; Bin NG JIA ; Chun-lei PENG ; Jin-zhi WEI
Journal of Leukemia & Lymphoma 2011;20(10):590-593
ObjectiveTo investigate the clinical value of ATP bioluminescence tumor chemosensitivity assay (ATP-TCA) for recurrent and refractory non-Hodgkin lymphoma (NHL) specimens in vitro.Methods Thirty-four freshlytaken recurrent andrefractoryNHL specimens weretestedin vitro for cancer chemosensitivity by ATP-TCA.ResultsDrug sensitivity of NHL specimens had heterogeneity.Different drugs had different tumor growth inhibition ratio in vitro.Response rate (RR) of the patients receiving chemotherapy according to in vitro assay was 82.4 % (28/34),complete response rate (CR) was 52.9 % (18/34).In DICE group RR was 60.0 % (18/30),CR rate was 33.3 % (10/30).In GDP group RR was 62.3 % (33/53),CR rate was 26.4 % (14/53).In ATP-TCA group RR was significantly higher than those in DICE and GDP groups (x2 =3.93,P =0.047; x2 =3.98,P =0.046).ConclusionThe results of ATP-TCA assay are correlated well with clinical treatment responses.The assay may be an important and useful method for individual-based chemotherapy of cancers.
5.The influence of continuous venovenous hemofiltration on parameter measurement by the transpulmonary thermodilution technique
Zhiyong WANG ; Jun LI ; Yingzhi QIN ; Lei XU ; Jie ZHANG ; Yongle ZHI
Chinese Critical Care Medicine 2015;(10):831-835
ObjectiveTo evaluate the influence of continuous venovenous hemofiltration (CVVH) on measurement of transpulmonary thermodilution parameters.MethodsA prospective observational study was conducted. Fifty-six patients who received CVVH and hemodynamic monitoring at the same time admitted to the Department of Critical Care Medicine of Tianjin Third Central Hospital from July 2012 to July 2014 were enrolled. In all the patients, the dialysis catheter was inserted through the femoral vein, and transpulmonary thermodilution measurements were performed by pulse indicator continuous cardiac output (PiCCO) monitoring technology at the same time. Mean arterial pressure (MAP), central blood temperature, cardiac index (CI), global end-diastolic volume index (GEDVI), intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI) were measured before CVVH, immediately after CVVH, and 30 minutes after CVVH, respectively.Results In the 56 patients, there were 36 males and 20 females, (66±16) years of old, height of (172±6) cm, body weight of (68±10) kg. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) scores was 26±6. After CVVH,the central blood temperature was gradually decreased, and blood temperature at 30 minutes after CVVH was significantly lower than that before CVVH (℃: 37.17±1.06 vs. 37.57±1.26,P< 0.01). There were no significant changes in MAP and EVLWI before and after CVVH, the MAP was (89±20), (86±16), (90±17) mmHg (1 mmHg = 0.133 kPa) at three time points respectively, and EVLWI was (9.4±3.2), (9.3±3.0), (9.4±2.9) mL/kg, respectively. After CVVH, CI, GEDVI and ITBVI showed a gradual downward tendency. Compared with those before CVVH, the decline of CI, GEDVI, and ITBVI immediately after CVVH was not statistically significant [CI (mL·s-1·m-2): 62.18±24.34 vs. 63.85±21.84, GEDVI (mL/m2): 705±103 vs. 727±100, ITBVI (mL/m2): 881±129 vs. 908±125, allP> 0.05]. CI, GEDVI, ITBVI at 30 minutes after CVVH were significantly decreased [CI (mL·s-1·m-2): 57.84±20.50 vs. 63.85±21.84, GEDVI (mL/m2):681±106 vs. 727±100, ITBVI (mL/m2): 851±133 vs. 908±125, allP< 0.05]. CVVH was associated with a decline of 6.01 mL·s-1·m-2 at 30 minutes after CVVH [95% confidence interval (95%CI) = -10.67 to -1.50,P = 0.011]. The declines of GEDVI and ITBVI were observed with 46 mL/m2 (95%CI = -81 to - 11,P = 0.014), 57 mL/m2 (95%CI =-101 to - 13,P = 0.014 ) respectively 30 minutes after CVVH.Conclusions CVVH had no significant effect on the transpulmonary thermodilution measurements of CI, GEDVI, ITBVI and EVLWI. Thirty minutes after the start of CVVH, CI, GEDVI and ITBVI was decreased significantly, but had no effect on EVLWI.
6.Malignant transformation in mature teratoma of the ovary:a clinicopathologic study of 22 cases
Xudan YANG ; Lei WANG ; Xiaoqing WANG ; Jing FU ; Yisha LIU ; Xiaoxiao ZHANG ; Zhi LIAO ; Gang XU
Chinese Journal of Clinical and Experimental Pathology 2015;(1):19-23,28
Purpose To study the clinicopathological characteristics in 22 cases of ovarian mature teratoma with malignant transforma-tion. Methods Clinical and pathologic features were collected and analyzed in 22 out of 1 826 cases of ovarian mature teratoma by retrospective studies, together with immunohistochemical staining. Results In our study, 22 cases (1. 2%) of ovarian mature terato-ma with malignant transformation were identified. The median age was 56. 5 (range, 31~79) years. The main clinical manifestations were pelvic masses, including 13 cases in the left ovary, 8 cases in the right, 1 case was bilateral. Gross cystic teratoma were saw in 19 cases, 3 cases of cystic and solid, the bilateral one was solid in the left which the right was cystic. The teratomas size were 5. 0~30 cm with average 12. 4 cm in diameter. The malignant components’ maximum diameter was about 1. 0~10. 0 cm with average 3. 7 cm. Microscopicically, there were poorly differentiated squamous cell carcinoma in 14 cases, carcinoid carcinoma in 4 cases, adeno-carcinoma in 2 cases, papillary thyroid carcinoma in 2 cases, and the last one was sarcomatoid carcinoma. The FIGO stage distribution was as follows:16 were stage IA, 1 was stage IB, 1 was stage IIA, 4 were stage IIB. Follow up showed 6 cases recurrened, 2 patients died, the rest are survival. Conclusions A low incidence of ovarian mature teratoma in somatic cells with malignant transformation, which are common in postmenopausal women and present with pelvic mass. The main malignant components is squamous cell carcino-ma, patients of stage I have better prognosis. Both clinic and pathology should take more attention to the comprehensive examination and diagnosis of teratoma for prevent misdiagnosis.
7.Effects on HepG2 cells growth of the different domains of genotype 1b hepatitis C virus core proteins
Xuebing YAN ; Lei MEI ; Zhi CHEN ; Min ZHEN ; Linfu ZHOU ; Xiaoyan XU ; Wei WU
Chinese Journal of Microbiology and Immunology 2008;28(5):411-415
Objective To study the function of core protein (CORE) of genotype 1b hepatitis C virus (HCV) of different strains (T: derived from tumor tissues; NT: derived from non-tumor tissues; C191: HCV-J6) and different domains (1-172, 1-126, 1-58, 59-126, 127-172 AA) of T CORE in the pathogenesis of HCV infection and to find the therapy target. Methods Different truncated genotype 1b HCV CORE eukaryotic expression plasmids (T, NT, C191) and different domains of T CORE were constructed and transfected to HepG2 cells. Cell apoptosis and necrosis were quantified by flow cytometry. Cell growth curves were observed with real time cell growth instrument. Results COREs from different strains of genotype 1b and different domains of CORE induced cell apoptosis and necrosis, and inhibited HepG2 cell growth at different levels. CORE derived from T induced apoptosis and necrosis and inhibited cell growth higher than that derived NT and C191. N terminal 1-58 AA of CORE derived from T induced cell apoptosis and necrosis and inhibited cell growth higher than any other domains. Conclusion COREs from different strains of genotype 1b HCV and different domains of CORE from the same HCV strain play different roles in their molecular pathogenesis of HCV. Among different domains of CORE, N terminal 1-58 AA might play an important role in its pathogenesis and be one target of gene therapy.
8.miR-27a rs895819 and lnc-LRFN2-2 rs61516247 polymorphism could increase risk of kidney transplantation rejection
Bengang WANG ; Zhi LYU ; Qian XU ; Liping SUN ; Lei YANG ; Hao LIU ; Yongfeng LIU
Chinese Journal of Organ Transplantation 2016;37(12):726-730
Objective To explore whether polymorphisms in non-coding RNA has potential as biomarkers for predicting the risk of kidney transplantation rejection.Methods A total of 79 patients who had received kidney transplants were recruited from the First Affiliated Hospital of China Medical University and divided into the rejection group (n =26) and non-rejection group (n =53).Four polymorphisms in miRNA and 8 polymorphisms in lncRNA were detected by MALDI-TOF-MS.Results When compared with the wild genotype,the mutation genotype in miR-27a rs895819 and lnc-LRFN2-2 rs61516247 had 11.72 and 4.87 folds increased risk of kidney transplantation rejection (P =0.046,OR=1.04-131.74 and P =0.047,95% CI =1.02-23.21,respectively).The other three polymorphisms in miRNA and 7 polymorphisms in lncRNA showed no significant associations with transplantation rejection risk (P > 0.05).Conclusion The miR-27a rs895819 and lnc-LRFN2-2 rs61516247 polymorphisms were associated with the risk of kidney transplantation rejection.
9.Assessment of fluid volume in critically ill patients with extravascular lung water index
Jun LI ; Yongle ZHI ; Yingzhi QIN ; Zhiyong WANG ; Dan WANG ; Lei XU ; Xingjing GAO
Chinese Critical Care Medicine 2015;27(1):33-37
Objective To examine the effect of rapid infusion test guided by extravascular lung water index (EVLWI) on hemodynamics in critically ill patients at different states in order to guide volume resuscitation.Methods A prospective observation was conducted.Forty critically ill patients admitted to Department of Critical Care Medicine of Tianjin Third Central Hospital from June 2012 to April 2014 were enrolled.Based on the levels of EVLWI and pulmonary vascular permeability index (PVPI) and the cardiac function,the patients were divided into four groups:septic patients with normal EVLWI and PVPI (n =17),septic patients with increased EVLWI and PVPI (n =3),septic patients with increased EVLWI and normal PVPI (n =4),and coronary heart disease and heart failure patients with normal EVLWI and PVPI (n =16).The rapid infusion test was conducted in all patients using lactated Ringer solution 250 mL,followed by infusion of crystalloid with rate of 150 mL/h.The conditions of mechanical ventilation and vasoactive drugs were not changed during study.The changes in EVLWI,intrathoracic blood volume index (ITBVI),and cardiac index (CI) before capacity load,at immediate capacity load,and 15,45,105 minutes after load were determined by pulse indicator continuous cardiac output (PiCCO).On the base of volume status before and after the liquid infusion,the standard for the changes were:stroke volume (SV) increased by 12%-15%,central venous pressure (CVP) greater ≥ 2 mmHg (1 mmHg =0.133 kPa),CI > 15%,and ITBVI change greater than 10%.Results There were no statistically significant differences in the observed indicators at the each time point before and after rapid infusion test among the four groups (all P > 0.05).In septic patients with normal EVLWI and PVPI group,ITBVI was slightly increased by 5.4%-9.7% from 15 minutes to 45 minutes after rapid infusion test.In coronary heart disease and heart failure patients with normal EVLWI and PVPI group,the EVLWI was increased by 11.9%,5.9%,and 14.7% respectirely at 15,45,and 105 minutes,ITBVI was slightly increased by 6.4% at 45 minutes,CI was increased by 29.5% immediately after rapid infusion.In septic patients with increased EVLWI and PVPI group,CVP was increased by 8 mmHg immediately,EVLWI was increased significantly by 15.8% at 45 minutes,ITBVI was slightly decreased by 10.0% at 45 minutes,CI was increased by 24.7% immediately,and increased by 17.0% at 105 minutes,and PVPI was increased by 15.6%-28.1% at 15-105 minutes after rapid infusion.In septic patients with increased EVLWI and normal PVPI group,CVP was increased by 1.5 mmHg at 15 minutes,EVLWI was increased immediately,which was increased by 17.4%,24.0%,and 31.4% respectively at 15,45,and 105 minutes,ITBVI was increased by 13.9% at 15 minutes,CI was increased by 16.1% at 15 minutes after rapid fluid infusion.Conclusions Rapid fluid replacement in critically ill patients with crystalloid,regardless of whether the EVLWI was normal or increased,the short-term response was affected by the volume and cardiac function of patients.Different status of patients showed different volume effect curve:no significant changes in hemodynamic parameters were found in patients with normal EVLWI and volume parameters.In patients with potential cardiac dysfunction,CI and EVLWI increased significantly; regardless of PVPI increased or normal,EVLWI and CI were increased in patients with elevated EVLWI; two different changes could be found in the two types of pulmonary edema while ITBVI was increased.
10.Cloning and Expression of Esterase Gene to Enantioselective Resolution of (S)-Ketoprofen in NK13
Li-Juan XU ; Zhi-Lei TAN ; Gang LIU ; Long MENG ; Jin-Hong ZHANG ;
China Biotechnology 2006;0(02):-
A strain NK13 was screened for a certain extent asymmetric hydrolyze the rac-ketoprofen chloroethyl ester and identified as Bacillus megaterium. For the preparation of gene libraries, a positive clones was obtained from the tributyrin flat. The sequence of this esterase gene had been analysised, and contained the whole ORF of an esterase gene with the length of 933bp. The esterase gene of NK13 was compared with the esterase genes of GenBank and the result showed that the esterase gene of NK13 was a novel gene(GenBank accession nember DQ196347).The new esterase gene was inserted into the plasmid pET21b+, then the recombinant plasmid transformed E.coli BL21. After being induced by IPTG, it was expressed in the host strain. SDS-PAGE analysis showed that the relative molecular mass of the esterase was about 34kDa. The result of TLC and HPLC showed that the recombinant strain had higher conversion ration than templet strain. 47.4%of the rac-ketoprofen Chloroethl ester was hydrolyzed to ketoprofen by the recombinant strain in 45min. The (S)- ketoprofen enantiomeric excess, in the later,was 55.46%, which indicated that the esterase could hydrolyze (S)-ketoprofen chloroethyl ester firstly.