1.Advances of omics analysis technology in precise diagnosis and treatment of tumor: from single level analysis to multi-omics integrative approaches
RAN Bingbing ; LIANG Nan ; SUN Hui
Chinese Journal of Cancer Biotherapy 2019;26(12):1297-1304
Tumor is a complex systemic disease, involving abnormalities at multiple levels, such as DNA, RNA, protein and metabolite. According to the central rule, the derived omics methods are genomics, transcriptomics, proteomics and metabonomics. In the past few decades, there have been remarkable achievements in the single omics study of tumor, but the exact mechanism of tumor development is still unclear. In order to reveal the process of tumorigenesis and development in a more systematic way, the research of multiomics came into being, which promoted the transformation of tumor research paradigm from single parameter model to multi parameter system model. The integration of multi-omics methods is expected to clarify the mechanism of tumor occurrence and development, find biomarkers with diagnostic, prognostic and predictive performance, explore new treatment targets, and finally achieve predictive, preventive, and personalized medicine (PPPM). This paper reviews the research methods and progress of different omics techniques in tumor research, especially emphasizes the importance and scientific value of the integration of multiple omics techniques in tumor research and clinical related results.
2.Research of exogenous HMGB1 regulate autophagy in peripheral blood monon-uclear cells of systemic lupus erythematosus
Bingbing FU ; Xiaopeng SUN ; Yinhuan ZHAO
Chinese Journal of Immunology 2014;(7):942-945,949
Objective:To stimulate the PBMCs of systemic lupus erythematosus patients with recombinant human high mobility group box1 (HMGB1) protein,observe the effect of HMGB1 on the expression of LC3Ⅱ/Ⅰ protein in active lupus nephritis and inactive lupus nephritis patients.Evaluate the effect of recombinant human high mobility group box 1 ( HMGB1 ) on the proliferation of PBMCs in patients with SLE.Methods:Western blot was used to detect the expression of LC 3II/I protein in PBMCs of active lupus ne-phritis and inactive lupus nephritis patients after stimulated by 1 μg/ml HMGB1 for 0,6,24 and 48 h.CCK-8 assay was used to detect the effects of PBMCs proliferation in patients with SLE after 1 μg/ml HMGB1 stimulation 72 hours.The statistical software SPSS17.0 was used to analyzed the results.Results: Western bolt showed an increasing expression of LC 3Ⅱ/Ⅰ protein in SLE patients after stimulated by HMGB1 ( P<0.05 ) , and this effect was time dependent.Compared with inactive lupus nephritis group , the increasing level of autophagy in active lupus nephritis group was more obviously.1 μg/ml HMGB1 could inhibit the proliferation of PBMCs in patients of SLE significantly ( P<0.001 ).Conclusion: HMGB1 may promote autophagy in SLE especially patients with active lupus nephritis and involved in the pathogenesis of SLE and lupus nephritis.Monoclonal antibodies targeting to HMGB 1 or modulators of mam-malian autophagy may provide new way for the treatment of SLE especially LN.
3.Analysis of cancer screening of 2013-2014 in Heilongjiang province
Huixin SUN ; Wangyang CHEN ; Bingbing SONG
Practical Oncology Journal 2015;(4):315-318
Objective To evaluate results of cancer early detection and early treated project screening and experience in Heilongjiang province from 2013 to 2014.Methods In Harbin and Daqing city resident popu-lation ,high-risk groups were screened through the risk factors questionnaire and screened corresponding clinical examine,respectively(lung cancer,liver cancer,breast cancer,upper gastrointestinal cancer and colorectal canc-er) .To explore cancer preventive effect of early detection and early treated in Heilongjiang province.Results We smoothly completed the cancer early detection and early treatment between 2013—2014 in Heilongjiang prov-ince,a total of 15628 people received a copy of risk factors questionnaire,10299 people in high-risk groups re-ceived clinical screening.A total of 66 cases of suspected cancer cases were screened.Conclusion completed Cancer early detection and early treatment are performed in Heilongjiang province between 2013—2014.Early de-tection can be treated early project for early discovery,early diagnosis and early treatment.It is important to im-prove the quality of screening survival time and survival of patients′.The project also promotes the early diagrosis and early treatment experience in Heilongjiang province.
4.Clinical evaluation of rotational atherectomy combining drug-eluting stents in severe coronary artery calcified lesions
Bingbing ZHAO ; Tao LI ; Gang TIAN ; Zhonghua SUN
Chinese Journal of Interventional Cardiology 2017;25(3):158-162
Objective Clinical data of patients who received rotational atherectomy (RA) combined with drug-eluting stent implantation (DES) in TEDA International Cardiovascular Hospital were retrospectively analyzed to evaluate it's safety,short-term and long-term prognosis.Methods A total of 60 patients who underwent RA were consecutively enrolled in the study in TEDA International Cardiovascular Hospital from September 2012 to September 2015.Pre and post procedure coronary angiography and clinical information were collected.Long term outcomes were obtained by outpatient clinical follow-up or telephone interview.We analysed angiographic data.Results Among 60 patients with 65 lesions,RA combined with drug-eluting stent implantation was successful performed in 62(95.3%) lesions and postoperative stenosis degree drop from (90.7±6.2)% to (19.5±6.6)%.4 cases(6.7%)developed complications and were treated accordingly during procedure with satisfactory results.Overall incidence of in-hospital MACCE was 1.7% with one case (1.7%) of myocardial infarction.The mean follow-up time was (23.3±10.6) months.In stent restenosis occurred in 1 case(1.7%) 10 months after operation.Stent thrombosis occurred in 1 case(1.7%) 16 months after operation and myocardial infarction (MI) occurred in 1 case(1.7%) 7 months after operation.One patient died 14 months after operation and another patient died 17 months after operation.Both of them were considered as cardiac death.There was no mortality of other causes recorded.Long-term MACCE was 9.5% and TLR is 5.1%.Conclusions Rotational atherectomy combined with DES implantation in the treatment of severe coronary artery calcification lesions has high success rate, good safety profile and good short and long-term prognosis.
5.Relationship Between 1h, 2h Post-load Blood Glucose Elevation and Carotid Intima-media Thickness in Healthy Population
Bingbing SUN ; Yulan ZHAO ; Jing DONG ; Yaping HUANG
Chinese Circulation Journal 2015;(12):1200-1203
Objective: To observe the relationship between 1h, 2h post-load plasma glucose (PG) elevation and carotid intima-media thickness (CIMT) in healthy population.
Methods: The healthy subjects from normal physical examinations in our hospital from 2013-09 to 2015-05 were selected and oral glucose tolerance test (OGTT) was conducted in them, plasma levels of fasting glucose (FPG), 1hPG and 2hPG were monitored. Finally, 482 subjects with normal fasting glucose, without diabetes were enrolled and divided into 4 groups:①Normal glucose tolerance (NGT) group,n=201,②1hHPG group, the subjects with 1h post-load high and 2h post-load normal glucose,n=83,③2hHPG group, the subjects with 1h post-load normal and 2h post-load high glucose,n=101 and④1hHPG/2hHPG group,n=97. The gender, age, BMI, blood pressure and lipid levels in all subjects were recorded, CIMT was evaluated by Doppler ultrasound; the relationship between 1hHPG, 2hHPG and CIMT were analyzed.
Results:①The gender, age, BMI, systemic blood pressure (SBP), DBP and the levels of TC, TG, LDL-C were similar among 4 groups,P>0.05.②For CIMT at both side, both bifurcations and both internal carotid arteries, 1hHPG/2hHPG group was higher than those in 1hHPG group and 2hHPG group; 1hHPG group was higher than 2hHPG group; CIMT in above 3 groups were all higher than NGT group, allP<0.05.③Multivariate logistic regression analysis presented that increased CIMT (CIMT≥1 mm) was related to 1hHPG (OR=2.630, 95% CI 1.497-2.884), 2hHP (OR=1.799, 95% CI 1.350-2.380) and 1hHPG/2hHPG (OR=3.166, 95% CI 2.566-5.231) respectively.
Conclusion: Abnormal 1hHPG and 2hHPG were related to increased CIMT.
6.Overexpression of SHP-1 mediated by lentivirus restrains atherosclerotic progression in mice
Bingbing ZHANG ; Hengliang SONG ; Tao SUN ; Daguo WAN
Chinese Journal of Pathophysiology 2015;(8):1395-1400
AIM:ToinvestigatetheroleofSH2-domain-containingprotein-tyrosinephosphatase-1(SHP-1) lentivirus in atherosclerotic mice .METHODS:ApoE knock-out mice were randomly assigned to 3 groups:control group , GFP transfection group and SHP-1 transfection group .All mice were placed with carotid collars on the right common carotid arteries near its bifurcation , following feeding with high-fat diet for 8 weeks and then transfected with GFP blank vector or SHP-1 lentivirus ( SHP-1-LV) .The fluorescence density of the plaques , body weight , the levels of plasma total cholesterol (TC) and triglyceride (TG) were determined at 1st, 2nd, and 6th week after lentivirus transfection.Furthermore, the mRNA and protein expression of SHP-1, interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), matrix metalloproteinase ( MMP)-2 and MMP-9 were analyzed by real-time PCR and Western blot .Additionally , pathological analysis of the plaques was also performed by HE and oil red O staining .RESULTS:The fluorescence of the plaques was observed at 1st, 2nd, and 6th week after lentivirus transfection , with a highest density at 2nd week.The body weight and the levels of TC and TG in the mice were not influenced by lentivirus transfection .Moreover, SHP-1-LV transfection significantly upregulated the expression of SHP-1 at mRNA and protein levels, but inhibited the expression of IL-6, TNF-α, MMP-2 and MMP-9.In addition, SHP-1-LV transfection also decreased the plaque size ratio and lipid content in right common carotid arteries . CONCLUSION:SHP-1 overexpression accelerates the regression of atherosclerotic plaque , thus emerging SHP-1 as a tar-get for prevention and treatment of atherosclerosis .
7.Changes m expression of hypoxia-inducible factor 1alpha in proliferated intima of pulmonary arterioles in rats with pulmonary hypertension
Qing SUN ; Yan SHEN ; Jie YAN ; Bingbing LI
Chinese Journal of Anesthesiology 2014;34(12):1471-1474
Objective To evaluate the changes in the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in the proliferated intima of pulmonary arterioles in rats with pulmonary hypertension.Methods Thirty-two pathogen-free male Sprague-Dawley rats,aged 2 months,weighing 200-230 g,were used in the study.Thirty-two rats were randomly divided into 4 groups with 8 animals in each group using a random number table:shamoperation group (group S),left pneumonectomy group (group P),monocrotaline group (group M),and left pneumonectomy combined with monocrotaline group (group PM).The rats underwent left pneumonectomy in P and PM groups.In M and PM groups,monocrotaline 60 mg/kg was injected subcutaneously at 7 days after operation.On day 35 after operation,mean pulmonary artery pressure (mPAP) and right ventricle systolic pressure (RVSP)were measured via direct puncture of right ventricle outflow tract with gauge 24 iv catheter connected to pressure transducer.At the end of experiment,the hearts and right lobes of the lung were excised for measurement of right ventricle hypertrophy index (RVHI) and the thickness of the medial layer (tunica media) of pulmonary arterioles (MT).Vascular occlusion score (VOS) was performed.The expression of HIF-1α,α-smooth muscle actin (α-SMA),and proliferating cell nuclear antigen (PCNA) in the pulmonary arterioles was determined.Results Compared with S group,MT was significandy increased,and the expression of α-SMA was up-regulated in P group,mPAP,RVSP,RVHI and MT were increased in M group,mPAP,RVSP,RVHI,MT and VOS were increased in PM group,and the expression of HIF-1α,α-SMA,and PCNA was up-regulated in M and PM groups.Compared with P group,mPAP,RVSP,RVHI and MT were significantly increased,and the expression of HIF1α,α-SMA,and PCNA was up-regulated in M and PM groups.Compared with M group,RVSP,RVHI,MT and VOS were si gnificantly increased,and the expression of HIF-1α,α-SMA,and PCNA was up-regulated in PM group.Conclusion The mechanism of pulmonary arteriole intimal proliferation is related to up-regulated HIF-1α expression and promoted proliferation of vascular smooth muscle cells in rats with pulmonary hypertension.
8.Analysis of the clinical phenotype in 20 children with 22q11.2 deletion syndrome
Bijun SUN ; Bingbing WU ; Xiaohong GUO ; Renchao LIU ; Lin YANG ; Wenhao ZHOU
Chinese Journal of Applied Clinical Pediatrics 2015;30(8):589-592
Objective To investigate the clinical manifestations in patients with 22q11.2 deletion syndrome (22q11.2DS) to improve the understanding of the disease.Methods Twenty patients with 22q11.2 DS were enrolled from Children's Hospital of Fudan University between August 2008 and April 2014.Cytogenetic and molecular genetic methods included fluorescence in situ hybridization (10 cases),and multiplex ligation-dependent probe amplification (10 cases).Age at the time of the diagnosis,sex and clinical manifestations were analyzed.Results The subject group consisted of 20 patients.Among them,13 cases (65%) were male and 7 cases (35%) were female.The median diagnostic age was 3.9 months.The presence of congenital heart diseases was identified in 17 patients (85%) and surgical correction was performed in 9 cases of them.The most frequent of complex congenital heart diseases were tetralogy of Fallot (20%) and pulmonary atresia (20%).Ten patients had varying degrees of T-cell immune function defects.Decrease in total lymphocytes and only CD8 counts were present in 45% and 5%,respectively.Hypogammaglobulinemia was not detected in any patient.Six eases with T-cell immune function defects were treated with thymosin,4 of which were followed up for months,and the prognosis was good.Hypocalcemia was detected in 6 patients (30%),3 of whom presented with hypocalcemic seizures and hypoparathyroidism.Craniofacial dysmorphisms were detected in 3 patients(15%),2 of them only presented with micrognathia.Otorhinolaryngologic abnormalities were found in 4 cases (20%),3 of whom had laryngeal abnormalities,one of whom had cleft palate.Psychomotor developmental delay was found in 9 cases.Conclusions Congenital heart defects,hypocalcemia and/or impaired immune function are diagnostic features for 22q1 1.2 deletion syndrome,and they should be considered for cytogenetic analysis.
9.High-intensity pulsed electromagnetic field induces the differentiation of neural stem cells from neonatal rats into neurons in vitro
Ting JIANG ; Tao XU ; Wei XIANG ; Xinlan LONG ; Bingbing LI ; Tao PENG ; Quqin SUN
Chinese Journal of Physical Medicine and Rehabilitation 2014;36(10):740-744
Objective To Investigate the influence of high-intensity pulsed electromagnetic field (HIPEMF) on neural differentiation of neonatal rats neural stem cells in vitro.Methods Neural stem cells (NSCs) were isolated from the subventricular zone of 3-day-old neonatal rats and cultured with serum-free condition medium for 14 days.All the NSCs were then randomly classified into an experimental group which received the stimulation of HIPEMF (0.1 Hz,4 T,8 pulses) and a control group which received no special intervention.Differentiation of the culture was induced by addition of 10% fetal bovine serum on the first day after intervention,the morphological changes of cells were observed under the microscope at different time points.The NSCs adhered to the wall and differentiated for seven days,the immunofluorescence was employed to observed and calculate the ratio of differentiated cells with astrocyte marker GFAP or neuronal markers TUJ1.RT-PCR and western blotting were used to measure the expression levels of the differentiated cells based on gene and protein levels,respectively.Results Immunofluorescence staining showed the number of TUJI positive cells in the experimental group(33.4% ± 5.1%)was significantly more than the control group (26.5% ± 7.0%),while the number of GFAP positive cells was decreased(23.9% ± 5.0%) as compared with the control group(36.2% ± 2.2%).RT-PCR showed that the TUJ1 mRNA expression levels in the experimental group was (1.682 ± 0.086) times of the control group.Western blot showed that the expression of TUJ1 (0.729 ±0.061) in the experimental group was higher than in the control group (0.590 ± 0.157),while the expression of GFAP in the experimental group (0.566 ± 0.056) was less than in the control group(1.034 ± 0.051).Conclusions HIPEMF facilitates differentiation of neural stem cells to neurons,at the cost of reducing astrocytic differentiation.
10.Diffusion Tensor Imaging of White Matter in Early Stage of Parkinson''s Disease Based on Tract-based Spatial Statistics Analysis
Bingbing LING ; Yi LU ; Wei ZHAO ; Yin MO ; Juan HU ; Xuejin SUN
Chinese Journal of Medical Imaging 2015;23(8):567-572
Purpose To observe white matter structure features of patients with early stage (Hoehn-Yahr 1-2 phase) Parkinson''s disease (PD) by using diffusion tensor imaging (DTI) based on the fiber bundle analysis tract-based spatial statistics (TBSS); and to explore the brain regions of PD patients in which DTI parameters are significantly correlated with unified Parkinson''s disease rating scale (UPDRS) score elevation. Materials and Methods DTI sequence was performed on 27 cases of PD and 30 cases of healthy volunteers. DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analyzed in all participants by using TBSS technique, and the parameters of two groups were compared. The correlation of clinical UPDRS score with FA value, MD and RD value in the PD group were analyzed.Results Compared with that in the control group, FA values of several brain regions in PD group decreased, while MD and RD value increased (P<0.05). AD showed no obvious change (P>0.05). UPDRS score of PD group was correlated with FA, MD and RD value (P=0.001). The brain regions that showed FA value decreased, MD and RD value increased included corpus callosum, left anterior limb of internal capsule, bilateral anterior radial crown, bilateral superior radial crown and left posterior thalamic radiation (P=0.001).Conclusion There is some changes in white matter structure of the patients with early stage Parkinson''s disease, which may due to demyelination or fiber integrity damaged.