1.Screening of Pim kinase inhibitors by the establishment of high-throughput ELISA system
Kun SHANG ; Peng ZHANG ; Lu ZHOU ; Zhen WANG ; Yue CAO ; Yingyi LI
China Oncology 2013;(4):260-266
10.3969/j.issn.1007-3969.2013.04.004
2.Study on changes of partial pressure of brain tissue oxygen and brain temperature in acute phase of severe head injury during mild hypothermia therapy.
Yan-xiang ZHU ; Jie YAO ; Shang-kun LU ; Geng-sheng ZHANG ; Guan-ren ZHOU
Chinese Journal of Traumatology 2003;6(3):152-155
OBJECTIVETo study the changes of partial pressure of brain tissue oxygen (PbtO2) and brain temperature in acute phase of severe head injury during mild hypothermia therapy and the clinical significance.
METHODSOne hundred and sixteen patients with severe head injury were selected and divided into a mild hypothermia group (n=58), and a control group (n=58) according to odd and even numbers of hospitalization. While mild hypothermia therapy was performed PbtO2 and brain temperature were monitored for 1-7 days (mean=86 hours), simultaneously, the intracranial pressure, rectum temperature, cerebral perfusion pressure, PaO2 and PaCO2 were also monitored. The patients were followed up for 6 months and the prognosis was evaluated with GOS (Glasgow outcome scale).
RESULTSThe mean value of PbtO2 within 24 hour monitoring in the 116 patients was 13.7 mm Hg +/- 4.94 mm Hg, lower than the normal value (16 mm Hg +/- 40 mm Hg ) The time of PbtO2 recovering to the normal value in the mild hypothermia group was shortened by 10 +/- 4.15 hours compared with the control group (P<0.05). The survival rate of the mild hypothermia group was 60.43%, higher than that of the control group (46.55%). After the recovery of the brain temperature, PbtO2 increased with the rise of the brain temperature.
CONCLUSIONSMild hypothermia can improve the survival rate of severe head injury. The technique of monitoring PbtO2 and the brain temperature is safe and reliable, and has important clinical significance in judging disease condition and instructing clinical therapy.
Adult ; Blood Gas Monitoring, Transcutaneous ; Body Temperature ; Brain ; metabolism ; Brain Chemistry ; Craniocerebral Trauma ; metabolism ; therapy ; Female ; Humans ; Hypothermia, Induced ; Male ; Oxygen ; metabolism ; Partial Pressure ; Regional Blood Flow ; Treatment Outcome
3.Clinical value of PET /CT imaging of cerebral blood flow and metabolism in patients with chronic disorders of consciousness
Kun SHANG ; Jie LU ; Yusheng SU ; Ze LI ; Dongmei SHUAI ; Zhigang LIANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(12):777-781
Objective To investigate the value of PET/CT imaging of cerebral glucose metabolism (CGM)and cerebral blood flow (CBF)in evaluating chronic disorders of consciousness (CDC).Methods A total of 10 CDC patients (5 males,5 females,age (50.9 ±17.2)years)and 10 healthy controls (5 males,5 females,age (52.0±10.3)years)from January 2016 to March 2017 were recruited to perform brain PET/CT of CGMand CBF.The brain PET imaging using 13 N-Ammonia was performed and followed by 18 F-fluorodeoxyglucose (FDG)PET.The mean standardized uptake values (SUVmean )of frontal,parietal, temporal and occipital lobes as well as basal ganglia,thalamus were obtained.The SUVmean of cerebral re-gions/SUVmean of cerebellum ratios (SUVr )were acquired.The SUVr were compared between the patients and controls.The imaging characteristics of CGM and CBF were investigated,and their relationships with clinical scores were further analyzed.Two-sample t test and Pearson correlation analysis were used to analyze the data.Results The radioactive distribution in the brain of healthy controls was symmetrical.SUVr of cer-ebral regions in the affected side of patients were significantly lower than those of the controls both in CGM imaging and CBF imaging (t values:2.90-5.19,all P<0.05).In 10 CDC patients,there were 9 with hypo-metabolism in basal ganglia and thalamus,8 with hypometabolism in frontal and parietal lobes,and 7 with hypometabolism in temporal and occipital lobes.At the same time,there were 7 with parietal hypoperfusion and 6 with hypoperfusion in other cerebral regions in the CDC patients.In the frontal,parietal lobes and basal ganglia,the CGMand CBF were both correlated with the clinical scores (r values:0.473-0.606,all P<0.05).Abnormal metabolism-perfusion patterns were divided into 3 types.Type Ⅰ included 2 patients and their hypometabolism and hypoperfusion were mismatched completely.Type Ⅱ included 3 patients and their hypometabolism and hypoperfusion were matched in frontal,parietal,occipital and temporal lobes,while mismatched in basal ganglia and thalamus.Type Ⅲ included 5 patients and their hypometabolism and hypoperfusion were matched completely.The clinical scores of typeⅠ,Ⅱand Ⅲ were 10.5,8.3 and 5.6, respectively.Conclusion The PET/CT imaging of cerebral blood flow and metabolism is useful in evalua-ting the disorders of consciousness.
4.Preoperative localization of 18F-FDG PET/MR in refractory epilepsy patients with negative MRI
Kun GUO ; Kun SHANG ; Bixiao CUI ; Yaqin HOU ; Hongwei YANG ; Xiaotong FAN ; Dongmei SHUAI ; Jie LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(7):410-414
Objective:To explore the accuracy of 18F-fluorodeoxyglucose (FDG) PET/MR in preoperative localization of refractory epilepsy patients with conventional MRI negative. Methods:From August 2016 to December 2018, 57 refractory epilepsy patients (36 males, 21 females, age (24.0±10.3) years) with conventional MRI negative who underwent surgery in Xuanwu Hospital were retrospectively enrolled. All patients received interictal 18F-FDG PET/MR before surgery and the epileptogenic foci were determined by using visual and semi-quantitative methods. Patients were followed up for 1 year and the surgical outcome was evaluated according to Engel classification. The sensitivity, specificity and accuracy of 18F-FDG PET/MR in locating epileptogenic foci were calculated according to surgical resection and followed-up results as the " gold standard" . Results:Of 57 patients, 51(89.5%, 51/57) showed single or multiple hypo-metabolism focus on 18F-FDG PET/MR, and 6(10.5%, 6/57) showed no abnormal metabolism changes. The microstructure abnormality was found in 18 patients (31.6%, 18/57) on 18F-FDG PET/MR images. Follow-up results were obtained from 46 patients, and 84.8%(39/46) with seizure improvement (Engel Ⅰ-Ⅲ). The sensitivity, specificity and accuracy of 18F-FDG PET/MR in preoperative localization of epileptic foci was 90.0%(27/30), 3/16 and 65.2%(30/46), respectively. Conclusion:18F-FDG PET/MR is helpful for the detection of epileptic foci in patients with MRI-negative refractory epilepsy, and can provide reliable information for further surgical treatment.
5.18F-FDG PET/CT imaging in temporal lobe epilepsy and extratemporal lobe epilepsy caused by focal cortical dysplasia
Yaqin HOU ; Kun GUO ; Kun SHANG ; Jingjuan WANG ; Zhenming WANG ; Haiqin ZHANG ; Yusheng SU ; Jie LU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(10):607-612
Objective:To analyze the differences in 18F-fluorodeoxyglucose (FDG) PET/CT imaging and preoperative localization between patients with temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETLE) caused by focal cortical dysplasia (FCD). Methods:From April 2015 to August 2018, a total of 71 patients (45 males, 26 females, age (24.3±9.1) years) with refractory epilepsy who underwent 18F-FDG PET/CT imaging before surgery and confirmed as FCD by pathology in Xuanwu Hospital were retrospectively analyzed. Patients were divided into TLE and ETLE groups based on pathological results. 18F-FDG PET/CT images were analyzed qualitatively and compared with the operation result, then region of interest (ROI) was used to calculate the asymmetry index (AI), and evaluated the hypometabolism of every cerebral region by |AI| semi-quantitatively. Engle classification were followed-up after surgery. Independent-sample t test and χ2 test were used to analyze data. Results:Of 71 FCD patients, 35 were TLE and 36 were ETLE. The onset age of ETLE patients were younger than TLE patients ((10.1±6.5) vs (14.9±9.7) years; t=2.48, P=0.02). In TLE group, 54.29%(19/35) were completely consistent with the operation results, and 42.86%(15/35) showed hypometabolized brain regions in extratemporal lobe. In ETLE group, 27.78%(10/36) were completely consistent with the operation results, and 47.22%(17/36) showed hypometabolized brain regions in temporal lobe. There were significant differences in the lateral accuracy and positioning accuracy of 18F-FDG PET/CT between TLE and ETLE patients (97.14%(34/35) vs 75.00%(27/36), 54.29%(19/35) vs 27.78%(10/36); χ2 values: 7.19, 6.27, both P<0.05). There was no significant difference in |AI| values between the brain regions of TLE and ETLE patients ( z values: from -1.25 to -0.06, all P>0.05). Conclusion:The lateral accuracy and positioning accuracy of 18F-FDG PET/CT in TLE patients are better than that in ETLE patients.
6.Value of blood apoH gene expression and urinary NAG and RBP in early diagnosis of renal function damage in neonates.
Zhi-Jun WU ; Shang-Ming HUANG ; Rui CHEN ; Bin HU ; You CHEN ; Yuan-Peng ZHU ; Guang-Jin LU ; Yu-Kun HAN
Chinese Journal of Contemporary Pediatrics 2009;11(8):649-652
OBJECTIVETo study the value of apolipoprotein H (apoH) gene expression in peripheral blood mononuclear cell (PBMC) and urinary N-Acetyl-beta-D-Glucosaminidase (NAG) and retinal-binding protein (RBP) in the early diagnosis of renal function damage in neonates.
METHODSSixty sick neonates who renal function damage probably occurred were enrolled. The blood and urinary samples were collected twice within 48 hrs following admission, with an interval of 12-24 hrs. Expression of apoH gene in PBMC was determined with RT-PCR. The levels of blood urea nitrogen (BUN) and creatinine, and urinary activities of NAG and RBP were measured with enzymatic reaction.
RESULTSThe abnormal rates of blood apoH and urinary NAG and RBP were 73.3%, 83.3% and 76.7%, respectively in the first detection. The second detection for blood apoH and urinary NAG and RBP showed abnormal rates of 70.0%, 66.7% and 76.7%, respectively. There were no significant differences in the abnormal rates between the three markers either in the first or the second detection (P>0.05). Beside there were no significant significances in the abnormal rates between urinary NAG and blood BUN in the second detection, the abnormal rates of blood apoH and urinary NAG and RBP in both detections were significantly higher than those of BUN or creatinine (P<0.01 or 0.05).
CONCLUSIONSThere are identical values of blood apoH gene expression and urinary NAG and RBP in the early diagnosis of renal function damage in neonates. The above three markers are more sensitive to early renal function damage than blood BUN and creatinine.
Acetylglucosaminidase ; urine ; Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Humans ; Infant, Newborn ; Kidney Diseases ; diagnosis ; physiopathology ; Male ; Retinol-Binding Proteins ; urine ; beta 2-Glycoprotein I ; blood ; genetics
7.Flow cytometric analysis of circulating microvesicles derived from myocardial Ischemic preconditioning and cardioprotection of Ischemia/reperfusion Injury in rats.
Miao LIU ; Yi-lu WANG ; Man SHANG ; Yao WANG ; Qi ZHANG ; Shao-xun WANG ; Su WEI ; Kun- wei ZHANG ; Chao LIU ; Yan-na WU ; Ming-lin LIU ; Jun-qiu SONG ; Yan-xia LIU
Chinese Journal of Applied Physiology 2015;31(6):524-531
OBJECTIVETo establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles (MVs) from myocardial ischemic preconditioning (IPC) treated rats (IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion (I/R) injury in rats.
METHODSMyocardial IPC was elicited by three.cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending (LAD) coronary artery. Platelet-free plasma (PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFR PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 µm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure (MAP), heart rate (HR) and ST-segment of electro-cardiogram (ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin (HE) staining. The activity of plasma lactate dehydrogenase (LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining.
RESULTSTotal IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs (LMVs) and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (<1 Vm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats (P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR (P<0.01), decreased ST-segment and LDH activity (P < 0.05, P < 0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment (P < 0.01).
CONCLUSIONThe method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.
Animals ; Cell-Derived Microparticles ; metabolism ; Coronary Vessels ; pathology ; Flow Cytometry ; Heart Rate ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Myocardium ; pathology ; Phenotype ; Rats
8.Controlling arachidonic acid metabolic network: from single- to multi-target inhibitors of key enzymes.
Ying LIU ; Zheng CHEN ; Er-chang SHANG ; Kun YANG ; Deng-guo WEI ; Lu ZHOU ; Xiao-lu JIANG ; Chong HE ; Lu-hua LAI
Acta Pharmaceutica Sinica 2009;44(3):231-241
Inflammatory diseases are common medical conditions seen in disorders of human immune system. There is a great demand for anti-inflammatory drugs. There are major inflammatory mediators in arachidonic acid metabolic network. Several enzymes in this network have been used as key targets for the development of anti-inflammatory drugs. However, specific single-target inhibitors can not sufficiently control the network balance and may cause side effects at the same time. Most inflammation induced diseases come from the complicated coupling of inflammatory cascades involving multiple targets. In order to treat these complicated diseases, drugs that can intervene multi-targets at the same time attracted much attention. The goal of this review is mainly focused on the key enzymes in arachidonic acid metabolic network, such as phospholipase A2, cyclooxygenase, 5-lipoxygenase and eukotriene A4 hydrolase. Advance in single target and multi-targe inhibitors is summarized.
Animals
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Anti-Inflammatory Agents
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therapeutic use
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Arachidonate 5-Lipoxygenase
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metabolism
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therapeutic use
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Arachidonic Acid
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metabolism
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Cyclooxygenase Inhibitors
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therapeutic use
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Drug Delivery Systems
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methods
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Epoxide Hydrolases
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antagonists & inhibitors
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metabolism
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therapeutic use
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Humans
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Inflammation
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drug therapy
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Lipoxygenase Inhibitors
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Metabolic Networks and Pathways
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drug effects
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Phospholipase A2 Inhibitors
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Phospholipases A2
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metabolism
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therapeutic use
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Prostaglandin-Endoperoxide Synthases
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metabolism
9.Correlations between apparent diffusion coefficient in diffusion?weighted magnetic resonance imaging and molecular subtypes of invasive breast cancer masses.
Liu-Tong SHANG ; Jia-Fei YANG ; Jing LU ; Ting-Ting WANG ; Ying ZHOU ; Xin-Bo XING ; Xin-Kun WANG ; Shu-Hui YANG ; Ming-Yan HU
Journal of Southern Medical University 2017;37(10):1410-1414
OBJECTIVETo study the correlation of apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging (MRI) with the molecular subtypes and biological prognostic factors of invasive breast cancer masses.
METHODSBreast MRI data (including dynamic enhanced and diffusion-weighted imaging) were collected from 64 patients with pathologically confirmed invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the lesions were calculated and their correlations were analyzed with the 5 molecular subtypes of invasive breast cancer and the biological prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 index.
RESULTSThe ADC values did not differ significantly among the 5 molecular subtypes of invasive breast cancer masses (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The mean ADC values were significantly higher in Ki-67-positive lesions than in the negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67 (r=-0.249).
CONCLUSIONADC value can not be used to identify the molecular subtypes of invasive breast cancer masses or to evaluate the biological prognosis of the lesions, but its correlation with Ki-67 expression may help in prognostic evaluation and guiding clinical therapy of the tumors.
10.The Establishment of a Fast and Safe Orthotopic Colon Cancer Model Using a Tissue Adhesive Technique
Hong-Tao HU ; Zhe WANG ; Myung Ji KIM ; Lu-Shang JIANG ; Shi-Jun XU ; Jaeyun JUNG ; Eunji LEE ; Jung-Hoon PARK ; Nader BAKHEET ; Sung Hwan YOON ; Kun Yung KIM ; Ho-Young SONG ; Suhwan CHANG
Cancer Research and Treatment 2021;53(3):733-743
Purpose:
We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method.
Materials and Methods:
RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis.
Results:
We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels.
Conclusion
We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.