2.Effects of bevacizumab and cisplatin on human lung adenocarcinoma A549/DDP xenografts in nude mice.
Ming DAI ; Rong-cheng LUO ; Da-yong ZHENG ; Cheng-wei LÜ ; Xue-mei DING
Journal of Southern Medical University 2007;27(9):1402-1405
OBJECTIVETo explore the effects of bevacizumab with or without cisplatin (DDP) on the growth of lung adenocarcinoma A549/DDP cell xenografts in mice.
METHODSHuman lung cancer A549/DDP cells was subcutaneously transplanted in to 25 nude mice, which were randomly divided into control group (group A), bevacizumab group (group B), DDP group (group C), combined treatment group (group D) and half-dose combined treatment group (group E). After corresponding treatments for 4 consecutive weeks, the tumor inhibition rate was evaluated, tumor microvessel density (MVD) measured with immunohistochemistry, and the mRNA expression of apoptosis-associated gene (bcl-2) and multidrug resistance genes (LRP and GST-pi) assessed by RT-PCR.
RESULTSThe tumor growth inhibition rates in groups B, D, and E with bevacizumab treatment were 20.96%, 51.67% and 50.95%, respectively, and the two combined treatment groups showed better effects. MVD in these 3 groups were 18.6-/+1.14, 13.6-/+1.14, and 14.4-/+0.55, respectively, and no significant difference was found in MVD between DDP group and the control group. Compared with the control group, the 3 bevacizumab-treated groups showed decreased expression of bcl-2 genes in A549/DDP tumors at a comparable amplitude, and LRP and GST-pi mRNA expression showed no significant differences between the 5 groups.
CONCLUSIONBevacizumab has synergetic inhibitory effect with conventional chemotherapy against lung adenocarcinoma A549/DDP cell xenografts in mice by inhibiting angiogenesis of the tumor, and may enhance the sensitivity of A549/DDP cells to DDP by inducing cell apoptosis.
Adenocarcinoma ; genetics ; pathology ; Animals ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Transformation, Neoplastic ; Cisplatin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays
3.Ultrasomics for Early Evaluation of Tumor Response to microRNA-122 in a Nude Mouse Hepatocellular Carcinoma Model
Huan-Ling GUO ; Wei LI ; Xin LI ; Xiao-Yan XIE ; Ming-De LÜ ; Ming KUANG ; Li-Da CHEN ; Wei WANG
Journal of Sun Yat-sen University(Medical Sciences) 2018;39(2):274-281
[Objective]To explore the evaluation value of ultrasomics based on contrast-enhanced ultrasound (CEUS)imaging in the therapy response of microRNA-122(miR-122)in hepatocellular carcinoma(HCC).[Method]Mice bearing subcutaneous HCC xenografts were injected intratumorally with microRNA-122 mimics(miR-122 mimics) and negative control mimics(NC mimics)in treatment group(n=6)and control group(n=6),respectively. The injec-tions were performed every 3 days for five times.Before each injection,two-dimension ultrasound(2D-US)imaging was performed.At 24 h after the last injection,2D-US and CEUS images of tumors were acquired,and then mice scarified for tumor miR-122 expression analysis by qRT-PCR.To evaluate the therapy response by RECIST,tumor volumes were mea-sured based on each 2D-US image. To analyze the tumor perfusion by mRECIST,perfusion parameters(maximum of intensity,rise time,time to peak,mean transit time,quality of fit)were analyzed off-line based on dynamic CEUS videos using SonoLiver?software. For ultrasomics,CEUS images at 10,30,60,90 second were used for features extraction, respectively. The corresponding ultrasomics formulas were built to evaluate the therapy response for miR-122.[Result]The tumors treated with miR-122 mimics resulted in a(763±60)folds increase in miR-122 levels compared to the tumors in control group(P<0.05).Effectively therapeutic response evaluated by tumor sizes change was detected after the third injection(P<0.05).For assessment using mRECIST,all the parameters of treatment group did not show significant difference from the ones of control group(P>0.05).Analysis using ultrasomics fail to detect different features of the static images of CEUS at 10 s,and models can be successfully built based on the rest of the three phases of CEUS images.The ultrasomics Scores between control group and treatment group were statistically different(P<0.05).The ultrasomics score at 30s were significantly lower than those at 60 s and 90 s,while there was no statistical difference between scores at 60 s and 90 s.[Conclusion]Ultrasomics analysis based on CEUS imaging is a useful method in evaluating the therapy response of miR-122 in HCC,and showed greater value than dynamic perfusion parameter.
4.Clinical comparison on the classical versus extensive Whipple's resection for adenocarcinoma of head of pancreas.
Xu-bao LIU ; Lü-nan YAN ; Hong-jun ZHAI ; Bing LU ; Wei-ming HU ; Bo-le TIAN ; Zhao-da ZHANG
Acta Academiae Medicinae Sinicae 2005;27(5):575-578
OBJECTIVETo evaluate the effect of extensive Whipple's resection to the adenocarcinoma of head of pancreas on the survival, complications, and surgical mortality.
METHODNinety three patients who received Whipple's surgery between January 1995 and March 2003 were divided into classical group (n = 51) and extensive group (n = 42). Their short-term outcome and survival rate were compared retrospectively.
RESULTSThe postoperative complication rate and mortality in classical group and extensive group were 19.61%/3.92% and 16.67%/2.38%, respectively. And 1- and 2- year survival rates in classical group and extensive group were 58.82%/20.59% and 63.33%/23.33%, respectively.
CONCLUSIONSPostoperative complications and mortality will not increase in extensive Whipple's resection for adenocarcinoma of head of pancreas. However, whether extensive Whipple's resection will improve long-term survival still requires further investigation.
Adenocarcinoma ; mortality ; surgery ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; mortality ; surgery ; Pancreaticoduodenectomy ; methods ; Postoperative Complications ; epidemiology ; Retrospective Studies ; Survival Rate
5.Analysis of the risk factors of acute renal insufficiency following coronary artery bypass grafting.
Xu-jun CHEN ; Ming-di XIAO ; Wen-hui FENG ; Bi-bo YANG ; Yong ZHANG ; Zhi-qian LÜ ; Da-lian LI
Chinese Journal of Surgery 2006;44(22):1532-1534
OBJECTIVETo study the risk factors of acute renal insufficiency (ARI) following coronary artery bypass grafting (CABG).
METHODSThe clinic data of 2242 patients undertaking CABG between July 1997 and July 2006 were retrospectively analyzed, and ARI following CABG was included.
RESULTSARI occurred in 219 patients, with an incidence of 9.8%. Univariate analysis revealed that advanced age, diabetes mellitus, preoperative chronic renal dysfunction, left main disease, low left ventricular erection faction, emergency operation, on-pump CABG, ascending aortic atherosclerosis, postoperative respiratory function insufficiency and low cardiac output syndrome were significantly related to ARI following CABG, and logistic multivariate regression analysis showed that presence of advanced age (P = 0.031), preoperatively chronic renal dysfunction (CrCl
CONCLUSIONSAdvanced age, preoperatively chronic renal dysfunction, on-pump CABG, postoperative respiratory function insufficiency and low cardiac output syndrome are the risk factors of ARI following CABG.
Acute Kidney Injury ; epidemiology ; etiology ; China ; epidemiology ; Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors
6.Preliminary study for classification of spino-pelvic sagittal alignment in adult volunteers.
Gang-Hui YIN ; Ling-Xiang ZHU ; Rui-Song CHEN ; Zhi-de LÜ ; Ming LU ; Hui-Bo YAN ; Zhong-Min ZHANG ; Qing-Chu LI ; Da-di JIN
Chinese Journal of Surgery 2013;51(6):522-526
OBJECTIVETo investigate the feasibility of the classification of the spino-pelvic sagittal alignment in adluts according to lumbar lordosis (LL) and inflection point (IP).
METHODSWhole spine, standing radiographs of 223 adult volunteers were taken from July to August in 2011 .There were 111 cases(56 female and 55 male) enrolled in the study based on the inclusion criteria. The pelvic and spinal parameters, including thoracic kyphosis(TK), thoracolumbar kyphosis(TLK), LL, sacral slope(SS), pelvic tilt(PT), pelvic incidence(PI), intervertebral endplate angle, sagittal vertical axis (SVA), spino-sacral angle (SSA) and IP were measured. The spino-pelvic sagittal alignment were classified in to 3 types according to LL and IP. Type I: LL > -40°, IP located below L2 ∼ 3; Type II: -60° ≤ LL ≤ -40°, IP located in L1 ∼ 2 or T12 ∼ L1; Type III: LL < -60°, P located above T11 ∼ 12. Pearson correlation analysis was used to test the correlation between the variables. The parameters in each type were compared by oneway-ANOVA respectively,then additional multiple comparisons were performed.
RESULTSThe mean value of LL was -49° ± 10°, TK was 36° ± 7°, TLK was 6° ± 7°, PT was 11° ± 7°, SS was 34° ± 8°, PI was 45° ± 9°, SSA was 127° ± 9° and SVA was (-2.7 ± 22.8)mm, respectively. Only LL had significant statistical correlation with all the other parameters. Negative correlation presented between LL and TK, PI, SS, SSA (r = -0.387, -0.536, -0.858, -0.801,P < 0.05). Positive correlation presented between LL and TLK, SVA, PT (r = 0.319, 0.296, 0.262, P < 0.05). All the volunteers were classified into the 3 types: Type I1 9 cases, Type II 75 cases,Type III 17 cases. Oneway-ANOVA results showed statistical difference in LL, TK, TLK, PT, SS, PI, SSA, SVA among the 3 types, (F = 164.559, 7.431, 14.099, 4.217, 53.856, 6.252, 35.995, 8.626, P < 0.05 ). Multiple comparisons showed that LL, SS, SSA, PI had statistical difference between each two types comparison (P < 0.05).
CONCLUSIONSLL is the central parameter of the spino-pelvic sagittal balance. The patterns of the spino-pelvic sagittal alignment in adults could be classified into three types, according to LL and IP. The classification could describe the morphological differences and balance of the spino-pelvic sagittal alignment.
Adult ; Analysis of Variance ; Anthropometry ; Female ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Pelvis ; anatomy & histology ; Postural Balance ; Radiography ; Spine ; anatomy & histology
7.Tetramethylpyrazine accelerated spinal cord repair through regulation of caspase-3 and neurofilament protein expression: an acute spinal cord injury model in rats.
Zheng-xiang SHEN ; Hong-bin LÜ ; Xiao-ming LI ; Da-qi XU ; Jian-zhong HU ; Xi-yang WANG
Journal of Central South University(Medical Sciences) 2008;33(8):693-699
OBJECTIVE:
To investigate the effect of tetramethylpyrazine on spinal cord repair through hypothesized pathways including regulation of caspase-3, neurofilament protein NF-L, NF-H, and NF-M expression.
METHODS:
Allenos weight drop method was used to establish acute spinal cord injury (SCI) rat model at T10 section and was conducted in 80 adult Sprague Dawley rats that were subsequently divided into pseudo-therapy group (sodium chloride group, n=40) and tetramethylpyrazine group (treatment group, n=40). Eight normal rats were included into the pseudo-surgery normal group (n=1 for each time point). The function of spinal cord was evaluated with animal behavioral scores by measuring modified Rivilin loxotic plate degree and counting BBB score at 1, 3, 7, 14, and 21 d postoperatively. The injured spinal cord tissue samples were harvested at 1 h, 3 h, 6 h, 1 d, 3 d, 7 d, 14 d, and 21 d postoperatively (n=5 for each time point) for the preparation of continuous histological sections that were analyzed the expression of caspase-3,NF-L,NF-H, and NF-M by immunohistochemistry method.
RESULTS:
At postoperative Day 7, 14, and 21, animal behavioral scores revealed higher modified Rivlin loxotic plate degree and BBB scores in the treatment group when compared with those of the control group (P<0.05). The cells in the injured spinal cord tissue expressed significantly less caspase-3 and significantly more NF (NF-L, NF-H and NF-M) in the treatment group than those in the control group at Day 3, 7, and 14 (P<0.05). There was positive correlation between modified Rivlin loxotic plate degree and NF expression, BBB score and NF expression; and negative correlations between BBB score and caspase-3 expression, caspase-3 expression and NF expression.
CONCLUSION
Tetramethylpyrazine improves spinal cord healing through regulation of caspase-3 and neurofilament protein expression.
Animals
;
Caspase 3
;
biosynthesis
;
genetics
;
Female
;
Male
;
Nerve Regeneration
;
drug effects
;
Neurofilament Proteins
;
biosynthesis
;
genetics
;
Pyrazines
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Spinal Cord Injuries
;
metabolism
;
physiopathology
8. Kinematic simulation of lower limb joints with local Euler angles
Da-Feng JI ; Hui-Qun WU ; Guang-Ming LÜ
Acta Anatomica Sinica 2021;52(6):972-978
Objective To explore the parameters and effects of local Euler angle in the kinematic simulation of lower limb joints. Methods The hip, femur, patella, tibia, fibula and foot bones were segmented and reconstructed based on one set of computed tomographic (CT) data. The virtual models were imported into 3DSMax for smoothing, optimization, axis regulation and other processing. Models were imported into Unity3D after being processed, and the hip, knee, ankle and metatarsophalangeal joints were simulated with local Euler angle. The scripts were tested to adjust the relevant parameters. The documents were released as executable documents. Results The movement of hip, knee, ankle and metatarsophalangeal joints could be simulated as real movement without exceeding the range of articular fossa (- 170°- 170° in flexion and extension, -30°-80° in abduction and adduction, -40°-60° in rotation of hip joint; 0-140 degrees in flexion of knee joint; -60°-55°in flexion and extension and -30°-20° in varus and evagination of ankle joint; -40°-30° in flexion and extension of metatarsophanlangeal joint). Conclusion The local Euler angle used in Unity3D based on "parent-children" relationship is adapt to simulate the real range of single and whole motion of lower limb joints.
9.Pre-clinical evaluation of a new indirectly labeled ⁹⁹mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator.
Fei YU ; Ming-Li LÜ ; Xiao-Ping ZHANG ; Da FU ; Min HOU ; Hai-Dong CAI ; Dan LI ; Jian WANG ; Xue-Yu YUAN ; Zhong-Wei LÜ ; Feng DONG
Chinese Medical Journal 2012;125(14):2538-2542
BACKGROUNDTechnetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator.
METHODSThe cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.
RESULTSThe molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).
CONCLUSIONThe findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.
Animals ; Cell Line, Tumor ; Humans ; Hydrazines ; chemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Nicotinic Acids ; chemistry ; Receptors, Somatostatin ; metabolism ; Technetium ; chemistry
10.Asymptomatic patients of chronic obstructive pulmonary disease in China.
Ming LU ; Wan-zhen YAO ; Nan-shan ZHONG ; Yu-min ZHOU ; Chen WANG ; Ping CHEN ; Jian KANG ; Shao-guang HUANG ; Bao-yuan CHEN ; Chang-zheng WANG ; Dian-tao NI ; Xiao-ping WANG ; Da-li WANG ; Sheng-ming LIU ; Jia-chun LÜ ; Ning SHEN ; Yan-ling DING ; Pi-xin RAN
Chinese Medical Journal 2010;123(12):1494-1499
BACKGROUNDChronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China.
METHODSA multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed.
RESULTSAmong the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients.
CONCLUSIONSThis large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.
Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; epidemiology ; Risk Factors ; Smoking ; Spirometry ; Surveys and Questionnaires