Covariates are factors which have significant impacts on the primary analysis prior to the subjects being treated. Covariates adjustment should be considered in the design and analysis stages of the clinical trial. Through controlling in the design stage is the optimal resolution; randomization, stratified randomization and restricted covariant values could be used to balance the covariates between comparative treatments. During data analysis stage, analysis of covariance, stratified analysis, linear or generalized linear model can be conducted for covariate adjustment according to different types of outcome and covariate. For confirmatory clinical trial, covariates should be defined in advance in the protocol and statistical analysis plan with the main statistical model.
Objective To observe the characteristics of images of ocular fundus obtained by computer-assisted imaging system of binocular indirect ophthalmosco p y (CABIO) in the healthy premature infants and the ones with retinopathy of prem aturity(ROP), and evaluate the value of the clinical practice of CABIO in ROP s creening. Methods From January, 2006 to December, 2006, we exa mined 150 prematur e infants in ROP screening procedure by using the computerassisted imaging sys t em of binocular indirect ophthalmoscope, beginning at the infantsprime;age of postn a tal 4-6 weeks or the corrected age above 32 weeks. The follow-up duration was co nfirmed according to the first examination results. The procedure of the operati on was recorded and the typical pictures were shot to obtain the images of the o cular fundus of the healthy premature infants and the ones with ROP. The charact eristics of the images were retrospectively analyzed and compared. Resu lts The typical images of normal ocular fundus and that with ROP in the 150 premature i nfants were successfully obtained by indirect ophthalmoscope. In normal fundus o f infants, the color of optic disc was pale, peripheral retina was not completel y vascularized and presented gray-tone in color;while all stages of ROP present ed dif ferent appearances under the indirect ophthalmoscope. Conclusions Computer-ass isted imaging system of the binocular indirect ophthalmoscopy can clearly observ e the characteristics of normal ocular fundus of premature infants and the ocula r fundus with ROP, and can save the objective examination results, which may pro vide significant references in screening and treating ROP.
Objective To observe the changes of the multifocal electr oretinograph (mf-ERG) in commotio retinae. Methods The affected eyes (traumatic group) and the fellow eyes (control group) of 31 patients with unilateral commotio retinae were examined by RETI scan 3.15 system. The responses of 61 retinal regions were recorded, and the average amplitude densities of the N1 (the first negative) wave and P1 (the first positive) wave in different regions of retinal were analyzed. Results The average amplitude densities of 1-4 rings in N1wave and 1-5 rings in P1wave were much lower in traumatic group than those in the control. Conclusions The average amplitude densities of N1wave and P1wave of mf-ERG in retin al affected regions decreases markedly in eyes with commotio retina; mf-ERG may provide the quantificational and orientational detection for the visual ability of the eyes with commotio retinae.(Chin J Ocul Fundus Dis，2004，20：226-228)
【摘要】 目的 研究沙利度胺对人慢性粒细胞白血病急变株K562细胞凋亡及血管内皮生长因子（vascular endothelia growth factor，VEGF）分泌的影响。 方法 采用不同浓度的沙立度胺（0.5、1.0、2.0 mmol/L）作用于K562细胞24、48、72、96 h，瑞-姬（Wright-Giemsa）染色法观察细胞形态；四甲基偶氮唑盐（methylthiazolyl tetrozolium，MTT）法检测细胞增殖；流式细胞仪膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染法检测凋亡率；琼脂糖凝胶电泳法检测脱氧核糖核酸梯状条带；酶联免疫吸附法检测VEGF浓度。 结果 培养24、48 h后，沙立度胺对K562细胞生长无抑制作用；作用72 h后，1.0、 2.0 mmol/L浓度组开始出现对K562细胞生长的抑制（Plt;0.001）；作用96 h后，0.5 mmol/L浓度组也产生对K562细胞生长的抑制（Plt;0.001），呈一定的浓度和时间依赖性。沙立度胺处理72 h后，K562细胞出现形态学改变，其体积缩小，出现空泡化，边缘出现突起，染色质浓缩、边集，核固缩、出现凋亡小体。经沙立度胺处理后，流式分析结果显示K562细胞凋亡率增加（Plt;0.001）。沙立度胺作用72 h后，琼脂糖凝胶电泳可见典型的DNA梯状条带。K562细胞培养48 h后，沙立度胺抑制VEGF的分泌（Plt;0.001），并且VEGF浓度与凋亡率呈负相关（r=-0.789）。 结论 沙利度胺抑制K562细胞的增殖，呈一定的浓度和时间依赖性；沙利度胺对K562细胞凋亡有明显诱导作用；沙利度胺抑制K562细胞VEGF的分泌。【Abstract】 Objective To investigate the effect of thalidomide on apoptosis of k562 cells and its vascular endothelial growth factor secretion. Methods K562 cells were cultured in vitro with 0.5, 1.0, and 2.0 mmol/L thalidomide for 24, 48, 72, and 96 hours. Morphology of the K562 cells was observed by the Wright-Giemsa staining method. Methylthiazolyl tetrozolium （MTT） assay was used to determine the cell growth. The rate of apoptosis was analyzed by flow cytometry (FCM) with annexin V-fluorescein isothiocyanate/propidium iodide （AnnexinV-FITC/PI）double-staining method. Agarose gel electrophoresis was used to detected Deoxyribonucleic acid Ladder（DNA Ladder）. The concentration of VEGF was quantified by the enzyme-linked immunosorbent assay (ELISA). Results Cultured for 24 or 48 hours, thalidomide had no effect on the proliferation of the K562 cells. But after cultured for 72 hours, thalidomide began to inhibit the growth of the K562 cells at the concentration of 1.0 and 2.0 mmol/L （Plt;0.001）. After cultured for 96 hours, the proliferation of the K562 cells was inhibited too at the concentration of 0.5 mmol/L thalidomide （Plt;0.001）. Thus, thalidomide inhibited the growth of the K562 cells with a dose-and time-dependent manner to some extent. After exposure to thalidomide for 72 hours, K562 cells underwent typical morphological changes of apoptosis such as vaculization, the budding of cytoplasm, chromatin condensation, margination, shrunken nucleus and apoptotic body. The results of flow cytometry showed that thalidomide could obviously increase the rates of the apoptosis of K562 cells （Plt;0.001）. After treated with thalidomide for 72 hours, DNA was extracted for Agarose gel electrophoresis and typical DNA ladder strips were observed. The secretion of VEGF was inhibited when exposure to thalidomide for 48 hours（Plt;0.001）, and there was negative correlation between VEGF concentrations and apoptotic rates（r=-0.789）. Conclusions Thalidomide could inhibite the growth of the K562 cells with a dose-and time-dependent manner to some extent. Thalidomide could obviously induce the apoptosis of the K562 cells and inhibit its secretion of VEGF.
Taking advantages of the sparsity or compressibility inherent in real world signals, compressed sensing (CS) can collect compressed data at the sampling rate much lower than that needed in Shannon’s theorem. The combination of CS and low rank modeling is used to medical imaging techniques to increase the scanning speed of cardiac magnetic resonance (CMR), alleviate the patients’ suffering and improve the images quality. The alternating direction method of multipliers (ADMM) algorithm is proposed for multiscale low rank matrix decomposition of CMR images. The algorithm performance is evaluated quantitatively by the peak signal to noise ratio (PSNR) and relative l2 norm error (RLNE), with the human visual system and the local region magnification as the qualitative comparison. Compared to L + S, kt FOCUSS, k-t SPARSE SENSE algorithms, experimental results demonstrate that the proposed algorithm can achieve the best performance indices, and maintain the most detail features and edge contours. The proposed algorithm can encourage the development of fast imaging techniques, and improve the diagnoses values of CMR in clinical applications.
Objective To study the predictive value of inspiratory capacity (IC) and total lung capacity (TLC) on acute exacerbation of patients with chronic obstructive pulmonary disease (COPD). Methods The in-patients due to acute exacerbation of COPD (AECOPD) from February 2017 to March 2019 were recruited in the study. Research data were collected during the recovery period and one year follow-up , and the patients were divided into two groups according to whether there was another acute exacerbation. Results A total of 372 patients were included in the study. In the patients with acute exacerbation, the age and TLC as a percentage of the expected value (TLC%pred) were higher, while IC as a percentage of the expected value (IC%pred) and the ratio of IC and TLC (IC/TLC) were lower. Univariate analysis revealed that IC/TLC≤25% was a significant predictor of acute exacerbation (P<0.001) after the AECOPD patients were discharged. Multivariable analysis revealed age (OR=1.25, 95%CI 1.17 to 1.44, P<0.001) and IC/TLC≤25% (OR=1.68, 95%CI 1.36 to 2.07, P<0.001) were independent risk factors of AECOPD.Conclusions Decreased IC/TLC significantly correlates with poor prognosis of COPD. IC/TLC≤25% is an independent risk factor for acute exacerbation.
【摘要】 目的 探讨丙型肝炎病毒非结构蛋白NS4B对肝细胞内p53表达的影响，以及在肝癌发生中的作用与机制。 方法 设置空白对照组、空白载体组、转染NS4B组、转染p53组、共转染NS4B及p53组。使用脂质体介导转染法，转染丙型肝炎病毒非结构蛋白重组质粒PCXN2-NS4B及突变型p53基因重组质粒pC53-CX22AN3进入Chang肝细胞内，并用G418筛选获得稳定表达细胞。采用免疫细胞化学法检测p53表达率。 结果 空白对照组无p53表达，空白载体组及转染NS4B组呈弱阳性表达，转染p53组及共转染组呈阳性表达；转染p53组、共转染组分别与空白对照组、空白载体组及转染NS4B组比较，差异均有统计学意义 （Plt;0.05）。 结论 NS4B可能抑制p53表达，也可能阻止其进入细胞核，但NS4B与突变型p53关系不明确。NS4B导致肝细胞异常增生，诱导肝癌发生可能不依赖p53的异常表达及突变。【Abstract】 Objective To investigate the effect of hepatitis C Virus on-structural protein 4B(HCV NS4B) on expression of p53 in hepatic cell, and to study the role and mechanism in development of hepatocellular carcinoma. Methods The experiment was divided into negative control, pure vector PCXN2, PCXN2-NS4B, PC53-cx22AN3, and co-transfection group. Recombinant plasmid PCXN2-NS4B and mutant p53 gene--PC53-cx22AN3, PC53-cx22AN3 with PCXN2-NS4B, blank vectors were transfected into Chang liver cell by liposome-mediated transfection respectively. Positive cells were screened by G418. The expression rate of p53 was measured by immunocytochemistry. Result No expression rate of p53 gene in control group was found, lower positive expression in group PCXN2 and PCXN2-NS4B. The expression of p53 gene in group PC53-CX22AN3 and co-transfection was ber than the others (Plt;0.005). Conclusion HCV-NS4B may inhibit the expression of p53 gene, and it may play a crucial role in inhibiting p53 transfered to hepatic cells nuclear. But it isn’t clear that the. HCV-NS4B can enhance the role of mutant p53 gene. It suggested that HCV-NS4B induce proliferation of hepatic cell not through regulating the expression of p53.
Objective To evaluate the efficacy of anti-oxidative treatment in cats with pancreaticobiliary maljunction. Methods Thirteen healthy cats as control group were made a model that resembling the common channel of pancreaticobiliary maljunction as in humans，and were divided randomly into two groups：7 cats in untreated group were not treated，6 cats in anti-oxidative group were treated with melatonin，vitamin C， and vitamin E. Six months later， the gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. The level of MDA，amylase concentration in the gallbladder bile，and percentage of proliferating cell nuclear antigen （PNCA） positive cells were also test. Results All cats had survived for 6 months after operation. The wall of gallbladder and the bile became thicker in untreated group than that in normal control group， and there were no significant differences between untreated group and anti-oxidative group. The gallbladder epithelium became villous in appearance in untreated group，although the epithelium of that in normal control group was flat with few folds. The epithelial cells of gallbladder arranged tightly in normal control group， while a significant change such as endoplasmic reticulum expanding， intercellular space broadening， and cellular nucleus deforming were observed in untreated group. The things in anti-oxidative group were better than untreated group. The amylase concentration in the gallbladder bile was （203.02±65.04）U in normal control group，（9 368.09±2 204.42） U in untreated group， and（8 746.25±2 077.95） U in anti-oxidative group， respectively. The amylase concentration in untreated group and anti-oxidative group were higher than that in normal control group （P=0.003），and there was no significant difference between the untreated group and anti-oxidative group （P=0.642）. The percentage of PNCA positive cells was （7.29±2.70）% in normal control group，（54.71±10.90）% in untreated group, and （48.17±13.06）% in anti-oxidative group， respectively （F=48.11，P=0.001），and the percentage of PNCA positive cells in untreated group was higher than that in anti-oxidative group （P=0.001）. The level of MDA was （1.095±0.653） nmol/mg prot in normal control group，（2.745±1.533） nmol/mg prot in untreated group, and （1.302±0.771） nmol/mg prot in anti-oxidative group， respectively （F=5.17，P=0.017）, and the level of MDA in untreated group was higher than that in anti-oxidative group （P=0.017）. Conclusion The anti-oxidative treatment is effective to pancreaticobiliary maljunction.
ObjectiveThrough researching the "Automated Production Quality Management Specification 5th Edition" (GAMP5) promulgated by the International Society for Pharmaceutical Engineering, combined with domestic and foreign guidelines and regulatory requirements, to explore the practical methods for the verification of the central randomization system of clinical trials.MethodsThe GAMP5 verification process and specifications of the clinical trial central randomization system was established according to the GAMP5 guideline and domestic and foreign computerized system verification guidelines and regulations in combination with the characteristics of the clinical trial central randomization system, and the existing clinical trials central randomization system was used as an example to show the verification results.ResultsThe verification framework and process of the central randomization system met the requirements of the relevant regulations of clinical trials that had been constructed. For the existing system, a verification team was established, a verification plan was developed, and a computerized system verification was conducted in accordance with the V model to form a set of standardized verification documents.ConclusionsThe verification process of the central randomization system proposed by this research follows the GAMP5 specification and has high operability and reference value.
Objective To investigate the effectiveness of endoscopic low-temperature plasma radiofrequency ablation with acellular dermal matrix patch for chronic abdominal wall sinus by comparing with the traditional surgical method. Methods Retrospective analysis was made on the clinical data of 53 cases of chronic abdominal wall sinus between January 2006 and May 2012. Of 53 patients, 18 underwent endoscopic low-temperature plasma radiofrequency ablation with acellular dermal matrix patch (trial group), and 35 underwent traditional surgical treatment (control group). No significant difference was found in gender, age, etiology, disease duration, and location between 2 groups (P gt; 0.05). Results The blood loss during sinus clearance, postoperative hospitalization days, and sinus union time of the trial group were significantly better than those of the control group (P lt; 0.05), but no significant difference was found in the operative time for sinus clearance (t=0.28, P=0.78). No postoperative sinus bleeding or infection occurred in the trial group, but bleeding and infection in 5 and 3 cases of the control group respectively, showing significant differences between 2 groups (P lt; 0.05). The follow-up time was 4-18 months (mean, 12.4 months) in the trial group, and was 6-48 months (mean, 38.5 months) in the control group. No sinus recurrence was observed during follow-up. Conclusion Endoscopic low-temperature plasma radiofrequency ablation with acellular dermal matrix patch has the following advantages in treating chronic abdominal wall sinus: clear view, thorough cleaning of granulation necrosis tissues, less bleeding, faster sinus union, and shorter hospitalization days; however, further observations on the long-term effectiveness and the safety are required .