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.
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.
【摘要】 目的 研究沙利度胺對人慢性粒細胞白血病急變株K562細胞凋亡及血管內皮生長因子（vascular endothelia growth factor，VEGF）分泌的影響。 方法 采用不同濃度的沙立度胺（0.5、1.0、2.0 mmol/L）作用于K562細胞24、48、72、96 h，瑞-姬（Wright-Giemsa）染色法觀察細胞形態；四甲基偶氮唑鹽（methylthiazolyl tetrozolium，MTT）法檢測細胞增殖；流式細胞儀膜聯蛋白V-異硫氰酸熒光素/碘化丙啶雙染法檢測凋亡率；瓊脂糖凝膠電泳法檢測脫氧核糖核酸梯狀條帶；酶聯免疫吸附法檢測VEGF濃度。 結果 培養24、48 h后，沙立度胺對K562細胞生長無抑制作用；作用72 h后，1.0、 2.0 mmol/L濃度組開始出現對K562細胞生長的抑制（Plt;0.001）；作用96 h后，0.5 mmol/L濃度組也產生對K562細胞生長的抑制（Plt;0.001），呈一定的濃度和時間依賴性。沙立度胺處理72 h后，K562細胞出現形態學改變，其體積縮小，出現空泡化，邊緣出現突起，染色質濃縮、邊集，核固縮、出現凋亡小體。經沙立度胺處理后，流式分析結果顯示K562細胞凋亡率增加（Plt;0.001）。沙立度胺作用72 h后，瓊脂糖凝膠電泳可見典型的DNA梯狀條帶。K562細胞培養48 h后，沙立度胺抑制VEGF的分泌（Plt;0.001），并且VEGF濃度與凋亡率呈負相關（r=-0.789）。 結論 沙利度胺抑制K562細胞的增殖，呈一定的濃度和時間依賴性；沙利度胺對K562細胞凋亡有明顯誘導作用；沙利度胺抑制K562細胞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.
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.
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)
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.
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 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.
【摘要】 目的 探討丙型肝炎病毒非結構蛋白NS4B對肝細胞內p53表達的影響，以及在肝癌發生中的作用與機制。 方法 設置空白對照組、空白載體組、轉染NS4B組、轉染p53組、共轉染NS4B及p53組。使用脂質體介導轉染法，轉染丙型肝炎病毒非結構蛋白重組質粒PCXN2-NS4B及突變型p53基因重組質粒pC53-CX22AN3進入Chang肝細胞內，并用G418篩選獲得穩定表達細胞。采用免疫細胞化學法檢測p53表達率。 結果 空白對照組無p53表達，空白載體組及轉染NS4B組呈弱陽性表達，轉染p53組及共轉染組呈陽性表達；轉染p53組、共轉染組分別與空白對照組、空白載體組及轉染NS4B組比較，差異均有統計學意義 （Plt;0.05）。 結論 NS4B可能抑制p53表達，也可能阻止其進入細胞核，但NS4B與突變型p53關系不明確。NS4B導致肝細胞異常增生，誘導肝癌發生可能不依賴p53的異常表達及突變。【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.
During the medical rescue after Wenchuan earthquake, based on the design and implementation of the management process of blood purification equipment, we gave the top priority to those patients with post-disaster crush syndrome to ensure their hemodialytic treatment. Through strict management of blood purification technology, the outcomes of these patients have been fundamentally improved and the incidence of complications was substantially reduced. Safe and effective hemodialytic treatment have been administered to 77 patients with crush syndrome (813 case-times).
