Objective To study the loss of imprinting(LOI) of insulin-like growth factor Ⅱ(IGF2) and H19 genes in cervical carcinomas.Methods Polymerase chain reaction(PCR) method was used on DNA samples extracted from 40 cases of cervical carcinoma and 20 cases of normal control tissues to detect the heterozygosity of IGF2 and H19 genes.The LOI of IGF2 and H19 genes was detected by RT-PCR.Results The heterozygous frequency of IGF2 was 52% in cervical cancer samples.Comparatively,in 20 matched normal samples,13 cases showed the heterozygosity(65%).The biallelic expression of IGF2 was detected in 10 cases among the 21 informative cervical cancer samples(47.6%),however,1 case in 13 heterozygous samples of control group(7.7%)((P0.05).Conclusion LOI and LOH of IGF-2 and H19 genes are involved in cervical carcinomas.LOI of IGF2 and H19 may be involved in the initiation stage of carcinogenesis of cervical carcinoma.

With the understanding of tumor metabolism, the process and mechanism of tumor metabolic reprogramming gradually attracted much attention in recent years.Oncogenes and tumor suppressor genes are constantly changing the pathway and flux of tumor metabolism in tumorigenesis to meet the needs of tumor growth and proliferation.The role of c-MYC, TP53, HIF-1αas well as the related signal pathways in tumor metabolic reprogramming would be discussed.

Objective To investigate the antitumor activity of the oncolytic adenovirus expressing lipocalin 2 gene for colorectal cancer in vivo.Methods BALB/C nude mice subcutaneously inoculated by SW620 cells and grown tumors were treated with injection of ZD-55 virus, Ad-lipocalin 2 virus and ZD55- lipocalin 2 virus respectively.The weight of implanted tumors and the tumor inhibition rate were calculated to evaluate the anti-tumor effect.Cell apoptosis was determined by TUNEL and the protein expression of VEGF and MVD were determined with immunohistochemistry.Results ZD55-lipocalin 2 inhibited the growth of transplanted tumor more significantly than ZD-55 virus and Ad-lipocalin 2 virus ( P ＜ 0.05 ).Tumor cell apoptosis was upregulated and the MVD reduced significantly in ZD55-lipocalin 2 group in contrast to the other two groups (P ＜0.05).Conclusions ZD55-lipocalin 2 induces apoptosis of colorectal tumor cells and inhibits tumor microvascular formation, slowing down the growth of transplantation tumors.

Objective:To study the HPLC fingerprint of Ningxinbao capsules, and establish a method for the simultaneous content determination of uracil, uridine, adenine and adenosine. Methods: The separation was carried out on an Agilent Zorbax SB-Aq C18 column(250 mm × 4. 6 mm, 5μm) with gradient elution using methanol-0. 05 mol·L-1 potassium dihydrogen phosphate at 30℃ and at a flow rate of 1. 0 ml·min-1 , the detection wavelength was 212 nm for fingerprint and 260 nm for the determination of the four nu-cleosines. Totally 10 batches of samples were analyzed with the developed HPLC fingerprint and the determination method, the data calculation was performed with similarity evaluation system in the chromatographic fingerprint of TCM. Results: In the fingerprint, 10 common peaks were marked and the separation of the four nucleosines was good. Conclusion:The method is simple and reliable. The HPLC fingerprint and contents of the four nucleosines in Ningxinbao capsules can be used for the quality control.

Objective:To explore the application value of MRI texture analysis in combination with imaging features to predict the WHO/International Society of Urological Pathology (ISUP) nuclear grading in pre-operative patients with clear cell renal carcinoma (ccRCC).Methods:MRI images of 78 patients diagnosed as ccRCC by surgical pathology from July 2016 to July 2020 in First Affiliated Hospital of Fujian Medical University were retrospectively analyzed. According to the WHO/ISUP grading system, the patients were divided into low grade group (49 cases, grade Ⅰ in 2 cases and grade Ⅱ in 47 cases) and high grade group (29 cases, grade Ⅲ in 25 cases and grade Ⅳ in 4 cases), and then were assigned to training set ( n= 63) and validation set ( n=15) in a ratio of 7∶3 using random indicator method. MRI radiological features were evaluated and MRI imaging texture features were extracted. The largest-diameter slice of lesion on cross-sectional images was selected and ROIs were drawn on T 2WI and corticomedullary phase (CMP) images, respectively. Quantitative texture analysis software MaZda was used to extract texture features, including gray-scale histogram, co-occurrence matrix, run-length matrix, gradient, autoregressive model and wavelet transform. The extracted texture features were preliminarily selected by the combination of Fisher, probability of classification errorand average correlation coefficient, and interaction information, and then the reduced texture parameters or imaging features were tested by the independent sample t test, Mann-Whitney U test or χ 2 test. Parameters with statistically significant differences were used to construct a multi-factors binary logistic regression model and the ROC curve was used to analyze its effectiveness in predicting high grade ccRCC. Results:In training set, there were significant differences intumor length, shape and margin, enhancement degree of CMP, vein thrombosis and 47 texture features between the low and high grade ccRCC groups. In the training set, 7 multi-factors binary logistic regression model were constructed, including radiological features model (M1), T 2WI texture features model (M2), CMP image texture features model (M3) and combination radiological features of T 2WI texture features model (M4), combination radiological features of CMP images texture features model (M5), combination T 2WI texture features of CMP images texture features model (M6) and combination of all features model (M7). The area under ROC curve of M7 in predicting nuclear grading of ccRCC was the largest, which were 0.901 (95% CI 0.828-0.974) and 0.820 (95% CI 0.564-0.974) in the training set and validation set, respectively. Conclusion:MRI texture analysis combined with imaging features is hopeful to be an effective preoperative noninvasive method in predicting WHO/ISUP grading of ccRCC.

Objective To investigate whether IL-24 can inhibit the growth of pancreatic cancer in immune-competent mice,which could be mediated by tumor-targeting oncolytic adenovirus (ZD55-IL-24).Methods Crystal violet staining assay was used to evaluate the anti-proliferative influence of ZD55-IL-24 on Panc02.The tumor growth curve,the tumor formation curve,TUNEL assay,cytotoxic T lymphocyte (CTL) killing assay and serum cytokines detection were used to assess anti-tumor efficacy of ZD55-IL-24 for pancreatic cancer in immune-competent mice.Results ZD55-IL-24 significantly inhibited the growth of pancreatic cancer cells in vitro.Lower tumor formation and slower tumor growth were identified in ZD55-IL-24 group,compared with ZD55-EGFP group or PBS group.ZD55-IL-24 induced pancreatic cancer cells'apoptosis,and mediated anti-cancer immunity by increasing killing responses of CTL to cancer cells and up-regulating serum γ-IFN and IL-6 levels.Conclusion ZD55-IL-24 can induce anti-tumor immunity and suppress pancreatic cancer growth in immune-competent mice.

ToprovidethemethodologyforrapidqualityevaluationofLonicerajaponica,wehaveestablished the stable quantitative model of near infrared spectroscopy ( NIR) . The performance of Bagging partial least squares (Bagging-PLS) model and Boosting partial least squares (Boosting-PLS) model was compared with that partial least squares ( PLS ) model based on the NIR data of ethanol precipitation process of Lonicera japonica. On this basis, the performance of these two models after variables selection was also studied by the methods of siPLS ( synergy interval partial least squares ) and CARS ( competitive adaptive reweighted sampling) . The experimental results showed that the prediction performance of Bagging-PLS and Boosting-PLS models was superior to PLS model with the latent factor of 10 . The band of 820-1029 . 5 nm and 1030-1239. 5 nm for the first batch was selected by the method of siPLS. In addition, the band of 820-1029. 5 nm and 1030-1239. 5 nm was selected for the second batch sample in the same method. Furthermore, the method of CARS was taken to select variables for the two batches samples with 5-fold cross-validation and 10-fold cross-validation. And the lowest RMSECV( root mean square error of cross-validation) values were used to take subset. Compared to the model performance without the method of CARS, the RMSEP value of the Bagging-PLS model and Boosting-PLS model for the concentration of chlorogenic acid reduced by 0 . 02-0 . 04 g/L and rp(correlation coefficient of prediction)value increased by 4%-5%. Generally, Bagging-PLS and Boosting-PLS could be regarded as rapid prediction methodsfor NIR quantitative models of ethanol precipitation process of Lonicera japonica.

This study was aimed to find out the correlation between chemical component contents and physical prop-erties of tanshinone extract powders. The contents of cryptotanshinone and tanshinone IIA from 50 batches of tanshi-none extract powders were determined by HPLC. And the physical properties were determined by classical methods. The correlation analysis between component contents and physical properties were also investigated. The results showed that two sets of variables had good intraclass correlation, especially for the contents of cryptotanshinone and tanshinone IIA, among D10, D50, D90, there were relatively strong correlation between the bulk density and tapped density, between the Hausner ratio and compressibility index. The angle of repose had a certain correlation with the uniformity, Hausner ratio and compressibility index, but with no strong correlation. The correlation coefficient be-tween two sets was below 0.400, suggesting there was a not so good inter-group correlation. After the canonical cor-relation analysis, three pairs of canonical variables had significant correlations with correlation coefficients being 0.851, 0.674 and 0.565, respectively. It was concluded that there was a good intraclass correlation for each of physi-cal and/or chemical quality set, but the correlation between the two sets was bad. Canonical variables performed bet-ter inter-group correlation compared with original variables, indicating there was a certain correlation between chem-ical and physical quality attributes of tanshinone extract powders.

Abstract: The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.