Rapid Morphological Measurement Method of Aortic Dissection Stent Based on Spatial Observation Point Set.

OBJECTIVES: Post-operative stent morphology of aortic dissection patients is important for performing clinical diagnosis and prognostic assessment. However, stent morphologies still need to be manually measured, which is a process prone to errors, high time consumption and difficulty in exploiting inter-data associations. Herein, we propose a method based on the stepwise combination of basic, non-divisible data sets to quickly obtain morphological parameters with high accuracy. METHODS: We performed the 3D reconstruction of 109 post-operative follow-up CT image data from 26 patients using mimics software. By extracting the spatial locations of the basic morphological observation points on the stent, we defined a basic and non-reducible set of observation points. Further, we implemented a fully automatic stent segmentation and an observation point extraction algorithm. We analyzed the stability and accuracy of the algorithms on a test set containing 8 cases and 408 points. Based on this dataset, we calculated three morphological parameters of different complexity for the different spatial structural features exhibited by the stent. Finally, we compared the two measurement schemes in four aspects: data variability, data stability, statistical process complexity and algorithmic error. RESULTS: The statistical results of the two methods on two low-complexity morphological parameters (spatial position of stent end and vascular stent end-slip volume) show good agreement (n = 26, P1, P2 < 0.001, r1 = 0.992, r2 = 0.988). The statistics of the proposed method for the morphological parameters of medium complexity (proximal support ring feature diameter and distal support ring feature diameter) avoid the errors caused by manual extraction, and the magnitude of this correction to the traditional method does not exceed 4 mm with an average correction of 1.38 mm. Meanwhile, our proposed automatic observation point extraction method has only 2.2% error rate on the test set, and the average spatial distance from the manually marked observation points is 0.73 mm. Thus, the proposed method is able to rapidly and accurately measure the stent circumferential deflection angle, which is highly complex and cannot be measured using traditional methods. CONCLUSIONS: The proposed method can significantly reduce the statistical observation time and information processing cost compared to the traditional morphological observation methods. Moreover, when new morphological parameters are required, one can quickly and accurately obtain the target parameters by new "combinatorial functions." Iterative modification of the data set itself is avoided.

Current Advances in Immunoassays for the Detection of ß2-Agonists.

ß2-agonists are a group of synthetic phenylethanolamine compounds which are traditionally used for treating bronchospasm. These compounds can also increase skeletal muscle mass and decrease body fat. The illegal use of ß2-agonists in food-producing animals results in residue of ß2-agonists in edible tissues and causes adverse health effects in humans. Thus, the detection of ß2-agonists at trace level in complex sample matrices is of great importance for monitoring the abuse of ß2-agonists. Many methods have been developed to detect ß2-agonists. Among them, a variety of antigen-antibody interaction-based techniques have been established to detect ß2-agonists in various samples, including animal feed, urine, serum, milk, tissues and hair. In this review, we summarized current achievement in the extraction of ß2-agonists from testing samples and detection of ß2-agonists using immunological techniques. Future perspectives were briefly discussed.

Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via ß2-adrenoceptor.

ß2-adrenoceptor (ß2AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through ß2AR. The activity of 25 ß2AR agonists was measured by ß2AR-cAMP response element (CRE) -luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of ß2AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of ß2AR agonists in activating the ß2AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.

High Fat Diet and High Cholesterol Diet Reduce Hepatic Vitamin D-25-Hydroxylase Expression and Serum 25-Hydroxyvitamin D3 Level through Elevating Circulating Cholesterol, Glucose, and Insulin Levels.

SCOPE: Low circulating 25-hydroxyvitamin D (25(OH)D) levels associate with obesity, diabetes, and hyperlipidemia, but the underlying mechanisms remain uncertain. As energy-dense diet contributes to these disorders, this study investigates whether diet could impair vitamin D metabolism. METHODS AND RESULTS: Compared with control chow-fed mice, high fat diet (HFD)-fed mice show lower serum 25(OH)D3 and 1,25(OH)2 D3 levels, lower hepatic vitamin D 25-hydroxylase Cyp2r1 expression but comparable renal vitamin D metabolic enzymes expression. Time course studies show that after HFD feeding, the serum concentrations of cholesterol, triglycerides, fatty acids, glucose, and insulin elevate sequentially and before the reduction of hepatic Cyp2r1 expression and serum 25(OH)D3 levels. Hepatic Cyp2r1 expression also reduces after consuming high fat and high sucrose diet. After high cholesterol diet feeding, serum total cholesterol rises and hepatic Cyp2r1 expression decreases ahead of the reduction of serum 25(OH)D3 . In vitro studies demonstrate that high concentrations of cholesterol, glucose, and insulin significantly inhibit Cyp2r1expression in primary murine hepatocytes. Further studies show that dietary restriction in HFD-fed mice ameliorates hypercholesterolemia, hyperglycemia, and hypertriglyceridemia, and elevates hepatic Cyp2r1 expression and serum 25(OH)D3 level. CONCLUSION: These findings suggest that diet-induced elevation of circulating cholesterol, glucose, and insulin reduces serum 25(OH)D3 level through suppressing hepatic Cyp2r1 expression.

FADB-China: A molecular-level food adulteration database in China based on molecular fingerprints and similarity algorithms prediction expansion.

Food adulteration is a growing concern worldwide. The collation and analysis of food adulteration cases is of immense significance for food safety regulation and research. We collected 961 cases of food adulteration between 1998 and 2019 from the literature reports and announcements released by the Chinese government. Critical molecules were manually annotated in food adulteration substances as determined by food chemists, to build the first food adulteration database in China (http://www.rxnfinder.org/FADB-China/). This database is also the first molecular-level food adulteration database worldwide. Additionally, we herein propose an in silico method for predicting potentially illegal food additives on the basis of molecular fingerprints and similarity algorithms. Using this algorithm, we predict 1919 chemicals that may be illegally added to food; these predictions can effectively assist in the discovery and prevention of emerging food adulteration.

Primary small cell carcinoma of the esophagus: Comparison between a Chinese cohort and Surveillance, Epidemiology, and End Results (SEER) data.

BACKGROUND: The optimal standard treatment for primary small cell carcinoma of the esophagus (SCCE) remains undetermined. In this study, we conducted two areas of research on SCCE. First, we analyzed differences in SCCE characteristics between Chinese and U.S. PATIENTS: Second, we evaluated optimal treatment strategies for SCCE in the Chinese cohort. METHODS: Data from 137 Chinese SCCE patients collected from two cancer centers in China were compared with 385 SCCE patients registered in the U.S. SEER program. Prognostic factors were further analyzed in the Chinese group. Propensity score matching (PSM) was used to balance baseline features between the groups. RESULTS: There were more Chinese SCCE patients with regional stage disease (41.6%) and surgery was the principal local therapy (78.1%), while 51.7% of U.S. patients was at advanced stages and tended to receive radiotherapy as the main therapy (45.2%). Median overall survival (MST) of Chinese patients was 15.0 months, compared with 8.0 months for U.S. patients (P < 0.001). However, the survival differences between groups disappeared after PSM (MST: 12.5 m vs 9.0 m, P = 0.144). Further analysis found that surgery tended to achieve clinical benefits only for patients with localized disease (T1-4aN0M0). Radiotherapy and chemotherapy may prolong survival in patients with regional and extensive disease. CONCLUSIONS: Although there are huge differences in the tumor characteristics and treatment modalities of SCCE between Chinese and U.S. patients, the prognosis of SCCE is equally poor in both. Surgery should be considered for patients with localized disease, while chemoradiotherapy is recommended for patients with regional and extensive disease.

Dosimetric comparison of left-sided whole breast irradiation with 3D-CRT, IP-IMRT and hybrid IMRT.

The aim of this study was to compare the dosimetric characteristics of left-sided whole breast irradiation among 3-dimensional conformal radiotherapy (3D-CRT), 4-field inverse-planned intensity-modulated radiotherapy (IP-IMRT) and hybrid IMRT technique (combining 3D-CRT beams and IP-IMRT beams) with respect to target coverage and irradiation of organs at risk. The 3 different planning techniques were analyzed for 8 patients with left-sided breast conserving surgery. Plans were compared on the basis of planning target volume (PTV) dose conformity, homogeneity and the volumes of normal tissues treated based on dose-volume histograms (DVHs). DVHs were calculated for the PTV, heart, and the bilateral lungs, contralateral breast, and soft tissue surrounding the breast PTV (VOB) volume. IP-IMRT and hybrid IMRT techniques comparably improved the PTV dose homogeneity and conformity (CI) significantly, compared to the conventional 3D-CRT technique (P<0.017); the IP-IMRT technique only could additionally benefit patients by decreasing the high-dose (40 Gy) volume for heart and ipsilateral lung compared with the hybrid IMRT technique (P<0.017); the hybrid IMRT plans achieved a further improvement by compromising the increase of low-dose volume (total lung V13, contralateral lung V5, heart V10 and soft tissue surrounding the breast V5) compared with IP-IMRT plans (P<0.017). Hybrid IMRT plans achieved equivalent PTV dose uniformity to IP-IMRT plans and compromised the low-dose volume and requirement of clinic resource between IP-IMRT and 3D-CRT plans, promoting it as a standard practice of left-sided breast irradiation for patients in good-ordered cardiopulmonary health.

Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma.

Single nucleotide polymorphisms (SNPs) in the p53, MDM2 and p21 genes of the p53 pathway have been extensively studied. The main aim of the current retrospective study was to evaluate the possible predictive value of SNPs in the p53 pathway in locoregionally advanced nasopharyngeal carcinoma (NPC) in response to radiotherapy. In total, 75 consecutive patients with locoregionally advanced NPC were enrolled. Three SNPs in the p53 pathway were identified using the Sanger sequencing method from retrospectively collected paraffin-embedded biopsy specimens. The effects of genetic polymorphisms on patient progression­free survival (PFS) were analyzed using the Cox proportional hazards model, Kaplan-Meier method and log-rank test. All of the selected subjects completed questionnaires on smoking habits prior to treatment. Multivariate analysis showed that the p53 codon 72 Pro/Pro genotype [hazard ratio (HR), 0.300; 95% confidence interval (CI), 0.092-0.983; P=0.047] and heavy smoking (≥30 pack-years) (HR, 2.899; 95% CI, 1.349-6.229; P=0.006) are independent significant prognostic factors for PFS in patients with locoregionally advanced NPC. Moreover, mean times to disease progression for heavy smokers (≥20 pack-years) carrying p53 codon 72 Arg/Arg, p21 codon 31 Arg/Arg and MDM2 309 SNP G/G genotypes were only 14.78 ± 3.00, 11.00 ± 0.58 and 11.17 ± 1.85 months, respectively. These time scales were less than half of those recorded for patients containing other genotypes and moderate smokers (<20 pack-years). In conclusion, the p53 codon 72 polymorphism is an independent prognostic marker for locoregionally advanced NPC. Moreover, analysis of SNPs in the p53 pathway may facilitate the identification of patients at high risk of poor disease outcome in subgroups of heavy smokers.

[Dosimetric comparison of left-side whole breast irradiation with IMRT and hybrid IMRT].

OBJECTIVE: To evaluate the potential dosimetric benefits and optimal indications of intensity modulated radiation therapy (IMRT) and hybrid intensity modulated radiation therapy (Hybrid IMRT) for the left side breast cancer patients after breast-conservation therapy. METHODS: Eight patients with left breast carcinoma who received breast-conservation surgery were selected for this study. Two plans were designed in 3-dimensional treatment planning system. The dose distributions of target volume and normal tissues, conformal index (CI) and heterogeneous index (HI) were analyzed by dose-volume histogram (DVH). RESULTS: The PTV coverage was the same in the two radiotherapy plans. A better dose uniformity throughout the whole breast in Hybrid IMRT plan was achieved. The CI, the percentage of PTV receiving more than 105% prescribed dose (V105%), the percentage of PTV receiving more than 110% prescribed dose (V110%), and the Dmax, Dmin and Dmean of PTV were similar in the two plans. We compared the Hybrid IMRT with IMRT: V13 of the ipsilateral lung decreased from 27.66% to 20.7%, V5 of the contralateral lung decreased from 8.01% to 2.25%, V10 and V20 of the heart decreased from 35.23% and 16.77% to 19.22% and 10.6% respectively, V5 and V10 of the contralateral breast decreased from 35% and 10.39% to 20.38% and 5.7% respectively, all with significant difference. V30 and V40 of the ipsilateral lung and V40 of the heart increased by 1.28%, 1.48%, and 2.48%, with significant difference. CONCLUSION: Hybrid IMRT is a better choice for patients whose treatment position is inaccurate or cannot be repeated well.

Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma.

BACKGROUND: Codon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment. MATERIALS AND METHODS: In total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan-Meier method, and log-rank test. RESULTS: The p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092-0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032). CONCLUSIONS: The p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.

Predictive value of Xrcc1 gene polymorphisms for side effects in patients undergoing whole breast radiotherapy: a meta-analysis.

Radiation-induced side effects on normal tissue are determined largely by the capacity of cells to repair radiation-induced DNA damage. X-ray repair cross-complementing group 1 (XRCC1) plays an important role in the repair of DNA single-strand breaks. Studies have shown conflicting results regarding the association between XRCC1 gene polymorphisms (Arg399Gln, Arg194Trp, -77T>C and Arg280His) and radiation-induced side effects in patients undergoing whole breast radiotherapy. Therefore, we conducted a meta-analysis to determine the predictive value of XRCC1 gene polymorphisms in this regard. Analysis of the 11 eligible studies comprising 2,199 cases showed that carriers of the XRCC1 399 Gln allele had a higher risk of radiation-induced toxicity than those with the 399 ArgArg genotype in studies based on high-quality genotyping methods [Gln vs. ArgArg: OR, 1.85; 95% CI, 1.20-2.86] or in studies with mixed treatment regimens of radiotherapy alone and in combination with chemotherapy [Gln vs. ArgArg: OR, 1.60; 95% CI, 1.09-2.23]. The XRCC1 Arg399Gln variant allele was associated with mixed acute and late adverse reactions when studies on late toxicity only were excluded [Gln allele vs. Arg allele: OR, 1.22; 95% CI, 1.00-1.49]. In contrast, the XRCC1 Arg280His variant allele was protective against radiation-induced toxicity in studies including patients treated by radiotherapy alone [His allele vs. Arg allele: OR, 0.58; 95% CI, 0.35-0.96]. Our results suggest that XRCC1 399Gln and XRCC1 280Arg may be independent predictors of radiation-induced toxicity in post-surgical breast cancer patients, and the selection of genotyping method is an important factor in determining risk factors. No evidence for any predictive value of XRCC1 Arg194Trp and XRCC1 -77T>C was found. So, larger and well-designed studies might be required to further evaluate the predictive value of XRCC1 gene variation on radiation-induced side effects in patients undergoing whole breast radiotherapy.

[Inhibitive effect of E1A gene on the cell growth of human cervical carcinoma cell in vitro].

OBJECTIVE: To investigate the inhibitive effect of E1A gene carried by PEI-Fe(3)O(4) nanometer particle (NP) on the cell growth of human cervical carcinoma cell in vitro and its mechanism, and to provide the experimental evidence for the feasibility of gene therapy for human cervical carcinoma. METHODS: E1A gene conjugated to PEI-Fe3O4 NP was transfected into human cervical carcinoma cell line Hela. The cell growth curve of Hela was drawn, the doubling time and the number of colony formations on the soft agar were calculated based on the cell count. RT-PCR and Western blot were used to detect the expression of the E1A and HER-2/neu in Hela cells. RESULTS: The cell doubling time of Hela cells transfected with E1A gene (Hela-E1A) was 1.53 times and 1.58 times longer than that of the Hela transfected with blank vector (Hela-vector) and blank Hela control (Hela), respectively. The E1A transfected Hela cells grew slower than those of the control group. The cell colony formation efficiency in the Hela-E1A (6.62%) group was significantly lower than that of Hela (30.48%) and Hela-vector (28.3%) groups (P<0.05). As compared to Hela and Hela-vector, the inhibition rate of Hela-E1A was 78.28% and 76.62% respectively. RT-PCR and Western blot demonstrated that the overexpression of E1A through gene transfection significantly inhibited mRNA and protein expression of HER-2/neu in Hela cells. CONCLUSION: E1A gene can suppress the cell growth of human cervical carcinoma cell Hela in vitro. Down-regulated expression of HER-2/neu gene by E1A overexpression in Hela might contribute to the Hela growth inhibitive effect of E1A.