[Single-center study of the abnormal concentration of bone imaging agent and prostate cancer bone metastasis prediction model].

Objective: To investigate the relationship between total prostate specific antigen (TPSA), free prostate specific antigen/total prostate specific antigen [RAT (F/T)], Gleason score, other factors and the whole-body bone plane imaging which was used to evaluate the bone metastasis of prostate cancer (PCa), and the diagnostic value of the abnormal concentration of bone imaging agent for single lesion. Methods: A retrospective analysis of (99)Tc(m)-methylene diphosphonate ((99)Tc(m)-MDP) whole-body bone imaging data of 93 patients with confirmed PCa in The First Hospital of Shanxi Medical University from Jan 2018 to Jan 2019 was conducted. The bone metastasis was diagnosed by whole-body bone imaging. The factors related to PCa bone metastasis, including age, TPSA, RAT (F/T), Gleason score were analyzed by Chi-square test and logistic two-class regression. The optimal cut-off point of TPSA was defined by receiver operating characteristic (ROC) curve. The region of interest (ROI) technique was used to repeatedly delineate the lesion (T) and the background area (NT) outside the bone and calculate the abnormal concentration value of bone imaging agent (T-NT)/NT, and the ROC curve was used to determine its diagnostic value. Results: The result of Chi-square analysis showed that Gleason score, TPSA and RAT (F/T) were associated with bone metastasis (P<0.05). Logistic regression analysis showed that TPSA and RAT (F/T) were associated with bone metastasis (P<0.01). TPSA >92.82 ng/ml was the best diagnosis for bone metastasis, and the sensitivity and specificity were 77.1% and 81.0%, respectively. There were 320 sites of high concentration of imaging agents in the whole-body bone imaging of PCa patients (194 in the metastatic group and 126 in the non-metastasis group). The (T-NT)/NT in the bone metastasis group was 7.11±0.29, the non-bone metastasis group was 2.69±0.20. (T-NT)/NT >3.52 was the best diagnosis for bone metastasis of single lesion, and the sensitivity and specificity were 86.1% and 80.2%, respectively. Conclusions: Gleason score, RAT (F/T) and TPSA are important risk factors of PCa bone metastasis. TPSA >92.82 ng/ml is the most supportive diagnosis for PCa bone metastasis. The abnormal concentration of bone imaging agent >3.52 owns the best diagnosis effect for the single lesion of PCa.

[Value of dynamic MRI in monitoring the microenvironmental changes of anti-vascular therapy in a xenograft model].

Objective: To explore the feasibility of dynamic-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent MRI (BOLD-MRI) in assessing the hemodynamics and tumor aggressiveness during treatment. Methods: The colon cancer xenograft model was established in BALB/C nude mice with HCT116 cell line. Sixteen nude mice were randomly divided into treatment and control groups (aged 6 to 8 weeks, weighted 15 to 18 g, Certificate No. 11400700325797), which were treated with bevacizumab and saline by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th day. DCE-MRI and BOLD-MRI were performed before and on the 3th, 6th, 9th, 12th, and 15th day after treatment. The vascular maturity and microenvironment hypoxia were confirmed by pathology. Results: The tumor volume of treatment group was significantly smaller than that of control group after 15 days ((712±43) vs (1 051±112) mm(3),P<0.01).The measurements of K(trans) were (0.135±0.005),(0.147±0.006),(0.175±0.009),(0.161±0.006), (0.140±0.005),(0.116±0.008)/min (F=81.386, P<0.01); K(ep) were (0.788±0.030),(0.804±0.036),(0.983±0.059), (1.105±0.091),(0.840±0.047),(0.786±0.041)/min(F=45.901,P<0.01);Ve were (0.652±0.006), (0.559±0.026), (0.466±0.016), (0.286±0.027), (0.363±0.020), (0.246±0.033) (F=384.290, P<0.01) and R2* values were (24.813±0.961), (24.675±1.070), (21.425±1.371), (17.850±0.885), (24.613±0.640), (27.013±0.734)/s (F=89.323, P<0.01) showed different trends with time in the treatment group, and the differences were statistically significant. The K(trans) values and tumor vessel maturity index (VMI) were higher than baseline values during 3-12 d after treatment. CD31 positive staining rate and VMI had the strongest correlations with K(trans) values (r=0.854 and 0.795), followed by AUC(180) (r=0.750 and 0.808), Ve (r=0.744 and 0.712) and K(ep) values (r=0.729 and 0.758), all P<0.05. R2* value positively correlated with the positive staining rate of HIF-1α and fibronectin (r=0.810 and 0.816), all P<0.05. Conclusion: DCE-MRI and BOLD-MRI are adequate to observe the tumor perfusion and hypoxia during anti-vascular treatment, and the R2* value can predict the tumor metastatic potential during the process of vascular normalization.

Association between GSTM1, GSTT1, and GSTP1 polymorphisms and gastric cancer risk, and their interactions with environmental factors.

Glutathione S-transferase (GST) is an important member of phase II metabolic enzymes; GSTM1, GSTT1, and GSTP1 belong to three subfamilies of the GST enzyme. Polymorphisms in GSTM1, GSTT1, and GSTP1 could affect detoxification processes, and increase individuals' susceptibility to cancers. We aimed to investigate the association between GSTM1, GSTT1, and GSTP1 polymorphisms and the risk of gastric cancer in a Chinese population. In addition, we also examined the effect of gene-environmental interactions, and their effect on risk of this cancer. Between July 2013 and June 2015, we recruited 242 gastric cancer patients and 396 healthy controls for our study. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to characterize genetic polymorphisms in GSTM1, GSTT1, and GSTP1. We observed that the Val/Val genotype of GSTP1 was associated with increased risk of gastric cancer when compared with the Ile/Ile genotype (OR = 3.19, 95%CI = 1.84-5.56). Moreover, the Val allele of GSTP1 was associated with higher susceptibility to gastric cancer as compared with the Ile allele (OR = 1.52, 95%CI = 1.19-1.93). However, GSTM1 and GSTT1 polymorphisms did not affect the development of gastric cancer. In conclusion, our study indicated that GSTP1 Ile105Val, but not GSTM1 and GSTT1 polymorphisms, was associated with risk of gastric cancer.

Analysis of ADH1B Arg47His, ALDH2 Glu487Lys, and CYP4502E1 polymorphisms in gastric cancer risk and interaction with environmental factors.

Gastric cancer is the fourth commonly diagnosed cancer and the second most frequent cause of cancer death worldwide. Genetic variations in ADH1B and ALDH2 may alter the function and activity of the corresponding enzymes, leading to differences in acetaldehyde exposure between drinkers. Cytochrome P4502E1 (CYP4502E1) is a phase I enzyme that plays an important role in metabolizing nitrosamine compounds and the bioactivation of procarcinogens. During the period of July 2013 to July 2015, 246 patients and 274 controls were enrolled from the First Affiliated Hospital of Jinan University. In the codominant model, the AA genotype of ALDH2 Glu487Lys significantly elevated the risk of gastric cancer in comparison with the GG genotype of ALDH2 Glu487Lys. In the recessive model, the AA genotype of ALDH2 Glu487Lys significantly increased the risk of gastric cancer compared to the GG+GA genotype (OR = 2.34 95%CI = 1.02-5.70). We found in the codominant model that individuals harboring the C2/C2 genotype of CYP4502E1 had a higher risk of developing gastric cancer than those with the C1/C1 genotype. In addition, in the recessive model, we found that the C2/C2 genotype correlated with an elevated risk of gastric cancer in comparison with the C1/C1+C1/C2 genotype (OR = 4.90, 95%CI = 2.04-13.51). However, no significant relationship was measured between ADH1B Arg47His and gastric cancer risk. In summary, the results of our study indicate that ALDH2 Glu487Lys and CYP4502E1 polymorphisms could be risk factors for the development of gastric cancer in the Chinese population.

Investigations on the genomic diversity of OXA from isolated Acinetobacter baumannii.

We distinguished the four OXA-type carbapenemase subgroup alleles present in 120 strains of Acinetobacter baumannii by using polymerase chain reaction (PCR) and investigated the distributions of the OXA subgroups in clinically isolated samples. Amplification of the OXA genes blaOXA-23, blaOXA-24, blaOXA-51, and blaOXA-58 was performed by multiplex PCR. Antibiotics susceptibility test was conducted for determine the sensitivity of the A. baumannii to clinical common used antibiotics by Kirby-Bauer method. Results revealed that 46 (51.69%) of the samples were positive for only the blaOXA51 gene and 41 (46.07%) were positive for both the blaOXA51 and blaOXA58 genes in the 89 isolates of A. baumannii. Among these, 45 were carbapenem-resistant and 44 carbapenem-sensitive. Strains containing either blaOXA51 or blaOXA58 showed resistance or sensitivity to carbapenems, respectively. A. baumannii isolated from intensive care units showed significantly higher resistance rate to Cefepime, Piperacillin-tazobactam, Amikacin, Ceftazidime, Cefotaxime, Sulfamethoxazole-trimethoprim, and Gentamicin than those isolated from other departments (P < 0.05). In conclusion, we found that the presence of blaOXA-51 and blaOXA-58 appears to convey a mechanism of resistance or sensitivity to carbapenems, respectively, in A. baumannii clinical isolates.

Direct detection of chloramphenicol in honey by neutral desorption-extractive electrospray ionization mass spectrometry.

Herein, we constructed a platform of neutral desorption-extractive electrospray ionization mass spectrometry (ND-EESI-MS) for direct and rapid detection of chloramphenicol (CAP) in honey samples diluted with methanol. Under the optimized working conditions, the quantitative information of CAP residues was acquired effectively by EESI-Ion Trap MS (n) . Using heated methanol-N2 as spray reagent, we reduced the limit of determination (LOD) from 73.3 ng/mL to 0.3 ng/mL, and the CAP detection is linear in the range of 1-5000 ng/mL (R = 0.9947). For the honey samples with CAP of 10, 100, and 1000 ng/mL, the recoveries were 133.0, 80.6, and 101.1%, and the relative standard deviations were 5.96, 8.82, and 8.71%, respectively. The reproducibility assays showed the stability of this method. Therefore, this ND-EESI-MS method is powerful for direct, rapid, and quantitative CAP analysis in honey samples with high sensitivity, precision, and specificity.

Association of DNA repair gene polymorphisms with response to chemotherapy and prognosis of gastric cancer.

We investigated the correlation between the response to chemotherapy in patients and excision repair cross-complimenta-ry group 1 gene (ERCC1) and xeroderma pigmentosum complemen-tation group F gene (XPF) polymorphisms and the effect of these polymorphisms on the clinical outcome of gastric cancer. Samples from a total of 255 patients with newly diagnosed and histopatho-logically confirmed primary gastric cancer were collected in our study. The ERCC1 rs11615, ERCC1 rs2298881, XPF rs2276465, and XPF rs6498486 polymorphisms were genotyped. Among the 255 patients, the median follow-up time was 29.7 months. A total of 103 patients (40.4%) died from gastric cancer during the follow-up period. We observed that the XPF rs6498486 CC genotype and the XPF rs2276465 GG genotype were associated with response to che-motherapy, with odds ratios and 95% confidence intervals of 3.88 (1.23-16.07) and 2.66 (1.17-6.45), respectively. In the Cox propor-tional hazards model, patients carrying the ERCC1 rs11615 AA gen-otype and the XPF rs2276465 GG genotype showed only a 0.22- and 0.30-fold increased risk of death from gastric cancer. We found that the XPF rs6498486 and XPF rs2276465 polymorphisms are mark-ers of response to oxaliplatin/5-fluorouracil-based chemotherapy in gastric cancer patients.

[The correlation between children's serum 25-hydroxyvitamin D and allergic rhinitis in Jiangxi Province].

Objective:We attempt to investigate the correlation between serum 25-hydroxyvitamin Dï¼»25(OH)Dï¼½ level and allergic rhinitis(AR) of children in Jiangxi Province,for providing new clues for the pathogenesis of AR in children.Method:Seventy-six AR children and 68 healthy controls from various counties and cities of Jiangxi Province were enrolled. All subjects recepted questionnaire survey, allergen skin prick test,serum specific IgE test,serum 25(OH)D test and routine blood test. AR children completed the visual analogue scale(VAS) scores and rhinoconjunctivitis quality of life questionnaire(RQLQ) scores.Result:The mean body mass index(BMI) of AR children in Jiangxi Province was significantly lower than that of healthy peers (P<0.000 1),but there was no correlation between BMI and serum 25(OH)D level.Serum 25(OH)D level of AR children was signtificantly lower,compared to the conrtols (P=0.0008),while the area under the receiver operating characteristic curve(AUC)of subjects was 0.6614, That is,serum 25(OH)D was not an efficient auxiliary diagnosis in AR children.Serum 25(OH)D level of AR children was not correlated with the severity, gender,peripheral blood eosinophils and asthma.Conclusion:AR can affect the growth and development of children.Children's serum 25(OH)D deficiency was correlated to AR, but its efficiency for auxiliary diagnosis in AR is not high.So it cannot be used as an auxiliary indicator for clinical diagnosis of AR.Serum 25(OH)D may not be directly involved in the pathogenesis of children's AR.

[Expression of LC3 and ECP in allergic rhinitis and their significance].

Objective:To investigate the expression of microtubuleassociated protein 1 light chain 3 beta(LC3) and eosinophil cationic protein in allergic rhinitis(AR) for further understanding of the pathogenesis of AR. Method: Twenty cases of normal nasal mucosa and 20 cases of AR nasal mucosa were collected. Histological changes of nasal mucosa were examined by hematoxylin and eosin(HE) staining. The expression of LC3 and ECP were measured by immunohistochemistry(IHC) and Western Blot(WB). Result: The tissue samples demonstrated a large number of eosinophils and lymphocytes infiltration in AR. IHC revealed that LC3 and ECP expression were higher in AR than in normal nasal mucosa(P<0.05). WB also showed that the relative expression levels of protein expression of LC3 and ECP were greater in AR than in controls. The expression level of LC3 was positively correlated with that of ECP protein in AR. Conclusion: LC3 and ECP were upregulated and positively correlated in AR, indicating that autophagy plays an important role in the toxicity of allergic rhinitis , which provides theoretical basis for the precise treatment of AR.

The lack of Raf-1 kinase feedback regulation enhances antiapoptosis in cancer cells.

Raf-1 has an important role in cellular antiapoptosis. So far, there is no solid evidence that shows that Raf-1 mutation is associated with cancer development. In the course of further study of Raf-1 signaling, we have reported that Raf-1 hyperphosphorylation inhibits its kinase activity toward its downstream mitogen-activated protein kinase kinase 1/2 (MEK1/2) and proposed a model for negative feedback regulation of Raf-1. Here, we show that there is no hyperphosphorylation in some cancer cells, which results in increased kinase activity and enhances the antiapoptotic ability. Inhibition of either Raf-1 or ALG-2 (apoptosis-linked gene 2) expression results in apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase (ASK1/JNK) signaling activation, and cell sensitivity to chemotherapeutic reagents, indicating that inhibition of ASK1/JNK apoptotic signaling by Raf-1 is mediated by ALG-2. A previous report indicated that extracellular signal-regulated kinase 1/2 (ERK1/2) were responsible for Raf-1 hyperphosphorylation. However, our evidence shows that when ERK1/2 are activated and the Raf-1 gene is not mutated, Raf-1 is not hyperphosphorylated in these cells, indicating that ERK1/2 are not responsible for the Raf-1 hyperphosphorylation in these cancer cell lines. Surprisingly, we also found that Raf-1 is not a necessary kinase for MEK1/2 activation under normal tissue culture conditions, but is required for MEK1/2 activation under apoptosis-inducing conditions. Our research demonstrates that although Raf-1 gene is not mutated, an abnormality of Raf-1 kinase feedback regulation enhances its antiapoptotic function, and Raf-1 can still be a pharmaceutical target to increase chemotherapy or radiotherapy sensitivity in these cancer cells.