Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Vitamin D is the precursor of 1, 25-dihydroxyvitamin D, which is considered as the critical hormone involved in the regulation of calcium and phosphate homeostasis and bone metabolism. Adequate vitamin D status is very important in the maintenance of bone health. However, recent controlled vitamin D intervention studies showed controversial results. One of the important reasons for this is the difference in the baseline of vitamin D status among studies. The vitamin D status in the Chinese population is much lower as compared to that in Western countries. Postmenopausal women and elderly with vitamin D deficiency should take appropriate vitamin D supplementation in order to achieve serum 25-hydroxyvitamin D levels greater than 20 ng/ml or even 30 ng/ml. However, it may be difficult to bring more benefits from excessive supplementation in order to maintain bone health.

Vitamin D participates in a variety of biological processes. 1,25-dihydroxyvitamin D [1,25-(OH)2D]is the active form of vitamin D. Besides its classical role in bone and calcium homeostasis, 1,25-(OH)2D has many non-classical functions such as regulating proliferation and differentiation of cells in various tissues, including tumor cells as well. However, the role of 1,25-(OH)2D in thyroid cancer is not clear yet. There are three integral components of the vitamin D pathway in thyroid cells. These components are the vitamin D receptor, 1α-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1). Differences in the expression levels of these components in normal thyroid tissue and thyroid cancer tissue may offer clues and lay the foundation for study of the inhibitory function in the pathogenesis of thyroid cancer.This review focuses on the insights gained in the elucidation of the role of 1,25-(OH)2D pathway in thyroid cancer, one of the most common endocrine malignancies.

Objective To quantifying the urine human cytomegalovirus(HCMV)DNA from the HCMV infection infants and its corresponding liver function indications,and investigate the relationship between their concentrations.Methods The u-rine samples were collected from HCMV infection infants.HCMV DNA was measured by fluorescence quantitative polymer-ase chain reaction (FQ-PCR).Serum ALT,AST,ALP,GGT,T-Bil and D-Bil liver function indications were detected and the positive rate was analyzed,simultaneously.The correlation between the logarithm urine HCMV DNA (log HCMV DNA) concentration and ALT,AST,ALP,GGT,T-Bil and D-Bil were analyzed by Spearman correlation analysis.Results The dis-tribution range ofurine log HCMV DNA in 444 HCMV infection infants was <2.70~7.90;the positive rate of serum ALT, AST,ALP,GGT,T-Bil and D-Bil were 24.8%,59.0%,95.7%,31.1%,16.7% and 16.3%,respectively.The urine log HC-MV DNA was associated with GGT and the correlation coefficient was 0.099 (P < 0.05),but no associated with ALT, AST,ALP,T-Bil and D-Bil.Conclusion The positive rate of liver function indications will rise in HCMV infection infants, the urine log HCMV DNA was associated with GGT,but not associated with other liver function indications.

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.
Gamma Rays ; Humans ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; instrumentation ; methods

To investigate the patient-specific dose verification method using ArcCHECK for total marrow irradiation (TMI) with Volumetric Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). The kVCT images collected from 8 patients were respectively designed for RapidArc and Tomotherapy plans in total marrow irradiation. ArcCHECK was used for dose verification for the head-neck, chest-abdomen and pelvic. The merging function of ArcCHECK was used in VMAT and the method of double plans (reference and delivery plans) were used in HT. The γ-analysis passing rates for the head-neck, chest-abdomen, pelvic were 98.9% ± 1.9%, 98.4% ± 1.8%, 97.4% ± 2.1% for VMAT plans and 94.3% ± 1.5%, 96.5 ± 1.2%, 94.1% ± 1.9% for HT plans. The results show that using the merging function of ArcCHECK can achieve the dose verification well for VMAT plans with TMI. The method of double plans was done for the dose verification of HT plans with TMI as well as the plans with the targets keeping away from the set-up center.
Bone Marrow ; radiation effects ; Humans ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

Objective To observe the correlation between the prevalence thyroid nodules and breast tumors in female subjects. Methods Perform thyroid and breast examination at the same time by utilizing color doppler ultrasound on 855 female subjects from the electric power enterprise of Huaihua city in Hunan province in July 2014. Results Thy-roid nodules were found in 240 subjects (28.1%) and breast tumors in 94 subjects (11.1%), while 34 subjects (4.0%) were found to have both thyroid nodules and breast tumors simultaneously. Our present data showed that thyroid nodule prevalence rate increased with age, while the highest prevalence rate of breast tumor was in the 40y's group (16.7%). There was a positive correlation between the prevalence rate of breast tumor and that of thyroid nodule in subject less than 50 years old (χ2=7.007,P=0.008,OR=2.196). Conclusion Thyroid nodule prevalence rate increased with age, and female subjects less than 50 years old with thyroid nodule have an increased risk of developing breast tumors.

To investigate the patient-specific dose verification method using ArcCHECK for total marrow irradiation (TMI) with Volumetric Modulated Arc Therapy(VMAT) and Helical Tomotherapy(HT) . The kVCT images col ected from 8 patients were respectively designed for RapidArc and Tomotherapy plans in total marrow irradiation. ArcCHECK was used for dose verification for the head-neck, chest-abdomen and pelvic. The merging function of ArcCHECK was used in VMAT and the method of double plans(reference and delivery plans) were used in HT. The γ-analysis passing rates for the head-neck, chest-abdomen, pelvic were 98.9%±1.9%, 98.4%±1.8%, 97.4%±2.1% for VMAT plans and 94.3%±1.5%, 96.5±1.2%, 94.1%±1.9% for HT plans. The results show that using the merging function of ArcCHECK can achieve the dose verification wel for VMAT plans with TMI, The method of double plans was done for the dose verification of HT plans with TMI as wel as the plans with the targets keeping away from the set-up center.

Objective To investigate the serum concentration of 25-hydroxyl vitamin D in the common autoimmune diseases and whether the differences of the 25-hydroxyl vitamin D level exist in different autoimmune diseases.Methods 137 cases of autoim-mune diseases,including 71 cases of rheumatoid arthritis(RA),36 cases of systemic lupus erythematosus(SLE),16 cases of Sjogren syndrome(SS)and 14 cases of ankylosing spondylitis(AS),in our hospital from January 2012 to April 2013 were selected as the re-spondents.The serum samples were collected for detecting the 25-hydroxyl vitamin D level by the electrochemiluminescence method and comparing the differences of the 25-hydroxyl vitamin D level among different autoimmune diseases.At the same time whether the differences in the proportion of the normal level,insufficiency and lack of 25-hydroxyl vitamin D exist among different kinds of disease.Results The serum 25-hydroxyl vitamin D concentration had statistically significant difference among the patients with dif-ferent autoimmune diseases(P =0.006),which in the RA group was significantly higher than that in the other groups;the propor-tion of 25-hydroxyl vitamin D insufficiency in RA,SLE,SS and AS were 29.6%,52.8%,62.5% and 57.1% respectively,which in the SLE,SS and AS groups was significantly higher than that in the RA group(P <0.05).Conclusion The 25-hydroxyl vitamin)D insufficiency is general in common autoimmune diseases,the vitamin D supplements needs to be strengthened.

Objective The aim of this work is to compare the performances of EDR2 film dosimetry with two-dimensional ion chamber array (2DICA) in quality assurance (QA) procedures and to investigate the origin of possible discrepancies between the two methods.Methods A 2DICA, I′mRT MatriXX and MULTICube equivalent solid water phantom from IBA Company were used to verify the dose distribution of 15 tomotherapy plan cases.The combined phantom which includes EDR2 film on the array was set up to measure the dose distribution from coronal and sagittal orientations.After the irradiation, the dose distributions of 2DICA and film were compared with those calculated in the planning system for verification.The results and efficiency were evaluated independently in the two methods.Results The mean number of points satifying γ parameter ≤1 in the coronal and sagittal planes was 97.00%±1.56%& 95.98%±2.52%(t=-2.22,P=0.043) and 98.28%±1.55%& 95.42%±1.99%(t=0.75,P=0.464) of the 15 cases respectively for 2DICA and EDR2 film.The ratio of more than 90% and 95% were 93.3% and 66.7%.The results we presented show a very good agreement between the two methods when used to assess the dose distribution between calculated and measured doses,and a certain degree of correlation (r=0.14,P=0.001).Conclusions The 2DICA may effectively replace both film and ion chamber dosimetry in routine IMRT QA.The good agreement between 2DICA and EDR2 film may give a possible check regularly just as a gold standard.