Interactive regulatory effect of histone H3K9ac acetylation and histone H3K9me3 methylation on cardiomyogenesis in mice / 中国当代儿科杂志

OBJECTIVE@#To study the interactive regulatory effect of histone acetylation and methylation on cardiomyogenesis, and to provide a theoretical basis for the prevention and treatment of congenital heart disease.@*METHODS@#A total of 24 Kunming mice were randomly divided into embryo day 14.5 (ED 14.5) group, embryo day 16.5 (ED 16.5) group, postnatal day 0.5 (PND 0.5) group, and postnatal day 7 (PND 7) group, with 6 mice in each group, and the heart tissue of fetal and neonatal mice was collected. Colorimetry was used to measure the activities of histone acetylases (HATs) and histone methyltransferases (HMTs) in the myocardium. Western blot was used to measure the expression of H3K9ac and H3K9me3 in the myocardium.@*RESULTS@#Colorimetry showed that the activities of HATs and HMTs were higher before birth and were lower after birth. There was a significant difference in the activity of HATs in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 group (P<0.05), as well as between the PND 7 group and the ED 16.5 group (P<0.05). There was also a significant difference in the activity of HMTs in the myocardium between the PND 7 group and the ED 14.5 and ED 16.5 groups (P<0.05). Western blot showed higher expression of H3K9ac and H3K9me3 before birth and lower expression of H3K9ac and H3K9me3 after birth, and there were significant differences in the expression H3K9ac and H3K9me3 in the myocardium between the PND 0.5 and PND 7 groups and the ED 14.5 and ED 16.5 groups (P<0.05).@*CONCLUSIONS@#The dynamic expression of HATs, HMTs, H3K9ac, and H3K9me3 is observed during cardiomyogenesis, suggesting that histone H3K9ac acetylation and histone H3K9me3 methylation mediated by HATs and HMTs may play a role in interactive regulation during cardiomyogenesis.

Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms / 한국실험동물학회지

The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50–60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.

Exploring Genome-wide DNA Methylation Profiles Altered in Kashin-Beck Disease Using Infinium Human Methylation 450 Bead Chips / 生物医学与环境科学（英文）

To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high-resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome-wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD.

Relationship bewteen gastric pH and hospital-acquired pneumonia in neurological intensive care unit patients / 中华神经科杂志

Objective To explore the relationship between gastric juice pH and hospital-acquired pneumonia ( HAP) , the gastric bacterial colonization and etiology of HAP in neurologic intensive care unit patients by monitoring gastric juice pH value.Methods From October 2014 to May 2015, consecutive seventy-two tube feeding patients admitted in the Department of Neurology Intensive Care Unit in Xijing Hospital were enrolled in this research.The type and concentration of pathogens from gastric contents were collected, while samples from upper respiratory tract and pharynx were detected dynamically at the same time.Results (1)The group with new onset HAP was higher in gastric juice pH (6.4(5.4,6.4) vs 5.4 (2.5, 6.4), Z=-2.37, P=0.01); (2) The isolation rate of colonized bacteria in gastric cavity was associated with the pH of gastric juice , achieving 60.8% ( 42/69 ) in HAP group; ( 3 ) When the gastric juice pH was >4, the isolation rate of Gram-negative bacilli in gastric cavity obviously increased (63.6%(28/44) vs 35.7%(10/28),χ2 =5.323, P=0.021); (4)The same pathogens were found in stomach-pharynx-upper respiratory tract in 7 cases ( 17.5%) of the total 40 HAP patients.Conclusion Increased gastric juice pH was associated with gastric colonization , especially Gram-negative bacilli , and may lead to a higher incidence of new onset HAP in patients on enteral feeding.

Analysis of 1H Magnetic Resonance Spectroscopy Pattern in Invasive Ductal Carcinoma of Breast / 의학물리

To evaluate the potential value of 1H Magnetic resonance spectroscopy (MRS) for detecting and characterizing invasive ductal carcinoma of breast. We conducted 1H Magnetic resonance spectroscopy (MRS), using a 3.0T MR scanner, on 40 patients who were histologically diagnosed to have invasive ductal carcinoma (IDC); tumor areas of the patients were designated as experimental samples, and non-tumor areas as control samples. The peak at 3.2 ppm is characteristically intense and observed in 34 cases of the total 40 invasive ductal carcinoma (sensitivity 86.2%; specificity 100%; positive predictive value 100%; negative predictive value 60%). In constrast peak at 1.3 ppm is characteristically intense and observed in normal breast (sensitivity 86.2%; specificity 100%; positive predictive value 100%; negative predictive value 60%). The study shows that 1H MRS can effectively discriminate invasive ductal carcinoma from normal breast in most cases. It also demonstrates the feasibility of localized in vivo 1H MRS technique as a new diagnostic modality in the detection of breast tumor.

SNR and ADC Changes at Increasing b Values among Patients with Lumbar Vertebral Compression Fracture on 1.5T MR Diffusion Weighted Images / 의학물리

To examine among patients with vertebral compression fracture the extent to which signal-to-noise ratio (SNR) and Apparent Diffusion Coefficient (ADC) values at the lumbar vertebral compression fracture site vary on diffusion-weighted MR images according to varying b values on the 1.5T MR device. Diffusion-weighted MR images of 30 patients with compression fracture due to chronic osteoporosis who underwent vertebral MRI from Jan. 2008 to Nov. 2009 were respectively obtained using a 1.5-T MR scanner with the b values increased from 400, 600, 800, 1,000 to 1,200 s/mm2. For diffusion-weighted MR images with different b values, the signal-to-noise ratio (SNR) was assessed at three sites: the site of compression fracture of the lumbar vertebral body at L1 to L5, and both the upper and lower discs of the said fracture site, while for ADC map images with different b values, the SNR and ADC were respectively assessed at those three sites. As a quantitative analysis, diffusion-weighted MR images and ADC map images with b value of 400 s/mm2 (the base b values) were respectively compared with the corresponding images with each different b value. As far as qualitative analysis is concerned, for both diffusion-weighted MR and ADC map images with b value of 400 s/mm2, the extent to which signal intensity values obtained at the site of compression fracture of the lumbar vertebral body at L1 to L5 vary according to the increasing b values were examined. The quantitative analysis found that for both diffusion-weighted MR and ADC map images, as the b values increased, the SNR were relatively lowered at all the three sites, compared to the base b value. Also, it was found that as the b values increased, ADC values were relatively lowered at all the three sites on ADC map images. On the other hand, the qualitative analysis found that as the b values increased to more than 400 s/mm2, the signal intensity gradually decreased at all the sites, while at the levels of more than 1,000 s/mm2, severe image noises appeared at all of the three sites. In addition, higher signal intensity was found at the site of compression fracture of the lumbar vertebral body than at the discs. Findings showed that with the b value being increased, both the signal-to-noise ratio (SNR) and Apparent Diffusion Coefficient (ADC) values gradually decreased at all the sites of the lumbar vertebral compression fracture and both the upper and lower discs of the fracture site, suggesting that there is a possibility of a wider range of applications to assessment of various vertebral pathologies by utilizing multi b values in the diffusion-weighted MRI examination.

MR T2 Map Technique: How to Assess Changes in Cartilage of Patients with Osteoarthritis of the Knee / 의학물리

By using the MR T2 map technique, this study intends, first, to measure the change of T2 values of cartilage between healthy people and patients with osteoarthritis and, second, to assess the form and the damage of cartilage in the knee-joint, through which this study would consider the utility of the T2 map technique. Thirty healthy people were selected based on their clinical history and current status and another thirty patients with osteoarthritis of the knee who were screened by simple X-ray from November 2007 to December 2008 were selected. Their T2 Spin Echo (SE hereafter) images for the cartilage of the knee joint were collected by using the T2 SE sequence, one of the multi-echo methods (TR: 1,000 ms; TE values: 6.5, 13, 19.5, 26, 32.5. 40, 45.5, 52). Based on these images, the changes in the signal intensity (SI hereafter) for each section of the cartilage of the knee joint were measured, which yielded average values of T2 through the Origin 7.0 Professional (Northampton, MA 01060 USA). With these T2s, the independent samples T-test was performed by SPSS Window version 12.0 to run the quantitative analysis and to test the statistical significance between the healthy group and the patient group. Closely looking at T2 values for each anterior and lateral articular cartilage of the sagittal plane and the coronal plane, in the sagittal plane, the average T2 of the femoral cartilage in the patient group with arthritis of the knee (42.22+/-2.91) was higher than the average T2 of the healthy group (36.26+/-5.01). Also, the average T2 of the tibial cartilage in the patient group (43.83+/-1.43) was higher than the average T2 in the healthy group (36.45+/-3.15). In the case of the coronal plane, the average T2 of the medial femoral cartilage in the patient group (45.65+/-7.10) was higher than the healthy group (36.49+/-8.41) and so did the average T2 of the anterior tibial cartilage (i.e., 44.46+/-3.44 for the patient group vs. 37.61+/-1.97 for the healthy group). As for the lateral femoral cartilage in the coronal plane, the patient group displayed the higher T2 (43.41+/-4.99) than the healthy group did (37.64+/-4.02) and this tendency was similar in the lateral tibial cartilage (i.e., 43.78+/-8.08 for the patient group vs. 36.62+/-7.81 for the healthy group). Along with the morphological MR imaging technique previously used, the T2 map technique seems to help patients with cartilage problems, in particular, those with the arthritis of the knee for early diagnosis by quantitatively analyzing the structural and functional changes of the cartilage.

Intravascular ultrasound study of coronary remodeling and determination of matrix metalloproteinase and hypersensitive C-reactive protein / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate remodeling characteristics of coronary lesions in patients with acute coronary syndromes (ACS) versus stable angina pectoris (SA) using intravascular ultrasound (IVUS), and to explore the relationship between arterial remodeling and clinical presentation or matrix metalloproteinase (MMPs) or hyper-sensitive C-reactive protein (hs-CRP).</p><p><b>METHODS</b>We studied culprit lesions of 38 patients with ACS and 18 patients with SA using IVUS before coronary intervention. The lesion site and a proximal or distal reference site including the external elastic membrane (EEM) area and lumen area were analyzed. Plaque area and remodeling index (RI) were calculated, and directions of arterial remodeling were determined. Positive remodeling was defined as RI > 1.05 and negative remodeling as RI < 0.95. We analyzed the culprit lesion qualitatively, identified high risk plaque and compared them in each group. The blood level of MMP-2, MMP-9 and hs-CRP in each group were also determined.</p><p><b>RESULTS</b>The plaque area at culprit lesions in patients with ACS was significantly larger (11.94 +/- 4.90 versus 9.17 +/- 3.36 mm2; P = 0.035), and also the RI in ACS group was significantly greater than that of patients with SA (0.972 +/- 0.222 versus 0.796 +/- 0.130; P = 0.003). The distribution of remodeling in these two groups was different: positive remodeling was more frequent in ACS group than in SA group (34.2% versus 5.6%, P = 0.047), whereas negative remodeling was more frequent in SA group (52.6% versus 88.9%, P = 0.003). There was higher incidence of high risk plaque in ACS group compared to SA (76.3% versus 50.0%, P = 0.040). The level of serum MMP-2 in ACS group was higher than that of SA group (250.65 +/- 47.97 microg/L versus 214.21 +/- 47.20 microg/L, P = 0.029). The same applied for plasma MMP-9 (84.26 +/- 9.78 microg/L versus 68.46 +/- 22.82 microg/L, P = 0.038) and serum hs-CRP (3.62 +/- 3.37 mg/L versus 1.48 +/- 1.52 mg/L, P = 0.041).</p><p><b>CONCLUSIONS</b>Positive remodeling, larger plaque area and higher incidence of high risk plaque are associated with ACS, whereas negative remodeling is more common in patients with SA. This association between the extent of remodeling and clinical presentation may reflect a greater tendency that plaques with positive remodeling can cause ACS. The change of level of MMP-2, MMP-9 and hs-CRP in ACS patients may be helpful in investigating vulnerable plaques.</p>