OBJECTIVETo investigate whether connective tissue growth factor (CGGF) is expressed in mast cells (MCs) in lung in the development of bleomycin (BLM)-induced pulmonary fibrosis.

METHODSThirty-two male SD rats were randomly divided into 2 groups: BLM group and control group (n=16). The rats in BLM group were received single intratracheal instillation of BLM (5 mg/kg), and the rats in control group received equal volume of 0.9% normal saline(NS) to BLM. The rats in each group were sacrificed for lung tissue sampling on day 14 and day 28 after intratracheal instillation respectively. As the index of the severity of pulmonary fibrosis, the content of hydroxyproline in lungs was analyzed by chloramine T method. Mast cells and CTGF expression in lungs were examined by toluidine blue stain and immunohistochemical assay respectively.

RESULTS(1) On day 28 after intratracheal instillation of BLM, the content of hydroxyproline in lungs of rats was higher than that of control rats (P < 0.01). (2) Compared to control rats, the rats on day 14 and day 28 after instillation of BLM showed increased number of mast cells (Both P < 0.01) and up-regulated CTGF expression (Both P < 0.01). (3) No CTGF immuno-positive MCs were seen in the lungs of control rats whereas CTGF immuno-positive MCs were observed in the pathological areas in lungs of rats on day 14 and day 28 after BLM.

CONCLUSIONCTGF is expressed in MCs in lungs in the development of pulmonary fibrosis, which might be one of the mechanisms underling promoting effect of MCs on fibrosis in lung.

Animals ; Bleomycin ; Connective Tissue Growth Factor ; metabolism ; Lung ; metabolism ; pathology ; Male ; Mast Cells ; metabolism ; Pulmonary Fibrosis ; chemically induced ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective: To investigate the clinical, radiological and pathological features of visceral parasitic migration of the liver. Methods: Seven cases of visceral parasitic migration of liver were identified at the Affiliated Drum Tower Hospital of Medical School of Nanjing University from January 2008 to July 2017. Clinical data, enhanced CT image and pathological features were analyzed, combining with literature review. Results: There were 5 male and 2 female patients. Five patients presented with abdominal pain or discomfort as the first symptom. Two patients were admitted to the hospital for physical examination with liver nodule. Blood eosinophils were mildly to moderately increased in 4 cases. Enhanced CT showed the liver irregular beaded nodules that showed no significant enhancement of arterial phase. Mild enhancement of round lesions (ring lesion) was seen in a few cases before surgery. By histopathology, the lesions showed central geographic necrosis, surrounded by epithelioid granuloma and inflammatory cell bands. A large number of eosinophils and scattered multinucleated giant cells were found, especially at the peripheral of the lesion. Charcot-Leyden crystals were present in all case and parasitic migrans was found in one case. Conclusions Visceral parasitic migration of liver is a rare liver disease and is easily misdiagnosed as other benign or malignant liver tumors. Combining clinical data, enhanced CT images and pathological examination can improve the preoperative and postoperative diagnosis of the disease.

Objective To clarify the effect of iodine intake on serum thyroglobulin (Tg). Methods A 5-year prospective study was conducted in the 3 different iodine intake areas in China [Panshan (miht deficiency) ,Zhangwu (more than adequate) and Huanghua (excess)]. A total of 3 099 people with normal serum levels of Tg in 1999 were followed and 2 448 of these participants were feasible to be observed in 2004 and included in the present study. The serum levels of Tg, thyraglobulin antibody(TgAb), thyroid peroxidase antibody(TPOAb) and TSH, thyroid volume, family and personal histories of thyroid diseases were measured and inquried. The general linear model (GLM) was used to explore the determinants of Tg. Results Among the study population at baseline, serum Tg were significantly different in three areas [7.5 (4.4-13. 1) μg/L at Panshan, 6.8 (3.6-11.2)μg/L at Huanghua, 5.9 (3.2-10.7) μg/L at Zhangwu, P<0.01]. They were associated with age, sex and the rate of positive TgAb, abnormal thyroid volume, abnormal TSH and positive personal history of thyroid diseases, in order to control the effects of confounding factors, the data from 1856 subjects with thyroid-related indexes all in normal range and without personal history of thyroid diseases were analyzed to clarify the effect of iodine intake on Tg. The serum Tg among three areas were significantly different in both 1999 and 2004, they were all increased in 5 years with significant augment (△ Tg) among the three areas[3.1 (-0.2-8.0) μg/L at Panshan, 3.5 (0.5-9.0)μg/L at Huanghua vs 2. 5(0.3-6.1) μg/L at Zhangwu,P<0.01]. The GLM analysis revealed that age, Tg and TSH levels at baseline were the determinants of △Tg in addition to iodine intake. Conclusion Iodine intake is a dominant determinant of serum Tg. Age and TSH should also be considered while indicating iodine intake by serum Tg.

OBJECTIVE：To evaluate the effects of nicorand il on the proliferation ，migration ability and Hippo/YAP signaling pathway of pulmonary artery smooth muscle cells （PASMCs）. METHODS ：Human primary PASMCs were divided into normal control group ，model group ，nicorandil low ，medium and high concentration groups （50，100，200 μmol/L），with 3 holes in each group. In addition to the normal control group ，the rest of the cells were inoculated on the gel coated medium to simulate the pulmonary hypertension environment ，so as to establish AS cell model. Then ，each drug group was added with corresponding drugs，and the normal control group and model group were added with the same volume of normal saline ，and cultured for 48 h. CCK-8 assay and Transwell assay were used for the examination of cell proliferation （by light density ）and migration ability ， respectively. mRNA expression of YAP target factors （CTGF and AREG ）were examined by qRT-PCR. Western blotting assay was used to detect the protein expression of CTGF and AREG. RESULTS ：Compared with normal control group ，light density of cells was increased significantly in model group ；the number of migration cells per field of view increased significantly ；mRNA and protein expression of CTGF and AREG were significantly increased （P＜0.01）. Compared with model group ，light density ，the number of migration cells per field of view ，mRNA and protein expression of CTGF and AREG in nicorandil low ，medium and high concentration groups were decreased significantly ， in concentration-dependent manner （P＜0.05 or P＜0.01）. CONCLUSIONS：Nicorandil can inhibit the proliferation and migration of PASMCs in AS model ，the mechanism of which cstc2019jscx-msxmX0174） may be associated with the Hippo/YAP signaling pathway.

The effect of altering the promoter region of ubiquitous chromatin-opening element (UCOE) and matrix attachment region (MAR) on stable and efficient expression of genes was investigated. Four different promoters were tested, namely, oct4 containing an enhancer region, sox2 having a CpG island, nanog having no regulatory elements, and CMV containing a CpG island and an enhancer region. Eight reporter plasmids were constructed: pOCT4-UCOE, pOCT4-MAR, pSOX2-UCOE, pSOX2-MAR, pNANOG-UCOE, pNANOG-MAR, pCMV-UCOE, and pCMV-MAR. Stable and efficient expression was observed when UCOE combined with the oct4 promoter, whereas the sox2 was the best promoter suited for MAR. Comparison of the stable clones of oct4-UCOE and sox2-MAR showed that UCOE-regulated expression is more stable and efficient than MAR-regulated expression. When CpG island-containing promoter is linked with UCOE, stable and efficient expression could be observed. These data suggest that an enhancer region in the promoter leads to high, yet unstable expression when combined with UCOE, whereas CpG islands stabilize expression. In conclusion, UCOE and MAR interact with regulatory elements on the promoter by altering the chromatin open state and chromatin loop to regulate gene expression.
Chromatin/genetics* ; CpG Islands/genetics* ; Gene Expression ; Gene Expression Regulation ; Promoter Regions, Genetic/genetics*