GPR97 deficiency suppresses Wnt/ß-catenin signaling in hypertensive nephropathy.

Accumulating evidence shows that renal fibrosis plays a key role in the development of hypertensive nephropathy (HTN). Therefore, a better understanding of the underlying mechanism of renal fibrosis regulation in HTN would be critical for designing rational strategies for therapeutic interventions. In this study, we revealed that GPR97, a novel identified adhesion G coupled receptor, plays an important role in the regulation of Wnt/ß-catenin signaling, which is the crucial driver of renal fibrosis in HTN. First, we identified that the expression of GPR97 correlated with the ß-catenin expression in renal biopsy from patients with HTN. Moreover, we found that GPR97 deficiency inhibited Wnt/ß-catenin signaling in mice with HTN, as evidenced by the reduction of ß-catenin expression and downstream target proteins, including MMP7 and Fibronectin. Mechanistically, we found that GPR97 could directly bind with Wnt1 in cultured tubular cells and TGF-ß1 treatment enhanced the binding ability of GPR97 and Wnt1. In addition, the gene silencing of GPR97 could decrease the Wnt1-induced fibrotic phenotype of tubular cells and inflammatory responses, suggesting that the binding of GPR97 and Wnt1 promoted Wnt/ß-catenin signaling. Collectively, our studies reveal that GPR97 is a regulator of Wnt/ß-catenin signaling in HTN, and targeting GPR97 may be a novel therapeutic strategy for HTN treatment.

CircSMAD2 accelerates endometrial cancer cell proliferation and metastasis by regulating the miR-1277-5p/MFGE8 axis / 부인종양

Objective@#Endometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown. @*Methods@#CircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC. Mechanism assays were conducted to confirm the binding between miR-1277-5p and circSMAD2 or MFGE8 expression. @*Results@#Upregulation of circSMAD2 was uncovered in both EC tissues and cell lines. Functionally, silencing of circSMAD2 apparently inhibited the proliferation, migration, invasion and angiogenesis of EC cell lines in vitro. Mechanistically, circSMAD2 sponged miR-1277-5p to upregulate MFGE8 expression. The decrease of miR-1277-5p and increase of MFGE8 were observed both in EC tissues and cell lines. Then MFGE8 knockdown or miR-1277-5p upregulation suppressed EC cell oncogenic biological behavior. Rescue experiments showed that miR-1277-5p mimics countervailed the anticancer effects of circSMAD2 silencing on EC. Besides that, MFGE8 overexpression also attenuated the inhibitory action of miR-1277-5p mimic in EC. Moreover, knockdown of circSMAD2 inhibited EC growth in vivo. @*Conclusion@#CircSMAD2 functions as an oncogene in promoting the progression of EC through miR-1277-5p/MFGE8 axis.

Expression of INPP4B in gastric cancer and its clinical significance / 肿瘤研究与临床

Objective@#To investigate the expression of INPP4B in gastric cancer and its relationship with clinicopathological features and prognosis.@*Methods@#The expressions of INPP4B mRNA in fresh cancer tissues of 36 patients with gastric cancer and the paracancerous normal gastric mucosa tissues in the Affiliated Cancer Hospital of Shanxi Medical University between July 2014 and December 2014 were detected by using real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of INPP4B protein and its downstream molecule phosphorylation AKT (p-AKT) in paraffin-embedded tumor tissues and the corresponding margin tissues of 49 gastric cancer patients between January 2010 and December 2010 were detected by using immunohistochemistry. The relationship between the expression of INPP4B and clinicopathological features and prognosis was analyzed.@*Results@#RT-qPCR results showed that the expression level of INPP4B mRNA was 0.21±0.04 compared with adjacent cancer normal tissues (t = -2.208, P < 0.05). Immunohistochemistry showed that INPP4B protein was highly expressed in normal margin tissues and lowly expressed in tumor tissues. There was a statistical difference in the positive intensity score between the two groups (u = 4.70, P < 0.01). However, p-AKT protein was overexpressed in tumor tissues and underexpressed in normal margin tissues. There was a statistical difference in the positive intensity score between the two groups (u = 5.77, P < 0.01). The expression of INPP4B and p-AKT protein was negatively correlated (r = -0.644, P < 0.01). The positive expression rate of INPP4B protein in gastric cancer patients was 34.7% (17/49). There were no statistical differences of the positive expression rate of INPP4B protein in gender, age, pathological type, depth of invasion and lymph node metastasis (all P > 0.05). The median overall survival time of patients with INPP4B negative expression was 47 months, and that of patients with INPP4B positive expression was 48 months, and there was no statistical difference (P > 0.05).@*Conclusion@#The expression of INPP4B in gastric cancer tissue is low, which may play a role of tumor suppressor in the occurrence and development of gastric cancer by affecting the activity of AKT.

Expression of INPP4B in gastric cancer and its clinical significance / 肿瘤研究与临床

Objective To investigate the expression of INPP4B in gastric cancer and its relationship with clinicopathological features and prognosis. Methods The expressions of INPP4B mRNA in fresh cancer tissues of 36 patients with gastric cancer and the paracancerous normal gastric mucosa tissues in the Affiliated Cancer Hospital of Shanxi Medical University between July 2014 and December 2014 were detected by using real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of INPP4B protein and its downstream molecule phosphorylation AKT (p-AKT) in paraffin-embedded tumor tissues and the corresponding margin tissues of 49 gastric cancer patients between January 2010 and December 2010 were detected by using immunohistochemistry. The relationship between the expression of INPP4B and clinicopathological features and prognosis was analyzed. Results RT-qPCR results showed that the expression level of INPP4B mRNA was 0.21 ±0.04 compared with adjacent cancer normal tissues (t= -2.208, P< 0.05). Immunohistochemistry showed that INPP4B protein was highly expressed in normal margin tissues and lowly expressed in tumor tissues. There was a statistical difference in the positive intensity score between the two groups (u=4.70, P<0.01). However, p-AKT protein was overexpressed in tumor tissues and underexpressed in normal margin tissues. There was a statistical difference in the positive intensity score between the two groups (u=5.77, P<0.01). The expression of INPP4B and p-AKT protein was negatively correlated (r= -0.644, P< 0.01). The positive expression rate of INPP4B protein in gastric cancer patients was 34.7％ (17/49). There were no statistical differences of the positive expression rate of INPP4B protein in gender, age, pathological type, depth of invasion and lymph node metastasis (all P > 0.05). The median overall survival time of patients with INPP4B negative expression was 47 months, and that of patients with INPP4B positive expression was 48 months, and there was no statistical difference (P> 0.05). Conclusion The expression of INPP4B in gastric cancer tissue is low, which may play a role of tumor suppressor in the occurrence and development of gastric cancer by affecting the activity of AKT.

Mild encephalitis/encephalopathy with a reversible splenial lesion in the corpus callosum / 中华实用儿科临床杂志

Mild encephalitis/ encephalopathy with a reversible splenial lesion (MERS)in the corpus callosum is a clinical - radiological syndrome with typical imaging characteristics,which can be divided into 2 types (MERS Ⅰand MERS Ⅱ)according to the affected parts. The main cause is infection in children. Patients can be presented with symptoms that are common for acute mild encephalitis or encephalopathy such as disturbance of consciousness,hea-dache,vomiting,seizure. Brain magnetic resonance imaging(MRI)indicates lesions in the splenium of the corpus callo-sum. The symptoms and brain MRI lesions disappear almost within 1 month,and the prognosis is usually good. Early recognition is necessary and excessive treatment should be avoided.

Research on miR-497 inhibiting the expression of inflammation-related genes in colon cancer cell line HCT116 using gene expression microarray / 肿瘤研究与临床

Objective To analyze the effect of miR-497 high expression on the gene expression profile of colon cancer cell line HCT116. Methods MiR-497 high expressing colon cancer cell model HCT116-497 and negative control HCT116-CON were established by lentiviral transduction. The human (V2) gene expression microarray was used to identify genes that were differentially expressed between colon cancer cells overexpressing miR-497 and the controls. The candidates were subjected to the gene ontology (GO) and KEGG pathway enrichment analysis by Molecule Annotation System 3.0 (MAS3.0). The differential expression of representative genes relative to inflammation were confirmed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results Of all the differently expressed genes, 582 genes were down-regulated by at least 3-folds, which were enriched in inflammation-related signaling pathways in colon cancer cells overexpressing miR-497. The decrease in 15 representative genes was validated by qPCR. Compared with those in HCT116-CON cells, expressions of 10 genes in HCT116-497 cells, including CACNB1, FOS, IL-29, RPS6KA2, TNFSF15, IL-11, INHBC, CSF1R, JAK3 and IL-2Rβ, were decreased significantly, and there were statistical differences (all P< 0.05) Conclusion MiR-497 inhibits the mRNA expression of inflammation-related genes in colon cancer cell line HCT116.

The improvement of micronucleus test method / 公共卫生与预防医学

Objective To simplify and optimize the micronucleus test method. Methods The preparation process of micronucleus test was simplified and optimized. In the improved method, the superfine solution was directly absorbed and discarded after cell culture, and then potassium chloride solution was added for hypotonic treatment. Then pre-fixation, centrifugation. Once the centrifugation was completed, the cells which fixed only once were directly dropped to the slide. Results The background of the slides was clear and the cells were slightly darker, but the observation of cells and micronucleus was not affected. There were a lot of binuclear cells, which can meet the counting requirements. With oil and high magnification, the image wais clearer and the background was cleaner. The cytoplasmic integrity rate, cell stain rate and the average number of cells per high magnification field of cells by the improvement method were significantly increased compared with that by the traditional methods, the probability P values were 0.0051 (χ2=7.8375), 0.0140 (χ2=6.0437) and 0.0025 (t=3.0951), respectively. The rate of micronucleus cells and cells group index had no statistical significance compared with the traditional method, the probability P values were 0.7749 (χ2=0.0817) and 0.5152 (U =0.0000), respectively. Conclusion The new method is more simple, easier to control the test quality, more reliable test results, and save time, manpower and material resources.

Risk factors associated with delayed encephalopathy occurrence in carbon monoxide poisoning / 中国医师进修杂志

Objective To investigate the risk factors associated with delayed encephalopathy (DE)occurrence in carbon monoxide (CO) poisoning.Methods The clinical data of 249 patients with CO poisoning were retrospectively reviewed.Potential risk factors associated with occurrence of DE,including gender,age,duration of exposure to CO,time interval between onset and arrival in hospital,mental status after onset,oxygen therapy approach,were evaluated by univariate analysis of x2 test and multivariate Logistic regression analysis.Results Age and duration of exposure to CO was significandy related with occurrence of DE in patients with CO poisoning.The occurrence of DE in patients with CO poisoning with age 60-75 years was 3.236 times and 2.119 times as much as that with age 3-17 years and 18-59 years respectively.Occurrence of DE was 4.338 times in patients with duration of exposure to CO ≥12 hours compared to that ＜ 12 hours.Conclusions Age ≥ 60 years and duration of exposure to CO ≥ 12 hours are independent risk factors for developing D E.Old patients have a inclination to develop D E.To evacuate patients from CO environment timely is important for preventing from DE.