MRI-Based Radiomics Nomogram for Predicting Prostate Cancer with Gray-Zone Prostate-Specific Antigen Levels to Reduce Unnecessary Biopsies.

OBJECTIVE: The aim of this study was to establish a predictive nomogram for predicting prostate cancer (PCa) in patients with gray-zone prostate-specific antigen (PSA) levels (4-10.0 ng/mL) based on radiomics and other traditional clinical parameters. METHODS: In all, 274 patients with gray-zone PSA levels were included in this retrospective study. They were randomly divided into training and validation sets (n = 191 and 83, respectively). Data on the clinical risk factors related to PCa with gray-zone PSA levels (such as Prostate Imaging Reporting and Data System, version 2.1 [PI-RADS V2.1] category, age, prostate volume, and serum PSA level) were collected for all patients. Lesion volumes of interest (VOI) from T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) imaging were annotated by two radiologists. The radiomics model, clinical model, and combined prediction model, which was presented on a nomogram by incorporating the radiomics signature and clinical and radiological risk factors for PCa, were developed using logistic regression. The area under the receiver operator characteristic (AUC-ROC) and decision, calibration curve were used to compare the three models for the diagnosis of PCa with gray-zone PSA levels. RESULTS: The predictive nomogram (AUC: 0.953) incorporating the radiomics score and PI-RADS V2.1 category, age, and the radiomics model (AUC: 0.941) afforded much higher diagnostic efficacy than the clinical model (AUC: 0.866). The addition of the rad score could improve the discriminatory performance of the clinical model. The decision curve analysis indicated that the radiomics or combined model could be more beneficial compared to the clinical model for the prediction of PCa. The nomogram showed good agreement for detecting PCa with gray-zone PSA levels between prediction and histopathologic confirmation. CONCLUSION: The nomogram, which combined the radiomics score and PI-RADS V2.1 category and age, is an effective and non-invasive method for predicting PCa. Furthermore, as well as good calibration and is clinically useful, which could reduce unnecessary prostate biopsies in patients having PCa with gray-zone PSA levels.

[Effect and molecular mechanism of interferon-α on podocyte apoptosis induced by hepatitis B virus X protein].

OBJECTIVE: To investigate the effect and molecular mechanism of interferon-α (INF-α) on the apoptosis of the mouse podocyte cell line MPC5 induced by hepatitis B virus X (HBx) protein. METHODS: MPC5 cells were transfected with the pEX plasmid carrying the HBx gene. RT-PCR was used to measure the mRNA expression of HBx at different time points. MPC5 cells were divided into 4 groups: control group (MPC5 cells cultured under normal conditions), INF-α group (MPC5 cells cultured with INF-α), HBx group (MPC5 cells induced by HBx), and HBx+INF-α group (MPC5 cells induced by HBx and cultured with INF-α). After 48 hours of intervention under different experimental conditions, flow cytometry was used to measure the apoptosis of MPC5 cells, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of slit diaphragm-related proteins (nephrin, CD2AP, and synaptopodin) and the cytoskeleton-related protein transient receptor potential cation channel 6 (TRPC6). RESULTS: MPC5 cells transfected by pEX-HBx had the highest expression of HBx mRNA at 48 hours after transfection (P<0.05). Compared with the control, INF-α and HBx+INF-α groups, the HBx group had a significant increase in the apoptosis rate of MPC5 cells (P<0.05). Compared with the control and INF-α groups, the HBx group had significant reductions in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant increases in the mRNA and protein expression of TRPC6 (P<0.05). Compared with the HBx group, the HBx+INF-α group had significant increases in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant reductions in the mRNA and protein expression of TRPC6 (P<0.05). CONCLUSIONS: INF-α can inhibit the apoptosis of podocytes induced by HBx, possibly through improving the abnormal expression of slit diaphragm-related proteins (CD2AP, nephrin, and synaptopodin) and cytoskeleton-related protein (TRPC6) induced by HBx.

[Dexamethasone Blocks Adriamycin-induced Podocytes'Mobility via Impacting Nephrin Expression].

OBJECTIVE: To explore how dexamethasone (Dex) directly restores kidney podocyte function in adriamycin (ADR)-induced nephrotic model and the effects of Dex on the motility of podocytes, to analyze whether nephrin is a key signal molecule in the process. METHODS: The cultured podocytes were divided into three growps: ADR treated group, ADR+Dex group, blank control group. The analyses of podocytes function were performed using scrape-wound, Transwell migration assays and FITC-BSA. Quantitative real-time PCR and Western blot were used to test the expression of nephrin. Male SD rats were used to generate ADR-induced nephrology model, and randomly divided into three groups: ADR group, ADR+Dex group and normal group. At 7 d, 14 d, 21 d and 28 d after ADR injection, 24 h urine protein was measured as well. Podocyte foot process effacement was observed under transmission electron microscopy. RESULTS: Podocytes' motility, permeability of a monolayer of podocytes incubated with FITC-BSA, the expression of nephrin were higher in ADR group than those in blank control group (P<0.05); on the contrary, the indexes above in Dex+ADR group were decreased when compared with ADR group (P<0.05). 24 h urine protein increased significantly at day 14 (vs. normal group P<0.001) and peaked at day 28 in ADR rats (vs. normal group P<0.001), whereas decreased at day 14, 21 and 28 in Dex+ADR group (vs. ADR group, P<0.001). The FWP of ADR-treated rats was greater than normal group and Dex+ADR group (P<0.01). CONCLUSION: Dex impacts the expression of nephrin, relieves the enhanced motility induced by ADR and decreases urine protein level.

Hepatitis B virus X protein decreases nephrin expression and induces podocyte apoptosis via activating STAT3.

The gene for hepatitis B virus X protein (HBx) comprises the smallest open reading frame in the HBV genome, and the protein product can activate various cell signaling pathways and regulate apoptosis, among other effects. However, in different cell types and under different external conditions, its mechanism of action differs. In the present study, the effect of HBx on the viability and apoptosis of mouse podocyte clone 5 (MPC5) cells was investigated. The cells were transfected with the HBx gene using pEX plasmid, and real-time quantitative PCR and western blot analysis were used to test the transfection efficiency and assess related protein expression. The highest expression of HBx occurred at 48 h after MPC5 cells were transfected with HBx. The expression of nephrin protein in the HBx transfection group was lower than that in blank and negative control groups. Following transfection of the HBx gene, podocyte viability was suppressed, while the rate of cell apoptosis was increased; moreover, the expression of signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 was increased compared with in the control groups. The present study suggests that STAT3 activation may be involved in the pathogenic mechanism of renal injuries caused by HBV injection. Thus STAT3 is a potential molecular target in the treatment of HBV-GN.

Relationship between genotypes and clinical manifestation, pathology, and cccDNA in Chinese children with hepatitis B virus-associated glomerulonephritis.

BACKGROUND: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is one of the extrahepatic manifestations after HBV infection, which would cause great clinical harm to people. The present study was undertaken to investigate the HBV-GN genotypes and its clinical relevance in Chinese children. METHODS: A total of 41 HBV-infected children diagnosed with HBV-GN were enrolled in the study. All patients underwent liver and kidney biopsy. The genotypes and cccDNA were detected in their serum samples to analyze the relationship between HBV genotypes and clinical characteristics, cccDNA, and pathology. RESULTS: Among the 41 children with HBV-GN, 29 (70.7%) had genotype C, 10 (24.4%) had genotype B, 2 (4.9%) had genotype B/C, and none of them had genotype non-B/C. Most children had genotypes B or C; moreover, the genotype C was the most frequent one. The incidence of hematuria and albuminuria, reduction in complement C3, increase in serum alanine aminotransferase levels and renal insufficiency in the children with genotype C were significantly higher than those in the children with genotype B (P<0.05); however, there was no statistically significant difference in hypertension and hepatomegaly (P>0.05). The frequency of HBV cccDNA positive in the genotype C group was significantly higher than that in the genotype B group (72.4% vs. 30.0%, P<0.05). No difference was observed in hepatic inflammation grades and stages of fibrosis between the two groups (P>0.05). CONCLUSIONS: Genotype C was the most frequent genotype in the described group of patients with HBV-GN, and the liver and kidney damage indicators were more likely to occur in patients with genotype C.

[Clinical and pathological differences between children with various genotypes of hepatitis B virus-associated glomerulonephritis].

OBJECTIVE: To compare the clinical and pathological features between children with various genotypes of hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Forty-one children with HBV-GN concurrently undergoing liver and renal biopsy were randomly selected. Serum specimens were collected for genotyping and hepatitis B virus (HBV) cccDNA assay. The clinical, pathological, and HBV cccDNA differences between HBV-GN children of various genotypes were analyzed. RESULTS: Among the 41 HBV-GN children, 29 (71%) were genotype C, 10 (24%) were genotype B, and 2 (5%) were genotype B/C. The incidence rates of hematuria, albuminuria, complement 3 decrease, alanine transaminase increase, and renal insufficiency in the genotype C group were significantly higher than those in the genotype B group (P<0.05). Similarly, the HBV cccDNA positive rate was significantly higher in the genotype C group than that in the genotype B group. No difference was observed in the distribution of pathological types of renal tissues betwee the two geonotype groups. There were no significant differences in the degrees of hepatic inflammation and fibrosis between the two groups. CONCLUSIONS: Mainly genotypes C and B occur in children with HBV-GN and the former genotype is dominant. The clinical symptoms of patients with genotype C are more serious than those with genotype B. However, there is no difference in the pathological features between them.

Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats.

BACKGROUND: Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI), little is known about the AQP4 expression in the early stage of TBI, or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema. The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI. METHODS: One hundred and twenty healthy adult Wistar rats were randomly divided into two groups: sham operation group (SO) and TBI group. The TBI group was divided into five sub-groups according to the different time intervals: 1, 3, 6, 12, and 24 hours. The brains of the animals were taken out at different time points after TBI to measure brain water content. The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM), and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting. The data were analyzed with SPSS 13.0 statistical software. RESULTS: In the SO group, tissue was negative for IgG, and there were no abnormalities in brain water content or AQP4 expression. In the TBI group, brain water content significantly increased at 6 hours and peaked at 24 hours following injury. IgG expression significantly increased from 1 to 6 hours following injury, and remained at a high level at 24 hours. Pathological observation revealed BBB damage at 1 hour following injury. Angioedema appeared at 1 hour, was gradually aggravated, and became obvious at 6 hours. Intracellular edema occurred at 3 hours, with the presence of large glial cell bodies and mitochondrial swelling. These phenomena were aggravated with time and became obvious at 12 hours. In addition, microglial proliferation was visible at 24 hours. AQP4 protein expression were reduced at 1 hour, lowest at 6 hours, and began to increase at 12 hours, showing a V-shaped curve. CONCLUSIONS: The angioedema characterized by BBB damage was the primary type of early traumatic brain edema. It was followed by mixed cerebral edema that consisted of angioedema and cellular edema and was aggravated with time. AQP4 expression was down-regulated during the angioedema attack, but AQP4 expression was upregulated during intracellular edema.

Upregulation of microRNA 181c expression in gastric cancer tissues and plasma.

OBJECTIVE: To test the microRNA-181c (miR-181c) expression in tissues and plasma of gastric cancer (GC) cases, analyze any correlations, and explore the possibility of miR-181c as a potential molecular marker for GC diagnosis. MATERIALS AND METHODS: Relative miR-181c expression levels in cancers and plasma from 30 GC patients was tested using reverse transcription?real-time fluorescent quantitation PCR and compared to that in samples from 30 gastric ulcer and 30 chronic gastritis patients. RESULTS: The miR-181c expression level in the GC tissues was significantly higher than that in the gastric ulcer and chronic gastritis tissues (P = 0.000), as was the miR-181c expression level in the GC plasma (P = 0.000). We determined that miR-181c expression in GC plasma was positively correlated to its expression in the GC tissues (P = 0.000). CONCLUSIONS: The expression of miR-181c is upregulated in GC tissues and plasma, and the miR-181c expression level in GC plasma is positively correlated to that in the corresponding cancer tissues. Plasma miR-181c is possibly a new serological marker for GC diagnosis.

[Relationship between B/C genotype of hepatitis B virus and hepatitis B virus related-nephritis in children].

OBJECTIVE: To investigate the relationship between genotype of hepatitis B virus and hepatitis B virus related-glomerular nephritis in (HBV-GN) children. METHOD: Totally 176 HBV-DNA positive children with chronic hepatitis B were randomly collected. Among the 176 patients, 92 were HBV carriers, 84 were cases with chronic hepatitis. The genotypes of their serum HBV, liver function, and HBV-DNA load were detected. When children showed nephrotic syndrome, renal biopsy was performed. RESULT: Of the serum samples of 176 cases, 85 (48.3%) were genotype C, 72 (40.9%) were genotype B, 13 (7.4%) were genotype B/C, and 6 (3.4%) were non-B/C genotype which were excluded. Among the analyzed 157 cases, the ratio of HBV-GN in the HBeAg positive group (78.3%) was significantly higher than that in the negative group (21.7%) (χ(2) = 18.301, P < 0.001). And, the ratio of HBV-GN in the genotype C group (73.9%) was significantly higher than that in the genotype B group (26.1%) (P < 0.039). The ratio of hematuria or proteinuria in the genotype C group (20%, 18.8%) was significantly higher than that in the genotype B group (8.3%, 5.6%) (P < 0.039; P value = 0.013); and the alteration of ALT or C3 in the genotype C group (10.2%, 15.3%) was more frequent than those in the genotype B group (2.8%, 2.8%) (P = 0.005; P = 0.008). There were no significant differences in kidney dysfunction or hepatomegaly. Further, the ratio of HBV-GN was more significantly frequent in HBV-DNA highly loading group (79.2%) than which in HBV-DNA lowly loading group (20.8%) (P = 0.000). Finally, in HBV-GN group, genotype C cases (88.2%) more frequently had high HBV-DNA load condition than genotype B cases (11.8%) (P = 0.021). CONCLUSION: Children with HBV infection in Gansu province showed mainly genotypes C or B, while genotype C seemingly predominant. Patients with genotype C more frequently showed proteinuria or hematuria. The high HBV-DNA load may be related with HBV-GN. It is a potential reason in the mechanism of HBV-GN that patients with genotype C had more possibility to have HBV-DNA high load. Analysis of HBV genotype for HBV patients maybe helpful in diagnosis and treatment.

[Research on serum HBV cccDNA and genotype of virus in children with chronic hepatitis B].

OBJECTIVE: To study the serum HBV cccDNA and genotype of hepatitis B virus in children in Gansu province. METHODS: 124 HBV-DNA positive children were randomly selected, with 84 males and 40 females. Among the 124 patients, 65 were HBV carriers, 59 were chronic hepatitis (31 mild, 18 moderate and 10 severe). Genotypes of their serum HBV, liver function, HBV-DNA load and serum HBV cccDNA were detected. RESULTS: In the moderate and severe groups, HBV cccDNA positive rate was higher than that in the HBV carriers or the mild group (F = 25.429, P < 0.01). The HBV cccDNA detection rate in HBeAg positive group was higher than that in the HBeAg negative group (F = 28.386, P < 0.01). In the HBV cccDNA positive group, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, total bilirubin were higher than that in the negative group (t respectively 13.241, 11.347, 15.013, P < 0.01). Both C and B genotypes appeared to be the majority while C genotype was dominant in the 124 cases of children hepatitis, with the rest as B/C and some other genotypes. The positive rate of HBV cccDNA C genotype was higher than that of the genotype B (F = 23.216, P < 0.01) and the negative rate of HBV cccDNA genotype was higher than that of the C genotype (F = 26.364, P < 0.01). CONCLUSION: Higher detection rate was found in those more severe cases in the peripheral blood streams. HBV cccDNA and genotype testing might better reflect the level of HBV replication and the clinical severity of the disease, showing its guiding role in clinical diagnosis and treatment of hepatitis B.

[Antioxidative activity of water-soluble extracts from Fructus Polygoni Orientalis].

OBJECTIVE: To study the antioxidative activity of the water-soluble extracts from Fructus Polygoni Orientalis. METHODS: Malondialdehyde and superoxide dismutase were measured by thiobarbituric acid assay, nitrite method, respectively. The activity of glutathione peroxidase was determined by 5,5'-dithionbis (2-nitrobenzoic acid) photometric method. Lipofuscin was determined by Sohal method in the brain of senile model mice induced by D-galactose. The extracts of 0.8, 1.6 and 3.2 g.kg(-1).d(-1) were administered to the mice separately through oral gavage daily for 7 weeks. RESULTS: Malondialdehyde content increased, activities of superoxide dismutase and glutathione peroxidase in the heart, liver and kidney decreased. Levels of lipofuscin in the brain of senile model mice induced by D-galactose increased. The three doses of the extracts could inhibit the levels of lipofuscin in the brain, malondialdehyde in the heart, liver and kidney. These results showed that there was a negative dose-effect relationship. The extracts also up-regulated the levels of superoxide dismutase and glutathione peroxidase in the heart, liver and kidney with a positive dose-effect relationship. CONCLUSION: The water-soluble extracts exert its antioxidative activity by eliminating free hydroxyl radicals, increasing activities of superoxide dismutase and glutathione peroxidase.