Antibody array-based proteomic screening of novel biomarkers in malignant biliary stricture.

BACKGROUND: Distinguishing between benign and malignant bile duct strictures has long been a diagnostic challenge in clinical practice. OBJECTIVE: This study aimed to discover novel biomarkers in bile to improve the diagnostic accuracy of malignant biliary strictures. METHODS: Bile samples were collected from 6 patients with malignant or benign biliary stricture, respectively. Protein profiles of the bile were analyzed with a semi-quantitative human antibody array of 440 proteins. Then the differential expressed proteins were screened by Venn diagram analysis. Following this, the accuracy of these potential biomarkers for discriminating between malignant and non-malignant biliary strictures was validated in a larger (n= 40) group of patients using ROC analysis and the best biomarker combination was further selected by lasso analysis. RESULTS: Twenty proteins were found differentially expressed in malignant versus benign biliary strictures, 6 of which were identified by Venn diagram analysis to be up-regulated regardless of the location of biliary strictures. Among the 6 biomarkers, bile lipocalin-2, P-cadherin, and adipsin showed better diagnostic utility than that of bile CA19-9. Lasso analysis identified that lipocalin-2, P-cadherin and CA19-9 as a group of makers best distinguished malignant from benign strictures. CONCLUSIONS: Lipocalin-2 and P-cadherin measurements in bile could be clinically useful for the detection of malignant biliary strictures.

Untargeted and targeted gingival metabolome in rodents reveal metabolic links between high-fat diet-induced obesity and periodontitis.

AIM: To characterize gingival metabolome in high-fat diet (HFD)-induced obesity in mice with/without periodontitis. METHODS: HFD-induced obesity mouse model was established by 16-week feeding, and a lean control group was fed with low-fat diet (n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non-targeted/targeted liquid chromatography-mass spectrometry. RESULTS: Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice; and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K-medoids clustering showed that HFD amplified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. CONCLUSION: The obese population consuming excessive HFD display amplified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.

Transjugular intrahepatic portosystemic shunt by using covered stents of different diameters for the treatment of esophagogastric varices rupture with bleeding / 介入放射学杂志

Objective To assess the efficacy and safety of different diameter covered stents used in transjugular intrahepatic portosystemic shunt (TIPS) for esophagogastric varices with bleeding (EGVB). Methods The clinical data of 68 patients with portal hypertension due to cirrhosis, who received TIPS for EGVB during the period from Desember 2010 to February 2015, were retrospectively analyzed. Among the 68 patients, covered stent with diameter of 7mm was used in 30 (small stent group) and covered stent with diameter of 8mm was employed in 38 (big stent group). Using Kaplan-Meier method, the cumulative digestive tract no-rebleeding rate, the patency rate of shunt and the survival rate of both groups were analyzed. Logrank test was used to make comparison between the two groups, and chi-square test was conducted to compare the incidence of hepatic encephalopathy between the two groups. Results The operative success rate was 100％ in 68 patients. The patients were followed up for 0.1-52.3 months, with a mean of (19.4±16.0) months. The 3-, 6-and 12-month cumulative digestive tract no-rebleeding rates were 86.54％, 79.30％ and 74.90％ respectively in the small stent group, which were 91.87％, 85.93％ and 81.63％ respectively in the big stent group, but the differences between the two groups were not statistically significantly (X2=0.05, P=0.83). The 3-, 6-and 12-month cumulative patency rates of shunt in the small stent group were 95.00％, 80.19％ and 70.17％ respectively, which in the big stent group were 96.15％, 91.97％ and 81.07％ respectively, and no statistically significant differences existed between the two groups (X2=0.40, P=0.53). The 3-, 12-, 24-and 48-month cumulative survival rates in the small stent group were 93.33％, 86.67％, 75.11％ and64.38％ respectively, while those in the big stent group were 97.37％, 94.23％, 88.68％ and 76.02％ respectively, and the differences between the two groups were not statistically significantly (X2=2.21, P=0.14). Postoperative hepatic encephalopathy occurred in 15 patients (15/68, 22.06％), the incidences of hepatic encephalopathy in the small stent group and in the big stent group were 20.00％ (6/30) and 23.68％ (9/38) respectively, the difference between the two groups was not statistically significantly (X2=0.13, P=0.72). Conclusion Compared with the use of 7mm covered stent, the use of 8mm covered stent in TIPS neither can improve the curative effect nor can reduce the incidence of hepatic encephalopathy.

Transjugular intrahepatic portasystemic shunt with Viatorr covered stent / 中国介入影像与治疗学

Objective To assess the efficacy and safety of transjugular intrahepatic portasystemic shunt (TIPS) with Viatorr covered stent in patients with portal hypertension-related complications.Methods Clinical data of 8 patients with por-tal hypertension-related complications were analyzed retrospectively.All the cases received TIPS with Viatorr covered stent.After the operation,the followed up was used to evaluate the therapeutic effect of TIPS by enhanced CT scan.Results All the operations of TIPS were technically successful.And all the cases were treated with Viatorr covered stents with diameter of 8 mm and covered segment length of 50-80 mm.For 1 case with cavernous transformation of portal vein,a 8 mm×40 mm E-Luminexx bare stent was implanted in the portal vein side.For 1 case with hepatic vein stenosis,a 8 mm× 40 mm Fluency covered stent was implanted in the hepatic vein side.After the operation,the portal pressure reduced from (33.08 [29.32,40.22])mmHg (preoperative) to (23.31 [21.43,26.51])mmHg (postoperative) with statistical difference (Z=-2.52,P=0.012).The patients were followed up for 1.1-7.7 months,and all the patients were alive without complications of portal hypertension.There were 2 cases with mild hepatic encephalopathy after operation.During the reexamination time of 1-7.7 months,all TIPS shunts remained patency.Conclusion TIPS with Viatorr stent is a safe and effective treatment for patients with portal hypertension-related complications.

Transjugular intrahepatic portasystemic shunt with Viatorr covered stent / 中国介入影像与治疗学

Objective To assess the efficacy and safety of transjugular intrahepatic portasystemic shunt (TIPS) with Viatorr covered stent in patients with portal hypertension-related complications.Methods Clinical data of 8 patients with por-tal hypertension-related complications were analyzed retrospectively.All the cases received TIPS with Viatorr covered stent.After the operation,the followed up was used to evaluate the therapeutic effect of TIPS by enhanced CT scan.Results All the operations of TIPS were technically successful.And all the cases were treated with Viatorr covered stents with diameter of 8 mm and covered segment length of 50-80 mm.For 1 case with cavernous transformation of portal vein,a 8 mm×40 mm E-Luminexx bare stent was implanted in the portal vein side.For 1 case with hepatic vein stenosis,a 8 mm× 40 mm Fluency covered stent was implanted in the hepatic vein side.After the operation,the portal pressure reduced from (33.08 [29.32,40.22])mmHg (preoperative) to (23.31 [21.43,26.51])mmHg (postoperative) with statistical difference (Z=-2.52,P=0.012).The patients were followed up for 1.1-7.7 months,and all the patients were alive without complications of portal hypertension.There were 2 cases with mild hepatic encephalopathy after operation.During the reexamination time of 1-7.7 months,all TIPS shunts remained patency.Conclusion TIPS with Viatorr stent is a safe and effective treatment for patients with portal hypertension-related complications.

Expression of NOTCH4 affects vasculogenic mimicry formation in hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the effect of NOTCH4 expression on vasculogenic mimicry (VM) formation in hepatocellular carcinoma (HCC). MethodsTumor tissues were collected from 85 patients diagnosed with HCC. The relationship between NOTCH4 expression and VM was examined using immunohistochemical staining and PAS/CD31 double staining. The influence of siRNA-mediated NOTCH4 silencing on VM network formation in HCC was observed in the 3D cell culture system in vitro. Experimental data were assessed with Mann-Whitney U test and one-way analysis of variance. ResultsNOTCH4 had significantly higher expression in VM-positive HCC tissues than in VM-negative HCC tissues (P=0.019). In siRNA-treated cells, NOTCH4 mRNA and protein expression was significantly down-regulated compared with those in mock-treated cells (P=0.007; P=0.003) and untreated cells (P=0.000; P=0.000). VM network formation was impaired by inhibition of NOTCH4 expression in the 3D cell culture system. ConclusionNOTCH4 plays an important role in VM formation in HCC and may provide a novel molecular target for anti-angiogenesis therapy for HCC.

Association between single nucleotide polymorphisms of 5'-untranslated region of GPx4 gene and male infertility / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the association between the single nucleotide polymorphisms (SNPs) of the 5'-untranslated region (5'-UTR) of phospholipid hydroperoxide glutathione peroxidase (GPx4 or PHGPx) gene and oligo- or asthenozoospermic male infertility.</p><p><b>METHODS</b>The 5'-UTR region of the GPx4 gene was amplified from infertile men and controls using the polymerase chain reaction and was analyzed for polymorphisms by direct sequencing.</p><p><b>RESULTS</b>A total of 9 SNPs were present in the cohort, however there were no significant differences in these 9 SNPs between the case and control groups. According to the results of linkage disequilibrium analysis and haplotype construction, one haplotype (rs757229-rs757230-rs4588110-rs3746165-rs3746166: C-G-G-T-A) was present only in the control men, and significant difference was detected(P< 0.01).</p><p><b>CONCLUSION</b>The SNPs of 5'-UTR region of the GPx4 gene might not be associated with oligo- or asthenozoospermic male infertility. However, the haplotype (rs757229-rs757230-rs4588110- rs3746165-rs3746166: C-G-G-T-A) might be a protective haplotype.</p>

Association between diversity of hypoxia at different altitude and the polymorphism of EPAS1 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the selection effect of endothelial PAS domain protein 1 (EPAS1) gene induced by high altitude hypoxia environment.</p><p><b>METHODS</b>Fourteen single nucleotide polymorphism sites (SNPs) of the EPAS1 gene were genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) in three Tibetan groups (58 samples from Tibetan living in an altitude of about 3700 meters above sea level, 47 from Qinghai province, about 3100 meters above sea level, 43 from Yunnan province, about 2500 meters above sea level), and Han of Shandong (47 samples, about 50 meters above sea level).</p><p><b>RESULTS</b>There were significant differences of most SNP allelic, genotypic and haplotypic frequencies when comparing Han of Shandong, Tibetan of Yunnan with Tibetan of Tibetan and Qinghai. But no difference between Han of Shandong and Tibetan of Yunnan was found.</p><p><b>CONCLUSION</b>The EPAS1 gene might be under hypoxic selection induced by high altitude.</p>

Study of nine single nucleotide polymorphism loci of human HIF1A gene in three Tibetan groups / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the effect of hypoxia environment induced by altitude on hypoxia inducible factor 1α (HIF1A) gene.</p><p><b>METHODS</b>Nine single nucleotide polymorphism (SNP) loci of the HIF1A gene from three Tibetan groups (Tibet, Qinghai Province and Yunnan Province) were genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) method.</p><p><b>RESULTS</b>For non-synonymous mutation SNP site, there was no significant difference among the three Tibetan groups, except for SNP rs11549465 between Tibet Tibetan and Yunnan Tibetan, as well as between Qinghai Tibetan and Yunnan Tibetan. Frequencies of genotypes and alleles in rs4899056, rs1957757, rs10873142 and rs3783752 had significant differences between Tibet Tibetan and Yunnan Tibetan, and between Qinghai Tibetan and Yunnan Tibetan (all P<0.05). We also observed that the difference was negatively correlated with the altitude.</p><p><b>CONCLUSION</b>The results suggested that the HIF1A gene might be under hypoxic selection induced by high altitude in the three groups.</p>