Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that is involved in the development of neuropathic pain. P2X7 receptor (P2X7) belongs to a class of ATP-gated nonselective cation channels that plays an important role in neuropathic pain. Nevertheless, little is known about the interaction between them for neuropathic pain. In this paper, we investigated role of TRPV4-P2X7 pathway in neuropathic pain. We evaluated the effect of TRPV4-P2X7 pathway on neuropathic pain in a chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) model. We analyzed the effect of P2X7 on mechanical and thermal hyperalgesia mediated by TRPV4 in CCD. Furthermore, we assessed the effect of TRPV4 on the expression of P2X7 and the release of IL-1ß and IL-6 in DRG after CCD. We found that intraperitoneal injection of TRPV4 agonist GSK-1016790A led to a significant increase of mechanical and thermal hyperalgesia in CCD, which was partially suppressed by P2X7 blockade with antagonist Brilliant Blue G (BBG). Then, we further noticed that GSK-1016790A injection increased the P2X7 expression of CCD, which was decreased by TRPV4 blockade with antagonist RN-1734 and HC-067047. Furthermore, we also discovered that the expressions of IL-1ß and IL-6 were upregulated by GSK-1016790A injection but reduced by RN-1734 and HC-067047. Our results provide evidence that P2X7 contributes to development of neuropathic pain mediated by TRPV4 in the CCD model, which may be the basis for treatment of neuropathic pain relief.

PIVKA-II level is correlated to development of portal vein tumor thrombus in patients with HBV-related hepatocellular carcinoma.

AIM: To evaluate the correlation of serum PIVKA-II levels and development of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. METHODS: One hundred and twenty-three patients with newly diagnosed HCC were included in this study between March 2016 and October 2018. Thirty-five of these patients were detected with PVTT and all subjects were randomly divided to analysis group (N = 73) and validation (N = 50) group. Serum levels of PIVKA-II, laboratory tests including serum aspartate aminotransferase, total bilirubin, platelet count, albumin levels were demonstrated in all the patients. T-test, chi-squared test and logistic regression was used for analyzing data. Diagnostic efficiency and cut-off value of PIVKA-II in PVTT development of HCC patients were calculated using receiver operator curve (ROC) analysis. RESULTS: Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than that in HCC patients without PVTT (995.8 mAU/ml vs 94.87 mAU/ml; P = 0.003), as well as D-dimer levels (2.12 mg/L vs 0.56 mg/L P = 0.001). Univariate analysis showed that high serum D-dimer level was an independent risk factor for development of PVTT (OR = 1.22, 95%CI 1.02-1.45). ROC curve showed that among analysis group, the area under ROC curve (AUROC) of PIVKA-II was 0.73 (95%CI 0.59-0.86). For the detection of PVTT in HCC, PIVKA-II had a sensitivity of 83.7% and a specificity of 69.2% at a cutoff of 221.26 mAU/ml, which had a sensitivity of 85.71% and a specificity of 55.56% in validation group, respectively. CONCLUSION: Serum PIVKA-II level is a potential marker for diagnosis of PVTT in HCC patients, which may guide therapeutic strategy and assessment of tumor prognosis of HCC.

Correlation between CYP4F2 gene rs2108622 polymorphism and susceptibility to ischemic stroke.

OBJECTIVE: To conduct a meta-analysis for the correlation between cytochrome P450 4F2 (CYP4F2) rs2108622 (V433M) gene polymorphism and ischemic stroke. METHODS: We retrieved the case-control studies on the correlation between CYP4F2 V433M polymorphism and ischemic stroke included in domestic and international databases before January 2015 and selected the best genetic model, using RevMan 5.2 software for meta-analysis. According to the heterogeneity test results of selected literature, the effect model of consolidated data was selected, and the combined OR and 95% CI were calculated. RESULTS: A total of six documents were included. Recessive model (VM + MM vs. VV) was selected as the best genetic model. The combined results showed that: compared with wild-type VV, there are significant association between ischemic stroke and CYP4F2 polymorphism (OR merge = 1.37, 95% CI: 1.21~1.54, P < 0.001). CONCLUSION: CYP4F2 V433M may be the susceptibility gene for ischemic stroke.

IL-17A G197A gene polymorphism contributes to susceptibility for liver cirrhosis development from patients with chronic hepatitis B infection in Chinese population.

BACKGROUND: IL-17A G197A and IL-17F A7488G gene polymorphisms are found to be associated with the risk of several diseases, however few studies have focused on their correlation with risk of liver cirrhosis (LC). AIMS: The aim of this study was to assess the impact of IL-17A G197A and IL-17F A7488G gene polymorphisms on development of LC from chronic hepatitis B (CHB) in Chinese patients. METHODS: A total of 163 HBV-related LC patients and 168 CHB patients were enrolled in the present study. IL-17A and IL-17F gene polymorphisms were analyzed using a polymerase chain reaction (PCR) restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: Frequencies of IL-17A G197A genotype AA and allele A were significantly higher in LC patients compared with that in CHB patients (AA 42.33% vs 27.98%, P = 0.032; A 56.34% vs 46.15%, P=0.011, respectively); While no significant difference in frequencies of genotypes and alleles of IL-17F A7488G was found between the two groups. The AA genotype of IL-17A G197A significantly increased LC risk (OR 4.186, 95% CI: 1.479-11.844), while A allele carriers were also associated with an increased LC risk (OR 1.856, 95% CI: 1.161-2.967). CONCLUSION: IL-17A G197A is a candidate gene that confers the genetic susceptibility for LC development from CHB in Chinese population.

Decreased expression of IL-27 and its correlation with Th1 and Th17 cells in progressive multiple sclerosis.

Progressive multiple sclerosis (MS) is an immune-mediated demyelinating disease in which both imbalanced T helper (Th) subsets and aberrant cytokine profiles have been found. Interleukin-27 (IL-27), a cytokine with pro-inflammatory and anti-inflammatory effects, plays pleiotropic roles in immunomodulation. In the present study, plasma levels of IL-27, interferon-gamma (IFN-γ), IL-17 and frequencies of peripheral Th1, Th17 cells were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry in 45 progressive MS and 25 healthy controls. mRNA expression levels of IL-27, IFN-γ, T-bet, IL-17 and RAR-related orphan receptor gamma t (RORγt) in peripheral blood mononuclear cells (PBMCs) were also quantified by real-time polymerase chain reaction. Plasma and mRNA levels of IL-27 in progressive MS patients were significantly lower than those in healthy controls, while plasma concentrations of IL-17, frequencies of circulating Th17, and mRNA expression levels of IL-17 as well as RORγt were all increased remarkably compared with healthy controls. No statistical significance was observed in IFN-γ and T-bet mRNA expression or plasma IFN-γ levels between progressive MS patients and healthy controls. Moreover, plasma levels of IL-27 were found to be negatively correlated to the percentages of circulating Th17 or plasma IL-17 concentrations in patients with progressive MS. Our data showed that progressive MS patients had decreased plasma and mRNA expression levels of IL-27, suggesting that it might be involved in the pathophysiological process of MS.

[Clinical observation on effect of electric acupuncture at Sishencong in treating insomnia].

OBJECTIVE: To evaluate the clinical therapeutic effect of electric acupuncture (EA) at Sishencong (EX-HN 1) on insomnia. METHODS: Two hundred and seventy-six patients were randomly assigned to 2 groups, 138 in each group, the EA group treated with EA at Sishencong, and the control group with oral administration of Tianmeng Capsule. The treatment course for both groups was 3 weeks. The quality and related parameters of sleep before and after treatment were evaluated with a multi-channel sleep detector. RESULTS: After treatment, the quality of sleep was improved in both groups (P < 0.05), as compared with before treatment, the difference in related parameters was significant respectively (P<0.05 or P <0.01), however, the improvement in the EA group was superior to that in the control group (P < 0.01). CONCLUSION: EA at Sishencong has obvious effect on insomnia.