Role of the Clinical Features and MRI Parameters on Ki-67 Expression in Hepatocellular Carcinoma Patients: Development of a Predictive Nomogram.

PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.

Mechanism study of tyrosine phosphatase shp-1 in inhibiting hepatocellular carcinoma progression by regulating the SHP2/GM-CSF pathway in TAMs.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Macrophage-mediated innate immune responses play a crucial role in tumor development. This study revealed the mechanism of SHP-1 in regulating HCC progression. SHP-1 inhibits tumour development in vivo. Increasing SHP-1 expression in macrophages promotes the expression of p-SHP-1, SHP2, and p-SHP-2. In macrophages GM-CSF recruits SHP-2 to the GM-CSF receptor GM-CSFR induces p-SHP-2 dephosphorylation. GM-CSF recruits p-SHP-2 for dephosphorylation by up-regulating HoxA10HOXA10 activates the transcription of TGFß2 by interacting with tandem cis-elements in the promoter thereby regulating the proliferation and migration of liver cancer cells. GM-CSF inhibits SHP-1 regulation of p-SHP-1, SHP2, and p-SHP-2 in macrophages. Detailed studies have shown that SHP-1 regulates SHP2 expression, and SHP-1 and SHP2 are involved in macrophage M2 polarisation. SHP-1 inhibits HOXA10 and TGFß2 which in turn regulates the expression of the migration-associated proteins, MMP2/9, and the migration of hepatocellular carcinoma cells. Overexpression of SHP-1 inhibits macrophage M2 polarisation via the p-STAT3/6 signalling pathway Classical markers arginase-1, CD206, CD163 and regulate the expression of M2 polarisation cytokines IL-4 and IL-10. In addition, hypoxia-induced ROS inhibited SHP-1 regulation by suppressing the expression of p-SHP-1. The combined effect of GM-CSF and ROS significantly increased p-HOXA10/TGFß2 and macrophage M2 polarisation, and the regulatory effect of ROS was significantly suppressed by GM-CSF knockdown. These findings suggest that increasing the expression of tyrosine phosphatase SHP-1 can inhibit hepatocellular carcinoma progression by modulating the SHP2/GM-CSF pathway in TAM and thus inhibit the progression of hepatocellular carcinoma.

[Molecule character of rabies virus in 3 counties in Hunan China].

OBJECTIVE: To study the rabies molecular biology features in animals between high incidence area of rabies and no rabies cases area in Hunan. METHODS: detect saliva of dogs and brains of dogs and cats by direct immunofluorescence assay, review positive samples by RT-PCR, sequencing extract RNA virus for genetic analysis. RESULTS: 12 were detected rabies virus antigen and positive nucleoside acid in 82 dogs from Wugang city also 1 in 17 from Dongkou county; the positive rate: Wugang 14.63 percent, Dongkou 5.88 percent. No rabies virus was detected in 67 samples of dog brains from Fenghuang County. Also none in 28 samples of cat brains. Amplificating N gene of rabies virus from positive samples of dog brain's tissue (No Wg13, Dk13) by RT-PCR, it shows that homology of nucleoside acid between two strain of virus is 99.4 percent; also 99.1 percent of amino acid. The homology of nucleoside acid (amonio acid) among Wg13 stain and Chinese strain CTN and aG strain is 89.4 percent (98.2 percent) and 86.1 percent (95.1 percent); The homology of nucleoside acid (amonio acid) among Dk13 stain Chinese strain CTN and aG strain is 89.1 percent (98.0 percent), 86.1 percent (94.9 percent).Compare with isolated rabies virus from abroad, the homology between two strains and Indonesia is 92.8 percent and 93.2 percent, the most similar of them. The strains isolated from other countries including Japan, Sri Lanka and India are relatively lower; The sequence of gene Wg13 and Dk13 were taken replacement of amino acid. CONCLUSION: Two strains are belong to type I rabies virus, comparing its N gene with current using vaccine strains, both are in same group, and homology are relatively higher.