Objective To investigate the differential diagnosis of early-stage Parkinson disease(PD) and vascular Parkinsonism(VP) by 99Tcm-TRODAT-1 single photon emission computed tomography brain imaging.Methods 99Tcm-TRODAT-1 SPECT brain imaging was performed on 47 patients with early-stage PD,26 with early-stage VP and 30 age-matched healthy control subjects.The radioactive ratio of striatum to cerebullum was calculated by region of interest(ROI) technique.The results were analyzed and compared.Results The distribution and quantities of 99Tcm-TRODAT-1 uptake were reduced in contralateral striatum to clinically symptomatic side of the patients with early-stage PD(P0.05).The radioactive ratio of striatum to cerebullum contralateral to the affected limb in the patients with early-stage PD was lower than that in the healthy control subjects while that to patients with early-stage VP were similar to that in the healthy control subjects.Conclusion 99Tcm-TRODAT-1 single photon emission computed tomography brain imaging and semiquantitative analysis are useful to differentiate VP from PD.

Objective This is the first study to explore clinical application value of serum Dickkopf-1 (DKK-1) detection in diagnosis of heptocellular carcinoma (HCC) by magnetic solid phase chemiluminescent immunoassay.Methods The level of serum DKK-1 and AFP in 205 cases of HCC,40 cases of liver cirrhosis,and 200 cases of healthy control were quantitatively detected by Magnetic solid phase chemiluminescent immunoassay.The area under ROC curve,sensitivity and specificity of DKK-1 and AFP for diagnosing HCC were calculated.Results The serum level of DKK-1 in HCC group was significantly higher than those of the liver cirrhosis group and healthy control group (P<0.01).DKK-1 maintained diagnostic sensitivity for patients with HCC who were alpha-fetoprotein (AFP) negative (66.3%).ROC curves showed optimum diagnostic cut-off value was 2.4 ng/mL,area under curve (AUC) was 0.822 (95% CI:0.783-0.856),sensitivity 65.9%,and specificity 87.5%).Moreover,measurement of DKK1 and AFP together improved diagnostic accuracy for HCC versus all controls compared with either test alone [AUC 0.915,95%CI:0.886-0.940),sensitivity 81.5 %(P<0.05)].Conclusion Serum DKK-1 detection has an important clinical value for diagnosis of HCC,especially for HCC with AFP negative.The combined detection of serum DKK-1 and AFP can greatly increase sensitivity and accuracy for diagnosing HCC.

In recent years, the regulatory role of microRNAs in liver pathological process has attracted more and more attention. In viral hepatitis and steatohepatitis, microRNA-335 (miRNA-335) regulates the progression of hepatitis via the transcription factor sex-determining region Y-box 4; in the development and progression of progressive liver fibrosis and liver cancer, miRNA-335 affects collagen production, deposition, and degradation in the liver via the target genes including hypoxia-inducible factor 1α, phosphatase and tensin homologue, Rho-associated coiled-coil containing protein kinase 1, plasminogen activator inhibitor-1, twist family bHLH transcription factor 1, and mesenchymal-epithelial transition factor and thus regulates the migration and invasion of hepatic stellate cells and hepatoma cells. This article summarizes the research advances in the role of miRNA-335 in hepatitis, liver fibrosis, and liver cancer in recent years, and based on existing data, it is pointed out that the miRNA-335/QSOX1 regulatory axis may mediate artesunate against schistosomal liver fibrosis by inhibiting hepatic stellate cell activation, so as to provide new ideas for the treatment of liver fibrosis and other liver diseases.

Objective:To evaluate the quantitative diagnostic value of controlled attenuation parameter (CAP) in health checkup groups with asymptomatic nonalcoholic fatty liver disease.Methods:A multicenter prospective study was conducted among Chinese individuals undergoing regular health checkups; a total of 173 subjects were investigated. Human body indexes such as height, weight, and blood pressure were measured, and complete blood count, liver function, blood lipid, FibroScan, and MRI-PDFF examinations were performed. Correlation between MRI-PDFF and CAP was described using Spearman′s and Pearson′s coefficients. Diagnostic efficacy of the CAP was evaluated using the subject work characteristic curve and the area under this curve, and the optimal cut-off value was determined according to the Youden index.Results:The average age and body mass index of the subjects were 45.0±10.5 years and 25.8±4.0 kg/m 2, respectively. A linear correlation was found between CAP and lg transformed magnetic resonance imaging-based proton density fat fraction results (Pearson′s coefficient 0.772, P<0.001). When optimized for ≥90% sensitivity, the CAP cutoff for staging ≥S1 steatosis was 244 dB/m. Conclusions:The CAP result was significantly correlated with the liver fat fraction measured by MRI-PDFF, and capable of differentiating steatosis grades. CAP can be used as a tool for screening fatty liver in health checkup groups.

The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases (CDKs) is a hallmark of cancer. The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs. In particular, third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition, exhibiting a perfect balance between anticancer efficacy and general toxicity. To date, three selective CDK4/6 inhibitors have received approval from the U.S. Food and Drug Administration (FDA), and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers. In this perspective, we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells, analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment, review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds, explain the mechanisms associated with CDK4/6 inhibitor resistance and describe solutions to overcome this issue, and briefly introduce proteolysis targeting chimera (PROTAC), a new and revolutionary technique used to degrade CDK4/6.