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 investigate the influence of environmental factors on body mass index of children and adolescents in China.Methods:Using data from the China Health and Nutrition Survey, the research object to 7 - 17 years old children and adolescents who participated in 2000, 2006, 2011, and 2015 round of survey with complete data, a total of 6 626 children and adolescents (male 3 473, female 3 153) were investigated under univariate analysis for each environmental factor variable before using Partial Least Square Regression fitting a linear model for further screening. Finally, we fitted a three-level linear mixed-effects model distinct by urban and rural area for analysis.Results:The three-level null model, log likelihood=-17 034.68, χ 2=483.06, P<0.001. Intern-class correlation coefficient ( ICC) showed that community-level was 9.97%, and both community and individual were 39.38%. The three-level model also showed that urban model's urbanization index ( β=-0.05, 95% CI: -0.09--0.01, P<0.05), the park location ( β=-0.88, 95% CI: -1.72 - -0.04, P<0.05), 15 - 17 age group ( β=-1.04, 95% CI:-1.78 - -0.30, P<0.05) were negatively correlated with BMI. The distance to the gym ( β=0.12, 95% CI: 0.02 - 0.22, P<0.05), the number of home TV sets ( β=0.50, 95% CI: 0.08 - 0.92, P<0.05) and the frequency of parents' alarm of fiction TV program contents ( β=1.85, 95% CI: 0.70 - 3.00, P<0.05) were correlated with BMI. Rural urbanization index ( β=-0.04, 95% CI:-0.07 - -0.01, P<0.05). Rural per capita income ( β=-7.29e -4, 95% CI:-1.00e -3 - -6.77e -5, P<0.05), parents' restricted frequency of watching TV ( β=-1.29, 95% CI:-2.36 - -0.21, P<0.05), adipo-energy ratio ( β=-0.03, 95% CI:-0.06 - -1.00e -3, P<0.05) were negatively correlated with the BMI. Factors as the frequency of parents' alarm of fiction TV program contents ( β=3.01, 95% CI: 0.03 - 6.00, P<0.05), the survey time was 2015 ( β=4.83, 95% CI: 1.96 - 7.69, P<0.05) were correlated with BMI. Conclusions:Environmental factors could indirectly influence the change of BMI of children and adolescents to different degrees and various aspects. Urbanization index and rural per capita income had a slight protective effect on increasing BMI of children and adolescents. At the community level, attention should be paid to the setting of activity places around the living environment of children and adolescents. Family members should also guide their children and adolescents to develop nice behavior in watching TV.

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.

Objectives:To investigate the clinical feasibility of three-dimensional(3D)high-resolution late gadolinium enhancement(LGE)MRI in accessing left atrial myocardial fibrosis in patients with atrial fibrillation(AF). Methods:A total of 34 AF patients referred for hybrid surgical ablation were retrospectively enrolled in this study.3D-LGE-MRI images were acquired by Siemens 3.0 T machine and analyzed by ADAS post-processing software by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE.Regional analysis was performed by one of the two radiologists at ten left atrial segments.The Kappa test was used to assess the agreement for scoring image quality,and the interclass correlation coefficient(ICC)was used to evaluate the interobserver agreement of LGE parameters.The parameters of left atrial morphology,area(and area percentage)of LGE,and location of LGE were compared between patients with persistent AF and paroxysmal AF. Results:Images of all 34 patients were considered to have diagnostic value.The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were(2.88±0.64)points and(3.26±0.75)points(radiologist 1),(2.97±0.58)points and(3.24±0.70)points(radiologist 2),respectively.The corresponding Kappa values were 0.724 and 0.859.Both the area and the area percentage of LGE showed good consistency among observers,and the ICCs were 0.969 and 0.950,respectively.The difference in the area of LGE and the area percentage of LGE between patients with paroxysmal and persistent atrial fibrillation was similar(both P＞0.05).Compared with patients with paroxysmal AF,patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum(all P＜0.05). Conclusions:3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis.The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF,with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.

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.

Randomized controlled trial (RCT) are considered the "gold standard" for evaluating the causal effects of interventions on outcome measures. However, due to high research costs and ethical constraints, conducting RCT in clinical practice, especially in the surgical field, faces numerous challenges such as difficulties in subject recruitment, implementation of blinding, and standardization of interventions. In such cases, using real-world data to perform causal inference under the framework of target trial emulation (TTE), based on the principles of RCT design, helps to identify and reduce biases arising from design flaws in traditional observational studies, such as immortal time bias, confounding, selection bias, or collider bias. This approach can produce high-quality evidence comparable to that of RCT, thereby enhancing the clinical guidance value of real-world data studies. However, TTE has limitations, such as the inability to completely eliminate confounding, high quality requirements for source data, and the current lack of reporting standards. Therefore, researchers should be fully aware of these limitations to avoid making incorrect causal inferences. This article intends to provide an overview of the TTE framework, implementation points, application scope, application cases, and advantages and disadvantages of the framework.