Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.

Objective To observe the value of the scoring model of MRI features for predicting proliferative hepatocellular carcinoma(HCC).Methods Data of 241 patients with pathologically confirmed HCC,including 90 cases of proliferative HCC and 151 cases of non-proliferative HCC were analyzed retrospectively.Univariate and multivariate logistic regression were used to compare the clinical and MRI findings evaluated according to liver imaging reporting and data system version 2018 between groups.The independent predictive factors of proliferative HCC were screened,and scores were assigned according to the weight,then a scoring model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curves(AUC)were calculated to assess the predictive efficacy of this model.The patients were divided into high and low proliferation risk subgroups based on the optimal score thresholds.The recurrence free survival(RFS)rates and early RFS rates were compared between groups and subgroups.Results MRI showed tumor corona enhancement,arterial phase annular hyper-enhancement,intratumoral vessels,much focus parenchymal low enhancement and irregular tumor margins were all independent predictive factors for proliferative HCC(OR=3.287,2.362,4.542,2.997,2.379,all P＜0.05),which were then were scored with 7,5,9,7 and 5,respectively,with a total score of 0-33.AUC of the obtained scoring model for predicting proliferative HCC was 0.818.Taken 9 points as the optimal score thresholds,97 cases were assigned into high proliferation subgroup and 144 into low proliferation risk subgroups).Significant differences of RFS rates and early RFS rates were found between groups and subgroups(all P＜0.05).Conclusion MRI features scoring model could effectively predict proliferative HCC.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.
Antigens, Neoplasm ; Coronary Disease/genetics* ; Gene Frequency ; Glycation End Products, Advanced ; Heart Rate ; Humans ; Mitogen-Activated Protein Kinases ; Polymorphism, Genetic

Objective:To explore the accuracy and clinical effect of computer navigation system in locating the tunnel position in anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective case-control study was conducted to analyze clinical data of 60 patients with ACL rupture treated in Daping Hospital of Army Military Medical University from March 2017 to March 2018, including 44 males and 16 females, aged 15-48 years (mean, 26.3 years). Computer navigation system was used to locate the internal orifice of intra-articular femoral and tibial tunnel in 30 patients (navigation group), and artificial location of intra-articular femoral and tibial tunnel in 30 patients (control group). The operation time and complications of two groups were recorded after operation. The tunnel position was evaluated by CT three-dimensional reconstruction, and the ratio of the tunnel position on the lateral surface of the femoral condyle to the tibial platform was evaluated by the grid method. The proportion sites from the deep posterior edge of lateral intercondylar surface of the femur to the shallow anterior edge (DS) and from the upper edge to the lower edge (HL) were used to represent the position of the femoral tunnel, and the proportion sites of the line connecting the anterior and posterior edge of the tibial plateau were used to represent the tibial tunnel position. The postoperative tunnel position was compared between the two groups. The knee joint stability (Lachman test, pivot shift test) and knee joint function score (Lysholm score, Tegner score) were compared between the two groups before operation and 12 months after operation.Results:All patients were followed up for 12-24 months (mean, 15 months). The operation time was (56.1±8.1)minutes in control group versus (76.0±6.7)minutes in navigation group ( P<0.05). In navigation group, 2 patients had skin edge necrosis at the place where the navigation needle was installed. The proportion of DS in femoral tunnel was (27.2±3.7)% in navigation group versus (33.9±4.4)% in control group ( P<0.05). HL proportion site was (36.6±4.8)% in navigation group versus (38.9±4.9)% in control group ( P<0.05). Proportion of the tibial tunnel at the anterior and posterior edge of the tibial plateau was (44.9±1.8)% in navigation group and (44.7±3.0)% in control group ( P>0.05). Both groups showed significant improvements in Lysholm score, Tegner score, Lachman test and pivot shift test 12 months after operation compared to the preoperative levels ( P<0.05), but the knee joint function score and knee joint stability score had no significant difference between the two groups 12 months after operation ( P>0.05). Conclusions:No significant differences are found between computer navigated and manually navigated ACL reconstruction with regards to knee joint stability, knee joint function, and tibial tunnel localization. However, computer assisted navigation enables the location of the lateral femoral tunnel closer to the anatomical position.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by bradykinesia,resting tremor,muscle rigidity,and abnormal gait posture.Ocular motor function test plays an important part in neurological examinations.It has been widely accepted that specific ocular motor patterns contribute to diagnosis of Parkinsonian syndrome including progressive supranuclear palsy and multiple system atrophy.However,recent studies have shown that patients of PD may also exhibit specific eye movement disorders,which will be helpful in the early diagnosis,evaluation and differential diagnosis of PD.In 2015,the Movement Disorder Society clinical diagnostic criteria for Parkinson's disease suggested that sustained staring evoked nystagmus could be used as an exclusive criterion for PD.The clinical features,detection methods and clinical significance of oculomotor dysfunction in PD are reviewed in this article.

Objective To investigate the clinical features of constipation in patients with Parkinson 's disease (PD) and explore the relationship between constipation and motor symptoms.Methods The data of 221 PD patients were collected.Patients were evaluated with following scales:Rome Ⅲ criteria for diagnosis of functional constipation,unified Parkinson's disease rating scale part Ⅲ (UPDRS Ⅲ),and simple mental status examination scale (MMSE).Results Among 221 PD patients,132 (59.7％) had constipation,and 48 (36.4％) experienced constipation before motor symptoms.Compared to those without constipation,PD patients with constipation had a higher UPDRS Ⅲ scores,posture/gait scores,and axis scores (P ＜ O.05).The most common symptoms of PD patients with constipation were defecation straining (93.9％).Conclusions PD patients with constipation have severer motor symptoms than those without constipation.Defecation straining is the most common subtypes of PD patients with constipation.

Objective To investigate the change of body mass index (BMI) in Parkinson's disease (PD) and its association with disease severity.Methods SPSS 22.0 was used for data analysis of one hundred and sixty-eight PD patients and one hundred and fifteen healthy controls.Results BMI value was obviously declined in PD (P =0.001).Decrease of BMI in PD was associated with increase of disease duration (r =-0.270,P =0.001),total score of Unified Parkinson~ Disease Rating Scale (UPDRS) (r =-0.195,P =0.008),score of UPDRS part Ⅱ (r =-0.147,P =0.045),score of UPDRS part Ⅲ (r =-0.159,P =0.030),H-Y grading (r =-0.256,P =0.001),and mini-mental state examination (MMSE) (r =0.291,P =O.001).Conclusions BMI declines more obviously in PD patients than in healthy controls.PD Patients with longer disease duration and severe motor symptoms have a higher risk of BMI loss.