The treatment choices of abdominal aortic aneurysm patients in China in the era of value-based healthcare.

Background: Endovascular aneurysm repair (EVAR) is often seen as the first choice treatment for patients with abdominal aortic aneurysm (AAA), particularly high-risk patients, yet the long-term survival rate and improvement in quality of life are still unclear. In order to seek the value of EVAR to the entire healthcare field, we conducted a retrospective study to evaluate whether the improvement EVAR can truly bring to the quality of medical care in the era of value-based healthcare. Methods: We included AAA patients who underwent surgical treatment in the Department of Vascular Surgery, First Hospital of China Medical University, from January 1, 2004, to December 31, 2019 and evaluated surgery procedure data, short-term and long-term mortality, complications, prognoses, and medical costs. Results: We analyzed 507 patients with AAA who underwent open repair (n = 232) or EVAR (n = 275) over a 15-year period. The operative time, blood loss, blood transfusion rate, and postoperative length of hospital stay of the EVAR group is significantly lower than which of the open repair group. Meanwhile, neither short-term nor long-term mortality rates shows significant differences between the two groups. On the other hand, the complication rate of the EVAR group was significantly higher than that of the open repair group. Lastly, the total cost of EVAR was significantly higher than that of open repair. Conclusion: Existing evidence suggests that EVAR improves neither short-term nor long-term survival rate compared with open surgery. In contrast, the complication rate and the reintervention rate in the EVAR group were higher than those in the open surgery group. Moreover, the cost of EVAR and that paid by medical insurance were higher than those for open surgery. For patients with a long-life expectancy, in order to ensure that patients receive appropriate and effective care, surgeons should choose a suitable method that considers both the quality of medical care as well as the expense accordingly.

Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality.

Background: Sleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET. Method: We enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted. Results: Global network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (r = -0.354, p =0.027). Conclusion: Our findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.

Disrupted Brain Functional Network Topology in Essential Tremor Patients With Poor Sleep Quality.

Sleep disturbances, especially poor quality of sleep (QoS), are common among essential tremor (ET) patients and may have adverse effects on their quality of life, but the etiology driving the poor QoS in these individuals remains inadequately understood. Few data are available on the neuroimaging alterations of ET with poor QoS. Thirty-eight ET patients with poor QoS (SleET), 48 ET patients with normal QoS (NorET), and 80 healthy controls (HCs) participated in this study. All subjects underwent a 3.0-T magnetic resonance imaging (MRI) scan for resting-state functional MRI data collection. Then, the whole-brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions. Graph theory and network-based statistical analyses were performed. We used a non-parametric permutation test for group comparisons of topological metrics. Partial correlation analyses between the topographical features and clinical characteristics were conducted. The SleET and NorET groups exhibited decreased clustering coefficients, global efficiency, and local efficiency and increased the characteristic path length. Both of these groups also showed reduced nodal degree and nodal efficiency in the left superior dorsolateral frontal gyrus, superior frontal medial gyrus (SFGmed), posterior cingulate gyrus (PCG), lingual gyrus, superior occipital gyrus, right middle occipital gyrus, and right fusiform gyrus. The SleET group additionally presented reduced nodal degrees and nodal efficiency in the right SFGmed relative to the NorET and HC groups, and nodal efficiency in the right SFGmed was negatively correlated with the Pittsburgh Sleep Quality Index score. The observed impaired topographical organizations of functional brain networks within the central executive network (CEN), default mode network (DMN), and visual network serve to further our knowledge of the complex interactions between tremor and sleep, adding to our understanding of the underlying neural mechanisms of ET with poor QoS.

Reclassification of patients with tremor syndrome and comparisons of essential tremor and essential tremor-plus patients.

BACKGROUND: The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort. METHODS: In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL. RESULTS: Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL. CONCLUSIONS: ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression.

Brain network topology and future development of freezing of gait in Parkinson's disease: a longitudinal study.

BACKGROUND: Freezing of gait (FOG) is a common disabling gait disturbance in Parkinson's disease (PD). The objectives of this study were to explore alterations in the topological organization of whole-brain functional networks in patients with PD who will develop FOG. METHODS: We recruited 20 patients with PD who developed FOG (PD-FOGt) during a 5-year follow-up period, 20 patients with PD who did not developed FOG (PD-FOGn) within the follow-up period, and 20 healthy control subjects. Using graph theory approaches, we performed a comparative analysis of the topological organization of whole-brain functional networks among the groups, and further explored their potential relationships with latency to develop FOG. RESULTS: At baseline, the global topological properties of functional brain networks in PD-FOGt and PD-FOGn showed no abnormalities. Additionally, regarding regional topological properties, compared with PD-FOGn patients, PD-FOGt patients exhibited decreased nodal centrality in the left middle frontal gyrus (MFG). Although there were no significant differences compared with PD-FOGn patients, the PD-FOGt group exhibited the lowest nodal centrality values in the frontal cortex (left gyrus rectus), and visual cortex (bilateral inferior occipital gyrus and left fusiform gyrus), and the highest nodal centrality values in the cerebellum (vermis_6) among the three groups. However, no relationship was found between the nodal centrality in above brain regions and latency to develop FOG. CONCLUSION: This study demonstrates the disrupted regional topological organization might contribute to the future development of FOG in PD patients, especially associated with damage to the left MFG.

Disrupted functional brain network topology in Parkinson's disease patients with freezing of gait.

BACKGROUND: Freezing of gait (FOG) is a common and debilitating gait disturbance in patients with Parkinson's disease (PD), but the potential mechanisms are still unclear. This study aimed to explore alterations in the topological organization of whole-brain functional networks in PD patients with FOG. METHODS: We recruited 75 patients with PD, 37 patients with FOG and 38 patients without FOG, to undergo resting-state functional magnetic resonance imaging (fMRI). The whole-brain functional networks were constructed, and the topological properties at three (global, nodal, and connectional) levels were analyzed using graph theory approaches. RESULTS: Compared with patients without FOG, patients with FOG exhibited altered global topological properties (a significant decrease in the normalized clustering coefficient and small-worldness), implying a shift toward randomization in their functional brain networks. At the node and connectional levels, patients with FOG showed increased nodal centralities and functional connectivity in the sensorimotor network, frontoparietal network, visual network, subcortical and limbic regions, and decreased nodal centralities in the frontoparietal network and the cerebellum. Furthermore, the altered nodal centralities in the right hippocampus (HIP) were positively correlated with FOG severity. CONCLUSIONS: This study suggests that FOG in PD is associated with disrupted topological organization of whole-brain functional networks, involving dysfunction of the multiple networks.

Disrupted Brain Network Topology in Drug-naïve Essential Tremor Patients with and Without Depression : A Resting State Functional Magnetic Resonance Imaging Study.

PURPOSE: This study was carried out to investigate brain functional connectome and its potential relationships with the disease severity and emotion function in patients with essential tremor with and without depressive symptoms by using resting-state functional magnetic resonance imaging and graph theory approaches. METHODS: In this study 33 essential tremor patients with depression, 45 essential tremor patients without depression and 79 age and gender-matched healthy controls were recruited to undergo a 3.0­T imaging scan. The whole brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions, and the topologic properties were analyzed by using graph theory approaches and network-based statistic approaches. Nonparametric permutation test was also used for group comparisons of topological metrics. Correlation analyses between topographic features and the clinical characteristics were performed. RESULTS: The functional connectome in both essential tremor patients with and without depression showed abnormalities at the global level (decrease in clustering coefficient, global efficiency, and local efficiency but increase in characteristic path length) and at the nodal level (decrease nodal centralities in the cerebellum, motor cortex, prefrontal-limbic regions, default mode network) (p < 0.05, false discovery rate corrected). Moreover, essential tremor patients with depression showed higher node efficiency in superior frontal gyrus and posterior cingulate gyrus compared to essential tremor without depression. CONCLUSION: Our results may provide insights into the underlying pathophysiology of essential tremor patients with and without depression and aid the development of some potential biomarkers of the depressive symptoms in patients with essential tremor.

A compound heterozygous PINK1-associated juvenile Parkinson's disease with pregnancy in Chinese.

BACKGROUND: PINK1 mutations are the second most common cause of recessive, early-onset Parkinson's disease (EOPD), of which 15% are cases of juvenile PD. PD is a progressive neurological disease that primarily affects middle-aged and older people. Thus PD patients experiencing pregnancy is uncommon, especially in patients with juvenile PD caused by PINK1 mutations. We are first to report a woman from a Chinese family diagnosed with sporadic juvenile PD and treated with levodopa/benserazide throughout pregnancy. METHODS: Whole exome sequencing was performed on this patient, and pedigree verification was performed on her parents. This patient received levodopa/benserazide treatment with regular outpatient follow-up exams. RESULTS: Whole exome sequencing and Sanger sequencing identified a heterozygous nonsense mutation (c.1474C > T, p.R492X) and a splicing mutation (c.1488 + 1G > A) that were in exon 7 of the PINK1 gene, co-segregating with the PD phenotype and exhibiting an autosomal recessive pattern. With regular outpatient follow-up exams, this patient delivered a healthy boy without complications. Her PD symptoms were stable with the levodopa/benserazide treatment throughout her pregnancy except in the postpartum period. CONCLUSION: Our findings further demonstrated the safety of levodopa with dopa-decarboxylase treatment in PINK1-associated juvenile PD during pregnancy.

Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study.

OBJECTIVES: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr. METHODS: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. RESULTS: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. DISCUSSION: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

Melatonin Plays a Critical Protective Role in Nicotine-Related Abdominal Aortic Aneurysm.

Aim: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. Methods: In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. Results: We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the in vivo model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype.

Whole-exome sequencing in early-onset Parkinson's disease among ethnic Chinese.

Although early-onset Parkinson's disease (EOPD) has a more penetrant genetic etiology, the genetic architecture of EOPD remains unclear. The objectives of this study were to assess the genetic and clinical features of EOPD among ethnic Chinese from mainland China. Using whole-exome sequencing, we performed genetic analyses of 240 participants including 193 with sporadic and 47 with familial EOPD (age of onset <50 years). In total, 18 patients (7.5%) harbored pathogenic or likely pathogenic variants in known PD genes. Among these variants, biallelic variants in Parkin and PINK1 were responsible for 4.2% of cases, and rare likely pathogenic variants in LRRK2 (1.7%) also appeared to be a relatively common cause of EOPD. Notably, 7.5% of patients carried risk variants in either LRRK2 or GBA, which should also be considered for EOPD. Nevertheless, 41 patients (17.1%) had rare variants of unknown significance. In conclusion, our findings provide a better understanding of the genetic architecture of PD among ethnic Chinese, and the pathogenicity of numerous rare variants should be further investigated.

Distinct non-motor features of essential tremor with head tremor patients.

BACKGROUND: There have been few comprehensive scale studies on the non-motor symptoms (NMS) of patients with essential tremor (ET) with head tremor (ETh) and those with ET without head tremor (ETol). We aimed to explore the motor symptoms and NMS of these two subgroups. METHODS: We enrolled 199 patients with ET (125, ETol; 74 ETh) and 132 healthy controls. We evaluated motor symptoms using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and NMS using the Non-Motor Symptom Scale (NMSS). We compared NMSS scores and the prevalence of each NMS between the patient subgroups. Finally, we conducted a logistic regression analysis of the correlation between head tremor and NMS severity, as well as other determinants. RESULTS: There were no significant between-subgroup differences in demographic characteristics. Further, they presented similar tremor clinical manifestation; however, the ETh subgroup showed a higher prevalence of rest tremor, feeling of sadness, forgetting things or events, and swallowing difficulty, as well as TRS scores, compared with the ETol subgroup. Both patient subgroups showed high scores and prevalence (>50%) in difficulty falling asleep. Logistic regression analysis indicated age as a tremor severity determinant; further, head tremor and tremor severity were NMS determinants. CONCLUSION: Both patient subgroups presented various NMS including sleep disturbances, cognitive deficits, and affective disorders. The ETh subgroup showed a high prevalence of certain NMS aspects including memory and affective disorder; further, they had aggravated NMS. ET with both upper limb tremor and head tremor may be regarded as a more severe clinical subtype.

Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson's disease.

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum_crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

Association of three candidate genetic variants in ACMSD/TMEM163, GPNMB and BCKDK /STX1B with sporadic Parkinson's disease in Han Chinese.

Large-scale meta-analyses of genome-wide association studies have identified that polymorphisms ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the role of these three polymorphisms in a Han Chinese population from mainland China still remains to be clarified. We conducted a large sample study to examine genetic associations of rs6430538, rs199347 and rs14235 with PD in a Han Chinese population of 989 sporadic PD patients and 1058 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. In addition, we conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, no significant differences were found in genotype and allele frequency distribution between PD patients and controls for the three loci, even after being stratified by age at onset. Moreover, we demonstrated that minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our study is the first to demonstrate that ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 do not confer a significant risk for sporadic PD in mainland China. Therefore, more replication studies in additional Chinese population and other cohorts and functional studies are warranted to further clarify the role of the three loci in PD susceptibility.

Long noncoding RNA H19 promotes vascular remodeling by sponging let-7a to upregulate the expression of cyclin D1.

Vascular remodeling is mainly caused by excessive proliferation of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) have emerged as important regulators in diverse pathological processes. Previous work has shown the functions and mechanisms of long noncoding RNA H19 (LncRNA H19) on VSMCs. As long noncoding RNAs (lncRNAs) are complex in their mechanisms of action, the aim of the study is to identify if there are any other molecular mechanisms of LncRNA H19 on VSMCs. In vivo studies demonstrated that cyclin D1 was overexpressed in neointima of balloon-injured artery. In vitro studies identified that the overexpression of LncRNA H19 promoted VSMCs proliferation and cyclin D1 upregulation. On the contrary, cellular proliferation and expression of cyclin D1 were inhibited in VSMCs after infection with let-7a. Furthermore, luciferase reporter assays and RNA pull-down assays were used to explore the regulatory mechanism, we found that LncRNA H19 functioned as a competing endogenous RNA (ceRNA) by sponging let-7a to promote the expression of the target gene cyclin D1. In conclusion, LncRNA H19 positively regulated cyclin D1 expression through directly binding to let-7a in VSMCs. Our findings provide new insight into the mechanism of LncRNA H19 in VSMCs proliferation and vascular remodeling, and further indicate the implications of LncRNA H19 in the diagnosis and treatment of vascular proliferative diseases.

High expression of microRNA­31 and its host gene LOC554202 predict favorable outcomes in patients with colorectal cancer treated with oxaliplatin.

The expression levels of microRNA­31 (miR­31) and LOC554202 have been previously investigated in colorectal cancer (CRC) and their oncogenic and/or tumor suppressive roles have been described. The aim of the present study was to examine the role of miR­31 and its host gene LOC554202 in the prognosis of patients with CRC. Patients with CRC treated with oxaliplatin­based chemotherapy between June 2005 and March 2010 were recruited to the First Affiliated Hospital of China Medical University. Tumor and adjacent mucosal tissues were collected. The detection of miR­31 and/or LOC554202 was performed with probe hybridization targeting. Correlation analysis was performed among the expression levels of miR­31, LOC554202, and their association with clinicopathological parameters and/or survival rates. miR­31 and LOC554202 were expressed at high levels in CRC (P<0.01) compared with adjacent intestinal mucosa. A linear correlation was noted for the two markers in CRC tissues (P<0.01). The expression of miR­31 was significantly higher in adenocarcinoma than in the adjacent intestinal mucosa (P<0.01), whereas the expression of LOC554202 was significantly higher in the adenocarcinoma and the rectal cancer tissue regions (P<0.01). The high expression levels of miR­31 and LOC554202 were associated with high disease­free survival (DFS) and overall survival (OS) rates (P<0.05). Associations between the increase in DFS and OS and the elevated expression levels of miR­31 and LOC554202 were present in patients with colon cancer but not in patients with rectal cancer (P<0.05). These data indicated that miR­31 and LOC554202 may be potential markers for evaluation of the prognosis of patients treated with oxaliplatin­based chemotherapy.