UPP1 enhances bladder cancer progression and gemcitabine resistance through AKT.

UPP1, a crucial pyrimidine metabolism-related enzyme, catalyzes the reversible phosphorylation of uridine to uracil and ribose-1-phosphate. However, the effects of UPP1 in bladder cancer (BLCA) have not been elucidated. AKT, which is activated mainly through dual phosphorylation (Thr308 and Ser473), promotes tumorigenesis by phosphorylating downstream substrates. This study demonstrated that UPP1 promotes BLCA cell proliferation, migration, invasion, and gemcitabine resistance by activating the AKT signaling pathway in vitro and in vivo. Additionally, UPP1 promoted AKT activation by facilitating the binding of AKT to PDK1 and PDK2 and the recruitment of phosphatidylinositol 3,4,5-triphosphate to AKT. Moreover, the beneficial effects of UPP1 on BLCA tumorigenesis were mitigated upon UPP1 mutation with Arg94 or MK2206 treatment (AKT-specific inhibitor). AKT overexpression or SC79 (AKT-specific activator) treatment restored tumor malignancy and drug resistance. Thus, this study revealed that UPP1 is a crucial oncogene and a potential therapeutic target for BLCA and that UPP1 activates the AKT signaling pathway and enhances tumorigenesis and drug resistance to gemcitabine.

Acyl-coenzyme A: cholesterol acyltransferase inhibitor avasimibe suppresses tumorigenesis and induces G1-phase cell-cycle arrest by activating PPARγ signaling pathway in bladder cancer.

Reprogramming of energy metabolism is one of the most important characteristics of tumors. Bladder cancer (BLCA) cells contain higher levels of cholesterol content compared to normal cells, and acyl-coenzyme A (CoA): cholesterol acyltransferase-1 (ACAT1) plays a crucial role in the esterification of cholesterol. Avasimibe is a drug that has been used in the treatment of atherosclerosis, and it can effectively inhibit ACAT1. We observed that ACAT1 was significantly up-regulated in BLCA and positively correlated with tumor grade. By avasimibe administration, the proliferation and migration ability of BLCA cells were reduced, while the production of ROS was strongly increased, accompanied by the up-regulated expression of ROS metabolism-related proteins SOD2 and catalase. Furthermore, BLCA cell cycle was arrested at the G1 phase, accompanied by the downregulation of cell cycle-related proteins (CCNA1/2, CCND1, CDK2 and CDK4), while the PPARγ was found to be up-regulated at both transcriptional and protein levels after avasimibe treatment. Then we found that the PPARγ antagonist GW9662 could reverse the effect of avasimibe on the cell cycle. Moreover, xenograft and pulmonary metastasis models further demonstrated that avasimibe could inhibit tumor cell growth and metastasis in vivo. Taken together, our results for the first time revealed that avasimibe can inhibit BLCA progression and metastasis, and PPARγ signaling pathway may play a key role in regulation of cell cycle distribution induced by avasimibe.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation.

BACKGROUND: Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. METHODS: A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa. The Student's t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. RESULTS: ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients' prognosis (HR = 0.60, 95% CI 0.40-0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. CONCLUSION: Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Thymoma-associated autoimmune encephalitis: Analysis of factors determining prognosis.

INTRODUCTION: Autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders caused by a misdirected immune response against self-antigens expressed in the central nervous system. The thymus is a central organ in the immune system and thymic tumors are thought to be possible initiators of many neurological disorders. Recently, there is growing evidence that thymomas are associated with autoimmune encephalitis. AIMS: Our study initially explored the characteristics of patients with autoimmune encephalitis combined with thymoma. METHODS: We used patient data from January 1, 2011 to October 1, 2021 from the PubMed, Web of Science, Ovid, and CNKI platforms to analyze overall demographics, frequency of symptoms and associations, and treatment prognosis outcomes. RESULTS: A total of 68 patients were included. There were 39 female cases (57.4%). The mean age was 50 years (IQR 40-66 years). All had acute and subacute onset. The clinical manifestations were mostly cognitive changes (70.6%), mental disorders (57.4%), and epilepsy (50.0%). The most common neuronal antibody was alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Magnetic resonance imaging (MRI) abnormalities were present in 81.0% of patients, mostly in the hippocampus, temporal lobe, and some in cortical and subcortical areas. Abnormalities in the electroencephalogram (EEG) in 69.8% of patients. Treatment involved immunotherapy and thymoma treatment, with 79.7% of patients improving after treatment. While 20.3% of patients had a poor prognosis. Further, 14.8% of patients relapsed. Mental disorders, autonomic dysfunction, sleep disturbances, anti-Ma2, and thymoma untreated were more frequent in patients with poor prognosis. CONCLUSION: Thymoma-associated autoimmune encephalitis is a unique disease entity. Long-term follow-up of chest CT findings is recommended for patients with autoimmune encephalitis.

Development and validation of a prognostic nomogram for neuroendocrine prostate cancer, based on the SEER database.

Background: The tumor biology of neuroendocrine prostate cancer (NEPC) is different from that of ordinary prostate cancer, herefore, existing clinical prognosis models for prostate cancer patients are unsuitable for NEPC. The specialized individual situation assessment and clinical decision-making tools for NEPC patients are urgently needed. This study aimed to develop a valid NEPC prognostic nomogram and risk stratification model to predict risk associated with patient outcomes. Methods: We collected 340 de-novo NEPC patients from the SEER database, and randomly selected 240 of them as the training set and the remaining 100 as the validation set. Cox regression model was used to screen for risk factors affecting overall survival (OS) and cancer-specific survival (CSS) and construct a corresponding nomogram. The receiver operating characteristic (ROC) curves, calibration curves, C-indexes, and decision curve analysis (DCA) curves are used to verify and calibrate nomograms. Results: NEPC prognosis nomograms were constructed by integrating independent risk factors. The C-indexes, ROC curves, calibration curves, and DCA curves revealed excellent prediction accuracy of the prognostic nomogram. Furthermore, we demonstrated that NEPC patients in the high-risk group had significantly lower OS and CSS than those in the low-risk group with risk scores calculated from nomograms. Conclusions: The nomogram established in this research has the potential to be applied to the clinic to evaluate the prognosis of NEPC patients and support corresponding clinical decision-making.

Seasonal variations of nonmotor symptoms in patients with Parkinson's disease in Southeast China.

BACKGROUND: Studies suggest seasonal fluctuations of symptoms in Parkinson's disease (PD) patients in Western countries. However, the association between seasonal change and variation in nonmotor symptoms (NMS) in Chinese PD patients is unclear. Here, we studied whether there is a change rule with annual cycle with severity of NMS for patients with PD in Southeast China. METHODS: We studied 1005 PD patients between April 2008 and October 2020. Patients were classified into four seasons according to the 24 Chinese solar terms, based on assessment date. We compared comprehensive NMS scales and polysomnography parameters among groups and conducted further analysis of disease severity. RESULTS: Among the 1005 patients studied, the mean age was 64.2 ±â€Š9.7 years and 569 (56.6%) of them were men. Relative to the summer group, patients assessed during winter had higher Scales for Outcomes in Parkinson's disease-Autonomic Dysfunction (SCOPA-AUT) scores ( P  = 0.045). The sleep efficiency factor scores of Pittsburgh Sleep Quality Index in patients were higher during spring than summer ( P  = 0.009). Among patients who completed polysomnography during the same period ( n  = 135), compared with summer follow-ups, we observed a higher percentage of NREMS1 in winter and spring follow-ups ( P  = 0.042, P  = 0.011), a higher NREMS1 time in spring follow-ups ( P  = 0.0024), a lower NREMS2 time in winter follow-ups ( P  = 0.007), and a higher percentage of phasic rapid eye movement (REM)-sleep without atonia in autumn and winter follow-ups ( P  = 0.026 and P  = 0.020, respectively). In a subset of patients with PD and REM sleep behavior disorder (RBD; n  = 182), those visited during winter had higher scores for RBD questionnaire-Hong Kong and its factor 1 (dream-related sub-score) than those visited during summer ( P  = 0.034, P  = 0.020). We observed similar findings for SCOPA-AUT and sleep efficiency factor scores in early stage patients in subgroup analysis. CONCLUSIONS: PD patients assessed for follow-up during summer showed less severe symptoms of autonomic dysfunction and RBD symptoms than those assessed in winter, and less sleep disturbance than those in spring and winter, suggesting that seasonal change and NMS fluctuation are related, especially in patients with early stage PD.

MYBL2 promotes proliferation and metastasis of bladder cancer through transactivation of CDCA3.

The transcription factor MYB proto-oncogene like 2 (MYBL2) is critical in regulating gene expression and tumorigenesis. However, the biological function of MYBL2 in bladder cancer (BLCA) remains to be elucidated. Here, we first revealed that MYBL2 was elevated in BLCA tissues and significantly correlated with clinicopathological parameters and cancer-specific survival in BLCA patients. Phenotypic assays showed that MYBL2 deficiency suppressed the proliferation and migration of BLCA cells in vitro and in vivo, whereas MYBL2 overexpression contributed to the opposite phenotype. Mechanistically, MYBL2 could bind to the promoter of its downstream target gene cell division cycle-associated protein 3 (CDCA3) and transactivate it, which in turn promoted the malignant phenotype of BLCA cells. Further investigations revealed that MYBL2 interacted with forkhead box M1 (FOXM1) to co-regulate the transcription of CDCA3. In addition, MYBL2/FOXM1 and CDCA3 might activate Wnt/ß-catenin signaling, thereby promoting the malignant phenotype of BLCA cells. In conclusion, the current study identifies MYBL2 as an oncogene in BLCA. MYBL2 can accelerate the proliferation and metastasis of BLCA through the transactivation of CDCA3.

Enhanced Recovery After Surgery Protocol Optimizes Results and Cost of Laparoscopic Radical Nephrectomy.

Purpose: To assess the impact of enhanced recovery after surgery (ERAS) protocols in laparoscopic radical nephrectomy (LRN). Methods: The clinical data of 89 patients underwent LRN in Zhongnan Hospital of Wuhan University from February 2019 to September 2021 were collected (40 in the ERAS group and 49 in the pre-ERAS group). The clinical characteristics, prognosis, and length of hospital stay (LOS) were compared between the two groups using t test, Mann-Whitney test, and chi-square test. Results: Total LOS and postoperative LOS were significantly shorter in ERAS group than in pre-ERAS group [15.0 (13.5-19.5) vs. 12.0 (10.0-14.0), P < 0.001; 8.0 (7.0-10.0) vs. 7.0 (5.0-8.8), P = 0.001]. Compared with the pre-ERAS group, the hospitalization expenses of the ERAS group were also lower (P = 0.023). In addition, the incidence of postoperative complications in the ERAS group also decreased (P = 0.054). Conclusions: ERAS protocol in LRN could help accelerate the recovery of patients and is worthy of clinical promotion.

The cholesterol esterification inhibitor avasimibe suppresses tumour proliferation and metastasis via the E2F-1 signalling pathway in prostate cancer.

BACKGROUND: New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer. METHODS: In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model. RESULTS: The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, ß-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group. CONCLUSIONS: Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.

Cognitive impairment and sleep disturbances after minor ischemic stroke.

PURPOSE: Post-stroke cognitive impairment (PSCI) is common among stroke survivors, although its risk factors are not well understood. Here, we assessed cognitive function in patients within 14 days after minor stroke and investigated the risk factors of PSCI, including sleep-related factors. METHODS: Patients with minor acute ischemic stroke (n = 86) were continuously recruited from November 2015 to October 2016. Demographic and clinical data were collected, and cognitive assessment and polysomnography were performed. Based on their cognitive performance, stroke patients were divided into PSCI and no PSCI groups. Age-, sex-, and education-matched participants (n = 36) were included as a healthy control (HC) group. RESULTS: Stroke patients showed impairments in multiple cognitive domains relative to HC participants (p < 0.01). Among stroke patients, the prevalence of PSCI and obstructive sleep apnea was 81.4 and 74.4%, respectively. Impairments in attention and working memory (87.1%) and executive function (84.3%) were the most common among stroke patients. Compared with no PSCI patients, PSCI patients showed a higher prevalence of obstructive sleep apnea (50.0 vs. 80.0%, p = 0.030) and shorter total sleep time (435.1 ± 104.0 vs. 347.3 ± 98.1 min, p = 0.002). Logistic regression analysis showed that education duration, total sleep time, and lowest SaO2 were independent risk factors for PSCI. CONCLUSIONS: The prevalence of PSCI is high after minor ischemic stroke. In particular, attention and working memory and executive function are most commonly impaired. Although the risk factors for PSCI are numerous, shorter total sleep time and degree of hypoxia at night warrant further attention.

Increased Serum Cystatin C in Early Parkinson's Disease with Objective Sleep Disturbances.

BACKGROUND: Sleep disturbance is one of the major non-motor symptoms which cause the disability of Parkinson's disease (PD) patients. Cystatin C (CysC) is a more sensitive biomarker than serum creatinine or estimated glomerular filtration rate. Previous studies have reported altered CysC levels in neurodegenerative disorders and sleep disorders. This study aimed to explore the correlations of serum CysC levels and objective sleep disturbances in early PD. METHODS: We recruited 106 early PD patients and 146 age- and sex-matched controls. All participants underwent clinical investigation and video-polysomnography. Sleep parameters and serum levels of CysC were measured. Then, we investigated the relationships between CysC and clinical variables and objective sleep disturbances in early PD patients. RESULTS: The mean serum level of CysC was significantly higher in patients with early PD (1.03 ± 0.19 mg/L) compared to controls (0.96 ± 0.15 mg/L, P = 0.009). There were significantly positive correlations between serum CysC levels and age (r = 0.334, P < 0.001), gender (r = 0.264, P = 0.013), and creatinine levels (r = 0.302, P = 0.018) in early PD patients. Increased serum CysC levels in early PD patients were significantly associated with higher apnea and hypopnea index (AHI) (r = 0.231, P = 0.017), especially hypopnea index (r = 0.333, P < 0.001). In early PD patients, elevated serum CysC levels were positively correlated with oxygen desaturation index (r = 0.223, P = 0.021), percentage of time spent at oxygen saturation (SaO2) <90% (r = 0.644, P < 0.001), arousal with respiratory event during sleep (r = 0.247, P = 0.013). On the contrary, the elevated serum CysC levels were negatively correlated with mean and minimal SaO2(r = -0.323, -0.315, both P = 0.001) in PD patients. CONCLUSIONS: The level of serum CysC was higher in early PD patients. PD patients with elevated serum CysC levels had more respiratory events and more severe oxygen desaturation. Therefore, the serum CysC levels may predict the severities of sleep-disordered breathing problems in early PD patients.

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease.

INTRODUCTION: Loss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD. METHODS: We conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep. RESULTS: Patients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group. CONCLUSION: Both DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.

Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease.

BACKGROUND: Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. METHODS: This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. RESULTS: No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (ß = 0.552, P < 0.001) and RBD (ß = 0.433, P < 0.001) as predictors of higher tonic EMG density. CONCLUSION: Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.

Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

PURPOSE: Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). METHODS: In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. RESULTS: For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). CONCLUSIONS: The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia: A Cross-sectional Study.

BACKGROUND: Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia. METHODS: cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups. RESULTS: Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088). CONCLUSIONS: LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

Elevated Serum Liver Enzymes in Patients with Obstructive Sleep Apnea-hypopnea Syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. METHODS: All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5-14 events/h, 15-29 events/h, and ≥30 events/h. RESULTS: A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO 2 ), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. CONCLUSIONS: Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS.

Increased CSF E-Selectin in Clinical Alzheimer's Disease without Altered CSF Aß42 and Tau.

Clinically diagnosed Alzheimer's disease (AD) is pathologically heterogeneous. In this multicenter cohort of 215 clinically diagnosed AD patients and 249 controls, E-selectin and vascular cell adhesion molecule 1 (VACM-1) were measured along with amyloid-ß peptide 1-42 (Aß42) and tau. We discovered that E-selectin, a biomarker of endothelial function/vascular injury, was inversely correlated with cerebrospinal fluid (CSF) tau/Aß42 ratio and significantly elevated in clinical AD patients without the typical AD CSF biomarker signature (i.e., low tau/Aß42 ratio) compared to those with the signature. These findings suggest that E-selectin may be an objective biomarker related to vascular mechanisms contributing to dementia.

[The neuroimaging features of Parkinson's disease and dystonia by transcranial sonography].

OBJECTIVE: To assess the neuroimaging features of Parkinson's Disease and dystonia by transcranial sonography (TCS). METHODS: 63 Parkinson's Disease patients, 32 dystonia patients and 81 controls underwent TCS in blind manner. The echo of the substantia nigra (SN) was classified into I-V as half quantitative data. The echo of SN≥III was considered to be positively enhanced, the hyperechogenicity were measured and the hyper-substantia nigra/midbrain (S/M) were calculated. The echo of the lentiform nucleus (LN) was classified into I-III as half quantitative data. The echo of LN≥II was considered to be positively increased and were measured. RESULT: Semi-quantitative analysis: the ratio of the patients with SN≥III was greater in Parkinson's Disease patients (60.32%, 38/63) than in dystonia patients (12.50%, 4/32) and normal controls (11.11%, 8/72, χ2=19.67, 36.22, P<0.01, respectively), the ratio of the patients with LN≥II was greater in dystonia patients (65.62%, 21/32) than in Parkinson's Disease patients (20.63%, 13/63) and in controls (8.33%, 6/72, χ2=18.69, 37.83, P<0.01, respectively). Quantitative analysis:the median and quartile (M/Q) of the SN hyperechogenieity area in Parkinson's Disease patients [0.73 (0.53) cm2] was greater than in dystonia patients [0.56 (0.53) cm2] and in controls [0.44 (0.19) cm2, H=10.05, P=0.007], the S/M in Parkinson's Disease patients was greater [15.7% (11.5%)] than in dystonia patients [(13.8% (14.2%)] and in controls [8.9% (2.9%), H=6.96, P=0.031]. The M/Q of LN hyperechogenieity area in dystonia patients was greater [0.50 (0.33) cm2] than in Parkinson's Disease patients [0.45 (0.22) cm2] and in controls [0.35 (0.17) cm2, H=10.87, P=0.004]. CONCLUSION: TCS might find the specific hyperechogenicity of SN in Parkinson's Disease patients (60.32%) and hyperechogenicity of LN in dystonia patients (65.63%), which could provide useful informations to distinguish Parkinson's Disease from dystonia.