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.

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.

Parkinson's disease patients with pain suffer from more severe non-motor symptoms.

Non-motor symptoms, including pain, depression, sleep disorder, and olfactory dysfunction, occur frequently in patients with Parkinson's disease (PD), even before the onset of motor symptoms. Although studies have examined the correlation between pain and depression or sleep disorder in PD, few studies have investigated the correlation between pain and a range of other non-motor symptoms of PD. PD patients (n = 142) with or without pain were included in the study. PD severity was evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H/Y) staging scale. Pain severity was analyzed with the Visual Analog Scale. The Hamilton Rating Scale for Depression (HRSD; 24 items), Montreal Cognitive Assessment Beijing Version (MoCA), and non-motor questionnaire (NMSQT) measured symptoms of depression, cognitive function, and non-motor symptoms. The incidence of pain was 47.9% in patients with PD, most of whom had moderate pain levels. Patients with pain showed higher HRSD, UPDRS, H/Y, and NMSQT scores and lower MoCA scores compared to those of patients without pain. HRSD and NMSQT scores were closely related with pain (P < 0.001). Non-motor symptoms were more prominent in patients with pain compared to that of controls and PD patients without pain.

[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.

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.

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.

Application and interpretation of current autophagy inhibitors and activators.

Autophagy is the major intracellular degradation system, by which cytoplasmic materials are delivered to and degraded in the lysosome. As a quality control mechanism for cytoplasmic proteins and organelles, autophagy plays important roles in a variety of human diseases, including neurodegenerative diseases, cancer, cardiovascular disease, diabetes and infectious and inflammatory diseases. The discovery of ATG genes and the dissection of the signaling pathways involved in regulating autophagy have greatly enriched our knowledge on the occurrence and development of this lysosomal degradation pathway. In addition to its role in degradation, autophagy may also promote a type of programmed cell death that is different from apoptosis, termed type II programmed cell death. Owing to the dual roles of autophagy in cell death and the specificity of diseases, the exact mechanisms of autophagy in various diseases require more investigation. The application of autophagy inhibitors and activators will help us understand the regulation of autophagy in human diseases, and provide insight into the use of autophagy-targeted drugs. In this review, we summarize the latest research on autophagy inhibitors and activators and discuss the possibility of their application in human disease therapy.

[Clinical characteristics in Parkinson's disease patients with cognitive impairment and effects of cognitive impairment on sleep].

OBJECTIVE: To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinson's disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep. METHODS: A total of 130 PD outpatients and inpatients of sleep center at our hospital were eligible for participation. According to Montreal cognitive assessment (MOCA), they were divided into cognitive normal group (MOCA ≥ 26) (n = 51) and cognitive impairment group (MOCA < 26) (n = 79). Their clinical characteristics were mainly evaluated by unified Parkinson's disease rating scale (UPDRS) , Hoehn-Yahr (H-Y) stage, Hamilton depression scale (HAMD-24 item) and Epworth sleepiness scale (ESS). And all of them underwent video-polysomnography (PSG). RESULTS: The proportion of cognitive impairment (MOCA < 26) was 60.76%. Compared to those without cognitive impairment, the PD patients with cognitive impairment had significantly higher score of HAMD (10 ± 7 vs 7 ± 4), increased incidence of hallucinations (40.50% vs 19.60%) and REM behavior disorders (RBD) (63.29% vs 39.21%), significantly higher H-Y stage [2.5(2.0-3.0) vs 2.0 (2.0-2.5)] , United Kingdom Parkinson Disease Society (UPDRS) part III (22 ± 10 vs 19 ± 10) and levodopa-equivalent daily dose (LED) (511 ± 302vs 380 ± 272) (all P < 0.05). However, no significant differences existed in the subscores of MOCA between PD patients with different sides of onset and motor subtypes of onset (all P > 0.05). Non-conditional Logistic regression analysis showed that PD duration, score of HAMD and H-Y stage were the major influencing factors of cognition. On PSG, significantly decreased sleep efficiency (57% ± 21% vs 66% ± 17%), higher percentage of non-REM sleep stage 1 (NREMS1) (37% ± 21% vs 27% ± 13%), lower percentage of NREMS2 (40% ± 17% vs 46% ± 13%) and REM sleep (39% ± 28% vs 54% ± 36%) were found for PD patients with cognitive impairment (all P < 0.05). CONCLUSION: The PD patients with cognitive impairment have more severe disease and partial nonmotor symptoms. And the severity of disease and depression is closely associated with cognitive impairment. Cognitive impairment may also affect sleep to cause decreased sleep efficiency and severe sleep structure disorder.

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.

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.

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.

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.

[Association between serum adipocyte fatty acid binding protein level and dyslipidemia in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To explore the association between serum adipocyte fatty acid binding protein (A-FABP) levels and dyslipidemia in patients with obstructive sleep apnea syndromes (OSAS). METHODS: Eighty snoring patients were monitored by overnight polysomnography (PSG) in Second Affiliated Hospital of Soochow University from November 2010 to May 2011. There were 63 males and 17 females with a mean age of (48 ± 14) years (range: 22 - 77 years). Based on the results of apnea-hypopnea index (AHI), they were divided into 3 groups: primary snoring group (AHI < 5/h, n = 19), mild-moderate OSAS group (5/h ≤ AHI ≤ 40/h, n = 22) and severe OSAS group (AHI > 40/h, n = 39). The levels of A-FABP, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured and compared between the primary snoring group and OSAS patients of different severities. And the correlations between serum A-FABP and plasma lipid as well as PSG parameters were further evaluated by partial correlation analysis. RESULTS: Compared with the primary snoring group ((15.7 ± 3.3) µg/L) and mild-moderate group ((17.3 ± 4.3) µg/L), there was a significant elevation of serum A-FABP level in the severe OSAS group ((20.4 ± 4.6) µg/L) (P = 0.001, P = 0.026). Additionally, after adjustment for body mass index and age, the serum A-FABP level showed significant positive correlations with TC, TG and LDL-C (r = 0.469, P = 0.000; r = 0.239, P = 0.035 and r = 0.366, P = 0.001). Serum A-FABP level was positively correlated with AHI and the time of oxygen saturation (SaO2) < 90% (r = 0.231, P = 0.042 and r = 0.226, P = 0.047). Nevertheless, the serum A-FABP level showed significant negative correlations with the lowest SaO2 and the mean SaO2 (r = -0.234, P = 0.039 and r = -0.270, P = 0.017). CONCLUSION: Dyslipidemia and elevated level of serum A-FABP are common in OSAS patients.

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.

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.

Neurocognitive impairment in Chinese patients with obstructive sleep apnoea hypopnoea syndrome.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing is known to be associated with impairment in cognitive function. The aim of this study was to characterize neurocognitive impairment in a cohort of Chinese patients with varying severities of obstructive sleep apnoea hypopnoea syndrome (OSAHS), and to develop a sensitive instrument for routine screening of cognitive impairment. METHODS: Eligible patients (n = 394) were categorized into a primary snoring group, and mild, moderate and severe OSAHS groups, based on assessment of AHI. The Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) questionnaires were administered to assess cognitive function, and the correlations between questionnaire scores and clinical and polysomnographic parameters were further evaluated by stepwise multivariate regression. RESULTS: MoCA scores decreased progressively across the spectrum from primary snoring to severe OSAHS. Importantly, mild neurocognitive impairment as defined by a MoCA score <26 was more common in the moderate (38.6%) and severe (41.4%) OSAHS groups than in the mild OSAHS (25.0%) and primary snoring (15.2%) groups. In contrast, MMSE scores were largely normal and comparable among all four groups. Evaluation of MoCA subdomains further revealed selective reduction in memory/delayed recall, visuospatial and executive function, and attention span in the severe OSAHS group compared with the other groups. Stepwise multivariate regression analysis demonstrated that MoCA scores correlated significantly with lowest oxygen saturation (L-SaO(2) ) and years of education. CONCLUSIONS: Neurocognitive impairment is common in patients with OSAHS. The MoCA is a brief and sensitive tool for the assessment of cognitive impairment in OSAHS patients, whose performance on the MMSE is in the normal range.

Daytime sleepiness and its determining factors in Chinese obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to characterize excessive daytime sleepiness (EDS) in a large cohort of Chinese patients with various severity of obstructive sleep apnea-hypopnea syndrome (OSAHS), and investigate its correlations with clinical/polysomnographic variables. MATERIALS AND METHODS: A total of 1,035 consecutive Chinese patients with snoring (mean age ± SD 45 ± 15 years, BMI 26.6 ± 4.3 kg/m(2)) were examined by overnight polysomnography, and subjective EDS was assessed using the Epworth Sleepiness Scale (ESS). RESULTS: The 1,035 patients were compared according to severity of sleep-disordered breathing: AHI <5 (primary snoring group or normal overall AHI) (24.1%), AHI 5-20 (mild OSAHS, 21.7%), AHI >20-40 (moderate OSAHS 16.5%), and AHI >40 (severe OSAHS 37.7%). ESS score progressively increased as the severity of OSAHS aggravated among these patients. More severe OSAHS patients were characterized by EDS, nocturnal hypoxemia, and disruption of sleep structure. Progressive worsening of nocturnal hypoxemia was observed from mild to severe OSAHS patients with a strong correlation with ESS score. The stepwise multiple regression analysis performed to evaluate the correlations of individual clinical and polysomnographic variables with the ESS score revealed that the ESS score significantly correlated with the oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and body mass index (BMI), and ODI was the strongest determinant of ESS score. CONCLUSION: EDS is correlated with the severity of OSAHS. More severe patients are characterized by higher ESS score, higher BMI, and progressive worsening of nocturnal hypoxemia. Nocturnal hypoxemia is a major determinant of EDS in Chinese OSAHS patients.

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.