Objective To establish an animal model of rapid eye movement (REM) sleep deprivation (SD) and an animal model for perifornical nucleus microdialysis and investigate the change of cognition, hypocretinergic system and GABAergic system in rats' hypothalamus after various degrees of REM sleep deprivation and sleep revival and two GABAergic drugs intervention. Methods The modified multiple platform method (MMPM)was used to establish sleep deprivation model and the cognitive function was assessed by Morris' water maze. Immunofluorescence technique was used to analyze the number of Hypocretin (Hcrt) immunoreactive neurons, total Fos immunoreactive neurons, Hcrt and Fos colabeled neurons, and the integrated optical density ( IA ) of GABAA Rαl immunoreactive area in rats' hypothalamus.High performance liquid chromatograph (HPLC) was used to quantitatively analyze the level of GABA and Gluin in the rats' hypothalamus. Two GABAergic drugs, a selective GABAA R antagonist, SR-95531, and a selective blocker of type 1 GABA transporter (uptake blocker), NO-711, were used for perifornical nucleus microdialysis. Results There was no statistically significant difference in tests between CC and TC ( Define CC and TC). There was a significant decrease (P ＜ 0. 05 ) of cognitive function measured by Morris maze test in SD 3 d, SD 5 d and RS 6 h of SD groups compared with CC and TC groups. Number of Fos immunoreactive, F+ &H+ immunoreactive neuronsand IA of GABAA Rαl immunoreactive area were all significantly increased ( P ＜ 0. 05 ). Content of GABA measured by HPLC was also increased ( P ＜ 0. 05 ). However, all these changes were partly reversed by sleep revival SR-95531 and NO-711 had different effect on these changes. Conclusions Sleep deprivation, no matter mild or severe, has adverse effects on cognitive function. Activities of both GABAergic and Hcrtergic system are increased during REMSD. These two neurons system could be regulated by each other and the relationship between them is positive correlation. GABAergic system also had self-regulation during REMSD, but microdialysision of either SR-95531 or NO-711 acquired adverse effects on cognitive function of rats. So GABAergic system is not an optimal therapeutic target. Because GABAergic and Hcrtergic system has inhibitory effect on each other,suppressing activity of Hcrtergic system might be a promising therapeutic target.

Objective To study the effects of sleep inertia (SI) of different time course sleeps on sleep stages and cognitions in healthy men after 30 h sleep deprivation,and also to investigate the mechanism of cognitive functions impairment in sleep inertia stages and the influential factors of sleep inertia.Methods Ten healthy men (age,(20.8 ±2.1) years) participated in the program.The program was divided into 2 stages.First,participants attended a series of tests after 20 min nap(20 min nap group)after 30 h sleep deprivation.The testing series included 3 parts:the continuous performance task,the Stroop Tests,and the Addition Tests.The series of tests were done 3 times immediately after the volunteers were awoken and each lasted about 15 minutes with an interval of 10 minutes between each test.The polysomnogram (PSG) was recorded during the nap.The following 7 days was set as washing-out period to ensure a complete recovery.Participants repeated the similar processes with 2 h nap(2 h nap group) instead of 20 min nap.The cognitive performance of each group was compared with each other along with the best cognitive performance in awakening to estimate whether or not the cognitive abilities regained the normal condition.Results ( 1 ) Sleep latency became shortened in both groups after 30 h sleep deprivation.There were no slow wave sleep (SWS) and rapid eye movement sleep (REM) sleep stages in the 20 min naps,while the percentage of SWS was increased and percentage of REM declined in 2 h naps.(2)In the early of SI (5 min after awaking),cognitive tasks showed that the abilities of continuous attention,selected attention and addition ability were all impaired (continuous performance task:(371.8 ± 21.3 ) times/3 min vs (334.4 ± 22.4) times/3 min,( 373.2 ± 19.0) times/3 min vs ( 323.7 ± 23.8) times/3 min,t =10.443,7.774,both P＜0.01; Stroop tests:(20.3 ±1.5) points vs(17.3 ± 1.0) points,(21.5 ±0.8)points vs( 16.1 ± 1.4 ) points,t =8.478,4.934,both P ＜ 0.05 ; Addition Tests:( 222.2 ± 13.2 ) s vs ( 266.6 ±23.7 ) s,( 226.3 ± 10.9) s vs ( 267.6 ± 23.4 ) s,t =5.748,6.685,both P ＜ 0.01 ).The cognitive functions impairments of 2 h nap group were more severe at the initiation of sleep inertia,but regained the normal condition more quickly.Different cognitive tasks recovered at different speeds.The dispersion of SI needed 30 min.Conclusions ( 1 ) There are difference in the sleep construction and awaked sleep stage between 20 min nap and 2 h nap groups.(2) SI exerts negative influences on cognitive performances of continuous attention,selected attention and addition after sleep deprivation.Many factors may influence the dispersion of SI,including sleep debt,compensation of sleep debt and others.(3) Fragments of sleep are unfavorable to the recovery of body.

Objective Analyze the effect of emergency thrombolytic therapy on door to needle time (DNT) in patients with acute ischemic stroke (AIS) and effect.Method Selected 182 cases of AIS patients underwent intravenous thrombolysis at the First Hospital of Qinhuangdao from May 2015 to June 2017.Thrombolytic therapy group (83 cases),for the May 2015-May 2016 after neurological consultation intravenous thrombolysis patients;Emergency thrombolytic group(99 cases),for the June 2016-June 2017 emergency thrombolysis group Emergency Department of intravenous thrombolysis patients.Compare the two groups of DNT,thrombolytic therapy 24 h symptomatic hemorrhage conversion rate,Thrombolysis 24 h,7 dNIHSS score,7 dthrombolysis and 3 months thrombolysis and thrombolysis 3 months improved Rankin score (mRs).Results There was no significant difference in baseline characteristics between the two groups (P＞0.05).Compared with the consultation group,the DNT[(69.77±11.66)min vs (80.12±15.49) min,t=5.745,P ＜ 0.01] of emergency thrombolytic group was significantly shortened,and the good score[39(39.4％) vs 21(25.3％),x2=4.272,P=0.039] at 3 months after treatment was significantly higher (P＜0.05);Treatment of 24 h intracranial hemorrhage conversion rate[12(12.12％) vs 5(6.02％),x2=1.982,P=0.159]、Treatment 7d mortality rate [10(10.10％) vs 6(7.22％),x2=0.464,P=0.496],3 months mortality rate [14(14.14％) vs 11 (13.25％),x2=0.030,P=0.862]、There was no significant difference in the 24h effective rate [57(57.6％) vs 53(63.8％),x2=0.745,P=0.388] and 7d effective rate [50(50.5％) vs 46(55.4％),x2=0.438,P0.508] after treatment (P＞0.05).Conclusions The emergency thrombolytic model can shorten the DNT of rt-PA intravenous thrombolysis in patients with AIS.The safety and efficacy of DNT are not different from the neurological consultation mode,and can improve the good prognosis rate.

Objective: To compare metabolic syndrome(MS)with Framingham risk score as predictors of cardiovascular disease(CVD)among Kazakhs population. Methods: The participants were the residents who had been followed up for more than 5 years in representative areas of Kazakhs in Xinjiang. We assigned MS a continuous risk score for predicting the development of CVD based on the weights of MS components. MS and Framingham risk score were compared in terms of their ability in predicting years in representative areas of Kazakhs in Xinjiang. We assigned MS a continuous risk score for predicting the development of CVD based on the weights of MS components. MS and Framingham risk score were compared in terms of their ability in predicting development of CVD using Cox regression and receiver operating characteristic curve. Results: The incidence of CVD was 13.87%. The incidence of CVD was higher in the MS group than it in the non-MS group(21.59% vs 11.10%, P<0.001). The area under the receiver operating characteristic(ROC)curve of MS risk score was significantly larger than that of MS classification(0.727 vs 0.585, P<0.001); the area under the curve of MS risk score was close to that of Framingham risk score(0.732 vs 0.727, P=0.673). The association between CVD and each quintile of MS risk score was more significant than that between Framingham risk score and CVD under the same exposed condition(4.61, 9.33, 14.15, 22.29 vs 3.69, 6.36, 8.47, 16.99). Conclusion MS risk score that included age may be a better predictor of CVD among Kazakhs population.

Objective:To compare the clinical utility of 18F-prostate specific membrane antigen (PSMA)-1007 and 18F-FDG PET/CT imaging in newly diagnosed hepatocellular carcinoma (HCC). Methods:From April 2022 to July 2022, 17 patients (14 males, 3 females, age 36-73(54.4±10.1) years) with newly diagnosed HCC who underwent 18F-FDG and 18F-PSMA-1007 PET/CT imaging within 3 d in the First Affiliated Hospital of Zhengzhou University were prospectively enrolled. ROIs were drawn from normal liver tissue (L), abdominal aorta (A), right gluteus medius (M), and SUV max of these regions were compared with the SUV max of primary tumor (T). Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to analyze the data. Results:18F-FDG PT/CT, 18F-PSMA-1007 PET/CT and enhanced MRI detected 1(0, 2), 2(1, 5) and 2(1, 4) tumor lesions of the liver in each patient respectively ( H=7.10, P=0.029), and 18F-PSMA-1007 detected more lesions than 18F-FDG ( P=0.024). Although SUV max of 18F-PSMA-1007 in HCC was significantly higher than that of 18F-FDG (25.7(17.1, 45.1) vs 6.3(2.9, 12.4); z=3.39, P=0.001), there was no significant difference of T/L ratio between 18F-PSMA-1007 and 18F-FDG PET/CT imaging (2.7(2.1, 4.7) vs 1.6(1.0, 4.5); z=0.52, P=0.602). T/A and T/M ratios were significantly higher in 18F-PSMA-1007 PET/CT imaging than those in 18F-FDG PET/CT imaging ( z values: 3.15, 3.53, P values: 0.002, <0.001). 18F-PSMA-1007 PET/CT imaging found high uptake foci in the liver and ribs in 2 cases, which were pathologically confirmed as bone metastasis of HCC, while those lesions were not found by 18F-FDG imaging. Conclusion:Compared with 18F-FDG, 18F-PSMA-1007 PET/CT demonstrates higher tumor uptake, more intrahepatic tumors foci and distant bone metastases.

Objective To establish a patient-derived tumor xenograft (PDTX) model and to observe the latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors. Methods Seven patients with chest tumor in Drum Tower Hospital from April to December 2015 were chosen. There were 5 males and 2 females with age ranging from 61-71 years, including 4 patients of esophageal tumor and 3 patients of lung tumor. PDTX model was established by surgical removal of fresh tumor tissues of these patients and transplantation in NODPrkdcem26Il2rgem26Nju subcutaneous (NCG) mice. The latency and rate of tumor formation, tumor size, tumor invasion and metastasis of transplanted tumors were observed, and pathology of HE staining and immunohistochemical testing results were compared between PDTX model and the patients. Results PDTX model was successfully established in 4 patients, and the success rate was 66.7%, including 2 patients of esophageal cancer. The PDTX model retained the differentiation, morphological and structural characteristics of original tumors. Conclusion Pathology and molecular biology characteristics of PDTX model are consistent with the original tumor, which can be an “avatar” of tumor patients for clinical pharmacodynamics screening and new drug research and development.

Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity. Furthermore, the Cullin 1-specific SCF complex containing β-TRCP has been identified to directly interact with and ubiquitinate ZNRF3 thereby regulating its protein stability. Similar with the degradation of β-catenin by β-TRCP, ZNRF3 is ubiquitinated by β-TRCP in both CKI-phosphorylation- and degron-dependent manners. Thus, our findings not only identify a novel substrate for β-TRCP oncogenic regulation, but also highlight the dual regulation of Wnt signaling by β-TRCP in a context-dependent manner where β-TRCP negatively regulates Wnt signaling by targeting β-catenin, and positively regulates Wnt signaling by targeting ZNRF3.
Cells, Cultured ; Humans ; Proteolysis ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; beta-Transducin Repeat-Containing Proteins ; metabolism

Humans ; Uric Acid ; Cross-Sectional Studies ; Spondylarthritis/diagnostic imaging* ; C-Reactive Protein ; Spondylitis, Ankylosing

Objective: To construct and confirm a predictive model for the risks of cardiovascular diseases (CVD) with metabolic syndrome (MS) and its factors in Xinjiang Kazakh population. Methods: A total of 2 286 Kazakh individuals were followed for 5 years from 2010 to 2012 as baseline survey. They were recruited in Xinyuan county, Yili city, Xinjiang. CVD cases were identified via medical records of the local hospitals in 2013, 2016 and 2017, respectively. Factor analysis was performed on 706 MS patients at baseline, and main factors, age, and sex were extracted from 18 medical examination indexs to construct a predictive model of CVD risk. After excluding the subjects with CVD at baseline and incomplete data, 2007 were used as internal validation, and 219 Kazakhs in Halabra Township were used as external validation. Logistic regression discriminations were used for internal validation and external validation, as well as to calculate the probability of CVD for each participant and receiver operating characteristic curves. Results: The prevalence of MS in Kazakh was 30.88%. Seven main factors were extracted from the Kazakh MS population, namely obesity factor, blood lipid and blood glucose factor, liver function factor, blood lipid factor, renal metabolic factor, blood pressure factor, and liver enzyme factor. The area under the curve (AUC) for predicting CVD in the internal validation was 0.773 (95%CI 0.754-0.792). In the external validation, the AUC for predicting CVD was 0.858 (95%CI 0.805-0.901). Conclusions The CVD risk prediction model constructed by 7 main factors extracted from Kazakh MS patients has high validation efficiency and can be used for risk assessment of CVD in Xinjiang Kazakh population.