Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P＜0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P＜0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P＜0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.

Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P＜0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P＜0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P＜0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.

Objective:To analyze the changes of thyroid volume before and after supplementation with lipiodol pills in children with goiter, and to evaluate the recovery effect of lipiodol pills supplementation on children with goiter in the short term.Methods:In October 2018, 4 townships and towns in Linxia Hui Autonomous Prefecture with relatively serious historical conditions and high goiter rate of children aged 8 to 10 were selected for thyroid examination in 19 primary schools within the jurisdiction. Sixty children with goiter were selected as research subjects; at the same time, 138 children of the same age with normal thyroid B-ultrasound examination results were selected as control in the same period. Under the condition of normal diet, children with goiter were intervened by taking 200 mg lipiodol pills at one time. After 6 months, the thyroid volume of children with goiter and control children was measured by B-ultrasound.Results:Fifty-three children with goiter were finally included, with a sex ratio of 1.00 ∶ 1.04 (26 ∶ 27). There were 138 control children in the same period, with a sex ratio of 1.00 ∶ 1.30 (60 ∶ 78). Six months after taking lipiodol pills, the median thyroid volume of children with goiter was 3.7 ml, which was significantly different from that before supplementing with lipidol pills (5.8 ml, Z = - 7.95, P < 0.001), and not significantly different from that of control children (4.1 ml) in the same period ( Z = - 0.91, P = 0.365). Among them, 90.6% (48/53) of children with goiter recovered to the normal range, and 100.0% (15/15), 81.8% (18/22) and 93.8% (15/16) children's thyroid recovered returned to the normal range in the 8-, 9-, and 10-year-old age groups, respectively, and the highest proportion was in the 8-year-old age group. Stratified by age and gender, the thyroid volume of children with goiter in all age groups and gender after supplementation with lipiodol pills was lower than that before supplementation with lipiodol pills ( P < 0.001), but there was no difference compared with the control children in the same period ( P > 0.05). After supplementing with lipiodol pills, the diameters of thyroid in children with goiter were significantly lower than those before supplementing with lipiodol pills ( P < 0.001). Compared with the control children in the same period, there were significant differences in the right width, left length and right long diameter of the thyroid ( P < 0.05). Conclusion:Supplementing lipiodol pills can restore the thyroid volume of 8 - 10 year old children with goiter to normal range in a short term, and can effectively treat simple goiter.

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.

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.

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

Objective: To determine the hemoglobin level and blood pressure and the factors that influence their recovery in relocated workers who were unfit for duties at high altitude. Methods: The physical examination data of 693 relocated workers who previously worked at high altitude were dynamically monitored from January 2006 to June 2015 in order to examine the recovery of hemoglobin level and blood pressure. Results: The rate of hemoglobin recovery was 81.37% among the 161 relocated workers with abnormal hemoglobin levels, and the rate of blood pressure recovery was 69.51% among the 164 relocated workers with abnormal blood pressure. The rates of hemoglobin and blood pressure recovery were decreased in individuals aged 40 years and older. The peak recovery time of hemoglobin was 11-15 months following relocation, and that of blood pressure was 5-7 months and 11-13 months following relocation. The half-year blood pressure recovery rate and 2-year hemoglobin recovery rate following relocation were significantly higher in workers who worked at 2500-3000 m altitude than in those at ≥3000 m (P<0.05) . Total cholesterol and educational level were factors that influence the half-year blood pressure recovery in relocated workers (P<0.05) . Conclusion The rate of hemoglobin and blood pressure recovery are high among relocated workers who previously worked at high altitude. Factors that influence blood pressure, such as total cholesterol, should be closely monitored so that high-altitude workers with abnormal blood pressure and hemoglobin level can be relocated as early as possible.

Objective To understand the cognitive level of urban and rural general practitioners in the concept, diagnosis and treatment of chronic obstructive pulmonary disease and to provide the basis for continuing medical education in basic level hospital for all general practitioners. Methods General practitioners from 21 urban community health service centers (group A) and 27 of the rural community health service centers (group B) were surveyed on chronic obstructive pulmonary disease knowledge through a anonymous questionnaire, the survey contents included five aspects of chronic obstructive pulmonary disease such as basic concept, diagnosis, grouping diagnosis, treatment on stable phase and acute exacerbation. Results The correct rates of five questions in group A were 25.89%, 17.26%, 5.58%, 4.06%, 18.78 and in group B were 8.97%, 8.55%, 5.13%, 4.27%, 17.52%. In chronic obstructive pulmonary disease concept and diagnosis, there was significant difference between two groups(χ2=21.99, P<0.05 and χ2=7.41, P<0.05) . Conclusion The level of the cognitive of COPD (chronic obstructive pulmonary disease) among the general practitioners is very poor, and is strong against to the management work of chronic obstructive pulmonary disease. We need more continuing medical ed-ucation on "the guidelines on diagnosis and treatment of chronic obstructive pulmonary disease " among the urban and rural general practitioners.