Objective: To investigate the effect of glycogen synthase kinase 3 β ( GSK-3 β) and its correlation with microtubule-associated protein 2 (MAP2) during cerebral hypoxia / reoxygenation (H / R) in zebrafish． Methods: The cerebral hypoxia / reoxygenation model of zebrafish was established．Healthy adult zebrafishes of the same size were divided into control group ( Control) ，hypoxia / reoxygenation group ( H / R) and hypoxia / reoxygenation + GSK-3 β inhibitor group (H / R + TDZD-8) for experiment．The brain tissues of zebrafish in each group were selected to determine the mRNA expressions of hypoxia inducible factor 1 αa and 1 αb (HiF-1αa and HIF-1 αb) at different reoxygenation time points by qRT-PCR , and the protein expression levels of HIF-1α , GSK-3 β , p-GSK-3 β (Ser 9) and MAP2 were detected by Western blot，TTC staining and TUNEL staining were used to detect cerebral infarction area and cell apoptosis ，and immunofluorescence was used to detect the distribution and expression of MAP2 in brain. Results: Compared with Control group，the mRNA levels of Hif-1αa and Hif-1 αb(P＜0. 01) and protein expression of Hif-1 α(P＜0. 01) increased in H / R group，the area of cerebral infarction (P ＜0. 01) and apoptotic cells(P ＜0. 01) increased，p-GSK-3 β ( Ser 9) / GSK-3 β ratio，MAP2 protein expression (P ＜0. 05) and immunofluorescence expression of MAP2 (P ＜0. 01 ) reduced ; Furthermore，TDZD-8 pretreatment could relieve the brain injury of H / R zebrafish by decreasing the infarct size and cell apoptosis，improving the ratio of p-GSK-3 β ( Ser 9 ) / GSK-3 β , and increasing the expression of MAP2． Conclusion Hypoxia / reoxygenation can cause brain neuron damage in zebrafish，and its mechanism may be related to inhibition of GSK-3 β phosphorylation and MAP2 expression．GSK-3 β specific inhibitor TDZD-8 can reverse the damage of brain neurons caused by hypoxia / reoxygenation by promoting the expression of P-GSK-3 β (Ser 9) and reducing MAP2 degradation.

In view of the problems existing in the traditional class of Advanced Nursing Practice for nursing masters and the learning characteristics of students, under the guidance of process orientated guided inquiry learning (POGIL) theory, with the medium of information technology, centered on the cultivation of students' clinical practice with different specialties of nursing practice as the carrier, the autonomous online teaching mode of teaching and learning is fully integrated into the teaching process. That has been adopted in the teaching of Advanced Nursing Practice for nursing students in grade 2019 of Nanjing Medical University. As a result, autonomous teaching and learning guided by POGIL theory can improve students' clinical nursing practice ability, critical thinking ability, problem-solving ability, communication and cooperation ability, thus achieving the teaching goal of this course.

Objective To investigate the difference between Han nationality residents and the Hani nationality residents in southern Yunnan about the effects of stroke risk factors on cerebral vascular hemodynamic indicators.Methods In the cohort crowds,Hani nationality outpatient patients were selected as the Hani nationality group,the Han nationality outpatient patients with the same gender and similar age were randomly selected as the Han nationality group with the ratio of nearly 1 ∶ 3.The risk factors of stroke and the differences of the hemodynamic indicators were compared between the two groups.Results The dyslipidemia proportion of the Hani nationality group was lower than that of the Han nationality group [48 cases (11.5 ％) vs.257 cases (17.5 ％),x2 =8.867,P =0.003],and the drinking proportion of the Hani nationality group was higher than that of the Han nationality group [79 cases (18.9％) vs.214 cases(14.6％),x2 =4.498,P =0.034],the other risk factors exposure rates had no statistically significant differences between the two groups (all P ＞ 0.05).The ratio of numbers of cerebral vascular hemodynamic indicators below 75 points(optimum truncation points) in the Hani nationality group and the Han nationality group were 30.3％ and 31.9％,respectively,the proportion of the two groups of integral value distribution had statistically significant difference (x2 =12.614,P ＜ 0.01);Vmean (left:t =0.632,P =0.527;right:t =0.642,P =0.532),Vmin (left:t =-0.349,P =0.727;right:t =-0.540,P =0.589),Wv(left:t =0.297,P =0.767;right:t =1.119,P =0.263),Zcv(left:t =0.297,P =0.767;right:t =1.247,P =0.213),Rv(left:t =0.837,P =0.403;right:t =1.222,P =0.222),DR(left:t =0.720,P =0.482;right:t =0.396,P =0.692),Cp(left:t =0.614,P =0.539;right:t =1.486,P =0.138) and other indicators of the two groups had no statistically significant differences.Conclusion The Hani nationality residents'stroke risk factors and CVHI integral distribution in different age groups are different from Han people in southern Yunnan.

Objective To investigate the exposure to stroke risk factors, the proportion of high?risk individuals, and the relationship between risk factor exposure and impaired cerebrovascular hemodynamics in patients at Pu'er People's Hospital. Methods Between April 2014 and June 2017, this study enrolled inpatients and outpatients of the neurology department of Pu'er People's Hospital who underwent cerebrovascular hemodynamic examinations to evaluate stroke risk. A total of 30 103 (12 793 males and 17 310 females) participants aged 22 to 99 (53.3±14.5) years were included. The distribution of exposure rates for stroke risk factors and proportion of high?risk individuals were determined according to age and sex. The relationships between integral scores of cerebrovascular hemodynamics and exposure to risk factors were also analyzed. Results Exposure rates for risk factors of hypertension, dyslipidemia, diabetes, heart disease, stroke family history, cigarette smoking, alcohol drinking, and overweight or obesity in males were 36.6%, 11.4%, 8.8%, 5.9%, 7.0%, 41.6%, 37.8%, and 51.4%, respectively. The exposure rates in females were 31.2%, 11.3%, 7.6%, 5.5%, 6.8%, 0.7%, 1.6%, and 48.8%, respectively. Differences between age groups for all risk factors were significant (P<0.01). Exposure rates for hypertension, diabetes, cigarette smoking, alcohol drinking, and overweight or obesity in males were significantly higher than in females (P<0.01). High?risk males and females accounted for 41.8% and 35.6% (χ2=119.82, P<0.01) and the rates in both groups increased significantly with age (χ2=1 838.2, 2 881.5, P<0.01). Risk factors including age, hypertension, dyslipidemia, diabetes, heart disease, stroke family history, alcohol drinking, and body mass index were independent predictors of increased individual risk of stroke. Conclusions Exposure levels for stroke risk factors and the proportion of individuals at high risk of stroke were relatively high in the hospital population. Cerebrovascular dysfunction is closely related to exposure to common risk factors for stroke.

Objective To explore the relationship between serum albumin (ALB) combined with red blood cell distribution width (RDW) in progression and prognosis of children with heart failure. Method A total of 144 children with heart failure were divided into light, medium, and heavy group according to the modified ROSS score; another aspect, they also were divided into survival group and death group. ALB, RDW, and modified ROSS score were measured to assess the relationship between the factors and the death by logistic regression analysis. Results There are 73 boys and 71 girls. The cases of mild, moderate, and severe group were 78, 39, and 27, respectively. Age and gender difference in three groups were not statistically significant (P>0.05). The ratio of high RDW was 54.86% (79/144), the ratio of low serum ALB was 33.33% (48/144). Chi-square analysis indicated that a severer status of the disease correlated with a lower ALB level (P <0.05) and a higher RDW. The analysis of rank correlation indicating the degree of heart failure was negatively correlated with the related trends of ALB and RDW (P<0.05). Logistic regression analysis indicating a higher risk of death of the disease correlated with a lower ALB level (P<0.05, OR=0.839)and a higher modified ROSS score(P<0.05,OR=1.324).Conclusions The ALB,RDW,and the modified ROSS score are closely related to the severity in heart failure children. The ALB and the modified ROSS score have important clinical prognostic significance in evaluating the prognosis.

Objective To explore the association of synovial fluid vasoactive intestinal peptide levels with cartilage damage,radiological changes and symptomatic severity in patients with ankle post-traumatic osteoarthritis. Methods 74 patients with ankle traumatic osteoarthritis undergoing ankle anthroscopic debridement or joint replacement and 69 healthy controls receiving body check were enrolled in the this study. Serum and synovial fluid VIP concentrations were measured by a special radioimmunoassay method. Cartilage degradation biomarker colla-gen type Ⅱ(CTX-II)and inflammatory marker interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). The symptomatic and functional severity was evaluated using Teeny & Wiss and AOFAS ankle-hindfoot rating scale. The radiographic progression of PTAOA was identified according to the modified ankle osteoar-thritis Kellgren-Lawrence (K-L) grading system. The mankin score was used for assessing the histopathological severity for cartilage lesions. Receiver operating characteristic (ROC) curve was conducted and the area under curve(AUC)was used to evaluate the diagnostic value of VIP,IL-6 and CTX-II levels for the prediction of the modified K-L grading by comparing with other biomarkers. Results There were no significant differences in serum VIP levels between PTAOA patients and controls. VIP levels in synovial fluid showed a negative correlation with modified ankle K-L grading,Mankin scores,CTX-Ⅱand IL-6. In addition,VIP levels were also positively associated with Teeny&Wiss and AOFAS ankle-hindfoot scores. The AUC area of VIP was similar to CTX-Ⅱat early stage of the disease. Conclusions Synovial fluid VIP levels show an independent and negative correlation with disease severity in patients with PTAOA. Low level of VIP in SF can be used as a potential biomarker for reflecting disease progression.

Objective To explore the effects of Bcl-2 and BaK gene silencing on cell apoptosis ,osteogen-esis activity and free Ca2+concentration of MG-63 cell lines. Methods The siRNA sequences targeted Bcl-2 and BaK respectively were designed;Bcl-2 and BaK silencing adenovirus vector scramble RNA vector and empty vec-tor were constructed to transfect MG-63 cell lines. MTT method was used to examine cell viability;ALP and flow cytometry were conducted to observe osteogenesis activity and free Ca2+concentration. Results Bcl-2 gene silenc-ing decreased cell viability,reduced osteogenesis activity and increased free Ca2+ concentration when compared with controls but BaK gene silencing had the opposite effects. The effect of Bcl-2+BaK gene silencing on cell was similar to the empty control. Conclusions Cell apoptosis,osteogenesis activity and free Ca2+concentration of MG-63 change following Bcl-2 and BaK gene silencing,implicating their roles in osteoporosis.

Objective To investigate the characteristics and the correlative factors of constipation in Parkinson's disease (PD) patients.Methods The demographic information,clinical features and history of medications of 193 patients with idiopathic PD consulting in the outpatient department of the First Affiliated Hospital,Anhui Medical University were collected.Patients were evaluated using following scales:Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ),Hoehn-Yahr stage,Bristol Scoring Scale,Cleveland Constipation Scoring Scale (CCS),Scale for Outcomes in PD-autonomic for Autonomic Symptoms,Simple Food Frequency Questionnaire,Hamilton Depression Scale (HAMD),Mini Mental State Examination.The patients were divided into constipation group and non-constipation group based on Rome Ⅲ Criteria for Diagnosis of Functional Constipation,and the correlative factors of constipation were compared and analyzed between the two groups.The severity of constipation and influencing factors were also compared between patients with early onset constipation (occurred before present of motor symptoms) and patients with late onset constipation (occurred after present of motor symptoms).The impacts of anti-PD medication adjustments on constipation were assessed by observing the alteration of constipation severity in 41 PD patients.Results The incidence of constipation was 56.4％ (109/193) in our cohort of PD patients,and 21.1％ (23/109) of constipation was severe according to the assessing by CCS.The spectrum of constipation symptoms included defecation straining (89.9％,98/109),poor stool output (67.9％,74/ 109),reduced stool frequency (63.3％,69/109) and dryness of stool (60.5％,66/109).The age,disease duration,scores of Hoehn-Yahr stage,UPDRS Ⅲ and HAMD,levodopa equivalent dose (LED),frequency of urination disturbance in constipation group were significantly higher than those in nonconstipation group,while the daily quantities of vegetable and water intake in constipation group were significantly lower than those in non-constipation group.Age and HAMD scores were the independent risk factors of constipation (OR=1.049,95％ CI 1.014-1.086,P=0.006;OR=1.316,95％ CI 1.185-1.461,P =0.000).Among the 109 constipation patients,the course of PD,scores of Hoehn-Yahr stage,UPDRSⅢ and LED were positively correlated with the severity of constipation (r =0.269,0.338,0.315,0.341,0.371,all P ＜ 0.05),with HAMD score being the independent risk factor of constipation severity (OR =1.175,95％ CI 1.044-1.322,P ＜ 0.05).The severity of constipation and risk factors of constipation in patients with early onset constipation were not distinct from those with late onset constipation.Conclusions The incidence of constipation increases with the increment of age,disease duration,Hoehn-Yahr stage,UPDRS Ⅲ scores,LED,HAMD scores,urination disorder severity and the decrement of daily water and vegetable intakes.The severity of constipation is positively related to the severity of motor symptoms,the daily dose of anti-PD drugs and depression levels.PD patients with early onset constipation are not distinct from the patients with late onset constipation in terms of severity and risk factors.The influences of anti-PD drugs on constipation are variable depending on the specific drug used and individual constitution.Individualized treatment regimes are proposed with respect to the management of constipation according to the specific risk factors in PD patients.

Objective To evaluate the olfactory functions in patients with Parkinson's disease (PD) with a smell identification test developed for the Chinese population and to examine possible factors contributing to PD patients' olfactory performance.Methods Fifty-five patients with idiopathic and nondementia PD and 55 demographically matched healthy controls (HC) were recruited and their olfactory identification tested using the Chinese Smell Identification Test developed by the Institute of Psychology at Chinese Academy of Sciences.Results Olfactory identification score was significantly lower (t =-6.827,P＜0.01) in the PD group (19.3 ±5.4) as compared with the HC group (26.5 ±5.7).Of all PD patients,63.6％ scored over 1 SD below the age norm.In particular,of those with Hoehn-Yahr ratings between 2 to 3,77.8％ scored over 1 SD below the age norm.Receiver operating characteristic (ROC) curve analysis indicated that a cut-off score of 22.5 on the Chinese Smell Identification Test distinguished between PD patients and HC with a sensitivity of 74.6％ and specificity of 70.9％.Within the PD group,age,education,Hoehn-Yahr rating and Mini-Mental State Examination score were not found to correlate with olfactory performance (all P ＞ 0.05).Conclusion PD patients in China show significant impairment of olfactory identification,which is effectively captured by the Chinese Smell Identification Test.

In the study of neurodegenerative diseases,a hypothesis of inflammation in central nervous system is raised:the activated microglia leads to sustained release of preinflammatory cytokines and injury of normal neural structures and function,resulting in learning and memory deficits,such as Alzheimer's disease (AD) and Parkinson's disease (PD).Synapses structural disorders are responsible for deficit of synaptic plasticity;after high frequency stimulation,changes of long-term potentiation (LTP) are most obvious in synaptic plasticity,characterized by decrease of amplitude and excitatory postsynaptic potential duration.Activated microglia and inflammatory cytokines released by activated microglia,such as interleukin-1β,tumor necrosis factor-α and nitric oxide are involved in the pathological process of LTP changes in these kinds of disease.The aim of this paper is to give a review about progress in the relations between microglia activation and LTP in neurodegenerative diseases researches in recent years and hope to have something to guide the research of neurodegenerative disease.