each group were sacrificed, respectively. Distributions of BrdU positive cels and ChAT positive cels were detected by S-P immunohistochemical method. The learning and memory abilities of rats were detected by Morris water maze system.
RESULTS AND CONCLUSION:BrdU positive cels were mainly distributed in the cortex and hippocampus, especialy around the blood vessels, and there was the presence of focal aggregation. A smal amount of BrdU positive cels were observed in the basal ganglia and thalamus as wel as in the ependyma. BrdU positive cels were counted at different time after operation. The number of BrdU positive cels decreased with time, and only a smal number of BrdU positive cels were observed at 60 days after transplantation. The number of ChAT positive cels at different time after transplantation was ranked as folows: neural stem cel transplantation group > model group > sham operated group (P < 0.05). Compared with the model group, the time for searching the platform was significantly lower in the neural stem transplantation group and sham operated group, but the number of crossing the platform was significantly higher in the neural stem cel transplantation group and sham operated group (P < 0.05). The results show that neural stem cels could be transplanted into the rats with vascular dementia, and the cels could survive and migrate in the brain of rats and significantly improve the learning and memory ability. This mechanism may be related to the differentiation and growth of cholinergic neurons in the hippocampus.

Objective To evaluate the hemocompatibility of polydioxanone(PDO)bioabsorbable stents.Methods Whole blood clotting time,prothrombin time(PT),activated partial thromboplastin time(APTT),platelet adhesion and hemolysis were used to evaluate the hemocompatibility of PDO bioabsorbable stents,and the results were compared with those of 316L stainless stents which are widely used clinically.Results The anticoagulant property of PDO bioabsorbable stents was similar to that of 316L stainless stents.Both PDO bioabsorbable and 316L stainless stents were not prone to activate blood coagulation factors.Compared with 316L stainless stents,PDO bioabsorbable stents had weaker platelet adhesion and activation.Hemolysis ratios of two groups were less than 5%.Conclusions PDO bioabsorbable stents had good hemocompatibility in vitro.

Objective To explore the intervention effect of active fraction of Angelica Sinensis Radix in mice under high altitude hypoxia condition. Methods Totally 72 healthy SPF mice were randomly divided into control group (K), model group (M), Rhodiola rosea group, and active fraction of Angelica Sinensis Radix groups (B, C, X). The mice were administerted corresponding treatment by gavage for 21 days. Control mice were given normal saline in same volume. From the 8th day, all mice excepted control mice were exposed to high altitude hypoxia cabin after 0.5 hour gavage treament. On the 22nd day, after got out of the cabin and their body weight were measured, mice were put to death through eyeball blood sampling to prepare splenic lymphocyte suspension. The proliferation and transformation capacities of lymphocyte cell and killing activity of NK cells were detected by MTT. The content of IL-2 in the serum of mice in each group were detected by ELISA. Results Compared with the control group, the body weight of mice, the proliferation and transformation capacities of lymphocyte cell, the killing activity of NK cells, and the content of IL-2 were all significantly decreased (P<0.05, P<0.01). Experiment tests showed that the proliferation and transformation abilities of lymphocyte cell and the killing activity of NK cells were all increased in the mice of group B, C, and X compared with those of the model group (P<0.05, P<0.01). The stimulate index of lymphocyte cell was raised after X intervention compared with those of the model group (P<0.05). The content of IL-2 in the serum was enhanced after intervention of active fraction C and X of Angelica Sinensis Radix compared with those of the model group (P<0.05, P<0.01). Conclusion Active fraction of Angelica Sinensis Radix shows increasing immunological function of mice exposed to hypoxia.

Objective: To investigate the visual acuity of primary and middle school students in Ningxia by using decision tree model and logistic regression, and to provide evidence for the prevention and control of visual acuity. Methods: Using stratified cluster sampling method, 3 257 children aged 7-18 years were randomly selected from Yinchuan and Wuzhong in Ningxia. Visual acuity test and questionnaire survey were conducted. The C 5.0 algorithm in Clementine12.0 and Logistic regression were used to analyze the factors associated with visual acuity. Results: The overall rate of low vision of the middle school of Ningxia was 62.6%, with girls (68.1%) higher than that of boys(56.8%)(P<0.01). There was a significant difference in the prevalence of low vision among different educational stages(P<0.01), with high school students had the highest detection rate(82.2%). Results of decision tree C 5.0 algorithm showed that educational stage, gender, time to do homework after school and frequency of moderate intensity exercise per week associated with poor eyesight of primary and secondary school students. Logistic regression results showed that girls, the distance between the eyes and the computer display screen <66 cm(OR=1.24, 95%CI=1.00-1.52), and the distance between the eyes and the textbook when reading was less than one foot (OR=2.05, 95%CI=1.23-3.40) were positively associated with poor vision. Low grade students and homework time <2 hours after school (OR=0.76, 95%CI=0.62-0.92) were negatively associated with lower risk of poor vision. Conclusion Educational stage, gender and time of homework after school are associated with the visual acuity of primary and secondary school students in Ningxia. It is suggested that prevention of myopia should start from the low-grade students, reducing after-school work for primary and secondary school students, and increasing outdoor activities. All the girls should be encouraged to engage in more outdoor activities, to prevent the occurrence and development of myopia.

Background and Objectives: p21, an important member of the Cip/Kip family, is involved in inhibitory effects of RUNX1b overexpression during the early stage of human hematopoiesis. Methods: and Results: We established a human embryonic stem cell (hESC) line with inducible expression of p21 (p21/hESCs). Overexpression of p21 did not influence either mesoderm induction or emergence of CD34＋ cells, but it significantly decreased the production of CD43＋ cells and changed the expression profile of hematopoiesis-related factors, leading to the negative effects of p21 on hematopoiesis. Conclusions In RUNX1b/hESC co-cultures when RUNX1b was induced from D0, perturbation of the cell cycle caused by upregulation of p21 probably prevented the appearance of CD43＋ cells, but not CD34＋ cells. The mechanisms via which CD34＋ cells are blocked by RUNX1b overexpression remain to be elucidated.

Objective: This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods: After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results: DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion: These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.

ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.

Objective:To observe the clinical efficacy of angiotensin-receptor neprilysin inhibitors (ARNI) in the treatment of maintenance hemodialysis (MHD) with heart failure.Methods:The clinical data of heart failure patients who accepted MHD in Central China Fuwai Hospital were retrospectively collected. All patients accepted regular treatments of heart failure, and then the treatment group was treated with ARNI, while the control group was treated with valsartan. The treatment course was 6 months. The cardiac parameters: left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), pulmonary artery pressure, right ventricular end-diastolic dimension (RVED), right atrial end-diastolic dimension (RAED), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), and serum potassium were collected and compared between the two groups. Multivariate ordered logistic regression analysis was adopted to analyze the influencing factors of treatment effect.Results:A total of 60 MHD patients with heart failure were enrolled with age of (53.92±11.88) years old, 37 males (61.7%), dialysis age of (27.83±12.92) months, and blood pressure of (154.22±15.27) mmHg/(85.43±12.31) mmHg. (1) There was no significant difference of the clinical data and cardiac parameters between the treatment group ( n=30) and the control group ( n=30) before treatment (all P>0.05); (2) After treatment of 6 months, the total effective rate [28/30(93.3%)] in the treatment group was significantly higher than that in the control group [20/30(66.7%)] and the rehospitalization rate [2/30(6.7%)] in the treatment group was significantly lower than that in the control group [10/30(33.3%)] (both P<0.05); (3) After treatment of 6 months, LVEF, LVEDD, LVESD, pulmonary artery pressure, RVED, RAED, NT-pro BNP, and blood pressure were all improved significantly compared with the baseline in both groups (all P<0.05) and there was no significant difference of serum potassium and body weight before and after treatment in the two groups (all P>0.05); (4) After treatment of 6 months, LVEF in the treatment group was higher than that in the control group and LVEDD, LVESD, pulmonary artery pressure, NT-pro BNP, and blood pressure in the treatment group were lower than those in the control group (all P<0.05). There was no significant difference of RVED, RAED, serum potassium and body weight between the two groups after treatment (all P>0.05); (5)The difference values before and after treatment of LVEF, LVEDD, LVESD, NT-pro BNP, body weight, systolic blood pressure, and diastolic blood pressure were different between the two groups (all P<0.05); (6)Therapy method ( β=-1.863, 95% CI -2.948-0.777, P=0.001) and residual urine ( β=-1.686, 95% CI -3.079- -0.293, P=0.018) were independent influencing factors of treatment effect (the treatment effect of ARNI was better than that of valsartan; the treatment effect of patients with normal urine volume was better than that of patients with oliguria and anuria). Conclusions:ARNI can effectively improve cardiac function in MHD patients with heart failure, inhibit ventricular remodeling, and improve disease prognosis.

Realtime xCELLigence analysis (RTCA) is a new cell detection technology to continuously monitor, record and analyze a variety of information generated by cell activity. In drug research, it plays an important role in assessing myocardial toxicity and cell biological activity. Here, we first introduce the underlying mechanisms and characteristics of RTCA. Then we review the applications of RTCA in the research of myocardial toxicity and cell biological activity, to provides the fundamental baseline for understanding and exploiting RTCA. With the real-time, unlabeled, non-invasive, high throughput, and high accuracy features, RTCA not only promotes drug research and development, but also has a broad and good application prospect in other fields.
Pharmaceutical Preparations

The generation of a tau-V337M point mutation mouse model using gene editing technology can provide an animal model with fast disease progression and more severe symptoms, which facilitate the study of pathogenesis and treatment of Alzheimer's disease (AD). In this study, single guide RNAs (sgRNA) and single-stranded oligonucleotides (ssODN) were designed and synthesized in vitro. The mixture of sgRNA, Cas9 protein and ssODN was microinjected into the zygotes of C57BL/6J mice. After DNA cutting and recombination, the site homologous to human 337 valine (GTG) in exon 11 was mutated into methionine (ATG). In order to improve the efficiency of recombination, a Rad51 protein was added. The female mice mated with the nonvasectomy male mice were used as the surrogates. Subsequently, the 2-cell stage gene edited embryos were transferred into the unilateral oviduct, and the F0 tau-V337M mutation mice were obtained. Higher mutation efficiency could be obtained by adding Rad51 protein. The F0 tau-V337M point mutation mice can pass the mutation on to the F1 generation mice. In conclusion, this study successfully established the first tau-V337M mutation mouse by using Cas9, ssODN and Rad51. These results provide a new method for developing AD mice model which can be used in further research on the pathogenesis and treatment of AD.
Animals ; Male ; Female ; Mice ; Humans ; CRISPR-Cas Systems/genetics* ; RNA, Guide, CRISPR-Cas Systems ; Rad51 Recombinase/genetics* ; Mice, Inbred C57BL ; Disease Models, Animal ; Recombination, Genetic