Objective To observe the influence of Hemin on both the expression of neuroglobin (Ngb) and Tau protein phosphorylation in rats with vascular dementia (VD),and explore the effect and mechanism of Ngb in VD. Methods VD model was established in rats with a permanent bilateral common carotid arteries occlusion(2-VO). Fifty four healthy male SD rats were randomly divided into 3 groups:sham operation group,VD group and Hemin group. According to ischemic time,the animals in each group were randomly allocated into 1 week subgroup,4 weeks subgroup and 8 weeks subgroup(n=6 in each subgroup). The learning and memory ability of rats were evaluated by Morris water maze test. The brain histopathological changes were observed by HE staining and the expression of Ngb and phosphorylated Tau ( p-Tau) was de-termined by Western blot. Results Compared with the sham operation group,after 2-VO the escape latency extended (all P<0. 05) and cross-platform performance reduced in rats in both VD group and Hemin group (all P<0. 05). The learning and memory ability of rats in Hemin group was better than that in VD group at the corresponding time point:the increase in the number of crossing platforms(1 week:Hemin group (7. 00± 0. 89) times vs VD group (5. 50±1. 22) times,t=2. 42,P<0. 05;4 weeks:Hemin group (5. 33±0. 52) times vs VD group (3. 50±1. 04) times,t=3. 84,P<0. 01;8 weeks:Hemin group (6. 50±0. 55) times vs VD group (4. 50±1. 05) times,t=4. 14,P<0. 01). The expression of Ngb and phosphorylated Tau (p-Tau) increased in VD group and Hemin group (P<0. 01). Compared with VD group,the expression of Ngb in Hemin group was increased(1 week:Hemin group (3. 45±0. 23) vs VD group (2. 56±0. 08),t=5. 67,P<0. 01;4 weeks:Hemin group (3. 08±0. 13) vs VD group (2. 28±0. 08),t=7. 96,P<0. 01;8 weeks:Hemin group (2. 82± 0. 12) vs VD group (2. 05±0. 10),t=7. 28,P<0. 01),while p-Tau was decreased (1 week:Hemin group (1. 57±0. 12) vs VD group (2. 40±0. 15),t=7. 62,P<0. 01;4 weeks:Hemin group ( 2. 14±0. 21) vs VD group (3. 18±0. 14),t=8. 23,P<0. 01;8 weeks:Hemin group (1. 83±0. 13) vs VD group (2. 79±0. 19), t=4. 91,P<0. 01). In VD group and Hemin group,the learning and memory ability exhibited a negative cor-relation with Ngb (r=-0. 892,P<0. 01),whereas a positive correlation with p-Tau (r=0. 932,P<0. 01). Conclusion Hemin induces high expression of Ngb and inhibits Tau phosphorylation in VD rats. Ngb may play a neuroprotective role in the development of VD by regulating Tau phosphorylation.

OBJECTIVE: To train convolutional networks using multi-lead ECG data and classify new data accurately to provide reliable information for clinical diagnosis. METHODS: The data were pre-processed with a bandpass filter, and signal framing was adopted to adjust the data of different lengths to the same size to facilitate network training and prediction. The dataset was expanded by increasing the sample size to improve the detection rate of abnormal samples. A depth-wise separable convolution structure was used for more specific feature extraction for different channels of twelve-lead ECG data. We trained the two classifiers for each label using the improved DenseNet to classify different labels. RESULTS: The propose model showed an accuracy of 80.13% for distinguishing between normal and abnormal ECG with a sensitivity of 80.38%, a specificity of 79.91% and a F1 score of 79.35%. CONCLUSIONS The model proposed herein can rapidly and effectively classify the ECG data. The running time of a single dataset on GPU is 33.59 ms, which allows real-time prediction to meet the clinical requirements.
Algorithms ; Arrhythmias, Cardiac ; diagnosis ; Databases as Topic ; Electrocardiography ; classification ; methods ; Humans ; Neural Networks (Computer) ; Sensitivity and Specificity

Objective To explore the perinatal risk factors of early onset thrombocytopenia (EOT) in full-term small for gestational age infants. Methods A 1:1 or 1:2 matched case control study was carried out. A total of 93 full-term small for gestational age infants with EOT were selected from April 2008 to July 2014 as the case group, and the non EOT full-term small for gestational age infants with the birth weight difference <250 g and the gestational age difference <3 days were selected as the control group. The clinical data during perinatal period and laboratory examination results after admission were collected retrospectively. And the differences between the two groups were compared. Results The incidence of intrauterine distress (41.9％ vs. 25.8％, χ2=7.35, P=0.007), amniotic fluid contamination (39.8％ vs. 27％, χ2=4.66, P=0.031), and early-onset sepsis (39.8％ vs. 27％, χ2=4.66, P=0.031) were significantly higher in the case group than those in the control group. Conditional logistics regression analysis showed that intrauterine distress (β=0.60, OR=1.82, 95％CI=1.04～3.17, P=0.035) and early-onset sepsis (β=1.69, OR=5.44, 95％CI=1.11～26.76, P=0.037) were related to EOT. Conclusions Intrauterine distress and early-onset sepsis are risk factors for the onset of EOT in full-term small for gestational age infants.

Objective: To compare the anti-inflammatory effect of Fraxini Cortex pieces between integrated production process and traditional processing method. Methods: The model of rat paw swelling induced by carrageenan was used to study the anti-inflammatory and swelling reliving effects of water extracts of Cortex Fraxini with different methods. The main chemical components of the 2 kinds of Cortex Fraxini herbal pieces were determined by high performance liquid phase. Results: Compared with the blank group, the water extracts of the 2 kinds of Cortex Fraxini could reduce the swelling of the rats and improve the various indicators of inflammation. However, the anti-inflammatory and swelling reliving effects of the integrated processing of Cortex Fraxini were more significant. The contents of 4 main active ingredients of esculine, fraxin, aesculetin and fraxetin in the integrated processing of Cortex Fraxini were higher than that of the traditionally processed Cortex Fraxini. The total amount of 4 kinds of coumarins in the integrated Cortex Fraxini was about 1.5 times that of the traditionally processed water extract of Cortex Fraxini. Conclusion: The integrated processing and traditional processing of Cortex Fraxini have similar effects on anti-inflammatory effects, and have the superiority of reducing the loss of active ingredients, which is worthy of popularization and application.

ABSTRACT:Objective To investigate the prevalence of thyroid nodules in Xi’an City by ultrasonography and study the correlation between thyroid nodules and the components of metabolic syndrome.Methods We recruited 4 527 subjects in this cross-sectional study and divided them into thyroid nodules (TN)group and non-thyroid nodules (NTN)group.The height,weight,blood pressure,blood sugar,lipid,and serum uric acid were measured and analyzed.The relationship between thyroid nodules and thyroid function was assessed in the subjects who received TT3,TT4,TSH,TGAB,and TPOAB tests.Results ① The prevalence of thyroid nodules was 31.8% and was significantly higher in the female patients (38.4% vs.27.1%,χ2=64.44,P<0.001).However,the prevalence of metabolic syndrome was 9.1% and was significantly higher in the male ones (11.4% vs.5.9%,χ2=40.39,P<0.001).② Compared with that in NTN group,TT3 in TN group was significantly increased (t=6.04,P<0.001), but the other indexes did not obviously change in the two groups (P>0.05).③ Age,systolic blood pressure,and TG,LDL-C and serum uric acid levels were remarkably higher in TN group than in NTN group (P<0.001 ). Conclusion The prevalence of thyroid nodules in Xi’an City is noticeably high.High systolic blood pressure level, dyslipidemia and elevated uric acid are associated with thyroid nodules.Therefore,screening and management of the individuals with aforementioned characteristics deserve more attention.

Objective To investigate therapeutic effect of the low dose clomiphene treatment of idiopathic oligoasthenospermia and effect on sperm epididymal protein level 4.Methods183 cases of idiopathic oligoasthenospermia were divided into three groups, vitamin group of 61 patients were given vitamin E,clomiphene group(61 cases)treated with low dose clomiphene, combined group of 61 patients were given low dose clomiphene and vitamin E, lasted for 12 weeks.Semen volume, sperm density, sperm motility, sperm survival rate and sperm reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), human epididymis protein 4 (HE4), follicle stimulating hormone, luteinizing hormone, testosterone concentration were observed before and after treatment.After treatment, the patients were followed up for 1 year, the observation of the natural pregnancy rate after treatment.ResultsSperm density, sperm survival rate and sperm and a A+B grade sperm in the clomiphene group were significantly higher comparedwith the vitamin group (P< 0.05), sperm density, sperm survival rate and sperm and a A+B grade sperm in the combined group were significantly increasedcompared with clomiphene group and vitamin group (P< 0.05),levels of HE4 after treatment was significantly lower compared with before treatment (P< 0.05), And the difference between the three groups were statistically significant (P< 0.05).Follicle stimulating hormone, luteinizing hormone, testosterone in clomiphene group and combined group after treatment, were significantly increased compared with before treatment (P< 0.05), and the combined group had no statistically difference compared with clomiphene group.The pregnancy rate in 1 year of vitamin group, clomiphene group and combined group were 24.59%, 42.62% and 62.29% (P< 0.05).ConclusionClomiphene treatment of idiopathic asthenospermia is better than vitamin E, the combination of the two has a synergistic effect.

Objective: To prepare the total saponins from Paris Polyphylla self-microemulsifying drug delivery system (SMEDDSs) and its solid fied granule, and investigate the in vitro release.Methods: The solubility of the total saponins from Paris Polyphylla in different excipients was investigated.The pseudo-ternary phase diagram composed of different oil phase, emulsifier and co-emulsifier was used to define the self-emulsifying area.The optimal formula of the total saponins from Paris Polyphylla SMEDDSs was prepared into granule.The appearance, morphology, particle size distribution, PdI and zeta potential of the microemulsion and the granule were determined by a dilution method.The drug release profile of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule were compared.Results: The optimal formula of SMEDDSs was as follows: propylene glycol monocaprylate as the oil phase, Tween-80 as the emulsifier and propylene glycol as the co-emulsifier with the optimum ratio of 7.0∶1.5∶1.5.After diluted by water,the total saponins from Paris PolyphyllaSMEDDSs and the granule formed a clear and transparent microemulsion solution with small homogeneous spheres as seen under a transmission electron microscope.The average particle size of the total saponins from Paris Polyphylla SMEDDSs and the granule was (58.6±16.4) nm and (68.1±12.1) nm with PdI of (0.183±0.04) and (0.209±0.05), respectively, and the zeta potential was (-20.2±1.9) mV and (-18.9±1.5) mV, respectively.The results of transmission electron microscopy showed the microemulsion was round, regular and spherical distribution.The in vitro release profile indicated that the accumulated release of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule was more than 85% in 45 min.Conclusion: The self-microemulsifying granule can significantly improve the in vitro dissolution rate of the total saponins from Paris Polyphylla, and the preparation process is simple and feasible.

Objective:To design and develop a formula of solid lipid nanoparticles containing the total saponins of Paris Polyphylla using a quality by design ( QbD) method. Methods:The target product profile of solid lipid nanoparticles was determined according to the properties of dosage form and administration. The risk assessment was carried out according to the theoretical knowledge and experi-ence to define the critical variables influencing the properties of solid lipid nanoparticles. Firstly, Plackett-Burman test was used to screen out the key variables significantly affecting the pharmacological properties of solid lipid nanoparticles, and then the Box-Behnken effect surface method was use to further optimize the selected variables. The physicochemical properties of solid lipid nanoparticles con-taining the total saponins of Paris Polyphylla were studied, such as the particle size distribution, polydispersity index ( PdI) , zeta po-tential, morphology and in vitro drug release behavior. Results: The optimum formula and preparation process were as follows: the concentration of glycerol monostearate was 5. 5％, the concentration of soybean phospholipid was 8. 0％, the number of homogenization was 6 times, the concentration of drug was 5. 0％, the surfactant was Tween 80, the mass pressure was 600 bar and the homogeneous temperature was 65℃. The mean particle size, PdI and zeta potential of the optimized solid lipid nanoparticles was (116. 5 ± 32. 1) nm, (0. 198 ± 0. 018) and ( -23. 6. 5 ± 0. 9) mV, respectively. Transmission electron microscopy showed that the solid lipid nanop-articles were spherical. The results of in vitro release showed a sustained release property, and the cumulative release was 63. 5％ in 24 h. Conclusion:It is feasible to design and develop solid lipid nanoparticles containing the total saponins of Paris Polyphylla by using the QbD method, which can ensure the product quality to meet the requirements.

Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS. Alternatively, phosphorylated Tyr18 (pY) and Ser13 (pS) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.
Crystallography, X-Ray ; Membrane Proteins ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Mitochondrial Degradation ; Mitochondrial Proteins ; chemistry ; metabolism ; Peptides ; chemistry ; metabolism ; Phosphorylation ; Protein Structure, Quaternary

Aim To investigate the effect of neferine on proliferation and invasion of human hepatocellular car-cinoma. Methods HepG2 and Bel-7402 cells were cultured in vitro with different concentrations of nefer-ine, then cell proliferation was observed by CCK-8 as-say; cell invasion was observed by transwell invasion assay; the protein expression of RhoA, RhoC and ROCK was detected by Western blot. Results CCK-8 results showed that neferine could significantly inhibit cell proliferation in a dose-dependent manner compared with the control group. Transwell invasion assay showed that cell invasion was significantly decreased with neferine 3 μmol · L-1 . Western blot results showed that RhoA, RhoC and ROCK protein expres-sion was decreased when neferine was co-incubated with hepatocellular carcinoma cells. Conclusion Nef-erine can inhibit proliferation and invasion of HepG2 and Bel-7402 cells, which is mediated mainly by the inhibition of RhoA, RhoC and ROCK protein expres-sion.