Multivariate time series problems widely exist in production and life in the society. Anomaly detection has provided people with a lot of valuable information in financial, hydrological, meteorological fields, and the research areas of earthquake, video surveillance, medicine and others. In order to quickly and efficiently find exceptions in time sequence so that it can be presented in front of people in an intuitive way, we in this study combined the Riemannian manifold with statistical process control charts, based on sliding window, with a description of the covariance matrix as the time sequence, to achieve the multivariate time series of anomaly detection and its visualization. We made MA analog data flow and abnormal electrocardiogram data from MIT-BIH as experimental objects, and verified the anomaly detection method. The results showed that the method was reasonable and effective.
Data Interpretation, Statistical ; Electrocardiography ; Humans ; Image Interpretation, Computer-Assisted ; Pattern Recognition, Automated

Polymeric micelles have exhibited attractive properties as drug carriers, such as high stability in vivo and good biocompatibility, and been successfully used to dissolve various drugs of poor aqueous solubilities. In this study, we developed a new type of polymeric micelles with mannose-mediated targeting and pH-responsive drug release properties for anticancer drug delivery. The polymeric micelles were prepared from an amphiphilic polymer, poly (glycidyl methacrylate)-g-mannose (PGMA-Mannose). An anticancer drug, doxorubicin (DOX), was encapsulated into the micelles during the micellization, and could be released rapidly under acidic condition. The specificity of cellular uptake of the micelles by two different cell lines was studied using confocal laser scanning microscopy and the MTT assay. DOX-loaded micelles were efficiently trapped by mannose-receptor-overexpressing cancer cells MDA-MB-231, whereas mannose- receptor-poor cells HEK293 showed much lower endocytosis towards the micelles under the same conditions. Thus, DOX-loaded micelles displayed higher cytotoxicity to MDA-MB-231 cancer cells as compared with free DOX. The present study demonstrates that PGMA-Mannose micelles are a promising targeted drug delivery system for cancer therapy.
Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Delivery Systems ; HEK293 Cells ; Humans ; Lectins, C-Type ; metabolism ; Mannose ; chemistry ; Mannose-Binding Lectins ; metabolism ; Micelles ; Receptors, Cell Surface ; metabolism

Objective To investigate the effects of different dietary patterns on brachial ankle pulse wave velocity in northern industrial cities. Methods According to the selection criteria,from 2014 to 2015, 22436 health checkup persons were selected as the subjects of Kailuan Group,they were followed up with health examination and questionnaire investigation, at the same time, the brachial ankle pulse wave velocity was detected. According to the dietary advice given by the Chinese dietary guidelines,the proportion of animal and plant food in the food frequency questionnaire and the supply of nutrients are divided into 4 groups,which are the traditional Chinese diet group (3 585 cases),the Western diet group (13 639 cases),the balanced diet group (1 309 cases),the Mediterranean diet group (3 903 cases). Logistic multivariate regression analysis was used to analyze he risk factors of atherosclerosis. Results The mean value of brachial ankle pulse wave velocity in 22 436 cases was ( 1 462. 46 ± 320. 69) cm/s, and the incidence of peripheral arteriosclerosis was 50. 78%(11 392/22 436). The incidence of arteriosclerosis around the balanced diet group, the Mediterranean diet group,the traditional Chinese diet group and the Western diet group were 48. 82%( 639/1 309), 49. 12%(1 917/3 903),50. 49%(1 810/3 585),51. 51%(7 026/13 639),and the difference between the groups was statistically significant (P＝0. 024); after adjusting other related risk factors,compared with the balanced diet group,the risk of peripheral arteriosclerosis in the Mediterranean diet group,the traditional diet group and the Western diet group was 121(95%CI:0. 557～2. 258),1. 015(95%CI:0. 663～1. 554),1. 033(95%CI:0. 677～1. 575), respectively. Conclusion The incidence of peripheral arteriosclerosis increased gradually in the balanced diet group,the Mediterranean diet group,the Chinese traditional diet group and the Western diet group, but there was no statistical significance in the risk of peripheral arteriosclerosis after adjusting other related risk factors. This Conclusion requires more large samples,long-term follow-up study to further confirm.

Objective To investigate the effect of the peroxide proliferator-activated receptorgamma (PPAR-γ) agonist rosiglitazone on the motor function recovery of hind limbs in rats with spinal cord injury.Methods Sixty-eight female SD rats were used to establish spinal cord injury model by modified Allen method.(1) Eight rats were randomly divided into negative control group and rosiglitazone group with four rats in each group.The expression of aspartate proteolytic enzyme-1 (caspase-1) in spinal cord of rats 7 days after injury was detected by immunohistochemical staining.(2) Forty-eight rats were randomly divided into negative control group,rosiglitazone group,rosiglitazone + Clostridium chitosans group [nuclear factor kappa B (NF-kappa B) activator],rosiglitazone + monosodium urate group [oligomerization domain-like receptor protein 3 (NLRP3) antagonist],with 12 rats in each group.BBB scores of hindlimb motor function were assessed at 1,3,14,21 and 28 days after injury in each group.The expression of interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in each group was detected by ELISA at 28 days after injury.Microglia were isolated from the spinal cord of 12 rats and cultured for 7 days.They were randomly divided into the following five groups:(1) negative control group:no drug treatment;(2) rosiglitazone group:1 micromol/L rosiglitazone treatment;(3) rosiglitazone + Clostridium chitin group:1 micromol/L rosiglitazone + 20 micromol/L Clostridium chitosporin treatment;(4) Clostridium chitosan treatment Mycoplasma group:20 μ mol/L shell Clostridium treatment;(5) Clostridium chitosanin + MCC950 group [(NLRP3) antagonist]:20 μmol/L Clostridium chitosanin + 100 nmol/L MCC950;Western blot was used to detect the expressions of caspase-1,NF-kappa B and NLRP3 in microglia cells;ELISA was used to detect the expressions of IL-1β and TNF-α in the supernatant of microglia culture.Results Compared with negative control group,caspase-1 expression was decreased in rosiglitazone group in spinal cord injury area [gray matter area:5.1 ± 0.8∶6.9 ± 1.1;white matter area:5.6 ± 0.9 ∶ 7.5 ± 1.1] (P ＜ 0.05).At 28 days after operation,the rosiglitazone group had the highest BBB score [(14.7 ± 1.6) points],and the BBB score of rosiglitazone + Clostridium chitosans group (10.5 ± 2.1) points was superior to that of rosiglitazone + monosodium urate group [(7.2 ± 1.3)points,P ＜ 0.05].The expressions of IL-1β and TNF-α in rosiglitazone + monosodium uric acid group were lower than those in other groups at 28 days after injury (P ＜ 0.05).In vitro,the expressions of caspase-1,NF-kappa B,IL-1β and TNF-α in rosiglitazone group were lower than those in negative control group (P ＜ O.05).The expressions of caspase-1,NLRP3,IL-1β and TNF-α in rosiglitazone + Clostridium chitosani group were higher than those in rosiglitazone group,(P ＜ 0.05).The expressions of caspase-1 and IL-1β were higher than those in Clostridium chitosani + MCC950 group (P ＜0.05),but there was no significant difference in the expression of TNF-α between the two groups (P ＞0.05).Conclusion Rosiglitazone can promote the recovery of hind limb motor function in rats with spinal cord injury by inhibiting the expression of NF-kappa B,thereby reducing the activation of NLRP3 inflammatory bodies in microglia and ultimately inhibiting the occurrence of inflammation.

AIM: To evaluate the bioequivalence of the test and reference preparations of solifenacin succinate tablets administered once orally under fasting and fed conditions in Chinese healthy volunteers. METHODS: The study was designed as single-center, randomized, open, self-crossover and twenty four healthy volunteers were recruited respectively in fasting and fed conditions. Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 10 mg. The plasma concentration of solifenacin was analyzed by LC-MS/MS. The major pharmacokinetic parameters were calculated by WinNonlin 7.0, then the bioequivalence was evaluated.RESULTS: The main pharmacokinetic parameters of a single oral solifenacin succinate under fasting condition for test and reference preparation were as follows: C