Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

Objective: To evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction. Materials and Methods: A total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male;mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test. Results: Compared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FSkurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013). Conclusion An integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.

Objective To observe the effects of Shenqi Xingnao Prescription on learning and memory ability, contents of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) in brain tissue in mice models with scopolamine-induced Alzheimer disease (AD); To investigate its mechanism for prevention and treatment for AD. Methods Totally 110 ICR mice were randomly divided into control group, control+Shenqi Xingnao Prescription high-dose group,model group,donepezil group,model+Shenqi Xingnao Prescription high-,medium-,and low-dose groups. The control and model group were given distilled water for gavage, and the other groups were given the corresponding medicine for gavage, once a day, for 14 days. On the 15th day, Morris water maze test and object recognition test were used to evaluate the learning and memory ability of each group. The model mice of memory impairment induced by intraperitoneal injection of scopolamine was established 20 minutes before the behavioral test. The expressions of ChAT and AChE in cortex and hippocampus were detected by Western blot. Results The results of Morris water maze test showed that compared with the control group, the model group had significant longer escape latency(P<0.05);Compared with the model group,Shenqi Xingnao Prescription medium-and high-dose groups could shorten the escape latency (P<0.05). The results of the object recognition test showed that compared with the control group, the ability of the model group to explore new things decreased and the discrimination index (DI) decreased (P<0.001);Compared with the model group,Shenqi Xingnao Prescription groups could increase the DI of model mice (P<0.05, P<0.01, P<0.001). The results of Western blot showed that the expression of AChE protein in the cortex and hippocampus of the model group was significantly higher than the control group (P<0.01); Compared with the model group, Shenqi Xingnao Prescription low- and medium-dose groups could decrease the expression of AChE in the cortex in different degrees(P<0.01);Shenqi Xingnao Prescription groups could decreaed the expression of AChE in the hippocampus (P<0.001); There was no significant statistical significance in the expression of ChAT in the cortex and hippocampus in each group.Conclusion Shenqi Xingnao Prescription can significantly improve the learning and memory ability of AD model mice induced by scopolamine, which may be related to the descent expression of AChE protein in the cortex and hippocampus of the model mice.

Objective To prepare a novel dual-modality imaging probe based on Cerasome nano-materials, and evaluate its in vivo biodistribution and pharmacokinetic properties. Methods ICG encapsu-lated Cerasome was modified with chelating agent DOTA for 111 In-labeling. Normal mice firstly were used for in vivo studies. Animals were sacrificed at different time points after tail vein administration, blood samples were taken and the organs of interest were captured to evaluate the pharmacokinetic properties and in vivo biodistribution of 111 In-ICG-DPDCs. The subcutaneous Lewis lung carcinoma ( LLC ) tumor model in C57BL/6 mouse was established. The tumor-bearing mice were subjected to optical imaging in small animal IVIS and SPECT imaging in small animal nanoScanSPECT/CT system for tumor uptake of 111 In-ICG-DPDCs. Results The size of the nanoparticle probe was about 90 nm, and the 111 In-labeling was successfully per-formed with 99.93% radiochemical purity after purification. 111 In-ICG-DPDCs showed excellent in vitro sta-bility with 97.10% radiochemical purity at 48 h post-purification. In vivo blood clearance experiments showed that 111 In-ICG-DPDCs had a relative long blood circulation time with the fast and slow phase half-lives of 40 and 132.7 min. 111In-ICG-DPDCs accumulated mainly in the liver and spleen, with long retention time. NanoScanSPECT/CT imaging showed that LLC tumors were significantly visualized at 4 h post-injection, and the other major accumulated organs were the liver and spleen, which were consistent with the results of biodistribution. Optical imaging showed significant uptake of the nanoparticle probe in the tumor, confirming the SPECT imaging results. Conclusion The Cerasome based probe designed could be used for tumor SPECT and optical dual-modality imaging, and has potential for therapeutic use.

Objective To develop a cellular shear stress loading system with an adjustable stress mode and relevant parameters, and subsequently verify the effectiveness and feasibility of this system. Methods The hardware of the system was developed by using a peristaltic pump and self-designed multi-channel flow chamber, and the mode control program of shear stress based on LabVIEW was designed to control the device via RS485 interfacing and Modbus protocol. Additionally, the relationship between the shear stress and system parameters was calibrated, and finite element analysis was also conducted. Finally, the feasibility of the system was confirmed via the in vitro cell experiment. Results The mode and magnitude of shear stress of the system could be controlled via either the peristaltic pump or computer, and the cellular long-term effect was also able to be detected. The calibration results of the system indicated that the level of shear stress exhibited significantly linear positive correlation with the revolution of the peristaltic pump (P<0.001). Finite element analysis demonstrated that the level of shear stress on the slide was uniformly distributed and the result of simulation was accordant with calibration. Cytoskeleton staining suggested that cellular morphology of MLO-Y4 cells was changed, and microfilament increased and arrayed along fluid flow direction. Conclusion The system is stable and reliable enough to provide different loading modes and magnitude of cellular shear stress to offer a convictive platform of the research for different cellular stress signal transduction mecha-nisms.

OBJECTIVETo investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese.

METHODSA total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression.

RESULTSIn the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P<0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls.

CONCLUSIONNo LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.

Asian Continental Ancestry Group ; genetics ; Body Mass Index ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Female ; Haplotypes ; Humans ; Logistic Models ; Low Density Lipoprotein Receptor-Related Protein-5 ; genetics ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Rural Population ; Triglycerides ; blood

Objective To explore the correlation between environmental selenium(Se) levels and cognitive ability among rural elderly population, and the effect of Se on cognitive skill of the elderly. Methods Two study sites(Zichuan district and Gaomi city of Shandong) with different environmental Se levels were selected according to rural elderly people ≥ 65 years were extracted by stratified random sampling method in each site. A retrospective survey was carried out using dietary intake questionnaire for the elderly for the past 1 year, and their daily total Se intake was calculated. Questionnaire was also used to obtain cognitive skill information in the elderly people. The Community Screening Instrument for Dementia, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test, the Indiana University (IU) Story Recall Test, the Animal Fluency Test, and the IU Token Test were applied to assess the cognitive ability. Se level in these samples was analyzed. Correlation between the Se levels of environment and those of human body were analyzed statistically. Results There were 0.163), (0.405 ± 0.086)]mg/kg and nail Se[(147.44 ± 17.42), (117.38 ± 22.48)μg/L]between the two groups (U = 31.59, 25.00, 23.67, all P ＜ 0.01 ). There were positive correlation among the nail Se, environmental Se and Se in all subjects(r = 0.51,0.46, 0.60, all P ＜ 0.01 ). The differences of the CSID total score, the CERAD Word List Learning Test, the CERAD Word List Recall Test and the IU Story Recall Test between the two sites were statistically significant(F = 2.56, 9.18, 7.48, 4.42, all P ＜ 0.05), excluding the Indiana University Story Recall Test.After eliminating possible confounding factors, the Se levels and the CSID total score, the IU Story Recall Test, the Animal Fluency Test and the IU Story Token Test had a significantly positive correlation (r = 0.076, 0.138, 0.042,0.107, P ＜ 0.05 or ＜ 0.01 ), excluding the CERAD Word List Learning Test. Conclusions This study supports the hypothesis that a life long low Se level is associated with lower cognitive ability. The cognitive abilities in the elderly population lived in areas with high environmental selenium levels are significantly higher than that of the elderly lived in areas with low environmental selenium levels.