Objective To determine the effects of treadmill training on the structure of hippocampal myelin and cognitive function in rats exposed to acute plateau hypoxia.Methods With 30 SPF-grade female SD rats (aged 6-8 weeks,weighing 200-220 g),6 of them were used for observation of myelin structure after injury,and the remaining 24 rats were randomly divided into control group,hypobaric hypoxia group and treadmill training group (n=8).The rats in above experimental groups were placed in a low-pressure oxygen chamber at an altitude of 6000 m for 7 consecutive days,and the rats of the control group were placed in the confined chamber for the same period without hypoxia.Then,the rats of the treadmill training group received a 4-week treadmill training scheme since the day after hypoxia.Finally,all the rats were tested for cognitive function with open field test (OFT)and Morris water maze (MWM).Transmission electron microscopy (TEM) was used to observe the changes of demyelination in the hippocampus. The expression of oligodendrocyte transcription factor 2 (Olig2)and myelin basic protein (MBP )in the hippocampal CA1 and CA3 regions was measured by immunofluorescence staining and Western blotting.Results Behavioral tests showed that the number into the central area,total distance,distance ratio in OFT and the number of platform crossings and distance to the target area in MWM were reduced in the hypobaric hypoxia group than the control group (P<0.05 ),while these indexes were increased in the treadmill training group than in the hypobaric hypoxia group (P<0.05).Immunofluorescence staining indicated that the number of Olig2 positive cells per unit area and the mean fluorescence intensity of MBP in the CA1 and CA3 regions were significantly lessen in the hypobaric hypoxia group than the control group (P<0.05 ),while these indicators were higher in the treadmill training group than the hypobaric hypoxia group (P<0.05 ).Western blotting displayed that the expression levels of Olig2 and MBP in the hippocampus were obviously lower in the hypobaric hypoxia group than the control group (P<0.01 ),while the levels were increased in the treadmill training group than the hypobaric hypoxia group (P<0.01 ).Conclusion Treadmill training promotes the number of the oligodendrocyte spectrum cells in CA1 and CA3 regions,enhances the expression of myelin-related proteins and improves myelin repair in hippocampus of hypobaric hypoxia rats,and thereby ameliorates hypoxia-induced anxiety-like behaviors and memory dysfunction.

Purpose/Significance To analyze the technical situation of patent owners in the field of clinical decision support system(CDSS)in China as a whole,so as to provide references for CDSS related technical research.Method/Process Firstly,the CDSS patent data are analyzed from the aspects of application trend,patent disclosure,technology field distribution,etc.,then the patentees are di-vided into different categories,and their technical concerns are analyzed by word frequency and interword vector.Finally,the technology correlation and patent exclusives are analyzed based on the active patentees.Result/Conclusion The number of CDSS patent disclosure shows an overall increasing trend.This field has not formed a technological monopoly in China.Government departments and research in-stitutions should pay attention to the possible financial risks.

The CRISPR/Cas is an immune defense system acquired by prokaryotes to resist the invasion of foreign genetic materials during their evolutionary process.In recent years,it has been developed into an efficient tool for genome editing,gene regulation and molecular diagnosis.Its programmable targeting mechanism has opened the door to use this system for genome manipulation and allows for dynamic regu-lation and control of gene expression within its activity range.As one of the most flexible and cost-effec-tive techniques among existing gene modification methods,it has been widely applied in clinical disease treatment,industrial and agricultural production,sustainable dye development,chemical processing and many other fields.With the continuous investigation and exploration of the CRISPR/Cas system,a large number of studies have been reported on the engineering modification and optimization approaches of gRNA,including changing the length of the spacer region,regulating the structure of constant and varia-ble sequence parts,adding extra functional sequences through the end or middle extension,and chemical synthesis modifications,in order to reduce off-target and mutation rates,improve the efficiency of the CRISPR system,and fully stimulate the potential of CRISPR gene manipulation tools in biomedical fields.Based on this,this review will introduce the latest progress in gRNA engineering design strategies and application research of CRISPR/Cas9 and CRISPR/Cas12 systems,analyze and discuss the opportu-nities and challenges in the current gRNA engineering technology,aiming to provide ideas and reference directions for obtaining gRNAs with better performance,thereby effectively improving the ability to probe the human genomes using the CRISPR/Cas system and bringing more possibilities to programmable biology.

Objective To explore the effect of KRT6A on radiation resistance in non-small cell lung cancer A549 cells and its mecha-nism of action.Methods The radiation-resistant A549(A549-RR)cells were induced and established.The successful construction of the cells were performed using the Cell Counting Kit 8(CCK-8)method,plate clone-formation experiments,and flow cytometry.Western blot-ting was used to detect the expression of KRT6A in A549 and A549-RR cells.A549-RR cells were divided into the sh-NC,sh-KRT6A,sh-KRT6A+ov-NC,and sh-KRT6A+ov-β-catenin groups.The expression of KRT6A;β-catenin;and epithelial-mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin,vimentin,Snail,and Slug were detected by Western blotting.The CCK-8 assay,plate clone-formation experiments,and flow cytometry were used to determine the radiation resistance of the cells.Results A549-RR cells were successfully cultured.and KRT6A expression was upregulated in A549-RR cells compared to A549 cells.Knocking down KRT6A reduced the proliferative activity and clonogenic ability of A549-RR cells;increased the apoptosis rate;upregulated the expression of E-cadherin protein;and downregulated N-cadherin,vimentin,Snail,Slug,andβ-catenin protein expression.Overexpression ofβ-catenin reversed the inhibitory effect of KRT6A knockdown on EMT and radiation resistance in A549-RR cells.Conclusion KRT6A is upregu-lated in A549-RR cells,and knocking down KRT6A reduces the radiation resistance of A549-RR cells,which may be related to the induc-tion of EMT by activation of the Wnt/βcatenin signaling pathway.

Objective:To compare the influence of single and staged percutaneous coronary intervention (PCI) on long-term prognosis in patients with multi-vessel coronary artery disease.Methods:Using prospective research methods, 1 832 patients with multi-vessel coronary artery disease from January to December 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences were selected. According to the time of PCI, the patients were divided into single PCI group (1 218 cases) and staged PCI group (614 cases). The patients were followed up for 2 years, the primary endpoint was major cardiovascular and cerebrovascular event (MACCE), including target vessel-related myocardial infarction (TV-MI), target vessel-related revascularization (TVR), cardiogenic death and stroke, and the secondary endpoint was stent thrombosis. The propensity score matching (PSM) was applied to balance the discrepancies between 2 groups, and the baseline and follow-up data were compared. The Kaplan-Meier survival curves were drawn to evaluate the survival rates events; multifactor Cox proportional risk regression was used to analyze whether staged PCI was an independent risk factor for the endpoint events.Results:The in-hospital stay, duration of procedure and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score in single PCI group were significantly lower than those in staged PCI group: (5.54±3.09) d vs. (9.50±4.06) d, (43.12±28.55) min vs. (79.54±44.35) min, (14.04±7.63) scores vs. (18.51±7.79) scores, and there were statistical differences ( P<0.01); there were no statistical difference in complete revascularization rate and SYNTAX score after PCI between 2 groups ( P>0.05). Based on 2-year follow-up, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.5% (6/1 218) and 2.0% (12/614) vs. 0.4% (5/1 218), and there were statistical differences ( P<0.01). Kaplan-Meier survival curves analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were better than those in staged PCI group (99.5% vs. 97.9% and 99.6% vs. 98.0%, P<0.01). Multifactor Cox proportional risk regression analysis results showed that staged PCI was an independent risk factor for stent thrombosis ( HR = 3.91, 95% CI 1.25 to 12.18, P = 0.019). After PSM, the incidences of TV-MI and stent thrombosis in staged PCI group were significantly higher than those in single PCI group: 2.1% (13/614) vs. 0.7% (4/614) and 2.0% (12/614) vs. 0.5% (3/614), and there were statistical differences ( P<0.05); Kaplan-Meier survival curve analysis results showed that the event-free survival rates of TV-MI and stent thrombosis in single PCI group were significantly higher than those in staged PCI group: (99.3% vs. 97.9% and 99.5% vs. 98.0%, P<0.05); multifactor Cox proportional risk regression analysis results showed that staged PCI was not an independent risk factor of stent thrombosis ( HR = 2.29, 95% CI 0.58 to 9.00, P = 0.234). Both before and after PSM, there were no evidences for interaction between the type of angina pectoris and staged PCI ( P>0.05). Conclusions:Although a seemingly increase exists in the incidence of TV-MI and stent thrombosis in the staged PCI group, staged PCI is an independent risk factor neither for MACCE and its components, nor for stent thrombosis. In addition single PCI reduces the in-hospital days and duration of PCI procedure, which may be a relatively reasonable approach to clinical practice.

During the pathogensis of rheumatoid arthritis (RA), activated RA fibroblast-like synoviocytes (RA-FLSs) combines similar proliferative features as tumor and inflammatory features as osteoarthritis, which eventually leads to joint erosion. Therefore, it is imperative to research and develop new compounds, which can effectively inhibit abnormal activation of RA-FLSs and retard RA progression. Neohesperidin (Neo) is a major active component of flavonoid compounds with anti-inflammation and anti-oxidant properties. In this study, the anti-inflammation, anti-migration, anti-invasion, anti-oxidant and apoptosis-induced effects of Neo on RA-FLSs were explored to investigate the underlying mechanism. The results suggested that Neo decreased the levels of interleukin IL-1β, IL-6, IL-8, TNF-α, MMP-3, MMP-9 and MMP-13 in FLSs. Moreover, Neo blocked the activation of the MAPK signaling pathway. Furthermore, treatment with Neo induced the apoptosis of FLSs, and inhibited the migration of FLSs. It was also found that Neo reduced the accumulation of reactive oxygen species (ROS) induced by TNF-α. Taken together, our results highlighted that Neo may act as a potential and promising therapeutic drug for the management of RA.
Arthritis, Rheumatoid/drug therapy* ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Fibroblasts ; Hesperidin/analogs & derivatives* ; Humans ; Synoviocytes ; Tumor Necrosis Factor-alpha/genetics*

Betacoronavirus ; Communicable Disease Control ; organization & administration ; Coronavirus Infections ; epidemiology ; prevention & control ; transmission ; Disaster Planning ; organization & administration ; Humans ; Nuclear Medicine ; organization & administration ; Pandemics ; prevention & control ; Pneumonia, Viral ; epidemiology ; prevention & control ; transmission ; Singapore

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
Aged ; China ; epidemiology ; Chlorides ; blood ; Coronary Artery Disease ; blood ; diagnosis ; mortality ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Sodium ; blood

Objective: To investigate the effects of Wilms’tumor 1-associating protein (WTAP) on proliferation, migration and invasion of human lung adenocarcinoma A549 cells. Methods: Human lung adenocarcinoma cell line A549 and HEK293T cells were chosen for this study. Two sets of shWTAP interference sequences were designed to construct lentiviral vector plasmid. Human lung adenocarcinomaA549 cells were infected after packaging lentivirus in HEK293T cells, and the control group was transfected with 277 empty vector plasmid. The mRNAand protein expression levels of WTAPinA549 cells were detected by qPCR and WB. Changes in proliferation, migration and invasion of A549 cells were detected by BrdU assay, cell scratch healing assay and Transwell assay, respectively. Results: Two plasmids, shWTAP-1 and shWTAP-2, were successfully constructed. Compared with the control group, the mRNA and protein expression levels of WTAP were significantly down-regulated inA549 cells with WTAP knockdown (both P<0.05), and the proliferation, migration and invasion ability of cells were significantly decreased (all P<0.05). Conclusion: Knockdown of WTAP significantly inhibited the proliferation, migration and invasion of human lung adenocarcinoma A549 cells. The expression of WTAP gene is associated with the occurrence and development of lung adenocarcinoma. WTAP may be a potential target for the diagnosis and treatment of lung adenocarcinoma.

Objective To investigate the impact of adopting different dose grid resolution during volumetric modulated arc therapy (VMAT) planning on COMPASS pass rate.Methods A total of 10 patients with cervical cancer were enrolled.Four types of VMAT plans (plan1,plan2,plan3,plan4) were designed for each patient,with dose grid resolution of 0.2 cm × 0.2 cm × 0.2 cm,0.3 cm × 0.3 cm ×0.3 cm,0.4 cm ×0.4 cm ×0.4 cm and 0.5 cm ×0.5 cm ×0.5 cm,respectively.The plans were exported to Linac and conducted,then measured by COMPASS.The discrepancies were analyzed,which were obtained by comparing reconstructed dose from COMPASS and dose from TPS optimization.Results For tumor volume,the mean value of Dmean and D95 were ＜ 0.5％ and ＜ 1.3％ respectively,and the standard deviation were both ＜ 1.0％.For organs at risk (OAR),the max discrepancies were Dmean of femur with-6.7％,-7.0％,-8.0％,-5.8％,and V35 of rectum with 4.9％,-6.3％,-6.1％,-5.7％ in four types of VMAT plans.The γ (3％,3 am) rate of tumor volume was ＞95％ with standard deviation ＜ 2.5％,with no statistically significant difference among the four types of plans (P ＞0.05).The γ (3％,3 mm) rate of OARs were ＞ 98％ except femur (＞ 95％),and the standard deviations were within 1.9％-6.1％,with no statistical significance (P ＞0.05).The average γ rate of tumor volume and OARs were ＜ 0.4 except femur (＞ 0.4),with no statistically significant difference among four types of VMAT plans (P ＞ 0.05).Conclusions COMPASS pass rate was not influenced by the dose grid resolution between 0.2 ～ 0.5 cm for VMAT plan.