BACKGROUNDMost of endovascular stent-graft modifications to preserve side branch must be customized according to extensive pre-operative assessment, which may not be possible in many hospitals and emergency settings. The study was to develop a novel stent-grafts system that would allow in situ "fenestration", with less reliance on preoperative imaging.

METHODSThe magnitude of pressure difference (PD) between left subclavian artery (LSA) and aortic arch were measured in 12 experimental pigs. Changes of PD before and after LSA was covered were analyzed respectively. The novel stent graft was made by multi-dimensional and multiple textiles forming technology. According to the PD measurement in pigs, we evaluated the feasibility of the stent-graft in a mock circulation system.

RESULTSIn pigs, the blood pressure of aortic arch was significantly higher than that of LSA after it was covered (P < 0.001) and PD was (42.78 ± 5.17) mmHg. After target vessel was covered and when PD between the LSA and aorta reached the magnitude measured in pigs, contrast media oozed from the cranny of graft to the LSA, which was generated by sliding and deformation of yarns of novel stent-graft.

CONCLUSIONSThe study proposes the design of pressure difference-induced perforation aortic stent-grafts system and verifies that the PD between LSA and aortic arch is high enough to allow in situ "fenestration" by stent graft made by multi-dimensional and multiple textiles forming technology.

Animals ; Aorta, Thoracic ; surgery ; Blood Pressure ; physiology ; Blood Vessel Prosthesis ; Blood Vessel Prosthesis Implantation ; Prosthesis Design ; Subclavian Artery ; Swine

Objective To explore the effects of probiotics on intestinal function, nutritional status and inflammatory response in critically ill patients with enteral nutrition (EN) support. Methods A total of 90 critically ill patients admitted to Intensive Care Unit (ICU) of the First Affiliated Hospital of Anhui Medical University from July 2016 to November 2018 were enrolled, and they were divided into a probiotics combined with EN group (27 cases) and an simple EN group (63 cases) according to random number table method. The patients in the simple EN group were treated with conventional nutrient preparations such as fresubin or fresubin energy fibre; the patients in probiotics combined with EN group were supplemented with probiotics on the basis of conventional EN support for consecutive 7 days in both groups. The changes of gastrointestinal function, nutritional index and inflammatory response index after treatment were observed in both groups. Results After treatment, the subjective global assessment (SGA) method was used to identify the gradation of the patients, it was shown that the proportion of SGA-B grade patients in simple EN group had an upward trend; while the proportion of SGA-B grade patients in probiotics combined with EN group had no significant change; and there was no significant difference in the proportion of SGA-B patients between simple EN group and probiotics combined with EN group after treatment [20.6% (13/63) vs. 7.4% (2/27),P > 0.05]. Compared with those before treatment, the levels of hemoglobin (Hb), white blood cell count (WBC), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-12) in both groups were significantly decreased, while the levels of albumin (Alb), pre-albumin (PA), total lymphocyte count (TLC) in both groups were increased after treatment, and the changes of Hb, TNF-α, IL-6 in probiotics combined with EN group were more significant than those in the simple EN group [Hb (g/L): 95.0 (78.0, 107.0) vs. 93.0 (80.0, 107.0), TNF-α (pg/L): 21.2±4.0 vs. 28.0±5.7, IL-6 (pg/L): 161.3±37.6 vs. 186.2±51.8];the differences in levels of Hb, CRP, TNF-α before and after treatment between the probiotics combined with EN group and simple EN group were statistically significant [Hb (g/L): 1.0 (-4.0, 12.0) vs. 11.0 (1.0, 20.0), CRP (mg/L): 44.3 (13.7, 57.7) vs. 7.5 (-20.1, 62.4), TNF-α (pg/L): 13.3±6.3 vs. 7.9±5.5, all P < 0.05]. There were no statistical significant differences in the other indicators between the two groups (all P > 0.05). Conclusion Probiotics can improve the gastrointestinal function and inflammatory status of critically ill patients with EN support, regretfully, in a short term, the improvement of nutritional status of such patients is not obvious, but probiotics has certain significance in preventing the risk of aggravation of malnutrition and reduction of Hb level.

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.
Anisomycin ; Apoptosis* ; Atherosclerosis ; Caspase 3 ; Cell Death ; Cholesterol ; Foam Cells* ; Humans* ; Lipoproteins ; Macrophages* ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Reactive Oxygen Species ; Receptors, Oxidized LDL ; Thioredoxins*

Objective To investigate the clinical utility of critical nutrients nutrition risk assessment (Nutric score) in neurological critical ill patients,laying the foundation for clinical nutrition support.Methods From July 2016 to March 2017,59 ICU patients with neurological critical ill in the First Affiliated Hospital of Anhui Medical University were divided into low score group (Nutric score 0-4) and high score group (Nutric score 5-9) according to Nutric score system.On the first and seventh day after ICU admission,the body mass index(BMI),triceps skinfold thickness (TSF),mid-upper ann circumference (MAC) and mid-upper ann muscle circumference (MAMC) were measured.The serum albumin(ALB),prealbumin (PA),hemoglobin (Hb) and lymphocyte (LY) were detected as nutritional indicators.And at the same time,recorded the 28-day outcomes,and made the SGA evaluation.Results At the first day admission in ICU,there were no statistically significant differences between the two groups in TSF,MAC and MAMC (all P ＞0.05).But at the seventh day,the TSF,MAC,MAMC of the high score group were (0.943 ± 0.484) cm,(24.143 ± 3.203) cm,(21.187 ± 2.625) cm,respectively,which were significantly lower than those of the low score group [(1.185 ± 0.403) cm,(26.981 ± 2.731) cm,(23.265 ± 2.327) cm],there were statistically significant differences between the two groups (t =2.090,3.672,3.223,all P ＜ 0.05).At the first day after admission,the serum levels of ALB and Hb in the high score group were (34.5 ± 7.3)g/L,(103.68 ± 13.5)g/L,which of the low score group were (39.0 ± 6.9) g/L,(122.29 ± 20.4) g/L,respectively,and there were statistically significant differences between the two groups(t =2.466,4.168,all P ＜ 0.05).And at the seventh day after admission,the serum levels of ALB,PA,Hb and Ly in the high score group were (30.6 ± 5.1) g/L,(146.0 ± 77.0) mg/L,(83.9 ± 11.9) g/L,(1.123 ± 0.535) x 109/L,respectively,which were significantly lower than those in the low score group [(35.8 ± 5.5) g/L,(209.9 ± 105.1) mg/L,(105.8 ± 19.2) g/L,(1.709 ± 1.377) x 109/L].Compared with the first day after admission,the ALB,Hb levels in the two groups at the seventh day after admission were significantly decreased (t =2.29,2.002,5.817,3.286,all P ＜0.05);the PA level in the low score group had no statistically significant difference at the seventh day after admission,but the PA level in the high score group was decreased significantly (t =2.024,P ＜ 0.05).The incidence rate of malnutrition,mortality of the high score group were 32.1％,32.1％,respectively,which were significantly higher than those in the low score group (9.7％,6.5％) (x2 =4.583,6.402,all P ＜ 0.05).Conclusion The Nutric score system can be used in the purpose of early nutrition assessment in neurological critical ill patients,and it is benefit for clinical early nutritional support.

Hypertension, a primary cause of cardiovascular and cerebrovascular events, has become a major global public health problem and caused a heavy burden of health economics on the society. In "the 20 Most Important and Most Preventable Health Problems" released by the Chinese Academy of Engineering, hypertension was ranked the second. Due to the disease complexity, many hypertension patients need to take antihypertensive drugs for life. Although significant progress has been achieved in blood pressure lowering by western medicines, the problems including adverse reactions, poor compliance due to long-term medication, and ineffective mitigation in clinical symptoms related to hypertension remain to be addressed. In the last decade, the research on traditional Chinese medicine(TCM) treatment of hypertension has received much attention and achieved remarkable progress. The TCM treatment of hypertension is the most active area of research with integrated Chinese and western medicine in China. In addition to lowering blood pressure smoothly, TCM can alleviate clinical symptoms, reverse risk factors, improve the quality of life, and protect target organs from the damage caused by hypertension. This article systematically reviews the research progress of TCM in treating hypertension in the last decade from the following four aspects: consensus on guideline, clinical trial, experimental study, and systematic review/Meta-analysis. It summarized the evidence of TCM in reducing blood pressure and clarified the mechanism of TCM in reducing blood pressure, aiming to provide a reference for the TCM diagnosis and treatment of hypertension and the development of new drugs.
Humans ; Antihypertensive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/drug therapy* ; Medicine, Chinese Traditional

Carboxylesterase 1 (CE1) is an important serine hydrolase in mammals, which involved in the hydrolysis of a variety of compounds (endogenous substrates like cholesterol and xenobiotic compounds like ester-contain drugs and pesticides). This study aimed to design and develop the fluorescent probe substrates for human carboxylesterase 1 (hCE1), on the basis of the structural features of hCE1 preferred substrates. Four carboxylic esters deriving from BODIPY-8-carboxylic acid were designed and synthesized. After then, reaction phenotyping assays and chemical inhibition assays were used to evaluate the selectivity of these four ester derivatives towards hCE1. Our results clearly demonstrated that the substrate specificity of these ester substrates towards hCE1 would be improved with the decrease of the alcohol group on BODIPY-8-carboxylesters, while BODIPY-8-carboxylesters with small alcohol groups including methyl (BCM) and ethyl (BCE) esters could serve as the ideal probe substrates for hCE1. Given that BCM exhibit rapid hydrolytic rate in hCE1, we further investigate the enzymatic kinetics of this fluorescent probe substrate in both human liver microsomes (HLM) and recombinant hCE1, as well as to explore its potential application in high-throughput screening of hCE1 inhibitors by using HLM as enzyme source. The results showed that the kinetic behaviors and the affinity of BCM in HLM is much closed to those in recombinant hCE1, implying that hCE1 played the key roles in BCM hydrolysis in HLM. Furthermore, the inhibition study demonstrated that BCM could be used for rapid screening and characterization of hCE1 inhibitors, by using HLM to replace recombinant hCE1 as enzyme source.

Interleukin-1 receptor associated kinase 4 (IRAK-4), acting as a serine threonine kinase, is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway. Studies have found that IRAK-4 has a hand in many signal pathways, involving the inflammatory response of human joints, intestines, liver and nervous system, as well as other autoimmune diseases. It is also one of the causes of drug resistance of some cancer cells. Therefore, IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer. The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness, enrich the clinical treatment of inflammatory and cancer diseases finally. This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4 signaling pathway according to structures of the compounds, in order to provide assistances and references for the research and development of related drugs.

Objective:To evaluate the efficacy and long-term effect of functional electrical stimulation (FES) on cerebral palsy. Methods:Literature retrieval was carried out in the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine Disc (CBM), CNKI, Wanfang Database and VIP. The time limit was from the establishment of these databases to March 26th, 2020. According to the inclusion and exclusion criteria, randomized controlled trials about FES for children with cerebral palsy were included. At least two evaluators extracted the data independently and used Cochrane 5.1.0 bias risk assessment tool to evaluate the quality of included studies. The data was analyzed with Review Manager 5.3 software. Results:A total of eleven studies with 513 children were included. The Gross Motor Function Measure-88 (GMFM-88) D/E scores (MD = 8.14, 95%CI 6.26 to 10.02, P < 0.001), GMFM-88 B score (MD = 8.77, 95%CI 4.00 to 13.53, P < 0.001), modified Ashworth Scale (MAS) score (MD = -1.05, 95%CI -1.25 to -0.84, P < 0.001), Kyphosis angle (MD = -10.67, 95%CI -12.21 to -9.13, P < 0.001), Cobb's angle (MD = -2.66, 95%CI -3.38 to -1.93, P < 0.001), step length (MD = 3.35, 95%CI 1.81 to 4.90, P < 0.001), walking speed (MD = 0.09, 95%CI 0.05 to 0.14, P < 0.001) and GMFM score at six weeks follow-up (MD = 4.84, 95%CI 1.90 to 7.77, P = 0.001) were better in FES group than in the control group. There was no significant difference in MAS score between two groups after six weeks of follow-up (MD = 0.04, 95%CI -0.30 to 0.37, P = 0.84). Conclusion:FES could improve the lower-limb and trunk function of children with cerebral palsy, however, the long-term effect of relieving muscle spasm was not significant.

Objective : To explore the relationship between geriatric nutritional risk index( GNRI) and perioperative nutritional status，postoperative recovery and complications in elderly patients with gastric cancer． Methods : In this retrospective study，212 elderly patients ( aged ≥60 years ) with gastric cancer who underwent gastrectomy were recruited．GNRI was used to retrospectively assess the patients' preoperative nutritional status ，and analyze the relationship between GNRI and perioperative nutritional status，postoperative recovery and complications．The ROC curve was applied to explore the value of GNRI in predicting postoperative complications. Results : The inci- dence of preoperative nutritional risk in elderly patients undergoing gastric cancer surgery was 45. 07%．Compared with the patients whose GNRI＞98 points，the patients whose GNRI&le;98 points had different degrees of decrease in serum total protein，albumin，prealbumin，hemoglobin and lymphocyte counts before surgery，day 1 and day 5－8 after surgery (P ＜0. 05) ．The patients whose GNRI ＜92 points had longer postoperative hospital stay than those with GNRI＞98 points (P＜0. 05) ．With the decrease of GNRI scores，the incidence of complications showed an upward trend(P＜0. 001) ．The multivariate analysis of the relationship between GNRI and postoperative complica- tions showed that TNM staging of III －IV and GNRI ＜92 points were independent risk factors for complications. GNRI had a good predictive value for the occurrence of complications (AUC = 0. 639，95% CI : 0. 570－0. 703，P = 0. 001，Cut-off value : 92. 21) ． Conclusion GNRI can be used for preoperative nutritional assessment for eld- erly gastric cancer patients．Patients with GNRI＜92. 21 points should be actively given nutritional therapy to im- prove perioperative nutritional status，speed up postoperative recovery，and reduce the occurrence of complications.