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OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.
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Objective:To construct a risk prediction score for the needs of coronary care unit (CCU) care in stable condition acute ST-segment elevation myocardial infarction (STEMI) patients who receive percutaneous coronary intervention (PCI) treatment.Methods:The clinical data of 805 STEMI patients who accepted PCI in the First Hospital of Jilin University from November 2017 to October 2018 were retrospectively analyzed. Among the patients, 654 patients from November 2017 to July 2018 were served as the modeling group, the patients with needs of CCU had 125 cases, and the patients without needs of CCU had 529 cases; 151 patients from August 2018 to October 2018 were served as the validation group, the patients with needs of CCU had 28 cases, and the patients without needs of CCU had 123 cases. Binary Logistic regression analysis was used to establish the risk prediction model and determine the score standards. The critical value was determined according to the best Youden index of receiver operating characteristic (ROC) curve.Results:Among 805 patients with STEMI, 153 cases (19.01%) had the needs of CCU, and the most common reason was pump failure (heart failure and cardiogenic shock, 113 cases). In the modeling group, age (60 to 74 years old, OR = 1.513, 95% CI 0.945 to 2.424, P = 0.085; ≥75 years old, OR = 2.740, 95% CI 1.371 to 5.478, P = 0.004), total ischemic time>4 h ( OR = 1.701, 95% CI 1.022 to 2.831, P = 0.041), admission shock index ≥0.8 ( OR = 1.910, 95% CI 1.178 to 3.099, P = 0.009), multi-vessel disease ( OR = 2.090, 95% CI 1.272 to 3.432, P = 0.004), preoperative diseased vessels thrombolysis in myocardial ischemia (TIMI) blood flow grade 0 ( OR = 2.099, 95% CI 1.313 to 3.353, P = 0.002), acute anterior myocardial infarction ( OR = 3.696, 95% CI 2.347 to 5.819, P<0.001) and previous history of stroke ( OR = 3.927, 95% CI 2.057 to 7.500, P<0.001) were independent risk factors for CCU needs in STEMI patients undergoing PCI. The scoring criteria were as followings: age<60 years old was given 0 score, 60 to 74 years old 1 score, ≥75 years old 2 score; total ischemic time>4 h in 1 score, admission shock index ≥0.8 2 scores, multi-vessel disease 2 scores, preoperative diseased vessels TIMI blood flow grade 0 2 scores, acute anterior myocardial infarction 3 scores, previous history of stroke 3 scores, and the total score was 15 scores. The patients with 0 to 6 scores were low-risk, and the patients with 7 to 15 scores were high-risk. ROC curve analysis result showed that, in modeling group, the area under curve (AUC) of risk prediction score for predicting the needs of CCU in STEMI patients was 0.740 (95% CI 0.692 to 0.788, P = 0.580); in validation group, the AUC of risk prediction score for predicting the needs of CCU in STEMI patients was 0.755 (95% CI 0.658 to 0.853, P = 0.755). Conclusions:A predictive risk score based on seven risk factors such as age, total ischemic time, admission shock index, multi-vessel disease, preoperative diseased vessels TIMI blood flow grade, acute anterior myocardial infarction and previous history of stroke is constructed in order to predict the needs of CCU in STEMI patients with stable condition who receive PCI treatment. It can be used to help doctors to identify high-risk patients before the admission to CCU, thus providing simple and practical clinical tool for rational allocation of limited CCU resources.
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Objective To explore the expression of glutathione-S-transferase-π(GST-π),P-glycoprotein (P-gp),topoisomerase Ⅱ (Topo Ⅱ) and thymidylate synthase (TS) in gastric adenocarcinoma tissues and the clinical significance.Methods Envision method of immunohistochemistry was used to detect the expression of GST-π,P-gp,Topo Ⅱ and TS in sample of 64 gastric adenocarcinoma tissues and 12 normal gastric mucosas,and their corresponding clinical data were comprehensive analyzed.Results The expression positive rates of GST-π,P-gp,Topo Ⅱand TS were respectively 76.6 ％(49/64),64.1％ (41/64),84.4 ％ (50/64) and 53.1％ (34/64),that were all higher than in gastric mucosa [8.3 ％ (1/12),8.3 ％(1/12),16.7 ％ (2/12),0],the differences were statistically significant respectively (P ＜ 0.01).Their positive expression rates were closely relevant to the degree of differentiation (P ＜ 0.05),but not to the patients' gender,age,tumour size,clinical staging,invasive depth and lymph node metastasis (P ＞ 0.05).The expressions of GST-π,P-gp and TS in high and middle differentiation adenocarcinoma were high.er than in low differentiation,but the expression of Topo Ⅱ in high and middle differentiation adenocarcinoma was lower than in low differentiation (P ＜ 0.05).Conclusion GST-π,P-gp,Topo Ⅱ and TS are over-expressed in gastric adenocarcinoma,which is related to the multidrug resistance of gastric adenocarcinoma.The joint detection of the expression of GST-π,P-gp,Topo Ⅱ and TS in gastric adenocarcinoma can be looked as an important symbol for guiding its chemotherapy drug and prognosis.