Efficacy of Zhenjingdingzhi decoction in treating insomnia with Qi-deficiency of heart and gallbladder: a randomized, double-blind, controlled trial

AbstractObjectiveTo evaluate the clinical efficacy of Zhenjingdingzhi decoction in treating insomnia with Qi-deficiency of heart and gallbladder.MethodsWe conducted a double-blind, randomized, controlled trial involving 100 patients with insomnia of Qi-deficiency of heart and gallbladder. Patients were randomly divided into the treatment group (n = 50) and the control group (n = 50) according to a random number table. The treatment group was given Zhenjingdingzhi decoction, while the control group was treated with Suanzaoren decoction. the pharmacological treatment lasted for 8 weeks. The clinical efficacy was assessed by using Spiegel scale, Pittsburgh sleep quality index (PSQI) and Traditional Chinese Medicine (TCM) syndrome scores.ResultsComparing Spiegel scores between the two groups at 4 and 8 weeks, the differences in curative effect between the two groups were both significant (both P < 0.05). The total effective rate was 46% in the treatment group and 27.7% in the control group at 4 weeks, and 80% and 53.2% at 8 weeks, respectively; After 8 weeks, PSQI scores showed that the total effective rates differed significantly between the two groups (P < 0.01): 84% in the treatment group and 59.6% in the control group; In improving sleep quality and sleep duration, the curative effect of the treatment group was better than that of the control group (P < 0.05). TCM syndrome, especially insomnia and palpitation, was improved better in the treatment group after 8 weeks as compared to that in the control group (P < 0.05). The total effective rate of the two groups was 84% and 66%, respectively.ConclusionZhenjingdingzhi decoction is effective and safe for the treatment of insomnia with Qi-deficiency of heart and gallbladder, especially for improving sleep quality and sleep duration

Analysis of spherical indentation of materials with plastically graded surface layer

AbstractIn the present work, a comprehensive parametric study for establishing contact mechanics of instrumented normal spherical indentation on homogeneous materials and materials with plastically graded surface layer (PGSL) was undertaken by dimensional analysis and finite element modeling. The spherical indentation response for homogeneous materials can be described only by two dimensionless parameters: strain hardening exponent and a unified parameter that can describe effects of both the normalized yield strength and the normalized indentation depth. The influences of these two parameters were investigated for a wide range of engineering materials, and the results may be used as an estimate of loading response and pile-up/sink-in behavior when the material properties are known. In the materials with PGSL, a linear gradient in yield strength, and no variation in elastic modulus and strain hardening exponent were explored. The indentation response of the materials with PGSL can be described only by three dimensionless parameters: the normalized indentation depth, the dimensionless strength gradient parameter, and the normalized PGSL thickness. The effects of these three parameters were studied systematically. The normalized pile-up/sink-in parameter is found to be an increasing function of the strength gradient parameter. The normalized pile-up/sink-in parameter increases (decreases) with increasing PGSL thickness for a fixed positive (negative) gradient case at large indentation depth. The results also indicate that the materials with positive PGSL can bear more loads and have significantly more resistance to contact crack formation

BaySize: Bayesian Sample Size Planning for Phase I Dose-Finding Trials

We propose BaySize, a sample size calculator for phase I clinical trials using Bayesian models. BaySize applies the concept of effect size in dose finding, assuming the MTD is defined based on an equivalence interval. Leveraging a decision framework that involves composite hypotheses, BaySize utilizes two prior distributions, the fitting prior (for model fitting) and sampling prior (for data generation), to conduct sample size calculation under desirable statistical power. Look-up tables are generated to facilitate practical applications. To our knowledge, BaySize is the first sample size tool that can be applied to a broad range of phase I trial designs

The role of AMPK/mTOR/S6K1 signaling axis in mediating the physiological process of exercise-induced insulin sensitization in skeletal muscle of C57BL/6 mice

AbstractThe crosstalk between mTORC1/S6K1 signaling and AMPK is emerging as a powerful and highly regulated way to gauge cellular energy and nutrient content. The aim of the current study was to determine the mechanism by which exercise training reverses lipid-induced insulin resistance and the role of AMPK/mTOR/S6K1 signaling axis in mediating this response in skeletal muscle. Our results showed that high-fat feeding resulted in decreased glucose tolerance, which was associated with decreased Akt expression and increased intramuscular triglyceride deposition in the skeletal muscle of C57BL/6 mice. Impairments in lipid metabolism were accompanied by increased total protein and phosphorylation of S6K1, SREBP-1c cleavage, and decreased AMPK phosphorylation. Exercise training reversed these impairments, resulting in improved serum lipid profiles and glucose tolerance. C2C12 myotubes were exposed to palmitate, resulting in an increased insulin-dependent Akt Ser473 phosphorylation, associated with a significant increase in the level of phosphorylation of S6K1 on T389. All these changes were reversed by activation of AMPK. Consistent with this, inhibition of AMPK by compound C induced an enhanced phosphorylation of both S6K1 and Akt, and silencing of S6K1 with siRNA showed no effect on Akt phosphorylation in both the absence and presence of palmitate cultured myotubes. In addition, compound C led to an elevated SREBP-1c cleavage but was blocked by S6K1 siRNA. In summary, exercise training inhibits SREBP-1c cleavage through AMPK/mTOR/S6K1 signaling, resulting in decreased intramyocellular lipid accumulation. Our results provide new insights into the mechanism by which AMPK/mTOR/S6K1 signaling axis mediates the physiological process of exercise-induced insulin sensitization