Advances in cGAS-STING pathway and its inhibitors in immune and inflammatory diseases / 中国药理学通报

The cGAS-STING signaling pathway is one of the main pathways of immune defense against many types of pathogens. cGAS catalyzes the production of the second messenger cGAMP (cyclic GMP-tVMP) by recognizing plasma DNA and cGAMP subsequently binds to the interferon gene stimulating factor (STING). The pathway induces the production of type I interferon (IFN-I) and activates the innate immune system. The activation of the cGAS-STI]NG pathway could facilitate self-protection,thus STI]NG agonists for tumor immunotherapy have attracted much attention in recent years,and several drug candidates have been in clinical trials. Meanwhile,aberrant activation of cGAS-STI]NG could lead to autoimmune diseases and has attracted extensive interest in developing its inhibitors. This paper summarizes the mechanism and regulatory sites of the cGAS-STI]NG pathway,and outlines the research progress of cGAS-STING pathway-related immune and inflammatory diseases and its inhibitors.

Effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo / 药学实践杂志

Objective To establish a UPLC-MS/MS method for the determination of dexmedetomidine in human plasma and investigate the effect of obstructive jaundice on pharmacokinetics of dexmedetomidine in vivo. Methods Samples were obtained by liquid-liquid extraction. Agilent Eclipse Plus C18 column was used for chromatograph with methanol and 0.1% formic acid-water solution as mobile phase. Flow rate was 0.2 ml/min. The column temperature was 35 ℃, and the MS detection was selected in MRM mode. Results The calibration curves of dexmedetomidine showed good linearity in the ranges of 0.01−10.00 ng/ml. The results of intra and inter-day precisions were both within 15%. The recovery rate was 85.5%−93.1%. Matrix effect was 91.2%−95.6%. Samples remained stable during analysis. Compared with the control group, cmax、AUC(0−t)、AUC(0−∞) and Vz of dexmedetomidine in the patients with obstructive jaundice were increased by 63.4%, 78.9, 66.4%, 82.5%, respectively (P<0.01). CLz was decreased by 42.1%. Conclusion This method is accurate, sensitive and reproducible. It is suitable for dexmedetomidine assay in human plasma. The elimination rate of dexmedetomidine is slower in obstructive jaundice.

Randomized controlled study on AMIE methods for treatment of movement disorder in the child of convulsive cerebral palsy / 中国针灸

<p><b>OBJECTIVE</b>To observe the curative effect of AMIE methods on movement disorder in the child of convulsive cerebral palsy (CP).</p><p><b>METHODS</b>One hundred and twenty cases of CP children were randomly divided into an integration treatment group and a rehabilitation group, 60 cases in each group. The integration treatment group were treated with acupuncture (A), massage (M), injection (I) and five animal exercise (E) therapies for 60 times, and the rehabilitation group were treated with Bobath training therapy for 60 times. Scores for movement function before and after treatment were used for assessment of therapeutic effect. Twelve months later, understand whether or not the children can walk on ones own.</p><p><b>RESULTS</b>The total effective rate was 76.70% in the integration treatment group and 58.4% in the rehabilitation group, with no significant difference between the two groups (P > 0.05); there were significant differences in the two groups in differences of movement function scores before and after treatment (P < 0.05). After one year's follow-up survey, 36 children could walk by themselves in the integration treatment group, which were significantly more than 24 children in the rehabilitation group (P < 0.05).</p><p><b>CONCLUSION</b>AMIE methods is effective for treatment of movement disorder in the child of convulsive cerebral palsy, and the short-term therapeutic effect is same as that of Bobath training method and the long-term therapeutic effect is better than that of Bobath training method.</p>

The testing and verification for interconnect faults based on cluster FPGA configuration / 中国医疗器械杂志

We have developed a hierarchical approach to define a set of FPGA configurations to solve the interconnect testing problem. This technique enables the detection, testing and verification of bridging faults involving intracluster interconnect and extracluster interconnect to be done easily.

Design and synthesis of quinoxaline derivatives and their antitumor activities / 药学学报

<p><b>AIM</b>To design and synthesize novel quinoxaline derivatives as antitumor agents.</p><p><b>METHODS</b>Using 4-chloro-2-nitroaniline as a starting compound, followed by substitution, reductive cyclization, oxidation, and chlorination, to give the key intermediate 2,7-dichloroquinoxaline (7), which reacted with different phenolic compounds to afford quinoxaline derivatives.</p><p><b>RESULTS</b>The structures of the target molecules were characterized by elemental analysis, 1H NMR, MS, and IR.</p><p><b>CONCLUSION</b>At concentration of 1 x 10(-4) mol x L(-1), some of the derivatives showed equal antitumor activities to XK469.</p>

Synthesis and pharmacology of 8-amino-3-(tetrahydro-2-furanyl)methyl benzomorphan / 药学学报

<p><b>AIM</b>To design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.</p><p><b>METHODS</b>Target compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.</p><p><b>RESULTS</b>Both 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.</p><p><b>CONCLUSION</b>The relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.</p>