Objective To detect different activated patterns of heavy smokers in different states as well as between smokers and non-smokers. Methods Seventeen subjects including 12 heavy smokers and 5 non-smokers (controls) were examined with functional magnetic resonance imaging (fMRI) performing smoking-related olfactory cue tasks. The data were processed with SPM2. These different patterns were compared between the two groups. Results When smokers were exposed to the smoking olfactory cue in the abstinent state, activation was found on the left superior frontal gyrus (BA8, 9, 10, 11), left middle frontal gyrus (BA8, 10, 11, 46), left inferior frontal gyrus (BA9), left medial frontal gyrus (BA6, 8, 10,11), right superior frontal gyrus (BA10), right middle frontal gyrus (BA8, 9), right inferior frontal gyrus (BA45, 47), right medial frontal gyrus (BA9, 11), left callosal gyrus (BA24, 31), right callosal gyrus (BA24, 37), right middle temporal gyrus (BA21) and both sides of the thalamus and cerebellum. When smokers were exposed to the smoking olfactory cue in the satiated state, activation could be found on both sides of the prefrontal lobe and cerebellar hemisphere, while there was no activation on the other brain regions. No activation was found on the whole brain of the nonsmokers,except for a little small volume active points appeared in individual subjects, possibly caused by the picture noise. Conclusion The Limbic system (cingulate cortex, thalamus) and the prefrontal lobe play an important role in the cue-induced smoking craving approved from the new perspective of the olfactory. It is feasible to research smoking addicts' brain activation and the role of neural mechanisms using olfactory stimulation with clinical 1.5T MRI equipment.

Objective To explore the normal range of the caudate nucleus' volume in Chinese adults of the Han nationality and provide morphological data for the construction of database for Chinese Standard Brain.Methods This was a clinical multi-center study.One thousand Chinese healthy volunteers (age range=18 to 70)recruited from 16 hospitals were divided into 5 groups,i.e.,Group A(age range=18 to 30),B(age range=31 to 40),C(age range=41 to 50),D(age range=51 to 60),and E(age range=61 to 70).Each group contained 100 males and 100 females.All of the volunteers were scanned by MR using T1 weighted three-dimensional magnetization prepared rapid acquisition gradient echo sequence.The volume of eaudate was measured manually using 3D volume analysis software.The difierence of volumes of the eaudate between male and female were analyzed by independent sample t-test,and among age groups by ANOVA.Pearson's correlation coefficient was used to characterize the relationship between volunles and age.The differences of measurements between left and right caudate nucleus were analyzed by paired t test.Results (1)rnle mean volume of bilateral caudate nucleus in healthy Chinese adults wag(10.973±1.647)cm3.The mean volume of the the male's left and right caudate nucleus were(5.656±0.860)and (5.671±0.855)cm3 respectively,no significant differences were found between the volume of left and right eaudate nucleus(t=1.230.P>0.05).The mean volume of the the female's left and right eaudate nucleus were(5.287±0.774)and(5.331±0.766)cm3 respectively,and the right's wag larger than the left's with significant differences(t=3.999,P<0.01);(2)Pearson correlation analysis showed a significant negative correlation between the nucleus volume and age(male and female's,left and fight)(r=-0.561,-0.568,-0.548,-0.552,P<0.05).Conclusion With high-resolution MRI and 3D volumetric analytic software(Midob),the volume of the caudate nucleus can be accurately measured,so as to provide the basic data for establishing Chinese adults' standard digital brain.and provide nomad control standards for caudate nucleus volume-related diseases.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.