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1.  Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies 
PLoS ONE  2013;8(7):e68621.
The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.
doi:10.1371/journal.pone.0068621
PMCID: PMC3712920  PMID: 23874692
2.  Structural Modulation of Brain Development by Oxygen: Evidence on Adolescents Migrating from High Altitude to Sea Level Environment 
PLoS ONE  2013;8(7):e67803.
The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15–18 years), who were born and raised in Qinghai-Tibetan Plateau (2900–4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.
doi:10.1371/journal.pone.0067803
PMCID: PMC3706444  PMID: 23874449
3.  Expression of Rab25 correlates with the invasion and metastasis of gastric cancer 
The objective of this study was to determine the expression of the important vesicle trafficking-regulating factor Rab25 in human gastric cancer tissues, to analyze the correlation between Rab25 protein expression with gastric cancer occurrence and development, and to discuss the correlation of Rab25 protein expression with gastric cancer cell metastasis. The overall aim was to provide experimental evidence that can be used to design future biological treatments of human gastric cancer. Human gastric cancer tissue and the adjacent normal gastric tissue were surgically removed, and immunohistochemistry and Western blotting were used to detect Rab25 protein expression. The correlation between Rab25 protein expression with the development and pathological characteristics of gastric cancer was analyzed. Using RNAi, Rab25 expression was reduced in the gastric cancer cell line MGC80-3, and the changes in MGC80-3 cell invasiveness were then monitored. Immunohistochemistry showed that the Rab25 protein expression rates were 78.21% and 23.08% in gastric carcinoma and the adjacent normal gastric tissue, respectively. Immunohistochemistry and Western blot results showed that Rab25 protein expression in gastric cancer was significantly higher than in adjacent normal gastric tissues (P<0.01). Less differentiated gastric cancer cells had higher expression of Rab25 protein (P<0.01). Gastric carcinomas from patients with a late pathological stage (III-IV) had significantly higher Rab25 protein expression than early stage (I-II) patients (P<0.01). Gastric carcinomas from patients with lymph node metastasis had significantly higher Rab25 protein expression than lymph node metastasis-free patients (P<0.01). Gastric carcinomas from patients with distant metastases had significantly higher Rab25 protein expression than the distant metastasis-negative patients (P<0.01). Rab25 protein expression in gastric cancer was not affected by the patients, sex, age, or tumor size (P>0.05). MGC80-3 cells transfected with Rab25 siRNA had significantly lower Rab25 protein expression (P<0.01) and a significantly lower number of cells that passed through a Transwell chamber compared with non-transfected controls and the transfected control group (P<0.01). Rab25 protein expression is associated with the development of gastric cancer. siRNA knockdown of Rab25 protein expression in MGC80-3 gastric cancer cells reduced MGC80-3 cell invasiveness and provided experimental evidence for potential future biological treatment strategies of human gastric cancer.
doi:10.3978/j.issn.1000-9604.2013.03.01
PMCID: PMC3626988  PMID: 23592900
Rab25; human gastric cancer; immunohistochemistry; Western blot; siRNA; invasion
4.  Grey and white matter abnormalities in chronic obstructive pulmonary disease: a case–control study 
BMJ Open  2012;2(2):e000844.
Objectives
The irreversible airflow limitation characterised by chronic obstructive pulmonary disease (COPD) causes a decrease in the oxygen supply to the brain. The aim of the present study was to investigate brain structural damage in COPD.
Design
Retrospective case–control study. Patients with COPD and healthy volunteers were recruited. The two groups were matched in age, gender and educational background.
Setting
A hospital and a number of communities: they are all located in southern Fujian province, China.
Participants
25 stable patients and 25 controls were enrolled from December 2009 to May 2011.
Methods
Using voxel-based morphometry and tract-based spatial statistics based on MRI to analyse grey matter (GM) density and white matter fractional anisotropy (FA), respectively, and a battery of neuropsychological tests were performed.
Results
Patients with COPD (vs controls) showed decreased GM density in the limbic and paralimbic structures, including right gyrus rectus, left precentral gyrus, bilateral anterior and middle cingulate gyri, bilateral superior temporal gyri, bilateral anterior insula extending to Rolandic operculum, bilateral thalamus/pulvinars and left caudate nucleus. Patients with COPD (vs controls) had decreased FA values in the bilateral superior corona radiata, bilateral superior and inferior longitudinal fasciculus, bilateral optic radiation, bilateral lingual gyri, left parahippocampal gyrus and fornix. Lower FA values in these regions were associated with increased radial diffusivity and no changes of longitudinal diffusivity. Patients with COPD had poor performances in the Mini-Mental State Examination, figure memory and visual reproduction. GM density in some decreased regions in COPD had positive correlations with arterial blood Po2, negative correlations with disease duration and also positive correlations with visual tasks.
Conclusion
The authors demonstrated that COPD exhibited loss of regional GM accompanied by impairment of white matter microstructural integrity, which was associated with disease severity and may underlie the pathophysiological and psychological changes of COPD.
Article summary
Article focus
Decreased oxygen supply to brain may cause neuronal damage in COPD. However, the damage remains largely uninvestigated.
Key messages
We found that COPD extends to the brain, with the loss of regional cortical grey matter accompanied by impairment in the white matter microstructural integrity.
Our findings would be help for clinical therapy of COPD.
Strengths and limitations of this study
Multiple analyses were used based on MR images. The statistic power for FA analysis was weak.
doi:10.1136/bmjopen-2012-000844
PMCID: PMC3341600  PMID: 22535793
5.  Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study 
BMC Neuroscience  2011;12:94.
Background
The impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them.
Results
Compared to SL controls, the HA group showed generally decreased cerebrovascular reactivity and longer delay in hemodynamic response. Clusters showing significant differences in the former aspect were located at the bilateral primary motor cortex, the right somatosensory association cortex, the right thalamus and the right caudate, the bilateral precuneus, the right cingulate gyrus and the right posterior cingulate cortex, as well as the left fusiform gyrus and the right lingual cortex; clusters showing significant differences in the latter aspect were located at the precuneus, the insula, the superior frontal and temporal gyrus, the somatosensory cortex (the postcentral gyrus) and the cerebellar tonsil. Inspiratory reserve volume (IRV), which is an important aspect of pulmonary function, demonstrated significant correlation with the amount of BOLD signal change in multiple brain regions, particularly at the bilateral insula among the HA group.
Conclusions
Native-born HA residents generally showed reduced cerebrovascular reactivity as demonstrated in the hemodynamic response during a visual cue guided maximum inspiration task conducted with BOLD-fMRI. This effect was particularly manifested among brain regions that are typically involved in cerebral modulation of respiration.
doi:10.1186/1471-2202-12-94
PMCID: PMC3213017  PMID: 21943208
6.  Structural Modifications of the Brain in Acclimatization to High-Altitude 
PLoS ONE  2010;5(7):e11449.
Adaptive changes in respiratory and cardiovascular responses at high altitude (HA) have been well clarified. However, the central mechanisms underlying HA acclimatization remain unclear. Using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) with fractional anisotropy (FA) calculation, we investigated 28 Han immigrant residents (17–22 yr) born and raised at HA of 2616–4200 m in Qinghai-Tibetan Plateau for at least 17 years and who currently attended college at sea-level (SL). Their family migrated from SL to HA 2–3 generations ago and has resided at HA ever since. Control subjects were matched SL residents. HA residents (vs. SL) showed decreased grey matter volume in the bilateral anterior insula, right anterior cingulate cortex, bilateral prefrontal cortex, left precentral cortex, and right lingual cortex. HA residents (vs. SL) had significantly higher FA mainly in the bilateral anterior limb of internal capsule, bilateral superior and inferior longitudinal fasciculus, corpus callosum, bilateral superior corona radiata, bilateral anterior external capsule, right posterior cingulum, and right corticospinal tract. Higher FA values in those regions were associated with decreased or unchanged radial diffusivity coinciding with no change of longitudinal diffusivity in HA vs. SL group. Conversely, HA residents had lower FA in the left optic radiation and left superior longitudinal fasciculus. Our data demonstrates that HA acclimatization is associated with brain structural modifications, including the loss of regional cortical grey matter accompanied by changes in the white matter, which may underlie the physiological adaptation of residents at HA.
doi:10.1371/journal.pone.0011449
PMCID: PMC2897842  PMID: 20625426

Results 1-6 (6)