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Objectives The current study aimed to investigate the value of the computed tomography-based left-versus-right adrenal gland volume ratio (L/Rv) in screening patients with unilateral primary aldosteronism. Methods The current study recruited 114 patients who underwent successful adrenal venous sampling (AVS) and adrenal computed tomography at West China Hospital of Sichuan University. The patients were divided into three groups according to the AVS results: AVS-left, AVS-bilateral, and AVS-right primary aldosteronism. The volumes of the left and right adrenal glands were semiautomatically calculated. The L/Rv of each patient was computed, and its value in identifying unilateral primary aldosteronism was analyzed. Results The mean value of the L/Rv was larger in AVS-left patients and smaller in AVS-right patients than that in AVS-bilateral patients. In AVS-left primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.344 [area under the curve (AUC) 0.851, sensitivity 80.0%, specificity 78.1%]. The optimal cutoff value was 1.908, of which 46.0% (23/50) of AVS-left primary aldosteronism patients could be identified (specificity 100.0%). In AVS-right primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.267 (AUC 0.868, specificity 72.8%, sensitivity 87.9%). The optimal cutoff value was 0.765, of which 27.3% (9/33) of AVS-right primary aldosteronism patients could be identified (specificity 100.0%). Patients with L/Rv more than 1.908 or less than 0.765 had higher complete success rate postsurgery. Conclusion Although not perfect, the L/Rv is an applicable index to screen unilateral primary aldosteronism patients for surgery. Primary aldosteronism patients, even those aged more than 35 years, with an L/Rv more than 1.908 or less than 0.765 can be spared AVS before surgery.

Although regional brain deficits have been demonstrated in schizophrenia patients by structural MRI studies, one important question that remains largely unanswered is whether the complex and subtle deficits revealed by MRI could be used as objective biomarkers to discriminate patients from healthy controls individually. To address this question, a total of 326 right-handed participants were recruited, including 163 drug-naive first-episode schizophrenia (FES) patients and 163 demographically matched healthy controls. High-resolution anatomic data were acquired from all subjects and processed via Freesurfer software to obtain cortical thickness and surface area measurements. Subsequently, the Support Vector Machine (SVM) was used to explore the potential utility for cortical thickness and surface area measurements in the differentiation of individual patients and healthy controls. The accuracy of correct classification of patients and controls was 85.0% (specificity 87.0%, sensitivity 83.0%) for surface area and 81.8% (specificity 85.0%, sensitivity 76.9%) for cortical thickness (p

Background Isoflurane can induce anterograde amnesia. Hippocampal ripples are high-frequency oscillatory events occurring in the local field potentials of cornu ammonis 1 involved in memory processes. The authors hypothesized that isoflurane suppresses hippocampal ripples at a subanesthetic concentration by modulating the excitability of cornu ammonis 1 neurons. Methods The potencies of isoflurane for memory impairment and anesthesia were measured in mice. Hippocampal ripples were measured by placing recording electrodes in the cornu ammonis 1. Effects of isoflurane on the excitability of hippocampal pyramidal neurons and interneurons were measured. A simulation model of ripples based on the firing frequency of hippocampal cornu ammonis 1 neurons was used to validate the effects of isoflurane on neuronal excitability in vitro and on ripples in vivo. Results Isoflurane at 0.5%, which did not induce loss of righting reflex, impaired hippocampus-dependent fear memory by 97.4 ± 3.1% (mean ± SD; n = 14; P < 0.001). Isoflurane at 0.5% reduced ripple amplitude (38 ± 13 vs. 42 ± 13 μV; n = 9; P = 0.003), rate (462 ± 66 vs. 538 ± 81 spikes/min; n = 9; P = 0.002) and duration (36 ± 5 vs. 48 ± 9 ms; n = 9; P < 0.001) and increased the interarrival time (78 ± 7 vs. 69 ± 6 ms; n = 9; P < 0.001) and frequency (148.2 ± 3.9 vs. 145.0 ± 2.9 Hz; n = 9; P = 0.001). Isoflurane at the same concentration depressed action potential frequency in fast-spiking interneurons while slightly enhancing action potential frequency in cornu ammonis 1 pyramidal neurons. The simulated effects of isoflurane on hippocampal ripples were comparable to recordings in vivo. Conclusions The authors’ results suggest that a subanesthetic concentration of isoflurane can suppress hippocampal ripples by differentially modulating the excitability of pyramidal neurons and interneurons, which may contribute to its amnestic action. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy whose neurobiological underpinnings remain poorly understood. The present study aimed to identify possible neurochemical alterations in the dorsolateral prefrontal cortex (DLPFC) in participants with SHE using proton magnetic resonance spectroscopy (1 H MRS). Thirty-nine participants with SHE (mean age, 30.7 years ± 11.3 [standard deviation], 24 men) and 59 controls (mean age, 29.4 years ± 10.4, 29 men) were consecutively and prospectively recruited and underwent brain magnetic resonance imaging and 1 H MRS in the bilateral DLPFCs. Brain concentrations of metabolites, including N-acetyl aspartate (NAA), myo-inositol (mI), choline, creatine, the sum of glutamate and glutamine, glutathione (GSH) and γ-aminobutyric acid, were estimated with LCModel and corrected for the partial volume effect of cerebrospinal fluid using tissue segmentation. ANCOVA analyses revealed lower concentration of NAA in the left DLPFC in participants with SHE compared with controls. A significant difference of NAA concentration between DLPFC in the two hemispheres (left > right) was observed only in the control group. We further confirmed a higher GSH concentration in men than in women in SHE participants, which probably indicates that men are more susceptible to this disease. The mI concentration in the right DLPFC was negatively correlated with epilepsy duration. This study demonstrates that DLPFC is an important brain region involved in the pathophysiology of SHE, in which both neurons and astrocytes appear impaired, and the elevated GSH level may suggest an abnormality related to oxidative stress.

Hippocampal volume deficits have been reported in chronically-treated schizophrenia patients, however, the longer-term effects of antipsychotic medications on hippocampal anatomy are unclear. This case-control study investigated volume differences in hippocampal subfields of never-treated and antipsychotic-treated patients with long-term schizophrenia. High spatial-resolution T1-weighted magnetic resonance images were collected from 29 never-treated and 40 antipsychotic-treated patients with long-term schizophrenia matched for illness duration (all ≥ 5 years), and 40 demographically-matched healthy controls. Hippocampal subfield volumes were measured using FreeSurfer v6.0, compared across groups and between hemispheres, and correlated with clinical features. Volume reductions were found in both patient groups compared to healthy controls in 8 of 26 hippocampal subfields (Cohen's d = 0.46 - 1.17, P = .001 - .03), and more diffusely and obviously in never-treated than treated patients (Cohen's d = 0.50 - 0.90, P = .001 - .04). Greater right-than-left volumes were seen in treated patients and healthy controls in 11 of 13 subfields (T = 2.30 - 7.29, P = .001 - .03), but not in never-treated patients, in whom the volumes were reduced more on the right than on the left. Subfield volumes were negatively correlated with symptom severity and illness duration, and declined with age in never-treated patients. Findings indicate clinically-relevant and age-related volume reductions in hippocampal subfields of never-treated patients with long-term schizophrenia. Broader and greater subfield deficits in never-treated than treated patients, especially in the right hippocampus, suggest that long-term antipsychotic treatment may benefit hippocampal structures over the longer-term course of illness.

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment—notably with greater cortical thickness relative to controls predicting better treatment response.

To characterize possible metabolic changes of the dorsolateral prefrontal cortex (DLPFC) in patients with temporal lobe epilepsy (TLE). Quantitative proton magnetic resonance spectroscopy (1H-MRS) studies were performed on 24 TLE patients and 22 healthy controls. Metabolite concentrations were calculated using a linear combination model (LCModel) and corrected for cerebrospinal fluid contamination. Comparisons were performed between the TLE patients and the controls and between the left DLPFC and right DLPFC in each group. Pearson correlation coefficients were calculated between the metabolite concentrations and epilepsy duration and between the metabolite concentrations and voxel tissue composition: [gray matter (GM)/(GM+white matter (WM))]. Metabolic asymmetry was found in controls between the left and right DLPFC, i.e., the NAA concentration of the left DLPFC was significantly higher than that of the right. However, such metabolic asymmetry was not observed in TLE patients. Compared with the controls, TLE patients showed significantly decreased NAA and Ins, and the reductions were greater in the left DLPFC. No significant correlation was found between the metabolite concentrations and epilepsy duration or between the metabolite concentrations and voxel tissue composition [GM/(GM+WM)]. This study suggests that TLE can produce metabolic changes to DLPFC that is remote from the seizure focus. • Magnetic resonance spectroscopy probes the brain metabolism noninvasively. • Dorsolateral prefrontal reductions in NAA (a neuronal marker) and Ins are observed in TLE. • Temporal lobe epilepsy can result in metabolic changes remote from the seizure focus.

Purpose To identify cerebral radiomic features related to diagnosis and subtyping of attention deficit hyperactivity disorder (ADHD) and to build and evaluate classification models for ADHD diagnosis and subtyping on the basis of the identified features. Materials and Methods A consecutive cohort of 83 age- and sex-matched children with newly diagnosed and never-treated ADHD (mean age 10.83 years ± 2.30; range, 7-14 years; 71 boys, 40 with ADHD-inattentive [ADHD-I] and 43 with ADHD-combined [ADHD-C, or inattentive and hyperactive]) and 87 healthy control subjects (mean age, 11.21 years ± 2.51; range, 7-15 years; 72 boys) underwent anatomic and diffusion-tensor magnetic resonance (MR) imaging. Features representing the shape properties of gray matter and diffusion properties of white matter were extracted for each participant. The initial feature set was input into an all-relevant feature selection procedure within cross-validation loops to identify features with significant discriminative power for diagnosis and subtyping. Random forest classifiers were constructed and evaluated on the basis of identified features. Results No overall difference was found between children with ADHD and control subjects in total brain volume (1069830.00 mm3 ± 90743.36 vs 1079 213.00 mm3 ± 92742.25, respectively; P = .51) or total gray and white matter volume (611978.10 mm3 ± 51622.81 vs 616960.20 mm3 ± 51872.93, respectively; P = .53; 413532.00 mm3 ± 41 114.33 vs 418173.60 mm3 ± 42395.48, respectively; P = .47). The mean classification accuracy achieved with classifiers to discriminate patients with ADHD from control subjects was 73.7%. Alteration in cortical shape in the left temporal lobe, bilateral cuneus, and regions around the left central sulcus contributed significantly to group discrimination. The mean classification accuracy with classifiers to discriminate ADHD-I from ADHD-C was 80.1%, with significant discriminating features located in the default mode network and insular cortex. Conclusion The results of this study provide preliminary evidence that cerebral morphometric alterations can allow discrimination between patients with ADHD and control subjects and also between the most common ADHD subtypes. By identifying features relevant for diagnosis and subtyping, these findings may advance the understanding of neurodevelopmental alterations related to ADHD. © RSNA, 2017 Online supplemental material is available for this article.

Purpose To detect biophysical abnormalities in patients with postmedication treatment-resistant depression (TRD) with magnetization transfer imaging. Materials and Methods This study was approved by the local ethics committee, and written informed consent was obtained from all participants. Participants included 69 patients with major depressive disorder (MDD) (30 with TRD; 39 with non-TRD) and 41 healthy control subjects. Age and sex were examined with one-way analysis of variance and χ2 tests and were well matched among the three groups. Whole-brain voxel-based analysis was used to compare the magnetization transfer ratio (MTR) between the three groups. Regional MTR values were used to analyze the correlations with symptom severity and illness duration. Results MTR differences were identified in the bilateral precentral gyrus, left cerebellum posterior lobe, left middle occipital lobe, left precuneus, and left temporal lobe among the three groups. Relative to patients with non-TRD, those with TRD had significantly lower MTR in the task-positive network regions, including the bilateral precentral gyrus and left middle occipital lobe, and had lower MTR in the default mode network regions, including the left precuneus and left temporal lobe. Regional MTRs were not associated with symptom severity or illness duration. Conclusion These results suggest that treatment resistance in patients with MDD may be mediated by macromolecular abnormalities in the task-positive and default mode functional networks. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 29, 2017.

Background An overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests that the two disorders exhibit similar brain mechanisms. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess the gray matter volume (GMV) and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients. Methods High-resolution T1-weighted images were acquired from 37 non-comorbid MDD patients, 24 non-comorbid SAD patients and 41 healthy controls (HCs). Voxel-based morphometry analysis of the GMV (corrected with a false discovery rate of p, Highlights • MDD and SAD share common gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience and dorsal attention network. • MDD patients show disorder-specific involvement of the visual processing regions. • SAD patients show disorder-specific involvement of the precentral cortex. An overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests similar brain mechanisms for the two disorders. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess gray matter volume and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients. We found that MDD and SAD shared a common pattern of gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience network and dorsal attention network. MDD patients showed disorder-specific involvement of the visual processing regions. SAD patients showed disorder-specific involvement of the precentral cortex.

Background Conventional MRI cannot be used to identify H3 K27M mutation status. This study aimed to investigate the feasibility of predicting H3 K27M mutation status by applying an automated machine learning (autoML) approach to the MR radiomics features of patients with midline gliomas. Methods This single-institution retrospective study included 100 patients with midline gliomas, including 40 patients with H3 K27M mutations and 60 wild-type patients. Radiomics features were extracted from fluid-attenuated inversion recovery images. Prior to autoML analysis, the dataset was randomly stratified into separate 75% training and 25% testing cohorts. The Tree-based Pipeline Optimization Tool (TPOT) was applied to optimize the machine learning pipeline and select important radiomics features. We compared the performance of 10 independent TPOT-generated models based on training and testing cohorts using the area under the curve (AUC) and average precision to obtain the final model. An independent cohort of 22 patients was used to validate the best model. Results Ten prediction models were generated by TPOT, and the accuracy obtained with the best pipeline ranged from 0.788 to 0.867 for the training cohort and from 0.60 to 0.84 for the testing cohort. After comparison, the AUC value and average precision of the final model were 0.903 and 0.911 in the testing cohort, respectively. In the validation set, the AUC was 0.85, and the average precision was 0.855 for the best model. Conclusions The autoML classifier using radiomics features of conventional MR images provides high discriminatory accuracy in predicting the H3 K27M mutation status of midline glioma.

Previous studies have shown that posttraumatic stress disorder (PTSD) is associated with dysfunction of the limbic system, in which the amygdala plays an important role. The purpose of this study was to evaluate whether the neurochemical concentrations assessed by proton magnetic resonance spectroscopy (1H-MRS) in the amygdala are abnormal in children and adolescents with PTSD. Twenty-eight pediatric PTSD patients (11 boys, 17 girls) and 24 matched trauma-exposed control subjects (9 boys, 15 girls) underwent magnetic resonance brain imaging and 1H-MRS of the bilateral amygdalae. The concentrations of N-acetylaspartate (NAA), myo-inositol (mI), total creatine (tCr) and total choline (tCho) in the right amygdala were significantly increased in PTSD patients compared with trauma-exposed control subjects. There were significant group-by-age interactions in the left amygdala NAA and right amygdala mI concentrations: older pediatric patients with PTSD had higher left amygdala NAA concentration and younger patients had higher right amygdala mI concentration than trauma-exposed control subjects. There was also a significant correlation between right mI concentration and time since trauma in PTSD patients. Finally, there was significant group-by-age interaction in the left amygdala volume; intragroup analysis revealed that the right amygdala volume was significantly lower than the left in the PTSD group, but not in the control group. These neurochemical abnormalities of the amygdala may indicate that dysfunctions of both neurons and glial cells are involved in the pathology of pediatric PTSD.

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality. The underlying neurobiological mechanisms are not well understood, and high-resolution structural magnetic resonance brain imaging studies have given inconsistent results. Here we aimed to psychoradiologically define the most prominent and replicable abnormalities of gray matter volume (GMV) in AN patients, and to examine their relationship to demographics and clinical characteristics, by means of a new coordinate-based meta-analytic technique called seed-based d mapping (SDM). In a pooled analysis of all AN patients we identified decreased GMV in the bilateral median cingulate cortices and posterior cingulate cortices extending to the bilateral precuneus, and the supplementary motor area. In subgroup analysis we found an additional decreased GMV in the right fusiform in adult AN, and a decreased GMV in the left amygdala and left anterior cingulate cortex in AN patients without comorbidity (pure AN). Thus, the most consistent GMV alterations in AN patients are in the default mode network and the sensorimotor network. These psychoradiological findings of the brain abnormalities might underpin the neuropathophysiology in AN.

This study tested for differences of white matter integrity between treated and never-treated long-term schizophrenia patients, matched on illness duration, and for differential changes in relation to age in these two groups relative to healthy comparison subjects.This cross-sectional diffusion tensor imaging study included 31 never-treated and 46 matched antipsychotic-treated patients with long-term schizophrenia and 58 healthy comparison subjects. Fractional anisotropy measures of white matter tracts were extracted and compared. Linear regression analysis was used to explore the association between age and fractional anisotropy among the three groups.Fractional anisotropy significantly differed among the three groups in 14 of 20 white matter tracts defined in the Johns Hopkins University white matter template. Never-treated patients displayed greater reduction of fractional anisotropy than antipsychotic-treated patients in the left anterior thalamic radiation, the left cingulum-hippocampus pathway, the splenium and genu of the corpus callosum, and the left superior longitudinal fasciculus, and greater fractional anisotropy in the right uncinate fasciculus. Both patient groups showed multiple reductions relative to healthy comparison subjects. Never-treated patients showed an accelerated and clinically relevant age-related reduction of fractional anisotropy in the genu of the corpus callosum.These psychoradiological findings provide insight into the regional distribution of white matter deficits in the years after illness onset in long-term schizophrenia. Findings of greater impairments in never-treated patients, and a greater age-related reduction in the genu of the corpus callosum in these patients, suggest that long-term antipsychotic treatment does not adversely affect white matter tracts over the longer-term course of illness and may confer benefits.

Background Previous psychoradiological studies of posttraumatic stress disorder (PTSD) were mainly of patients at a chronic stage, focusing on brain regions outside the amygdala. The goals of this study were to investigate the early biochemical and structural changes of anterior cingulate cortex (ACC) and amygdala in patients with PTSD and to explore their relationships. Methods Seventy-eight drug-naive PTSD subjects and 71 non-PTSD age- and sex-matched control subjects were enrolled, all of whom had suffered the same earthquake about one year before. Single-voxel proton magnetic resonance spectroscopy (1H-MRS) was performed and absolute metabolite concentrations in ACC and bilateral amygdalae were estimated with LCModel. Bilateral amygdalae were manually outlined and their volumes were calculated and corrected for the total intracranial volume. Results The PTSD group showed significantly increased N-acetylaspartate (NAA) concentration in the ACC, increased creatine (Cr) concentration in the left amygdala, and increased myo-inositol (mI) concentration in the right amygdala, compared to non-PTSD controls. The NAA concentration in ACC was negatively correlated with the time since trauma. The PTSD group showed significantly decreased volumes of bilateral amygdalae compared to non-PTSD controls, but amygdala volumes were not correlated with metabolite concentrations. Limitations Longitudinal studies are needed to explore the metabolic and structural changes of PTSD at different stages. The volume of ACC was not measured. Conclusions This concurrent increase in some metabolite concentrations and decrease of amygdala volumes may represent a pattern of biochemical and morphological changes in recent-onset PTSD which is different from that reported in chronic PTSD.

We applied resting-state functional magnetic resonance imaging(rfMRI)combined with graph theory to analyze 90 regions of the infantile small world neural network of the whole brain.We tried to get the following two points clear:1 whether the parameters of the node property of the infantile small world neural network are correlated with the level of infantile intelligence development;2 whether the parameters of the infantile small world neural network are correlated with the children’s baseline parameters,i.e.,the demographic parameters such as gender,age,parents’ education level,etc.Twelve cases of healthy infants were included in the investigation(9males and 3females with the average age of 33.42±8.42 months.)We then evaluated the level of infantile intelligence of all the cases and graded by Gesell Development Scale Test.We used a Siemens 3.0T Trio imaging system to perform resting-state(rs)EPI scans,and collected the BOLD functional Magnetic Resonance Imaging(fMRI)data.We performed the data processing with Statistical Parametric Mapping 5(SPM5)based on Matlab environment.Furthermore,we got the attributes of the whole brain small world and node attributes of 90 encephalic regions of templates of Anatomatic Automatic Labeling(ALL).At last,we carried out correlation study between the above-mentioned attitudes,intelligence scale parameters and demographic data.The results showed that many node attributes of small world neural network were closely correlated with intelligence scale parameters.Betweeness was mainly centered in thalamus,superior frontal gyrus,and occipital lobe(negative correlation).The r value of superior occipital gyrus associated with the individual and social intelligent scale was-0.729(P=0.007);degree was mainly centered in amygdaloid nucleus,superior frontal gyrus,and inferior parietal gyrus(positive correlation).The r value of inferior parietal gyrus associated with the gross motor intelligent scale was 0.725(P=0.008);efficiency was mainly centered in inferior frontal gyrus,inferior parietal gyrus,and insular lobe(positive correlation).The r value of inferior parietal gyrus associated with the language intelligent scale was 0.738(P=0.006);Anoda cluster coefficient(anodalCp)was centered in frontal lobe,inferior parietal gyrus,and paracentral lobule(positive correlation);Node shortest path length(nlp)was centered in frontal lobe,inferior parietal gyrus,and insular lobe.The distribution of the encephalic regions in the left and right brain was different.However,no statistical significance was found between the correlation of monolithic attributes of small world and intelligence scale.The encephalic regions,in which node attributes of small world were related to other demographic indices,were mainly centered in temporal lobe,cuneus,cingulated gyrus,angular gyrus,and paracentral lobule areas.Most of them belong to the default mode network(DMN).The node attributes of small world neural network are widely related to infantile intelligence level,moreover the distribution is characteristic in different encephalic regions.The distribution of dominant encephalic is in accordance the related functions.The existing correlations reflect the ever changing small world nervous network during infantile development.

Background Currently-used cerebellomedullary cistern puncture method for collecting cerebrospinal fluid (CSF) from monkeys is simple, inexpensive, and practical, but with high risk for brainstem injury and CSF blood contamination. An improved technique was thus developed and characterized. Method Magnetic resonance imaging was used to identify the space and position of the cisterna magna in monkeys. Accordingly, a newly defined procedure for needle punctuation was tested in comparison with the traditional method. Blood contamination in CSF samples and brainstem injury were determined to define the superior of the improved method over the transitional method. Results The cisterna magna in monkeys was found to be a “▽” shape. The needle was punctured into the cisterna magna aiming at the wider superior gap avoided brainstem injury. The improved method showed that the rate of blood contamination in the CSF samples was reduced from 66.7% to 16.7%, the higher rate of blood contamination was associated with higher risk for brainstem injury. Comparison with existing methods: In traditional method, the needle is punctured aiming at the inferior gap with high density of blood vessels. In improved method, the needle is punctured aiming at the superior gap, pointing to the nose root while advancing the needle and avoiding injury to blood vessels. Conclusions This improved technique not only avoids blood contamination of CSF, but also prevents brainstem injury during the process of CSF collection. It is recommended for adaptation for CSF collection in monkeys.

Background While suppressor of cytokine signaling 3 (SOCS3) plays a crucial role in suppressing dysplasia and tumorigenesis, it also offers a typical instance of DNA methylation in the regulation of gene transcription, since the promoter region of the SOCS3 gene is rich in CpG islands (CGIs). During liver regeneration initiated by partial hepatectomy, SOCS3 acts as a suppressor to balance the acute-phase response and terminate the regeneration. This study aimed to determine whether the variation of SOCS3 expression throughout liver regeneration is also regulated by its DNA methylation. Methods We established a 70% partial hepatectomy mouse model and the animals were sacrificed at indicated times to assess the SOCS3 expression. We performed bisulfite sequencing PCR and DNA sequencing to investigate the detailed cytosine methylation in the SOCS3 gene. Results Within the promoter sequence, 58 CGIs were identified and 30 were found variously methylated before or after operation; however, methylation remained at a very low level. No evidence indicated that the total methylation level or the methylation of any CpG site regularly changed throughout liver regeneration. Conclusion DNA methylation or demethylation seems to be a relatively stable modification of cytosine, but not a dynamic and reversible process to regulate gene transcription in daily and acute pathophysiological events.

To date, serum biochemistry examination and routine biopsy are the most commonly used methods to assess renal function after allogenic kidney transplantation. Connective tissue growth factor (CTGF) has been considered as a biomarker of chronic renal allograft injury characterized by tubular atrophy and interstitial fibrosis (TA/IF). This study explored the potential value of urinary CTGF as an early predictor of TA/IF using a rat model.A Fisher to Lewis allogenic rat kidney transplant model was established and the recipients were killed at weeks 4, 8 and 12 post-transplantation. TA/IF was graded based on Banff Schema 1997. The location and expression of CTGF mRNA were detected by oligonucleotide-primed in situ DNA synthesis and quantitative polymerase chain reaction. CTGF protein expression was examined with immunohistochemistry and immunoblotting. Urinary CTGF concentration was measured by enzyme-linked immunosorbent assay. The correlation between urinary CTGF concentration and serum creatinine (SCr) and Banff score was analysed statistically.Typical morphological changes including TA/IF in allograft appeared at week 8 and became very severe at week 12 post-transplantation. CTGF expression in epithelium was up-regulated early and urinary CTGF was markedly elevated from week 4. SCr in recipients was stable before week 8 but increased tremendously at week 12. Urinary CTGF concentration was positively correlated with SCr and degree of interstitial fibrosis.Urinary CTGF increases earlier than the appearance of biochemical abnormalities and pathological changes. Measurement of urinary CTGF may offer a potential non-invasive strategy to predict the early onset of chronic renal allograft injury.

SUMMARY: Aim: Many strategies are explored to ameliorate kidney allograft tubular atrophy and interstitial fibrosis (TA/IF), but little progress has been achieved. The latest evidence suggested that CD133+ cell in kidney represent a potential multipotent adult resident stem cell population that may contribute to the renal injury repair. Here we investigate whether the CD133+ cells exist in transplanted renal and exert a growth and self-repair procedure in TA/IF. Methods: Allografts from rat kidney transplant models were harvested at 4 weeks, 8 weeks and 12 weeks post transplantation. We performed immunohistochemistry to detect the CD133+ cells and immunofluorescence to detect the co-expression of CD133 or Pax-2 with Ki-67. We furthermore analysed the E-cadherin using serial sections. Results: CD133+ cells were seldom seen in control kidney, but distributed sporadically in the cortex parenchyma along with the deterioration of TA/IF. The number of CD133+ cell increased after 4 weeks and reached the peak at 8 weeks, then decreased at 12 weeks. From 8 weeks, some new tubules expressing E-cadherin were constructed with CD133+ cells. Almost all the CD133+ cells were Ki-67-positive, but not all the Ki-67+ cells expressed CD133. The rest Ki-67+ cells almost expressed Pax-2. Conclusion: Our study reveals that when majority of the tubules are damaged, a self-repair mechanism is evoked by potential adult stem cells to compensate the renal function. Thus, potential adult resident stem cells offer a new avenue for autologous cell therapies in TA/IF.

The dose-dependent effect of isoflurane on cerebral regional activity and functional connectivity (FC) in 14 rhesus monkeys was investigated using resting-state functional MRI. Amplitude of low-frequency fluctuations (ALFF) decreased in the cerebellum, visual cortex, and cortico-subcortical network when the isoflurane dose changed from 1.0 to 1.3 MAC. ALFF decreased in the arousal system, cerebellum, sensory, visual areas, cortico-subcortical network and default mode network and increased in the bilateral dorsal prefrontal cortices, frontal eye fields and motor-related areas from 1.0 to 1.6 MAC. FC of the default mode network, frontal-parietal, cortico-subcortical, motor, sensory, auditory and visual areas was reduced when isoflurane increased from 1.0 to 1.3 MAC. FC decreased in more widespread areas, especially in regions of cortico-subcortical networks and limbic systems, when isoflurane further increased from 1.0 to 1.6 MAC. Both dose-dependent decreased and increased ALFF were separately observed, while FC deteriorated as the anesthesia deepened. These results suggest that changes continue to occur past the loss of consciousness, and the dose-dependent effects of isoflurane are different with regard to regional function and neural network integration.

Importance Accumulating evidence supports the hypothesis that cerebral white matter abnormalities are involved in the pathophysiology of schizophrenia; however, findings from in vivo neuroimaging studies have been inconsistent. Besides confounding factors, including age, illness duration, and medication effects, an additional cause for the inconsistent results may be heterogeneity in the nature of white matter alterations associated with the disorder. Objective To investigate whether different patterns of white matter abnormalities exist in a large cohort of medication-naive patients with first-episode schizophrenia and the relationship between such patterns and clinical parameters. Design, Setting, and Participants A cross-sectional diffusion tensor imaging study of 113 medication-naive patients with first-episode schizophrenia and 110 demographically matched healthy control individuals. The study was conducted in the mental health center of West China Hospital, Sichuan University, Chengdu, China, from January 2006 to June 2014. Main Outcomes and Measures The patterns of white matter abnormalities revealed by tract-specific analysis in conjunction with hierarchical clustering. Results With diffusion features extracted from 18 fiber tracts, cluster analysis revealed 2 patterns of abnormalities. One pattern (42.5% of patient sample) showed widespread white matter abnormalities compared with matched healthy control individuals, while another pattern (57.5% of patient sample) only showed circumscribed regional white matter abnormalities, mainly in the left superior longitudinal fasciculus. Patients in these subgroups did not differ in demographic features; however, negative symptoms were more severe in patients with widespread white matter abnormalities. Conclusions and Relevance Two distinct patterns of white matter abnormalities exist at the early phase of schizophrenia, with those having global abnormalities experiencing more severe negative symptoms. The finding that distinct subgroups of patients with schizophrenia have different forms of white matter pathology may reflect qualitatively distinct genetic influences or neurodevelopmental alterations and thus represents a promising strategy for resolving neurobiological heterogeneity in the schizophrenia syndrome.

Previous structural imaging studies have found evidence of brain morphometric changes in patients with major depressive disorder (MDD), but these studies rarely excluded compounding effects of certain important factors, such as medications and long duration of illnesses. Furthermore, the neurobiological mechanism of the macroscopic findings of structural alterations in MDD patients remains unclear. In this study, we utilized magnetization transfer imaging, a quantitative measure of the macromolecular structural integrity of brain tissue, to identify biophysical alterations, which are represented by a magnetization transfer ratio (MTR), in MDD patients. To ascertain whether MTR changes occur independent of volume loss, we also conduct voxel-based morphometry (VBM) analysis. The participants included 27 first-episode, drug-naive MDD patients and 28 healthy controls matched for age and gender. Whole-brain voxel-based analysis was used to compare MTR and gray matter volume across groups and to analyse correlations between MTR and age, symptom severity, and illness duration. The patients exhibited significantly lower MTR in the left superior parietal lobule and left middle occipital gyrus compared with healthy controls, which may be related to the attentional and cognitive dysfunction in MDD patients. The VBM analysis revealed significantly increased gray matter volume in right postcentral gyrus in MDD patients. These findings in first-episode, drug-naive MDD patients may reflect microstructural gray matter changes in the parietal and occipital cortices close to illness onset that existed before volume loss, and thus potentially provide important new insight into the early neurobiology of depression.

The mechanisms by which hepatic function is maintained after extensive parenchymal loss are unclear. In this study, we propose a novel concept of “functional heterogeneity” of hepatocytes based on their different expression of acetylated histones, the markers of active gene transcription, to explain the powerful compensatory capability of the liver. In the healthy human liver, only a fraction of the hepatocytes were marked by acetylated histones (ac-H2AK5, ac-H2BK5, ac-H3K9, ac-H3K14, ac-H3K27, and ac-H3K9/14). With the progression of cirrhosis, the ratio of the positive cells was gradually elevated, accompanied by the gradual exhaustion of the negative cells. By examining the global transcriptome of the mouse hepatocytes, we observed that the primed genes in the positive cells were much more numerous than those in negative cells. In a 70% hepatectomized mouse, the remnant hepatocytes were extensively activated, and the liver function was well maintained even when regeneration was severely inhibited. The functional compensation was absolutely dependent on the elevated expression of acetyl-histones. Additionally, when liver regeneration was blocked, the metabolism-related genes seemed to be preferentially transcribed. In conclusion, we demonstrate that normally, part of the active hepatocytes are competent for routine physiological requirements. The inactive hepatocytes, delicately regulated by acetyl-histones, act as a functional reservoir for future activation to restore the liver function after massive parenchymal loss.

Innovative cell-based therapies, including hepatic tissue engineering following hepatocyte transplantation, are considered as theoretical alternatives to liver transplant or for partial replacement of liver function in patients. However, recent progress in hepatic tissue engineering has been hampered by low initial hepatocyte engraftment and insufficient blood supply in vivo. We developed an intact 3D scaffold of an extracellular matrix (ECM) derived from a decellularized liver lobe, with layer-by-layer (LbL) heparin deposition to avoid thrombosis, which we repopulated with hepatocytes and successfully implanted as a tissue-engineered liver (TEL) into the portal system. The TEL provided sufficient volume for transplantation of cell numbers representing up to 10% of whole-liver equivalents and was perfused by portal vein blood. Treatment of extended hepatectomized rats with a TEL improved liver function and prolonged survival; mean lifespan was extended from 16 to 72 h. At 72 h postoperation, the TEL sustained functional and viable hepatocytes. In conclusion, we propose the TEL as a state-of-the-art substitute for whole-liver transplantation and as a proof of concept for the technology that will eventually allow for the transplantation of a reconstituted liver.

Chronic allograft nephropathy (CAN) is a leading cause of kidney graft failure. The latest evidence suggests that connective tissue growth factor (CTGF) may be a biomarker of CAN. Detection of urinary CTGF levels is a potential noninvasive strategy to predict the early onset of CAN. Compared to the traditional "sandwich" enzyme-linked immunosorbent assay (ELISA), we established a novel, accurate, faster, one-step competitive indirect ELISA (Ci-ELISA) to estimate the urinary CTGF concentrations in humans, rats, and mice.We used recombinant human CTGF, which is an 11.2 kDa protein of 98 amino acid residues containing the C-terminal portion of the full-length CTGF protein having 96% and 94% homology with rats and mice, as the coating antigen and standard competitor. We then applied polyclonal antibody against the CTGF C-terminal portion, secondary antibody conjugated with horseradish peroxidase (HRP), and urine samples to establish one-step Ci-ELISA. Rat kidney allograft recipients were sacrificed at 4, 8, or 12 weeks posttransplantation. We harvested serum, urine, and transplanted kidneys. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson trichrome stains were used to estimate the histopathologic changes according to the Banff schema. Serum creatinine (SCr) levels were measured to represent renal function. CTGF in kidney was detected by immunohistochemistry. Urinary CTGF concentrations were measured using the one-step Ci-ELISA.The whole one-step Ci-ELISA test can be accomplished within 2 hours. The detection limit of the assay was 0.16 ng/mL CTGF. The time-dependent elevated recipient concentration of urinary CTGF was positively correlated with SCr, histologic changes, and CTGF in the kidney after transplantation. The 95% confidence intervals of urinary CTGF concentrations in control rats were 24.4 to 35.2 ng/mL; at 4, 8, and 12 weeks posttransplantation they were 139.4 to 395.6, 826.7 to 1429.5, and 3206.0 to 4448.2 ng/mL, respectively.A rapid one-step Ci-ELISA was successfully established to detect the CTGF levels in urine. These results further indicated that detection of urinary CTGF is a potential noninvasive strategy to predict the early onset of CAN.

To study age-related metabolic changes in different brain regions.Point-resolved spectroscopy (repetition time/echo time = 2000 ms/30 ms) was performed in the left and right hippocampus, the left thalamus and the left centrum semiovale of 80 healthy subjects (37 females and 43 males aged 7-64 years). Analysis of covariance and linear regression were used for statistical analysis. Both metabolite concentration ratios with respect to total creatine (tCr) and absolute metabolite concentrations were included for analysis.Ins (myo-inositol)/tCr (p 0.001) and absolute Ins concentration (p = 0.031) were significantly increased with age after adolescence. NAA (N-acetylaspartic acid)/tCr (p 0.001) and absolute NAA concentration (p = 0.010) significantly declined with age after adolescence.Age-related increase of Ins and decline of NAA are found in all three regions, especially at the hippocampus, indicating possible gliosis in the ageing brain.We could use NAA/tCr and Ins/tCr as an indicator to estimate the neurons-to-glial cells ratio at the thalamus. This may be an index to distinguish normal tissues from gliosis.