Study on the clinical efficacy of Mongolian medicine in the treatment of osteoarthritis.

OBJECTIVE: The object of this paper was to evaluate the clinical efficacy and safety of Mongolian medicine in the treatment of osteoarthritis (OA). This was completed by offering evidence to provide a clinical basis for the treatment of OA. We explored the mechanism of the sticking application of Mongolian medicine. METHOD: A total of 123 patients with OA diagnosed in the Affiliated Hospital of Inner Mongolia Medical University from January 2017 to December 2017 were enrolled. The clinical data of the patients were retrospectively analyzed. Patients were divided into three groups according to the medication they were using at the time: The strapping group, the glucosamine hydrochloride group, and the Mongolian medicine group, with 41 patients in each group. The treatment indicators of the included patients 2 weeks after the treatment and 4 weeks after the treatment were fully recorded in our hospital. The levels of CGRP, TNF-α, MMP-3, VEGF, and IL-10 before and after treatment were measured by ELISA. The auxiliary diagnostic index was X-ray film. RESULTS: Compared with the control group, the Mongolian medicine group improved the symptoms of pain, swelling, limited movement, and daily life quality of patients to different degrees. There was a significant decrease in the VAS score at each time point of the Mongolian medicine group (P < 0.05). tThe scores of bodily pain in SF-36 QOL were significantly higher in the Mongolian medicine group at different time points (P < 0.05). After treatment, the levels of MMP-3, TNF-α, VEGF, and CGRP in the Mongolian medicine group were significantly lower than those before the treatment (P < 0.05). CONCLUSION: Mongolian medicine can inhibit the expression of MMP-3, TNF-α, VEGF, and CGRP in serum, and up-regulate the trend of IL-10, alleviating the inflammatory reaction. It has a good curative effect in the treatment of OA patients. It is better than western medicine in pain, swelling, and improving bone and joint function index.

Identification of a HOXD13 variant in a Mongolian family with incomplete penetrance syndactyly by exon sequencing.

BACKGROUND: Syndactyly (SD) refers to a deformity caused by the fusion and limb differentiation disorder of soft tissues and/or skeletons to varying extents between adjacent fingers (toes). The main features of this disease are phenotypic heterogeneity and genetic heterogeneity. In this study, we examined four generations of a Chinese Mongolian with different phenotypes of syndactylia and analysed and identified the pathogenic genetic variants of SD by exon sequencing. METHODS: The clinical phenotypes of patients were analysed, and the hands and feet were examined by X-ray. The pedigree was drawn, and the family data were analysed. Peripheral blood was collected from the family members, and genomic DNA was extracted. The candidate genes of SD were identified by exon sequencing, and the mutation sites of the captured candidate genes were amplified by PCR and verified by Sanger sequencing. RESULTS: The family has congenital syndactyly, which is an autosomal dominant disease. At present, this condition has been passed down for 4 generations and was identified in 9 patients, including 4 males and 5 females. Five patients, I2, II4, III5, III,7 and III10, had unilateral syndactyly, and four patients, III16, IV3, IV6 and IV7, had bilateral finger syndactyly. All of their toes were unaffected. The proband and the other patients in this family had a c.917G > A (p.R306Q) mutation, which is located at position 917 of the second exon of the HOXD13 gene. This mutation results in a change in the amino acid at position 306, in which arginine is changed to glutamine. This mutation cosegregates in unaffected individuals and affected patients in this family. Moreover, 201 Mongolian genome databases and a thousand human genome databases were referenced to further confirm that the pathogenic genetic variant that causes syndactyly in this family is found in HOXD13. CONCLUSION: This study found that the mutation site of the pathogenic gene in this family was HOXD13, c.917G > A (p.R306Q). The phenotype of the family member III12 was normal, but this member was also a carrier of the pathogenic genetic variant. This indicates that the disease of this family has incomplete penetrance characteristics. Our results further enrich the expression profile of the HOXD13 gene.

Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events.

Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.

A novel pathogenic variant in OSBPL2 linked to hereditary late-onset deafness in a Mongolian family.

BACKGROUND: To investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease. METHODS: Family data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing. RESULTS: The family is composed of a total of 6 generations, with 53 traceable individuals. In this family,19 of them were diagnosed with post lingual deafness with the age of onset between 10 and 40 years, displaying delayed and progressive hearing loss. Patients with hearing loss showed bilateral symmetry and mild to severe sensorineural deafness. The pattern of deafness inheritance in this family is autosomal dominant. Whole genome sequencing identified a novel pathogenic frameshift mutation, c.158_159delAA (p.Gln53Arg fs*100) in the gene OSBPL2 (Oxysterol-binding protein-related protein 2, NM_144498.2), which is absent from genomic data of 201 unrelated normal subjects. This pathogenic variant was further validated by Sanger sequencing, and was found to co-segregate in this family. CONCLUSIONS: Whole genome sequencing identified a two-nucleotide deletion in OSBPL2 (c.158_159delAA) as the pathogenic variant for deafness in the family. Our finding expands the mutational spectrum of OSBPL2 and contributes to the pathogenic variant list in genetic counseling for deafness screening.

Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease.

OBJECTIVE: Congenital heart disease (CHD) is the most frequent birth defect worldwide. The number of adult patients with CHD, now referred to as ACHD, is increasing with improved surgical and treatment interventions. However the mechanisms whereby ACHD predisposes patients to heart dysfunction are still unclear. ACHD is strongly associated with metabolic syndrome, but how ACHD interacts with poor modern lifestyle choices and other comorbidities, such as hypertension, obesity, and diabetes, is mostly unknown. METHODS: We used a newly characterized mouse genetic model of ACHD to investigate the consequences and the mechanisms associated with combined obesity and ACHD predisposition. Metformin intervention was used to further evaluate potential therapeutic amelioration of cardiac dysfunction in this model. RESULTS: ACHD mice placed under metabolic stress (high fat diet) displayed decreased left ventricular ejection fraction. Comprehensive physiological, biochemical, and molecular analysis showed that ACHD hearts exhibited early changes in energy metabolism with increased glucose dependence as main cardiac energy source. These changes preceded cardiac dysfunction mediated by exposure to high fat diet and were associated with increased disease severity. Restoration of metabolic balance by metformin administration prevented the development of heart dysfunction in ACHD predisposed mice. CONCLUSIONS: This study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise the prospect for a translational reassessment of ACHD presentation in the clinic.

The relationship of anxious and depressive symptoms in Parkinson's disease with voxel-based neuroanatomical and functional connectivity measures.

BACKGROUND: Anxiety and depression are two frequent comorbidities of Parkinson's disease (PD). However, the underlying neural mechanism is still unclear and the studies on their neural correlates were insufficient. METHODS: Using voxel-based neuroanatomical and functional connectivity (FC) measures, i.e. grey matter volume, fractional anisotropy, and weighted degree centrality (WD), we examined their correlations with the severity levels of anxious and depressive symptoms in 36 PD patients. RESULTS: Positive correlations were shown between anxiety and the WDs in the left amygdala, and between depression and short-ranged WDs in the left parahippocampal gyrus. Using these two regions as the seeds, we found that the severity levels of anxiety and depression were positively correlated with the FCs between the two seeds and the areas in the default mode network (DMN), while negatively correlated with the FCs between the two seeds and the prefrontal and superior temporal cortices. Anxiety was also positively correlated with the FC between the amygdala and the superior parietal lobule. LIMITATIONS: The severity levels of anxious and depressive symptoms of our participants is relatively mild than some previous studies. The cross-sectional design of this study cannot clarify the etiological relationship between PD and two comorbidities. CONCLUSIONS: Our results were in line with the key roles of the amygdala and parahippocampal gyrus in anxiety and depression, and reflected the distinct effects of the DMN, prefrontal and superior temporal cortices, and sensory-motor regions on emotional regulation. The identification of these neural substrates might assist clinical monitoring mood disturbances in PD.

Whole-genome sequencing of 175 Mongolians uncovers population-specific genetic architecture and gene flow throughout North and East Asia.

The genetic variation in Northern Asian populations is currently undersampled. To address this, we generated a new genetic variation reference panel by whole-genome sequencing of 175 ethnic Mongolians, representing six tribes. The cataloged variation in the panel shows strong population stratification among these tribes, which correlates with the diverse demographic histories in the region. Incorporating our results with the 1000 Genomes Project panel identifies derived alleles shared between Finns and Mongolians/Siberians, suggesting that substantial gene flow between northern Eurasian populations has occurred in the past. Furthermore, we highlight that North, East, and Southeast Asian populations are more aligned with each other than these groups are with South Asian and Oceanian populations.

Reorganization of cerebro-cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting-state functional MRI study.

The role of cerebellum and cerebro-cerebellar system in neural plasticity induced by cerebral gliomas involving language network has long been ignored. Moreover, whether or not the process of reorganization is different in glioma patients with different growth kinetics remains largely unknown. To address this issue, we utilized preoperative structural and resting-state functional MRI data of 78 patients with left cerebral gliomas involving language network areas, including 46 patients with low-grade glioma (LGG, WHO grade II), 32 with high-grade glioma (HGG, WHO grade III/IV), and 44 healthy controls. Spontaneous brain activity, resting-state functional connectivity and gray matter volume alterations of the cerebellum were examined. We found that both LGG and HGG patients exhibited bidirectional alteration of brain activity in language-related cerebellar areas. Brain activity in areas with increased alteration was significantly correlated with the language and MMSE scores. Structurally, LGG patients exhibited greater gray matter volume in regions with increased brain activity, suggesting a structure-function coupled alteration in cerebellum. Furthermore, we observed that cerebellar regions with decreased brain activity exhibited increased functional connectivity with contralesional cerebro-cerebellar system in LGG patients. Together, our findings provide empirical evidence for a vital role of cerebellum and cerebro-cerebellar circuit in neural plasticity following lesional damage to cerebral language network. Moreover, we highlight the possible different reorganizational mechanisms of brain functional connectivity underlying different levels of behavioral impairments in LGG and HGG patients.

Oxytocin selectively modulates brain processing of disgust in Huntington's disease gene carriers.

People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain networks. We examined whether oxytocin, when given intranasally, would normalise aberrant brain reactivity to emotional faces in participants with the gene-expansion for HD. In a double-blind placebo-controlled cross-over design, we measured brain activity, using functional magnetic resonance imaging, whilst nine medication-free HD carriers, and ten control participants viewed emotional (disgust, fear, angry, sad, surprise, happy) and neutral faces, following acute intranasal oxytocin (24IU) and placebo. Subjective mood changes were assessed before and after the neuroimaging on each visit. Permutation-based non-parametric statistical testing for the whole brain, showed significant group×drug interactions (p's<0.05, TFCE corrected) in areas of the left frontal pole, superior frontal, and middle frontal gyri cortically, and left putamen and thalamus sub-cortically. Parameter estimates extracted from the middle frontal gyrus and putamen showed that, under placebo, the HD group had lower brain activity to disgust stimuli, compared with controls. After intranasal oxytocin, the pattern of activation to disgust stimuli was normalised in the HD group to similar levels as controls; eight of the nine HD carriers showed increased response in the middle frontal gyrus, and seven of the nine HD carriers showed increased response in the putamen. The observed effects of oxytocin occurred in the absence of changes in subjective mood or state anxiety. These findings provide early evidence for a physiological role of oxytocin in the neuropathology of HD. Our findings are the first reported oxytocin effects in a neurodegenerative disease. Further research should examine the therapeutic benefits of oxytocin in alleviating emotional and social cognition deficits in HD and related disorders.

Occipital GABA levels in older adults and their relationship to visual perceptual suppression.

Several studies have attributed certain visual perceptual alterations in older adults to a likely decrease in GABA (Gamma Aminobutyric Acid) concentration in visual cortex, an assumption based on findings in aged non-human primates. However, to our knowledge, there is no direct evidence for an age-related decrease in GABA concentration in human visual cortex. Here, we estimated visual cortical GABA levels and Glx (combined estimate of glutamate and glutamine) levels using magnetic resonance spectroscopy. We also measured performance for two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion and binocular rivalry. Our results show increased visual cortical GABA levels, and reduced Glx levels, in older adults. Perceptual performance differed between younger and older groups for both tasks. When subjects of all ages were combined, visual cortical GABA levels but not Glx levels correlated with perceptual performance. No relationship was found between perception and GABA levels in dorsolateral prefrontal cortex. Perceptual measures and GABA were not correlated when either age group was considered separately. Our results challenge current assumptions regarding neurobiological changes that occur within the aging human visual cortex and their association with certain age-related changes in visual perception.

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

PURPOSE: The aim of this study is to examine whether advanced magnetic resonance imaging (MRI) techniques can detect early brain injury caused by intrauterine inflammation and inappropriate initial respiratory support in preterm lambs. HYPOTHESIS: Neuropathology caused by intrauterine inflammation is exacerbated by mechanical ventilation at birth and is detectable with advanced MRI techniques. METHODS: Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days prior to delivery at ~125 days of gestation (85% of gestation), whereupon lambs were delivered and randomised to receive an injurious (LPS + INJ, n = 6) or protective (LPS + PROT, n = 6) ventilation strategy. MRI of the brain was conducted 90 min after preterm delivery, using structural, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) techniques. A colour map threshold technique was utilised to compare distributions of low diffusivity voxels in the brains of LPS-exposed lambs with those not exposed to LPS (PROT, n = 7 PROT and INJ, n = 10). RESULTS: No overt cerebral injury was identified on structural MRI images of any lamb. However, on DTI, axial diffusivity, radial diffusivity, and mean diffusivity values were lower and significantly more heterogeneous in specific brain regions of lambs in the LPS + INJ group compared to the LPS + PROT group. Colour mapping revealed lower diffusivity in the thalamus, periventricular white matter, internal capsule, and frontal white matter in the LPS + INJ group compared to LPS + PROT group. The MRS peak area ratios of lactate, relative to those for the metabolites creatine, choline, and N-acetylaspartate, were not different between LPS-exposed groups. Lambs exposed to LPS had lower diffusivity within the white matter regions assessed than non-LPS-treated control lambs. CONCLUSION: DTI colour map threshold techniques detected early brain injury in preterm lambs exposed to intrauterine inflammation and detected differences between injurious and protective ventilation strategies. DTI mapping approaches are potentially useful for early detection of subtle brain injury in premature infants.

Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging.

Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepentaacetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24-48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology.NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

Point mutations in murine Nkx2-5 phenocopy human congenital heart disease and induce pathogenic Wnt signaling.

Mutations in the Nkx2-5 gene are a main cause of congenital heart disease. Several studies have addressed the phenotypic consequences of disrupting the Nkx2-5 gene locus, although animal models to date failed to recapitulate the full spectrum of the human disease. Here, we describe a new Nkx2-5 point mutation murine model, akin to its human counterpart disease-generating mutation. Our model fully reproduces the morphological and physiological clinical presentations of the disease and reveals an understudied aspect of Nkx2-5-driven pathology, a primary right ventricular dysfunction. We further describe the molecular consequences of disrupting the transcriptional network regulated by Nkx2-5 in the heart and show that Nkx2-5-dependent perturbation of the Wnt signaling pathway promotes heart dysfunction through alteration of cardiomyocyte metabolism. Our data provide mechanistic insights on how Nkx2-5 regulates heart function and metabolism, a link in the study of congenital heart disease, and confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients.

Discriminative Analysis of Migraine without Aura: Using Functional and Structural MRI with a Multi-Feature Classification Approach.

Magnetic resonance imaging (MRI) is by nature a multi-modality technique that provides complementary information about different aspects of diseases. So far no attempts have been reported to assess the potential of multi-modal MRI in discriminating individuals with and without migraine, so in this study, we proposed a classification approach to examine whether or not the integration of multiple MRI features could improve the classification performance between migraine patients without aura (MWoA) and healthy controls. Twenty-one MWoA patients and 28 healthy controls participated in this study. Resting-state functional MRI data was acquired to derive three functional measures: the amplitude of low-frequency fluctuations, regional homogeneity and regional functional correlation strength; and structural MRI data was obtained to measure the regional gray matter volume. For each measure, the values of 116 pre-defined regions of interest were extracted as classification features. Features were first selected and combined by a multi-kernel strategy; then a support vector machine classifier was trained to distinguish the subjects at individual level. The performance of the classifier was evaluated using a leave-one-out cross-validation method, and the final classification accuracy obtained was 83.67% (with a sensitivity of 92.86% and a specificity of 71.43%). The anterior cingulate cortex, prefrontal cortex, orbitofrontal cortex and the insula contributed the most discriminative features. In general, our proposed framework shows a promising classification capability for MWoA by integrating information from multiple MRI features.

Multimodal MRI-Based Classification of Trauma Survivors with and without Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. It can be difficult to discern the symptoms of PTSD and obtain an accurate diagnosis. Different magnetic resonance imaging (MRI) modalities focus on different aspects, which may provide complementary information for PTSD discrimination. However, none of the published studies assessed the diagnostic potential of multimodal MRI in identifying individuals with and without PTSD. In the current study, we investigated whether the complementary information conveyed by multimodal MRI scans could be combined to improve PTSD classification performance. Structural and resting-state functional MRI (rs-fMRI) scans were conducted on 17 PTSD patients, 20 trauma-exposed controls without PTSD (TEC) and 20 non-traumatized healthy controls (HC). Gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and regional homogeneity were extracted as classification features, and in order to integrate the information of structural and functional MRI data, the extracted features were combined by a multi-kernel combination strategy. Then a support vector machine (SVM) classifier was trained to distinguish the subjects at individual level. The performance of the classifier was evaluated using the leave-one-out cross-validation (LOOCV) method. In the pairwise comparison of PTSD, TEC, and HC groups, classification accuracies obtained by the proposed approach were 2.70, 2.50, and 2.71% higher than the best single feature way, with the accuracies of 89.19, 90.00, and 67.57% for PTSD vs. HC, TEC vs. HC, and PTSD vs. TEC respectively. The proposed approach could improve PTSD identification at individual level. Additionally, it provides preliminary support to develop the multimodal MRI method as a clinical diagnostic aid.

Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder.

Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto-striatal-thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD.

Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve.

BACKGROUND: Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. OBJECTIVE: In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. METHODS: The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. RESULTS: In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. CONCLUSION: These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.

[STUDY ON RELATIONSHIP BETWEEN DIFFUSION TENSOR IMAGING AND VISUAL EVOKED POTENTIAL IN VISUAL PATHWAY OF NEUROMYELITIS OPTICA].

OBJECTIVE: To study the relationship between brain white matter fiber occult lesions and P100 wave latency of visual evoked potential (VEP) in neuromyelitis optica (NMO) patients by diffusion tensor imaging (DTI). METHODS: Twenty patients with NMO who were treated between July 2008 and April 2009 were selected as the trial group. According to the VEP test, the latency of P100 wave was prolonged, the NMO patients were divided into VEP abnormal group (trial group 1) and VEP normal group (trial group 2). Twenty healthy adult volunteers served as the control group. The DTI examination in brain was done to measure the fractional anisotropy (FA) value of optic nerve (FAn), optic tract (FAt), and optic radiation (FAr); and the mean diffusivity (MD) value of optic nerve (MDn), optic tract (MDt), and optic radiation (MDr). The FA, MD, and P100 wave latency were compared between groups, and the correlation between MD, FA, and P100 wave latency of NMO were analyzed. RESULTS: In the 20 NMO patients, 13 patients with VEP had prolonged bilateral P100 wave latency prolongation or no wave (trial group 1), and 7 patients had normal bilateral P100 wave latency (trial group 2). Compared with the trial group 2 and the control group, the FA values were significantly decreased, and the MD values were significantly increased in the trial group 1 (P < 0.05). There was no significant difference in the FA and MD values between the trial group 2 and the control group (P > 0.05). All FA (FAn, FAt, and FAr) values of each part of NMO patients were negatively correlated with the latency of P100 wave (P < 0.05), all MD (MDn, MDt, and MDr) values were positively correlated with the latency of P100 wave (P < 0.05). CONCLUSION: DTI could show small pathylogical changes in the white matter fibers of visual pathway, and there is a correlation between DTI and VEP in NMO, suggesting that a more comprehensive assessment to the condition and prognosis can be made through the VEP in the clinical indicators.

Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China.

The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations.

The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.

Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.