A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood.

Background: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level. Objective: This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children. Methods: A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets. Results: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets. Conclusions: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Analysis of varieties and standards of Saxifragaceae medicinal plants used in Tibetan medicine / 中国中药杂志

On the basis of literatures and standards relating to Tibetan medicine, the varieties, origin, standards and efficacy of Saxifragaceae plant used in Tibetan medicine were summarized. According to the findings, 75 species(including varieties) in 8 genera of Saxifragaceae plants, involving 21 varieties, are used in Tibetan medicine. Among them, 9 commonly used varieties, namely Songdi, Sedi, Yajima, Aoledansaierbao, Jiansidawu, Saiguo, Katuer, Sangdi, Maoqinghong, are recorded in Chinese Pharmacopoeia, Ministry Standards for Tibetan Medicine, Tibetan Medicine Standards and other local standards, accounting for 42.9% of the total number of varieties. Tibetan names, Tibetan translation of Chinese names, as well as original plant of Tibetan medicine varieties are quite different in relevant Tibetan medicine standards and literatures, which resulted in common phenomena of synonym and homonym. The standards of most varieties only involve characters, and microscopic, physical and chemical identification, with low quality standards. Based on the results of the analysis, this paper suggests strengthening surveys on herbal textual research, resources and current utilization of Saxifragaceae plants used in Tibetan medicine, summarizing the varieties, establishing improved quality standards, and perfor-ming a comparative study on therapeutic material basis and biological activity of different original plants, in order to promote rational use of these medicinal plant resources, and ensuring the accuracy, safety, and effectiveness of clinical medication.

A Volumetric and Functional Connectivity MRI Study of Brain Arginine-Vasopressin Pathways in Autistic Children.

Dysfunction of brain-derived arginine-vasopressin (AVP) systems may be involved in the etiology of autism spectrum disorder (ASD). Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors. The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity (FC) of specific brain regions in autistic children compared with typically developing children (TDC) aged from 3 to 5 years. The results showed: (1) children with ASD had a significantly increased volume in the left amygdala and left hippocampus, and a significantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level. (2) Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist. (3) The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD. (4) Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC. (5) The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale. These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.

Research Progress in Zingiber officinale / 中国药学杂志

Zingiber officinale has a long application history in China, it is used as medicine, also condiment, food and drinks. The chemical constituents of Zingiber officinale include volatile oil, gingerol, diaryl-heptnaoids and so on. Scientific research showed that Zingiber officinale is widely used in anti-nausea, resisting gastric ulcer, anti-bacterial, anti-phlogistic, analgesia, antioxidant, resisting motion sickness, anti-tumor, hypoglycemic, antilipidemic, and improving cardiocerebral vascular system and so on. Zingiber officinale is recommended as a healthy food by doctor of traditional Chinese medicine in all times. In summary, it's worth to be researched and developed in detail.

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms.

Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The "twin" nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

Design and analyze mathematical algorithms of intestinal absorption and metabolism of multicomponent drug / 中国中药杂志

Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.

Analysis of multicomponent drug metabolism used in clinical pharmacy research of traditional Chinese medicine / 中国中药杂志

Multicomponent drug metabolism can be defined as a research area that, rather than pharmacokinetics and pharmacodynamics, is a concerted dynamic metabolic variation of one component in several other compounds circumstance with the interaction of transport protein and drug metabolizing enzymes, and the study of the dynamic course of multiple components must be simultaneously determined. By the use of multicomponent drug metabolism in the clinical pharmacy research of traditional Chinese medicine (TCM), it can become a useful tool with the integration of the overall dialectical method and the concrete molecular approach.

Combination analysis of new drug discovery with "Xiaohe Silian" method and traditional Chinese medicine clinical pharmacy / 中国中药杂志

With the kernel of efficacy, "Xiaohe Silian" was a pattern and method for new drug discovery which was constituted with "metabolism-efficacy, toxicity-efficacy, quality-efficacy and structure-efficacy". Its connotation was in keeping with traditional Chinese medicine (TCM) clinical pharmacy. This paper systematically summarized the research method of new drug discovery practice process for TCM. To avoid western drug like in TCM new drug discovery, we carried out combination analysis with TCM clinical pharmacy. The correlation analysis between basic elements of "Xiaohe Silian(n) and TCM clinical pharmacy was studied to guarantee this method could integrate closely with TCM clinic from all angles. Hence, this method aimed to provide a new method for TCM new drug discovery on the basis of TCM clinical pharmacy with insisting on holistic view of multicomponent study, kinetic view of metabolic process when the curative effect occurred and molecular material view of quality control and structure-activity exposition.

Mothers of autistic children: lower plasma levels of oxytocin and Arg-vasopressin and a higher level of testosterone.

BACKGROUND: Autism is a pervasive neurodevelopmental disorder,thought to be caused by a combination of genetic heritability and environmental risk factors. Some autistic-like traits have been reported in mothers of autistic children. We hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex hormones, found in autistic children, may also exist in their mothers. METHODS: We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal children by enzyme immunoassay and radioimmunoassay, respectively and investigated their relationships with the children's autistic behavior scores (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)). RESULTS: Significantly lower plasma concentrations of OXT (p<0.001) and AVP (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found in mothers of autistic children vs. those of control. The children's autistic behavior scores were negatively associated with maternal plasma levels of OXT and AVP. CONCLUSIONS: These results suggest that dysregulation of OXT, AVP and/or testosterone systems exist in mothers of autistic children, which may impact children's susceptibility to autism.

Transcutaneous electrical acupoint stimulation in children with autism and its impact on plasma levels of arginine-vasopressin and oxytocin: a prospective single-blinded controlled study.

Acupuncture increases brain levels of arginine-vasopressin (AVP) and oxytocin (OXT), which are known to be involved in the modulation of mammalian social behavior. Transcutaneous electrical acupoint stimulation (TEAS) is often used clinically to produce a similar stimulation to that of acupuncture on the acupoints. In the present study, TEAS was applied to children with autism to assess its therapeutic efficacy. Seventy-six autistic children receiving rehabilitation training were divided into 2 groups: a treatment group receiving TEAS 30min per day, 5 days per week for 12 weeks (n=37) and a control group without TEAS treatment (n=39). A series of rating scales was used in outcome assessment. Plasma levels of AVP and OXT were determined by enzyme immunoassay (EIA) before and after treatment. The TEAS group showed a significant improvement over the control in their emotional response, fear or anxiety, level/consistency of intellective relations and general impressions on the Childhood Autism Rating Scale (CARS) as well as improvements in the sensory and related factors in the Autism Behavior Checklist (ABC). In addition, the varieties of accepted food increased after TEAS treatment. It appears that TEAS was effective in autistic children who showed passive and aloof behavior, but not in those who were active but odd. The plasma level of AVP was significantly higher in the TEAS group than in the control group after the intervention. In addition, the change in the plasma AVP level paralleled the improvement of some of the behavior factors in CARS, including adaptation to environmental change, listening response, perceptive response and fear or anxiety. It is concluded that TEAS is effective for the treatment of autistic children with a passive and aloof social interaction style. Changes in plasma levels of AVP and possibly OXT may be involved in mediating the therapeutic effect of TEAS.

Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios.

The glutamate pathways are involved in diverse processes such as learning and memory, epilepsy, and they play important roles in neural plasticity, neural development, and neurodegeneration. It has been proposed that autism could be a hypoglutamatergic disorder. Recently, Jamain et al. reported that the glutamate receptor 6 (GluR6 or GRIK2) is in linkage disequilibrium with autism. In the present study, the transmission disequilibrium test (TDT) and the haplotype transmission were performed to analyze the four SNPs (SNP1: rs995640; SNP2: rs2227281; SNP3: rs2227283; SNP4: rs2235076) of GluR6 in 174 Chinese Han parent-offspring trios. The TDT demonstrated that the two SNPs (SNP2 and SNP3) showed preferential transmission (TDT P = 0.032). The global chi(2) test for haplotype transmission also revealed an association between GluR6 and autism (chi(2) = 10.78, df = 3, P = 0.013). Our results suggested that GluR6 is in linkage disequilibrium with autism.