OBJECTIVETo explore the recognition ability and abnormal processing characteristics to basic emotional faces in the early phase in children with autism spectrum disorders (ASD).

METHODSPhotos of Chinese static faces with four basic emotions (fearful, happy, angry and sad) were used as stimulus. Twenty-five ASD children and twenty-two age- and gender-matched typical developed children (normal controls) were asked to match the emotional faces with words. Event-related potential (ERP) data were recorded concurrently.

RESULTSN170 latencies for total emotion and fearful face in the left temporal region were faster than in the right one in normal controls (P<0.05), but the results were not noted in ASD children. Further, N170 latencies in the left temporal region of ASD children were slower than normal controls for total emotion, fearful and happy faces (P<0.05), and their N170 latencies in the right temporal region were prone to slower than normal controls for angry and fearful faces.

CONCLUSIONSThe holistic perception speed of emotional faces in the early cognitive processing phase in ASD children is slower than normal controls. The lateralized response in the early phase of recognizing emotional faces may be aberrant in children with ASD.

BackgroundPostmenopausal women with metabolic syndrome (MetS) have increased cardiovascular morbidity and left ventricular diastolic dysfunction (LVDD). The various protective effects of astragalus membranaceus (AM) have been described in previous studies. Therefore, this study aimed to evaluate the effects of different doses of AM on diastolic function in postmenopausal hypertensive women with MetS.

MethodsThis was a prospective, randomized controlled study. The postmenopausal hypertensive patients with MetS were enrolled from Lanzhou University Second Hospital from March 2014 to April 2015. Patients were divided into three groups: control group (received conventional medical treatment), AM Group 1 (received AM capsules at 5 g/d additionally), and AM Group 2 (received AM capsules at 10 g/d additionally). Echocardiographic and clinical characteristics were evaluated before and 12 months after treatment. Quantitative data were analyzed using unpaired t-test, analysis of variance, and multiple linear regression analysis.

ResultsA total of 154 patients were subjected to final analysis. In the AM Group 2, significant improvements were noted in diastolic function 12 months after treatment than those of the control group, including the early diastolic mitral annular velocity (E'; 0.065 ± 0.007 m/s vs. 0.061 ± 0.008 m/s, P = 0.014), the ratio of the early diastolic mitral peak flow velocity to the late diastolic mitral peak flow velocity (E/A; 0.81 ± 0.05 vs. 0.80 ± 0.06, P = 0.012), the ratio of E' to the late diastolic mitral annular velocity (E'/A'; 0.56 ± 0.12 vs. 0.51 ± 0.13, P = 0.048), and the ratio of the early diastolic mitral peak flow velocity (E) to E' (E/E'; 10.70 ± 1.30 vs. 11.37 ± 1.73, P = 0.031). After treatment, E/E' (10.70 ± 1.30 vs. 11.24 ± 1.56, P = 0.021), deceleration time (DT; 261.49 ± 44.41 ms vs. 268.74 ± 53.87 ms, P = 0.046), and E'/A' (0.56 ± 0.12 vs. 0.52 ± 0.13, P = 0.019) values improved more significantly than those of AM Group 2 before treatment. Besides, waist circumference was positively correlated with E' (r = 0.472; P = 0.003) and E'/A' (r = 0.321; P = 0.047). In addition, the waist-to-hip ratio was a significant predictor of DT (r = 0.276; P = 0.041), E' (r = -0.590; P < 0.001), E/E' (r = 0.454; P = 0.004), and E'/A' (r = -0.377; P = 0.018).

ConclusionsConventional medical plus AM therapy improved diastolic function. Moreover, WC and WHR might be risk factors for LVDD.

Chinese Clinical Trial RegisterChiCTR-TRC-11001747. http://www.chictr.org.cn/showprojen.aspx?proj=7798.

BACKGROUNDMatrix metalloproteinase (MMP)-2 plays an important role in the remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated the differences of MMP-2 expression between LV and RV in response to nandrolone decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice, based on their structural, functional, and biochemical characteristics.

METHODSTotally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups, including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups. After respective treatments for 8 weeks, echocardiographic examination was used to assess the cardiac structure and function. Van Gieson stain was used to examine the fibrosis of LV and RV in response to different treatments, and Western blotting analysis was performed to explore different MMP-2 expressions between LV and RV in response to ND and/or ST. Analysis of variance was used for comparing the four groups.

RESULTSAt 8 weeks, right ventricular dimension/body weight in the ND group was larger than the other three groups (F = 7.12, P < 0.05) according to the echocardiographic examination. Fibrosis induced by ND administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2 expression of the ND group in RV was significantly greater than the control and NS groups in RV and the corresponding ND group in LV.

CONCLUSIONThe experimental data support the hypothesis that ND administration induces greater MMP-2 expression increase in RV compared to LV, leading to consequent RV dilation.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

OBJECTIVETo compare the effect and differences sex the influence of hormone levels of perimenopau-sal syndrome patients between manual acupuncture and electroacupuncture (EA).

METHODSA total of 50 cases with perimenopausal syndrome were randomly assigned into an manual acupuncture group (27 cases) and an EA group (23 cases), and 1 case dropped in the EA group. The acupoints in the two groups were Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), and Sanyinjiao (SP 6). Acupuncture with 3-time small and even manipulation of lifting, thrusting and twirling was used in the acupuncture group, once 10 min. EA with sparse-dense wave and 10 Hz/50 Hz was applied in the EA group for 30 min. The treatments in the two groups were for continuous 8 weeks (24 times in total), once the other day, 3 times a week. The scores of 24-hour hot flashes even, menopausal rating scale (MRS) and menopause-specific quality of life questionnaire (MENQOL) were recorded before treatment and after 4-week and 8-week treatment, as well as 12 and 24 weeks after treatment. Serum sex hormone levels were tested before and after 8-week treatment as well as 12 weeks after treatment, including serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estracliol (E).

RESULTSCompared with those before treatment, the 24-hour hot flashes even score, MRS and MENQOL scores were significantly lower after 4-week and 8-week treatments, 12 and 24 weeks after treatment (all<0.05). All the above scores after 8-week treatment were lower than those after 4-week treatment (all<0.05); and the scores 12 and 24 weeks after treatment were lower than those after 4-week and 8-week treatments (all<0.05); all the scores after treatment were not significantly different at any time between the two groups (all>0.05). Compared with those before treatment, serum FSH and Eapparently improved in the two groups after 8-week treatment and 12 weeks after treatment (all<0.05). LH levels did not significantly change in the two groups (all>0.05). All the serum sex hormone levels showed no significant difference between the two groups (all>0.05).

CONCLUSIONSBoth acupuncture and EA can improve perimenopausal symptoms and serum sex hormone. The effects are similar.

OBJECTIVETo investigate the influence of home nurture environment on language development and social emotion in children with developmental language disorder (DLD).

METHODSThe 1-3 Years Child Home Nurture Environment Scale, Gesell Developmental Scale, and Infant-Toddler Social and Emotional Assessment Scale were used for the evaluation of 125 children with DLD. A total of 130 children with normal language development matched for age and sex were enrolled as control group.

RESULTSCompared with the control group, the DLD group had a significantly higher proportion of children in a bad home nurture environment and significantly lower scores of all domains of home nurture environment (P<0.05). In children with DLD, the home nurture environment score was positively correlated with the level of language development (r=0.536, P<0.01) and the score of ability domain in social emotion (r=0.397, P<0.01) and was negatively correlated with the scores of the domains of explicit behavior, covert behavior, and imbalance in social emotion (r=-0.455, -0.438, and -0.390 respectively, P<0.01). Home nurture environment had direct influence on language development in children with DLD and affected their language development via the mediating effect of social emotion.

CONCLUSIONSHome nurture environment influences language development and social emotion in children with DLD, and social emotion has a partial mediating effect between home nurture environment and language development.

Child, Preschool ; Emotions ; Environment ; Female ; Humans ; Infant ; Language Development ; Language Development Disorders ; psychology ; Male ; Social Behavior

BACKGROUNDAccording to the renal phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (iMN) could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN.

METHODSA total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 (80.5%) with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson's Chi-square test or Fisher's exact test.

RESULTSOf the 231 iMN patients, 189 showed renal detectable PLA2R expression (81.8%). The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated (n = 145) and non-PLA2R-associated iMN patients (n = 41). However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN (31.7% vs. 8.3%, P = 0.000). The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN (P = 0.004). The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants (complete remission [CR] 42.9%; partial remission [PR] 14.3%) compared with PLA2R-associated iMN (CR 3.2%; PR 48.4%, P = 0.004) at the 3rd month.

CONCLUSIONSThere were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with PLA2R-associated iMN.

Adult ; Autoantibodies ; metabolism ; Female ; Glomerulonephritis, Membranous ; drug therapy ; metabolism ; pathology ; urine ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney ; metabolism ; pathology ; Male ; Middle Aged ; Receptors, Phospholipase A2 ; metabolism ; Retrospective Studies

BACKGROUNDHypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.

METHODSThree affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided.

RESULTSIn Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations.

CONCLUSIONSThis study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

Child ; Female ; GATA3 Transcription Factor ; genetics ; Genotype ; Hearing Loss ; genetics ; Hearing Loss, Sensorineural ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypoparathyroidism ; genetics ; Male ; Mutation ; genetics ; Nephrosis ; genetics ; Pedigree

Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

To systematically review the adjuvant effects of Zhenyuan capsule on improving the cardiac function of patients with chronic heart failure. Databases including PubMed, EMbase, the Cochrane Library, CBM, CNKI, VIP and Wanfang Data were searched electronically from inception to October 2016 to collect randomized controlled trials (RCTs) about Zhenyuan capsule for adjuvant treatment of chronic heart failure. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 14 RCTs involving 1 204 patients were included. The results of Meta-analysis showed that the Zhenyuan capsule group had significantly better effectiveness in cardiac function (RR=1.27, 95%CI 1.20 to 1.35, P < 0.000 01), stroke volume (WMD=7.62, 95%CI 6.39 to 8.84,P < 0.000 01), scores of HAMA (WMD=-4.16, 95%CI -5.59 to -2.72, P < 0.000 01), psychological effect of HAMA (RR=1.47, 95%CI 1.15 to 1.89, P=0.002), and traditional Chinese medical syndrome (RR=1.46, 95%CI 1.25 to 1.72, P < 0.000 01) than those of the control group, with statistically significant differences. Current evidence showed that Zhenyuan capsule combined with routine treatment could improve the cardiac function and quality of life of patients with chronic heart failure, and with high safety. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.