Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study.

BACKGROUND: Complex immune-brain interactions that affect neural development, survival and function might have causal and therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation and schizophrenia (SCZ) have yielded inconsistent findings. METHODS: Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and SCZ in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and SCZ risk. A total of four types of immune signatures (median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP)) were included. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. RESULTS: After FDR correction, SCZ had no statistically significant effect on immunophenotypes. It was worth mentioning some phenotypes with unadjusted low P-values, including FSC-A on NKT (ß = 0.119, 95% CI = 0.044 ~ 0.194, P = 0.002), DN (CD4-CD8-) NKT %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.208, P = 9.03 × 10- 4), and SSC-A on lymphocytes (ß = 0.136, 95% CI = 0.059 ~ 0.213, P = 5.43 × 10- 4). The causal effect of SCZ IgD on transitional was estimated to 0.127 (95% CI = 0.051 ~ 0.203, P = 1.09 × 10- 3). SCZ also had a causal effect on IgD+ %B cell (ß = 0.130, 95% CI = 0.054 ~ 0.207, P = 8.69 × 10- 4), and DP (CD4+CD8+) %T cell (ß = 0.131, 95% CI = 0.054 ~ 0.207, P = 8.05 × 10- 4). Furthermore, four immunophenotypes were identified to be significantly associated with SCZ risk: naive CD4+ %T cell (OR = 0.986, 95% CI = 0.979 ~ 0.992, P = 1.37 × 10- 5), HLA DR on CD14- CD16- (OR = 0.738 (95% CI = 0.642 ~ 0.849, P = 2.00 × 10- 5), CD33dim HLA DR+ CD11b- AC (OR = 0.631, 95% CI = 0.529 ~ 0.753, P = 3.40 × 10- 7) and activated & resting Treg % CD4 Treg (OR = 0.937, 95% CI = 0.906 ~ 0.970, P = 1.96 × 10- 4). CONCLUSIONS: Our study has demonstrated the close connection between immune cells and SCZ by genetic means, thus providing guidance for future clinical research.

Indoor metabolites and chemicals outperform microbiome in classifying childhood asthma and allergic rhinitis.

Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus, Pseudomonas, and Psychrobacter, and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate < 0.05). A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids, indoles, and pyridines. Conversely, homes of diseased children were enriched with mycotoxins and synthetic chemicals, including herbicides, insecticides, and food/cosmetic additives. Using a random forest model, characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools (N = 1290). Indoor metabolites achieved an average accuracy of 74.9% and 77.1% in differentiating schools with high and low prevalence of asthma and AR, respectively, whereas indoor microorganisms only achieved 51.0% and 59.5%, respectively. These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR. This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR, thereby revealing potential novel intervention strategies for these diseases.

Sex-Related Differences in the Relationship between Sugar-Sweetened Beverage Consumption and Cardiorespiratory Fitness: Results from Chinese Cross-Sectional Study on Children.

Sugar-sweetened beverage (SSB) consumption continues to increase among children, with adverse health effects, and China is no exception. Our study investigates the association between SSB consumption and cardiopulmonary fitness. We used stratified whole group sampling to investigate and test SSB consumption and cardiopulmonary fitness in 21,055 children aged 13−15 years in China. A chi-square test and one-way ANOVA were used to compare different categories of SSB consumption. General linear regression analysis and logistic regression analysis were used to analyze the relationship between different SSB consumption and cardiopulmonary fitness in Chinese children. Our research results show the proportions of Chinese children with SSB consumption ≤ 1 time/week, 2−4 times/week, and ≥5 times/week were 33.3%, 52.8%, and 13.9%, respectively. VO2max in children consuming ≥ 5 times/week was lower than those consuming 2−4 times/week and ≤2 times/week of SSB by 0.15 and 0.301 mL·kg−1·min−1, with statistically significant differences (F-value 18.807, p < 0.001). After relevant confounders were adjusted, children in the SSB consumption ≥ 5 times/week group had a higher risk of developing poorer cardiopulmonary fitness than those in the SSB consumption ≤ 1 time/week group (OR: 1.336, 95% CI: 1.181, 1.511) (p < 0.001). In conclusion, the consumption of SSBs among children aged 13−15 in China is higher than the recommended intake by the World Health Organization, and boys are higher than girls. In addition, after adjusting for relevant confounders, the association between SSB consumption and an increased risk of poor cardiorespiratory fitness remained. The relationship between SSB consumption and cardiopulmonary fitness was higher in girls compared with boys.

Lack of Emotional Experience, Resistance to Innovation, and Dissatisfied Musicians Influence on Music Unattractive Education.

Music education is frequently growing around the globe and needs emotional attachments and adoption innovation for the attractive music education that needs researcher's emphasis. Thus, the current article investigates the impact of lack of emotional experience and resistance to innovation on unattractive music education in China. The current research also investigates the mediating impact of dissatisfied musicians among the association of lack of emotional experience, resistance to innovation, and unattractive music education in China. The study has used the primary data collected using questionnaires. The current article examines the validity and reliability using the measurement assessment model and also tests the hypotheses using the structural assessment model with the help of smart-PLS. The results indicated that the lack of emotional experience and resistance to innovation has a positive and significant impact on unattractive music education in China. The findings also revealed that dissatisfied musicians significantly mediate among lack of emotional experience, resistance to innovation, and unattractive music education in China. This article helps policymakers establish policies about making music education attractive for musicians by adopting innovation.

Simple single-shot complete spatiotemporal intensity and phase measurement of an arbitrary ultrashort pulse using coherent modulation imaging.

We propose a simple single-shot spatiotemporal measurement technique called coherent modulation imaging for the spatio-spectrum (CMISS), which reconstructs the full three-dimensional high-resolution characteristics of ultrashort pulses based on frequency-space division and coherent modulation imaging. We demonstrated it experimentally by measuring the spatiotemporal amplitude and phase of a single pulse with a spatial resolution of 44 µm and a phase accuracy of 0.04 rad. CMISS has good potential for high-power ultrashort-pulse laser facilities and can measure even spatiotemporally complicated pulses with important applications.

Temporal contrast enhancement of ultrashort pulses using a spatiotemporal plasma-lens filter.

The spatiotemporal plasma-lens filter proposed here enhances the temporal contrast of the ultrashort pulse laser by combining plasma optics and spatial filtering. Experimentally, the spatiotemporal plasma-lens filter has improved the temporal contrast by 2 orders of magnitude with 80% laser transmission efficiency under a 1 Hz repetitive laser operation. Not only were the pre-pulse and the pedestal cleaned out, but also the rising edge of the main pulse was sharpened.

Dynamic chromatic aberration pre-compensation scheme for ultrashort petawatt laser systems.

A novel chromatic aberration pre-compensation scheme for ultrashort petawatt laser systems was proposed. The pre-compensation scheme consists of a convex lens, group of concave lenses, and a spherical reflector combined with a conventional vacuum chamber. It provides a versatile method to accurately compensate the chromatic aberration of an entire laser system via controlling the amount of propagation time delay (PTD) induced by the compensator without changing the input and output beam size. A compensator, tailored based on the proposed scheme, was designed and experimentally evaluated for the Shen-Guang-II 5PW (SG-II 5PW) laser system at Shanghai Institute of Optics and Fine Mechanics (SIOM). The experimental results verified that chromatic aberration in the laser system was almost fully compensated: the size of laser beam focused by an f/2.42 off-axis parabolic mirror (OAP) was reduced tremendously from 32×18µm2to about 4×4µm2at full width at half maximum (FWHM). The proposed scheme provides the flexibility to accurately correct chromatic aberration in high-power laser systems within a wide dynamic range.

Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells.

Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism. Scutellarin enhanced the sensitivity of prostate cancer cells to cisplatin. MTT assays revealed that cell viability was significantly decreased in the prostate cancer cells treated with Scutellarin. Flow cytometric analysis indicated that Scutellarin suppressed cell proliferation by promoting G2/M arrest and inducing apoptosis. We employed western blotting to delineate the underlying mechanisms involved in the G2/M arrest and apoptosis. Comet assay and γH2AX immunocytochemistry were used to detect levels of DNA damage in PC3 cells exposed to Scutellarin and/or cisplatin. Our data revealed that Scutellarin significantly induced prostate cancer cell apoptosis by activating the caspase cascade. An increase in the Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential and cell cycle arrest at G2/M phase were accompanied by the apoptosis induction. Additionally, Scutellarin altered the protein expression of cell cycle and apoptosis regulatory genes by downregulating Cdc2, cyclin B1 and Bcl-2 and upregulating caspase-3, caspase-9 and Bax in prostate cancer cells. Furthermore, Scutellarin sensitized PC3 cells to cisplastin treatment in a dose-dependent manner. Taken together, our data confirmed the cytotoxicity of Scutellarin against prostate cancer PC3 cells and provide new findings in regards to Scutellarin sensitizing prostate cancer cells to chemotherapy. Our findings suggest that Scutellarin has potential to be used as a novel antineoplastic therapeutic candidate for prostate cancer patients.

Gender differences in emotion experience perception under different facial muscle manipulations.

According to embodied emotion theory, facial manipulations should modulate and initiate particular emotions. However, whether there are gender differences in emotion experience perception under different facial muscle manipulations is not clear. Therefore, we conducted two behavioral experiments to examine gender differences in emotional perception in response to facial expressions (sad, neutral, and happy) under three conditions: (1) holding a pen using only the teeth (HPT), which facilitates the muscles typically associated with smiling; (2) holding a pen using only the lips (HPL), which inhibits the muscles typically associated with smiling; and (3) a control condition--hold no pen (HNP). We found that HPT made the emotional feelings more positive, and that the change degree of female's ratings of sad facial expressions between conditions (HPL to HPT) was larger than males'. These results suggested cognition can be affected by the interaction of the stimuli and the body, especially the female.

Natural YMDD-motif mutants affect clinical course of lamivudine in chronic hepatitis B.

AIM: To investigate the prevalence of nature tyrosine-methionine-aspartic acid-aspartic acid motif mutations in chronic hepatitis B (CHB) patients and to evaluate the efficacy of lamivudine. METHODS: A total of 1268 CHB patients were recruited from the outpatient and inpatient departments of six centers. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutations were analyzed using the hepatitis B virus (HBV) drug resistance line probe assay. Forty voluntary patients were selected from those with positive or negative natural YMDD mutations to undergo treatment with lamivudine. RESULTS: YMDD mutations were detected in 288 (22.71%) of the 1268 CHB patients. Multivariate analysis revealed that the patients' HBV DNA level (P=0.0282) and hepatitis B e antigen status (P=0.0133) were also associated with natural YMDD mutations. The rates of normalization of alanine aminotransferase levels and HBV DNA nondetection at 6, 24, 36, and 48 wk were compared between the patients with natural YMDD mutations and those without, and the differences were not significant. However, there was a significant difference in the cumulative emergence rates of virological breakthrough at 48 wk in the patients with natural YMDD mutations and those without (32.5% vs 12.5%, P=0.032). CONCLUSION: Naturally occurring YMDD mutations are detectable in a large proportion of CHB patients; breakthrough hepatitis tended to occur in patients with natural YMDD mutations.

[The Role of c-fos in the Production of Follicle-Stimulating Hormone and the Related Signal Transduction Pathways].

As an immediate early gene, c-fos plays a critical role in stimulating the synthesis and release of pituitary FSH via GnRH. To better understanding the mechanism how c-fos works in the transcription of FSHbeta under different frequency of pulsatile GnRH stimulation, this paper reviewed the signal trans- ductions initiated by c-fos in pituitary, which include cAMP pathway, MAPK pathway, Ca2+ /calmodulin-dependent kinases pathway and nuclear factor of activated T-cells (NFAT) pathway. It will be helpful for research in molecular targeted immunotherapy and eventually effective treatment to the infertility which resulted from defection or mutation of c-fos and c-fos related signal pathway elements.

YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study.

OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

RTMS may be a good choice for pregnant women with depression.

Due to the possible adverse effects on fetus, the treatment of pregnant women with depression is a difficult problem in the field of psychiatry. Repetitive transcranial magnetic stimulation (rTMS) was used to treat three pregnant women with depression in the early pregnancy. After systemic treatments, the patient's depressive symptoms significantly relieved, and each of them smoothly provided a healthy baby. Up to now, we have not found that rTMS can be harmful to fetuses. RTMS may be a good choice for pregnant women with depression.

[A study on characteristics of the criminals with alcohol-related offence in forensic psychiatry].

OBJECTIVE: To explore the criminal characteristics of alcohol-related offence in forensic psychiatric practice. METHODS: Ninety cases were collected according to our research criteria and were divided into two groups, ordinary drinking (OD) (63 cases) and chronic alcoholic (CA) (27 cases). Descriptive and comparative studies were conducted between the two groups. RESULTS: 54.0% OD group had induced incident compare with 22.2% CA group; 58.7% of OD group had a motive while 55.6% of CA group were with no clear motive; 66.6% of OD group had a chosen target, 51.8% of CA group with no clear target; 19.0% of OD group chose criminal time while only 3.7% of CA group did; 61.9% of OD took certain anti-detection means while 59.3% of CA group stayed at the scene. 98.4% of OD group was found guilty and only 3.7% of CA was found guilty. CONCLUSION: OD group tends to have induced events, criminal motive, often are found to be guilty; CA group tends to be older, lacks awareness of self-protection during and after committing the crime, and usually is found not guilty or only partially responsible.

The effects of Shuxuetong on the pathology of cerebral ischemia-reperfusion injury and GABA and TNF-alpha expression in gerbil models.

Objective To study the protective effect and mechanism of Shuxuetong on gerbil brain tissue from the area of ischemia-reperfusion. Methods Cerebral ischemia-reperfusion animal model has made by transient clipping bilateral common carotid arteries in gerbils. Pathological changes in the hippocampal tissue were observed at different reperfusion time (12h, 3 d, 7 d). The expression levels of GABA and TNF-alpha in the hippocampal CA1 subfield were observed using immunohistochemitry at 12 h, 3 d after reperfusion. The difference of above indices among false operation group, ischemia-reperfusion group and treatment group were compared. Results The injuries of pathology to hippocampal area in ischemia reperfusion group were more serious than treatment group. The expression levels of GABA in treatment group were significantly increased compared with ischemia-reperfusion group, but the expression levels of TNF-alpha between the two groups have no difference. Conclusion Shuxuetong has protective effect on brain tissue of ischemia-reperfusion by enhancing the expression of GABA in the hippocampal tissue.