Insight into modulators of sphingosine-1-phosphate receptor and implications for cardiovascular therapeutics.

Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.

Correlation between 23 metals and metalloids elements in the urine and thyroid function of traffic police / 公共卫生与预防医学

Objective To investigate the correlation between 23 metals and metalloids elements in the urine and thyroid function indicators in the blood of traffic police. Methods A cross-sectional study was performed to assess the effects of 23 metals and metalloids elements in the urine on blood thyroid function indicators in 166 traffic policemen (122 field staff and 44 internal staff) in Wuhan, Hubei Province. Each subject received an occupational health examination. Results After multiple corrections for false detection rates, in the polymetallic model, the levels of urinary manganese and urinary uranium were positively correlated with the levels of thyroid peroxidase antibody (TPOAb) in the blood (β = 66.57, 95% CI 2.92-130.22, P = 0.040 and β = 62.43, 95% CI 14.37-110.49, P = 0.011), and the level of urinary uranium was positively correlated with thyroid stimulating hormone (TSH) levels in the blood (β = 6.20, 95% CI 2.68-9.72 , P = 0.001). Urinary uranium level was negatively correlated with free thyroxine level in the blood (FT4) (β = -2.03, 95 % CI (-3.67 )- (-0.39), P = 0.015), and urinary lead level was negatively correlated with blood TSH level (β = -4.59, 95% CI (-8.67) - (-0.51), P = 0.027). Conclusion Manganese exposure is related to the increase of TPOAb level in blood, uranium exposure is related to the increase of TPOAb and TSH levels and the decrease of FT4 level in blood, and lead exposure is related to the decrease of TSH level in blood, suggesting that more attention should be paid to the effects of heavy metals on the thyroid of traffic police.

The characteristics of optical coherence tomography angiography in aquaporin-4 antibody positive neuromyelitis optica spectrum disorders / 中华眼底病杂志

Objective:To investigate the alteration of retinal perfusion in aquaporin-4 antibody (AQP4-ab) positive neuromyelitis optica spectrum disorders (NMOSD) patients by optical coherence tomography angiography (OCTA).Methods:A case-control study. Forty-eight AQP4-ab positive NMOSD patients (96 eyes) and 20 age and gender matched healthy controls (40 eyes) were recruited from September 2015 to August 2017 at the Eye & ENT Hospital of Fudan University. Patients of both eyes were included in the groups. The patients were further divided into 4 subgroups (0 ON, 1 ON, 2 ON, 3+ ON group) according to the number of episodes of ON (0, 1, 2, or 3+) with respect to 30、22、31、13 eyes. 0 ON group had no history of ON episodes; 1 ON group, 2 ON group, and 3+ ON group had ON episodes 1, 2, ≥3 times, respectively. All patients underwent complete ophthalmological examinations including BCVA, visual field and OCTA examination. The BCVA was recorded for each eye using metric notation from the Snellen chart, and then converted to the logarithm of the minimum angle of resolution. The central visual field was assessed using a Humphrey Field Analyzer 750 and the mean deviation (MD) was determined. OCTA scans of the optic disc (4.5 mm × 4.5 mm) and macula (6 mm × 6 mm) were acquired. Radial peripapillary capillary (RPC) vessel density, superficial capillary plexus vessel density (SVD), the thickness of ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were determined. The generalized estimating equations was performed to compare the difference of BCVA, MD, pRNFL thickness, GCIPL thickness, RPC vessel density and SVD among the groups and the correlations between retinal perfusion and retinal structure, visual function were analyzed.Results:The RPC vessel density and SVD were significant lower in the 0 ON group compared with healthy group (Wald χ2=7.190, 10.134; P<0.01), however, the BCVA, pRNFL and GCIPL thickness were not significant difference between the two groups (Wald χ2=2.308, 1.020, 2.558; P>0.05). The BCVA, visual field MD, RPC vessel density, SVD, pRNFL and GCIPL were significant lower in 1 ON, 2 ON and 3+ ON groups compared with healthy group and 0 ON group (Wald χ2=12.390, 11.346, 38.860, 18.040, 45.418, 26.608; P<0.001 ), but the parameters had no significant difference among the three groups ( P>0.05). The RPC vessel density was significantly correlated with pRNFL thickness ( β=0.372, standard error=0.018, P<0.001), and the SVD was significantly correlated with GCIPL thickness ( β=0.115, standard error=0.204, P<0.001). The MD and BCVA was significantly correlated with peripapillary vessel density after adjustment for other variables (BCVA: β=0.025, standard error=0.005, P=0.000; visual field MD: β=0.737, standard error=0.185, P=0.000). Conclusions:Subclinical primary retinal vasculopathy may occur in NMOSD prior to ON attack, the ON attack may further impair visual function, retinal structure and perfusion, however, the extent of injure is not relevant with the increase of ON attack. The peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients.

Painful tonic spasm and spinal cord injury in patients with neuromyelitis optica spectrum disorder / 中华物理医学与康复杂志

Objective:To investigate the relationship between painful tonic spasm (PTS) and spinal cord injury in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data, serum AQP4-IgG antibody levels and magnetic resonance data of 138 patients with NMOSD were analyzed. Those with spinal cord involvement were assessed using the American Spinal Injury Association Impairment Scale (AIS) to investigate the relationship between PTS and spinal cord injury.Results:The prevalence of PTS among the NMOSD patients was 36% (51/138), and all of the 51 NMOSD patients with PTS showed spinal cord lesions, an incidence significantly different from those without PTS. However, there were no significant differences in the age of onset, gender, disease duration, AQP4-IgG levels, lesion location, range of spinal cord lesions, or AIS grade between the NMOSD patients with and without PTS.Conclusion:PTS is a prevalent concomitant of NMOSD. As a common symptom of remission and recurrent remission, PTS is associated with myelopathy. This study failed to find any correlation between PTS and the affected spinal cord site or segment range. There was also no correlation between PTS and AIS grading among these subjects.

The mediating effect of health-related hardiness on the degree of physical disability and perceived stress in Chinese female patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare and chronic disease of the central nervous system. The characteristics and main symptoms of recurrent NMOSD lead to an increase in psychological stress and accelerate a decline in the patients' quality of life. The incidence of NMOSD in the Chinese population is much higher than that for other countries and the majority of NMOSD patients are female. In general, there are sex differences in the perception and management of stress, with females experiencing higher levels of perceived stress than males. Thus, we should be concerned about the psychological issues experienced by Chinese female NMOSD patients. Health-related hardness is a psychological adjustment factor that could affect perceptions of illness that impact on NMOSD patients. The objective of this study was to evaluate the mediating role of health-related hardiness on physical disability and perceived stress in Chinese NMOSD female patients. METHODS: Participants were 68 females patients with NMOSD treated at the Department of Neurology, Huashan Hospital, Fudan University, China, between March and September 2018. Patients were evaluated for their degree of physical disability, perceived stress, and health-related hardiness. Measures included the Expanded Disability Status Scale (EDSS), Perceived Stress Scale (PSS), and Health-related Hardiness Scale (HRHS). Pearson's correlation analyses and stepwise multiple linear regression analysis were used. RESULTS: Findings indicated a positive correlation between the PSS and EDSS (r = 0.735, P < 0.001) and a negative correlation between the PSS and HRHS total score (r = -0.441, P < 0.001). After adjusting for the confounding factors, the EDSS was found to have a positive predictive effect on the PSS (ß = 2.743, P = 0.000), and the HRHS was found to have a negative predictive effect on the PSS (ß = -0.152, P = 0.04). Mediation analysis showed a direct effect of the EDSS on the PSS, and as a mediating variable for health-related hardiness (α = -1.928, b = -0.152, c = 2.743, c' = 2.481), which was statistically significant (P < 0.05). The mediating effect of health-related hardiness accounted for 10.68% of the total effect. CONCLUSIONS: As a mediating variable, health-related hardiness indirectly affected perceived stress caused by physical disability and improved health-related hardiness. This was beneficial in reducing psychological stress and promoting mental health in NMOSD female patients.

A retrospective study of ocular manifestations and aquaporin 4 antibody concentrations in 132 patients with neuromyelitis optica / 中华眼底病杂志

Objective To observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients,and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.Methods A retrospective case study.From September 2009 to March 2014,132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study.Among the patients,74 patients (56.06％) were involved in optic nerve for the first time,among which 63 patients (47.72％) were involved in optic nerve alone,and 11 patients (8.33％) were involved in optic nerve and spinal cord at the same time.The recurrence rate was 62.88％ (twice or more).All patients underwent BCVA,slit lamp microscope,fundus examination,thyroid function,sex hormones,and serum AQP-4Ab detection.BCVA was recorded at admission and before discharge from hospital,and worse BCVA was recorded in binocular patients.The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.Results Among the 74 patients with optic nerve involved in the first onset,50 patients with BCVA＜0.1 at the initial diagnosis (67.57％);AQP-4Ab positive was found in 56 patients,which including 13,9 and 34 patients of AQP-4Ab titer 5-60,61-100 and ＞ 100 RSRU/ml.After 2 weeks of treatment,BCVA improved in 40 patients (71.42％),including 11 (84.62％),6 (66.67％) and 23 (67.64％) ofAQP-4Ab titer 5-60,61-100 and ＞ 100 RSRU/ml.Among 132 patients,98 patients (74.24％) were AQP-4Ab positive.There were 73 patients (55.30％) with abnormal immune rheumatoid index.Conclusions The optic nerve is involved in 56.06％ patients with NMO for the first time,and 67.57％ of the patients had poor vision with BCVA＜0.1.BCVA prognosis is better in patients with serum AQP-4Ab titer of 5-60 RSRU/ml.

Lumen degradation analysis of LED lamps based on the subsystem isolation method.

The lumen degradation of LED lamps undergoing an accelerated aging test is investigated. The entire LED lamp is divided into three subsystems, namely, driver, lampshade, and LED light source. The parameters of output power [Watts (W)], transmittance (%), and lumen flux (lm) are adopted in the analysis of the degradation of the driver, lampshade, and LED light source, respectively. Two groups of LED lamps are aged under the ambient temperatures of 25°C and 85°C, respectively, with the aging time of 2000 h. The lumen degradation of the lamps is from 3.8% to 4.9% for the group under a temperature of 25°C and from 10.6% to 12.7% for the group under a temperature of 85°C. The LED light source is the most aggressive part of the three subsystems, which accounts for 70.5% of the lumen degradation of the LED lamp on average. The lampshade is the second degradation source, which causes 21.5% of the total amount on average. The driver is the third degradation source, which causes 6.5% under 25°C and 2.8% under 85°C of the total amount on average.

Analysis on the Influencing Factors of Hospitalization Expenses in 7558 Cases of Patients with Mental Illness / 中国卫生经济

Objective: To analyze the cost of mental illness inpatients in Heilongjiang Neuropathy and Psychopathy Hospital in the past 5 years, to understand the current situation and explore its influencing factors. Methods: The cost composition of 7 558 patients discharged from hospital from 2013 to 2017 was analyzed, and the single factor analysis and multiple factor regression analysis were carried out. Results:The hospitalization cost was increasing year by year, the drug cost ratio decreased year by year, and the treatment cost ratio increased year by year. The main factors that affected the average daily cost of bed, according to its effect on the average daily cost of bed, were: days of hospitalization, emotional disorders(mood disorders), age, patient source, full out-of-pocket expenses, full public expenses and number of hospitalizations. Other mental disorders, schizophrenia, schizophrenia, schizophrenia and paranoid disorders, New Rural Cooperative Medical Insurance. Conclusion: The hospitalization costs of mental illness patients were affected by varied factors, and comprehensive control measures should be adopted to effectively control the increase of medical expenses of inpatients.

Effects of bisphenol A on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells / 中华劳动卫生职业病杂志

Objective@#To explore the effects of BPA on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells.@*Methods@#Primary Sertoli cells collected from prepuberty rats (18-21 d) were cultured for 48 h, and then they were treated with 0, 30, 50, 70 μmol/L BPA respectively for 24 h. The methods of MTT, real-time quantitative PCR and Western blotting were utilized to measure the cell ability of Sertoli cells, the mRNA and protein expression levels of N-cadherin, Vimentin and FSHR respectively.@*Results@#Compared with control, the cell abilities of Sertoli cells in 50 μmol/L BPA group and 70 μmol/L BPA group increased significantly (P<0.05) . The cell abilities of Sertoli cells decreased with the increases of exposure doses of BPA. Compared with control, the expression of N-cadherin mRNA only increased in 30 μmol/L BPA group (P<0.05) , the expression of Vimentin mRNA decreased significantly in all doses group of BPA (P<0.05) , the expression of FSHR mRNA increased in all doses group of BPA (P<0.05) . Compared with the control, the protein levels of N-cadherin increased significantly in 50 μmol/L BPA group (P<0.05) , the protein levels of Vimentin decreased significantly in all doses group of BPA (P<0.05) , the protein levels of FSHR decreased significantly in 50 μmol/L BPA group and 70 μmol/L BPA group (P<0.05) .@*Conclusion@#The mechanism of testicular toxicity from BPA might be the alterations of N-cadherin, Vimentin and FSHR by disturbing normal spermatogenesis.

Relationships between training burnout, body mass index, plasma glucose and blood lipids of soldiers / 军事医学

Objective To explore the relationships between training burnout , body mass index (BMI), fasting plasma glucose ( FPG) and blood lipids of soldiers .Methods A total of 140 soldiers stationed in Xinjiang who had received intensive behavioral stress training before entering the plateau ( referred to as the "great intensity training") were studied by the integrated method of a questionnaire survey with test in situ .The questionnaire was a self-compiled soldiers′training burnout questionnaire ,in which BMI , FPG, and blood lipids were the observation indices .The relationships between the indices and training burnout were analyzed by linear regression analysis .Results The total score of training burnout and scores of training alienation among soldiers were significantly increased after high intensity training (P<0.01).While the values of FPG, TC, TG and BMI among soldiers were significantly decreased after high intensity training (P<0.05, P<0.01).After high intensity training, the total scores of training burnout and score of training alienation among overweight soldiers were significantly compared to higher than those who had normal BMI (P<0.05, P<0.01).After high intensity training, the total score of training burnout and scores of physical and mental exhaustion and training alienation among soldiers that had high levels of FPG were significantly increased those who had low levels of FPG (P<0.01).And the total score of training burnout and scores of physical and mental exhaustion and training alienation among soldiers that had high levels of cholesterol were significantly higher than those of soldiers who had low levels of cholesterol (P<0.01).Regres-sion analysis showed that there was a linear regression relationship between physical and mental exhaustion , training aliena-tion on one hand, and BMI, FPG, total cholesterol (TC),and triglycerides (TG) on the other hand among soldiers before and after intensive training (P<0.05, P<0.01).Conclusion Physical and mental exhaustion are important influencing factors of FPG and TC, while training alienation is an important influencing factor of TC and TG .

Relationships between training burnout, body mass index, plasma glucose and blood lipids of soldiers / 军事医学

Objective To explore the relationships between training burnout , body mass index (BMI), fasting plasma glucose ( FPG) and blood lipids of soldiers .Methods A total of 140 soldiers stationed in Xinjiang who had received intensive behavioral stress training before entering the plateau ( referred to as the "great intensity training") were studied by the integrated method of a questionnaire survey with test in situ .The questionnaire was a self-compiled soldiers′training burnout questionnaire ,in which BMI , FPG, and blood lipids were the observation indices .The relationships between the indices and training burnout were analyzed by linear regression analysis .Results The total score of training burnout and scores of training alienation among soldiers were significantly increased after high intensity training (P<0.01).While the values of FPG, TC, TG and BMI among soldiers were significantly decreased after high intensity training (P<0.05, P<0.01).After high intensity training, the total scores of training burnout and score of training alienation among overweight soldiers were significantly compared to higher than those who had normal BMI (P<0.05, P<0.01).After high intensity training, the total score of training burnout and scores of physical and mental exhaustion and training alienation among soldiers that had high levels of FPG were significantly increased those who had low levels of FPG (P<0.01).And the total score of training burnout and scores of physical and mental exhaustion and training alienation among soldiers that had high levels of cholesterol were significantly higher than those of soldiers who had low levels of cholesterol (P<0.01).Regres-sion analysis showed that there was a linear regression relationship between physical and mental exhaustion , training aliena-tion on one hand, and BMI, FPG, total cholesterol (TC),and triglycerides (TG) on the other hand among soldiers before and after intensive training (P<0.05, P<0.01).Conclusion Physical and mental exhaustion are important influencing factors of FPG and TC, while training alienation is an important influencing factor of TC and TG .

PI3K-Akt/LKB1-AMPK-mTOR-p70S6K/4EBP1 signaling pathways participate in the regulation of testis development and spermatogenesis: An update / 中华男科学杂志

Male infertility is closely associated with spermatogenesis disorders triggered by aberrant gene expression or abnormal signaling pathways in the testis. The mammalian target of rapamycin (mTOR) is a central regulator of cell metabolism, playing an important role in regulating cell proliferation, differentiation, translation, actin polymerization, cycle progression, energy metabolism, autophagy, and other cellular activities. PI3K-Akt and LKB1-AMPK, the two well-defined classic signal transduction pathways, regulate the expressions of mTOR and its downstream p70S6K/4EBP1 through different molecular pathways. Recent studies show that mTOR-p70S6K/4EBP1 signaling participates in the regulation of the proliferation and differentiation of testicular cells and spermatogenesis. This review focuses on the role of PI3K-Akt/LKB1- AMPK-mTOR signaling cascades in testis development and spermatogenesis, providing some new perspectives for the studies of the molecular mechanism underlying male sterility.

MiR-139-5p inhibits migration and invasion of colorectal cancer by downregulating AMFR and NOTCH1

MicroRNAs (miRNAs) that exert function by posttranscriptional suppression have recently brought insight in our understanding of the role of non-protein-coding RNAs in carcinogenesis and metastasis. In this study, we described the function and molecular mechanism of miR-139-5p in colorectal cancer (CRC) and its potential clinical application in CRC. We found that miR-139-5p was significantly downregulated in 73.8% CRC samples compared with adjacent noncancerous tissues (NCTs), and decreased miR-139-5p was associated with poor prognosis. Functional analyses demonstrated that ectopic expression of miR-139-5p suppressed CRC cell migration and invasion in vitro and metastasis in vivo. Mechanistic investigations revealed that miR-139-5p suppress CRC cell invasion and metastasis by targeting AMFR and NOTCH1. Knockdown of the two genes phenocopied the inhibitory effect of miR-139-5p on CRC metastasis. Furthermore, the protein levels of the two genes were upregulated in CRC samples compared with NCTs, and inversely correlated with the miR-139-5p expression. Increased NOTCH1 protein expression was correlated with poor prognosis of CRC patients. Together, our data indicate that miR-139-5p is a potential tumor suppressor and prognostic factor for CRC, and targeting miR-139-5p may repress the metastasis of CRC and improve survival.

[Effects of sleep deprivation on the intelligence structure of school-age children in Changsha, China].

OBJECTIVE: To investigate the effects of sleep deprivation on intelligence development in primary school students. METHODS: Between June 2009 and April 2010, 316 grade 5 students aged 10-11 years were selected from four primary schools in four administrative districts of Changsha, China by stratified random sampling. The intelligence characteristics of children with varying degrees of sleep deprivation were investigated using the Chinese Wechsler Intelligence Scale for Children. RESULTS: A total of 286 valid questionnaires were received, with a response rate of 90.5%. The survey was comprised of a sleep deprivation group (sleep time <8 hours per night; n=180) and a control group (sleep time ≥8 hours per night; n=106). The sleep deprivation group had significantly lower subtest scores, verbal intelligence quotient (IQ) (VIQ), performance IQ (PIQ) and full scale IQ (P<0.05) and significantly lower verbal comprehension factor score and memory/attention factor score compared with the control group (P<0.05). Compared with the control group, the moderate sleep deprivation subgroup had significantly decreased VIQ and full scale IQ as well as verbal comprehension factor score and memory/attention factor score (P<0.05), and the severe sleep deprivation subgroup showed decreases in all scores (P<0.05). The sleep deprivation group and moderate and severe sleep deprivation subgroups had significantly higher proportions of children with VIQ-PIQ imbalance than the control group. CONCLUSIONS: Sleep deprivation adversely affects intelligence development, especially VIQ, in primary school students, and the adverse effects of sleep deprivation are mainly seen in students with moderate and severe sleep deprivation.

Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines.

BACKGROUND: Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood. METHODS: This work was conducted to analyze the implication of Rac3 in the aggressiveness of two breast cancer cell lines, MDA-MB-231 and MCF-7: both express Rac3, but MDA-MB-231 expresses more activated RhoA. The effect of Rac3 in cancer cells was also compared with its effect on the non-tumorigenic mammary epithelial cells MCF-10A. We analyzed the consequences of Rac3 depletion by anti-Rac3 siRNA. RESULTS: Firstly, we analyzed the effects of Rac3 depletion on the breast cancer cells' aggressiveness. In the invasive MDA-MB-231 cells, Rac3 inhibition caused a marked reduction of both invasion (40%) and cell adhesion to collagen (84%), accompanied by an increase in TNF-induced apoptosis (72%). This indicates that Rac3 is involved in the cancer cells' aggressiveness. Secondly, we investigated the effects of Rac3 inhibition on the expression and activation of related signaling molecules, including NF-κB and ERK. Cytokine secretion profiles were also analyzed. In the non-invasive MCF-7 line; Rac3 did not influence any of the parameters of aggressiveness. CONCLUSIONS: This discrepancy between the effects of Rac3 knockdown in the two cell lines could be explained as follows: in the MDA-MB-231 line, the Rac3-dependent aggressiveness of the cancer cells is due to the Rac3/ERK-2/NF-κB signaling pathway, which is responsible for MMP-9, interleukin-6, -8 and GRO secretion, as well as the resistance to TNF-induced apoptosis, whereas in the MCF-7 line, this pathway is not functional because of the low expression of NF-κB subunits in these cells. Rac3 may be a potent target for inhibiting aggressive breast cancer.

Effects of sleep deprivation on the intelligence structure of school-age children in Changsha, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of sleep deprivation on intelligence development in primary school students.</p><p><b>METHODS</b>Between June 2009 and April 2010, 316 grade 5 students aged 10-11 years were selected from four primary schools in four administrative districts of Changsha, China by stratified random sampling. The intelligence characteristics of children with varying degrees of sleep deprivation were investigated using the Chinese Wechsler Intelligence Scale for Children.</p><p><b>RESULTS</b>A total of 286 valid questionnaires were received, with a response rate of 90.5%. The survey was comprised of a sleep deprivation group (sleep time <8 hours per night; n=180) and a control group (sleep time ≥8 hours per night; n=106). The sleep deprivation group had significantly lower subtest scores, verbal intelligence quotient (IQ) (VIQ), performance IQ (PIQ) and full scale IQ (P<0.05) and significantly lower verbal comprehension factor score and memory/attention factor score compared with the control group (P<0.05). Compared with the control group, the moderate sleep deprivation subgroup had significantly decreased VIQ and full scale IQ as well as verbal comprehension factor score and memory/attention factor score (P<0.05), and the severe sleep deprivation subgroup showed decreases in all scores (P<0.05). The sleep deprivation group and moderate and severe sleep deprivation subgroups had significantly higher proportions of children with VIQ-PIQ imbalance than the control group.</p><p><b>CONCLUSIONS</b>Sleep deprivation adversely affects intelligence development, especially VIQ, in primary school students, and the adverse effects of sleep deprivation are mainly seen in students with moderate and severe sleep deprivation.</p>

[Quantified research about the effects of sleep quality on attention in class and acadamic achievements in primary school children].

OBJECTIVE: To study the adverse effects of sleep problems and sleep insufficiency on attention in class and pupils' acadamic achievements. METHODS: A total of 1138 students from four primary schools at ages of 6-12 years were randomly sampled from four districts of Changsha city, Hunan Province June 2009 to April 2010. The inquired items included sleep problems, sleep time, sleep quality, attention in class and academic achievements. Teachers and parents observed the pupils according to the unified requirements for 3 months and then filled out the questionnaires. RESULTS: The total valid inquiry tables were 1091 with the answering rate of 95.87%, including 549 boys and 542 girls. The sleep quality was more poor in children with sleep problems or sleep insufficiency than in children with normal sleep. The sleep quality was reduced and aggravated along with the increasing sleep problems and the reducing sleep time. The attention in class and academic achievements in children with sleep problems or sleep insufficiency were more poor than in children with normal sleep. The sleep quality index was negatively correlated with attention in class and academic achievements. The attention in class was positively correlated with academic achievements. CONCLUSIONS: The decline in sleep quality directly affects the attention in class and reduce the academic achievements in primary school children.

Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats.

1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent studies suggest that pharmacological activation of AMPK inhibits cardiac hypertrophy. In the present study, we examined whether long-term treatment with metformin could attenuate ventricular hypertrophy in a rat model. The potential involvement of nitric oxide (NO) in the effects of metformin was also investigated. 2. Ventricular hypertrophy was established in rats by transaortic constriction (TAC). Starting 1 week after the TAC procedure, rats were treated with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were used to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10⁻6 mol/L) for 24 h under serum-free conditions in the presence or absence of metformin (10⁻³ mol/L), compound C (10⁻6 mol/L), L-NAME (10⁻6 mol/L) or their combination. The rate of incorporation of [³H]-leucine was determined, western blotting analyses of AMPK-eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were undertaken and the concentration of NO in culture media was determined. 4. Transaortic constriction resulted in significant haemodynamic dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident. Treatment with metformin improved haemodynamic function and significantly attenuated ventricular hypertrophy. Most of the effects of metformin were abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on haemodynamic function and ventricular hypertrophy in TAC rats. 5. In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME. The improvement in cardiac structure and function following metformin treatment was associated with enhanced phosphorylation of AMPK and eNOS and increased NO production. 6. The findings of the present study indicate that long-term treatment with metformin could attenuate ventricular hypertrophy induced by pressure overload via activation of AMPK and a downstream signalling pathway involving eNOS-NO.

Quantified research about the effects of sleep quality on attention in class and acadamic achievements in primary school children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the adverse effects of sleep problems and sleep insufficiency on attention in class and pupils' acadamic achievements.</p><p><b>METHODS</b>A total of 1138 students from four primary schools at ages of 6-12 years were randomly sampled from four districts of Changsha city, Hunan Province June 2009 to April 2010. The inquired items included sleep problems, sleep time, sleep quality, attention in class and academic achievements. Teachers and parents observed the pupils according to the unified requirements for 3 months and then filled out the questionnaires.</p><p><b>RESULTS</b>The total valid inquiry tables were 1091 with the answering rate of 95.87%, including 549 boys and 542 girls. The sleep quality was more poor in children with sleep problems or sleep insufficiency than in children with normal sleep. The sleep quality was reduced and aggravated along with the increasing sleep problems and the reducing sleep time. The attention in class and academic achievements in children with sleep problems or sleep insufficiency were more poor than in children with normal sleep. The sleep quality index was negatively correlated with attention in class and academic achievements. The attention in class was positively correlated with academic achievements.</p><p><b>CONCLUSIONS</b>The decline in sleep quality directly affects the attention in class and reduce the academic achievements in primary school children.</p>

Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.

HYPB is a human histone H3 lysine 36 (H3K36)-specific methyltransferase and acts as the ortholog of yeast Set2. This study explored the physiological function of mammalian HYPB using knockout mice. Homozygous disruption of Hypb impaired H3K36 trimethylation but not mono- or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the Hypb(-/-) embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant embryos and yolk sacs could not be remodeled into large blood vessels or intricate networks, and the aberrantly rounded mesodermal cells exhibited weakened interaction with endothelial cells. The embryonic vessels failed to invade the labyrinthine layer of placenta, which impaired the embryonic-maternal vascular connection. These defects could not be rescued by wild-type tetraploid blastocysts, excluding the possibility that they were caused by the extraembryonic tissues. Consistent with these phenotypes, gene expression profiling in wild-type and Hypb(-/-) yolk sacs revealed that the Hypb disruption altered the expression of some genes involved in vascular remodeling. At the cellular level, Hypb(-/-) embryonic stem cell-derived embryonic bodies, as well as in vitro-cultured human endothelial cells with siRNA-mediated suppression of HYPB, showed obvious defects in cell migration and invasion during vessel formation, suggesting an intrinsic role of Hypb in vascular development. Taken together, these results indicate that Hypb is required for embryonic vascular remodeling and provide a tool to study the function of H3K36 methylation in vasculogenesis/angiogenesis.