Maternal Deprivation Enhances Contextual Fear Memory via Epigenetically Programming Second-Hit Stress-Induced Reelin Expression in Adult Rats.

Background: Early-life stress increases the risk for posttraumatic stress disorder. However, the epigenetic mechanism of early-life stress-induced susceptibility to posttraumatic stress disorder in adulthood remains unclear. Methods: Rat pups were exposed to maternal deprivation during postnatal days 1 to 14 for 3 hours daily and treated with the DNA methyltransferase inhibitor zebularine, L-methionine, or vehicle 7 days before contextual fear conditioning, which was used as a second stress and to mimic the reexperiencing symptom of posttraumatic stress disorder in adulthood. Long-term potentiation, dendritic spine density, DNA methyltransferase mRNA, Reelin gene methylation, and Reelin protein expression in the hippocampal CA1 were measured. Results: Maternal deprivation enhanced contextual fear memory in adulthood. Meanwhile, maternal deprivation decreased DNA methyltransferase mRNA and Reelin gene methylation in the hippocampal CA1 on postnatal days 22 and 90. Reelin protein expression was increased in the hippocampal CA1 following contextual fear conditioning in adulthood. Furthermore, compared with rats that experienced maternal deprivation alone, rats also exposed to contextual fear conditioning showed an enhanced induction of hippocampal long-term potentiation and increased dendritic spine density in the hippocampal CA1 following contextual fear conditioning in adulthood. Zebularine pretreatment led to an enhancement of contextual fear memory, hypomethylation of the Reelin gene, and increased Reelin protein expression in adult rats, while L-methionine had the opposite effects. Conclusions: Maternal deprivation can epigenetically program second-hit stress-induced Reelin expression and enhance the susceptibility to contextual fear memory in adulthood. These findings provide a new framework for understanding the cumulative stress hypothesis.

Prevalence and risk factors of fatty liver disease in young and middle-aged population: one center study in Southwestern China.

BACKGROUND AND AIM: Fatty liver disease has become common hepatic disease not only in western countries but also in developing countries in Asia-Pacific area. Our aim was to determine the prevalence and risk factors of fatty liver disease as well as its correlation with metabolic syndrome in young and middle-aged population. METHODS: Data were collected from check-up center at the 1st Affiliated Hospital of Chongqing Medical University in 2011. Relationships of fatty liver disease and age, body mass index, and metabolic syndrome were determined. Logistic regression was performed to identify the risk factors for fatty liver disease. RESULTS: Data of 18 676 subjects (mean age 40.55 ± 9.94 ranging from 18 to 59) were analyzed. The prevalence of fatty liver disease was 22.0% and increased along with age, body mass index, and the presence and severity of metabolic syndrome. In logistic regression, living area was significantly associated with fatty liver in total population. Male, overweight and obese, waist-to-height ratio ≥ 0.5, hypertension, hypercholesterolemia, high triglyceride, low high-density lipoprotein cholesterol, and fasting plasma glucose ≥ 7.0 mmol/L were common independent risk factors for fatty liver disease in urban and rural areas. Older age and white blood cell over 5.5 ×10(9) /L were related to fatty liver disease in urban area. Obesity was the most important factors in both areas. CONCLUSION: Fatty liver disease was prevalent in young and middle-aged population and mainly associated to multiple metabolic disorders.

[Ornithine aspartate and naloxone combined therapy for hepatic encephalopathy affects cognitive function, prognosis, and neuropeptide levels].

OBJECTIVE: To investigate the potential effects on cognitive function, prognosis, and neuropeptide levels of patients in response to combination therapy with ornithine aspartate plus naloxone for hepatic encephalopathy. METHODS: Eighty-four consecutive patients diagnosed with hepatic encephalopathy were randomly divided into two equal groups. The control group (n = 42) received traditional medical treatment, and the research group (n = 42) received the traditional medical treatment as well as the combination therapy with ornithine aspartate plus naloxone. The supplemental treatment was comprised of daily intravenous injection of 10-15 g ornithine aspartate in 250 ml of 5% glucose plus intravenous drip of 3 mg naloxone in 100 ml of 5% glucose, and was given in 7-day cycles for one or two cycles. The cognitive function of patients was assessed by Hasegawa Intelligence Scale (HDS) and Mini-Mental State Examination (MMSE) questionnaires. The effective rate and time duration from coma to consciousness were recorded. Changes in blood ammonia level, markers of liver function, and neuropeptide levels were measured by standard biochemical assays. Intergroup differences were assessed by the Chi-squared test. RESULTS: The HDS and MMSE scores of the research group were significantly higher than those of the control group after therapy. The effective rate, time duration from coma to consciousness, blood ammonia, the liver function markers alanine aminotransferase, gamma-glutamyl-transpeptidase and total bilirubin, and the neuropeptides arginine vasopressin and beta-endorphin were remarkably improved after treatment in the research group, as compared with that in the control group. CONCLUSION: Supplementing the traditional treatment for hepatic encephalopathy with ornithine aspartate plus naloxone combination therapy provides better therapeutic outcome than traditional treatment alone.

Soil microbiomes divergently respond to heavy metals and polycyclic aromatic hydrocarbons in contaminated industrial sites.

Contaminated sites from electronic waste (e-waste) dismantling and coking plants feature high concentrations of heavy metals (HMs) and/or polycyclic aromatic hydrocarbons (PAHs) in soil. Mixed contamination (HMs + PAHs) hinders land reclamation and affects the microbial diversity and function of soil microbiomes. In this study, we analyzed HM and PAH contamination from an e-waste dismantling plant and a coking plant and evaluated the influences of HM and PAH contamination on soil microbiomes. It was noticed that HMs and PAHs were found in all sites, although the major contaminants of the e-waste dismantling plant site were HMs (such as Cu at 5,947.58 ± 433.44 mg kg-1, Zn at 4,961.38 ± 436.51 mg kg-1, and Mn at 2,379.07 ± 227.46 mg kg-1), and the major contaminants of the coking plant site were PAHs (such as fluorene at 11,740.06 ± 620.1 mg kg-1, acenaphthylene at 211.69 ± 7.04 mg kg-1, and pyrene at 183.14 ± 18.89 mg kg-1). The microbiomes (diversity and abundance) of all sites were determined via high-throughput sequencing of 16S rRNA genes, and redundancy analysis was conducted to investigate the relations between soil microbiomes and contaminants. The results showed that the microbiomes of the contaminated sites divergently responded to HMs and PAHs. The abundances of the bacterial genera Sulfuritalea, Pseudomonas, and Sphingobium were positively related to PAHs, while the abundances of the bacterial genera Bryobacter, Nitrospira, and Steroidobacter were positively related to HMs. This study promotes an understanding of how soil microbiomes respond to single and mixed contamination with HMs and PAHs.

Knockdown of CLC-3 in the hippocampal CA1 impairs contextual fear memory.

Previous studies support a critical role of hippocampus in contextual fear memory. Structural and functional alterations of hippocampus occur frequently in posttraumatic stress disorders (PTSD). Recent reports reveal that knockout of CLC-3, a member of the CLC family of anion channels and transporters, leads to neuronal degeneration and loss of hippocampus. However, the role of CLC-3 in contextual fear memory remains unknown. Using adenovirus and adeno-associated virus gene transfer to knockdown CLC-3 in hippocampal CA1, we investigate the role of CLC-3 in contextual fear memory. CLC-3 expression is increased in hippocampal CA1 after formation of long-term contextual fear memory. Knockdown of CLC-3 by adenovirus infusion in hippocampal CA1 significantly attenuates the contextual fear memory, reduces spine density, induces defects of excitatory synaptic ultrastructure showed by the decreased PSD length, PSD thickness and active zone length, and impairs L-LTP induction and maintenance. Knockdown of CLC-3 also induces the synaptic NMDAR subunit composition to an increased GluN2A/GluN2B ratio pattern and reduces the activity of CaMKII-α. Furthermore, selectively knockdown of CLC-3 in excitatory neurons by adeno-associated virus driven from CaMKII-α promoter is sufficient to impair long-term contextual fear memory. These findings highlight that CLC-3 in hippocampal CA1 is necessary for contextual fear memory.

The prevalence of dementia in the People's Republic of China: a systematic analysis of 1980-2004 studies.

BACKGROUND: Dementia has been a major public health problem. However, there has not yet been a nationwide investigation or systematic analysis of the prevalence of dementia in China from 1980 to 2004. OBJECTIVES: The aim of this study was to analyse the prevalence of dementia and its major subtypes [Alzheimer disease (AD), vascular dementia (VD)] among the population aged 60 years and older in China from 1980 to 2004. METHODS: Epidemiological investigations on dementia in China published in journals and covering the period from 1980 to 2004 were identified manually and on-line by using CBMDISK, Chongqing VIP database and CNKI database. Those reported in English journals were identified using MEDLINE. Selected studies had to describe an original study defined by strict screening and diagnostic criteria. The fixed effects model or random effects model was employed according to statistical test for homogeneity. RESULTS: Twenty-five studies were selected, the statistical information of which was collected for systematic analysis. Our results showed that AD and VD were the two major subtypes of dementia in China, and the pooled prevalence of AD and VD for the population aged 60 years and older was 1.6 and 0.8%, respectively. There was a higher prevalence of AD in the illiterate elderly population (3.2%) than in those who received years of education. The chronological prevalence of AD increased significantly from 1980 to 2004. In southern and northern China, the prevalence of AD was 2.0 and 1.2%, respectively, while VD was 0.6 and 1.1%, respectively. CONCLUSIONS: In the last 24 years, AD and VD were the two major subtypes of dementia in China. The prevalence of AD may be affected by sex, education, occupation or age. The prevalence of VD, which was higher in northern than in southern China, seems not to be affected by age, sex or education.

[Applications of multiple seasonal autoregressive integrated moving average (ARIMA) model on predictive incidence of tuberculosis].

OBJECTIVE: To discuss the application of multiple seasonal autoregressive integrated moving average (ARIMA) predictive model of time series and to establish a predictive incidence model of tuberculosis. METHODS: Parameters of the model were estimated using conditional least squares method according to the data of tuberculosis incidence and the averaged population in a district in Chongqing from 1993 to 2004. In a structure determined according to criteria of residual un-correlation and conclusion, ARIMA predictive model was established and the order of model was confirmed by Akaike's Information Criterion (AIC, for short) and Schwartz's Bayesian Information Criterion (SBC or BIC, for short). RESULTS: There were significant differences of the fitted multiple seasonal moving-average coefficients with the nonseasonal and the seasonal moving-average coefficients being 0.84076 and 0.46602 respectively. The estimated variance was 0.088589, AIC = 19.75979, SBC = 23.28219. Autocorrelation check of residuals of model was white-noise residual. ARIMA(0,1,1)(0,1,1)4NOINT seemed to be the most appropriate model by chi2 test. CONCLUSION: The multiple seasonal ARIMA model can be used to forecast for tuberculosis incidence with high prediction and precision in a short-term.

Involvement of the dopaminergic system in the consolidation of fear conditioning in hippocampal CA3 subregion.

The hippocampus, the primary brain structure related to learning and memory, receives sparse but comprehensive dopamine innervations and contains dopamine D1 and D2 receptors. Systematic hippocampal dopaminergic dysfunction can cause deficits in spatial working memory and impair consolidation of contextual fear memories. CA3 is involved in the rapid acquisition of new memories and has extensive nerve fibre connections with other brain structures such as CA1, the amygdala, and the medial prefrontal cortex (mPFC). A bidirectional fibrous connection between CA3 and the amygdala reflects the importance of CA3 in fear conditioning. The present study evaluated the effects of a 6-OHDA lesion in CA3 on the acquisition and expression of conditioned fear. The results showed CA3 involvement in the expression but not the acquisition of conditioned fear. Injection of SCH23390 and quinpirole into the bilateral CA3 attenuated a conditioned fear-related freezing response, whereas SKF38393 and sulpiride were not associated with this effect. The present study found that a 6-OHDA lesion in CA3 up-regulated the expression of GluR1 in BLA and down-regulated NR2B in CA1 and the basolateral amygdala (BLA). Our data suggest that dopamine depletion in hippocampal subdivision CA3 may not be necessary for the acquisition of conditioned fear, but the expression of conditioned fear is likely dependent on the integrity of mesohippocampal dopaminergic connections. It is probable that both D1 and D2 dopaminergic receptors modulate the expression of conditioned fear. Changes in the expression of NR2B and GluR1 indicate that CA3 may modulate the activities of other brain structures.

[Necessity of splenectomy in radical resection of gastric cancer: a meta-analysis].

OBJECTIVE: To evaluate the necessity of splenectomy in radical resection of gastric cancer. METHODS: Twelve studies comparing outcomes after radical resection of gastric cancer with or without splenectomy were identified. Both fixed effect model and random effect model were used. RESULTS: There were 2628 patients in total. There were significant differences in complications between splenectomy group and spleen-preserving group(OR=1.91, 95% CI:1.28-2.87, P<0.05), while no significant difference in 5-year survival rate was noticed(HR=0.90, 95% CI:0.73-1.11, P>0.05). CONCLUSION: Radical resection of gastric cancer combined with splenectomy is not associated with improved survival but increased postoperative complications.

[Meta-analysis of laparoscopic and open repair of perforated peptic ulcer].

OBJECTIVE: To assess the safety and feasibility of laparoscopic and open repair of perforated peptic ulcer. METHODS: Studies on comparison between laparoscopic repair(LR) and open repair(OR) of perforated peptic ulcer were collected. Data of operating time, blood loss, time to first flatus, postoperative hospital stay, postoperative complications and mortality between LR group and OR group were meta-analyzed using fixed effect model and random effect model. RESULTS: Nineteen studies including 1507 patients were selected for this study,including laparoscopic surgery(n=673) and open surgery(n=834). There were significant differences in blood loss, time to first flatus, postoperative hospital stay, wound infection rate and mortality between LR group and OR group. However, no significant differences existed in operative time, postoperative sepsis, pulmonary infection, abdominal abscess, and suture leakage between the two groups. CONCLUSIONS: Laparoscopic repair of perforated peptic ulcer is associated with improved outcomes in terms of less blood loss, quicker recovery, and lower rates of wound infection and mortality. Laparoscopic repair of perforated peptic ulcer is safe and feasible.

[Prediction of food allergy by using cord blood IgE levels].

OBJECTIVE: As more attention is paid to food allergy which is already regarded as a public health problem, there is still a lot of uncertainty as to the mechanisms and there are limited therapeutic methods for this problem. It is of importance to screen the susceptible infants as early as possible. The present study was conducted to learn whether cord blood IgE levels (CBIgE) could be used as a predictor of food allergy, and to find out factors which influence the predictive accuracy of CBIgE. METHODS: The present study enrolled 118 infants born between April 2001and July 2001, and the authors followed up the infants until they were 4 months old. At the end of follow up, 105 infants had complete data for evaluation. Paper radioimmunosorbent tests (PRIST) were used for CBIgE assay, and parents were required to answer the standard questionnaires and the food skin prick tests (SPT) were taken for all infants. RESULTS: At the end of follow-up, the infants were divided into 3 groups based on food allergy status: FA group with obvious food allergy, SFA group with suspected food allergy and NFA group without allergy. The median values of CBIgE levels in FA group were higher than those in SFA and NFA groups (4.80 IU/L, 0.55 IU/L, 0.87 IU/L, P < 0.01). When the cutoff value for CBIgE was set at 0.9 IU/L (CBIgE(0.9)), 42.9% of infants were found to have food allergy in the higher CBIgE group, 6.7% in the lower CBIgE group (P < 0.01, RR 95% CI = 2.715 approximately 15.221); when the cutoff value was set at 0.5 IU/L (CBIgE(0.5)), 30.9% in the higher CBIgE group and 5.00% in the lower CBIgE group (P < 0.01, RR 95% CI = 1.954 approximately 19.552). In addition, the sensitivity of CBIgE(0.9).as a predictor of food allergy, was 78.95% and the specificity, efficiency and odd product were 73.68%, 74.74%, and 10.50, generally better than CBIgE(0.5) of which the sensitivity, specificity, efficiency, odd product were 89.47%, 5.00%, 57.89%, 8.5 (P < 0.01). With the multi-factor stepwise regression analysis, our study indicated that exposure to cigarette smoke (OR 95%CI = 4.3340 approximately 71.2432), animal fur (OR 95% CI = 1.9869 approximately 30.7472), and egg supplement (OR 95% CI = 1.9340 approximately 25.8885) before 4 months of age might be the risk factors which may result in the predictive uncertainty of CBIgE. CONCLUSIONS: Increased CBIgE levels might be the risk factor which result in food allergy; CBIgE(0.9), as a predictor of food allergy, is superior to CBIgE(0.5). However, some environmental factors, such as early exposure to cigarette smoke, animal fur and too early egg supplement would lead to predictive uncertainty of CBIgE.