Does Periconceptional Fish Consumption by Parents Affect the Incidence of Autism Spectrum Disorder and Intelligence Deficiency? A Case-control Study in Tianjin, China.

OBJECTIVE: This study aimed to explore the association between periconceptional fish consumption by parents and autism spectrum disorder (ASD) and intelligence deficiency (ID). METHODS: A case-control study was conducted through a questionnaire with 108 ASD cases, 79 ID cases, and 108 controls. The ASD and ID cases were students from special educational schools in Tianjin from 2012 to 2014. The age- and sex-matched controls were from a high school, three primary schools, and a kindergarten in Tianjin. Multivariate logistic regression was performed. RESULTS: Paternal habit of eating hairtail before fertilization, maternal preference for fruits during pregnancy, and maternal habit of eating grass carp during pregnancy were preventive factors for ASD. Paternal habit of drinking alcohol before fertilization was a risk factor for ID, whereas maternal preference for fruits during pregnancy and maternal habit of eating crucian carp during pregnancy were protective factors for ID. CONCLUSION: Parental fish consumption is beneficial for the prevention of ASD and ID. Meanwhile, the protective effects of fish consumption on ASD and ID differ. More attention should be paid to the combined effect of other food when eating fish.

Prevalence and early signs of autism spectrum disorder (ASD) among 18-36 month-old children of Tianjin in China.

OBJECTIVE: The aim of this study is to estimate the prevalence of autism spectrum disorder (ASD) among 18-36 month old children in the Tianjin Municipality of China, and to identify early signs of autistic children and the predictability of each individual symptom. METHODS: A total of 8 000 children were screened to do a questionnaire based on CHAT modified to include more early signs of autism at the age of 18-36 months. Then the at-risk children were reexamined 1.5 years later and ASD children were identified based on DSM-IV. Early signs of autism were analyzed retrospectively by using discriminant function analysis performed among ASD children, children not followed up and children followed up but failing to meet ASD criteria. RESULTS: Three hundred and sixty seven children were screened as being at-risk to ASD, and 22 of them were identified as having ASD in the subsequent diagnosis. The prevalence of ASD was 27.5 per 10 000 in Tianjin of China with a male to female ratio of 4:1. Items addressing social interactions and communications had higher predictability than other items to distinguish autistic children from non-autistic ones. Pretend play, functional play, showing and reading parents' facial expressions distinguished autistic children from those not followed up, nevertheless those followed up but failing to meet ASD criteria were not included. CONCLUSION: The prevalence of ASD found in our study was lower than that reported in some studies by western researchers. Autism has its specific symptoms, such as deficits in social awareness, social relatedness, and social referencing.

Gonioscopy and ultrasound biomicroscopy in the detection of angle closure in patients with shallow anterior chamber.

OBJECTIVE: To assess the agreement between gonioscopy and ultrasound biomicroscopy (UBM) in detecting angle closure in Chinese patients with shallow anterior chamber. METHODS: An observational comparative study of the two different examination methods was conducted. Patients with normal intraocular pressure and temporal peripheral anterior chamber depth less than a quarter of corneal thickness based on slit lamp examination were included in this study from December 2007 to May 2009 in the outpatient clinic of First Hospital of Tsinghua University. Gonioscopy was performed with a Goldman goniolens in dark room first and followed by full beam light and indentation. If the filtering trabecular meshwork was invisible or any peripheral anterior synechia was found, that quadrant of the angle was considered closed. UBM was first undertaken in a darkened room then repeated with normal room lighting. If iridotrabecular apposition was showed, that quadrant of the angle was considered closed. The status of angle closure of each quadrant with different methods was recorded. RESULTS: 85 eyes of 46 patients were included in this study. The agreement between gonioscopy and UBM was poor (Κ<0.4) with Kappa analysis in both dark and light conditions in each quadrant. The accordance of agreement between gonioscopy and UBM was hardly affected by age or sex, while in dark condition, eyes with deeper anterior chamber (P=0.005) or plateau iris configuration tended to produce different results (P=0.075) in the 2 methods. CONCLUSION: Gonioscopy and UBM are both indispensable methods for detecting angle closure, neither can completely replace the other.

Astrocytic c-Jun N-terminal kinase-histone deacetylase-2 cascade contributes to glutamate transporter-1 decrease and mechanical allodynia following peripheral nerve injury in rats.

Decrease of glutamate transporter-1 (GLT-1) in the spinal dorsal horn after nerve injury induces enhanced excitatory transmission and causes persistent pain. Histone deacetylases (HDACs)-catalyzed deacetylation might contribute to the decrease of GLT-1, while the detailed mechanisms have yet to be fully elaborated. Spinal nerve ligation (SNL) induced significant increases of HDAC2 and decreases of GLT-1 in spinal astrocytes. Intrathecal infusion of the HDAC2 inhibitors attenuated the decrease of GLT-1 and enhanced phosphorylation of glutamate receptors. GLT-1 and phosphorylated c-Jun N-terminal kinase (JNK) were highly colocalized in the spinal cord, and a large number of pJNK positive cells were HDAC2 positive. Intrathecally infusion of the JNK inhibitor SP600125 significantly inhibited SNL-induced upregulation of HDAC2. SNL-induced HDAC2 up-regulation could be inhibited by the neutralizing anti-tumor necrosis factor-α (TNF-α) binding protein etanercept or the microglial inhibitor minocycline. In cultured astrocytes, TNF-α induced enhanced phosphorylation of JNK and a significant increase of HDAC2, as well as a remarkable decrease of GLT-1, which could be prevented by SP600125 or the HDAC2 specific inhibitor CAY10683. Our data suggest that astrocytic JNK-HDAC2 cascade contributes to GLT-1 decrease and mechanical allodynia following peripheral nerve injury. Neuroimmune activation after peripheral nerve injury could induce epigenetic modification changes in astrocytes and contribute to chronic pain maintenance.

The Factors Influencing the Renal Glucose Threshold in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

OBJECTIVE: This study aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed. RESULTS: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient's age (r = -0.14539, P = 0.0001); MBG (r = -0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = -0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = -0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = -0.11093, P = 0.0004), creatinine (r = -0.26414, P = 0.0001), uric acid (r = -0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = -0.06346, P = 0.0460), beta-2 microglobulin (r = -0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05). CONCLUSION: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI.

Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation.

Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and neuroprotective effects. It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms. We explored the effects of glucagon-like peptide-1 receptor on nociception, cognition, and neuroinflammation in chronic pain. A rat model of chronic pain was established using left L5 spinal nerve ligation. The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation. Electrophysiological examinations showed that, after treatment with exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6. All of these effects could be reversed by exendin-4 treatment. These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.

Overexpression of miR-381 relieves neuropathic pain development via targeting HMGB1 and CXCR4.

MicroRNA are significant regulators of neuropathic pain development. Neuroinflammation contributes a lot to the progression of neuropathic pain. miR-381 is involved in various pathological processes. However, the role of miR-381 in neuropathic pain development remains barely understood. Therefore, in our study, we aimed to investigate the effects of miR-381 on the process of neuropathic pain progression by establishing a rat model using chronic sciatic nerve injury (CCI). Here, we observed that miR-381 was dramatically decreased in CCI rats. Up-regulation of miR-381 strongly reduced neuropathic pain behaviors including mechanical and thermal hyperalgesia. In addition, inflammatory cytokine expression, including IL-6, IL-10 and TNF-α were significantly repressed by overexpression of miR-381. High mobility group box 1 protein (HMGB1) and Chemokine CXC receptor 4 (CXCR4) participate in neuropathic pain development. In our present study, HMGB1 and CXCR4 were predicted as direct targets of miR-381 by employing bioinformatics analysis. Overexpression of miR-381 was able to restrain the expression of HMGB1 and CXCR4 greatly. The direct correlation between HMGB1 and CXCR4 and miR-381 was confirmed in our research. Furthermore, we found that HMGB1 and CXCR4 were increased in CCI rats time-dependently. Moreover, it was demonstrated that silence of HMGB1 and CXCR4 in CCI rats depressed neuropathic pain progression greatly. In conclusion, it was indicated that miR-381could inhibit neuropathic pain development through targeting HMGB1 and CXCR4.

Predictors for attending annual eye screening for diabetic retinopathy amongst patients with diabetes in an urban community of Beijing.

AIM: To gain a better understanding of possible factors that may influence the decision of diabetes persons to participate in annual eye screening in an urban community setting of China. METHODS: A structured interview including questions on attendance of eye screening, knowledge and awareness of diabetic retinopathy was conducted. The presence and degree of retinopathy were assessed using two field non-mydriatic retinal photography. RESULTS: Totally 720 diabetes persons were recruited and 519 were enrolled in this cross-sectional study. In this urban setting of Beijing, among diabetes patients of average of 10y duration, 77% confirmed having undergone at least one eye examination and 61% reported having at least one eye examination with dilated pupil. As for the last 12mo, the number decreased to 210 (47%) and 131 (30%) separately. Most of the participants (95%) were aware that diabetes could affect their vision and that regular eye examination was necessary. Very few of them (12%) however were aware that the early stages of diabetic retinopathy presented without symptoms of vision loss. Having attended patient education on diabetes was effective in building awareness about diabetic eye disease and was a significant positive predictor for attending eye screening [education in a year, Adj. OR=0.47 (0.29-0.74), P<0.001, education years ago, Adj. OR=0.56 (0.33-0.96), P=0.036]. The duration of disease also increased the likelihood of having undergone eye screening (Adj. OR=0.96, P<0.05). CONCLUSION: Being exposed to education about the complications of diabetes increases the probability of attending diabetic eye screening. An appropriate patient knowledge building strategy should be made available to patients from the time of diagnosis.

Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain?

Chronic pain is a complex clinical condition that reduces the quality of life for billions of people. In recent years, the role of epigenetic modulation in the control of long-term neuronal plasticity has attracted the attention of pain researchers. The epigenetic mechanisms include covalent modifications of DNA and/or histone proteins. Mounting evidence suggests that the activity of histone deacetylases (HDACs) and levels of histone acetylation are dynamic and that these enzymes modulate pain-related synaptic plasticity. Therefore, HDACs play essential roles in chronic pain development and maintenance. In this mini review, we will discuss the role of HDACs in the pathogenesis of chronic pain and will consider the therapeutic value of HDAC inhibitors in treating chronic pain.

Suberoylanilide hydroxamic acid prevents downregulation of spinal glutamate transporter-1 and attenuates spinal nerve ligation-induced neuropathic pain behavior.

Glutamate transporter-1 (GLT-1) reduction causes dysregulation of excitatory-inhibitory balance, contributing toward neuropathic pain development. However, the mechanisms underlying GLT-1 downregulation are still unclear. Histone acetylation plays a pivotal role in the regulation of gene expression. We sought to examine the contribution of histone acetylation on pain hypersensitivity and GLT-1 downregulation in neuropathic pain development. Histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) was intrathecally infused to rats through osmotic pumps from -5 days to 7 days after spinal nerve ligation (SNL). Behavioral tests indicated that SAHA could significantly prevent SNL-induced mechanical allodynia and thermal hyperalgesia. The effect was dose related and lasted to 10 days after SNL when the SAHA infusion was stopped on day 7. Immunohistochemistry, western blot, and real-time reverse transcription PCR analysis showed that SAHA significantly prevented SNL-induced downregulation of GLT-1 in the spinal dorsal horn. In addition, SNL-induced weakened acetylation of histone H3 (AcH3) was significantly inhibited by SAHA. Immunofluorescent histochemistry showed that both GLT-1 and AcH3 had high expressions in the dorsal horn. Double staining indicated that several GLT-1-positive cells were colocalized with AcH3. Our data provide evidence that histone deacetylation may contribute toward the loss of GLT-1 and this could be a new consideration for the development of more effective strategies for treating neuropathic pain.