Purpose To explore the effect of Levothyroxine on spatial working memory in patients with subclinical hypothyroidism (SCH) using blood oxygenation level dependent-functional MRI (BOLD-fMRI). Materials and Methods Sixteen patients with SCH before and after 6 months levothyroxine (LT4) treatment and 16 matched euthyroid volunteers underwent n-back task fMRI scanning. AFNI software was used for localization and quantification. Results All the subjects demonstrated activated areas including bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal area (PA) and right caudate nucleus/thalamus, with right hemisphere dominance. Quantitative analysis of regions of interests showed that all these regions had load effect related to memory load in the control group (P<0.001), whereas only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in SCH group. After 6-month treatment with LT4, BOLD signal change was observed in SCH patients within the right DLPFC, right PA and anterior cingulate/supplementary motor cortex (P<0.001). The activation intensity of working memory related brain regions was lower in SCH group compared with that of the control group. Conclusion Spatial working memory impairments in SCH patients are likely related to decreased right DLPFC and right posterior parietal function. LT4 replacement therapy is important to improve and reverse the memory impairment.

Background The excessive growth of human Tenon fibroblasts (HTFs) is a primary cause of failure of anti-glaucomatous filtering surgery.To seek a drug of anti-fibrosis is of an important significance for improving the successful rate of anti-glaucomatous filtration surgery.Objective The goal of this study was to investigate the effect of paclitaxel on proliferation of HTFs in vitro.Methods Human Tenon tissue was obtained during the anti-glaucomatous filtering surgery.HTFs were cultivated using explant method and 3-6 generations of cells were used in the experiment.The cells were identified by immunochemistry using keratin,vimentin,fibronectin and S-100.Different concentrations (0,1 ×10-s,1 × 10-7,1 × 10-6 mol/L) of paclitaxel were added into the medium,and then the cell indexes (CI) in the various groups were detected by real-time cell electronic sensing (RT-CES) 24 hours after affection of paclitaxel.Apoptosis of the cells was examined using DAPI staining,and the proportion of the cells in different cycles were assayed by flow cytorneter 12 hours after addition of paclitaxel.The expressions of matrix metalloproteinase-1 (MMP-1) protein and mRNA were detected by ELISA and real-time PCR,respectively.Results The cells migrated from the cultivated tissue within 7 days with the fibrocyte-like shape.The cells showed the positive response for vimentin and absent response for keratin,fibronectin and S-100.The CI values were 1.093 ±0.191,0.665 ± 0.093 and 0.473 ± 0.117 in the 1 × 10-8,1 × 10-7 and 1 × 10-6 mol/L paclitaxel groups,showing significant rise in comparison with the 1.514 ±0.283 of the 0 mol/L paclitaxel group (all at P =0.000).The cell nuclei were normal in the 0 mol/L paclitaxel group,however,blue-fluorescent particles and apoptotic bodied were found in the cell nuclei after affection of paclitaxel.The proportion of G2/M phase of cells were (9.20±0.80) ％,(12.37±0.45)％ and (13.80±0.35)％ in the 1×10-8 mol/L,1×10-7 mol/L and 1×10-6 mol/L paclitaxel groups,which were higher than the (7.17±0.50) ％ in the 0 mol/L paclitaxel group (P=0.005,0.000,0.000).In addition,the relative expressing level of M MP-1 mRNA (MMP-1 mRNA/GAPDH mRNA) and the expression level of MMP-1 protein in the HTFs were significantly lower in the 1 ×10-8 mol/L,1 × 10-7 mol/L and 1 × 10-6 mol/L paclitaxel groups than those in the 0 mol/L group (all at P＜0.05).Conclusions Paclitaxel at the concentrations of 1 × 10-8 mol/L-1 × 10-6 mol/L inhibits the proliferation of HTFs in vitro by arresting the cellular mitosis and inducing cell apoptosis.These effects probably associated with down-regulation of MMP-1 expression in the HTFs.

Objective To investigate the expression and influence to tumor angiogenesis of urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF) in esophageal carcinoma. Methods The expression of uPA and VEGF in the tissue of normal (18 cases) and esophageal carcinoma (68 cases) were evaluated by SP immunohistochemistry, CD34 was detected as marking tumor microvessel density (MVD). uPA and VEGF expression were assessed as to the pathologically biological features of esophageal cancer and to the influence to tumor angiogenesis. Results The positive rates of uPA were 27.8 % (5/18) and 70.6 % (48/68) in the tissue of normal and esophageal carcinoma, respectively, there was significant difference in two tissues (x2 =11.63, P <0.05). The positive rates of VEGF were 22.2 % (4/18)and 63.2 % (43/68) in the tissue of normal and esophageal carcinoma, respectively, there was significant difference in two eissues (x2 =9.78, P <0.05). The expressions of uPA and VEGF in esophageal carcinoma were uniformity (x2 =9.72, P <0.05). The mean of MVD was 42.38±11.62. The positive rates of uPA and VEGF were higher in the high MVD group than those in the low MVD group (x2 =6.13, P <0.05, x2 =10.12, P <0.05,respectively). uPA and VEGF expressions in malignant tumors weren' t associated with age, gender and pathological types (P >0.05), but associated with clinical stage, histologic grading and lymph node metastasis (P <0.05). Conclusion Rising expression levels of uPA and VEGF are common in esophageal carcinoma. Altered expression of uPA and VEGF may contribute to tumor angiogenesis of esophageal carcinoma, whose overexpression indicate worse prognosis.

Objective To investigate the effect of amiloride on the invasion capacity of esophageal carcinoma EC9706 cell line in vitro and to elucidate its possible mechanism.Methods The invasion capacities of EC9706 cells pretreated with amiloride were measured by transwell chamber assay. The urokinase-type plasminogen activator (uPA) transcription were determined by RT-PCR.The protein expression of uPA were assessed by Western blot.Results After the EC9706 cells were pretreated with amiloride at different concentrations,the number of invaded cells was obviously less than those of control group with obvious dosage dependent pattern (96±7,78±6,57±6,33±4,15±3,F =43.46,P ＜ 0.01).The transcription levels of uPA mRNA and the protein expression levels of uPA in EC9706 cells decreased significantly compared with the control (mRNA:0.623±0.065,0.526±0.054,0.389±0.041,0.312±0.038,0.247±0.025,F =6.71,P ＜0.01; protein:0.732±0.064,0.644±0.057,0.533±0.058,0.391±0.036,0.267±0.043,F =6.71,P ＜0.01).Conclusion Amiloride inhibits the invasion capacity of esophageal carcinoma EC9706 cells.The mechanism might be associated with down-regulation of the expression of uPA.

Objective To establish a SYBR Green real-time PCR detection method with tissue-specific miRNAs and explore a novel approach for forensic body fluid identification. Methods The frequently reported 6 standard miRNAs were synthesized to establish a SYBR Green method, and verify with body fluid. The relative expression data for the 6 miRNAs were obtained using SYBR Green real-time PCR method in peripheral blood, menstrual blood, saliva and semen. Results The assays showed that miRNA205 permitted the unequivocal identification among different fluids. miRNA451 and miRNA144 could be used to distinguish blood from non-blood. Menstrual blood or peripheral blood could be identified through miRNA214. miRNA888 and miRNA891 was highly expressed in semen. Conclusion The results of this study indicate that miRNA SYBR Green profiling may provide a feasible and effective approach to body fluid identification for forensic casework.

Antipsychotic medications are commonly used to treat schizophrenia,but they can have negative effects on lipid metabolism,leading to an increased risk of cardiovascular diseases,reduced life expectancy,and difficulties with treatment adherence.The specific mechanisms by which antipsychotics disrupt lipid metabolism are not well understood.Sterol regulatory element-binding proteins(SREBPs)are important transcriptional factors that regulate lipid metabolism.Proprotein convertase subtilisin/kexin type 9(PCSK9),a gene regulated by SREBPs,plays a critical role in controlling levels of low-density lipoprotein cholesterol(LDL-C)and has become a focus of research on lipid-lowering drugs.Recent studies have shown that antipsychotic drugs can affect lipid metabolism through the SREBP/PCSK9 pathway.A deep understanding of the mechanism for this pathway in antipsychotic drug-related metabolic abnormalities will promote the prevention of lipid metabolism disorders in patients with schizophrenia and the development and application of new drugs.

Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.

Objective: To investigate the genotype and genetic characteristics of the pathogens associated with the epidemic outbreak of acute gastroenteritis(AGE) in Guangyuan city, Sichuan province. Methods: Eighteen stool samples and 15 anal swab samples from 4 AGE outbreaks were collected from Feb 2017 to May 2017. Norovirus (NoV) nucleic acid was detected by Real-time PCR method , and the positive samples were amplified by conventional reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing. Results: Four AGE outbreaks were all caused by NoV. And 20 (60.6%) samples were positive for NoV GⅡ. Gene sequence comparison and phylogenetic analysis showed that 4 AGE outbreaks were all caused by GⅡ.P16/GⅡ.2 NoV. All the strains of GⅡ.P16/GⅡ.2 NoV shared high homology in nucleotides. One of the outbreaks was caused by GⅡ.P16/GⅡ.2 and GⅡ.P7/GⅡ.14 NoV co-infection. Conclusions The 4 outbreaks of AGE in Guangyuan city, Sichuan province were major caused by GⅡ.P16/GⅡ.2 NoV, meanwhile GⅡ.P16/GⅡ.2 and GⅡ.P7/GⅡ.14 NoV co-infection existed.

BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.

OBJECTIVETo investigate the detection rate and correlates of behavioral problems among eco-migrant children in Hui and Han ethnicities.

METHODSUsing multistage randomized sampling method, 2 653 eco-migrant teenagers, 3 174 indigenous and 2 334 homeland peers were selected. Their parents were asked to finish the Achenbach's Child Behavior Checklist (CBCL) and a self-developed correlates questionnaire.

RESULTS765 eco-migrant children with behavioral problems were detected, with detection rate as 28.8%, higher than that of homeland group (24.2%) and native group (19.3%) (χ(2) = 73.547, P < 0.012 5). Ecological migration mainly influenced factors as bad contacts, depression, obsessive-compulsive, discipline, attack for boys aged 6-11, bad contacts for boys aged 12-16 and extraversion behavioral problems for girls aged 12-16, in Hui. These factors both associated to eco-migrant children's behavioral problems in Hui and Han:cesarean section (OR = 1.863, 95% CI:1.144-3.035, for Han) and (OR = 2.979, 95% CI:2.067-4.293, for Hui), physical defects (OR = 1.730, 95%CI:1.087-2.751, for Han) and (OR = 2.552, 95%CI:1.649-3.950, for Hui), arable as a main income way(OR = 1.272, 95%CI:1.066-1.518, for Han) and (OR = 1.212, 95%CI: 1.033-1.422, for Hui), parents' education level above middle school (OR = 0.709, 95% CI: 0.539-0.932, for Han) and (OR = 0.698, 95%CI: 0.542-0.898, for Hui), parents' frequently in good mood (OR = 0.710, 95%CI:0.613-0.821, for Han) and (OR = 0.826, 95%CI:0.718-0.949, for Hui). However, major diseases in the process of growth (OR = 1.794, 95% CI:1.163-2.767), and parents with chronic illness or disability (OR = 1.463, 95% CI:1.061-2.016) only associated with that in Han;single-parent or remarried families(OR = 1.583, 95% CI:1.078-2.325), parents often drinking (OR = 1.557, 95%CI:1.019- 2.379), the time of parents' work longer than half a year (OR = 1.494, 95% CI:1.197-1.864), parents' more content to life now(OR = 0.813, 95% CI:0.700-0.945), and children in older age (OR = 0.939, 95%CI:0.889-0.991) only related to that in Hui.

CONCLUSIONThe eco-migrant children showed a low state in mental health, especially among Hui peers, and the correlated factors were different in Han and Hui, which was supposed to get great importance when taking effective intervention.

Adolescent ; Child ; Child Behavior Disorders ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Surveys and Questionnaires ; Transients and Migrants ; psychology