Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Objective:To evaluate and compare the postoperative visual quality after phacoemulsification combined with toric (ART) and non-toric (ReSTOR) multifocal intraocular lens (IOL) implantation.Methods:A cohort study was conducted.Thirty-nine cataract patients (50 eyes) who underwent phacoemulsification combined with ART IOL implantation were enrolled as ART group, and 32 patients (41 eyes) who received ReSTOR IOL implantation were enrolled as ReSTOR group in Tianjin Medical University Eye Hospital from January 2017 to January 2018.Three months after surgery, the uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA) and uncorrected near visual acuity (UNVA), manifest refraction, defocus curve, contrast sensitivity (CS), modulation transfer function cutoff, Strehl2D ratio (SR), objective scattering index, OQAS values under 100%, 20%, 9% contrasts (OV 100%, OV 20%, OV 9%), total aberrations, total lower-order aberrations, total higher-order aberrations, spherical aberrations, coma and trefoil aberrations of the two groups were tested and compared.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2019KY[L]-04). Written informed consent was obtained from each subject prior to entering the cohort.Results:UDVA at 3 months after surgery was (0.07±0.09)LogMAR and (0.09±0.12)LogMAR in ART group and ReSTOR group, and CDVA was (-0.01±0.07)LogMAR and (-0.01±0.07)LogMAR, and UIVA was (0.23±0.11)LogMAR and (0.22±0.13)LogMAR, and UNVA was (0.11±0.15)LogMAR and (0.06±0.11)LogMAR.UNVA was slightly better in ReSTOR group than ART group, and the difference was statistically significant ( t=2.085, P=0.040). The mean depth of focus was (4.12±0.79)D in ART group and (4.24±0.95)D in ReSTOR group.The postoperative residual astigmatism (0.32±0.31)D was significantly lower than preoperative corneal astigmatism (1.27±0.40)D in ART group ( t=13.209, P<0.001). CS values at 6, 12, and 18 c/d under photopic without glare, 12 and 18 c/d under photopic with glare, 3, 6, and 12 c/d under scotopic without glare in ART group were slightly lower than those in ReSTOR group, showing statistically significant differences (all at P<0.05) without clinical significance.SR and OV 20% values in ART group were 0.14±0.05 and 0.55±0.24, which were slightly lower than 0.17±0.06 and 0.66±0.29 in ReSTOR group, with statistically significant differences ( t=-2.012, P=0.048; t=-2.557, P=0.043). Total aberrations and coma aberration under 5 mm pupil diameter in ART group were 0.88(0.59, 1.13)μm and 0.21(0.13, 0.30)μm, which were higher than 0.58(0.47, 0.74)μm and 0.10(0.08, 0.21)μm in ReSTOR group, showing statistically significant differences ( Z=-2.073, P=0.038; Z=-2.101, P=0.036). Conclusions:Cataract phacoemulsification combined with ART IOL implantation can provide good vision and visual quality while correcting preoperative corneal astigmatism, and the resolution in dim light or low to medium spatial frequencies is slightly weaker than eyes implanted with ReSTOR IOL.

Objective:To investigate the protein expression changes of human umbilical cord mesenchymal stem cells (hUCMSCs) modified with pigment epithelium-derived factor ( PEDF) gene mediated by lentivirus. Methods:The hUCMSCs were divided into the control group and experimental group.Cells in the control group were normal hUCMSCs and the cells in experimental group were hUCMSCs with PEDF modification.The proteins from the two groups were collected and processed by FASP method.Samples were fractionated by liquid chromatography and analyzed by tandem mass spectrometry, and SWATH mode was applied.Differential protein analysis, Gene Ontology (GO) analysis and Reactome pathway enrichment analysis were performed. Results:A total of 5 361 quantified proteins were detected in this experiment, of which 432 proteins were differentially expressed (fold change>1.5, P<0.05). There were 219 of the 432 proteins up-regulated, including serpin family F member 1 (SERPINF1) (PEDF), DEAD-box helicase 59 (DDX59) and thrombospondin 1 (THBS1), etc., whereas 213 proteins were down-regulated, including collagen type Ⅰ alpha 1 (COL1A1), COL18A1, etc.GO analysis indicated that the differential proteins were mainly involved in fibrinolysis, extracellular structure organization, regulation of transporter activity, biosynthetic process of secondary alcohol and cholesterol, coenzyme metabolic process and regulation of peptidase activity, etc.Reactome pathway analysis showed that the differential proteins were mostly involved in regulation of insulin like growth factor (IGF) transport and uptake by IGF binding protein, post-translational protein phosphorylation, extracellular matrix organization, metabolism of steroids. Conclusions:After gene modification with PEDF mediated by lentivirus, the expression of many proteins in hUCMSCs were changed. PEDF gene modification can alter the structure of extracellular matrix and regulate the expression of proteins associated with cell proliferation, self-renewal and multipotency.

【Objective】 To investigate the changes of platelet microRNA (miRNA) expression profiles on d1 and d5 during storage with riboflavin and ultraviolet-B (UVB) light (VB2-PRT) treatment, and to explore the molecular mechanism of miRNAs involved in the regulation of platelet storage lesion (PSL) under VB2-PRT treatment. 【Methods】 20 apheresis platelet concentrates (5mL / sample) were collected from voluntary blood donors. After mixing and shaking, the samples was treated with riboflavin (final concentration 50 μmol/L) and 6.24J/mL UVB light for 8min, then split into two aliquots and agitated stored at (22±2) ℃. The concentrates were sampled (5mL) on d1 and d5, respectively, and sequenced by DNA nanoball (DNB) sequencing technology. The differentially expressed miRNAs between the two groups (at different storage periods) were screened by DEGseq and MA-plot analysis software. The miRNAs, reached more than 2 times different expression between groups, were considered significant different(P<0.01). The miRanda and TargetScan softwares were used to predict the target genes. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the target genes of significant differentially expressed miRNAs. The expression of miRNAs was verified by real-time fluorescence quantitative PCR (qRT-PCR). 【Results】 miRNA expression profile: compared with d1 platelets, there were 590 miRNAs with significantly different expression (P< 0.01) in d5 group, including 255 up-regulated miRNAs (such as miR-99b, miR-7) and 335 down regulated miRNAs (such as miR-451a, miR-19b). Among the 272 known miRNAs, 112 were up-regulated and 160 were down regulated. There were 318 new miRNAs sequences. The enriched GO terms of target genes of differentially expressed miRNAs in d5 and d1 groups included cell components, organelles, cell membranes and other cellular structures, molecular functions such as adhesion, catalysis, molecular conversion, transportation, transcription factor and receptor activity, and biological processes such as cell processing, metabolism, biological regulation and stress. The corresponding pathways in the top 10 of KEGG enrichment were mainly secretion, glucose metabolism, signal transduction, membrane transport, translation, environmental adaptation and other signal pathways. The six randomly selected differentially expressed miRNAs verified by qRT-PCR was consistent with those of DNB sequencing. 【Conclusion】 The expression profiles of platelets miRNAs has changed significantly between d1- and d5-storage under VB2-PRT treatment. Functional prediction suggests that these miRNAs might be involved in the regulation of platelet PSL underVB2-PRT treatment.

【Objective】 To investigate the changes of platelet microRNA (miRNA) expression profiles of storage in vitro, and to explore the molecular mechanism of miRNAs involved in the regulation of platelet storage lesion (PSL). 【Methods】 20 platelet samples (5 mL / sample) were collected from apheresis platelet donors, fully mixed and stored in a shaker with (22±2) ℃ horizontal agitation, sampled on day 1 and day 5, and sequenced by DNA nanoball (DNB) sequencing technology. The miRNAs with more than 2 times expressions (P<0.01) were considered as significantly differences between d5 and d1 groups. The miRanda and TargetScan softwares were used to predict the target genes. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the target genes of significant differentially expressed miRNAs. The expression of miRNAs was verified by real-time fluorescence quantitative PCR (qRT-PCR). 【Results】 Compared with d1 group, 315 miRNAs with significantly different expression (P<0.01) were screened in d5 group, including 146 up-regulated miRNAs (such as miR-146a, let-7b), and 169 down-regulated miRNAs (such as mir-30d, mir-142). Among 126 known miRNAs, 43 were up-regulated and 83 were down-regulated. There are 189 new miRNA sequences. The enriched GO terms of target genes of differentially expressed miRNAs in d5 and d1 groups included cell components, organelles, cell membrane and other cell structures, molecular functions such as adhesion, catalysis and activity, and biological processes such as cell processing, metabolism, biological regulation and stress. The corresponding pathways in the top 10 of KEGG enrichment were mainly signal transduction, secretion, membrane transport, amino acid metabolism, polysaccharide metabolism, protein synthesis and environmental adaptation. The 6 randomly selected differentially expressed miRNAs verified by qRT-PCR were consistent with those of DNB sequencing. 【Conclusion】 The expression profiles of platelets miRNAs have changed significantly between the d1 and d5 of storage in vitro. Functional prediction suggested that these miRNAs might be involved in the regulation of platelet PSL.

【Objective】 To analyze the changes of microRNA (miRNA) expression profiles on day 1 and day 5 after storage with or without riboflavin and ultraviolet-B (UVB) light (VB2-PRT) treatment, and to explore the molecular mechanism of miRNAs involved in the regulation of platelet storage lesion (PSL) under VB2-PRT treatment. 【Methods】 20 apheresis platelet concentrates (5mL / sample), collected from voluntary donors, were split into two group after mixing and agitation. One was treated with riboflavin (final concentration 50 μmol/L) plus 6.24 J/mL UVB light(E group), and the other worked as a control group (C group) without any treatment. Both groups were subjected to agitated storage at (22±2) ℃ horizontally. The platelet concentrates were sampled on d1 and d5 (5mL) during storage, named as E1, E5, C1 and C5 groups, respectively, and sequenced by DNA nanoball (DNB) sequencing technology. The differentially expressed miRNAs between E and C groups were screened by using DEGseq and MA-plot analysis software, and GO function enrichment analysis and KEGG pathway enrichment analysis were further performed when the different expression between groups reached twofold and above. 【Results】 Compared with C1 group, 487 miRNAs with significantly different expression (P<0.01) were screened in E1 group, including 220 up-regulated miRNAs, such as miR-146a and let-7b, and 267 down regulated miRNAs, such as miR-7 and miR-1260. Compared with C5 group, 229 miRNAs with significantly different expression (P<0.01) were screened in E5, including 80 miRNAs with up-regulated expression, such as miR-423 and miR-378, and 149 down regulated miRNAs, such as miR-451 and miR-30.The target genes with differentially expressed miRNAs in E1 vs C1 groups and E5 vs C5 groups were similar in the numbers of enriched GO terms, including cell components, organelles, cell membrane and other cell structures, molecular functions such as adhesion, catalysis, molecular transformation, transportation, transcription factors and receptor activity, cell processing, metabolism, biological regulation, stress and other biological processes etc. Compared with E1 and C1 groups, E5 and C5 groups lacked of signal pathways related to environmental adaptation, translation and mucin synthesis, however, it increased inositol phosphate metabolism, phosphatidylinositol signaling system and chemokine signaling pathway. 【Conclusion】 The expression profiles of platelets miRNAs treated with VB2-PRT has changed significantly after storage for a period of time. Functional prediction suggests that these miRNAs might be involved in the regulation of platelet PSL induced by VB2-PRT.

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity. Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance. Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

Objective To evaluate the effectiveness of internet-based cognitive behavior therapy (CBT-I) on blood pressure in patients with hypertension comorbid with insomnia.Methods One hundred and six patients met the JNC-8 diagnostic criteria for hypertension and DSM-5 diagnostic criteria for insomnia were selected,and randomly assigned to CBT-I group (n=53) and regular treatment group (n=53).All the patients accepted relevant treatment for 8 consecutive weeks.Changes of systolic blood pressure (SBP),diastolic blood pressure (DBP),the sleep parameters and the anxiety and depression levels were observed between baseline and 8 weeks of follow-up.Results Compared with pre-treatment,SBP and DBP decreased significantly in both CBT-I group and regular treatment group (P＜0.01),the decrease was more significant in CBT-I group than in regular treatment group (P＜0.01).The sleep latency,sleep efficiency,bed time and rating anxiety scale were improved more significantly in CBT-I group than in regular treatment group (44.49 ± 22.75min vs.55.50 ± 34.96min;72.31％ ± 9.15％ vs.57.70％ ± 11.53％;302.65 ± 43.76min vs.262.70 ± 50.64min and 17.14 ± 6.45 vs.21.02 ± 6.64,respectively),the differences were of statistical significance (P＜0.05).In addition,no significant difference was found in the level of depression between CBT-I group and regular treatment group.Conclusion CBT-I can effectively shorten sleep latency,improve sleep efficiency,extend bed time and improve anxiety,meanwhile effectively lower the blood pressure of patients with hypertension comorbid with insomnia by optimizing sleep quality.

Objective To screen the incidence of transient hypertension in conventional hypertensive management population of hypertension and analysis it's related etiology and constituent ratio.Methods People who met the diagnosis of hypertension were selected from inpatient and outpatient of this department.All patients were followed up for 2 months of home blood pressure monitoring,if the patients who were normal when monitoring home blood pressure were included in the trial and symptomatic hypertension was excluded.Results Three hundred of patients met the diagnostic criteria for hypertension,46 cases (15.3％) met the standard of transient hypertension,the etiology and constituent ratio of transient hypertension in the observed cases were as follows:25 cases (54.3％) of anxiety and depression,8 cases (17.4％) of acute cerebrovascular disease,7 cases (15.2％) of sleep disorders,4 cases(8.7％) of a variety of head and face pain,1 (2.2％)case of epilepsy tonic clonus,1 (2.2％)case of vertigo.Conclusion The application of interactive management of home blood pressure measurement is particularly helpful for screening patients with transient hypertension,and it can timely avoid excessive anti-hypertensive treatment.