Objective To evaluate the therapeutic efficacy of atomoxetine hydrochloride for attention deficit hyperactivity disorder (ADHID) combined with Tourette syndrome (TS).Methods Twenty-six cases of children with ADHD combined with TS were firstly diagnosed American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-Ⅳ) of ADHD and TS were treated with atomoxetine.The symptoms were improved and conditions were assessed based on the fourth version of ADHD parent rating scale and the severity of Yale comprehensive pumping quantity during pre-treatment,the 2nd,4th,6th and the 8 week of therapeutic courses,respectively.The adverse reaction was observed.Results 1.Compared with pre-treatment,attention deficit scores after treatment were statistically different (t =8.41,9.97,all P ＜ 0.05) in the 6th,8th week of therapeutic courses;hyperactivity /imnpulsivity scores were statistically different (Z =-4.39,-4.47,-4.46,all P ＜0.05) in the 4th,6th,8th week; Motor tics scores were statistically different (t =18.30,18.67,20.32,all P ＜ 0.05) in the 4th,6th,8th week; The vocal tic score:the second weeks already had statistically different(t =5.45,P ＜ 0.05); And the impaired function score were statistical significance (Z =-3.95,-3.94,all P ＜ 0.05) at the 6th and 8th week.2.The effective rate of ADHD and TS was 7.69％ and 15.38％,respectively in the 2td week.The curative effect had no statistical significance (x2 =0.188,P ＞0.05).But at the tourth week of assessment,and the rates of curative effect were respectively 19.23％ and 46.15 ％.It had statistical significance (x2 =3.923,P ＜ 0.05).In the 6th,8th weeks,there was no significant difference between the 2 efficiency (x2 =0.083,0.103,all P ＞0.05).3.During the treatment,no severe adverse reaction had appeared.Conclusions Atomoxetine in ADHD comorbid TS had exact curative effect and no obvious adverse reactions.In the treatment of ADHD,hyperactivity / impulsivity effect is better than the attention deficit.In the treatment of TS,vocal tics onset is better than the motor tics.In comparison of ADHD with TS,TS symptoms improve faster than ADHD in the onset,but the final effect is quite.

ObjectiveTo investigate the diagnostic value of interferon gamma release assays (IGRAs) in children with tuberculous meningitis.MethodsThe prospective case-control study was applied. From January 2012 to March 2013, 32 children diagnosed with tuberculous meningitis (TBM group) and 30 children diagnosed with non-tuberculous meningitis (non-TBM group) were recruited. The positive rates of the interferon gamma release assays (IGRAs), tuberculin skin test (TST), mycobacterium tuberculosis antibody test (TB-IgG), cerebrospinal lfuid of mycobacterium tuberculosis DNA test (TB-DNA), and the sensitivity, speciifcity, negative and positive predictive value of all these tests were compared between TBM group and non-TBM group.Results The positive rate of IGRAs, TST, TB-IgG, and TB-DNA was 87.50%, 56.25%, 46.88% and 34.38%respectively in TBM group, and 6.67%, 23.33%, 20% and 0% respectively in non-TBM group. The differences were statistically signiifcant (P<0.05). The sensitivity of IGRAs, TST, TB-IgG, and TB-DNA was 87.5%, 56.25%, 6.88% and 34.38% respectively. The speciifcity of IGRAs, TST, TB-IgG, and TB-DNA was 93.33%, 76.67%, 80.00% and 100% respectively. The differences of sensitivity and speciifcity were statistically signiifcant (P<0.05). The sensitivity of IGRAs was higher than that of other tests (P<0.017). The positive predictive value of IGRAs, TST, TB-IgG, and TB-DNA was 93.33%, 72%, 71.43% and 100% respec-tively. The negative predictive value was 87.50%, 62.16%, 58.54% and 58.82% respectively.Conclusions IGRAs, TST, TB-IgG, and TB-DNA are valuable in the diagnosis of tuberculous meningitis. IGRAs has a relatively higher sensitivity and speciifcity.

Objectlve To investigate the inhibition of Coxsackievirus B3(CVB3)infection in cardiac myocytes cultured by small interfering RNA(siRNA)-mediated RNA interference and to evaluate the feasibility of siRNA as the prophylaxis and therapy for CVB3 infection.Methods Cardiac myocytes were prepared in vitro and infected with CVB3,and transfected with siRNA by lipofectamin and electroporation.The numbers of beating cardiac myocytes were counted under the microscope.Neutral red staining was used to evaluate the mortality of cardiac myocytes.Antiviral activities of these siRNAs were estimated by observing cytopathic effect(CPE),plaque reduction assay,Western blot assay and RT-PCR.Results siRNA-3753,which aimed at sequence in 2B section of CVB3 genome,displayed a stronger inhibition of CVB3 infection through screening in HeLa cells,siRNA-3753,chosen to transfect cultured neonatal mice cardiac myocytes,Wag observed to keep a good states of growing and beating at 24 h after CVB3 infection.Whereas the cytopathic signature of controlled cells became stopping beating,round and finally the cell fell off the culture plate.The results showed that siRNA-3753 could protect cells significantly,98.1%inhibition of CVB3 replication with electroporation transfection and 78.2%inhibition of CVB3 with liposome transfection.Transfection efficiencies were 56.0 3%and 9.0%by electroporation and lipofectamin,respectively.Conclusion siRNA,which aims at sequence in 2B section of CVB3 genome,can inhibit CVB3 infection in cultured cardiac myocytes.

Objective: To evaluate the effects and partly mechanism of Qileng decoction(QLD,芪棱汤) resisting focal cerebral ischemia/reperfusion(I/R) injury in rats by apoptosis and signal transduction pathway.Methods: The rats were randomly divided into three groups including sham operation group,normal saline(NS) control group and QLD group.The model of focal cerebral I/R injury was induced by using modified thread embolizing in rats.Rats were evaluated by neurologic function score at 2 hours after ischemia and 2,4,6,12,24 and 48 hours after cerebral reperfusion,and the pathological changes of nerve cells and mitochondria ultrastructure at pallium and hippocampus CA1 region were observed at 24 hours after reperfusion.Immunohistochemical method was performed to examine the expression of cytochrome C(cyt C) and caspase-9 at different time points after reperfusion.Apoptosis of nerve cells in ischemic penumbra(IP) was also characterized by terminal deoxynucleotidyl-transferase mediated dUTP-biotin nick end labeling(TUNEL) method.Results: Compared with NS control group,neurologic function scores at different reperfusion time points were improved and the pathological changes were ameliorated at 24 hours after cerebral I/R in QLD group.Mitochondria hydropsia was alleviated,mitochondrial cristae fragmentation and granulum basale shedding were diminished,and mitochondrial basical morphology was retained.Meanwhile,apoptosis index(AI) was decreased and the expressions of cyt C and caspase-9 were reduced in IP in QLD group.Conclusion: QLD intervenes in mitochondria mediated and caspase-9 dependent apoptopic pathway.QLD lowers AI and plays a role of protecting nerve by maintaining mitochondrial basical form,stabilizing mitochondrial membrane and inhibiting the release of cyt C and activation of caspase-9.The above actions are possibly some parts of mechanisms of QLD resisting focal cerebral I/R injury.

Objective:To screen the ectodysplasin A (EDA)gene mutation in the patients with non-syndromic tooth agenesis and ectodermal dysplasia,and to analyze the phenotype of missing teeth pattern in these two groups of patients.Methods:In the study,174 patients with tooth agenesis (143:non-syn-dromic,31:ectodermal dysplasia)and 451 health control volunteers were enrolled from the clinic,and the genome DNA was extracted from either peripheral blood or oral mucosal swab.The coding region of EDA gene was then amplified by PCR,sequenced and blasted to online NCBI database.The missing teeth were recorded for all patients,and the missing teeth from patients with EDA mutation were com-pared among the different dentition sites.Results:33 patients were identified with EDA mutation.In the non-syndromic patients,13 /143(9.09%)were identified with EDA mutation,while in patients with ec-todermal dysplasia,20 /31 (64.52%)were found with EDA mutation.Ten novel EDA mutations were identified (c.769G >C[p.G257R],c.936C >G[p.I312M],c.223G >A[p.E75K],c.1166C >T[p. P389L],c.133G >C[p.G45R],c.1109G >A[p.E370K],c.914G >T[p.S305I],c.916C >T[p. Q306X],c.602G >T[p.G201V],c.88 -89insG[p.A30GfsX69]).For each dentition site there was no statistic difference in the number of missing teeth between the left and right sides,so the number from both sides were combined later in the analysis.In the patients with EDA mutation,the non-syndromic pa-tients had fewer missing teeth (15.9 ±6.4 missing teeth for each,207 /364 in total)than the patients with ectodermal dysplasia (23.9 ±4.3,478 /560).In the non-syndromic patients with EDA mutation, the maxillay central incisors and first molars were less affected,with the same missing rate as 19.2% (5 /26).While the mandibular central incisors (with a missing rate of 76.9%,20 /26),the maxillary late-ral incisors (the missing rate:88.5%,23 /26 ),the mandibular lateral incisors (the missing rate:80.8%,21 /26),and the maxillary first premolars (the missing rate:80.8%,21 /26)were more likely to be missing.In the ectodermal dysplasia patients with EDA mutation,only maxillary central incisors (the missing rate:60%,24 /40),maxillary canines (the missing rate:70%,28 /40),mandibular ca-nines (the missing rate:67.5%,27 /40),maxillary first molars (the missing rate:65%,26 /40)and mandibular first molars (the missing rate:72.5%,29 /40)had higher possibility of persistence.Teeth at other dentition sites were more likely to be affected (the minimum missing rate:87.5%,35 /40). Conclusion:The findings would help to reveal the EDA gene and its function in ectodermal organogene-sis.

Epilepsy is one of the most common chronic neurological diseases, which results from diverse etiologies, and its mechanism is very complicated.Ion channel gene mutation is a common genetic cause of epilepsy.Voltage-gated chloride channels (ClCs) can change the chloride ion concentration and electric potential difference across the plasma membrane, and thereby regulate the electrical excitability of neurons.CLCN-1, CLCN-2, CLCN-3, CLCN-4 and CLCN-6 are reported to be associated with epilepsy, which could increase susceptibility to epilepsy or cause seizures.This review is focused on recent advances in ClCs and epilepsy.

Objective K93T point mutation exists in the quinoid dihydropteridine reductase ( QDPR) of OLEFT rats which catalyzes QDPR into tetrahydrobinopterin(BH4), while dihydrofolate reductase(DHFR) can reduce QDPR to BH4, which implies crosstalk between hydrobiopterin and folate metabolism.By investigating the influence of QDPR expression on DHFR expression of NRK-52E cells, the article aimed to find out the possible underlying mechanism of QDPR gene in diabetic nephropathy ( DN). Methods Western blot was performed to identify the expression level in NRK-52E cell under high glucose ambience and DHFR pro-tein expression of OLETF rats.NRK-52E cells were transfected by the lentivirus to establish no-load overexpression, overexpressed QDPR and knockdown QDPR models.Each group was given 5.4 mmol/L normal sugar medium and 30mmol/L in high glucose ambi-ence for 72 hours'cell cultivation to simulate DN model.Observation was made on the influence of QDPR gene expression levels on DHFR in high glucose ambience. Results The western blot analysis revealed that DHFR protein decreased in NHG group( [0.33 ± 0.16] vs [0.64 ±0.5], P<0.05) and OLETF rats cortex ([0.56 ±0.16] vs [1.03 ±0.12], P<0.01).In high glucose ambi-ence, compared with LV-OCON-HG group, the protein expression of DHFR was significantly decreased in LV-QDPR-HG group ([0.12 ±0.09] vs [0.63 ±0.08], P<0.01).No difference was found in the comparison of DHFR expression levels between LV-SHQDPR-HG and LV-SHCON-HG group. Conclusion DHFR protein expression decreases in NRK-52E cells of high glucose and LOLETF rat model, which suggests that DHFR protein plays an important role in the development of DN.QDPR overexpression leads to the decreased expression of DHFR, which implies that overexpressed QDPR influences the occurrence and process of DN by down-regulating DHFR expression level.

OBJECTIVETo study the effect of chronic intermittent hypoxia-induced inflammatory cytokines and reoxygenation on glucose transporter 4 (GLUT-4) expression in rat skeletal muscles.

METHODSTwenty-four male Sprague-Dawley rats were randomly assigned to blank control group, chronic intermittent hypoxia (CIH) group, and reoxygenation group. At the end of the experiment, fasting blood glucose (FBG), fasting blood insulin (FINS) and serum inflammatory cytokine levels were measured with glucose oxidase-peroxidase, insulin radioimmunoassay and ELISA, respectively. Homeostasis model assessment (IRI) was used to evaluate insulin resistance in the rats, and GLUT-4 protein expression in the skeletal muscles was measured with Western blotting.

RESULTSCompared with the blank control group, CIH resulted in significantly increased fasting blood glucose, blood insulin levels and insulin resistance index (IRI) (P<0.05); fasting blood glucose was significantly elevated in reoxygenation group (P<0.05). Inflammatory cytokines levels (IL-6 and TNF-α) were significantly higher in CIH group than in the blank control and reoxygenation groups (P<0.05), and were higher in reoxygenation group than in the blank control group. GLUT-4 expression in the skeletal muscles was significantly reduced after CIH (P<0.05) but increased after subsequent reoxygenation (P<0.05).

CONCLUSIONCIH can cause increased release of inflammatory cytokines to lower GLUT-4 protein expression in the skeletal muscles, which contributes to insulin resistance in adult rats.

Animals ; Blood Glucose ; Glucose Transporter Type 4 ; metabolism ; Hypoxia ; Insulin ; blood ; Insulin Resistance ; Interleukin-6 ; Male ; Muscle, Skeletal ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

Objective:To screen the differential metabolites and metabolic pathways in silicosis model by analyzing plasma metabolomics of silicosis rats.Methods:In May 2021, twenty male SD rats were randomly divided into control group (C), 1-week silicosis group (S1W), 2-week silicosis group (S2W) and 4-week silicosis group (S4W), with 5 rats in each group. Rats were intratracheally instillated with 1ml crystalline SiO 2 suspension (50 mg/ml) or normal saline and were sacrificed after 1 week, 2 weeks and 4 weeks, HE staining was used to observe the lung pathology of rats. The plasma samples were analyzed by UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze their lipid enrichment. Results:HE results showed that nodules formed in the silicosis model group, and with the extension of time, nodules gradually increased and alveolar structure was gradually destroyed. Metabolomics screened out 14 differential metabolites in S1W, 24 in S2W, and 28 in S4W, and found that the differential metabolites were mainly enriched in the metabolism of glycerophospholipid metabolism, fatty acid degradation, Glycosylphosphatidylinositol (GPI) -anchor biosynthesis, fatty acid elongation and other metabolic pathways.Conclusion:There are significant changes in plasma lipid metabolites in silicosis rat models.

Objective:To investigate the mechanism of Sulfo-N-succinimidyloleate (SSO) regulating lipid metabolism disorder induced by silicon dioxide (SiO 2) . Methods:In March 2023, Rat alveolar macrophages NR8383 were cultured in vitro and randomly divided into control group (C), SSO exposure group (SSO), SiO 2 exposure group (SiO 2) and SiO 2+SSO exposure group (SiO 2+SSO). NR8383 cells were exposure separately or jointly by SSO and SiO 2 for 36 h to construct cell models. Immunofluorescence and BODIPY 493/ 503 staining were used to detect cluster of differentiation (CD36) and intracellular lipid levels, the protein expression levels of CD36, liver X receptors (LXR), P-mammalian target of rapamycin (P-mTOR) and cholinephosphotransferase 1 (CHPT1) were detected by Western blot, respectively, and lipid metabolomics was used to screen for different lipid metabolites and enrichment pathways. Single-factor ANOVA was used for multi-group comparison, and LSD test was used for pair-to-group comparison. Results:SiO 2 caused the expression of CD36 and P-mTOR to increase ( P=0.012, 0.020), the expression of LXR to decrease ( P=0.005), and the intracellular lipid level to increase. After SSO treatment, CD36 expression decreased ( P=0.023) and LXR expression increased ( P=0.000) in SiO 2+SSO exposure group compared with SiO 2 exposure group. Metabolomics identified 87 different metabolites in the C group and SiO 2 exposure group, 19 different metabolites in the SiO 2 exposure group and SiO 2+SSO group, and 5 overlaps of different metabolites in the two comparison groups, they are PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), and Sphinganine. In addition, the differential metabolites of the two comparison groups were mainly concentrated in the glycerophospholipid metabolism and sphingolipid metabolism pathways. The differential gene CHPT1 in glycerophospholipid metabolic pathway was verified, and the expression of CHPT1 decreased after SiO 2 exposure. Conclusion:SSO may improve SiO 2-induced lipid metabolism disorders by regulating PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), SPA, glycerophospholipid metabolism and sphingolipid metabolism pathways.