To observe the clinical efficacy of dopamine modulator methylphenidate (MPH) of extended-release formulations (MPH-ER) augmentation of ongoing fluvoxamine treatment in refractory obsessive-compulsive disorder (OCD) and its effects on patient's anxiety and sleep quality.
 Methods: A pilot randomized, placebo-controlled, and double-blind trial was conducted at an outpatient, single-center academic setting. Participants included 44 adults with serotonin reuptake inhibitor treatment-refractory OCD and they received a stable fluvoxamine pharmacotherapy with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores higher than 20. The 44 patients were randomly assigned into a study group and a control group, with 22 patiencs in each group. Fluvoxamine and MPH-ER were given to the study group, while fluvoxamine and placebo were given to the control group, with 8 weeks of the treatment course. Y-BOCS, Hamilton Anxiety Scale (HAMA) were used to assess the efficacy, Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality, and Treatment Emergent Symptom Scale (TESS) was used to evaluate the side effects. Data were analyzed in the intention-to-treat sample.
 Results: The improvement in the Y-BOCS total score, Y-BOCS obsession subscale score and HAMA score were more prominent in the study group than those in the control group (P<0.001). There was no significant difference in PSQI score and TESS score between the two groups. MPH-ER was well tolerated.
 Conclusion: Fluvoxamine combined with MPH-ER is effective in the treatment of refractory obsessive-compulsive disorder. It can improve anxiety and has no adverse effect on sleep quality.
Adult ; Double-Blind Method ; Drug Therapy, Combination ; Fluvoxamine ; therapeutic use ; Humans ; Methylphenidate ; therapeutic use ; Obsessive-Compulsive Disorder ; drug therapy ; Psychiatric Status Rating Scales ; Treatment Outcome

Objective To investigate the abnormal brain activity of first-episode depression by rest-ing state functional magnetic resonance imaging ( fMRI) .Methods Twenty-one adolescent participants diag-nosed with depression(AD) and 18 healthy controls ( HC) were recruited.Resting state fMRI brain scans were performed on all participants.Regional homogeneity ( ReHo) approach was applied to preprocess the fMRI datasets.The value of ReHo maps were obtained in the whole brain.Results ReHo values in the AD group were higher than those in the healthy controls in the right inferior temporal gyrus ( MINI:66,-24,-20) ,left upper cingulate cortex (-27,47,-6) ,frontal polar (-24,59,14) ,after upper left cingulate cortex (-1,-16,35),after the bottom left cingulate cortex (-2,-38,32),left praecuneus (-1,-48,65) com-pared with that in the healthy controls (P<0.05) .ReHo in the AD group decreased in the right middle tempo-ral gyrus (45,-34,32) compared with that in the healthy controls (P<0.05).Conclusion Extensive ReHo abnormalities were found in the brains of patients with first-episode,drug-naive depression,and these abnor-malities in spontaneous neural activity may contribute to the neuropathology of adolescent depression.

Objective To discuss the difference of handwriting characteristics of schizophrenia,neurosis and healthy people according to the gender,the age and the level of educated.Methods The handwriting data were obtained under the standard condition of handwriting,then the 24 Chinese characters handwriting image information were transformed into digital data using the quantitative characteristics of Chinese characters handwriting recognition system (CCQAS4.0),finally the data of 99 patients with schizophrenia and 131 patients with neurosis were analyzed.Results Many significant differences had been found in schizophrenia,neurosis and norm group (P ＜0.05,P＜0.01),such as footer space((198.33±26.50) mm,(180.31±39.31)mm,(192.39±35.08) mm),average line spacing ((4.02 ± 1.68) mm,(5.34 ± 2.20) mm,(4.76 ± 2.00) mm) etc ; and there were also some important differences between the schizophrenia patient and the neurosis patient from different gender,age and education level in the 24 handwriting characteristics (P＜0.05,P＜0.01).Conclusions (1) Significant handwriting characteristic differences have surely been found among the schizophrenia/neurosis patient and normal people.(2) Gender,age and education level have impact on the characteristic in the schizophrenia patient and the neurosis patient.

Objective To investigate the relationship between C734A and G-2964A polymorphism of cytochrome P450 1A2 gene and clinical efficacy of duloxetine.Methods 223 patients with depression were treated with duloxetine for six weeks.The clinical efficacy was evaluated with the Hamilton rating scale for depression (HAMD) ;single nucleotide polymorphism (SNP) at position C734A and G-2964A of CYP1A2 gene were identified with restriction fragment length polymorphism(RFLPs) ;then one-way ANOVA was adopted to analyze the relationship between SNP and clinical efficacy.Results (1) In 223 patients,the frequency of allele A at locus 734 was 63.64％,while that of allele A at locus-2964 was 26.82％.(2) 220 patient underwent the whole treating course.The conjoint analysis of two locuses indicated that the decreasing ratio of HAMD score of high-activity group,middle-activity group and low-activity after treatment was (56.05± 10.13) ％,(66.36± 8.66) ％ and (73.82± 7.10) ％ respectively,the differences obtained by pairwise comparison of the three groups were of statistical significance(P＜0.01).Conclusion There is close relationship between C734A and G-2964A polymorphism of CYP1A2 gene and clinical efficacy of duloxetine in the treatment for depression.

Objective To evaluate the risk factors for healthcare-associated infection(HAI)in senile dementia pa-tients,so as to adopt effective nursing measures to reduce the incidence of HAI.Methods Clinical data of 82 senile dementia patients aged≥60 years and hospitalized between January 2011 and June 2013 were analyzed retrospective-ly.Results Of 82 patients,28 (34.15%)developed HAI.The main infection site was lower respiratory tract(n=15,53.57%),followed by urinary tract(n=6,21 .43%).Univariate analysis revealed that risk factors for HAI in senile dementia patients were bedridden,long length of hospital stay ,dysphagia,indwelling urinary catheter,irra-tional use of antimicrobial agents,combined with tumor,and hypoproteinemia (all P <0.05 ).The main isolated bacteria were gram-negative bacilli(n=40,62.50%),the top three pathogens were Klebsiella pneumoniae (n=12, 18.75%),Escherichia coli (n =10,15.63%),and Pseudomonas aeruginosa (n =8,12.50%).Conclusion Reali-zing the risk factors and common pathogens of HAI in senile dementia patients is helpful for taking effective meas-ures to prevent and control the incidence of HAI .

Objective To analyze the clinical characteristics and risk factors of nosocomial infection (NI) in elder patients with cerebral infarction Methods A retrospective study was performed.Three hundred and two patients over 60 years old with cerebral infarction were selected as our subjects,who were in a cadre ward from Jan.2011 to Jun.2013.The incidence rate of NI and the predisposing factors of NI were investigated.Results Of 302 patients with cerebral infarction,46 cases developed NI and the incidence was 15.23％.The most common site of NI was lower respiratory tract infection,counting for 60.87％ (28/46),followed by urinary tract infection(21.74％ (10/46)).The risk factors of NI included age,prolonged hospitalization,disturbance of consciousness,invasive operation and the use of antibiotics (x2 =5.720,11.517,5.185,4.218,11.931 ; P ＜ 0.05).Conclusion The clinical staff should pay close attention to the risk factors of NI in elder patients with cerebral infarction.The methods include controlling the disease as soon as possible,shortening hospital stays,reducing invasive operation and the rational use of antibiotics can reduce the incidence of NI.

KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHD1KDM5B interacts with unmethylated H3K4me0. Our NMR structure of PHD1KDM5B in complex with H3K4me0 revealed that the binding mode is slightly different from that of other reported PHD fingers. The disruption of this interaction by double mutations on the residues in the interface (L325A/D328A) decreases the H3K4me2/3 demethylation activity of KDM5B in cells by approximately 50% and increases the transcriptional repression of tumor suppressor genes by approximately twofold. These findings imply that PHD1KDM5B may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B.
Binding Sites ; genetics ; Crystallography, X-Ray ; Gene Expression Regulation ; HEK293 Cells ; Histones ; chemistry ; metabolism ; Humans ; Jumonji Domain-Containing Histone Demethylases ; chemistry ; genetics ; metabolism ; Lysine ; chemistry ; metabolism ; Magnetic Resonance Spectroscopy ; Methylation ; Microscopy, Fluorescence ; Models, Molecular ; Mutation ; Nuclear Proteins ; chemistry ; genetics ; metabolism ; Peptides ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins ; chemistry ; genetics ; metabolism

Objective To investigate the effects of signal pathway inhibitors PD98059 and LY294002 on cell proliferation, apoptosis, expressions of phosphorylated extracellular signal-regulared kinase (p-ERK) and phosphorylated protein kinase B ( p-Akt) in endometrial carcinoma xenografts. Methods Human endometrial carcinoma Ishikawa cells were cultured in vitro. The effects of PD98059 and LY294002 on proliferation, apoptosis, and cell cycle distribution of endometrial cancer cells were detected by monotetrazolium ( MTT) assay and fluorescence-activated cell sorting technique. The models of xenografted tumor were established by the subcutaneous inoculation in 24 nude mice, and then they were randomly divided into 4 groups ( n = 6) , normal saline group, PD98059 group (PD group) , LY294002 group ( LY group) or PD98059 + LY294002 group ( PD + LY group) by intraperitoneal injections, respectively. The anti-tumor efficacy was evaluated by measuring tumor volume and tumor growth status. The histopathological change of tumor specimens was observed using HE staining and terminal deoxynucleotidyl transferasemediated dUTP-digoxigen in nick and labeling method (TUNEL) testing and the expression levels of p-ERK and p-Akt were detected by immunohistochemistry method. Results ( 1) The proliferation of Ishikawa cells were suppressed after treated by PD98059 and ( or) Y294002, in which A570 values of cells decreased showing both time-dependent and concentration-dependent manner ( LY294002: Fgroup = 9. 801, P = 0. 002; Ftime = 10. 398, P = 0. 001. PD98059: Fgroup= 8. 213, P = 0. 015; Ftime = 6. 839, P = 0. 036). Cell cycle distribution analysis revealed that percentage of Ishikawa cells at G0/G1 phase(Ftime =35.049, P= 0.004; Fgroup = 32. 024, P ＜0. 01) increased and percentage of S phase cells (Ftime = 7. 789, P = 0. 049; Fgroup = 30. 132, P ＜0. 01) decreased significantly. The percentage of apoptotic cells increased significantly among PD group, LY group and PD + LY group, in which there were significant difference [(63. 3 ±0.5)% vs (30. 7 ± 20. 1) % vs(40. 8 ± 1. 3) % ; F = 621. 059, P ＜ 0. 01]. (2) Compared with the control group, the increasing of transplanting tumor volume in the treated groups were obviously ( F = 23. 545 , P ＜ 0. 01) , and the inhibited rate of the tumor was higher in PD + LY group than that in PD group or LY group [(68 ± 9 ) % vs ( 32 ± 16 ) % or ( 38 ± 17 ) % ; F = 10. 283 , P ＜ 0. 05]. ( 3 ) HE staining shown that there were different degrees of necrosis for endometrial carcinoma cell in different groups. The apoptosis of tumor cells were significantly increased in treated groups by TUNEL testing [(13. 7 ± 1. 5)% , ( 14. 1 ± 1. 2)% , (29. 0 ± 1. 8 ) % ; F = 320. 344, P ＜ 0. 01]. Immunohistochemistry results demonstrated that the expressions of p-ERK and p-Akt in treated groups were lower than that in control group, of which LY + PD group was the lowest one. Conclusion The signal pathway inhibitors PD98059 and LY294002 could inhibit the growth of human endometrial carcinoma in vivo and in vitro, in which may induce cell apoptosis.

Objective: To investigate the effect of moxibustion on telomerase activity and genes expression in tissues of senescent rats. Methods: Subacute aging rats model were established by injection with D-gal solution. Points Shenshu (BL 23) were treated with moxibustion in treatment group, contrasting with a model group and a normal group. Enzyme-Linked Immunosorbent Assays(ELISA) was used for the level oftelomerase activity in liver tissues, and In Situ Hybridization(ISH) was used for the condition of expression of telomerase genes in liver tissues. Results: The level of telomerase activity in the aging model group was obviously lower than that in normal control group (P＜0.01), the level in moxibustion group was obviously higher than that in model group(P＜0.05). In comparison with normal rats, the positive-expressed areas and photodensity of telomerase genes in aging model group were all significantly lower (P＜0.01,P＜0.01), and the positive-expressed areas in moxibustion group was significantly higher than that in model group (P＜0.01). Conclusions: Moxibustion could regulate telomerase activity of senile rats, hence delaying aging.

In order to study whether patients with schizophrenia have cerebral injury, neuron-specific enolase (NSE) and myelin basic protein (MBP)in cerebrospinal fluid (CSF) of 33 patients with first episode schizophrenia and 9 from the control group were determined by double antibody sandwich enzyme immunoassay method. The results showed that there was significant difference in the NSE contents between the experimental group and control group (P＜0.01). The NSE contents in CSF in the experimental group were positively correlated with MBP in schizophrenia patients (P＜0.05). These findings suggested that patients with schizophrenia had cerebral injury.