OBJECTIVE： To conduct bibliometric analysis of off-label use in domestic and foreign. METHODS： Retrieved from CNKI， Wanfang database， VIP， PubMed， Embase and Web of Science during Jan. 1991 （in foreign） or Jan. 2007 （in domestic） to Dec. 2018， related literatures of off-label use were collected. General information （publication numbers distribution， journals distribution）， article cooperation （core researchers， research content） and keywords of domestic and foreign literatures were analyzed and summarized. RESULTS： A total of 1 647 domestic and 4 418 foreign literatures were retrieved， including 1 570 domestic and 4 238 foreign valid literatures. Publications increased over the past decade， with the largest number of domestic and foreign publication numbers in 2017 （355 in domestic and 465 in foreign）. The most published domestic and foreign journals were China Pharmacy （105 literatures） and European Journal of Clinical Pharmacology （51 literatures）. The core researchers in domestic and foreign were Li Youping and de la Torre JC. The contents of domestic researches included off-label use policy， current situation of off-label use in children， off-label use in ophthalmology， off-label use of Chinese patent medicine， etc. The contents of foreign researches included off-label use in antiviral drugs， off-label use in special population （children， alcoholic dependence patients， etc.）. Off-label use， rational drug use and drug instructions as well as human， off-label use and article were the top 3 keywords in domestic and foreign literatures， respectively. CONCLUSIONS： Off-label use research at home and abroad is increasing year by year. Research teams carry out co-operations actively. Bibliometric methods can help researchers broaden research directions， track research hotspots and select contributing journals.

Objective To evaluate the role of cholinergic anti-inflammatory pathway in dexmedeto-midine pretreatment-induced reduction of acute lung injury in a rat model of intestinal ischemia-reperfusion ( I∕R) . Methods Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 200-250 g, were divided into 4 groups ( n=6) using a random number table method: sham operation group ( S group) , intestinal I∕R group ( II∕R group ) , dexmetomidine group ( DEX group) and α7 nicotinic acetyl-choline receptor antagonistα-bungarotoxin (α-BGT) group (α-BGT group) . Intestinal I∕R was produced by occlusion of the superior mesenteric artery ( SMA) for 60 min followed by 120 min of reperfusion in anesthe-tized rats. Dexmetomidine 5 μg·kg-1 ·h-1 was injected via the tail vein at 1 h before operation in DEX group andα-BGT group. α-BGT 1μg∕kg was intraperitoneally injected at 15 min before dexmetomidine in-jection in α-BGT group. Rats were sacrificed at 120 min of reperfusion, and lung tissues were obtained for microscopic examination of pathological changes ( with a light microscope) and for determination of wet∕dry weight ratio ( W∕D ratio) , tumor necrosis factor-alpha ( TNF-α) and interleukin-6 ( IL-6) contents ( using enzyme-linked immunosorbent assay) , malondialdehyde ( MDA) content ( using thiobarbital acid method) and superoxide dismutase ( SOD) activity ( by xanthine oxidase method) . Results Compared with group S, the W∕D ratio and contents of MDA, TNF-αand IL-6 were significantly increased, and the SOD activi-ty was decreased in II∕R and α-BGT groups, and TNF-α and IL-6 contents were significantly increased in group DEX ( P<0. 05) . Compared with group II∕R, the W∕D ratio and contents of MDA, TNF-αand IL-6 were significantly decreased, SOD activity was increased (P<0. 05), and the pathological changes were significantly attenuated in group DEX. Compared with group DEX, the W∕D ratio and contents of MDA, TNF-α and IL-6 were significantly increased, SOD activity was decreased ( P<0. 05) , and the pathological changes were accentuated in group α-BGT. Conclusion Activation of cholinergic anti-inflammatory path-way is involved in the mechanism by which dexmedetomidine pretreatment reduces acute lung injury in a rat model of intestinal I∕R.

OBJECTIVE:To evaluate the association between UGT1A1 gene polymorphism and irinotecan-induced 3-4 degree neutropenia,and to provide evidenced-based reference for clinical treatment. METHODS:Retrieved from CJFD,Wanfang data-base,VIP,PubMed,EMBase,Science direct and Cochrane library,related studies about UGT1A1*28 and UGT1A1*6 gene polymorphism and irinotecan-induced 3-4 degree neutropenia were collected. After data extraction and quality evaluation of included studies,Meta-analysis was conducted by using Review Man 5.3 software. RESULTS:A total of 29 studies were included,involv-ing 2408 patients. UGT1A1*28 includ wild genotype TA 6/6(UGT1A1*1/*1)and mutations genotype TA 6/7(UGT1A1*1/*28)、TA 7/7(UGT1A1*28/*28),UGT1A1*6 includ wild genotype GG and mutations genotype GA、AA. Results of Meta-analysis showed:the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=1.92,95%CI(1.52,2.44),P<0.001;UGT1A1*6:OR=2.49, 95%CI(1.46,4.26),P<0.001]. Using medium-dose and high-dose of irinotecan,the incidence of 3-4 degree neutropenia in UGT1A1*28 and UGT1A1*6 mutations genotype were significantly higher than wild genotype,with statistical significance [UGT1A1*28:OR=2.06,95%CI(1.57,2.70),P<0.001);UGT1A1*6:OR=1.92,95%CI(1.35,2.74),P<0.001]. Using low-dose of irinotecan,there was no statistical significance in the incidence of 3-4 degree neutropenia between UGT1A1*28,UGT1A1*6 mutations genotype and wild genotype [UGT1A1*28:OR=1.20,95%CI(0.70,2.08),P=0.51;UGT1A1*6:OR=3.19,95%CI (0.85,11.89),P=0.08]. CONCLUSIONS:Using medium-dose and high-dose of irinotecan,UGT1A1*28 and UGT1A1*6 muta-tions will increase the risk of severe neutropenia in cancer patients. Using low-dose of irinotecan,there is no clear correlation be-tween gene polymorphism and the neutropenia.

Objective To explore the state of cardiac autonomic nerve function in schizophrenia patients with metabolic syndrome and analyze its influence factors and to reduce the occurrence of sudden cardiac death of the patients. Methods A total of 168 cases of patients according with the ICD-10 schizophrenia diagnostic criteria were divided into group A(78 cases of schizophrenia with metabolic syndrome),group B(90 cases of schizophre-nia without metabolic syndrome)and another 92 normal cases were included as control group(group C). Twenty-four hours dynamic electrocardiogram was conducted respectively and the heart rate variability (HRV) was ana-lyzed. Results Values of LF,HF,SDNN,SDANN,RMSSD and PNN50 in group A and group B were much low-er than those in group C and they were statistically significant(P < 0.05). Values of LF,HF,SDNN,SDANN, RMSSD and PNN50 in group B were much higher than those in group A and they were statistically significant(P<0.05). Excluding the influence of schizophrenia ,logistic regression analysis showed that the influence factors of HRV values were course of the disease(OR = 1.864,95%CI 1.110~3.128),age(OR = 1.170,95%CI 1.018~2.491),types of antipsychotic drugs(OR=2.419,95%CI 0.976~1.835),abdominal obesity(OR=2.425,95%CI 1.347~4.366),blood pressure value(OR=1.263,95%CI 1.575~3.937),blood glucose value(OR=3.376, 95%CI 1.359~2.923)and blood lipid value(OR = 2.178,95%CI 1.492~6.756). Conclusions Schizophrenia patients with metabolic syndrome have obvious cardiac autonomic nerve dysfunction. Excluding the influence of schizophrenia itself,the other possible risk factors include course of the disease,age,types of antipsychotic drugs,abdominal obesity,blood pressure value,blood glucose value and blood lipid value.

Objective To study the features of treatment on neurochemical metabolites in prefrontal lobe and thalamus by proton magnetic resonance spectroscopy (1H-MRS) in first-episode drug-naive patients with early-onset schizophrenia (EOS).Methods Forty-two EOS (study group) met with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-Ⅳ) were recruited.Prefrontal lobe and thalamus were evaluated by multi-voxel 1H-MRS before and 4-week after treatment with a single atypical antipsychotic.The levels of N-acetylaspartate (NAA),creatine compounds (Cr) and choline-containing compounds (Cho) were measured.The patients also received Positive and Negative Syndrome Scale (PANSS).Forty normal controls (normal control group) underwent the same 1H-MRS detection.Results Before treatment,the NAA/Cr ratios in left prefrontal lobe,right prefrontal lobe and lefi thalamus in study group were lower than those in normal control group (1.45 ± 0.26 vs 1.60 ± 0.34,t =2.251,P =0.027;1.43 ±0.26 vs 1.60 ±0.35,t =2.505,P=0.014;1.48 ±0.27 vs 1.65 ±0.35,t =2.470,P =0.016).After 4-week treatment,the NAA/Cr ratios in both left prefrontal lobe and left thalamus of study group were significantly increased compared with those before treatment (1.58 ± 0.30 vs 1.45 ± 0.26,t =2.122,P =0.037;1.62 ± 0.32 vs 1.48 ± 0.27,t =2.167,P =0.033).After 4-week treatment in study group,the total score,positive symptom score,negative symptom score and general pathologic score of PANSS,and the total score of Clinical Global Impression (CGI) were significantly lower compared with those before treatment (59.1 ± 10.2 vs 82.0 ± 13.2,t =8.896,P=0.000;15.3 ±5.1 vs 22.9 ±7.1,t =5.634,P =0.000;16.4 ±5.2 vs 21.1 ±7.8,t =3.249,P =0.002;27.4 ±7.6 vs 38.1 ± 8.8,t =5.963,P =0.000;3.6 ± 0.4 vs 4.4 ± 0.5,t =8.097,P =0.000).There was no correlation between the changes of neurochemical metabolite levels such as NAA/Cr and Cho/Cr both in prefrontal lobe and left thalamus,and the clinical symptoms changes,such as total score and every score of PANSS,the total score of CGI in study group after treatment (all P ＞ 0.05).Conclusions The ratios of NAA/Cr are decreased not only in bilateral prefrontal lobe,but also in left thalamus,and the ratios may increase both in left prefrontal lobe and left thalamus after 4 weeks' treatment with atypical antipsychotics in EOS.The treatment outcomes of NAA/Cr do not agree with the improvement of the clinical symptoms.

Objective To evaluate the effects of 6-week atypical antipsychotics treatment on serum brain-derived neurotrophic factor (BDNF)level,and the correlation between BDNF level and clinical efficiency in first-episode antipsychotic-na?ve schizophrenia.Methods We recruited 39 hospitalized patients with first-episode antipsychotic-na?ve schizophrenia that met with Diagnostic and Statistical Manual of Mental Disorders—4th Edition (DSM-IV).Both Positive and Negative Syndrome Scale (PANSS)and the level of serum BDNF were measured before and after 6 weeks’treatment with atypical antipsychotics.We also studied 30 healthy controls.Serum BDNF was assayed at baseline.Results Pre-treatment BDNF level was significantly lower in the schizophrenic patients than in the controls [(6.82±2.1 5 )μg/L vs .(1 1.6 ± 3.32 )μg/L,t = 7.239,P < 0.001 ].Although BDNF level increased with treatment (t =2.349,P =0.021)in the schizophrenics,post-treatment BDNF level was still lower than in the normal controls (t =4.634,P <0.001).After 6 weeks’treatment for schizophrenia,the total score of PANSS,the scores of positive and negative symptoms,and the score of general psychopathology scale were all decreased (t =6.1 64,P < 0.001;t = 4.520,P < 0.001;t = 4.132,P < 0.001;t = 5.142,P < 0.001 ).Pre-treatment BDNF levels were directly correlated not only with the rate of decreased PANSS total score (r =0.348, P <0.05),but also with the rate of decreased negative symptoms score (r = 0.35 1,P < 0.05 ).However,pre-treatment BDNF levels were not correlated with improved positive symptoms,general psychopathology (r =0.204, 0.186,P >0.05),or duration of illness (r = - 0.058,P > 0.05 ).Changes in BDNF levels with treatment were correlated with the duration of illness (r =-0.345,P <0.05),but not with psychiatric improvement (r =0.036-0.1 74,P >0.05).Conclusion BDNF level is significantly lower in patients with first-episode antipsychotic-na?ve schizophrenia than in normal controls.It could be improved by using antipsychotics.Higher pre-treatment BDNF level may predict better response to antipsychotics.

Objective To investigate the effects of mental health and sleep quality of the armored military performance ,pro-viding a theoretical basis for improving the performance of military officers and soldiers .Methods 276 armored military were se-lected randomly to study the performance ,including military training program evaluation(40% ) ,armored vehicles operating assess-ment(40% ) and leadership assessment(20% ) ,the test results as a percentage of the sum to exceed 80 divided into good and poor performance for the military .Symptom Checklist(SCL-90) and Scale Pittsburgh Sleep Quality Index(PSQI) were assessed ,and to evaluate the performance differences between good and poor military .Results (1)The good performance of armored military were 61 .2% ,and 38 .8% ones were poor .(2)The SCL-90 scores ,interpersonal sensitivity ,anxiety and hostility factors of good military performance were significantly lower than those with poor military performance(P<0 .05) .(3)The PSQI scores of Good military performance was 5 .83 ± 2 .94 ,and the poor was 7 .63 ± 3 .85 ;The sleep quality ,sleep latency ,sleep efficiency and daytime dysfunc-tion factors of good military performance subjective were significantly lower than those of poor military performance(P<0 .05) . Conclusion Psychological status and quality of sleep are important factors to influence performance of military armored force .

Objective To compare with the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) between the left and the right prefrontal on refractory negative symptoms and serum brain-derived neurotrophic factor (BDNF). Methods 80 hospitalized schizophrenics with refractory negative symptoms were divided into study group (n=40) and control group (n=40) randomly. Both groups were received 4-week treatment of 10 Hz rTMS. The stimulus lo?cation of the study group was the left prefrontal, and the control group was the right prefrontal. The type and dose of anti?psychotics remained unchanged during the treatment. The evaluation of positive and negative symptom scale (PANSS) and the measurement of BDNF concentration before treatment and after 4 weeks treatment was analyzed. Results Com?pared with before treatment, the total score of PANSS after treatment significantly decreased (P<0.05) both in the study group [(71.2±13.8) vs. (63.3±11.4)] and the control group [(70.3±13.4) vs. (63.7±12.2)]. The score of negative symptoms in the study group decreased [(22.8±6.6) vs. (18.4±5.9), P<0.01]. The BDNF concentration increased in the study group ](6.78±2.16) vs. (8.74±2.76)] and the control group [(6.83±2.32) vs. (8.66±2.70)]. Conclusion 10Hz rTMS on the left pre?frontal combined with drugs are helpful to improve the refractory negative symptom of the patients with schizophrenia. Stimulation on both left and right prefrontal lobe could increase serum BDNF concentration.

Objective To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on serum brain-derived neurotrophic factor (BDNF) level in patients with schizophrenia.Methods Eighty hospitalized schizophrenics with refractory negative symptoms,admitted to our hospital from September 2012 to October 2013 and met the diagnostic and statistical manual of Mental Disorders-4th Edition (DSM-Ⅳ),were randomly divided into study group (n=40) and sham-operated group (n=40).The rTMS of 10 Hz on left prefrontal lobe was performed in study group and sham stimulation was used in sham-operated group; and the kinds and dosages of antipsychotics were preserved as before; other 40 healthy subjects were used as control group.Positive and Negative Syndrome Scale (PANSS) was performed and serum BDNF level was measured before and 4 weeks after treatment in all patients.Results BDNF level in both study group and sham-operated group before and after treatment was significantly lower than that in the control group (P＜0.05).The total PANSS scores and negative symptom scale scores in the study group after treatment were significantly decreased as compared with those before treatment (71.2±13.8 vs.63.3±11.4,t=2.721,P=0.008; 18.4±5.9 vs.22.8±6.6,t=3.064,P=0.003),and the BDNF level was statistically increased (8.74±2.76 vs.6.78±2.16,t=3.447,P=0.001).After treatment,the study group had significantly lower negative symptom scale scores and higher BDNF concentration than sham-operated group (t=2.470,P=0.016; t=3.180,P=0.002).For total PANSS scores,negative symptom scale scores and general psychopathology scale scores,the changed values before and after treatment of study group were all significantly higher than those in the sham-operated group (7.8±3.5 vs.2.0±0.9,t=9.893,P=0.000; 4.4±1.9 vs.0.5±0.2,t=12.584,P=0.000; 2.8±1.0 vs.0.9±0.4,t=10.875,P=0.000).For the study group,the changes of BDNF concentration showed no obvious correlation with the total PANSS scores or negative symptom scale scores (r=-0.156-0.247,P＞0.05).Conclusions The rTMS of 10 Hz on the left prefrontal lobe can increase the serum BDNF concentration of the schizophrenia.There is no correlation between the changes of BDNF concentration and improved negative symptoms.

ObjectivesTo explore the characteristic of different subtypes of depression on prefrontal lobe and hippocampus by proton magnetic resonance spectroscopy (1H-MRS),and its relationship.Methods 46 patients of depression,which were met with the third edition of the Chinese Classification of Mental Disorders (CC-MD-Ⅲ ) since December 2010 to March 2012 from Mental Diseases Prevention and Treatment Institute,were examined at prefrontal lobe and hippocampus by multi-voxel 1 H-MRS.They were divided into male ( n =25) and female ( n =21 ),early-onset subtype ( n =26) and late-onset subtype ( n =20 ),short-duration of illness ( n =23 )and long-duration of illness ( n =23 ) by different criteria.The N-acetylaspartate ( NAA),Choline-congtaining compounds (Cho),and Creatine compounds (Cr) were measured and the ratios of NAA/Cr,Cho/Cr were determined.ResultsOn left prefrontal lobe,the NAA/Cr ratios in patients of male ( 1.83 ± 0.19),late-onset subtype (1.86 ±0.16),and short-duration of illness ( 1.83 ±0.17) showed higher than those in female ( 1.70 ±0.12,t=2.711,P ＜ 0.01 ),early-onset subtype ( 1.70 ± 0.19,t =3.028,P ＜ 0.01 ),and long-duration of illness ( 1.71±0.20,t =2.192,P＜0.05).Both on left prefrontal and on left thalamus,the ratios of NAA/Cr were positively correlated with the age of onset ( r=0.493 and 0.478,P＜0.01 ),and were negatively correlated with the duration of illness ( r =- 0.482 and - 0.470,P ＜ 0.01 ).ConclusionsDifferent subtypes of depression maybe have different characteristics of 1H-MRS due to the age of onset and the duration of illness.