Modeling methodologies developed for studying pharmacokinetic(PK)/pharmacodynamic(PD) processes confront many challenges related in part to the severe restrictions on the number and type of measurements that are available from laboratory experiments and clinical trials, as well as the variability in the experiments and the uncertainty associated with the processes themselves. Bayesian methods have provided a framework for PK/PD modeling and drug development that can address some of the above-mentioned challenges. This paper presents two illustrations of the application of Bayesian methods: the first involves a population modeling study of the cellular kinetics of the antiretroviral compound Lamivudine in the PBMCs of HIV-1 infected adolescents; the second uses a population mixture modeling approach to identifying hidden subpopulations that can not be identified by available measured covariates.

Objective To investigate the effect of integrin-linked kinase (ILK) on inducing mesenchymal stem cells (MSCs) to neuron stem-like cell in vitro. Methods MSCs isolated from umbilical cord were transfected with plasmid DNA encoding green fluorescent protein (GFP) and GFP-fusion ILK, wild and mutant, respectively; and cultured in serum-free media with basic fibroblast growth factor, epidermal growth factor and B27. It was assessed with the proliferative activity and the efficiency of differentiation into neural stem-like cell. Results MSCs transfected with GFP-fusion wild ILK expressed ILK and kinase-dead mutant ILK stably. The activity of proliferation increased and more of them differentiated into neural stem-like cell, which express CD133 and Nestin validated by PCR and Western blotting, and more of wild than of mutant. Conclusion Integrin-linked kinase may play a positive role in MSC differentiation into neural stem-like cell, which may associate with the activity of kinase.

ObjectiveTo investigate the association between the common variant rs1512268 single nucleotide polymorphism(SNP) of NKX3.1 gene and the risk of prostate cancer,and to explore its interaction with related risk factors.MethodsTotally 122 patients with prostate cancer and 105 age matched male people (prostatic specific antigen ＜ 4 μg/L,without family history of prostate cancer) as control group were enrolled.Polymerase chain reaction - high resolution melting curve(PCR - HRM) combined with gene sequencing methods were used to determine the distribution of allele and genotype frequencies of the rs1512268 SNP.ResultsThe distributions of GG,AG,AA genotypes were 42 cases(33.4％),66 cases(54.1％),14 cases(11.5％) in patients with prostate cancer,and 45 cases(42.9％),51 cases(48.6％),9 cases(8.6％) in healthy control,respectively.There were no significant differences in the distribution of genotype(x2 =1.70,0.69,0.52) and allele frequency (x2 =1.575) between the two groups(P＞ 0.05).The different genotypes of rs1512268 of NKX3.1 gene were not associated with age,Gleason score,PSA levels and clinical stage of prostate cancer (P＞0.05). Conclusions rs1512268 SNP of NKX3.1 gene is not obviously associated with prostate cancer and may be not the genetic risk factor in Chinese.

[Objective]To investigate the genetic polymorphisms of the CYP2C19 gene in the elderly Chinese Han populations of Guangzhou,and compare the frequencies of CYP2C19 gene polymorphisms in different populations,in order to provide accurate data for the appropriate prescription.[Methods]To detect the genetic polymorphisms of the CYP2C19 gene by the DNA microarray,and compare the frequencies of CYP2C19 gene polymorphisms in Chinese Han populations from different areas and the different races.[Results]There were 2312 case samples in our study. The allele frequencies of CYP2C19*1,CYP2C19*2 and CYP2C19*3 were 64.27%,30.75%,and 4.98%,respectively. As the genotype,EM(*1/*1)was 41.44%(n=958),IM(*1/*2,*1/*3)was 45.67%(n=1056),and PM(*2/*2,*2/*3 and*3/*3)was 12.89%(n=298). The ratios of EM and IM in Chinese Han populations from different areas and all the subtypes of the CYP2C19 genotype in different minority were statistically significant. As the races,there were difference in all the subtypes of the CYP2C19 genotype when Asian populations were compared with white races(P<1304.64)and black races(P<0.01),which was also statistically significant.[Conclusions]The distributions of the CYP2C19 gene polymorphisms were significantly different in Chinese han populations and in different races,and the main subtypes of the CYP2C19 genotype in the elderly of Chinese han populations were IM and EM,which is beneficial for prescribing appropriate in the elderly populations.

Objective To investigate the efficacy and safety of isosorbide mononitrate sustained release tables plus vinorelbine and cisplatin in patients with previously untreated advanced non-small-cell lung cancer (NSCLC).Methods One hundred and ten patients with stage ⅢB-Ⅳ NSCLC were randomly assigned to group A (57 cases) and group B (53 cases) by random mumber table.Patients in group A were treated with vinorelbine 25 mg/m2 on the first and eighth day and cisplatin 25 mg/m2 on day 2-4,with transdermally applied isosorbide mononitrate sustained release tables (40 mg,daily for 8 days),and patients in group B were treated with vinorelbine and cisplatin.Response to treatment was assessed by RECIST1.1 and adverse effect was assessed by NCI-CTC(3.0).Results The response rate in group A (58.2％,32/55 patients) was significandy higher than that for patients in group B (30.8％,16/52 patients; x2 =8.120,P =0.004).Median TTP and median OS in group A were longer than those in group B (8.2 vs 5.8 months,x2 =10.684,P =0.001 ; 11.6 vs 9.0 months,x2 =11.231,P =0.001).While,patients with squamous carcinoma showed better response to chemotherapy (RR =2.438,95％ CI:1.136-5.231,P =0.022).Adverse effect difference was not significant between group A and group B,except headache.The rate of grade 1 to 2 headache in group A (34.5％ ; 19 of 55 patients) was significantly higher than that in group B (3.8％ ; 2 of 52 patients; P ＜0.001).Conclusion Use of isosorbide mononitrate sustained release tables combined with vinorelbine and cisplatin may improve overall response,TTP and OS in patients with advanced stage NSCLC.

Adolescent ; Blood Vessel Prosthesis Implantation ; Child ; Child, Preschool ; Ductus Arteriosus, Patent ; therapy ; Equipment and Supplies ; Female ; Humans ; Infant ; Male ; Video Recording

OBJECTIVETo compare the differences in the clinical function and lumbar and abdominal myodynamia in patiants of lumbar disc herniation treated with moxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and acupuncture.

METHODSForty cases were randomized into a moxibustion group and an acupuncture group, 20 cases in each group. In the moxibustion group, the warm moxibustion was applied alternatively at Dazhui (GV 14) and Guanyuan (CV 4) once every other day, 1 h each time, once every day. In the acupuncture group, acupuncture was applied to the corresponding acupoints based on the affected lumbar vertebras, such as Jiaji (EX-B 2), Shens-hu (BL 23), Dachangshu (BL 25) and Huantiao (GB 30), etc. , once evey day 30 min each time. The treatment for 3 weeks was taken as one session in each group. Totally, one session treatment was required. Surface electromyography (SEMG) of bilateral paraspinal muscle and rectus muscle, and JOA score of low back pain were observed in the two groups.

RESULTS(1) JOA score: the score of subjective symptoms, score of activity of daily living (ADL) and total score were improved obviously as compared with those before treatment in the two groups (P<0.01, P<0.05). The results of subjective symptoms score, score of ADL and total score in the acupuncture group were superior to those in the moxibustion group after treatment (6.95+/-0.94 vs 5.50 +/-0.89,10. 90+/-1.86 vs 8.90+/- 1. 92,22.50 +/- 2.82 vs 19.35 +/- 2. 70, all P<0. 05). (2) SEMG comparison: root-mean-square value (RMS) was all reduced in SEMG of the anteflexion, rear protraction, orthostatism, bilateral bending and neck and leg rear flexion for strengthening lumbar muscle as compared with those before treatment in the two groups (P< 0.05, P<0. 01). RMS of the anteflexion and bilateral bending in the acupunture group were reduced much obviously as compared with the moxibustion group. In terms of sitting position anteflexion, rear protraction, orthostatism, bilateral bending and neck and leg rear flexion for strengthening lumbar muscle, median frequency (MF) after treatment was all improved as compared with that before treatment in the two groups (P<0. 05, P<0. 01). In terms of anteflexion, the electrode MF after treatment was improved much obviously in the acupuncture group(P<0. 05).

CONCLUSIONMoxibustion at Dazhui (GV 14) and Guanyuan (CV 4) and conventional acupuncture all improve muscle function, relieve muscle fatigue, increase the ability of anti-muscle fatigue, strengthen lumbar vertebral stability, release subjective symptoms and improve ADL. But, the effects of moxibustion are slightly lower than those of acupuncture.

Acupuncture Therapy ; Adult ; Aged ; Electromyography ; Female ; Humans ; Intervertebral Disc Displacement ; physiopathology ; therapy ; Lumbar Vertebrae ; physiopathology ; Male ; Middle Aged ; Moxibustion ; Young Adult

OBJECTIVETo investigate the hazards of aluminum dusts to the exposed workers and the clinical features of aluminosis.

METHODRetrospective investigation on 75 aluminosis patients from a certain factory diagnosed in Shanghai Occupational Diseases Hospital from 1972 to 2004 was carried out.

RESULTSThere were 27 cases of aluminosis I (36.0%), 28 cases of aluminosis II (37.3%) and 20 cases of aluminosis III (26.7%) among 75 cases. The shortest exposure duration was 3 years, and the longest 17 years, and 37 cases of aluminosis occurred after exposure less than 10 years. hest radiographic examination mainly showed irregular micro-shadows: t (22/75), s (4/75), t/u (1/75), t/s (2/75), or predominantly irregular mixed microshadows s/p (5/75), s/r (1/75), t/p (9/75), t/q (5/75); some showed round shape micro-shadows: p (6/75), q (1/75), p/q (3/75), q/p (1/75). 27 cases showed large shadows, 20 cases of them were diagnosed as pneumoconiosis III. A lot of irregular micro-shadows gathered and developed to form uneven, loose and border-irregular masses. Most massive fibrosis looked like stripe or plait, located mostly in middle and upper lung field. 8 patients suffered from aluminosis with single side of massive fibrosis and 12 with both sides of massive fibrosis, accounting for 40% and 60% respectively. Mediastinal and bronchopulmonary lymph nodes were enlarged and calcified, accompanied with pleural thickening.

CONCLUSIONSShort exposure to high concentration of black fused alumina may cause serious aluminosis to the exposes. The hazards of aluminum dusts should not be ignored.

Aluminum Oxide ; toxicity ; Female ; Humans ; Male ; Occupational Diseases ; etiology ; Occupational Exposure ; Pneumoconiosis ; etiology ; Retrospective Studies ; Workplace

Objective To investigate the mechanism of neural processing of emotional words under distinct awareness conditions using spatiotemporal pattern of event-related potentials (ERP). Methods The ERPs were recorded in 11 healthy subjects while they performed a task of perceptual judgement on facial photograph gender, which were arrayed behind emotional words. Word valence was an implicit processing factor. The 2 (consciousness: awareness, unawareness)×2 (positive/neutral, negative/neutral) factorial design of repeated-measure was applied to utilize the difference wave between emotional word under distinct awareness conditions. The analysis results were revealed by the statistical parametric mapping (SPM) of F value resulting from repeated measurement ANOVA. Results The SPM of F-value suggested significant interaction effect between awareness and word valence in left frontal-temporal areas and right occipital regions (60-80 ms). The significant awareness effects occurred separately in bilateral frontal-partial and right temporal regions (110-150 ms). The significant emotion effects occurred in left and right extensive cerebral hemisphere regions (60-90 ms). Conclusion The spatiotemporal patterns of ERPs suggest the underlying mechanisms are that the emotional words processing of both unawareness and awareness might involve the same neural modules in earlier period.The former decreases the strength of those neural assemblies' activation than the latter. Either positive or negative words can activate left cerebral hemisphere simultaneously with right cerebral hemisphere.

Hippocampal formation is important in spatial learning and memory. Members of the cadherin superfamily are observed in the neural system with diverse spatial and temporal expression patterns and are involved in many biological processes. To date, the avian hippocampal formation is not well understood. In this study, we examined the expression of cadherin mRNA in chicken and mouse brains to investigate the morphological and cytoarchitectural bases of hippocampal formation. Profiles of the spatiotemporal expression of cadherin mRNAs in the developing chicken embryonic parahippocampal area (APH) are provided, and layer-specific expression and spatiotemporal expression were observed in different subdivisions of the APH. That fact that some cadherins (Cdh2, Cdh8, Pcdh8 and Pcdh10) showed conserved regional expression both in the hippocampus and entorhinal cortex of mice and the hippocampal formation of chickens partially confirmed the structural homology proposed by previous scientists. This study indicates that some cadherins can be used as special markers of the avian hippocampal formation.