The theoretical basis of premature aging originates from The Yellow Emperor's Inner Classic. The etiology of premature aging is complex， and the disease mechanism is based on deficiency. The treatment for premature aging is based on tonicity. The essence-Qi-spirit theory of Qiluo doctrine summarizes that "essence is the origin of life， Qi is the driving force of life， and spirit is the embodiment of life"， which is the law of life. The theory puts forward the core disease mechanism of aging， which states that "deficiency of kidney essence is the root of aging， deficiency of primordial Qi is the key to aging， impairment of soma and spirit is the manifestation of aging". The theory also proposes the treatment of "tonifying kidney and supplementing essence， harmonizing Yin and Yang， warming and supporting primordial Qi， and nourishing soma and spirit" and the representative anti-aging drugs. The article unfolds from the perspective of the concepts of natural life span， premature senility before fifty， decline， and aging and also explains the origins and connotations of premature aging. The article explains the disease mechanism of premature aging under the guidance of the essence-Qi-spirit theory of Qiluo doctrine， which is "early deprivation of kidney essence， deficiency of primordial Qi， accumulation of deficiencies into impairment， and decline and impairment of soma and spirit"， summarizes the progress of modern medical research on the treatment of premature aging and representative drugs， and finds that Bazi Bushen capsules have a precise therapeutic effect on the overall premature aging， systematic functional decline， and related diseases. The study provides theoretical basis and new ideas to solve the problems of premature aging and geriatric diseases.

Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.

OBJECTIVE: Whether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. MATERIALS AND METHODS: Five aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (Ktrans) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex in vivo. The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry. RESULTS: As compared with WKY rats, the Ktrans values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min−1 vs. 0.084 ± 0.017 min−1, p < 0.001 for hippocampus; 0.302 ± 0.072 min−1 vs. 0.052 ± 0.047 min−1, p < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant. CONCLUSION: Blood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.
Alzheimer Disease ; Amyloid ; Animals ; Blood-Brain Barrier* ; Brain* ; Hippocampus ; Hypertension* ; Immunoglobulin G ; Immunohistochemistry ; Magnetic Resonance Imaging* ; Methods ; Occludin ; Permeability ; Rats* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tight Junctions

Objective To undertake a systematic review to evaluate the efficacy and safety of olanzapine combined with fluoxetine in the treatment of negative symptoms of schizophrenia. Methods Articles published before May 31, 2017 were identified by searching the PubMed, Medline,Web of science excerpta medica database (EMBASE), Cochrane Library,China national knowledge infrastructure (CNKI), WanFang data, using the key words fluoxetine, olanzapine, schizophren* and schizophrenia. Statistical analysis were conducted by Review Manager 5.3 software according to Cochrane Handbook for meta analysis. Result A total of 5 randomized,controlled studies were included(3 Chinese and 2 English). Meta analysis showed that the efficacy of olanzapine combined with fluoxetine (combination group) in the treatment of the negative symptoms in schizophrenia was not significant difference from olanzapine alone (standradization of mean difference(SMD)=-0.61,95% CI:-1.30~0.08,P=0.08).Due to the high heterogeneity of the five studies (I2=83%>75%), Subgroup analysis which was conducted in three domestic research revealed that combination group exhibited a better efficacy in the treatment of negative symptoms in negative symptoms predominant schizophrenia (defined as score of PANSS negative subscale >30)(SMD=-1.19, 95% CI:-1.52~-0.86, P<0.01) and a lower risk to develop weight gain (SMD=0.28, 95% CI:0.13~0.57, P<0.01). Conclusion Domestic studies have provided the initial evidence that olanzapine in combination with fluoxetine is more effective and has a lower risk of weight gain than olanzapine alone in the treatment of negative symptoms for schizophrenics..

Objective To investigate the relationship between the catechol-O-methyl transferase (COMT) gene polymorphism and the clinical efficacy and cognitive function of risperidone in the treatment of schizophrenia.Methods 105 cases of Han Chinese patients with schizophrenia who were treated with risperidone for 12 weeks and healthy controls of 168 cases were collected.The effect of the drug therapy with the PANSS,digit vigilance test,Raven Standard Progressive Matrices,forward and backward subtests of the digit span test were evaluated,and then the rs 165599,rs4680,rs6267,rs737865 loci in COMT gene were detected.Results (1)rs737865 was not the polymorphic locus in this sample.(2) There was statistically significant between schizophrenia patients and controls in the distribution of allele frequency and genotype frequency in rs4680 (x2=8.16,P=0.02).Haplotype GA in rs165599-rs4680 was statistically significant in schizophrenia patients and controls (x2 =4.35,P =0.04).(3) After treatment,the total score ((47.64±5.75) points),subscale scores (positive symptoms (11.66±2.90) points,negative symptoms (13.79±3.18)points,general psychotic symptoms (22.09±3.59) points) and scores of five factors model in PANSS decreased and the difference was significant (P＜0.05);the scores of digital cancellation test increased significantly compared with those before treatment(t value respectively were 12.34,10.17,4.34,all P＜0.05);the scores of forward and backward subtests of the digit span test were significantly increased compared with those before treatment (t=-5.57,P=0.00) and Raven standard reasoning test scores had increased significant (t=-19.05,P=0.00).(4) The difference of instantaneous memory score changes among rs 165599 genotypes was statistically significant after treatment (F=4.06,P=0.02).(5) The difference of negative syndromes of PANSS among rs 165599 genotypes was statistically significant after treatment (F=3.11,P=0.049).(6) The difference of negative symptoms (F=4.64,P=0.01),cognitive impairment (F=3.21,P =0.045) and instantaneous memory (F=4.86,P=0.03) among rs 6267 genotype were statistically significant after treatment.Condusion Risperidone can effectively improve the psychotic symptoms of schizophrenia patients,and promote the recovery of cognitive function.Rs165599-rs4680 haplotype GA might be risk factor for the onset of schizophrenia.

Objective To investigate the relationship between the polymorphisms of CYP2D6 gene and clinical efficacy of risperidone in schizophrenia.Methods 114 schizophrenia patients were recruited and completed 12 weeks of treatment with risperidone monotherapy.Positive and Negative Syndrome Scale (PANSS),Personal and Social Performance Scale (PSP),Digit Span Test in Wechsler Intelligence Scale,Raven's Standard Progressive Matrices,Digital Cancellation Test were used to assess patients psychotic symptoms and cognitive symptom,and all patients were evaluated at baseline and weekend of 12.178 healthy controls were also collected.Five SNPs (rs1065852,rs1135840,rs16947,rs1080985,rs5030655) in CYP2D6 were genotyped by using TaqMan((R)) SNP Genotyping Assays.SHEsis online software were used to detect the Hardy-Weinberg equilibrium,pairs of polymorphic loci linkage disequilibrium,genotype and allele frequency analysis and haplotype analysis.SPSS17.0 statistical package was used for statistical analysis.Results rs5030655 was found only homozygous,suggesting not polymorphic site.Schizophrenia and control groups were not statistically different in genotype distributions and allele frequencies of four polymorphic sites (P＞0.05).There was a strong linkage disequilibrium between rs16947 and rs1080985 (r2=0.655).Haplotype frequency of three SNPs rs16947/rs1065852/rs1080985 AGG in schizophrenia group was significantly greater than in healthy people (14.26 vs.7.07;x2=8.008,P=0.004).At baseline,CC patients of rs1135840 genotype scored less than CG and GG genotype patients in Raven's Standard Progressive Matrices (F=3.205,P＜0.05),the results still showed statistical significance after Bonferroni corrections (P=0.038).After the treatment of 12 weeks,CC and CG patients of rs1135840 genotype had greater score changes in Raven's Standard Progressive Matrices than patients of the GG genotype (F=3.590,P=0.031),the results still showed statistical significance after Bonferroni corrections (P=0.036,0.038),but there was no significant difference between the scores of genotype CC and genotype CG patients (P＞0.05).After treatment,AA patients of rs16947 genotype had smallest score changes in Digital Cancellation Test(F=3.249,P=0.043),the results still showed statistical significance after Bonferroni corrections (P=0.022,0.042),and there was no statistical significant difference between the genotype GG and AG (P＞0.05).Conclusions There is no relationship between the polymorphism of CYP2D6 gene and the susceptibility of schizophrenia,but rs1135840 may be associated with intellectual impairment at baseline and improvement after treatment in patients with schizophrenia.rs16947 may be associated with improved attention in the treatment of schizophrenia.

Objective To investigate the relationship between the polymorphisms of CYP2D6 gene and clinical efficacy of risperidone in schizophrenia.Methods 114 schizophrenia patients were recruited and completed 12 weeks of treatment with risperidone monotherapy.Positive and Negative Syndrome Scale (PANSS),Personal and Social Performance Scale (PSP),Digit Span Test in Wechsler Intelligence Scale,Raven's Standard Progressive Matrices,Digital Cancellation Test were used to assess patients psychotic symptoms and cognitive symptom,and all patients were evaluated at baseline and weekend of 12.178 healthy controls were also collected.Five SNPs (rs1065852,rs1135840,rs16947,rs1080985,rs5030655) in CYP2D6 were genotyped by using TaqMan((R)) SNP Genotyping Assays.SHEsis online software were used to detect the Hardy-Weinberg equilibrium,pairs of polymorphic loci linkage disequilibrium,genotype and allele frequency analysis and haplotype analysis.SPSS17.0 statistical package was used for statistical analysis.Results rs5030655 was found only homozygous,suggesting not polymorphic site.Schizophrenia and control groups were not statistically different in genotype distributions and allele frequencies of four polymorphic sites (P＞0.05).There was a strong linkage disequilibrium between rs16947 and rs1080985 (r2=0.655).Haplotype frequency of three SNPs rs16947/rs1065852/rs1080985 AGG in schizophrenia group was significantly greater than in healthy people (14.26 vs.7.07;x2=8.008,P=0.004).At baseline,CC patients of rs1135840 genotype scored less than CG and GG genotype patients in Raven's Standard Progressive Matrices (F=3.205,P＜0.05),the results still showed statistical significance after Bonferroni corrections (P=0.038).After the treatment of 12 weeks,CC and CG patients of rs1135840 genotype had greater score changes in Raven's Standard Progressive Matrices than patients of the GG genotype (F=3.590,P=0.031),the results still showed statistical significance after Bonferroni corrections (P=0.036,0.038),but there was no significant difference between the scores of genotype CC and genotype CG patients (P＞0.05).After treatment,AA patients of rs16947 genotype had smallest score changes in Digital Cancellation Test(F=3.249,P=0.043),the results still showed statistical significance after Bonferroni corrections (P=0.022,0.042),and there was no statistical significant difference between the genotype GG and AG (P＞0.05).Conclusions There is no relationship between the polymorphism of CYP2D6 gene and the susceptibility of schizophrenia,but rs1135840 may be associated with intellectual impairment at baseline and improvement after treatment in patients with schizophrenia.rs16947 may be associated with improved attention in the treatment of schizophrenia.

Objective To investigate the influence of hyperactivity, Stereotyped behaviors , self-injury and irritabili?ty on parenting stress and emotions of the caregivers for patients with pervasive developmental disorders (PDDs). Methods Abnormal behaviors during last month were assessed in 138 PDDs patients by using Aberrant Behavior Checklist (ABC) and Conners Index of Hyperactivity (CIH). The parenting stress and the emotional state of the patients’parents were evalu?ated by the Caregiver Strain Questionnaire (CGSQ) and Hospital Anxiety and Depression Scale (HAD), respectively. Re?sults Anxiety, depression and combination of anxiety and depression were present in 6.2%, 17.8%and 29.5%of PDDs caregivers, respectively. The partial correlation analysis showed that CGSQ score of patients’parents positively correlated with CIH score (r=0.201, P=0.023) and stereotyped act (r=0.189, P=0.033) of the patients, and negatively correlated with stereotyped speech (r=-0.219, P=0.013). The anxious mood of parents positively correlated with stereotyped act (r=0.206, P=0.021). Conclusions Anxiety and depression are common in caregivers of PDDs. Except for stereotyped speech, aber?rant behaviors of the PDDs increase parenting stress and worsen anxious mood of caregivers.

Objective To evaluate the incidence of four aberrant behaviors in patients with pervasive developmental disorders (PDDs).Methods The abnormal behaviors during the last month in 138 PDDs patients were assessed with Aberrant Behavior Checklist and Conners Index of Hyperactivity.Results The incidence of aberrant behaviors was 61.6％ for hyperactivity,81.9％ for stereotyped behaviors,13.77％ for self-injury,and 58.70％ for irritability in PDDs patients.The occurance of irritability in autism patients was higher than that of asperger syndrome (AS) patients (x2 =5.623,P=0.018).Conclusion Stereotyped behaviors,hyperactivity and irritability are common in children with PDDs.Autism patients are more likely to exhibit irritability behaviors than AS patients.

Objective: To investigate the effect of cobalt chloride (CoCl2) on transgene expression and viral particle titers in tumor cells infected by conditionally replicating adenovirus expression vector with hypoxia response elements(HRE)-regulated E1AE1B expression (Ad-5HRE-E1AE1B-RFP) and non-HRE regulated replication-deficient adenovirus expression vector (Ad-EGFP, Ad-Luc) in vitro and in vivo. Methods: Ad-5HRE-E1AE1B-RFP had five duplicated HRE and mini CMV acted as a promoter to drive E1AE1B expression and constitutive expression of RFP as reporter. The hypoxia model was optimized by exposing tumor cells to different concentrations of CoCl2. The hypoxia-inducible factor 1 alpha (HIF-1α) protein expression was determined by Western blotting. Under the optimized hypoxia model, the positive expression of exogenous gene and virus replication of Ad-5HRE-E1AE1B-RFP or Ad-EGFP-infected tumor cells were examined by conversed microscopic observation, FACS analysis and plaques formation test. Furthermore, transgene expression induced by combined application of hypoxia-inducible replicative adenovirus and replication deficient adenovirus (Ad-Luc) was also evaluated by examining the lucifererse activity in xenografted tumor models in nude mice by micro PET. Results: Western blotting results showed that CoCl2 at 0.4 and 0.08 μg/mL could stabilize and acumulate HIF-1α protein in gastric cancer SGC7901 cells, which could better mimic hypoxia condition. The microscopic observation and FACS analysis showed that CoCl2 at 0.4 μg/mL could remarkably increase the transduction efficacy of Ad-5HRE-E1AE1B-RFP, which was verified by significant increase in the percentage of positive expression of exogenous gene RFP and fluorescence intensity. But plaques formation test showed that Ad-5HRE-E1AE1B-RFP had no replication. CoCl2 0.4 μg/mL augmented the tranduction efficacy and expression levels of non-HRE regulated replication deficient adenovirus Ad-EGFP and Ad-Luc. Combined intratumoral injection of Ad-5HRE-E1AE1B-RFP and Ad-Luc significantly increased the expression of Ad-Luc in nude mice.Conclusion: CoCl2 markedly enhances transgene expression of recombinant adenovirus. However, the underlying mechanism is not only related to the CoCl2-induced hypoxia, but also probably related to regulation of gene transcription.