Human gene therapy needs to express exogenous DNA at the targeting cells,producing a practical and efficient therapeutic dosage at an approp-riate time(quantitative pharmacology)with a safe man-ner.Recombinant adeno-associated virus(rAAV)Vec-tom possess a number of properties and recent progress in rAAV production made it rapidly become the reagent of choice for therapeutic gene tmasfer.Over 60 clinical trials of gene therapy based on rAAV have been carried out.The dose response reaction between rAAV vectors and gene expression activity or clinical outcome is one of major aspects of these trials.Most studies showed that vector genomes(vg)and gene expression had a concentration-dependent relationship during a certain scope.However,gene expr~sion Can be afffected by viral serotypes,tissue tropisms,cell targeting,drug regulation,injection route,age and sex,etc.Thus,these aspects should be carefully comidered by scienti-sts,pharmacologisis and physicians during animal ex-periments or clinical trails.KEY WORDS gene therapy;viral vector;dose-re-sponse;quantitative pharmacology;clinical thempy

OBJECTIVE:To observe the clinical efficacy of Tanreqing injection in the treatment of children's viral pneumonia.METHODS:A total of sixty children with viral pneumonia were randomly divided into 2 groups:the treatment group(n=30)were treated with Tanreqing injection(20mL)plus Glucose(250mL)qd for 7d while the control group(n=30)with Cibavirin(10～15mg?kg-1)plus Glucose(250mL)bid for 7d.The primary outcome measures were clinical efficacy and adverse drug effects(ADRs).RESULTS:The effective rate was 100% in the treatment group as compared with 80% in the control group,showing significant differences between the two groups(P

Objective To evaluate the feasibility of community treatment and management mode in elderly patients with hypertension.Methods A total of 286 elderly patients with hypertension were treated with community therapy and management for 6 months.The improvements in life style and hypertension control were observed before and after the community treatment and management.Results There were significant differences in systolic blood pressure and diastolic blood pressure in the elderly patients before and after the treatment and management [(158.4± 11.3) mm Hg vs.(131.3±5.9) mm Hg,(99.6±8.9) mm Hg vs.(81.5±5.6) mm Hg,respectively,both P＜0.05].Compared with pretreatment,the blood pressure control rate,the awareness rate of diagnostic criteria and the drug compliance were significantly increased after the treatment and management [38.5％ (110/286) vs.96.9％ (277/286),66.4％ (190/286) vs.100％ (286/286),49％ (140/286)vs.91.3％ (261/286),x2 =98.87,115.36,122.13,respectively,all P＜0.01].Conclusions The community treatment and management can increase the blood pressure control rate and improve the quality of life in elderly patients with hypertension.It is a feasible method to comprehensively prevent and control hypertension.

Objective To investigate the relationship between H-type hypertension and unstable angina (UA).Methods Totally 147 elderly inpatients with hypertension and angina in our hospital were selected.Patients were divided into H-type hypertension group [n=72,serum homocysteine (Hcy) level ≥10 μmol/L] and primary hypertension group [n=75,serum homocysteine (Hcy) level ＜10 μmol/L].All patients underwent coronary angiography.Serum Hcy level was measured by enzyme method and compared between groups.Results There were statistical differences in the UA incidence,Gensini's score and high sensitive C-reactive protein (hsCRP) level between the H-type hypertension group and primary hypertension group [(44.4％ (32/72) vs.12.0％ (9/75),(44.2± 21.3) vs.(31.9±18.4),(4.3±2.1) μg/L vs.(2.0±1.9) μg/L,respectively,all P＜0.01].Serum Hcy level in H-type hypertension group was higher during UA attack than during UA remission [(22.2±7.1)μmol/L vs.(13.7±3.7)μmol/L,P＜ 0.01].Serum Hcy level during UA attack was increased in H-type hypertension group than in stable angina group [(22.2±7.1)μmol/L vs.(12.0± 4.2) μmol/L,P ＜ 0.01].Serum levels of Hcy,total cholesterol and low density lipoprotein cholesterol in primary hypertension group were higher in UA patients than in stable angina patients [(8.9±2.2)μmol/L vs.(6.6± 1.2)μmol/L,(6.9±0.7)mmol/L vs.(4.5±0.5)mmol/L,(4.6±0.8)mmol/L vs.(2.7 ± 0.6) mmol/L,respectively,P＜ 0.01 or P＜0.05].Logistic regression analysis showed that H-type hypertension was the independent risk factor for unstable angina in the elderly (OR =5.691,P ＜ 0.01).Conclusions H-type hypertension is closely correlated with unstable angina,which is the independent risk factor for unstable angina in the elderly.Serum Hcy level has significant correlation with coronary atherosclerotic plaque stability and the severity of coronary artery disease.

Objective To investigate the role of endoscopic sphincterotomy(EST)and endoscopic nasobiliary drainage(ENBD)in the treatment of non-biliary severe acute pancreatitis(SAP).Methods 73 patients were randomly divided into the endoscopic treatment group(35 cases)and control group(38 cases).The patients in control group received non-surgical treatment.EST plus ENBD were performed in patients in the endoscopic treatment group 72h within hospitalization.Serum levels of amylase before EST and 1d,3 d,7 d after EST were measured;the ease of pain and recovery of bowel function were documented;the mortality rate,complication rate,surgery rote and hospital stay were also observed.Results The successful cannulation rate in the EST group was 94.3%(33/35),and there was no procedure related complication.Serum levels of amylase before EST and 1d,3 d,7 d after EST were(1376±131)U/L,(675±49)U/L,(238±49)U/L,(75±13)U/L,the serum levels of amylase before EST and 1d after EST in the EST group were not significantly different from those in the control group,but the corresponding values at 3 d,7 d were significantly lower than those in the control group(P＜0.01).The apparent effective rate and total effective rate of pain relief was 37.1%and 48.6%.which was significantly higher than those in the control group (26.3%and 28.9%,P＜0.05).There was no mortality in both groups.The complication rate in the EST group within 30 d was 14.3%,which was signiilcanfly higher than that in the control group(44.7%,P＜0.01).The gurgery rate in EST group was 2.86%,which was significantly lower than that in the control group (21.1%,P＜0.05).The hospital stay in EST group was(27.6±4.0)d,which was significantly shorter than that in the control group[(41.7±5.9)d,P＜0.05].Conclusions EST and ENBD treatment for non-biliary SAP was superior to non-surgical treatment within 72 h of symptom onset with excellent safety and feasibility profile.

Objective To evaluate the clinical application value of multi-slice helical CT volumetric (VH) scanning in lumber spine. Methods One thousand of patients with back and leg pain who underwent CT examinations were selected as subjects. We simulated the traditional protocol of single-slice(SS) discrete scanning for L3/4, L4/5, and LS/S1 intervertebral discs. The VH scanning mode was performed with 120 kV, 210 mAs,pitch of 1.5 and coverage of 97. 5 mm. The simulated SS scanning mode was performed with 120 kV, 240 mAs and coverage of 45.0 mm. The diagnostic outcomes and the radiation doses were compared between the two scanning modes. Two groups doctors observed ten terms, including the osseous spinal stenosis,narrowed intervertebral space and so on in two scanning modes respectively. Then consistency analysis of the data was carried out. Results The VH scanning mode showed far more features than the SS mode. The detection rates of the VH mode in the osseous spinal stenosis, narrowed intervertebral space,herniated nucleus pulposus, narrowed lateral recess, vertebral lesion, hypertrophy of L5 transverse process,abnormal direction of facet, facet degeneration, lumbar spondyloschisis, and paraspinal soft tissue were 11.8% (n =118), 38. 5% (n =385), 9. 3% (n =93), 46. 8% (n =468), 31.4% (n =314), 5.7% (n =57), 25.4% (n = 254), 49. 7% (n = 497), 9.9% (n = 99), and 0. 6% (n = 6) respectively, while the detection rates of the SS mode in ten terms were 5.6% (n = 56), 0, 0. 6% (n = 6), 27. 9% (n = 279),22.4% (n =224), 1.2% (n = 12), 16.7% (n = 167), 37.2% (n =372), 0.5% (n =5), and 0.2%(n = 2) respectively. The difference between the two groups had statistically significance (average P <0.05), except the paraspinal soft tissue abnormal (P > 0.05). The detection rates of the VH mode were higher than the SS mode in the osseous spinal stenosis, narrowed intervertebral space, herniated nucleus pulposus, lumbar spondyloschisis, being 6.2% (n = 62) , 38. 5% (n = 385) , 8.7% (n = 87), and 9.4%(n =94), respectively. In addition, VH mode only partially showed the articular facets, narrowed lateral recess, hypertrophy of L.5 transverse process, and paraspinal soft tissue. We could not acquire the imaging slices paralleling to intervertebral discs in SS mode in 467 patients (46.7%) with lumbosacral angle greater than 35°. The radiation dose of VH mode (164.9 mGy/em) was slightly higher than SS mode (147.0 mGy/cm) Conclusion MSCT VH scanning mode can significantly improve the diagnostic rate of lumbar spine diseases compared with SS mode, and was not restricted by the lumbosacral angle with slightly increasing radiation dosage.

OBJECTIVETo study the association of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels with hyperlipidemia.

METHODSBlood samples were collected from 1591 adults for detecting MTHFR gene C677T polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), plasma Hcy levels with enzymatic cycling method, and blood lipid levels as well. The patients were divided according to the lipid levels into hyperlipidemia group (n=694) and healthy control group (n=897) and the differences in MTHFR gene C677T polymorphisms and plasma Hcy levels were compared.

RESULTSThe hyperlipidemia group and healthy control group showed no significant differences in CC, CT, or TT genotype frequencies or C and T allele frequencies of MTHFR C677T gene, and had comparable plasma Hcy levels (P>0.05). Patients with 3 different MTHFR C677T genotypes had significant differences in plasma Hcy levels (P<0.01) but not in blood lipid levels (P>0.05). Pairwise comparison indicated a significantly higher plasma Hcy level in TT genotype than in CC and CT genotypes (P<0.01), and the latter two genotypes showed no significant difference (P>0.05).

CONCLUSIONMTHFR C677T polymorphisms and plasma Hcy levels are closely related but neither of them is associated with hyperlipidemia. The TT genotype is associated with a significantly higher plasma Hcy level than CC and CT genotypes.

Adult ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Hyperlipidemias ; blood ; genetics ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

Kallistatin, which protects organs and cells against inflammation, fibrosis and oxidative stress, is mainly synthesized and secreted in liver. However, its relationship to human liver disease remains unclear. The purpose of this study was to explore the relationship between serum kallistatin and clinical evidence of both cirrhosis and hepatocellular carcinoma (HCC), and to determine if serum kallistatin levels could be used as a diagnostic indicator of hepatic health status, especially human liver cirrhosis (LC). Our cohort consisted of 115 patients with clinically proven liver fibrosis (LF), LC, or HCC by liver biopsies, and 31 healthy controls (CON). Serum kallistatin levels were quantified by ELISA. Results of the present study demonstrated that irrespective of the underlying etiology, serum kallistatin levels were significantly lower in the LF/LC group when compared with the CON group. A decrease in serum kallistatin levels appeared to reflect the extent of cirrhosis, with the lowest levels associated with higher grades of cirrhosis. Patients with LC had a noticeable correlation between serum kallistatin levels and other serum biochemical indicators. The area under the curve (AUC) for LC, viral liver cirrhosis (VLC) and alcoholic liver cirrhosis (ALC) was 0.845, 0.757 and 0.931, respectively. In conclusion, our findings demonstrated that kallistatin, a plasma protein produced by the liver, can be a useful and reliable diagnostic indicator of hepatic health status, especially for LC.

Adolescent ; Adult ; Brain ; abnormalities ; pathology ; physiopathology ; Child ; Female ; Humans ; Image Processing, Computer-Assisted ; Male ; Nerve Net ; pathology ; physiopathology ; Schizophrenia ; etiology ; physiopathology ; Schizophrenic Psychology