〔Abstract〕 Based on analyzing the background of generic drugs research and development, the paper elaborates the utilization meth-ods of drugs invalid patents, including information sources optimization and retrieval, invalid patents selection indexes and methods, in-fringement avoidance strategy.It takes the gastrointestinal stromal tumor drugs for example to find out drugs which can be imitated, pros-pects the future application of invalid patents information.

ObjectiveTo study the effect of head acupuncture combined with rehabilitation techniques on movement function of upper limbs after stroke.Methods80 patients with stroke were divided randomly into four groups, group 1 for head acupuncture and rehabilitation techniques, group 2 for rehabilitation techniques, group 3 for head acupuncture and group 4 for control. Fugl Meyer Assessment(FMA) and Facility Assessment For Function of Upper Limbs were applied to assess movement function before and after treatment.ResultsThe scores of FMA and Facility Assessment For Function of Upper Limbs rised more significantly in group 1,2, and 3 than group 4 (P<0.01) and group 1 outgo group 2,3 yet(P<0.05).Conclusions Head acupuncture combined with rehabilitation techniques can improve the movement function of upper limbs of the stroke patients.

ObjectiveTo investigate the correlation between the level of resistin and the insulin resistance(IR) and the incorporation of microamount albuminuria(MA) of type 2 diabetes mellitus (T2DM).MethodsTwo hundred and twenty T2DM patients and 40 normal subjects (control group) were enrolled in this study.Two hundred and twenty T2DM patients were divided into 4 groups,IR group (group A,79 cases),non-IR group (group B,48 cases),IR complicating MA group (group C,51 cases),non-IR complicating MA group(group D,42 cases).The fasting serum resistin was measured by enzyme-linked immunosorbant assay (ELISA),and the fasting plasma glucose (FPG),glycosylated hemoglobin (HbA1c),fasting insulin (FINS) was also determined.ResultsThe level of fasting serum resistin in group A,B,C and D was higher than that in control group [(33.45 ± 1.37),(23.36 ± 1.47),(44.45 ± 1.39),(37.45 ±1.57) μ g/L vs.( 17.44 ± 1.26 ) μ g/L],and there was significant difference among 5 groups (P ＜ 0.01 ).The level of fasting serum resistin in group A was higher than that in group B (P ＜ 0.01 ),and the level of fasting serum resistin in group C was higher than that in group D (P ＜ 0.01 ).The level of fasting serum resistin was both higher in group C and D than that in goup A and B (P＜ 0.01 ).Correlation analysis showed the fasting serum resistin was positively correlated with body mass index(BMI),FPG,HbA1c and FINS in group A(r =0.35,0.46,0.37,0.49,P ＜0.05),and the fasting serum resistin was positively correlated with HbA1c,BMI,systolic blood pressure and diastolic blood pressure in group C(r =0.45,0.32,0.37,0.29,P ＜ 0.05 ).ConclusionsSerum resistin may participate in the process of IR and the formation of MA.It may become one of the diagnostic standard of the IR and one of the important index to estimate the MA.

Objective To evaluate clinical application of phage amplified biologically assay (PhaB) in susceptibility test of Mycobacterium tuberculosis (MTB) in sputum. Methods The drug susceptibility of MTB was detected by PhaB in 143 patients with sputum-positive pulmonary tuberculosis (PTB),and the chemotherapy regimens were adjusted according to the results of susceptibility test.Independent samples t-tests were used for comparison of means.Count numbers were compared with Chisquare test.If there were count number of 0,Fisher probabilities should be used.ResultsThe total positive rate of PhaB was 94.4％ (135/143) with no differences between three types of PTB (x2 =1.886,P ＞ 0.05 ).The duration of testing for PhaB group was (6.6 ± 1.8) days,while for control was (29.4 ±8.7) days (t =29.01,P ＜ 0.01 ).Compared with control group,the 2-month negative-conversion rate (63.2％ vs.35.1％,x2 =3.989,P ＜ 0.05 ) and cure rate ( 100％ vs.78.4％,P ＜ 0.05 ) of PhaB group in type Ⅱ patients were significantly higher.But there were no differences between PhaB and control groups in type Ⅰ and Ⅲ PTB patients.ConclusionThe results of PhaB drug susceptibility test can be helpful for choosing effective chemotherapy regimen for PTB patients rapidly.

Objective To evaluate the value of 18F-FDG PET/CT in assessing radiosensitivity enhancement by irisquinone (IR) on rabbit xenografted VX2 lung tumor models.Methods Twenty-four tumor-beating rabbits were randomly divided into 3 groups (8 rabbits/group):group A with radiotherapy alone,group B with combined radiotherapy and IR,and group C without radiotherapy (the control group).18F-FDG PET/CT imaging was performed before radiotherapy and 24 h and one week after radiotherapy.The tumor SUVmax on delayed imaging was calculated in all rabbits.Two rabbits in each group were sacrificed after PET/CT imaging.HE staining was used to assess the differences in cancer cells among groups.Paired t test,one-way analysis of variance and Kaplan-Meier analysis were performed to analyze the data using SPSS 13.0.Results Before radiotherapy,the tumor SUVmax of all the 24 rabbits on standard and delayed imaging were 2.200 ± 0.761 and 3.162 ± 0.833 (t =-5.582,P ＜ 0.01).At 24 h post-radiotherapy,the delayed SUVmax of groups A,B and C were 2.614 ± 0.654,2.349 ± 0.869 and 5.663 ± 1.144,respectively.The differences between pre-radiotherapy and 24 h post-radiotherapy were statistically significant in all three groups (t =2.527,3.620,11.011,all P ＜0.05).One week after radiotherapy,the delayed SUVmax of groups A,B and C were 3.625 ± 1.064,3.058 ±0.850 and 7.424 ± 1.751,respectively.The differences among groups A,B and C were statistically significant (tA∶ B =2.652,tA∶C =3.799,tB∶C =4.366,all P ＜0.05).The cancer cells of group B were fewer than those of groups A and C by pathological findings,which was consistent with 18F-FDG PET/CT results.The survival times of groups A,B and C were (62.375 ±4.534),(69.000 ±4.660) and (54.125 ±5.276) d,respectively.Kaplan-Meier survival curves revealed better survival of group B as compared to groups A and C,respectively (Log-rank,x2 =7.355,16.943,both P ＜ 0.01).Conclusion 18 F-FDG PET/CT is able to evaluate the effect of irisquinone on tumor radiosensitivity enhancement.

OBJECTIVE:To study the chemical constituents in antioxidant activity part of Semiaquilegia adoxoides. METH-ODS:The antioxidant activity part of S. adoxoides were isolated and purified by chromatography on silicagel and Sephadex LH-20 column,and compound structures were identified physicochemical properties and spectral data analysis. RESULTS:Nine com-pounds were isolated from the antioxidant activity part of S. adoxoides,namely magnoflorine (1),griffonilide (2),salidroside (3),ferulic acid(4),genistein(5),2,4-dihydroxybenzoic acid(6),chlorogenic acid(7),caffeic acid(8)and p-coumaric acid (9). CONCLUSIONS:The study confirms the active material basis in antioxidant activity part of S. adoxoides for the first time.

Objective: To observe the effect of phenylephrine (PE) on pressure overload induced myocardial ifbrosis (MF) with its relevance to transforming growth factor-β1 (TGF-β1), drosophila mothers against decapentaplegic protein 3 (smad3) and connective tissue growth factor (CTGF) signal pathway in experimental rats.
Methods: A total of 28 male SD rats were randomly divided into 4 groups: Control group, AAC (abdominal aorta coarctation) group, AAC+PE group and AAC+prazosin group.n=7 in each group. Collagen volume fraction (CVF) of left ventricle was observed by myocardial collagen morphology, left ventricular myocardial tissue protein expressions of α-smooth muscle actin (α-SMA), TGF-β1, smad3 and CTGF were measured by immunohistochemistry, protein expression of α-SMA was also examined by Western blot analysis.
Results:①Myocardial collagen morphology presented that compared with Control group, AAC, AAC+PE and AAC+prazosin groups had increased CVF, allP<0.01; compared with AAC group, AAC+PE group had decreased CVF, P<0.01.②Immunohistochemistry demonstrated that compared with Control group, AAC, AAC+PE and AAC+prazosin groups had up-regulated protein expressions of α-SMA, TGF-β1, smad3 and CTGF, allP<0.01; compared with AAC group, AAC+PE group had down-regulated protein expressions of α-SMA, TGF-β1, smad3 and CTGF, allP<0.01.③Western blot analysis indicated that compared with Control group, AAC, AAC+PE and AAC+prazosin groups had the higher α-SMA expression, allP<0.05; compared with AAC group, AAC+PE group had the lower α-SMA expression, P<0.01.
Conclusion: Phenylephrine could improve pressure overload induced MF in experimental rats which might be related to TGF-β1/smads signal pathway inhibition and CTGF down-regulation.

Objective To investigate the relationship of the serum levels of high sensitivity C-reactive protein(hs-CRP) and homocysteine with middle cerebral artery(MCA) intraplaque hemorrhage.Methods A total of 63 patients who met the inclusion criteria showed high-grade(≥ 70％)MCA stenosis.The levels of serum hs-CRP and Hcy were detected.All patients were divided into symptomatic group and asymptomatic group,intraplaque hemorrhage group and non-intraplaque hemorrhage group.All patients performed conventional MRI and high-resolution MRI(HR-MRI).The correlation of the serum levels of hs-CRP and homocysteine with middle cerebral artery intraplaque hemorrhage was analyzed.Results Totally 37 symptomatic and 26 asymptomatic MCA stenoses were analyzed.The occurrence rate of intraplaque hemorrhage was significantly higher in symptomatic MCA stenosis group than in asymptomatic MCA stenosis group (40.5 ％ vs.11.5 ％,x2 =6.29,P＜ 0.05).Symptomatic group displayed a higher hs-CRP and Hey levels (8.97 ± 3.36 mg/L and 20.00 ± 3.16 μmol/L,respectively) than did asymptomatic group [(5.26 ± 3.12) mg/L and (12.22 ± 1.88) μmol/L,t =4.43 and 11.23,respectively,each P ＜ 0.001].The hs-CRP and Hcy levels were higher in intraplaque hemorrhage group [(10.53 ± 3.59) mg/L and (21.70 ± 2.40) μmol/L,respectively] than in non-intraplaque hemorrhage group[(6.20 ± 3.02) mg/L and(11.77±1.69) μmol/L,t=4.87 and 18.58,respectively,each P＜0.001].The hs-CRP and Hcy levels were positively correlated with the risk for middle cerebral artery intraplaque hemorrhage(r=0.461 and 0.519,each P＜0.001).Conclusions The serum levels of hs-CRP and Hcy are closely associated with middle cerebral artery intraplaque hemorrhage,which can be used to evaluate the stability of plaque.The MCA intraplaque hemorrhage is associated with ipsilateral stroke.

Objective To investigate the relationship between plasminogen activator inhibitor-1(PAI-1) activity and PAI-1 promoter 4G/5G polymorphism in patients with type 2 diabetes from the coastal areas of Shandong province.Methods The 4G/5G allele polymorphism in the PAI1 gene promoter region were tested by allele specific PCR in 116 type 2 diabetes and 40 normal controls.The activity of plasma PAI-1 was assayed by chromogenic substrate method.Results The plasma PAI-1 activity in patients was higher than that in controls(P

Objective To explore the clinical effect of two different connecting tubes in hemodialysis combined with hemoperfusion. Methods A total of 25 patients were selected and divided into observation group and control group by self- control method. In the observation group, the hemodialysis combined with hemoperfusion was used 8 times, and the control group was treated with hemodialysis combined with hemoperfusion 8 times using conventional connecting tube. The time of the unloading of the perfusate and the amount of physiological saline required were compared between the two groups. There was no blood spillover during the unloading of the perfusate, the number of cases of allergic reaction during the treatment, and the coagulation of the dialyzer and the pipeline after the treatment. Results There was no allergic reaction in both groups. There was no significant difference between the two groups in the amount of saline needed to return blood (t=46.412, P=0.307). In the control group, there was 15 cases of blood spillover, while the observation group did not show blood spillover. There was significant difference between the two groups in unloading perfusion time(4.43±0.14)min vs. (3.02±0.11) min (t=10.784, P=0.003). The level Ⅰ and Ⅱ blood coagulation of dialyzer and pipeline was 12, 2 cases in the control group after the treatment and 5, 0 case in the observation group, no level Ⅲ blood coagulation cases, and there was a significant difference between the two groups (χ2=10.667, P<0.01). Conclusion In the hemodialysis combined with hemoperfusion therapy, multi-function group of the application effect is superior to conventional piping, is worthy of clinical application.