Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

Objective:To prepare the egg yolk immunoglobulin Y ( IgY) against human Sucrase and study its stability,in vitro activity. Methods:Hy-line laying hens were immunized with human Sucrase protein,IgY was isolated and purified from egg yolks of im-munized hens using water dilution and salting out method. Indirect ELISA was used to evaluate the titer and stability of IgY. The purity and specificity of IgY were analysed by SDS-PAGE and Western blot respectively. The inhibitory effects of IgY on α-glucosidase was studied by PNPG method. Results:Indirect ELISA results showed IgY could be detected on the tenth day after the first immunization, and the peak titer of IgY was 1:12 800 after the 40th day of immunization. SDS-PAGE showed that the heavy chain and light chain of IgY were 65 kD and 25 kD respectively, and the IgY against human Sucrase could specifically recognize the protein of human Sucrase. The IgY maintained primary titer when it was kept between 29-69℃ for 15 min,and pH 4-7,37℃,4 h. The titer of IgY was maintained 50% after digestion by pepsin and trypsin respectively for 2 hours. IgY had a higher resistence to pepsin than trypsin after longer digestion time. IgY showed an inhibitory effect on α-glucosidase in concentration dependent manner. The half inhibitory concentration (IC50) was 0. 540 mg/ml. Conclusion:The IgY against human Sucrase has been successfully obtained,which established foundations for its study of Type 2 diabetes mellitus rat models in vivo.

Objective To study the therapeutic and toxic effects of 32 P-chromic phosphate-poly (L-lactic) acid (32p-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma.Methods Twenty four nude mice bearing tumors were injected with 0,9.3,18.5 and 37.0 M Bq 32p-CP-PLLA microparticle,respectively.The relative tumor growth rates were observed every day,and white blood cells,platelets and body weight were measured.At 14 d after administration,the tumors were removed,histological examination and immunohistochemical analysis were performed.Results The relative tumor growth rates of each treatment group was lower than 40％.Histological examination showed the degenerative necrosis at the site nearby the mircoparticle.Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast,the expression of bax in treated group were higher than those in control group.The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43,0.47 ± 0.13,1.10 ± 0.32,2.19 ± 0.57 for 0,9.3,18.5 and 37.0 MBq 32 P-CP-PLLA microparticle,respectively ( t =2.36 - 2.77,P ＜ 0.05).MVD were 31.2 ± 2.3,23.8 ± 1.5,14.8 ±0.8,11.0 ± 1.2,respectively.Dose dependence was observed in both HE and IHC staining after 14 d treatment ( t =2.30 - 2.57,P ＜ 0.05 ).Conclusions Intratumoral injection of 32p-CP-PLLA microparticle might be a safe,easy and effective radionuclide interventional therapy for pancreatic carcinoma.

Objective To investigate the correlation of position movement of primary tumor with interested organs and skin markers,and to investigate the correlation of volume variation of primary tumors and lungs during different respiration phases for patients with lung cancer at free breath condition scanned by four-dimensional CT (4DCT) simulation.Methods 16 patients with lung cancer were scanned at free breath condition by simulation 4DCT which connected to a respiration-monitoring system.A coordinate system was created based on image of T5 phase,gross tumor volume (GTV) and normal tissue structures of 10 phases were contoured.The three dimensional position variation of them were measured and their correlation were analyzed,and the same for the volume variation of GTV and lungs of 10 respiratory phases.Results Movement range of lung cancer in different lobe differed extinct:0.8 - 5.0 mm in upper lobe,5.7 -5.9 mm in middle lobe and 10.2 - 13.7 mm in lower lobe,respectively.Movement range of lung cancer in three dimensional direction was different:z-axis 4.3 mm ± 4.3 mm＞ y-axis 2.2 mm ± 1.0 mm ＞ x-axis 1.7 mm ± 1.5 mm ( x2 =16.22,P =0.000),respectively.There was no statistical significant correlation for movement vector of GTV and interested structures (r =-0.50 - -0.01,P =0.058 - -0.961 ),nor for volume variation of tumor and lung ( r =0.23,P =0.520 ).Conclusions Based on 4DCT,statistically significant differences of GTV centroid movement are observed at different pulmonary lobes and in three dimensional directions.So individual 4DCT measurement is necessary for definition of internal target volume margin for lung cancer.

Background and purpose:Diffusion-weighted imaging (DWI) is a non-invasive technique of breast magnetic resonance imaging (MRI). DWI is an alternative to dynamic contrast-enhanced (DCE) MRI for differentiating malignant from benign lesions in breast screening or not. This study aimed to evaluate the potential role of DWI in differentiating malignant breast lesions from benign lesions.Methods:Seventy-four patients underwent digital mammography, DCE and DWI (49 patients’b-value of 0, 400, 600 and 800 s/mm2). The detectability, sensitivity and speciifcity of DWI and DCE were compared. Absolute apparent diffusion coefifcient (ADC) was compared with standardized ADC for quantitative analysis.Results:Sixty-four of 74 patients had positive pathologic findings (38 malignant, 26 benign). All of the malignant lesions were detected on DWI and DCE. The sensitivity of DWI was 83.33%, 90.00% and 93.33%, and the specificity was 85.91%, 76.19% and 72.72%, forb-value of 400, 600 and 800 s/mm2, respectively. The sensitivity and speciifcity of DCE were 86.61% and 90.48%. There was no signiifcant difference between absolute and standardized ADC in detecting breast cancer (P>0.05).Conclusion:DWI is an important complemented technique to DCE-MRI for differentiating malignant from benign lesions in breast MRI.

Objective To evaluate the impact of respiratory motion for dose of target and organ at risk during external-beam partial breast irradiation (EB-PBI).Methods 4D-CT scan sets were acquired for 20 patients who underwent EB-PBI.The volume of the tumour bed (TB) was determined based on seroma or surgical clips on the ten sets of 4D-CT images.For each patient a conventional 3D conformal plan (3D-CRT) was generated based on the 4D-CT end inhalation phase images,then copied and applied to the other phases.The following parameters were calculated to analyse:mean dose (D),homogeneity index (HI),conformal index (CI),and the volumes that received ≥ x Gy (Vx).Results During free breathing,the TB centroid motion was 0.90,0.75 and 0.80 mm in the lateral,anteroposterior and superior-inferior directions,respectively.The medium spatial motion vector was 0.95 mm.In the superiorinferior direction,TB motion significantly correlated with D HI,and CI of PTV (r =-0.458,-0.451 and 0.462,P ＜ 0.05),as well as D V20 and V30 received by the ipsilateral normal breast (r=0.527,0.488 and0.526,P ＜0.05).And in the motion vector,the D V5,V10,V20 of the ipsilateral lung all correlated with TB motion (r =0.416,0.503,0.522 and 0.498,P ＜ 0.05).A correlation also existed between dose and percent volume of heart and volume variation of heart (Dmean,V5 and V10) (r =0.727,0.704 and 0.695,P ＜ 0.05).Conclusions Small TB motion caused by respiratory motion during free breathing result in dosimetric variation of the target and potential dosimetric off-target or suboptimal dose coverage for EB-PBI.The doses of lung during free breathing were relatively sensitive to TB motion and thorax expansion,while heart doses were not influenced notably.

To determine the content of dendrobine in Dendrobium nobile from different harvest times and plant parts, to research the inherent rule about it. GC with internal standard was used to determine. The content of dendrobine had significant differences in different periods and parts. The dendrobine content is higher in four-year root than in three-year root. The dendrobine content in the upper segment of stem is the highest, secondly is in the middle seg-ment, and in the low segment is the lowest. This offered evidence to determine the most appropriate harvest time and fair use of different parts for D.nobil.

This study examined the current changes of human ether-a-go-go-related gene (hERG) mutation derived from a LQT2 Chinese family with a highly penetrating phenotype. Mutation was identified and site-directed mutagenesis was performed to induce the mutation in wild-type (WT) hERG. WT hERG and mutated V535M were cloned and transiently expressed in HEK293 cells. At the 48th and 72nd h after transfection, membrane currents were recorded using whole cell patch-clamp procedures. An A>G transition at 1605 resulting in replacement of V535M was identified. Compared to WT, V535M mutation significantly decreased tail currents of hERG. At test potential of -40 mV after depolarizing at +50 mV, tail current densities were 83.35±7.06 pA/pF in WT and 50.38±7.74 pA/pF in V535M respectively (n=20, P<0.01). Gating kinetics of hERG revealed that V (1/2) of steady-state inactivation shifted to negative potential in the mutant (V (1/2,V535M): -61.81±1.7 mV vs. V (1/2, WT): -43.1±0.71 mV). The time constant of recovery from inactivation was markedly prolonged in the mutant compared to WT among test potentials. V535M hERG mutation demonstrated markedly decreased tail current densities, which suggests that V535M is a new loss-of-function mutation of hERG channel responsible for LQT2.

Caused by Helminthosporium carposaprum, tomato brown lea f spot was a serious disease in green house in Henan Province. The condition for promoting sporulation of fungi were tested in this paper. The results showed th at the number of sporulation were different on the different medium,the fungi c ould sporulate a lot on the PDA+tomato leaf and Czapek medium, but V8、PSA and t omato juice restrained sporulation.The best carbon source and nitrogen source f or the fungi promoting sporulation were fructose and ammonium chloride respectiv ely,mannitol and Peptone ammonium sulfate restrained sporulation. Light and ult raviolet radiation were in favor of sporulation , ultraviolet radiation irradiat ing for 60～80min promoted sporulation. The fungi were promoted sporulation on the condition of lower or higher temperature and alkalescence,which 15℃o r 30℃,pH 8～9.

ObjectiveTo explore the feasibility,efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation (EB-PBI) after breast-conserving surgery for the selected Chinese early stage breast cancer patients.MethodsFrom June 2003 to December 2010,Forty-four early stage breast cancer patients underwent EB-PBI after breast-conserving surgery.Twenty patients had CT simulation scan in moderate deep inspiration breathing hold,and twenty-four patients in free breathing.EB-PBI was planned and delivered by three-dimensional conformal radiotherapy (3DCRT)with four noncoplanar beams.The prescribed dose was 3.40 Gy per fraction in thirty-nine patients and 3.85 Gy per fraction in five patients,twice per day at an interval of at least six hours,in five consecutive days.Results The number of patients with follow up time of 2,3 and 5 years were 39,31 and 16.Grade 1 acute radiationinduced dermatitis was observed in 17 patients (39％) at three months.Cosmesis was good or excellent in all cases at six months after radiotherapy and in 95％ cases at two years after radiotherapy.The 2-,3-and 5-year local control rates were 100％,99％ and 94％,respectively.The 2-,3-,and 5-year survival rates were all 100％ and no metastases occurred.Conclusions EB-PBI delivered by 3DCRT is feasible for selected Chinese early stage breast cancer patients after breast-conserving surgery.The cosmetic effect,local control rate and long-term survival rate are satisfactory,and acute radiation toxicity is very low.