Objective Network pharmacology,Molecular docking and Label-free DIA quantitative phosphoproteomics were used to reveal the potential mechanism of Peiminine against colon cancer.Methods 1The target of peiminine was obtained by SwissTargetPrediction,TargetNet and pharmmapper,and the target of colon cancer was obtained by DisGeNET,GeneCards and OMIM.Then the intersection target of Peiminine and Colon cancer was obtained by Venny2.1.0 online platform.Then,String database and Cytoscape3.8.2 software were used to map the PPI network of intersection targets,and the main targets of Peiminine against Colon cancer were obtained.GO analysis and KEGG pathway analysis were carried out through David database and Weisenxin visual cloud platform.② MOE(molecular operating environment)software was used to perform molecular docking of peiminine and the main target.③ Label-free DIA quantitative phosphoproteomics was used to detect and analyze the biological function of DT group(DT1-DT3)treated with Peiminine and control group(NC1-NC3).Results ① There were 275 intersection targets between peiminine and colon cancer.Molecular docking showed that peiminine could stably dock and interact with the protein structures of AKT1,EGFR,HSP90AA1 and SRC:Peiminine interacted with the amino acid residues of AKT1 mainly through hydrogen bonding.Peiminine interacted with amino acid residues of EGFR,HSP90AA1 and SRC mainly through ionic bond and hydrogen bonding.② Phosphoproteomics analysis showed that:Compared with the NC group,880 phosphorylated modification sites were significantly up-regulated in the DT group(including S124 and S126 sites of AKT1 and T648 and S643 sites of EGFR),and 425 phosphorylated modification sites were significantly down-regulated in the DT group(including T317 sites of HSP90AA1).③ Comparing the results of network pharmacology and phosphoproteomics analysis,it was found that:The main targets of Peiminine against Colon cancer are AKT1,EGFR and HSP90AA1.It promotes apoptosis of colon cancer cells by regulating 17 pathways including AMPK signaling pathway,mTOR signaling pathway and Choline metabolism in cancer.Conclusion This study revealed the potential mechanism of peiminine in the treatment of colon cancer with multiple targets and multiple pathways,and provided a certain direction and reference for subsequent research.

Objective Network pharmacology,Molecular docking and Label-free DIA quantitative phosphoproteomics were used to reveal the potential mechanism of Peiminine against colon cancer.Methods 1The target of peiminine was obtained by SwissTargetPrediction,TargetNet and pharmmapper,and the target of colon cancer was obtained by DisGeNET,GeneCards and OMIM.Then the intersection target of Peiminine and Colon cancer was obtained by Venny2.1.0 online platform.Then,String database and Cytoscape3.8.2 software were used to map the PPI network of intersection targets,and the main targets of Peiminine against Colon cancer were obtained.GO analysis and KEGG pathway analysis were carried out through David database and Weisenxin visual cloud platform.② MOE(molecular operating environment)software was used to perform molecular docking of peiminine and the main target.③ Label-free DIA quantitative phosphoproteomics was used to detect and analyze the biological function of DT group(DT1-DT3)treated with Peiminine and control group(NC1-NC3).Results ① There were 275 intersection targets between peiminine and colon cancer.Molecular docking showed that peiminine could stably dock and interact with the protein structures of AKT1,EGFR,HSP90AA1 and SRC:Peiminine interacted with the amino acid residues of AKT1 mainly through hydrogen bonding.Peiminine interacted with amino acid residues of EGFR,HSP90AA1 and SRC mainly through ionic bond and hydrogen bonding.② Phosphoproteomics analysis showed that:Compared with the NC group,880 phosphorylated modification sites were significantly up-regulated in the DT group(including S124 and S126 sites of AKT1 and T648 and S643 sites of EGFR),and 425 phosphorylated modification sites were significantly down-regulated in the DT group(including T317 sites of HSP90AA1).③ Comparing the results of network pharmacology and phosphoproteomics analysis,it was found that:The main targets of Peiminine against Colon cancer are AKT1,EGFR and HSP90AA1.It promotes apoptosis of colon cancer cells by regulating 17 pathways including AMPK signaling pathway,mTOR signaling pathway and Choline metabolism in cancer.Conclusion This study revealed the potential mechanism of peiminine in the treatment of colon cancer with multiple targets and multiple pathways,and provided a certain direction and reference for subsequent research.

Objective To investigate the clinical application of the modified keystone perforator island flap for reconstruction of skin defects at head and face.Methods From January 2013 to September 2014,13 cases with skin defects at head and face were repaired by modified keystone perforator island flap.The skin defects ranged from 0.8 cm× 1.0 cm to 20.0 cm × 10.0 cm.And the flap size ranged from 1.5 cm × 1.0 cm to 22.0 cm × 12.0 cm.The flap was designed along the edge of the defect,the vascular supply was supported by muscular perforators.In order to relieve suture tension and have a good cosmetic effect,auxiliary incisions should be as less as possible.Flap should be designed to hide parts of facial incision or surgical margins within the natural borders of each facial unit,or along the direction of striae.Incision within the hairline should be taken to minimize damage to the hair follicles.The direction of hair growth shouldn't be changed after the flap transfer.Results All cases had 1-12 months' follow-up period.12 flaps survived completely,with one partial flap necrosis.The flaps had good appearance with high aesthetic satisfactory.Conclusions The modified keystone perforator island flap produces excellent aesthetic results.It can be a very useful flap for tbe individual reconstruction of skin defects at head and face.

Objective To investigate the clinical application of the modified keystone perforator island flap for reconstruction of skin defects at head and face.Methods From January 2013 to September 2014,13 cases with skin defects at head and face were repaired by modified keystone perforator island flap.The skin defects ranged from 0.8 cm× 1.0 cm to 20.0 cm × 10.0 cm.And the flap size ranged from 1.5 cm × 1.0 cm to 22.0 cm × 12.0 cm.The flap was designed along the edge of the defect,the vascular supply was supported by muscular perforators.In order to relieve suture tension and have a good cosmetic effect,auxiliary incisions should be as less as possible.Flap should be designed to hide parts of facial incision or surgical margins within the natural borders of each facial unit,or along the direction of striae.Incision within the hairline should be taken to minimize damage to the hair follicles.The direction of hair growth shouldn't be changed after the flap transfer.Results All cases had 1-12 months' follow-up period.12 flaps survived completely,with one partial flap necrosis.The flaps had good appearance with high aesthetic satisfactory.Conclusions The modified keystone perforator island flap produces excellent aesthetic results.It can be a very useful flap for tbe individual reconstruction of skin defects at head and face.

OBJECTIVE: To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD). METHODS: Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared. RESULTS: (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/-0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003). CONCLUSION In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation.
Aged ; Cells, Cultured ; Collateral Circulation ; immunology ; physiology ; Coronary Circulation ; immunology ; physiology ; Coronary Disease ; blood ; immunology ; physiopathology ; Coronary Stenosis ; blood ; immunology ; physiopathology ; Dendritic Cells ; immunology ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocytes ; cytology ; immunology

Purpose To purify recombinant angiogenesis inhibitor r-K4K5 and investigate its inhibitoryeffects on bovine capillary endothelial (BCE) cell proliferation, chick embryo chorioallantoic membrane(CAM) angiogenesis and growth of experimental human non-small cell lung cancer (adeno). Methodsr-K4K5 was obtained by salting out and gel filtration with the purity of 95% determined by SDS-PAGE.BCE cells were cultured with DMEM media containing r-K4K5. The cells were counted in 24,48,72 hrespectively. r-K4K5 was injected daily into all 7-day chick embryo CAMs and CAM angiogenesis wasobserved at 72 h after incubation. The Balb/c (nu/nu) mice implanted with human SPC-Al tumor pieceswere grown for 10 days and then randomly divided into three groups. One group was treated with PBS, theother two groups were treated with local subcutaneous injection of purified r-K4K5 at 8 μg and 80 μg lpermouse every other day. They were daily observed and sacrificed in 14 days. Each tumor was weighed.Results The number of BCE cells, blood vessels diameter less than 50 μn of chick embryo CAM and theaverage weight of experimental tumor were decreased markedly in all the groups treated with r-K4K5.Conclusions r-K4K5 inhibits proliferation of BCE cells, angiogenesis of chick embryo CAMs and thegrowth of experimental human SPC-A1 non small lung cancer (adeno).

Objective To evaluate the changes of the right atrium,right ventriculum,left atrium and left ventriculum after transcatheter closure of atrial septal defect(ASD) during a short to mid-term follow-up.Methods The right ventricular end-diastolic anterior-posterior diameter(RVEDD),right atrial long diameter(RADl),right atrial transverse diameter(RADt),left ventricular end-diastolic ante-posterior diameter(LVEDD),left ventricular end-diastolic volume(LVEDV) and left atrial anterior-posterior diameter(LAD) in 36 patients with secundum ASD were measured before ASD closure,after 3 days,3 months and 6 months of ASD closure with transthoracic echocardiography(TTE).Results RVEDD,RADl and RADt were significantly decreased,while LVEDD,LVEDV and LAD significantly increased 3 days after ASD closure.During 3 months follow-up,RVEDD,RADl and RADt continuously became smaller;LVEDD,LVEDV and LAD continuously became larger.At 6 months,RVEDD was significantly smaller and LVEDD,LVEDV were significantly larger than those at 3 months.No remarkable difference of RADl,RADt and LAD was found between 6 months and 3months follow-up.Conclusion Transcatheter closure of ASD not only decreases the preload of right heart and causes right atrium and right ventriculum become smaller,but also improves the geometry of left heart and causes the narrowed left atrium and left ventriculum gradually return to almost normal status.