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Objective To investigate the clinical efficacy and related adverse reactions of the combination of camrelizumab with anlotinib as the third-line therapy on advanced non-small cell lung cancer. Methods We retrospectively analyzed the clinical data of 84 patients with advanced non-small cell lung cancer after second-line treatment. According to different treatment methods, 44 patients who received camrelizumab combined with anlotinib were included in the observation group, and 40 patients who received anlotinib alone were included in the control group. The PFS, ORR, DCR and incidence of adverse reactions were analyzed and compared between the two groups. Results The median PFS of the observation group was longer than that of the control group (7.0 vs. 5.6 months, P=0.001). No statistically significant difference was observed in ORR, DCR, the incidence of adverse reactions or the incidence of adverse reactions above grade 3 between two groups (all P > 0.05). Conclusion The clinical efficacy of camrelizumab combined with anlotinib as third-line therapy on advanced non-small cell lung cancer is better than anlotinib alone, and the safety is good.
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OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group，Shenfu yixin granule low-dose and high-dose groups （1.76，8.8 g/kg），Fosinopril sodium tablets group （positive control ，4 mg/kg），sham operation group was set up （only threading without ligation at the same position ），with 8 rats in each group. After 4 weeks of drug intervention ，the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes ， mitochondrial membrane potential ，protein expression of PTEN-induced putative kinase 1（PINK1），E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ，the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure （LVESP），maximum rate of rise of left ventricular internal pressure （+dp/dtmax）， maximun rate of decrease of left ventricular internal pressure （－dp/dtmax），total antioxidant capacity ，mitochondrial membrane potential，PINK1，Parkin and P 62 protein expression were significantly decreased in model group （P＜0.01）. The left ventricular end diastolic pressure （LVEDP），the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased （P＜0.01）. Compared with model group ，the pathological injuries of myocardial tissue in intervention groups were alleviated ，and above indexes were improved in varying degrees（P＜0.01 or P＜0.05）. CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ，which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.
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OBJECTIVE:To study the extraction rate and speciation of antivitiligo-related elements in Opercalina turperthum by water extraction and semi-bionic extraction. METHODS:Water extraction and semi-bionic extraction were respectively used. Wa-ter-soluble state and suspension state in extract of O. turperthum were separated by microporous filtering film;organic and inorgan-ic trace elements in water-soluble state were separated by macroporous resin. The contents of Cu,Zn,Fe,Ca,Mg,Mn and Sr were detected by flame atomic adsorption spectrophotometry,and speciation analysis was conducted. RESULTS:After water extrac-tion,extraction rates of 7 trace elements were 40.47%-72.49%;ratio of suspended particles was 3.69%-8.78%;ratio of organic state/inorganic state was 104.36% in water-soluble state of Sr and 3.94%-48.39% in water-soluble state of Cu,Zn,Fe,Ca,Mg, Mn. After semi-bionic extraction,except for Mn,extraction rates of trace elements were higher than water extraction,extraction rates of Cu,Zn,Fe,Ca,Mg,Sr were 77.69%-90.19%;ratio of suspended particles was 0.39%-8.57%;the ratio of organic state/inorganic state was 72.74%-180.79% in water-soluble state of elements. CONCLUSIONS:Cu,Zn,Fe,Ca,Mg,Mn and Sr in O. turperthum are dissolved easily,mainly existing in the form of inorganic state. After semi-bionic extraction,except for Mn,the dis-solution rate of other elements and the proportion of organic trace elements after dissolution increase significantly. Both dissolution and effective utilization rate of trace elements by semi-bionic extraction are higher than water extraction.
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Objective To investigate the characteristics of coronary vessel re-endothelialization after placement of drug-eluting stents (DES), and to provide clinical evidence for the double anti-platelet treatment. Methods Optical coherence tomography (OCT) was performed in 43 patients in 1 year after DES implantation. Characteristics of re-endothelialization and percentage of neointimal coverage of stent struts were evaluated by OCT. Results The rate of stent struts intimal coverage was 90.70%, and the remain was lack of endothelial coverage; The ratio of neointimal thickness (NIT) between 0-99, 100-199 and above 200 microns was 19.92%, 37.55% and 42.53%, respectively. The rate of neointimal coverage was higher and the degree of neointimal hy-perplasia was more extensive in patients with DM and in patients with ACS than those of patients without DM and of patients with stable angina pectoris. Conclusion One year after stent placement, most of the stent struts were covered with neointima and few struts obtained poor coverage of endothelial. DM and ACS may be impact factors for the progress of re-endothelialization after DES placement.
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Objective: To compare the percutaneous transluminal septal myocardial ablation (PTSMA) and percutaneous transluminal septal tunnel myocardial ablation (PTSTMA) on cardiac function in experimental canines. Methods: According to CAG determined coronary septal branches, a total of 25 hybrized canines were divided into 2 groups:PTSMA group, n=13 canines with the bigger septal branches and PTSTMA group, n=12 canines with the smaller or uneven septal branches. Alcohol ablation model was established. Electrocardiograph (ECG) at before and after the operation, biomarkers for myocardial injury, echocardiography and hemodynamic changes were recorded. The animals were scariifes at 1 week after operation, the pathological changes in ventricular septal were observed by HE and Masson staining. Results: Myocardial infarction (MI) could be induced by either PTSMA or PTSTMA and the thickness of septal was decreased. LVEDd, LVEF and hemodynamic indexes were similar between 2 groups. The alcohol volume used in operation, EKG and echocardiography ifndings were similar between 2 groups, P>0.05. Pathological staining indicated that there was a well-demarcate between the ablation focal and normal myocardium, merging area had neutrophiles invasion, infarcted cells were partially having the ghost cell sample and they were gradually replaced by ifbrous tissue. There was nest-like necrosis in ablated lumen and the normal vessel wall disappeared. PTSMA group had vessel lumen conifguration in septal branch and the necrosis limited inside the lumen;while in PTSTMA group, the vessel wall of was discontinued and some necrosis materials move out to from lumen. Conclusion: Both PTSMA and PTSTMA were effective for alcohol septal ablation in different coronary septal branches, the impacts on cardiac function and hemodynamic changes were similar in experimental canines.
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Objective To understand the epidemiological characteristics of human brucellosis in Baotou City of Inner Mongolia from 2008 to 2011.Methods Datas were collected from surveillance and investigation of human brucellosis in Baotou City during 2008-2011,and analyzed by descriptive study and statistics methods,including the main outcome measures:incidence,time distribution,endemic distribution,occupation distribution,age and sex distribution.Results About 2 338 cases were reported during the 4 years,the average annual incidence rate was 25.52/one hundred thousand,the annual incidence rate was in the range of 5.37/one hundred thousand to 38.65/one hundred thousand,and the incidence rate was rising year by year.The incidence mainly concentrated from April to August,and total reported cases were 1 423,accounting for 60.86％(1 423/2 338).Damaoqi and Guyangxian were regions with high prevalence rate of human brucellosis,and total reported cases were 1 652,accounting for 70.66％(1 652/2 338).The incidence of farmers was higher,accounting for 75.53％ (1 766/2 338).The 31-60 years old group had the highest incidence,accounting for 75.02％(1 754/2 338).The incidence of male was higher than that of female,male accounted for 75.19％ (1 758/2 338).Conclusions The infection of human brucellosis in Baotou City shows an increasing trend and widening scope.The incidence of human brucellosis has significant seasonal,regional,gender and age differences.
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Objective To investigate the effect of protein inhibitor of activated signal transducer and activator of transcription 1 ( PIAS1 ) gene silencing on the inflammatory response of rat pancreatic acinar cell lines AR42J with cerulein stimulation, to study its role in the pathogenesis of acute pancreatitis.Methods The siRNA targeting PIASI was designed, synthesized, transfected into AR42J cells by lipofectmine 2000.24 h later, cerulean was added and cultured for another 24 h.Subsequent AR42J cells with cerulein stimulation were divided into 4 groups: cerulein, liposome, negative-siRNA and PIAS1-siRNA groups.In addition, a group with PBS was as control group.The activity of p38 mitogen- activated protein kinase (p38MAPK) was detected by western blotting.TNF-α, IL-1β, IL-6, matrix metalloproteinase (MMP) 9 expression were analyzed by RT-PCR and western blotting, respectively.Results The expression of p38MAPK in PIAS1-siRNA, negative-siRNA, liposome, cerulein,and control group was 1.93 ±0.11, 1.22 ±0.10, 1.30 ±0.17,1.32 ± 0.21, 0.12 ± 0.02;while the expression of phosphorylated p38MAPK was 2.10 ± 0.25, 1.36 ± 0.20,1.26 ±0.15, 1.23 ±0.25, 0.58 ±0.48, the expression in PIAS1-siRNA group was significantly increased when compared with other groups (P＜0.05).The levels of TNF-α, IL-1β, IL-6, MMP-9 mRNA were 1.66 ±0.15,1.66 ± 0.15,1.90 ±0.01, 1.56 ±0.20 in PIAS1-siRNA group, while the expression of protein was 2.06 ±0.37,2.20 ±0.34, 1.80 ±0.10, 1.17 ±0.05, which was markedly higher than those in other group (P ＜0.05).Conclusions PIAS1 gene silencing could enhance p38MAPK activity, and improve inflammatory mediator expression in pancreatic acinar cells with cerulein stimulation.
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Background and purpose: In recent years indirubin-3'-monoxime has been found to be capable of inhibiting some cell proliferation in vitro and in vivo studies, but human colon cancer HT-29 cells, therefore the purpose in this paper was to study the effect of indirubin-3'-monoxime on proliferation and apoptosis of HT-29 cells and its associated mechanism. Methods: HT-29 cells were treated with indirubin-3'-monoxime. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay, flow cytometry (FCM) was used to measure the apoptosis rate. RT-PCR was used to measure the transcription of apoptosis suppressor gene bcl-2, survivin and apoptosis promoting gene Bar. Results: Indimbin-3'-monoxime inhibited growth of HT-29 cells in a dose-dependent and time-dependent manner (F=11.25, P<0.01). The apoptosis rate increased after the treatment by indirubin-3'-monoxime at 10 μmol/L. There were significant differences between different time groups (F=195.25, P<0.01). The transcription of survivin (F=78.75, P<0.01) and Bax (F=87.61, P<0.01) mRNA in HT-29 cells were increased; the transcription of bcl-2 was significantly decreased (F=95.82, P<0.01). Conclusion: Indirubin-3'-monoxime has obviously inhibited proliferation and induce apoptosis of colon cancer HT-29 cells, its mechanism may be related to decrease the bcl-2/Bax ratio.
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Objective To elucidate the effect of clavulanic acid (CLA) in suppressing the antibiotic resistance of Helicobacter pylori (Hp) to metronidazole (MZ) and its mechanism. Methods All Hp strains were isolated from biopsy specimens taken endoscopically and random amplified polymorphic DNA assay (RAPD) was used to certificate the distinct origin of these strains. The minimum inhibitory concentration (MIC) of CLA and MZ aganst Hp were determined by using agar dilution procedure and Epailometer test (E-test). The effect of CLA on the morphology of Hp was examined by transmission electron microscopy. Fluorescein-C6-aminopenicillanic acid (FLU-C6-APA) competition assay was used to detect the binding between CLA and penicillin-binding proteins (PBPs). Results Eleven strains were isolated. In vitro CLA could decrease the MIC of MZ resistant(1.442±0.459 vs 0.376±0.288, P=0.0077), but not affect the MIC for MZ sensitive strains significantly (P>0.05). Exposure to CLA resulted in morphological changes of Hp, including cell wall disintegration and cell lysis. Furthermore, CLA inhibited the binding of FLU-C6-APA to PBPs(30.5-33.5×103). Conclusions CLA suppresses the antibiotic resistance of Hp to MZ through its binding with PBPs which results in the morphology changes of Hp.