Purpose:To study the response and toxicity of the regimen of oxaliplatin combined with fluorouracil and calcium folinate in the treatment of consisting of advanced colorectal cancer.Methods:Thirty-seven patients with advanced colorectal cancer received chemotherapy of regimen:oxaliplatin 130 mg/m~2 2 hours iv on day 1,calcium folinate 200 mg/ m~2 iv 2 hours on days 1 to 5,followed by fluorouracil 300 mg/m~2(≤500 mg/d) iv 4 h on days 1 to 5,three or four weeks as one cycle.Results:The total response rate was 29.7%,the main toxicity was bone marrow suppression and neuro-sensory toxicity,leukopenia was observed in 45.9% of the patients,but grade Ⅲ and Ⅳ in only 8.1%,neuro-sensory toxicity was observed in 81.9.%,but grade Ⅲ and Ⅳ in only 5.4%.Conclusions:This study shows that the regimen of oxaliplatin combined fluorouracil and calcium folinate is effective and tolerable in advanced colorectal cancer therapy.

Objective To explore impact of high pulmonary blood flow on the content and metabolism of collagen in rats.Methods Thirty-two male SD rats were randomly divided into shunt group and control group.Rats in shunt group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary blood flow.In control group,rats experienced the same expe-rimental processes except the shunting procedure.After 4 and 11 weeks of experiment,these changes of pulmonaryartery collagen Ⅰ,collagen Ⅲ,matrix metalloproteinase(MMP-13)and tissue inhibitor of metalloproteinase(TIMP-1) protein expression of rat were investigated by immunohistochemistry.Results After 4 weeks and 11 weeks of shunt,the collagen Ⅰ,collagen Ⅲ,MMP-13 and TIMP-1 of pulmonary artery in rats of shunt group increased significantly compared with those of control group,respectively(all P

At present, majority of the small molecular drugs used in clinics target proteins, they exert the efficacy through the binding to specific sites on the target protein. However, the "druggable" protein targets account for a small portion of the total number of proteins, and "non-druggable" proteins account for 80%, because of not having suitable drug binding sites. In the central rule, RNA is located in the upstream of proteins and controls the transcription of proteins. The research of small molecule drugs targeting RNA can solve the problem of protein "undruggable proteins" in some extent. This review summarizes the representative research achievements of small molecular drugs targeting RNA in recent years, and the screening methods applied to this field, with the focuses on the latest progress of small molecular drugs targeting novel coronavirus RNA.

Benzene ; analysis ; Chemical Industry ; Chromatography, Gas ; methods ; Humans ; Occupational Exposure ; analysis ; Toluene ; analysis ; Trichloroethylene ; analysis ; Xylenes ; analysis

The purpose of the present study was to examine the effects of oxidative stress on ventricular arrhythmias in rabbits with adriamycin-induced cardiomyopathy and the relationship between oxidative stress and ventricular arrhythmia. Forty Japanese white rabbits were randomly divided into four groups (n=10 in each): control group, metoprolol (a selective β1 receptor blocker) group, carvedilol (a nonselective β blocker/α-1 blocker) group and adriamycin group. Models of adriamycin-induced cardiomyopathy were established by intravenously injecting adriamycin hydrochloride (1 mg/kg) to rabbits via the auri-edge vein twice a week for 8 weeks in the adriamycin, metoprolol and carvedilol groups. Rabbits in the control group were given equal volume of saline through the auri-edge vein. Rabbits in the metoprolol and carvedilol groups were then intragastrically administrated metoprolol (5 mg/kg/d) and carvedilol (5 mg/kg/d) respectively for 2 months, while those in the adriamycin and control groups were treated with equal volume of saline in the same manner as in the metroprolol and carvedilol groups. Left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Plasma levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), malondialdehyde (MAD) and superoxide dismutase (SOD) were detected. The left ventricular wedge preparations were perfused with Tyrode's solution. The transmural electrocardiogram, transmural action potentials from epicardium (Epi) and endocardium (Endo), transmural repolarization dispersion (TDR) were recorded, and the incidences of triggered activity and ventricular arrhythmias were obtained at rapid cycle lengths. The results showed that TDR and the serum MDA and NT-proBNP levels were increased, and LVEF and the serum SOD level decreased in the adriamycin group compared with the control group. The incidences of triggered activity and ventricular arrhythmia were significantly higher in the adriamycin group than those in the control group (P<0.05). In the carvedilol group as compared with the adriamycin group, the serum SOD level and the LVEF were substantially increased; the TDR, and the serum MDA and NT-proBNP levels were significantly decreased; the incidences of triggered activity and ventricular arrhythmia were obviously reduced (P<0.05). There were no significant differences in the levels of MDA and SOD, LVEF, TDR and the incidences of triggered activity and ventricular arrhythmia between the adriamycin group and the metoprolol group. It was concluded that carvedilol may inhibit triggered activity and ventricular arrhythmias in rabbit with adriamycin-induced cardiomyopathy, which is related to the decrease in oxygen free radials.

AIMTo explore the possible impact of endogenous hydrogen sulfide (H2S) on the content and metabolism of collagen in rats with high pulmonary blood flow.

METHODSThirty-two male SD rats, weighing 120-140 g, were randomly divided into 4 groups (n = 8), shunt group, shunt + PPG (propargylglycine, an antagonist of endogenous H2S producing enzyme) group, sham group and sham + PPG group. Rats in shunt group and shunt + PPG group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the sham group and sham + PPG group, rats experienced the same experimental processes except the shunting procedure. After 4 weeks of experiment, lung tissue H2S content of rat was determined by a modified sulfide electrode method. Pulmonary artery collagen I, collagen III, MMP-13 and TIMP-1 protein expressions of rat were investigated by immunohistochemistry.

RESULTSAfter 4 weeks of experiment, lung tissue H2S content increased significantly in rats of shunt group as compared with that of sham group (P < 0.05). Pulmonary artery collagen I and collagen III protein expression increased obviously in rats of shunt group as compared with that of sham group (P < 0.01). After administration of PPG for 4 weeks, lung tissue H2S content decreased significantly in rats of shunt + PPG group as compared with that of shunt group (P < 0.05). In contrast to rats in shunt group, collagen I and collagen III protein expression in pulmonary arteries of shunt + PPG group increased significantly, respectively (P < 0.05). Compared with rats of shunt group, pulmonary artery MMP-13, TIMP-1 and the ratio of MMP-13/TIMP-1 in shunt + PPG group down-regulated significantly (P < 0.05).

CONCLUSIONEndogenous H2S might play a protective regulatory role in the development of pulmonary hypertension and pulmonary vascular structural remodelling in rats by decreasing the content of pulmonary artery collagen resulting from catabolism of collagen.

Animals ; Collagen ; metabolism ; Hydrogen Sulfide ; metabolism ; Lung ; blood supply ; metabolism ; Male ; Matrix Metalloproteinase 13 ; metabolism ; Pulmonary Artery ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

Objective To investigate the clinicopathologic relationship between serum platelet derived growth factor-BB(PDGF-BB)and IgA nephropathy in children.Methods The level of serum PDGF-BB was detected by double antibody enzyme linked immunosorbent assay(ELISA) in 15 cases healthy children and 30 cases IgA nephropathy.According to patholgical degree constituted by WHO in 1982,the IgA nephropathy group divided into 5 degrees:Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅴ(Ⅰ,Ⅱ were light patholgic change group;Ⅲ,Ⅳ were moderate patholgic change group;Ⅴ was severe patholgic change group).The serum PDGF-BB in IgA nephropathy group and none-IgA nephropathy group,and in different renal pathology type IgA nephropathy group were analyzed.Data were analyzed by using SAS 6.12 software.Results The level of serum PDGF-BB were(247.35?55.79) ng/L in control group and(869.16?200.73) ng/L in IgA nephropathy group.It was higher in IgA nephropathy group than in control group,the difference was significant(P

AIM:To investigate the characteristics of Ets-1 and VEGF expression and distribution in the experimental diabetic rat retina.METHODS:Diabetes was induced by intraperitoneal injection of streptozotocin (STZ).At 4 weeks after STZ-injection,animals were sacrificed.Total proteins were isolated from retinas of experimental and control eyes and were assessed by Western blot analysis.Frozen cross sections of eyeballs with 14um thickness were used to perform double immunoffuorescence staining with anti-Ets-1 and anti-VEGF antibodies.RESULTS:Both Ets-1 and VEGF expression were up-regulaled in the diabetic retina,the distribution of Ets-1 and VEGF was identical to each other,and the two proteins were almostlocalized in all retinal layers.CONCLUSION:Ets-1 might contribute to the pathologic progress of the diabetic retina induced by VEGF.

AIM: To determine the involvement of Ets-1 in the pathological progress of the experimental diabetic retina. METHODS: Diabetes was induced by intraperitoneal injection of STZ. Total RNA and Total proteins were isolated from retinas of experimental and control eyes at 4 weeks after STZ-injection and were assessed by Northern blot analysis and Western blot analysis, respectively.RESULTS: Expression of both Ets-1 mRNA and Ets-1 protein was significantly increased in the experimental diabetic rat's retina after STZ-injection compared with the control group (P＜0.001).CONCLUSION: Our results indicated that Ets-1 was involved in the pathological progress of experimental diabetic retina.Further studies should be conducted to focus on the relationship between Ets-1 and VEGF in the diabetic retina.

With the deepening of research in recent years, tumor metabolic reprogramming has gradually become the focus of research, and targeting tumor cell metabolism has also become a new means of tumor therapy. The metabolic process affects almost all the physiological processes of the organism, and lipid metabolism is an important part of the metabolic process. Studies have shown that changes in lipid uptake, storage and fatty acid synthesis and decomposition have occurred in a variety of tumors. Abnormal lipid metabolism will promote the rapid proliferation of tumors. Abnormal expression of a variety of key metabolic enzymes in the process of lipid metabolism is the key to tumor progression. The purpose of this paper is to explain the metabolic regulation of lipid metabolism and related metabolic enzymes in hematological tumors, and to provide ideas for the treatment of hematological tumors.