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Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.
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The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area. Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.
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Objective@#The aim of this study is to investigate the effect of sublingual immunotherapy with Dermatophagoides Farinae on the expression of specific IgG4（sIgG4） in patients with allergic rhinitis （AR） in Hainan area.@*Method@#Seventy-two patients with dust-mite allergic rhinitis, all three generations of whom were local islanders in Hainan, were randomly divided into control group（36 cases） and SLIT group（36 cases）. sIgG4 and sIgE expression levels were detected before treatment, 6 months after treatment, 12 months after treatment, and 18 months after treatment. The patient's symptom score, medication score, VAS score and adverse reactions was also assessed. Finally, through statistical analysis of the relevant data collected at 4 time points in the two groups of patients, the efficacy, safety and changes of sIgG4 antibody expression level in patients with allergic rhinitis receiving sublingual specific immunotherapy in Hainan were observed. @*Result@#Symptoms scores, medication scores and VAS scores were significantly improved in the SLIT group after treatment compared with before treatment（P<0.05）, and serum sIgG4 increased significantly（P<0.01）, serum sIgE showed no significant change（P>0.05）. In the control group, symptom scores, medication scores and VAS scores were also significantly improved compared with before treatment（P<0.05）, while serum sIgG4 and sIgE showed no significant change（P>0.05）. When comparing the two groups, Symptoms scores, medication scores and VAS scores of the SLIT group were significantly lower than those of the control group at 12 months and 18 months after treatment（P<0.05）. sIgG4 expression levels in the SLIT group were significantly higher than those in the control group after 6, 12 and 18 months of treatment（P<0.01）. There was no significant difference in sIgE expression level between the two groups（P>0.05）. No severe systemic adverse reactions occurred in the two groups, and 3 patients showed mild adverse reactions in the SLIT group. @*Conclusion@#Sublingual immunotherapy of Dermatophagoides Farinae was effective and could increase the expression of sIgG4 in patients with Dermatophagoides farinae AR, sIgG4 is expected to be an immunological marker for the objective evaluation of the clinical efficacy of Hapten.
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Objective To analyze the CT features in the early stage of asymptomatic active pulmonary tuberculosis (PTB)in adolescence after PTB outbreak.Methods After PTB outbreak in a boarding school of a certain county in northern Jiangsu province,the clinical data, X-ray and CT findings of 47 cases with active PTB were analyzed retrospectively and compared with CT findings after treatment.Results In 47 cases,the incidence of male was higher than that of female,and 27 cases were negative on chest X-ray.The difference of X-ray and CT detection rate in the early stage of active PTB was statistically significant (P<0.001).Of 47 cases,46 patients had pulmonary parenchymal lesions and 1 had pleural effusion on CT.The lesions were found on 58 lobes and 60 lung segments,and 35 cases demonstrate lesions on the upper lobes,22 cases on the lower lobes,1 case on the middle lobe.CT images showed tree-in-bud opacities (68.1%),micronodules (89.4%) and consolidation (21.3%).All of patients got better after antituberculous therapy.Conclusion Active PTB should be considered first when CT scan shows micronodules or tree-in-bud signs in adolescences with PTB exposure.
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AIM:To investigate the effect of short-chain acyl-CoA dehydrogenase ( SCAD) on collagen expres-sion and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis . METHODS:The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was es -tablished.After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels , fatty acids beta oxida-tion rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined . RESULTS:The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells , and the expression of collagen I and collagen III was significantly upregulated .Com-pared with negative control group , SCAD expression and activity , fatty acid beta-oxidation rate and ATP significantly de-creased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts , and the expression of collagen I and collagen III was significantly up-regulated.CONCLUSION:The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD .SCAD may be a promising therapeutic target for myocar-dial fibrosis .
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AIM:To investigate the change of short-chain acyl-CoA dehydrogenase (SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis .METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide (tBHP) were used as the model of cardiomyocyte apoptosis . The cell viability , the expression of SCAD at mRNA and protein levels , the activity of SCAD and the content of free fatty acids were determined .RESULTS:The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model.Compared with negative control group , SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes .Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP .CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis .Increase in the expression of SCAD may become an impor-tant part in intervening cardiomyocyte apoptosis .
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[ABSTRACT]AIM:ToinvestigatethedifferenteffectsofERK1/2/PPARα/SCAD(short-chainacyl-CoAdehy-drogenase) signal pathways on the cardiac hypertrophy induced by insulin-like growth factors 1 ( IGF-1) or phenylephrine ( PE) .METHODS:The neonatal rat cardiomyocytes induced by IGF-1 were used as the model of physiological cardiac hypertrophy , and those induced by PE were used as the model of pathological cardiac hypertrophy .The surface area of the cardiomyocytes, the expression of p-ERK1/2, PPARαand SCAD, the activity of SCAD and the content of free fatty acid in the cardiomyocytes were measured .RESULTS:Compared with the control cells , the surface area of the cardiomyocytes in-duced by IGF-1 and PE were both increased .Compared with the controls , the expression of SCAD and PPARα, and the activity of SCAD in the cardiomyocytes induced by IGF-1 were increased , while the expression of p-ERK1/2 was de-creased.However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activ-ity of SCAD and increased expression of p-ERK1/2.Meanwhile, the decrease in free fatty acid in IGF-1-induced cardio-myocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardio -myocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE .CONCLUSION: The changes of p-ERK1/2, PPARαand SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK 1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertro -phy , and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy .
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Objective:To investigate the rational use and effective management countermeasures of medical x-ray protective equipment in the hospital interventional catheter lab. Methods:Retrospective analysis of proportion in the medical x-ray the daily use of protective equipment and management situation in our hospital has been involved in the catheter lab in operation since June 2004 to December 2012. Results:Some experience medical x-ray equipment for clinical use and management have been accumulated for more than 8 years in our Interventional catheterization room. Conclusion:For more account, expensive price and frequency clinical usage, It is extremely necessary and effective management for the use of medical x-ray equipment in interventional catheterization room.
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Aim: To study the effects of astragaloside IV on experimental ventricular remodeling in mice and its mechanism from matrix metalloproteinase aspect.Method: Ventricular remodeling in mice was induced by con-secutively subcutaneous injection of isoproterenol for 14 days.Astragaloside IV(40,80 mg/kg)and propranolol(40 mg/kg,positive control)were administered by gavage to mice.Echocardiography was used to observe the left ventricular end diastolic diameter(LVIDd),left ventricular end systolic diameter(LVIDs),fractional shortening(FS)and ejection fraction(EF).The myocardial pathological pattern was detected by HE staining.Expressions of matrix metalloproteinases(MMP2,MMP9)and tissue inhibitor of metalloproteinases(TIMP1,TIMP2)mRNA in myocardium were detected by RT-PCR.Activities of MMP2 and MMP9 were assayed by zymography.Results:Compared with those of control mice,LVIDd and LVIDs were increased,FS and EF were decreased in the model group.Myocardial injury and fibrosis existed in histop at hological slices of the model group.In addition,the mRNA expressions and activities of MMP2 and MMP9 were increased in the model group.However,there were no markable changes to TIMP1 and TIMP2.Treatment with astragaloside IV reduced LVIDd and LVIDs,increased FS and EF,attenuated myocardial injury,and down-regulated mRNA expressions and activities of MMP2 and MMP9 compared with the model group.Conclusion: Astragaloside IV can greatly improve ventricular remodeling and dysfunction via decreasing MMP2 and MMP9 mRNA expression and activities in cardiac ventricles.
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DIA3 typing for human tissues was carried out by IEF- The results showed that the DIA3 typescould be demonstrated in testis, ovary, uterus and dental pulps ;but could not be demonstrated in thehuman brain, liver, kidney, adrenal gland, spleen, intestine, pancrease, heart, lung, skin, muscle, blood,vaginal secretion and hair root. The relative activty of DIA in different human tissues,blood and vagi-nal secretion DIA activity of different tissues and the DIA band intensity by PAGIEF were basecallyconsistent. The author were examined by spectrophotometric analysis. The relative suggests that theDIA3 typing of reproductive organs and teeth by PAGIEF plays a significant role for medicolegal individualization,The vaginal sectetion did not interfere with DIA3 typing of semen in mixed stain for theindividualization.