ABSTRACT
Objective To investigate the effect of neoadjuvant chemotherapy on the expression of four molecular markers ER,PR,HER-2 and Ki6 7 ,so as to provide the basis for accurate individualized treatment of breast cancer patients.Methods We enrolled 165 breast cancer patients who underwent radical surgery in the First Affiliated Hospital of Xi'an Jiaotong University from January 1,2013 to December 31,2015.Among them,62 patients received preoperative neoadjuvant chemotherapy (NAC group),and 103 received no adjuvant (control group).We collected all the patients'preoperative and postoperative pathological specimens;we detected the expression levels of ER,PR,HER-2 and Ki67 by immunohistochemical method.Results Compared with that in control group patients,in NAC group the change rate of ER expression was 12.1% (7/58)and 7.8% (8/103) before and after chemotherapy,respectively,with no significant difference (P=0.3 78);the change rate of PR expression was 10.3% (3/58)and 10.7% (11/103),with no significant difference (P=0.227);the change rate of HER-2 expression was 8.6% (5/58)and 22.3 (23/103),with significant difference (P=0.026);the change rate of Ki67 expression was 39.7% (23/58)and 19.4% (20/103),with significant difference (P=0.006).In addition,the effective rate of neoadjuvant chemotherapy for breast cancer patients with high Ki67 expression was 63.8% (30/47), that of neoadjuvant chemotherapy in patients with low Ki6 7 expression was 3 3 .3 % (5/15),with significant differences between the two groups (P=0.038).Conclusion Neoadjuvant chemotherapy can change the status of HER-2 and Ki6 7 in breast cancer patients,in which the high Ki6 7 expression level predicts better effect of chemo-therapy.
ABSTRACT
Dermcidin (DCD) was found in isolated human skin sweat glands with antimicrobial effect, and was defined as a kind of new small molecule antimicrobial peptide. It was a part of human sweat glands in the skin as the immune system's innate defense. With the studies of DCD, its extensive biological functions are gradually discovered. Since 2010, a number of studies have shown that DCD may be a new risk factor for atherosclerosis. And the role of DCD in ischemic heart disease has drawn increasing attention in particular its relationship with insulin secretion and glycemic control, nitric oxide (NO) synthesis and hypertension, platelet aggregation and acute myocardial infarction (AMI). In those experiments, it was also confirmed that aspirin had antagonistic and reverse effects on various biological functions of DCD. Further research on the role of DCD in cardiovascular and cerebrovascular diseases may lead to the prevention, early warning, prognosis evaluation and treatment breakthrough of cardiovascular and cerebrovascular events.
ABSTRACT
Objective To investigate the predictive value of 4 183 Da peptide of dermcidin protein in the early diagnosis and differential diagnosis of ischemic heart disease.Methods A prospective controlled study was conducted.Serum samples were drawn from 161 patients with acute coronary syndrome [ACS,including 46 patients with unstable angina (UA),23 with acute non-ST elevation myocardial infarction,and 92 with acute ST segment elevation myocardial infarction],111 subjects for routine physical examination,including 45 patients with hypertension history,42 with coronary heart disease,22 with diabetes,and 54 patients with non-ACS (including pulmonary embolism,aortic dissection aneurysm,arrhythmia,myocarditis,coronary myocardial bridge,pleurisy,pneumothorax,pneumomediastinum,rib fracture,reflux esophagitis,peptic ulcer,and pancreatitis) to serve as controls.4 183 Da peptide of dermcidin protein was assessed with matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology,and myeloperoxidase [MPO,determined by point-of-care testing (POCT) and enzyme linked i mmunosorbent assay (ELISA),respectively],high sensitive C-reactive protein (hs-CRP),heart type fatty acid binding protein (H-FABP),myoglobin (MYO),cardiac troponin Ⅰ (cTnⅠ),and MB isoenzyme of creatine kinase (CK-MB) were quantitated with biochemical analysis.The power of the biomarkers above for early diagnosis and differential diagnosis for ischemic heart disease were judged by comparison of their sensitivity and specificity.Results ① It was showed by one-way ANOVA that 4 183 Da peptide was higher in ACS group than that in control group (relative abundance:22.05 ± 16.97 vs.15.52 ± 14.09,P =0.001),but no difference was found between ACS group and non-ACS group (relative abundance:22.05 ± 16.97 vs.19.99 ± 17.63,P =0.416).② The specificity and sensitivity of the 4 183 Da polypeptide and MPO for predicting ACS and UA were compared with the receiver operating characteristic curve (ROC).It was showed that the 4 183 Da polypeptide had predictive values for ACS and UA,and the areas under the ROC curve (AUC) was 0.625 and 0.651 (both P ＜ 0.01),but MPO was not found to have predictive value (AUC was 0.440 and 0.336,respectively,both P ＞ 0.05).③ It was showed by the values of multi-markers in differential diagnosis of ACS and non-ACS disease that the specificity and sensitivity of 4 183 Da peptide in the differential diagnosis of acute myocardial infarction (AMI) and non-ACS disease were less than those of MYO,cTnⅠ,H-FABP,markers of myocardial damage,which AUCs were 0.569 vs.0.796,0.833,0.838,and equal to MPO (POCT/ELISA) and hs-CRP,AUC of which was 0.569 vs.0.505 (POCT)/0.477 (ELISA) and 0.545.But both the value of 4 183 Da peptide and MYO,cTnⅠ,H-FABP in the differential diagnosis of UA and non-ACS disease was not found,where AUC was 0.456,0.525,0.658,0.568.Conclusion 4 183 Da polypeptide,a fragment of dermcidin protein,may have association with the onset of ischemic heart disease,and may be helpful in the early diagnosis of ACS.
ABSTRACT
Objective To establish a sensitiv e and specific LC-MS/MS method for the simultaneous determination of cefoperazone and sulbactam in plasma and ultrafiltrate of patients undergone continuous renal replacement therapy(CRRT). Methods Cefuroxime axetil was used as the internal standard,the plasma samples were separated on an WatersAtlantis dC18 column (150 mm× 4.6 mm, 5.0 μm). A tandem mass spectrometer equipped with ESI was used as the detector and operated in the mode of multiple reaction monitoring.Quantitive analysis of[M-H]-ions were m/z 644.1→528.1(cefoperazone), m/z 231.8→188.0(sulbactam) and m/z 509.3→206.9(the internal standard, IS), respectively. Results The linear range of cefoperazone and sulbactam in human plasma and ultrafiltrate were(10-500) and(6-300)μg/ml, respectively. Extraction recoveries were more than 90.0%, and intra- and inter-day relative standard deviation was less than 15%. The matrix effect of plasma and ultrafiltrate showed that the matrix effect of the two media had little influence on the measurement of cefoperazone, sulbactam and IS. Conclusion The method is simple, fast, and highly sensitive. The two drugs can be detected simultaneously in the same sample. It is appropriate to monitor drug concentration in plasma and ultrafiltrate of the patients undergone CRRT. Sieving coefficient could be calculated and provide an accurate basis for dose adjustment.
ABSTRACT
Objective To analyze the profile of dermcidin (DCD) changes in different stages of acute coronary syndrome (ACS) by quantifying the serum 4 183Da DCD peptide fragment deriving from different ACS patients treated with early antithrombotic therapy.Methods A total of 118 patients with confirmed diagnosis of ACS were enrolled. Immediately after visiting a doctor, the venous blood was collected and afterwards instantly the patient was given orally 300 mg of aspirin and 300 mg clopidogrel, and according to the patient's condition and the consent of his/her or acknowledgement of family members achieved, emergency percutaneous coronary interference (PCI) or thrombolysis or conservative treatment was adopted separately. After anti-thrombotic treatment, at 2, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, 48, 60 and 72 hours, venous blood was collected and serum isolated respectively. The concentration of 4 183Da DCD fragment in serum was determined by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Simultaneously, the myoglobin (Myo), cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK-MB) were also detected.Results The mean relative strength of nature logarithmic transformations of 4 183Da DCD fragment of 118 patients with ACS was 2.75±1.02 before treatment on admission, and after intervention therapy (mainly antithrombotic therapy) it was decreased to 1.84±1.19 (P = 0.005) and 1.74±1.12 (P = 0.000) at 2 hours and 4 hours, respectively, and then after 4 hours it was slightly elevated. 4 183Da polypeptide increased earlier than myocardial injury markers.Conclusion Aspirin and clopidogrel can significantly decrease the concentration of 4 183Da DCD peptide fragment in serum in patients with ACS, which indicates that the DCD fragment could be used as one of the indexes for observation on early efficacy of antithrombotic therapy.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of polyinosinic-polycytidylic acid (polyI:C) on the production of thymic stromal lymphopoietin (TSLP) and airway inflammation in mice with exacerbated asthma induced by respiratory syncytial virus (RSV).</p><p><b>METHODS</b>Thirty-two female BALB/c mice were randomly divided into 4 groups, namely the PBS control group, OVA group, OVA/RSV group, and OVA/RSV/polyI:C group. In the latter 3 groups, the mice were sensitized by OVA and stimulated with nebulized OVA. RSV was inoculated into the nasal cavity of the sensitized mice and polyI:C (1 mg/kg) was intramuscularly administered. The airway response to metacholine was examined, and the serum levels of IL-4, IL-5, IL-13, and IFN-γ and TSLP in the supernatants of bronchoalveolar lavage fluid (BALF) were detected using ELISA. The total BALF cells, eosinophils, lymphocytes and neutrophils were counted. The lung specimens were collected to observe the inflammation with HE staining, and immunohistochemistry was employed to determine TSLP production in the airway epithelial cells.</p><p><b>RESULTS</b>The mice in RSV/OVA/polyI:C group showed a significantly lower airway responsiveness to metacholine than those in OVA/RSV group (P<0.01). Compared with OVA/RSV group, RSV/OVA/polyI:C group showed significantly lower serum levels of IL-4, IL-5, IL-13 and TSLP in BALF (P<0.05), with also lower total BALF cells, eosinophils and lymphocytes (P<0.05) and lessened infiltration of the airway inflammatory cells. Immunohistochemistry of TSLP also demonstrated a lower production of TSLP in the airway epithelial cells in RSV/OVA/polyI:C group than in OVA/RSV group.</p><p><b>CONCLUSIONS</b>polyI:C can inhibit the increase in TSLP production in the airway epithelial cells after RSV infection and relieve airway inflammation in mice with RSV-induced asthma exacerbation.</p>
Subject(s)
Animals , Female , Mice , Asthma , Blood , Metabolism , Virology , Bronchoalveolar Lavage Fluid , Cytokines , Bodily Secretions , Inflammation , Pathology , Interleukin-13 , Blood , Interleukin-4 , Blood , Interleukin-5 , Blood , Mice, Inbred BALB C , Poly I-C , Pharmacology , Respiratory Syncytial Virus Infections , Blood , Metabolism , Respiratory Syncytial VirusesABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of different factors on the expressions of thymic stromal lymphopoietin (TSLP) in respiratory syncytial virus (RSV)-infected human airway epithelial cell line 16HBE cells.</p><p><b>METHODS</b>RSV amplified by infecting Hep-2 cells was identified for its virulence. 16HBE cells were divided into six groups, namely the control group, RSV group, RSV/anti-TLR3 group, RSV/IFN-gamma group, RSV/IL-4 group and RSV/dexamethasone group with corresponding treatments. Real-time RT-PCR was used to examine the expression of TSLP mRNA in the cells 6 h after RSV infection. Western blotting was used to examine TSLP protein expression in the cells 24 h after the infection.</p><p><b>RESULTS</b>The expression of TSLP mRNA in 16HBE cells 6 h after RSV infection increased by 1.63-/+0.08 folds as compared to the expression level in the control cells. The expression of TSLP mRNA was significantly decreased in RSV-infected cells treated with anti-TLR3 antibody (P=0.034) and recombinant human IFN-gamma (P<0.001), but increased with the treatment by recombinant human IL-4 (P=0.025). Dexamethasone significantly inhibited the expression of TSLP mRNA in RSV-infected cells (P<0.001). The production of TSLP protein in 16HBE cells increased by 1.9 folds (P<0.001) 24 h after RSV infection, but underwent no significant changes after treatment with anti-TLR3 antibody (P=0.114). Recombinant human IFN-gamma significantly decreased while IL-4 enhanced the expression of TSLP protein in the infected cells (P=0.020 and 0.014, respectively). Dexamethasone significantly inhibited the increment of TSLP protein expression in RSV-infected cells (P<0.001).</p><p><b>CONCLUSIONS</b>RSV infection can enhance the expressions of TSLP in human airway epithelial cells. IFN-gamma, anti-TLR3 and dexamethasone can inhibit the elevation of TSLP expression induced by RSV infection, but IL-4 synergistically enhances its expression.</p>
Subject(s)
Humans , Bronchi , Cell Biology , Metabolism , Cell Line , Cytokines , Genetics , Metabolism , Epithelial Cells , Metabolism , Virology , Interferon-gamma , Pharmacology , Interleukin-4 , Pharmacology , RNA, Messenger , Genetics , Metabolism , Respiratory Syncytial Virus Infections , Metabolism , Respiratory Syncytial Viruses , VirulenceABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of respiratory syncytial virus (RSV) infection on the production of thymic stromal lymphopoietin (TSLP) and Th1/Th2 balance in asthmatic mice.</p><p><b>METHODS</b>Thirty-two female BALB/c mice were randomly divided into 4 groups, namely the PBS group, ovalbumin (OVA) group, RSV group and OVA/RSV group. The mice were sensitized by OVA and then stimulated with nebulized OVA, and RSV was inoculated into the nasal cavity of the mice. BUXCO noninvasive lung function detection was performed to examine the airway response to metacholine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The cells in the bronchoalveolar lavage fluid (BALF) were counted and classified, and the supernatants of the BALF were used for the detection of TSLP. Histopathological changes in the lung tissues of the mice were examined using HE staining, and immunohistochemistry using anti-mouse TSLP antibody was performed to examine TSLP expressions in the airway epithelial cells.</p><p><b>RESULTS</b>RSV infection promoted the production of TSLP in the asthmatic mice, and the concentration of TSLP in OVA/RSV group (2.13-/+0.05 ng/ml) was significantly higher than that in the other groups (P<0.01). RSV infection increased the serum levels of IL-4, IL-5, IL-13, and IFN-gamma in the mice. The total BALF cells, eosinophils, lymphocytes and neutrophils in OVA/RSV group were significantly higher than those in the other groups; noninvasive lung function examination showed higher Penh value in OVA/RSV group (318.66-/+50.87) than in the other groups when the inhaled metacholine increased to 6.25 mg/ml (P<0.01). More obvious and extensive airway inflammatory cell infiltration in OVA/RSV group were observed, and immunohistochemical staining also showed higher expression of TSLP in the airway epithelial cells of OVA/RSV group.</p><p><b>CONCLUSIONS</b>RSV infection promotes the production of TSLP in the airway epithelial cells and increases the level of Th2 cytokines in asthmatic mice. Concurrent RSV infection can exacerbate Th2 inflammatory reaction in asthmatic mice.</p>
Subject(s)
Animals , Female , Mice , Bronchoalveolar Lavage Fluid , Cytokines , Bodily Secretions , Immunohistochemistry , Inflammation , Allergy and Immunology , Virology , Interferon-gamma , Blood , Interleukins , Blood , Lung , Allergy and Immunology , Metabolism , Virology , Mice, Inbred BALB C , Respiratory Syncytial Virus Infections , Blood , Allergy and Immunology , Metabolism , Th2 Cells , Cell Biology , Allergy and Immunology , VirologyABSTRACT
Objective: To investigate the combined inhibitive effect of TNP-470 and rhES on the growth of lung adenocarcinoma LA795 in T739 mice. Methods: The purified rhES was acquired by using methanol to induce the recombinant pichia pastoris. GS115 and heparin affinity chromatography. The T739 mice inoculated with LA795 cells were randomized into three groups, 10 mice per group, one group was injected with PBS for 14 days, the other two groups were respectively treated with rhES and TNP-470+rhES. To observe the tumor growth in different groups, and the tumor volume was measured with caliper. The microvessel density(MVD) of tumors were measured by using immunohistochemistry. Results: The purified rhES was acquired. In compared with PBS group, the tumor growth of other two groups was inhibited significantly. And the tumor volume of TNP-470+rhES group are smaller than the rhES group (P