Diffusion-weighted MR imaging in prediction of response to neoadjuvant chemotherapy in patients with breast cancer.

This study aims to evaluate the potential of apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging for predicting the treatment response to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Magnetic resonance imaging was performed prior to NACT and after two cycles of NACT. The correlation between mean ADCpre values, mean ADCpost values, changes in ADC values and changes in tumor diameters after NACT was examined using Spearman rank correlation. A total of 164 breast cancers were enrolled in this study. Mean ADCpre values of responders ([0.85 ± 0.16] × 10-3 mm2/s) and non-responders ([0.84 ± 0.21] × 10-3 mm2/s) had no significant difference (P = 0.759). While mean ADCpost value of responders was significantly higher than that of non-responders ([1.17 ± 0.37] × 10-3 mm2/s vs. [1.01 ± 0.28] × 10-3 mm2/s; P = 0.002). Both mean ADCpost values (r = 0.288, P = 0.000) and changes in mean ADC values (r = 0.222, P = 0.004) were positively correlated to changes in tumor diameter after NACT, except for mean ADCpre values (r = 0.031, P = 0.695). Our results indicated that mean ADCpost values and changes in ADC values after NACT might be a biological marker for assessing the efficacy of chemotherapy.

GSTP1 polymorphism predicts treatment outcome and toxicities for breast cancer.

This study aimed to investigate the association of the GSTP1 gene polymorphism with the outcomes and toxicities of treatments in breast cancer. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the association of GSTP1 polymorphism with tumour response and toxicities, and the hazard ratios (HRs) and 95% CIs were calculated for the association between GSTP1 polymorphism and overall survival (OS). The statistical analysis showed that the GSTP1 polymorphism was not associated with tumour response or OS. A significant increase in the incidence of toxicities was observed (GA vs. AA OR = 1.45, 95% CI = 1.04-2.01, P = 0.028; GG vs. AA OR = 1.47, 95% CI = 1.03-2.10, P = 0.036; recessive model OR = 1.54, 95% CI = 1.13-2.09, P = 0.006; and allele model OR = 1.35, 95% CI = 1.07-1.71, P = 0.011), especially in the chemotherapy ± surgery group (GA vs. AA OR = 1.64, 95% CI = 1.05-2.56, P = 0.030; recessive model OR = 1.72, 95% CI = 1.17-2.54, P = 0.006; and allele model OR = 1.57, 95% CI = 1.11-2.21, P = 0.010). Our results indicate that the GSTP1 polymorphism may be associated with increased toxicity, especially in patients treated with chemotherapy ± surgery.

GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Diagnostic performance of ADCs in different ROIs for breast lesions.

OBJECTIVE: The purpose of this study was to explore the diagnostic performance of apparent diffusion coefficient (ADC) values for breast lesions by different measuring methods and find out the optimum measuring method. METHODS: ADCW-mean and ADCW-min were obtained by whole-measurement method, while ADCmean and ADCmin were extracted by spot-measurement method. Four ADCs were analyzed by One-way ANOVA and Independent T-test. The diagnostic performances of these four ADCs were calculated by receiver operating characteristics (ROC) curves and the area under the curves (AUC) were compared through Z-test. RESULTS: For the whole-measurement method, there were significant differences between malignant and benign lesions (ADCW-mean=1.014±0.197 for malignant, ADCW-mean=1.650±0.348 for benign, F=37.511, P<0.001; ADCW-min=0.627±0.144 for malignant, ADCW-min=1.245±0.290 for benign, F=41.446, P<0.001), as well as the spot-measurement method (ADCmean=1.010±0.234 for malignant, ADCmean=1.648±0.392 for benign, F=34.580, P<0.001; ADCmin=0.817±0.203 for malignant, ADCmin=1.411±0.357 for benign, F=40.039, P<0.001). The optimal diagnostic threshold of ADCW-mean, ADCW-min, ADCmean, and ADCmin values were 1.223×10(-3) mm(2)/s, 0.897×10(-3) mm(2)/s, 1.315×10(-3) mm(2)/s, and 1.111×10(-3) mm(2)/s, respectively. ROC curves indicated that the AUC for ADCW-min (0.969) was statistically significant higher than the AUC for ADCW-mean (0.940; Z=2.473, p=0.013), ADCmean (0.919; Z=3.691, P=0.000), and ADCmin (0.928; Z=3.634, P=0.000). The AUC for ADCW-mean was also significantly higher than the AUC for ADCmean (Z=2.863, P=0.004). CONCLUSION: The results provided evidence that the most reliable and accurate value in demonstrating the limitation of diffusion may be ADCW-min, and it has the highest diagnostic value in distinguishing breast lesions from malignant to benign.

Efficacy and safety of laparoscopic splenectomy in thrombocytopenia secondary to systemic lupus erythematosus.

This study aims to investigate the efficacy and safety of laparoscopic splenectomy (LS) in the management of refractory thrombocytopenia associated with systemic lupus erythematosus (SLE). From January 2003 to February 2012, 20 patients underwent splenectomy for thrombocytopenia associated with SLE. Of these, 11 underwent open (SLE-OS group) and 9 underwent laparoscopic splenectomy (SLE-LS group). Another 15 patients with ITP underwent LS (ITP-LS group) were categorized as the control group. Surgical indications, perioperative details, and short- (90 days) and long- (median, 42 months) term hematological outcomes were assessed. Splenectomy was successful in all 20 SLE patients. The mean platelet count increased from 23 × 10(9)/L before splenectomy to 289.2 × 10(9)/L and 144.2 × 10(9)/L after 3 and 6 months, respectively, and was 115.5 × 10(9)/L at the last visit, with a 3-month complete response (CR) rate of 100 %. After a median follow-up of 42 months, 17 patients (85 %) had a CR or partial response (PR) to splenectomy plus medical therapy. SLEDAI score and dosage of steroids decreased significantly after splenectomy. None of these patients experienced any postoperative infection, bleeding, or thrombotic events. SLE-LS group had lower volumes of estimated blood loss and postoperative drainage and shorter postoperative hospital stay than SLE-OS group. There were no statistically significant differences between the SLE-LS and ITP-LS groups in operation time, estimated blood loss, and postoperative hospital stay. Splenectomy is effective and safe in the management of refractory thrombocytopenia secondary to SLE. LS may be safe and effective in thrombocytopenia associated with SLE.

Meta-analysis of diffusion-weighted magnetic resonance imaging in detecting prostate cancer.

PURPOSE: The objective of this study was to determine the diagnostic performance of quantitative diffusion-weighted magnetic resonance imaging in detection of prostate cancer. METHODS: A comprehensive search was performed for English articles published before May 2012 that fulfilled the following criteria: patients had histopathologically proved prostate cancer; diffusion-weighted imaging (DWI) was performed for the detection of prostate cancer, and data for calculating sensitivity and specificity were included. Methodological quality was assessed by using the quality assessment of diagnostic studies instrument. Publication bias analysis, homogeneity, inconsistency index, and threshold effect were performed by STATA version 12. RESULTS: Of 119 eligible studies, 12 with 1637 malignant and 4803 benign lesions were included. There was notable heterogeneity beyond threshold effect and publication bias. The sensitivity and specificity with 95% confidence interval (CI) estimates of DWI on a per-lesion basis were 77% (CI, 0.76-0.84) and 84% (CI, 0.78-0.89), respectively, and the area under the curve of summary receiver operating characteristic curve was 0.88 (CI, 0.85-0.90). The overall positive and negative likelihood ratios with 95% CI were 4.93 (3.39-7.17) and 0.278 (0.19-0.39), respectively. CONCLUSIONS: Quantitative DWI has a relative sensitivity and specificity to distinguish malignant from benign in prostate lesions. However, large-scale randomized control trials are necessary to assess its clinical value because of nonuniformed diffusion gradient b factor, diagnosis threshold, and small number of studies.

[Peripheral blood leukocyte double strand RNA-dependent protein kinase gene expression in patients with systemic lupus erythematosus].

OBJECTIVE: To investigate the expression of the double-stranded RNA-dependent protein kinase (PKR) gene in the peripheral blood leukocyte of patients with systemic lupus erythematosus (SLE), and to evaluate the relationship between the gene expression and the disease activity. METHODS: The clinical data of 100 SLE patients, 40 non-SLE patients with rheumatic diseases, and 40 normal controls were collected. Total RNA was extracted from the peripheral blood and then reverse transcribed into cDNA. Sybr green dye based real-time quantitative PCR method was used to compare the expression levels (indicated as 2(-ΔCt) value) of PKR in the three groups. RESULTS: (1) The 2(-ΔCt) value of PKR expression level in the SLE patients was (14.69 ± 7.62), which was significantly higher than those in the non-SLE patients (5.09 ± 4.73, P = 0.012)and normal controls(4.79 ± 3.49, P = 0.005). (2) The 2(-ΔCt) value of PKR expression level in the SLE patients with severe activity was (22.57 ± 2.61), which was significantly higher than those in the SLE patients with mild activity and no activity (12.94 ± 2.41, P = 0.000; 8.85 ± 2.17, P = 0.000). (3) The 2(-ΔCt) value of PKR expression level in the SLE patients with lupus nephritis was significantly higher than that in the SLE patients without lupus nephritis (16.85 ± 7.32 vs 8.35 ± 2.04, P = 0.034). (4) The 2(-ΔCt) value of PKR was correlated with the systemic lupus erythematosus index (SLEDAI) scores (r = 0.32, P = 0.000), WBC (r = 0.46, P = 0.000), Hb (r = -0.22, P = 0.035), the quantitation of urine protein in 24 hours (r = 0.21, P = 0.000), HDL-C (r = 0.21, P = 0.022), and anti-RNP antibody (r(s) = -0.21, P = 0.025). CONCLUSIONS: The expression of PKR in the SLE patients is up-regulated, especially in those with severe activity. The expression level of PKR gene is associated with SLE disease activity.

Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte infiltration.

Autoimmune pancreatitis (AIP) is a rare form of pancreatitis characterized by prominent lymphocyte infiltration and pancreatic fibrosis resulting in organ dysfunction. The pathogenesis and pathology of AIP remain unknown. A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas, elevated IgG levels, and negative autoimmune antibody responses. A pylorus-preserving pancreatoduodenectomy was performed and a pancreatic tumor was suspected. However, periductal lymphoplasmacytic infiltration and fibrosis were found in the head of pancreas and nearby organs instead of tumor cells. Four months after surgery, the patient was readmitted because of reoccurrence of severe jaundice and sustained abdominal distension. Prednisone 30 mg/d was administered orally as an AIP was suspected. One and a half months later, the symptoms of the patient disappeared, and globulin, aminotransferase and bilirubin levels decreased significantly. Over a 9-mo follow-up period, the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition. We further demonstrated dominant CD3+/CD8+ populations, CD20+ cells and a few CD4+ cells in the pancreatic parenchyma, duodenum and gallbladder wall by immunohistochemical assay. This AIP case presented with significant CD8+ T lymphocyte infiltration in the pancreas and extra-pancreatic lesions, indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.

[Interferon-inducible genes 2', 5'-ollgoadenylate synthetase-like and tetratricopeptide repeats 2 are correlated with clinical features of patients with systemic lupus erythematosus].

OBJECTIVE: To investigate the expression levels of 2', 5'-oligoadenylate synthetase-like (OASL) and interferon induced protein with tetratricopeptide repeats 2 (IFIT2) genes in the peripheral blood leukocyte of patients with systemic lupus erythematosus (SLE), and to evaluate the relations between these gene expression levels and disease activity. METHODS: The clinical data of 50 SLE patients, 25 non-SLE patients with rheumatic diseases, and 25 normal controls were collected. Specimens of peripheral blood were collected; total RNA was extracted and transcribed into cDNA. SYBR green dye based real-time quantitative PCR method was applied to compare the expression levels (indicated as deltaCT value) of OASL and IFIT2 in patients with SLE and those in the controls. RESULTS: The deltaCT value of OASL expression level of the SLE patients was (4.83 +/- 0.41), significantly higher than those of the non-SLE patients (3.26 +/- 0.47) and normal controls (3.07 +/- 0.54, both P < 0.05), The deltaCT value of IFIT2 expression level of the SLE patients was (2.85 +/- 0.41), significantly higher than those of the non-SLE patients (1.19 +/- 0.52) and normal controls (1.07 +/- 0.47, both P < 0.05). The deltaCT value of OASL is related with the SLEDAI scores and immunoglobulin A. (Both P < 0.05). The deltaCT value of IFIT2 is related with the SLEDAI scores and IgA, white blood cell (both P < 0.05). CONCLUSION: The value of IFIT2 and OASL expression level of the SLE patients is up-regulation, the real time expression levels of OASL and IFIT2 genes are associated with SLE disease activity. To inhibit the expression of OASL and IFIT2 may become a novel therapeutic approach for SLE.

[Effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080].

OBJECTIVE: To investigate the effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080. METHODS: The proliferation inhibitory rate of HT1080 cells treated by LY294002 at doses of 5, 10, 25, 50, 100 micromol/L for 12 and 24 h, respectively, was evaluated using SunBio Am-Blue method. HT1080 cells were divided into two groups, that is, A and B. The A group was control group without treatment. The B group received LY294002 (100 micromol/L) for 24 h. The changes of cell morphology and quantity were observed by phase contrast microscope. The apoptosis rate of HT1080 cells was detected by flow cytometry. And the protein expression of p-Akt and p-mTOR in HT1080 cells were detected by Western Blotting. RESULTS: The proliferation of HT1080 cells was inhibited in time- and dose- dependent manner by LY294002. After the treatment of 100 micromol/L LY294002 for 24 h, the growth of HT1080 cell line was remarkably inhibited by LY294002. The rate of apoptosis increased. And the protein expression of p-Akt (0.23 +/- 0.01) and p-mTOR (0.32 +/- 0.06) in LY294002 group was lower than p-Akt (0.63 +/- 0.02) and p-mTOR (0.71 +/- 0.02) in control group (P<0. 01). CONCLUSION: LY294002 can inhibit the growth of HT1080 cells through PI3K-mTOR pathway. PI3K-mTOR pathway presents an appealing therapeutic target on fibrosarcoma.

Simvastatin attenuates experimental small airway remodelling in rats.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the beneficial effects of simvastatin on cigarette smoke-induced small airway remodeling in rats. METHODS: Simvastatin was administered at different doses for 16 weeks to rats with cigarette smoke-induced small airway remodelling. Morphological analyses were performed, and collagen deposition, production of growth factors, inflammatory parameters and RhoA, as well as the Smad signalling pathway in the lungs, were examined. RESULTS: Simvastatin attenuated small airway wall thickening and prevented the increase in lung hydroxyproline content and collagen deposition induced in airway walls by cigarette smoking. In addition, simvastatin downregulated transforming growth factor-beta1 and connective tissue growth factor protein and gene expression in the lungs. Furthermore, accumulation of macrophages and neutrophils and increases in tumour necrosis factor-alpha concentration in BAL fluid were inhibited by simvastatin. Simultaneously, the expression of RhoA and the phosphorylation of Smad2 and Smad3 in lungs exposed to cigarette smoke were inhibited during simvastatin administration. However, the increased expression of Smad2 and Smad3 proteins and the decreased level of Smad7 protein in remodelled lungs were not affected by simvastatin. CONCLUSIONS: Simvastatin attenuated experimental small airway remodelling, as indicated by decreases in collagen deposition and small airway wall thickening. Simvastatin may inhibit cigarette smoke-induced small airway remodelling by reducing growth factor expression and inflammation. The mechanism of action of simvastatin on small airway remodelling involved RhoA and the Smad signalling pathway. These findings indicate that simvastatin may have potential beneficial effects in the treatment of COPD.

[The correlation of myxovirus resistance 1 and 2'5'-ollgoadenylate synthetase 1 with clinical features of systemic lupus erythematosus].

OBJECTIVE: To investigate the expression of myxovirus resistance 1(MX1) and 2'5'-oligoadenylate synthetase 1(OAS1) genes in the peripheral blood leukocyte of patients with systemic lupus erythematosus (SLE), and to evaluated the relations between these genes expression levels and disease activity. METHODS: In this study, there were 50 SLE petients, 20 non-SLE patients with rheumatic dieases, and 25 normal controls. The peripheral blood samples of these patients were collected, and the expression levels (indicated as delta Ct value) of MX1 and OAS1 were measured by Sybr green dye based real-time quantitative PCR method. RESULTS: The deltaCt value of MX1 expression in SLE patients was 3.55 +/- 1.39, which was significantly higher than those of non-SLE patients (2.31 +/- 0.52, P = 0.000) and normal controls (2.23 +/- 1.05, P = 0.000). (2) The deltaCt value of OAS1 expression in SLE patients was 4.45 +/- 1.56, which also was significantly higher than those of non-SLE patients (3.03 +/- 0.76, P = 0.000) and normal controls (2.75 +/- 0.64, P = 0.000). (3) The deltaCt value of OAS1 was correlated with the SLEDAI scores (r = 0.338, P = 0.019) and serum IgA level. (4) The ACt value of MX1 was not correlated with the SLEDAI scores (r = 0.064, P = 0.661), but correlated with the serum levels of triglyceride (TG), cholesterol (TC), low density lipoprotein (LDL), albuminuria of 24 hours (r = 0.428, P = 0.003 r = 0.383, P = 0.009 r = 0.394, P = 0.007; r = 0.316, P = 0.025); (5) The deltaCt values of MX1 and OAS1 in the SLE patients with arthritis were significantly higher than those in non-arthritis SLE patients (3.04 +/- 1.42, P = 0.004; 3.89 +/- 1.49, P = 0.006). CONCLUSION: The expression levels of both MX1 and OAS1 in SLE patients are up-regulated, the expression levels of OAS1 genes are associated with SLE disease activity. As IFN-induced genes, MX1 and OAS1 play their respective role in SLE.

VEGFR-2 antagonist SU5416 attenuates bleomycin-induced pulmonary fibrosis in mice.

OBJECTIVE: Abnormal angiogenesis is a central hallmark for the development and progression of idiopathic pulmonary fibrosis. It has been shown that vascular endothelial growth factor (VEGF) is one of the critical angiogenic factors in angiogenesis. The aim of the present study was to assess whether disruption of VEGF pathway would attenuate bleomycin-induced pulmonary fibrosis. METHODS: Bleomycin-induced pulmonary fibrosis mice were treated intraperitoneally with VEGF receptor tyrosine kinase inhibitor SU5416 at different phases after bleomycin infusion. We measured angiogenesis and inflammatory response in both bleomycin-treated and control mice, and correlated these levels with pulmonary fibrosis. RESULTS: The increased expressions of VEGF/VEGFR (Flk-1) were correlated to a larger number of microvessels and a higher score of pulmonary fibrosis. Early administration of SU5416 inhibited pulmonary collagen deposition, histopathologic fibroplasias and the activation of TGF-beta1/Smad3 signaling pathway in bleomycin-stimulated lung. These were also paralleled by a reduction of VEGF/VEGFR-2 (Flk-1) expression and microvessel numbers in lung. Furthermore, SU5416 inhibited inflammatory cell numbers and LDH activity in BALF and IL-13 expression in lung tissue at early inflammatory phase of bleomycin-induced pulmonary fibrosis. CONCLUSION: These results suggest that the VEGFR-2 inhibitor, SU5416, attenuates histopathologic fibroplasias and collagen deposition by regulating angiogenesis and inflammation in the lung.

Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice.

BACKGROUND: Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice. METHODS: Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis. RESULTS: Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration. CONCLUSIONS: Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats.

BACKGROUND: Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS). METHODS: Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR), immunohistochemistry or Western blotting. Tumor necrosis factor (TNF)-alpha and IL-8 in bronchoalveolar lavage fluid (BALF) were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA). RESULTS: Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P <0.05). Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-alpha and IL-8 in BALF follows LPS stimulation (P < 0.05). The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P <0.05). Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P < 0.05). However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration. CONCLUSIONS: Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and inflammatory cytokine release via inactivation of RhoA and p38 signaling pathway.

[Effects of delayed opening of infarct-related artery on late left ventricular remodeling in patients with acute anterior myocardial infarction].

OBJECTIVE: To assess the effect of delayed opening of the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) on the late left ventricular remodeling after acute anterior myocardial infarction (AAMI). METHODS: Sixty four patients with initial Q-wave AAMI and with the total occluded IRA conformed by angiogram at 9.1 +/- 2.3 (2 - 14) days after the onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re-opened). Two-D echocardiogram was performed at acute phase (about 3 weeks), 2 and 6 months after onset of AAMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. RESULTS: VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were similar in 2 groups at acute phase and 2 months after the onset of AAMI. There were no differences between the parameters above at acute phase and 2 months in each group too. VWMA scores and LVEF did not changed significantly at 6 months in each group compared with those at acute phase and 2 months (P > 0.05). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than those in the control group (P < 0.01, P < 0.05). The rate of congestive heart failure events was 19% in control group and 2.0% in successful PCI group (P > 0.05) respectively. CONCLUSIONS: Delayed opening of IRA in AAMI could prevent the late phase but not the early phase of left ventricular remodeling after AMI.

[Peripheral blood mRNA and interferon gene expression in systemic lupus erythematosus].

OBJECTIVE: To investigate the expression levels of interferon (IFN)-alpha, -beta, -omega and -gamma genes and proteins in the peripheral blood of patients with systemic lupus erythematosus (SLE), and to evaluate any possible connections between these expression levels with clinical features. METHODS: 144 SLE patients, 27 non-SLE patients with rheumatisms and 59 normal controls were recruited for the research, and all subjects were drawn blood to isolate plasma and elute total RNA. SYBR Green Dye based real-time quantitative PCR method was used to compare the expression levels of 4 IFNs in patients with SLE and those in the controls. The significance for the correlation of these expression levels and disease activity and specificity was studied. RESULTS: (1) mRNA expression levels of all 4 IFNs in SLE patients were remarkably lower than those observed in normal controls (P < 0.01 in all); IFN-alpha expression levels in SLE patients were increased than those observed in non-SLE group (P < 0.01). (2) The expression levels of all 4 IFNs in active SLE patients were similar to those observed in inactive SLE patients (P > 0.05 in all), and expression levels of all 4 IFNs in patients with SLE were not correlated with involvements of kidney, lung, brain, blood. (3) IFN score in SLE patients was remarkably lower than that observed in normal controls (P < 0.01). (4) The expression levels of all 4 IFNs in both SLE patients and normal controls were positively correlated with each other (P < 0.01 in all). (5) Protein levels of IFN-alpha, IFN-beta and IFN-omega in patients with SLE were similar to those observed in normal group (P > 0.05 in all), protein level of IFN-alpha in active SLE group was apparently elevated than in inactive SLE group (P < 0.01), and protein level of IFN-gamma has a trend to increase in SLE group than in normal group. CONCLUSIONS: Decreased expression levels of IFN-alpha, -beta, -omega and -gamma have implicated significance in the determination of SLE disease specificity, of which IFN-alpha is the best. Lower expression level of IFN score has also significance in the determination of SLE disease specificity. Higher protein level of IFN-alpha is helpful to judging SLE disease activity.