Correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value

Purpose To analyze the correlation between contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value. Methods In this study, 64 patients with axillary lymph node metastasis of primary breast cancer diagnosed and treated in our hospital from February 2011 to March 2013 were collected as an observation group, and 54 patients without axillary lymph node metastasis were collected as a control group. All patients underwent a contrast-enhanced ultrasound examination, and the correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis and its diagnostic value were analyzed. They were divided into two groups according to their survival conditions: the group with good efficacy and group with poor efficacy, and the prognostic factors of breast cancer in the two groups were analyzed. Results There were statistical differences in the peripheral acoustic halo, blood flow classification, ratio of length to diameter (L/D), maximum cortical thickness, and enhancement mode of lymph nodes between the two groups (p < 0.05). The area under ROC curve for diagnosis of axillary lymph node metastasis by contrast-enhanced ultrasound was 0.854, sensitivity was 83.33%, and specificity was 87.5%; L/D and enhancement mode were independent prognostic factors for breast cancer. Conclusions Contrast-enhanced ultrasound image features have diagnostic and prognostic value for axillary lymph node metastasis of breast cancer (AU)

Correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value.

PURPOSE: To analyze the correlation between contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value. METHODS: In this study, 64 patients with axillary lymph node metastasis of primary breast cancer diagnosed and treated in our hospital from February 2011 to March 2013 were collected as an observation group, and 54 patients without axillary lymph node metastasis were collected as a control group. All patients underwent a contrast-enhanced ultrasound examination, and the correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis and its diagnostic value were analyzed. They were divided into two groups according to their survival conditions: the group with good efficacy and group with poor efficacy, and the prognostic factors of breast cancer in the two groups were analyzed. RESULTS: There were statistical differences in the peripheral acoustic halo, blood flow classification, ratio of length to diameter (L/D), maximum cortical thickness, and enhancement mode of lymph nodes between the two groups (p < 0.05). The area under ROC curve for diagnosis of axillary lymph node metastasis by contrast-enhanced ultrasound was 0.854, sensitivity was 83.33%, and specificity was 87.5%; L/D and enhancement mode were independent prognostic factors for breast cancer. CONCLUSIONS: Contrast-enhanced ultrasound image features have diagnostic and prognostic value for axillary lymph node metastasis of breast cancer.

[Meta-analysis on safety and efficacy of dual antiplatelet therapy combining with proton pump inhibitors for patients after percutaneous coronary intervention].

Objective: To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI). Methods: The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI. Results: MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01). Conclusions: The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

[Study on the effect of activated carbon on formaldehyde in clean workshop].

Objective: To study the effect of activated carbon on the purification of formaldehyde in the clean workshop return air purification device and its influencing factors. Methods: From May to June 2018, choosed 4 different commercial activated carbons (bamboo charcoal, 1-3 mm, 3-5 mm; coconut shell charcoal, 6-12 mesh, 8-16 mesh) to make 5 types of activated carbon purification net. In the simulated clean plant laboratory, the detection of occupational disease hazards was used to test the purification effect of different types of activated carbon purification nets on formaldehyde. Results: The purification effect of different types of activated carbon increased with the prolongation of purification time, and the difference was statistically significant (P<0.05) . Compared with other types of activated carbon, coconut shell charcoal (8-16 mesh, double layer) had the best purification effect, 15 min and 30 min purification efficiency was 58.72% and 85.20% respectively, and the difference was statistically significant (P<0.05) . The purification effect of double-layer coconut shell charcoal was better than single layer (P<0.05) . The purification effect of double-layer coconut shell charcoal (8-16 mesh) was better than double-layer coconut shell charcoal (6-12 mesh) , the difference was statistically significant (P<0.05) . Coconut shell charcoal (8-16 mesh, double layer) had better purification effect than bamboo charcoal (P<0.05) . Conclusion: Different specific surface area, particle size, and thickness of activated carbon have a certain effect on the purification effect of formaldehyde, and its selection has a certain significance in improving the occupational health protection level in the clean plant, solving the safe use of return air and reducing energy consumption.

[Influential factors for failure of enhanced recovery after surgery from hepatectomy for hepatocellular carcinoma and the establishment of risk prediction model].

Objective: To investigate the influential factors for failure of enhanced recovery after surgery(ERAS) from hepatectomy for hepatocellular carcinoma(HCC) patients and then to establish a risk prediction model. Methods: The relevant clinical data of 180 patients with HCC undergoing hepatectomy at Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University from January 2016 to June 2017 were analyzed retrospectively.There were 149 male patients and 31 female patients aging of (56.5±11.0)years(from 33 to 84 years old). The factors affecting postoperative failure of ERAS of HCC patients were identified by univariate and multivariate analyses, and then, all the obtained factors and their statistical values were used to establish the risk prediction model. Results: A total of 23 patients failed in the ERAS protocol(12.8%). The preoperative total bilirubin (TBIL), alanine aminotransferase(ALT) and amount of intraoperative bleeding were independent risk factors for failure of ERAS from hepatectomy(all P<0.05). The obtained risk prediction model was presented as follows: risk coefficient(R)=0.114×(TBIL)+ 0.082×(ALT)+ 0.008×(amount of intraoperative bleeding). At the cut of value of R=7.90, the area under the ROC curve of this model for predicting failure of ERAS was 0.866(95%CI: 0.788-0.945, P<0.01), with the sensitivity and specificity of 69.6% and 91.1%, respectively.External validation results indicated that the scoring system had good differential ability(area under the ROC curve=0.889, 95%CI: 0.811-0.967, P<0.01). Conclusions: Higher level of preoperative TBIL(>21 µmol/L) and ALT(>50 U/L) and the larger amount of intraoperative bleeding (more than 400 ml) are independent risk factors for failure of ERAS inpatients undergoing hepatectomy for HCC and the established prediction model may have certain value for risk assessment.

Bio-informatics analysis of renal carcinoma gene matrix metalloproteinase-7.

BACKGROUND: Renal cancer is one of the common malignant tumors of the urinary system, seriously threatening human being's health. The current discoveries, however, are far enough for efficient and secure treatment of renal cancer. AIMS: The aim was to explore the mechanism of matrix metalloproteinase-7 (MMP-7) protein in renal carcinoma cell metastasis by bioinformatics analysis. MATERIALS AND METHODS: Bioinformatics methods were used to analyze the composition of amino acids, as well as transmembrane structure, coiled coils, subcellular localization, signal peptide, functions and structures at all levels. RESULTS AND CONCLUSIONS: It showed that the gene MMP-7 totally had 1131 bp. A peptide chain containing 267 amino acids was encoded in the coding region. Based on random coil, α helix, and further super-helix, it had formed a stable neutral hydrophilic protein. The subcellular location analysis indicated that the protein was located outside the cell. The mature peptide started from the 18th amino acid, and its front-end was the sequence of the signal peptide, belonging to the secreted protein. Analysis of the functional domain showed that this protein had two functional domains, the PG binding domain, and the zinc finger binding domain. Moreover, the protein, which was cross-linked with it, was also one related to cancer cell proliferation and metastasis. To sum up, MMP-7 is a stable neutral hydrophilic secreted protein, and it may play a vital role in the invasion and metastasis of cancer cells.

High preoparative levels of serum periostin are associated with poor prognosis in patients with hepatocellular carcinoma after hepatectomy.

AIMS: Periostin (POSTN) is implicated in cancer development and progression. The aim of this study was to evaluate the diagnostic and prognostic significance of serum POSTN in patients with hepatocellular carcinoma (HCC) receiving curative surgery. METHODS: Enzyme-linked immunosorbent assay was performed to determine serum POSTN levels in 69 healthy volunteers, 30 patients with hepatolithiasis, 27 patients with cirrhosis, and 56 HCC patients. The relationships between serum POSTN and clinicopathologic features were analyzed. Receiver operating characteristics analysis was used to calculate diagnostic accuracy of serum POSTN, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of serum POSTN on overall survival (OS) and relapse-free survival (RFS) was also investigated. RESULTS: The median serum POSTN level was significantly (P < 0.05) increased in HCC patients, compared to healthy controls, patients with hepatolithiasis, and patients with liver cirrhosis. Elevated serum POSTN was only significantly associated with Edmondson grade (P = 0.007). The combination of serum POSTN and AFP had a markedly higher area under the curve (0.805 (95% confidence interval [CI]: 0.677-0.932)) than POSTN (0.582 (95% CI: 0.427-0.736)) or AFP (0.655 (95% CI: 0.504-0.806)) alone. Kaplan-Meier analysis indicated that elevated serum POSTN was associated with OS (P = 0.031) and RFS (P = 0.027). Moreover, multivariate analysis revealed elevated serum POSTN as an independent poor prognostic marker for OS and RFS. CONCLUSIONS: Preoperative serum POSTN has limited diagnostic value in distinguishing HCC from non-malignant liver diseases, but serves as independent prognostic biomarker in HCC patients.

Development and validation of a high-performance liquid chromatography coupled with ultraviolet detection method for the determination of isocorydine in rat plasma and its application in pharmacokinetics.

A new HPLC-UV method has been developed, validated and applied for the determination of isocorydine (CAS 475-67-2) in rat plasma after oral or intravenous (i. v.) administration. Caffeine was used as the internal standard (IS). The analyte and IS were extracted from rat plasma by liquid-liquid extraction (LLE) with methyl tert-butyl ether and they were separated on an XTerra C18 column (250×4.6 mm, 5 µm, pH 1-12) with UV detection at 264 nm. The mobile phase consisted of methanol and 0.02 mol/L potassium dihydrogen phosphate-phosphoric acid buffer solution (pH 3.2) (30:70, v/v) at a flow rate of 1 mL/min for 8.5 min. The retention times of isocorydine and caffeine were approximately 6.5 and 5.1 min, respectively. The good linearity of the calibration curves was observed over the concentration range of 0.05-8 µg/mL (n=8, r 2≥0.9995). The lower limit of quantification (LLOQ) was 0.05 µg/mL [signal to noise ratio (S/N)≥10], and the limit of detection (LOD) was demonstrated as 0.01 µg/mL (S/N≥3). The mean extraction recovery ranged from 83.7% to 89.5% at 3 quality control (QC) concentrations. Intra-day and inter-day precision (relative standard deviation, RSD%) were within 4.7% and accuracy (relative error, RE%) ranged from -1.2% to 4.5%. The developed method was successfully applied to determination of the pharmacokinetic properties of isocorydine in rats after oral administration at a dose of 20 mg/kg and i. v. injection at 5 mg/kg.

Endoscopic ultrasound combined with submucosal saline injection for differentiation of T1a and T1b esophageal squamous cell carcinoma: a novel technique.

Endoscopic ultrasound (EUS) is the optimum method for investigation of early esophageal squamous cell carcinoma (ESCC). However, it is difficult to substage early ESCC as T1a or T1b. The aim of this study was to improve the staging accuracy of early ESCC by using EUS combined with submucosal saline injection (SSI). The study enrolled 15 patients with suspected early ESCC who were examined by EUS and subsequently by SSI combined with EUS. The patients then underwent endoscopic or surgical resection within 10 days. The accuracy of EUS staging (alone or following SSI) was evaluated and compared with the pathological results postoperatively. No severe complications of the SSI arose. EUS plus SSI easily distinguished the mucosa from the lesion and the submucosa because of the low-echoic saline-filled cushion in the submucosa. The accuracy of SSI combined with EUS for staging T1a or T1b was 86.7 %, which was better than that using EUS alone (60.0 %).

Deep brain stimulation.

Deep brain stimulation (DBS) has provided remarkable therapeutic benefits for people with a variety of neurological disorders. Despite the uncertainty of the precise mechanisms underlying its efficacy, DBS is clinically effective in improving motor function of essential tremor, Parkinson's disease and primary dystonia and in relieving obsessive-compulsive disorder. Recently, this surgical technique has continued to expand to other numerous neurological diseases with encouraging results. This review highlighted the current and potential future clinical applications of DBS.

Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 µ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

Effect of stenting on patients with chronic internal carotid artery occlusion.

AIM: Effects of carotid artery stenting (CAS) on patients with chronic internal carotid artery occlusion are unknown. METHODS: This study included 21 patients who underwent successful CAS treatment and 41 patients who received optimal medical therapy. Modified Rankin Scale (mRS) and cardiocerebral vascular events were compared between CAS and medical therapy group. RESULTS: The mRS in CAS group was lower than in control group during a 2-year follow up (P<0.05 or 0.01). The combined cerebrovascular events and mortality in study group was lower than in the control group (33.4% vs. 56.1%, P=0.045), but there was no statistically significant difference in the cerebrovascular event (28.6% vs. 46.3%, P=0.088) or mortality rate (4.8% vs. 9.8%, P=0.247) between the two groups. Cox regression analysis revealed that smoking (RR=3.189, 95% CI 1.020-9.968, P=0.046), diabetes (RR=2.717, 95% CI 1.113-6.631, P=0.028), and baseline National Institute of Health stroke scale (RR=2.984, 95% CI 1.049-8.485, P=0.040) were independent risk factors for major cerebrovascular events following CAS. CONCLUSION: CAS was superior to drug therapy in achieving better functional outcomes in patients with chronic internal carotid artery occlusion. However, CAS was not associated with a statistically significant reduction in cerebrovascular events or mortality. Larger and randomized clinical trials are required to ascertain the long-term benefits of CAS in patients with chronic internal carotid artery occlusion.

Determination of the plasma pharmacokinetic and tissue distributions of swertiamarin in rats by liquid chromatography with tandem mass spectrometry.

An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C18 column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH3COO] - →179 and m/z 415 [M + CH3COO] - →179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.

A meta-analysis of the prevalence of somatic mutations in the hMLH1 and hMSH2 genes in colorectal cancer.

AIM: The study aimed to understand better the somatic mutations in the human MutL Homolog 1 (hMLH1) and human MutS Homolog 2 (hMSH2) genes in colorectal cancer (CRC) and to investigate the differences derived from ethnicity, family history, detection method and microsatellite instability (MSI). METHOD: The terms 'hMSH2' or 'hMLH1' and 'colorectal cancer' 'colorectal carcinoma' or 'colorectal tumour' were searched in the PubMed, Springer, Lippincott, Williams & Wilkins and HighWire Press databases for the publication period December 1993 to September 2010. The Comprehensive Meta Analysis V2 software (Biostat Inc.) was used to explore the prevalence and 95% confidence intervals. RESULTS: The prevalence of somatic mutations in the hMLH1 and hMSH2 genes in CRC was 0.15 (95% CI 0.10-0.22) and 0.10 (95% CI 0.07-0.16), respectively. A higher prevalence of somatic mutations in hMSH2 was found in hereditary non-polyposis CRC than in sporadic CRC: 0.36 (95% CI 0.14-0.67) and 0.10 (95% CI 0.07-0.13) respectively. In addition, a higher prevalence of somatic mutations in the hMLH1 gene was observed relative to hMSH2 in the European group. The prevalence was higher in the high-level instability (MSI-H) group than in both the low-level instability (MSI-L) and the microsatellite stable (MSS) groups. CONCLUSION: Somatic mutations in the hMLH1 and hMSH2 genes play a vital role in CRC and a high prevalence was found in this meta-analysis. Furthermore, more studies are needed which focus on somatic mutations in the American population and in patients with MSI-L and MSS.

Expression of IGF-1R in colorectal polyps and its role in colorectal carcinogenesis.

Insulin-like Growth Factor Receptor 1 (IGF-1R) may play a role in the neoplastic progression of colorectal cancer because it is related to both cellular proliferation and differentiation. The aim of this study was to further elucidate the role of IGF-1R in colorectal carcinogenesis by evaluating IGF-1R expression in different types of precancerous colorectal polyps and comparing its expression to normal mucosa and colorectal carcinoma. A total of 47 colorectal polyps and their respective adjacent normal mucosa were collected from 32 patients. In addition, 20 colorectal adenocarcinoma tissues were obtained from patients undergoing colorectal resection, and 12 normal non-malignant colorectal mucosal tissues collected from outpatients served as the control group. The pit patterns of polyps were classified by the Kudo classification scheme through magnifying chromoendoscopy. Immunohistochemistry and quantitative real-time RT-PCR were utilized for expression analysis of IGF-1R in colorectal mucosa, polyps, and adenocarcinoma tissue. The results of immunohistochemistry showed no significant differences in IGF-1R expression in inflammatory polyps compared with their surrounding normal mucosa by the Mann-Whitney U test (p=0.251); however, tubular adenoma and villous adenoma tissues exhibited significantly higher levels of IGF-1R expression (p=0.000). The results of real-time RT-PCR showed that IGF-1R was transcribed at a high level in colorectal adenomatous polyps and adenocarcinoma compared with their respective paired normal mucosa. Spearman's rank correlation two-variable analysis was used to demonstrate a significant correlation between the expression of IGF-1R and neoplastic progression from normal mucosa to adenomatous polyps and finally to colorectal cancer (r=0.574, p=0.000). This study suggests that the expression of IGF-1R correlates with the degree of carcinogenesis. In addition, these results demonstrated that there is a significant correlation between the level of IGF-1R expression and pit patterns of polyps (r=0.432, p=0.002). Thus, IGF-1R might be a factor in the morphological change of colorectal mucosal crypts, and it may play an important role in the growth and malignant transformation of precancerous polyps. These results suggest that IGF-1R can be considered a biomarker for the stage and risk of carcinogenesis during neoplastic initiation and progression along the colorectal normal mucosa-polyp-cancer sequence. Inhibitors of IGF-1R are not only a promising targeted anticancer strategy, but also a possible option for the chemoprevention of colorectal cancer.

Combined inhibitory effects of celecoxib and fluvastatin on the growth of human hepatocellular carcinoma xenografts in nude mice.

This study was designed to investigate the in vivo growth inhibitory effects of celecoxib, a cyclo-oxygenase-2 inhibitor, and fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the hepatocellular carcinoma (HCC) cell line, BEL-7402. Athymic nude mice implanted with BEL-7402 cells were given celecoxib and fluvastatin, either alone or in combination, and the effect of treatment on tumour growth was evaluated after 6 weeks. The combination of celecoxib and fluvastatin enhanced inhibition of tumour growth, induction of apoptosis, inhibition of tumour cell proliferation, and inhibition of tumour angiogenesis compared with either treatment alone. The combination of celecoxib and fluvastatin also increased levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), decreased levels of p-Akt, myeloid cell leukaemia-1 (Mcl-1) and survivin protein, but had no effect on Akt protein levels in tumours. These results suggest that celecoxib combined with fluvastatin would be more efficacious for the treatment of HCC than either treatment alone and this combination of therapy warrants further research.

Predictive factors for in-stent restenosis after balloon-mounted stent placement for symptomatic intracranial atherosclerosis.

OBJECTIVES: We sought to evaluate whether clinical, lesion-related and procedural factors may predict in-stent restenosis (ISR) after intracranial stenting. METHODS: Sixty-one Chinese patients with 65 lesions treated with single bare metal balloon-mounted stent for symptomatic intracranial arterial stenosis underwent conventional angiographic follow-up after procedures between March 2004 and July 2009. Clinical, lesion-related and procedural factors were analysed for any predictive power for the ISR using univariate and multivariate analysis. ISR was defined as >50% stenosis within or at the edge of the stent or absolute luminal loss >20%. RESULTS: ISR was found in 18 patients (18/61, 29.5%) with 20 lesions (20/65, 30.8%) at a median follow-up of 7 months (range, 5-30 months). Univariate analysis revealed that diabetes, Mori classification, lesion length and stent diameter were associated with ISR. In addition, diabetes (hazard ratio (HR), 2.661; 95% confidence interval (CI), 1.044-6.787; P=0.040) and lesion length (HR, 1.206; 95% CI, 1.023-1.421; P=0.026) were detected as two independent predictors for ISR by stepwise multivariate Cox regression analysis. CONCLUSIONS: ISR after intracranial stenting with bare metal balloon-mounted stents in our series seems to be more frequent than those reported by the majority of the published case series. Diabetes and lesion length are associated with increased risk of ISR.

A role for trichosanthin in the expansion of CD4CD25 regulatory T cells.

CD4(+)CD25(+) regulatory T cells (Tregs) are critical for the peripheral immune tolerance. Understanding the signals for the generation of Tregs is important for the clinical immunotherapy, but only limited progress has been made on obtaining enough peripheral Tregs. The aim of this study was to evaluate the role of trichosanthin (Tk) extracted from Chinese medicinal herb Trichosanthes kirilowi on the function of Tregs in vitro and in vivo. We reported here that Tk is needed for the expansion of freshly isolated CD4(+)CD25(+)Tregs (nTregs) into Tk-expanded CD4(+)CD25(+)Tregs (Tk-Tregs) through up-regulating CD25 and Foxp3 expression. The dose-response analyses indicated that 100 ng/ml Tk was the most appropriate dose. The result of real-time PCR showed that Tk-Tregs expressed 1.5-fold higher levels of Foxp3 than those observed in nTregs. Tk-Tregs markedly suppressed activation of effector T cells at a suppressor/responder ratio of 1:1, 1:2, 1:4, 1:8 or 1:16, and their effect was dose dependent. Moreover, Tk-Tregs secreted more immunosuppressive cytokines interleukin (IL)-10 and transforming growth factor (TGF)-beta1 after stimulating with antigen and antigen-presenting cells (APC). Transwell experiments showed that not only cell-to-cell contact but also soluble cytokines were involved in suppressive mechanism of Tk-Tregs. And Tk-Tregs were more efficient in suppressing CD25(-)T cell response to specific antigen than to irrelative antigen. Most importantly, it was revealed for the first time that Tk-Tregs could prolong the survival duration of mice with acute graft-versus-host disease (aGVHD). In conclusion, the study suggests a possible therapeutic potential of Tk-Tregs for clinical treatment on aGVHD.

Effects of renin-angiotensin system blockade on islet function in diabetic rats.

AIMS: To investigate the effects of renin-angiotensin system (RAS) blockade on islet structure and function in diabetic rats, and its mechanisms. METHODS: Diabetic rat models were created by high-fat high-caloric laboratory chow plus small dose (30 mg/kg) streptozotocin ip injection. After 8-week intervention with perindopril (AE, no.=10) or valsartan (AR, no.=10), all the animals' islet function was evaluated by iv glucose tolerance test. Pancreases were stained by immunohistochemistry technique to qualitative and/or quantitative analysis the content of insulin, inducible nitric oxide synthase (iNOS), transforming growth factors-beta1 (TGF-beta1) in islets. The apoptosis of islet cells was detected by transferase-mediated dUTP nick-end labeling dUTP nick end labeling (TUNEL). The expression level of angiotensinogen (AGT) and insulin mRNA in islets were detected by RT-PCR. RESULTS: Compared with normal control group (NC, no.=10), area under the curve of insulin from 0 to 10 min (AUCI0-10) of diabetes group (DM, no.=8) was decreased by 66.9%, the relative expression of local AGT was increased by 69.2%, the insulin relative concentration (IRC) of beta-cell and the expression of insulin mRNA were decreased significantly, the amount of apoptotic cells in unit islet area was increased by 2.1 times, the relative content of iNOS and TGF-beta1 positive cell relative volume (TRV) was increased by 23.0% and 2.52 times, respectively (all p<0.01). Compared with DM group, AUCI0-10 of AE and AR group was increased by 41.4% and 33.2%, respectively; the relative expression of local AGT was decreased by 21.4% and 23.4%, respectively; IRC and the expression of insulin mRNA were increased significantly; the amount of apoptotic islet cells was decreased by 79.0% and 36.2%, respectively; the relative content of iNOS was decreased by 16.5% and 18.9%, respectively; TRV was decreased by 43.8% and 35.6%, respectively (all p<0.01). There were no significant differences between group AE and AR. CONCLUSION: Blockade of RAS may improve diabetic rats islet function via the amelioration of intra-islets oxidative stress, fibrosis and apoptosis.