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Objective. This study was intended to evaluate the efficacy and safety of ligustrazine injection for chronic pulmonary heart disease (CPHD). Method. Randomized controlled trials (RCTs) of clinical therapeutic studies on CPHD when using ligustrazine injection were included. Searches were applied to the following electronic databases: the PubMed, the Cochrane Library, EMBASE, CBM, and AMED. No language restriction was used. All trials included were analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.0 software was used for data analysis. Result. 34 RCTs with low methodological quality were included. Compared to conventional medicine treatment alone, ligustrazine injection plus conventional medicine treatment showed improvement in New York Heart Association classification of clinical status (Odds ratio 0.22; 95% CI 0.17 to 0.28) and depression of pulmonary artery hypertension (weighted mean difference −4.77; 95% CI −5.85 to −3.68). Three studies had reported adverse events. No serious adverse effects were reported. Conclusion. While there is some evidence that suggests potential effectiveness of ligustrazine injection for CPHD, the results were limited by the methodological flaws of the studies. High quality studies are needed to provide clear evidence for the future use of ligustrazine injection.

Chronic obstructive pulmonary disease (COPD) is a serious disease constituting a major threat to public health. Current popularity of traditional Chinese medicine (TCM) in treating COPD implies its potential advantage in improving symptoms, reducing the frequency of acute exacerbation and improving the patients' quality of life. This study is to evaluate the efficacy and safety of a comprehensive intervention, Bufei Yishen Granule combined with acupoint-sticking therapy, in patients with stable COPD.A multicenter, double-blind, double-dummy and randomized controlled design will be adopted. A total of 244 cases meeting the inclusion criteria will be enrolled into this study with 122 cases in the trial group and 122 in the control group, respectively. Patients in the trial group will receive Bufei Yishen Granule combined with acupoint-sticking therapy and dummy sustained-release theophylline, while patients in the control group will receive sustained-release theophylline and dummy Bufei Yishen Granule combined with dummy acupoint-sticking therapy. The frequency and duration of acute exacerbation, lung function, clinical symptoms, six-minute walking distance, dyspnea grade and quality of life will be observed during a four-month treatment period and a further six-month follow-up.It is hypothesized that Bufei Yishen Granule combined with acupoint-sticking therapy will have beneficial effects in reducing the frequency and duration of acute exacerbation, ameliorating the symptoms, and improving the quality of life of patients with stable COPD. The results of this study will provide evidence for developing a TCM-based regimen for patients with COPD.ChiCTR-TRC-11001409.

To evaluate the efficacy of Bufei Yishen Granule BFYSG) combined with Shufei Tie acupoint sticking therapy on quality of life of patients with stable chronic obstructive pulmonary disease (COPD).A multi-center, double-blinded, double-dummy and randomized controlled method was adopted in this trial. A total of 244 patients were randomly assigned to a trial group and a control group according to the random number, each with 122 patients; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent form. In the trial group, patients were treated with BFYSG combined with "Shufei Tie" acupoint sticking therapy and sustained-release theophylline dummy, and in the control group patients were treated with oral sustained-release theophylline and BFYSG dummy combined with "Shufei Tie" acupoint sticking therapy dummy. The therapeutic course for two groups was 4 months and the follow-up was 6 months. The frequency and duration of acute exacerbation calculated by adding up each frequency and duration of acute exacerbation in treatment and follow-up time respectively, the quality of life measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and adult COPD quality of life (COPD-QOL) scale were observed.Among the 244 enrolled patients, 234 were screened for full analysis set (FAS); 221 were screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month follow-up there were differences between the trial group and the control group in frequency of acute exacerbation (FAS: P=0.013; PPS: P=0.046); duration of acute exacerbation (FAS: P=0.005; PPS: P=0.006); scores of physiological, psychological and environment aspects of the WHOQOL-BREF questionnaire (FAS: P=0.002, P=0.006, P=0.000; PPS: P=0.00, P=0.001, P=0.000); scores of daily living ability, social activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS: P=0.000, P=0.000, P=0.006; PPS: P=0.002, P=0.001, P=0.001).BFYSG combined with acupoint sticking therapy could improve the quality of life of patients with stable COPD.

Chronic obstructive pulmonary disease (COPD) remains a severe public health problem. Acute exacerbation of COPD (AECOPD) is a major factor that influences the process of COPD. Strengthening the treatment of AECOPD is very essential. AECOPD risk window (AECOPD-RW) refers to the period from AECOPD remission to the time before the stable phase. The condition is very unstable. Symptoms are relieved but continually exist. The lung function has not restored to the levels of the stable phase. The inflammatory reactions continually exist. In this period patients are most liable to suffer from AECOPD, resulting in higher hospital admission rate and higher mortality. Dispelling pathogens should be taken as the main principle for AECOPD treatment. However, when it transforms from AECOPD to AECOPD-RW, strengthening the body resistance should be taken as the main principle. The proposal of AECOPD-RW has provided new thoughts and strategies for COPD. In this period deficiency syndrome dominates, most being lingering pathogens due to deficient vital qi. Qi deficiency and qi-yin deficiency are the most common syndromes, involving Fei, Pi, and Shen. Deficiency of both Fei and Shen dominates, complicated with phlegm and stasis. Therefore, the treatment principle of AECOPD-RW should focus on tonifying the deficiency and strengthening the body resistance, assisted with dissipating phlegm and activating blood circulation.

To investigate the common syndromes, clinical symptoms and characteristics of chronic obstructive pulmonary disease at acute exacerbation stage (AECOPD).Delphi method was used to organize the AECOPD expert questionnaire. This questionnaire was distributed to 30 selected experts of respiratory diseases. The resulting data were statistically analyzed by Chi-square test and statistical description such as mean, coefficient of variation and ratio of full marks. Common syndrome: mean≥3.00, coefficient of variation30% and ratio of full marks≥10% and common clinical symptoms: for major symptoms present, the index mean≥4.00 and coefficient of variation30% and for minor symptom, index mean≥3.00 and coefficient of variation30% were used as criteria.Twenty-nine valid expert questionnaires were received. The coefficient of positivity was 96.67%, of authority was 0.835 and of coordination equals 0.359 (χ(2)=463.15, P=0.001). The mean, coefficient of variation and ratio of full marks for AECOPD syndrome of wind and cold invasion of lung were 4.12, 21.50%, and 34.48%, respectively. Those for syndrome of exogenous cold-evil and fluid-retention were 4.39, 14.32%, 48.28%; those for syndrome of wind and heat invasion of lung were 3.54, 30.77%, 6.90%;those for syndrome of phlegm-heat obstruction of the lung were 4.85, 9.23%, 89.66%; those for syndrome of pulmonary stagnation of phlegm were 4.36, 15.57%, 48.28%; those for syndrome of external cold and internal heat were 4.59, 16.27%, 65.52%; those for syndrome of retention of phlegm and blood stasis in the lung were 4.54, 12.70%, 55.17%; those for syndrome of qi deficiency of the lung and spleen were 3.25, 27.30%, 13.79%; those for syndrome of qi deficiency of the lung and kidney were 3.32, 27.24%, 13.79%; those for syndrome of qi-yin deficiency of the lung and kidney were 3.29, 28.98%, 24.14%; those for syndrome of yin deficiency of the lung and kidney were 2.98, 32.71%, 3.45%; those for syndrome of blood stasis were 4.67, 10.29%, 62.07% and those for syndrome of fu shi were 3.07, 30.01%, 6.90%, all respectively. The blood stasis and fu shi were accompanying syndromes.Seven common syndromes of AECOPD are wind and cold invasion of lung, exogenous cold-evil and fluid-retention, phlegm-heat obstruction in the lung, pulmonary stagnation of phlegm qi deficiency of the lung and spleen, qi deficiency of the lung and kidney, as well as qi-yin deficiency of the lung and kidney. One additional syndrome that accompanies many of the afore-mentioned syndromes was blood stasis.

To explore the influence of recombination granulocyte colony stimulating factor (rG-CSF) on mobilization and distribution of bone marrow stem cells (BMSCs) in blood and brain tissue, and its role in protecting brain in rats with cerebral ischemia.One hundred and six Sprague-Dawley (SD) rats were divided into sham-operated group (n=10),model group (n=48), rG-CSF group (n=48) according to the method of random digital table, and rats in model and rG-CSF groups were divided into four subgroups: i.e. 2, 3, 7 and 14 days subgroups, with 12 rats in each subgroup. Middle cerebral artery occlusion (MCAO) model was reproduced with nylon thread. In rats of rG-CSF group rG-CSF (10 μg/kg) was administered by subcutaneous injection 3 days before and 2 days after operation respectively, once a day. Rats in sham-operated and model groups were administered with normal saline in the same volume, once a day. At the corresponding time after operation, general neural function score (GNFS) of rats was measured. Blood was collected through abdominal aorta, then white blood cell (WBC) and CD34+ cells in peripheral blood were counted. Brain pathologic changes were observed, and expression of CD34+ cells in rats brain tissue was determined by using immunohistochemical method.(1) GNFS was lower obviously in 2-day model group compared with that in sham-operated group, and then increased gradually. At 7 days and 14 days after operation, GNFS in rG-CSF group was higher significantly than that in model group (7 days: 11.86±0.69 vs. 10.53±0.76, 14 days: 13.38±0.52 vs. 12.38±0.52, both P0.01). (2) WBC and CD34+ cells in peripheral blood in model group increased obviously, with the highest level appeared at 3 days and lowered at 7 days and 14 days. Increase of WBC and CD34+ cells in rats of rG-CSF group was more obvious than that of model group at each time point except CD34+ in 14 days group [WBC (×10(9)/L) 2 days: 11.75±1.76 vs. 8.07±1.27, 3 days: 13.07±1.70 vs. 10.88±1.78, 7 days: 8.63±1.36 vs. 5.58±1.57, 14 days: 6.98±0.98 vs. 4.87±0.92; CD34+ (cells/μl) 2 days: 8.83±2.14 vs. 3.17±0.75, 3 days: 13.50±1.87 vs. 5.00±1.55, 7 days: 5.33±1.21 vs. 2.33±1.21, P0.05 or P0.01]. (3) Expression of CD34+ cells in the brain of rats in 2-day model group increased significantly, and the highest level appeared at 7 days and decreased at 14 days. Absorbance (A) value of CD34+ cells expression in rat brains of each rG-CSF group was more significant than that in model group (2 days: 43.21±4.41 vs. 22.04±2.95, 3 days: 45.79±1.76 vs. 25.69±2.44, 7 days: 52.09±2.86 vs. 33.04±2.62, 14 days: 29.73±1.99 vs. 16.91±2.95, all P0.01). (4) The signs of injury to brain in pathological examination were less obvious in 14 days rG-CSF group.BMSCs could be induced to enter peripheral blood and "home" to brain tissue after cerebral ischemia. It was showed that BMSCs increased in number at first and then decreased in peripheral blood and brain, the peak number was found on 3rd day in peripheral blood and 7th day in brain. Mobilization with rG-CSF could increase the number of BMSCs in peripheral blood and brain tissue. The effect of mobilization of BMSCs on protecting brain was significant after cerebral ischemia, and effect appeared to be more pronounced with prolongation of mobilization.

Osteopontin (OPN) has been implicated in tumor development and progression for several years. However, the prognostic value of OPN overexpression in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to assess the relationship between OPN overexpression and clinical outcome of HCC. A meta-analysis of seven studies (1,158 patients) was carried out to evaluate the association between OPN and overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between OPN and tumor vascular invasion or other invasion-related parameters was also assessed. Data were synthesized with random effect model of DerSimonian and Laird, hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that high OPN expression predicted poor OS (HR: 1.37, 95% CI: 1.21–1.55) and DFS (HR: 1.62, 95% CI: 1.24-2.11) of HCC. OPN overexpression tended to be associated with the presence of tumor vascular invasion (OR: 1.93, 95% CI: 0.97–3.84) and advanced tumor grade (OR: 1.74, 95% CI: 0.95–3.18). By this study, we conclude that OPN overexpression indicates a poor prognosis for patients with HCC, it may also have predictive potential for HCC invasion and metastasis.

To develop and validate a clinical rule to predict treatment failure in middle-aged and elderly patients suffering from community-acquired pneumonia (CAP) in China, and to compare it with other prognostic rules.Data of 58 variables affiliated to 6 aspects, including demographics, underlaying diseases, previous status, complications, symptoms, signs and laboratory examination results from the CAP patients aged≥45 years admitted to the respiratory departments in three university affiliated hospitals between December 17, 2006 and December 22, 2008 were enrolled prospectively and then validated in two groups to create a derivation cohort with 75% of the patients for rule development and an internal validation cohort with the other 25% for internal test. An external validation cohort was formed at the same time with patients admitted to the other university affiliated hospital for external test. The single outcome was treatment failure at the time of 14 days after admitted or at discharge from hospital. Univariate analysis, multivariate analysis and receiver operating characteristics (ROC) curve were used for the rule establishment, assessment and comparison among the pneumonia severity index (PSI), CURB65 [confusion, blood urea nitrogen6.8 mmol/L, respiratory rate (RR)≥30 breaths per minute, systolic blood pressure (SBP)90 mm Hg (1 mm Hg=0.133 kPa) or diastolic blood pressure (DBP)≤60 mm Hg, age≥65 years] and CRB65 (confusion, RR≥30 breaths per minute, SBP90 mm Hg or DBP ≤60 mm Hg, age≥65 years).The data of a total of 539 patients in three hospitals were enrolled for analysis. Of those, 400 and 139 patients were randomly allocated into the derivation cohort or internal validation cohort respectively. Meanwhile, 159 patients were enrolled in the external validation cohort. Analyzing the data from 400 patients in the derivation cohort, 33 variables of 6 aspects had significant difference between cure and treatment failure outcome in the univariate analysis. Then, in the multivariate analyses, five independent predictive factors showed significant difference, including confusion (C), creatinine60 μmol/L, electrolyte disturbances (E), respiratory failure (R), white blood cell (WBC)7.5×10(9)/L. A clinical prediction rule CCERW based on these variables showed that the treatment failure outcome increased directly with increasing scores: 5.5%-9.1%, 12.8%-20.0% and 31.0%-40.5% for scores of 0-1, 2 and 3-6, respectively. ROC curve analysis yielded an area under the curve (AUC) for CCERW of 0.709 [95% confidence intervals (95%CI) 0.638-0.780], 0.725 (95%CI 0.613-0.838) and 0.686 (95%CI 0.590-0.782) in the derivation, internal and external validation cohorts respectively; and in the same manner, of 0.710 (95%CI 0.659-0.761) for total 698 patients, which was better than PSI, CURB65 and CRB65, at 0.667 (95%CI 0.614-0.719), 0.648 (95%CI 0.592-0.705), and 0.584 (95%CI 0.530-0.638), respectively.CCERW can help physicians to distinguish high and low risk leading to treatment failure in middle-aged and elder patients with CAP, and has better predictable capability than PSI, CURB65 and CRB65. We prudent recommend the simple rule can be used in the middle-aged and elder patients with CAP of Han race people in China.

To investigate the expression and its clinical significance of estrogen receptor (ERα) and phosphorylated estrogen receptor (p-ERα) in patients with hepatocellular carcinoma. The associations between ERα, p-ERα and IL-6 were also analyzed.Immunohistochemistry was used to detect the expression of ERα, p-ERα and IL-6 in tumor tissues from 77 cases with hepatocellular carcinoma. The relations between ERα and the clinical pathological parameters and prognosis were also analyzed.The positive rates of ERα, p-ERα and IL-6 in hepatocellular carcinoma were 39.0% (30/77), 45.4% (35/77) and 72.7% (56/77), respectively. The expression of ERα and p-ERα were negatively correlated with the expression of IL-6 (r=-0.468, P0.01; r=-0.370, P0.01, respectively). The positive rate of ERα in patients with tumor size≤5 cm, serum level of alpha-fetoprotein400 µg/L, with complete encapsulation and non-microvascular invasion was significantly higher than those with tumor size5 cm, serum level of alpha-fetoprotein≥400 µg/L, non-complete encapsulation and with microvascular invasion (all P0.05). The overall survival rates of ERα-positive and ERα-negative patients were 66.7% and 23.4% (P0.05). And the disease-free survival rates of ERα-positive and ERα-negative patients were 83.3% and 57.4% (P0.05).The tumor biological features of ERα-positive patients are better than that of ERα-negative patients. The role of ERα in hepatocellular carcinoma may be related to IL-6 level.

To evaluate effects of celecoxib (a selective cox-2 inhibitor)combined with fluvastatin (a HMG-CoA reductase inhibitor) on tumor growth and cell apoptosis in hepatocellular carcinoma xenograft in nude mice.Hepatocellular carcinoma BEL-7402 cells were inoculated subcutaneously into the left armpit of nude mice, the mice (n = 32) were then randomly divided into 4 groups: the control group, the celecoxib group,the fluvastatin group and the combination group. At the end of the study, Tumor Tissues were collected for analysis. Cell apoptosis was determined by flow cytometry analysis and TUNEL assay. Akt, p-Akt and survivin protein levels were measured by Western blot. Statistical comparisons were made using factorial analysis of variance (ANOVA) and multiple comparisons between each two groups were calculated using SNK-q test.The combination of Celecoxib and fluvastatin resulted in a greater inhibition of tumor growth than either agent alone, the tumor inhibitory rate was 34.0% in the Celecoxib group, 25.0% in the fluvastatin group and 72.2% in the combination group. The percentages of TUNEL--positive cancer cells in the celecoxib and fluvastatin alone treatment groups were 8.5%+/-1.4% and 9.4%+/-1.7% respectively as compared to the control group which was 3.5%+/-0.8%. Combination therapy showed a significantly greater increase in tumor cell apoptosis in comparison with the control and single-therapy groups (apoptotic index: 19.4%+/-3.0%; P value is less than 0.01 versus celecoxib or fluvastatin groups). The results of flow cytometry analysis also showed the same tendency. a small number of apoptotic cells were detected in the control tumours (4.1%+/-1.6%), whereas a large number of apoptotic cells were detected in tumours treated with celecoxib (9.1%+/-2.1%) or fluvastatin (10.1%+/-2.3%) alone; and the combination therapy resulted in even more apoptotic cells (23.6%+/-5.8%; P value is less than 0.01 versus celecoxib or fluvastatin groups). Western blot analysis demonstrated that the combination of celecoxib and fluvastatin significantly down-regulated p-Akt (0.23+/-0.08 versus 1.12+/-0.07 and surviving (0.50+/-0.07 versus 1.47+/-0.19) in BEL-7402 tumours compared with the control (P value is less than 0.01 for all).The present study provided evidence that treatment with celecoxib in combination with fluvastatin resulted in the inhibition of HCC tumour growth in an in vivo mouse model.

Extracellular matrix protein 1 (ECM1) is a glycoprotein involved in a number of biologic processes. To investigate the expression of ECM1 in hepatocellular carcinoma (HCC) and determine its correlation with tumor progression and prognosis, the expression levels of ECM1 in three HCC and one normal liver cell lines, tumor, and corresponding adjacent tissues from 18 HCC patients were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Immunohistochemistry assay was used to determine the expression of ECM1 in HCC and corresponding paracarcinomatous tissues from 77 patients. The results of Western blotting were consistent with the results from RT-PCR analysis of ECM1 mRNA expression. Among the four cell lines, the expression level in HCCLM3, which with the highest metastatic potential, was significantly higher than that with lower (P < 0.05); while ECM1 expression was not detected in normal liver cell line. Expression level of ECM1 was significantly increased in HCC compared with adjacent and normal liver tissues (P < 0.05). Immunohistochemically, the expression of ECM1 in HCC was judged to be positive in 57 (74.0%) cases, significantly higher than that in corresponding paracarcinomatous tissues (P < 0.01), and it was associated with tumor size (P = 0.036), number of tumor nodules (P = 0.048), TNM stage (P = 0.029), and vascular invasion (P = 0.007). In particular, the expression of ECM1 was found to be an independent factor for predicting overall and disease-free survival of HCC. The expression level of ECM1 was associated with metastatic potential of HCC, and its abnormal expression may be used as a predictive factor of unfavorable prognosis and recurrence for HCC after surgery.

To elucidate the mechanism of angiogenesis after cerebral ischemia/reperfusion (I/R) in the aged rats by observing the changes in expressions of basic fibroblast growth factor (bFGF) and transformation growth factor-β1 (TGF-β1).Young Sprague-Dawley (SD) rats were classified into groups by random digits table, and aged SD rats were stratified by different body weight. Rats were randomly divided into groups of sham operation, ischemia (I) 3 hours, I/R 1, 3, 6, 12 days, with 6 rats in each group. Focal cerebral I/R model was reproduced by intraluminal filament technique. Microvessel density (MVD) of brain tissue, sum area of lumens were observed, and the expressions of bFGF protein, TGF-β1 protein and TGF-β1 mRNA were assessed with immunohistochemistry and hybridization in situ.MVD in young model group began to increase at I 3 hours, peaking at I/R 6 days, maintained up to I/R 12 days. MVD in aged model group began to descend at I 3 hours and continued to I/R 12 days. Sum area of lumens in young model group increased markedly at I/R 1 day, gradually lowered at I/R 1-6 days, and increased obviously again at I/R 12 days. Sum area of lumens in aged model group reached peak at I/R 1 day, gradually decreased subsequently. MVD in aged sham operation group were higher than that in young sham operation group (6.88±1.60 vs. 5.50±1.53, P0.01). MVD and sum area of lumens in aged model group at I/R 1, 3, 6, 12 days were lower than young model group. Expressions of bFGF protein, TGF-β1 protein in young and aged model group were both gradually up-regulated, all of them reaching peak at I/R 3 days, and lowered gradually at I/R 3-12 days subsequently. Expressions of bFGF protein (grey level) in both aged sham operation group and those of model group at I 3 hours, I/R 1, 3, 12 days were lower than those of young sham operation and those of the model group at the same time points (176.80±5.10 vs. 172.82±1.53, 171.81±2.43 vs. 167.85±2.41, 167.99±5.51 vs. 164.90±2.15, 152.98±4.11 vs. 150.75±1.11, 165.67±3.55 vs. 161.73±1.29, P0.05 or P0.01). Expressions of TGF-β1 protein (grey level) in both aged sham operation and those of model group at I 3 hours, I/R 1, 3, 6, 12 days were all lower than those of young sham operation and those of model group at the same time points (182.69±3.12 vs. 176.13±4.08, 176.89±2.30 vs. 170.56±7.47, 171.74±2.70 vs. 165.43±2.91, 157.17±5.20 vs. 150.43±4.28, 161.72±4.81 vs. 155.37±2.92, 167.69±2.18 vs. 160.28±3.59, all P0.01). TGF-β1 mRNA expressions in both young model group and aged model group reached peak at I/R 1 day, gradually lowered subsequently. Expressions of TGF-β1 mRNA (gray level) in both aged sham operation and those of model group at I 3 hours, I/R 3, 6, 12 days were lower than those of young sham operation and also model group at the same time points (176.51±9.52 vs. 169.09±5.08, 176.75±5.74 vs. 165.36±4.78, 177.33±5.68 vs. 165.25±8.14, 178.46±4.91 vs. 170.51±4.29, 203.95±4.51 vs. 181.98±5.59, all P0.01).Angiogenesis is obviously weak after cerebral I/R in the aged, and the mechanism of which might be related to the down-regulation of expressions of bFGF protein, TGF-β1 protein and TGF-β1 mRNA. Aging factor may be one of the main reasons which induce the down regulation of expressions mentioned above.

To observe the effects of S-adenosylmethionine (SAM) on cell proliferation, cell cycles, apoptosis and invasive capacity of gastric cancer cell lines SGC-7901 and BGC-823 and detect the methylation status and expression of c-myc and urokinase-type plasminogen activator (uPA).The effect of SAM on proliferation of SGC-7901 and BGC-823 cells were determined by MTT assay. SGC-7901 and BGC-823 cells were treated with different concentrations of SAM (0, 2, 4 mmol/L) for 72 h. Then flow cytometry was used to detect the change of cell cycles and apoptosis; Transwell assay to detect the invasion; RT-PCR and Western blot to detect the expression of c-myc and uPA; and MSP to detect the methylation of c-myc and uPA.SAM displayed a growth-inhibiting effect on SGC-7901 and BGC-823 cells in a dose- and time-dependent manner after exposure to SAM at different concentrations (0.5 - 32 mmol/L) for 24, 48 and 72 h, cell proliferation were significantly restrained (all P0.05); 72 h IC50 SGC-7901 5.40 mmol/L and BGC-823 4.01 mmol/L. After treating SGC-7901 and BGC-823 with different concentrations of SAM, the cell percentages of G0/G1 phase significantly increased (P0.05 and P0.01) while the cell proliferation indices significantly decreased (P0.05 and P0.01). Compared with control group (0.33 +/- 0.09), the cell apoptosis of 2 mmol/L (5.79 +/- 0.75) and 4 mmol/L groups (10.19 +/- 0.60) of SGC-7901 were obviously reduced (all P0.01). Compared with control group (0.95 +/- 0.19), the cell apoptosis of 2 mmol/L (6.23 +/- 0.75) and 4 mmol/L groups (11.82 +/- 1.14) of BGC-823 were obviously reduced (all P0.01). The cell invasive capacity were significantly restrained (P0.01). The invasion inhibition ratio of 2 mmol/L and 4 mmol/L groups of SGC-7901 were 51.07% and 80.69% respectively. The invasion inhibition ratio of 2 mmol/L and 4 mmol/L groups of BGC-823 were 48.57% and 84.10% respectively. The expressions of c-myc and uPA significantly decreased (P0.05 and P0.01). There was no expression of c-myc in 2 mmol/L group of BGC-823. The methylation of c-myc and uPA genes in two cell lines were reversed after SAM treatment.SAM can induce the apoptosis of SGC-7901 and BGC-823, block the cell cycles at G0/G1 phase and suppress the proliferation and invasion of these two cell lines. SAM can reverse the methylation of c-myc and uPA in these two cell lines and reduce their expression. SAM may act as a methyl donor to restrain the development and progression of tumor when hypomethylation is widely present in cancer.

Background : To investigate the feasibility of detecting methylated tissue factor pathway inhibitor (TFPI2) and quantifying human long DNA with fluorescent quantitative Alu PCR in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC). Materials and Methods : Methylation-specific PCR (MSP) was performed to analyze TFPI2 gene promoter methylation status in a blinded fashion in stool samples taken from 30 endoscopically diagnosed healthy controls, 20 patients with adenomas, and 60 patients with colorectal cancer. Real-time Alu PCR was used to quantify human long DNA. Results : The specificity of fecal TFPI2 MSP assay and long DNA assay was 100% and 83.3%, respectively. The sensitivity of fecal TFPI2 MSP assay and long DNA assay was 68.3% and 53.3%, respectively. The sensitivity of fecal DNA assay (either marker being positive) was 86.7%, which was high for CRC. Conclusions : Our results have demonstrated the feasibility of using TFPI2 methylation and quantify human long DNA with fluorescent quantitative Alu PCR in fecal samples as a new noninvasive test for CRC.

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 p21Waf1/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.

Vasculogenic mimicry (VM), including tubular VM and patterned matrix VM, has been generally recognized as a new pattern of tumor neovascularization. Pilot studies of tubular VM showed that it was present in hepatocellular carcinoma (HCC) and associated with poor clinical prognosis. However, whether patterned matrix VM is clinically significant in HCC is unknown. To elucidate the effects of patterned matrix VM on prognosis of HCC and the mechanisms involved in VM formation, we examined 151 cases of surgically resected human HCC by immunohistochemistry and transmission electron microscopy and conducted hypoxic experiments on human HCC cell line MHCC97-H. We observed 31 of 151 (20.5%) cases exhibited evidence of patterned matrix VM. The expression of patterned matrix VM was associated with larger tumors (P = 0.042), vascular invasion (P = 0.016), high-grade HCC (P = 0.022), and late-stage HCC (P = 0.013). Kaplan–Meier survival analysis revealed that cases of the VM group had lower overall survival (OS) rate (P < 0.001) and disease-free survival (DFS) rate (P = 0.002) than that of the non-VM group. Univariate and multivariate analysis indicated that the presence of patterned matrix VM was independent adverse prognostic factor for both OS (P = 0.004) and DFS (P = 0.011). Expression of hypoxia-inducible factor 1 alpha (HIF-1alpha), matrix metalloproteinase (MMP)-2, and MMP-9 were higher in the VM group than in the non-VM group (P = 0.001, P = 0.030, P = 0.007, respectively). After VM formation was induced by hypoxia, up-regulated expression of HIF-1α, MMP-2, and MMP-9 was also detected in cells cultured under hypoxia condition. Our results indicate that patterned matrix VM exists in HCC, and it might serve as an unfavorable prognostic factor for HCC patients. It is possible that hypoxia via induction of expression of HIF-1alpha, MMP-2, and MMP-9 may enhance VM formation in HCC.

To develop a simple method to extract and analyze the cytomorphology of epithelial cells from fecal samples and to compare the efficacy of fecal cytology with the immunofecal occult blood test (IFOBT) in colorectal cancer screening.Fecal cytology and IFOBT were performed on fecal samples obtained from 41 patients with colorectal cancer; 34 patients with a small, single adenoma (0.5 cm); and 20 without abnormality. The samples were obtained prior to colonoscopic examination. For fecal cytology, epithelial cells were exacted through filtration, centrifugation and cytocentrifugation and stained with hematoxylin-eosin prior to morphologic analysis.Fecal cytology and IFOBT test had similar levels of sensitivity for detecting colorectal cancer (75.6% vs. 68.3%, respectively), but fecal cytology had higher specificity than IFOBT (100% as compared to 85.2%, respectively, p0.05 by chi2 test). Seven of 41 colorectal cancer patients (17.1%) with negative IFOBT were positive by fecal cytology analysis. Combining fecal cytology with the IFOBT test in an either/or scenario significantly increased the sensitivity of IFOBT test to 92.68% for colorectal cancer detection (p0.05 by chi2 test) without compromising the specificity.Fecal cytology augments the sensitivity of IFOBT in detecting colorectal cancers, and combining fecal cytology and IFOBT may provide an important simple and cost-effective alternative for colon cancer screening.

BACKGROUND AND OBJECTIVE S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on breast cancer, liver cancer and colon carcinoma. This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro, and the antitumor mechanisms. METHODS The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 µmol/(kg · day)], high concentration group [768 µmol/(kg · day)], and control group [normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP. RESULTS SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51 ± 149.27) mm³] and high concentration group [(444.32 ± 118.51) mm³] than in control group [(1018.22 ± 223.07) mm³] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment. CONCLUSIONS SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.

To compare phlegm-heat syndrome with phlegm-dampness syndrome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in regard to inflammatory response, hormone level, lung pathological examination and lung function.Fifty-six Wistar rats were randomly divided into four groups, including normal control group, AECOPD group, phlegm-heat syndrome of AECOPD group (PHs group), phlegm-dampness syndrome of AECOPD group (PDs group). The level of white blood cell (WBC) count, neutrophil ratio, free triiodothyronine (FT(3)), free thyroxine (FT(4)), epinephrine (E), norepinephrine (NE), cortisol (COR), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) in blood, and TNF-alpha, IL-8, intercellular adhesion molecule-1 (ICAM-1) in broncho-alveolar lavage fluid (BALF) were determined with radioimmunology. Lung function was tested by whole-body plethysmography.(1)The count of WBC and neutrophil ratio in PDs group were higher than in PHs group, AECOPD group and normal group, there was significant difference in multiple comparison. The levels of inflammatory mediators in serum and BALF in three model groups were evidently higher than in normal group, and IL-8 [(4.13+/-1.28) microg/L] and CRP [(3.07+/-0.69) microg/L ] in serum in PDs group were higher than those in PHs group [(1.75+/-0.53) microg/L, (1.98+/-0.42) microg/L, both P0.01]. (2)FT(3) level in blood in both AECOPD group and PHs group [(9.44+/-3.17) pmol/L , (9.95+/-3.68) pmol/L] was significantly higher than that in normal control group [(4.53+/-2.80) pmol/L], FT(3) in PDs group [(2.13+/-1.31) pmol/L] was evidently lower than that in normal group (P0.05 or P0.01). The level of FT(4) [(2.23+/-0.71) pmol/L], E [(87.27+/-29.32) nmol/L] and NE [(71.69+/-21.24) nmol/L] in PDs group were all obviously lower than those in normal group [FT(4): (4.64+/-1.49) pmol/L, E: (143.94+/-32.90) nmol/L, NE: (100.32+/-27.73) nmol/L, P0.05 or P0.01]. There was no significant difference in the above three parameters between AECOPD group and normal group. Each parameter in PHs group was markedly higher than that in AECOPD group. The content of COR in PDs group was higher than in PHs group, in which COR was higher than in AECOPD group, which was equal to that in normal group. (3)The pathological changes in lung included inflammatory cell infiltration , exfoliation of cilia, dilatation of alveolar spaces of lung tissue in AECOPD group, which were more significant in PHs group and PD group. Inflammatory cells infiltration around the bronchi, thickening of interalveolar spaces, and vasodilatation were more pronounced in PHs group and PDs group than in AECOPD group. Inflammatory cell infiltration around the bronchi were about the same between PHs and PDs groups. (4)The levels of peak expiratory velocity (PEV), tidal volume (V(T)), minute ventilation (MV) were significantly lower in AECOPD group, PHs group and PDs group than in normal control group, but the levels of frequency (f) and inspiratory resistance (Rin) were evidently higher. Compared with AECOPD group, the levels of PEV, V(T), MV were significantly decreased, the level of respiratory f and Rin evidently increased in PDs group. Compared with PHs group, the levels of PEV, V(T), MV significantly decreased in PDs group, while the level of f and Rin evidently increased. There was no significant difference in the above five parameters between AECOPD group and PHs group.The changes in local and systemic inflammatory response, lung histopathological injury in PHs group and PDs group were more evident than changes in AECOPD group. The changes in systemic inflammatory response, decrease in functional indicators of thyroid and adrenal medulla, and decline in lung function were more marked in PDs group than in PHs group.

To investigate the role and clinicopathological significance of RECK and MMP-2 expressions in esophageal squamous cell carcinoma (ESCC).We collected 57 samples of ESCC tissue and 57 samples of corresponding normal esophageal epithelium tissues in Henan Cancer Hospital. The expression of RECK and MMP-2 was detected with tissue array and immunohistochemistry. Chi-square test and Spearman corrilation analysis were used to analyze the results.The positive rate of MMP-2 protein expression in cancer tissues was 42.1% (24/57), higher than in normal esophageal epithelia 19.3% (11/57), with a significant difference (chi(2) = 6.968, P0.05). For ESCC, a difference was not found in MMP-2 expression among patients with different degree of differentiation and different depth of invasion. The expression levels of RECK in ESCC tissues and normal esophageal epithelia were 36.8% (21/57) and 61.4% (35/57), respectively, with a significant difference (chi(2) = 6.879, P0.05). For ESCC, the expression level of RECK was not related to the degree of differentiation, depth of invasion and lymph node metastasis (P0.05). For ESCC patients, the expression rates of RECK and MMP-2 were not correlated with age or gender.The abnormal expression level of the RECK and MMP-2 protein may play an important role in carcinogenesis of esophageal squamous carcinoma. Decreased expression of RECK and increased expression of MMP-2 may be correlated with the esophageal squamous cell carcinoma development, but there is no connection observed between the expression of MMP-2 and RECK.

Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Studies in recent years indicated that survivin(sur) expression was associated with the biological behaviors of gastric carcinoma. In the present study, targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell were investigated, the recombinant pSCT vector containing CD and TK genes driven by sur promoter was constructed and transfected into SGC-7901 cells. After adding the CCV and 5-FC, the effects of double suicide genes on cell growth, cell cycle and proliferation were determined by MTT assay and flow cytometry (FCM). The results showed that sur promoter could specifically drive the expression of double CD/TK gene in SGC-7901 cells, whereas not in the normal GES-1 cell. After using CCV and 5-FC, the growth of SGC-7901 cells was inhibited. G1 phase proportion was significantly higher in SGC-7901 cells transfected with double suicide genes than the untransfected cells. These results suggest that CD and TK double suicide genes driven by sur promoter could provide a new approach for enhancing selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.

To explore common syndromes and their characteristics of acute exacerbation of the chronic obstructive pulmonary disease (AECOPD) based on dynamic fuzzy kohonen network.. By means of Fisher-iris data and Epidata software, information database, the study was established concerning patients with AECOPD , who were enrolled from four hospitals at 3 A -levels. The detailed procedures were as follows: (1) Selected kohonen net and fuzzy system, as the output of kohonen net can be reflect the graphical distribution characteristics of input samples; (2) On this base, a dynamic self-adaptive neural network was formed by increasing dynamic neurons; (3) guided by fuzzy theory, a dynamic neuro-fuzzy inference system was builded up with MATLAB6.5 software programming; (4) the model’s rationality was tested by Fisher-iris data and eventually obtaining characteristics of the common syndromes of AECOPD based on clinical data mining results and basic theories of traditional Chinese medicine. Through the rules conversion for the main and secondary symptom screening, nine syndromes and their corresponding main and secondary symptoms were determined. They included pattern of stagnated phlegm obstructing the lung, pattern of qi-yin deficiency of the lung and kidney, pattern of phlegm-dampness obstructing the lung, pattern of wind-cold attacking the lung, pattern of accumulated phlegm-heat in the lung, lung-kidney qi deficiency pattern, pattern of wind-heat invading the lung, lung-spleen qi deficiency pattern, pattern of exterior cold and interior heat. The pass rate reached 75.8.% approved by the data test on its rationality. The model can be used to study characteristics of TCM syndromes of AECOPD.

To explore classification and characteristics of the common syndromes of chronic respiratory failure (CRF ) based on self-adaptive fuzzy inference system. The methods applied were in the following: collecting the data of patients with CRF from four 3 A-level hospitals and establishing a database with Epidata software; selecting the artificial neural network, fuzzy system to build up a self-adaptive fuzzy inference system and then programming with MATLAB6.5 software; testing the model’s reliability by means of Fisher-iris data and eventually obtaining characteristics of the common syndromes of CRF based on clinical data mining results. Finally the rationality was tested. Through the rule conversion for the main and secondary symptom screening, seven syndromes and their corresponding main and secondary symptoms were determined, including syndrome of accumulated phlegm-heat in the lung, stagnated phlegm obstructing the lung, edema due to yang deficiency, accumulated phlegm-dampness in the lung, deficiency of both qi and yin, stagnated phlegm obstructing the lung accompanied by yin deficiency pattern, mental confusion due to phlegm. The coincident diagnostic rate reached 74.% approved by the test results of syndrome diagnostic criteria. By the Fisher-iris data test of the model, acquisition of fuzzy classification rules reflected accurately regularity of centralized learning samples, which suggests reliability of the model and thus it can be applied to study of classification and characteristics of TCM syndromes.

Occurrence of second primary tumors and metastasis remains the major obstacles to prolonged survival of patients with primary hepatocellular carcinoma (HCC). A somatostatin analogue, octreotide, has been previously reported to inhibit the growth of human HCC xenografts in nude mice through its anti-angiogenic activity. It is therefore important to investigate whether octreotide could prevent second primary hepatomas or distant metastasis following resection of primary HCC. In this study, nude mice, bearing the human HCC xenografts with highly metastatic potential (LCI-D20) in the left liver lobe, underwent tumor resection, and received intraperitoneal administration of octreotide or saline as a control for 35 consecutive days. Compared with the control group, octreotide at the doses of 100 and 200 microg/kg/day significantly inhibited the growth (P < 0.001 and P < 0.001, respectively) and incidence of second primary tumors (P = 0.016 and P = 0.001, respectively), decreased lung metastasis (P < 0.001 and P < 0.001, respectively), and prolonged the life span (P = 0.029 and P = 0.006, respectively). Moreover, intratumoral angiogenesis quantified by microvessel density as well as serum and tissue vascular endothelial growth factor (VEGF) levels were considerably decreased in octreotide-treated animals compared to the control animals. These findings suggest that octreotide may prevent the occurrence of second primary hepatomas and lung metastasis after resection of primary HCC, which may be partially attributed to down-regulation of VEGF and subsequent reduction in tumor angiogenesis. Octreotide administration may be useful as an adjuvant therapy to improve survival of patients with HCC.

The fatty acid concentrations in maize grain were analyzed with a set of 294 samples including normal inbred lines, high-oil inbred lines and high-oil recombinant inbred lines (RIL). The method of partial least squares (PLS) regression with internal cross validation was employed to develop the measuring models of near-infrared reflectance spectroscopy (NIRS) for concentrations of four major fatty acids, palmitic, stearic, oleic and linoleic acids, as well as oil concentration in maize grain. The NIRS models were accurate for oleic acid, linoleic acid and oil concentrations. The determination coefficients of these models in cross validation were 0.89, 0.88 and 0.91, respectively; the determination coefficients in external validation were 0.86, 0.84 and 0.92, respectively; and the ratio of standard deviation (SD) to root mean square error of validation (RMSEV) in both calibration and external validation sets (RSC(P)) was higher than 2.5. But the models for palmitic and stearic acid concentrations were not accurate enough with determination coefficients in cross validation and external validation lower than 0.80, and RSC(P) lower than 2.5. Further practical validation showed that the predicted results by using NIRS models for oleic acid, linoleic acid and oil concentrations were accurate and reliable, which will be a useful approach to the measurement of a large number of breeding samples during genetic improvement of oil quality and quantity in maize.

An experimental rat hepatocellular carcinoma (HCC) model was established using diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague-Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8, 12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and semi-quantitative reverse transcriptase-polymerase chain reaction at different stages in the rat HCC model. Twenty weeks after induction of hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA significantly increased compared with week 0. Microvessel density (MVD) increased considerably once liver cancer developed. There was a significant positive correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles in tumour occurrence and development during rat hepatocarcinogenesis, possibly through promoting tumour angiogenesis.

To review and analyze the prevailing information and quality of published systematic reviews and Meta-analysis of pneumonia in China.After a CNKI, VIP, Wanfang and CMB database retrieval of systematic reviews and Meta-analysis of pneumonia published in Chinese journals, two reviewers, blinded to author (s), et al, independently collected and analyzed the common information and quality, using the form of Cochrane systematic reviews (CSR) and the quality of reporting of Meta-analysis (QUOROM) statement.Eleven papers, of which 4 were systematic reviews, 7 Meta-analysis were identified. Three hundred and twenty-six studies were analyzed with involvement of 17 971 individuals distributed in 30 domestic administrative regions and 7 foreign countries. None of these articles used the form of CSR or the QUOROM statement to report their results. In all 4 domains and 40 items of the form of CSR, 4 articles addressed 25 items, 3 addressed 2, 2 addressed 1, 1 addressed 5, 0 addressed 7, and the overall proportion for correspondent item information presented was 70.6% (113/160). In all 6 domains and 18 minor terms of the QUOROM statement, 7 articles addressed 10 items, 5 addressed 2, 4 addressed 2, 2 addressed 2, 1 addressed 1, 0 addressed 1, and the overall proportion for correspondent minor terms information presented was 73.8% (93/126). In all 48 checklist items, 7 articles addressed 10 items, 6 addressed 2, 5 addressed 1, 4 addressed 3, 3 addressed 5, 2 addressed 7, 1 addressed 6, 0 addressed 14, and the overall proportion for correspondent item information presented was 39.9% (134/336).These studies of systematic reviews and Meta-analyses of pneumonia in China starts late, only a few of researchers and participants join in the project, and the financial support is insufficient. The quality of literature is passable, but it is weak in some areas such as data sources, selection searching, validity assessment, review methods, study characteristics, etc. The authors suggest that advanced methodological training is necessary for reviewers and stronger financial support is needed.

To reproduce a model of bacterial multiple organ injury (MOI) in aged rats.Male Sprague-Dawley (SD) rats were used. The young rats were divided into young control group (YCG, n=10) and young model group (YMG, n=15), and the elderly, aged control group (ACG, n=10) and aged model group (AMG, n=25). The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality.Between YMG and AMG, the mortality rates were 33.33% (5/15) and 60.00% (15/25), respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell (WBC) counts in peripheral blood increased significantly in YMG and AMG groups (all P0.01), the rates of dysfunction of the lungs, the heart and the liver, were 60%-100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide (PaCO(2), P0.01), and a decrease in the arterial partial pressure of oxygen (PaO(2), P0.05 or P0.01). Myocardial dysfunction was shown by a the sharp increase in creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH), and that of the liver by changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P0.05 or P0.01). The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO(2) in AMG dropped significantly, PaCO(2) increased, CK, CK-MB, LDH, ALT and AST also increased significantly (P0.05 or P0.01). The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group (all P0.05), and the same was trend in the liver and the kidney.The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome (MODS) which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.

To test the effect of rapamycin (RAPA) on hepatic tumor growth and metastasis in Sprague-Dawley (SD) rat model and explore the possible mechanism.SD rat hepatocellular carcinoma (HCC) model with metastatic potential was induced by diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR). 120 SD rats were randomized into four groups 16 weeks after DEN and NMOR treatment, and received 4-week intraperitoneal injection of RAPA (1.5 or 4.5 mg x kg(-1) x d(-1)), CsA (25 mg x kg(-1) x d(-1)) or equal volume of 0.9% saline, respectively. Tumor growth and metastasis were checked after the 4-week treatment. Serum vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay (ELISA). Antiangiogenetic effects were assessed by CD34 immunostaining. The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF proteins and mRNAs were detected by immunohistochemistry, western blot and reverse transcriptase-polymerase chain reaction (RT-PCR).The mean liver weight (5.58% +/- 0.42% and 5.69% +/- 0.74%), the metastatic liver nodules (5.12 +/- 0.68 and 5.67 +/-1.12), the metastasis lung nodules (0.43 +/- 0.11 and 0.45 +/- 0.83), and the lung metastasis rate (17.2% and 14.8%) were lower in rats treated with RAPA 1.5 mg x kg(-1) x d(-1) or 4.5 mg x kg(-1) x d(-1) than those in rats treated with saline, which were 10.42% +/- 1.86%, 12.36 +/- 3.45, 1.81 +/- 0.3 and 50.0% respectively (P0.01 or P0.05). The intratumoral microvessel density (MVD), serum VEGF, and the levels of HIF-1 alpha and VEGF were lower in RAPA-treated rats than those in control rats. However, CsA-treated rats showed an opposite trend compared with the RAPA-treated rats.RAPA can repress the expression of angiogenesis-promoting factors HIF-1 alpha and VEGF, and significantly inhibits the growth and metastasis of HCC.

To detect the expression of TFPI-2 gene in pancreatic carcinoma, and to evaluate its prognostic significance in patients with pancreatic carcinoma.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of TFPI-2 mRNA and protein in the pancreatic carcinoma tissue samples from 41 patients. The correlation of its expression with clinicopathological features and its prognostic significance were analyzed.The expression of TFPI-2 mRNA and protein in moderately or poorly differentiated pancreatic carcinoma tissues, or in cases with nerve-involvement, lymph node and blood vessel invasion was significantly lower than that in the highly differentiated one, or without nerve involvement, or neither lymphatic nor blood vessel invasion (P0.05). The median survival time of patients with high expression of TFPI-2 (12.0 months) was significantly longer than that with low expression of TFPI-2 (5.1 months, P0.05). The Cox model analysis showed that the expression of TFPI-2 was an independent marker for prognosis in patients with pancreatic carcinoma.The expression of TFPI-2 is correlated with clinical stage and differentiation of pancreatic carcinoma, and can be used as a prognostic marker for pancreatic carcinoma.

To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats.Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO). Rats were divided randomly into sham control and I/R groups in young rats [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/R 6 d). The change in cerebro-cortex microvessel basement membrane structure, basement membrane type IV collagen (Col IV) and laminin (LN) contents, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression in every group were determined with immunohistochemical method and zymogram analysis.With the increase in age, Col IV and LN contents of the microvessel basement membrane were increased, and MMP-2 and MMP-9 expressions were stronger. With prolongation of I/R, the degradation of microvessel basement membrane components (Col IV and LN) was positively correlated with the duration of cerebral I/R. MMP-2 expression was increased gradually, and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently. Col IV(I 3 h, I/R 6 h , I/R 12 h), LN (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 3 h, I/R 6-24 h) expression level in aged rats with I/R injury were higher, and TIMP-1 (I/R 24 h) expression was lower than those in young rats (P0.05 or P0.01). In addition, changes in MMP-2 and MMP-9 contents as determined by zymogram analysis method coincided with their immunoexpression.With the increase of age, alteration in membrane components of cerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats. Changes in cerebro-microvessel basement membrane injury in aged rats is related with gelatinase system change.

Background Esophageal carcinoma is a common kind of malignant tumor and about 90% of which is esophageal squamous cell carcinoma (ESCC), and it has a high incidence in China. In recent years it has been argued that angiogenesis plays a key role in tumor growth and metastasis and it is a complex process influenced by many factors. This study was aimed to investigate the expression of PC cell-derived growth factor (PC DGF or progranulin) and vascular endothelial growth factor (VEGF) in ESCC tissue and their relationship with clinical pathological parameters of ESCC, clarify the role of PCDGF and VEGF in the angiogenesis of ESCC. Methods The expression of PCDGF and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry. The vascular endothelial cells in tumor tissues were labeled by antibody to CD105 for counting microvessel density (MVD). Results The expression of PCDGF and VEGF in ESCC was significantly higher than that in normal mucosa. Expression correlated with the depth of tumor invasion, lymph node metastasis, and TNM (classification tumor, nodes, metastasis). In ESCC, both the expression level of PCDGF and VEGF had a positive correlation with MVD and the expression of PCDGF had a significant correlation with the expression of VEGF. Conclusions These results show that both of PCDGF and VEGE have higher expression in ESCC, which indicate that they have a close relationship with angiogenesis. They may be involved in tumor growth, infiltration and metastasis through promoting tumor angiogenesis and may be an important index reflecting biological behavior and prognosis of ESCC.

OBJECTIVE To observe the effects of rhubarb aglycone on pathological changes and activity of matrix metalloproteinase in cerebral ischemic tissue in rats with bone marrow mesenchymal stem cell (BMSC) transplantation, and to explore the action mechanisms of rhubarb aglycone in protecting against brain micrangium injury in rats. METHODS The BMSCs were purified and amplified by methods of adherence and selection in vitro. One hundred and ninety rats were randomly divided into sham-operated group, untreated group, rhubarb aglycone group, BMSC transplantation group (abbreviated as transplantation group) and BMSCs combined with rhubarb aglycone group (abbreviated as combination group). Middle cerebral artery occlusion (MCAO) model was duplicated with nylon thread. Rats of transplantation and combination group were transplanted with BMSCs via carotid artery after 24-hour reperfusion. Rhubarb aglycone was used by intragastric administration in the rhubarb aglycone group and the combination group. The brain samples were taken at 7, 14 and 28 days after transplantation. Brain micrangium pathological changes were observed by light microscope, and immunohistochemical method was used to determine the expressions of immunoglobulin G (IgG), type IV collagen (Col IV), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS Comparison with the normal control group revealed that brain micrangium in rats in the untreated group was obviously mutilated and damaged, the expression of IgG and MMP-9 increased, and showed a progressively enhanced tendency following the prolongation of reperfusion, while the expressions of Col IV and TIMP-1 were decreased, and TIMP-1 showed a attenuated tendency following the prolongation of reperfusion. Comparing with the untreated group, the improvements of brain micrangium structure in the rhubarb aglycone group (7 days after transplantation), the transplantation group (14 and 28 days after transplantation) and the combination group were significant; expression of IgG and activity of MMP-9 were decreased, while expressions of Col IV and TIMP-1 were increased in the rhubarb aglycone group and the combination group at each time point. The brain micrangium was integral and the expression of Col IV was enhanced in combination group (7 days after transplantation) as compared with those in transplantation group. MMP-9 activity in combination group (14 days after transplantation) was lower than that in the rhubarb aglycone group (14 days after transplantation), while expression of TIMP-1 in combination group also increased significantly as compared with that in transplantation group (28 days after transplantation). CONCLUSION Rhubarb aglycone can decrease the degradation of basal lamina Col IV and the permeability of brain micrangium in cerebral ischemic rats with BMSC transplantation, and its mechanisms may be related to regulating the balance of MMP-9, especially by increasing the expression of TIMP-1.

This paper explores a method for establishing diagnostic criterion of TCM (traditional Chinese medicine) syndrome differentiation by studying the set-up of diagnostic standard model of syndrome differentiation of Type 2 diabetes. We present, based on dynamic Kohonen network, the artificial neural net (ANN), fuzzy system (FS) that were used to build up adaptive fuzzy inference system model. The system was tested for its reliability via fisher-iris determination. Then with the help of this model the clinical data was studied, simultaneously, according to TCM basic theories. We obtained the diagnostic criterion of commonly-seen syndrome of Type 2 diabetes, whose rationality was verified by data check-up.

Magnetic photocatalysts (TiO2/Fe3O4), which are liable to be separated and recovered, were prepared using Fe3O4 as the support. The surface morphology and crystal pattern were investigated by means of XRD, SEM, XPS and FTIR. The results showed that TiO2 wraps on the surface of Fe3O4. The photocatalytic activity of the catalysts was investigated by photocatalytic decolorization of (TNR). The photocatalytic activity of the catalysts is high and the separating ratio is good.

To study the modulation effect of Naomaitong on gelatinase system after cerebral ische-Focal cerebral I/R rat model was duplicated by method of the intralumimia/reperfusion (I/R) in rats.nal filament technique. Rats were randomly divided into the sham-operative group, the model group, the Naomaitong group and the Nimodipine group, the latter three groups were also divided into the 3 hrs after ischemia group, and 6 hrs, 12 hrs, 24 hrs, 3 d, 6 d after IR groups. Immunohistochemical method and zymogram analysis method, etc. were adopted to observe the change of microvessel structure, gelatinase and its inhibitor expression.MMP-2 (IR 24 h-6 d)and MMP-9 (I/R 12 h-3 d) expression levels could be lowered and TIMP-1 expression level (IR 24 h-6 d) improved by Naomaitong. Besides, comparison of MMP-2 and MMP-9 content in zymogram analysis in each group showed that changes of its quantity were in accordance with the laws of immune expression.The protective effect of Naomaitong on cerebromicrovessel basement membrane injury in rats is related to its modulation on gelatinase system.

OBJECTIVE: To determine the inhibitory effects of all-trans-retinoic acid (ATRA) on cell growth, cell cycle and vascular endothelial growth factor (VEGF) expression in the human gastric cancer cell line BGC-823 in vitro. METHODS: Human gastric cancer BGC-823 cells were treated with various concentrations of ATRA and the cell growth was then determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability assay. The cell cycle distribution was analyzed using a flow cytometer. The VEGF mRNA and protein expression were analyzed by semi-quantitative RT-PCR and Western blotting, respectively. RESULTS: ATRA at concentrations of 0.1–10 µmol/L inhibited the growth of BGC-823 cells grown in culture; a time- and dose-dependent inhibitory influence was found. ATRA arrested BGC-823 cells at the G0/G1 phase in a dose-dependent way. Both VEGF mRNA and protein were decreased by ATRA in a dose-dependent way. CONCLUSION: The anti-tumor effects of ATRA on human gastric cancer cells are associated with G0/G1 phase arrest and decreased VEGF expression.

To study the protective effect of Naomaitong on inflammatory cascade response after focal cerebral ischemia reperfusion in aged rats.We duplicated focal cerebral ischemia model with MCAO, with ischemia 3 h and I/R 1, 3, 6, 12 d points. The effect of Naomaitong on the nervous dysfunction score, the water content of cerebral constitution and the expression of TNF-alpha, VCAM-1, ICAM-1 and its mRNA were observed, and the group with nimodipine was as control.The nervous dysfunction score (I/R1, 3, 6 d), the water content of cerebral constitution (all the time points), the expression of TNF-alpha, VCAM-1 (I 3 h, I/R 1, 3, 6 d), ICAM-1 (I 3 h,I/R 1, 3, 6 d) and its Mrna (all the time points) in model group were higher than those of the sham-operated group; The nervous dysfunction score, the water content of cerebral constitution (I/R 3, 6, 12 d), the expression of TNF-alpha, VCAM-1 (I 3 h, I/R 1, 3 d), ICAM-1 and its mRNA (I 3 h, I/R 1, 3 d) in model group were decreased compared with that of model group. The nervous dysfunction score (I/R 6, 12 d), the expression of TNF-alpha, ICAM-1 (I/R 1d) and its mRNA (I/R 1, 3 d) in Naomaitong group were higher than that of Nimodipine group.Naomaitong could protect brain cell from damage after focal cerebral ischemia reperfusion injury by inhibiting the expression of TNF-alpha, adhesion molecule.

To investigate the changes in expression of tumor necrosis factor-alpha(TNF-alpha), vascular cellular adhesive molecule-1 (VCAM-1), intercellular adhesion molecular-1 (ICAM-1) and its mRNA expression, and the pathogenetic mechanism of cerebral ischemia/reperfusion(I/R) in elderly.Thirty six male young SD rats (5-6 months old) and 36 male aged SD rats (20-21 months old) were randomly divided into young sham operated group, young model group, aged sham operated group and aged model group, respectively. The two model groups were randomly divided into ischemia 3 hours (I 3 h), I/R 1, 3, 6, 12 days groups. There were 6 rats in each group. Focal cerebral I/R model was replicated with middle cerebral artery occlusion (MCAO). The changes of the nervous dysfunction score, the water content of cerebral constitution and the expression of TNF-alpha, VCAM-1, ICAM-1 and ICAM-1 mRNA were observed at each time point.The expression of TNF-alpha in the aged sham operated group were higher than that of the young sham operated group. The nervous dysfunction score (I 3 h and I/R 1-12 d), the water content of cerebral constitution (I/R 1-6 d), the expression of TNF-alpha (I 3 h and I/R 1-6 d), VCAM-1 (I 3 h and I/R 1 d), ICAM-1 (I 3 h and I/R 1-6 d) and ICAM-1 mRNA (I 3 h and I/R 1-12 d) in young model group and aged model group were higher than those of the young sham operated group and the aged sham operated group respectively. The nervous dysfunction score (I 3 h, I/R 6 d), the expression of TNF-alpha (I/R 1, 3 d), VCAM-1 (I/R 3, 6 d), ICAM-1 (I 3 h, I/R 1 d) and ICAM-1 mRNA (I/R 1-6 d) in aged model group were higher than that of young model group.The cerebral I/R injury is correlated with the up regulation of TNF-alpha, VCAM-1,ICAM-1 and its mRNA expression. The cerebral I/R injury of aged rats is more serious than that of young rats which might be associated with up regulation of TNF-alpha, adhesion molecules expression with aging.

To investigate gene expression profile in response to aluminum stress and to cloning the key genes related to aluminum tolerance, are crucial to genetic improvement of plant aluminum tolerance. In this study, suppression subtractive hybridization method was adopted to construct SSH-cDNA libraries at seedling stage of two maize inbred lines (Fig. 1), of which Mo17 is sensitive to aluminum toxicity and TL94B is tolerant. As a result, a forward SSH-cDNA library including 762 clones and a reverse SSH-cDNA library including 382 clones were constructed for Mo17. In the same way, a forward SSH-cDNA library including 760 clones and a reverse SSH-cDNA library including 380 clones were constructed for TL94B. Identification of these SSH-cDNA libraries shows that the length of inserted fragments ranges from 250 bp to 1.0 kb (Fig. 2), of which nearly 18% are positive clones. Through differential hybridization screening (Fig. 3), 124 and 47 positive clones were screened from forward and reverse SSH-cDNA libraries of Mo17 respectively; 103 and 64 positive clones from forward and reverse SSH-cDNA libraries of TL94B respectively. Total 338 positive clones from four SSH-cDNA libraries were sequenced, and all of the sequences of inserted fragments were analyzed using bioinformatical methods. A total of 232 kinds of EST sequences were obtained. Among these ESTs, 70.2% had significant homology with known genes, and the remaining 29.8% were function-unknown including 21 kinds of newly found ESTs (Table 1). An aluminum tolerant gene, GDP dissociation inhibitor gene, was detected its expression character by Northern hybridization (Fig. 4). These results indicate that the responses of maize to aluminum stress involve the interactions among different signal/metabolism pathways, such as signal transduction of stress-related factors, transcription and regulation of responsive genes, synthesis and transport of substances, changes in cell structures and functions.