Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway.

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.

Regulation of γδT17 cells by Mycobacterium vaccae through interference with Notch/Jagged1 signaling pathway

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.

Nrf2 Activator RTA-408 Protects Against Ozone-Induced Acute Asthma Exacerbation by Suppressing ROS and γδT17 Cells.

Ozone is a strong oxidant in air pollution that exacerbates respiratory disorders and is a major risk factor for acute asthma exacerbation. Ozone can induce reactive oxygen species (ROS) and airway neutrophilic inflammation. In addition, γδT17 cells contribute to IL-17A production upon ozone challenge, resulting in neutrophilic inflammation. It is known, however, that Nrf2 can ameliorate oxidative stress. We therefore investigated whether RTA-408, an Nrf2 activator, can attenuate airway inflammation and inhibit ROS production and whether this effect involves γδT17 cells. Balb/c mice were sensitized/challenged with ovalbumin (OVA) and followed by ozone exposure. We investigated the effect of Nrf2 activator RTA-408 on airway hyperresponsiveness, neutrophilic airway inflammation, cytokine/chemokine production, and OVA-specific IgE level in a mouse model of O3 induced asthma exacerbation. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels in lung and intracellular ROS were measured. IL-17+ γδT cell percentage by flow cytometer was determined. Nrf2 protein expression by western blot was also examined. We observed that RTA-408 attenuated ROS release during ozone-induced asthma exacerbation and suppressed neutrophil lung infiltration. RTA-408 decreased pro-inflammatory cytokine production and reduced the percentage of IL-17+ γδT cells. Thus, our results suggest that RTA-408 does attenuate airway inflammation in a murine model of ozone-induced asthma exacerbation.

Imbalance of γδT17/γδTreg cells in the pathogenesis of allergic asthma induced by ovalbumin.

We aimed to explore the imbalance between the T helper 17 γδT cells (γδT17) and the regulatory γδT cells (γδTreg) in asthmatic mice. Male Balb/c mice were randomly divided into the normal control group and the asthmatic model group. The asthmatic model group mice were intraperitoneally injected with the mixture of ovalbumin (OVA)/Al(OH)3 and then activated by exposure of the animals to OVA atomization. Airway hyperresponsiveness (AHR) was determined by a non-invasive lung function machine. Hematoxylin and eosin and Alcian blue-periodic acid Schiff staining were done for histopathological analysis. Interleukin (IL)-17 and IL-35 levels in bronchoalveolar lavage fluid were detected by ELISA. The percentage of IL-17+ γδT cells and Foxp3+ γδT cells in spleen cells suspension were detected and the transcription levels of RORγt and Foxp3 in the lung tissue were determined. Compared with the normal control, the severity of airway inflammation and AHR were higher in the asthmatic mice. Furthermore, mice in the asthmatic group displayed significant increases of IL-17+ γδT cells, expression of IL-17A, and RORγt, whereas control mice displayed marked decreases of Foxp3+ γδT cells, expression of IL-35, and transcription factor Foxp3. In addition, the mRNA expression of RORγt was positively correlated with the percentage of IL-17+γδT cells, and the mRNA level of Foxp3 was positively correlated with the percentage of Foxp3+ γδT cells. The imbalance of γδT17/γδTreg in the asthmatic mice may contribute to the pathogenesis of OVA-induced asthma.

Imbalance of Th17/Treg in the Pathogenesis of Mice with Paraquat-induced Acute Lung Injury.

Recent studies suggest that imbalances in the ratios of CD4+ T helper cell subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment. Hematoxylin-eosin and TUNEL staining procedures were performed to examine inflammation and apoptosis. The presence of Th17 and Treg cells was measured by flow cytometry; the expression of putative Th17 cytokines and transcription factors was measured by ELISA and western blot analysis. Compared with control mice, lung inflammation and apoptosis were dramatically increased in PQP mice at 12 and 24 hours after poisoning. In addition, poisoned mice displayed significant increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of IL-17A and IL-17, as measured by flow cytometry and western blot assays. This increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg) and in the expression of IL-35 and the transcription factor Foxp3. These results suggest that an imbalanced ratio of Th17/Treg cells may contribute to the pathogenesis of PQ-induced ALI.

Obesity enhances Th2 inflammatory response via natural killer T cells in a murine model of allergic asthma.

BACKGROUND: Obesity increases the incidence of asthma, but mechanism between asthma and obesity isn't utterly understood. NKT cells are intermediary activist between the innate and adaptive immune. It may play an equally important role in both obesity and asthma. We studied an obese mouse model of allergic asthma to test whether NKT cells act as a linkage in the development of obesity with asthma. METHODS: Balb/c mice were divided into control group (A), asthma model group (B), the obesity group (C) and obesity with asthma group (D), asthma model made by OVA. Obesity was induced. AHR were measured; HE staining of lung was made; NKT cells were detected and IL-4 and IFN-γ concentration were determined. RESULTS: Lung histology showed airway inflammatory in obesity with asthma are significant than in asthma. IL-4 levels were increased compared with the control group. IFN-γ levels were decreased compared with the control group. More CD69+NKT cells of asthma group and obese asthma group correlated to the enhancement of airway inflammation and AHR. IFN-γ+NKT cells vary in different states not paralleling with CD69+NKT cells. CONCLUSION: The activity level of NKT cells in obesity with asthma mice enhances Th2 Inflammatory response by regulating IL-4 and IFN-γ secretion. The activation of NKT enhanced asthma TH2 inflammatory responce. NKT cells play an important role in the development of asthma in obesity.

[Effects of future climate change on climatic suitability of rubber plantation in China].

Global warming may seriously affect the climatic suitability distribution of rubber plantation in China. Five main climate factors affecting rubber planting were mean temperature of the coldest month, mean extremely minimum temperature, the number of monthly, mean temperature ≥18 °C, annual mean temperature and annual mean precipitation. Climatic suitability areas of rubber plantation in 1981-2010, 2041-2060, 2061-2080 were analyzed by the maximum entropy model based on the five main climate factors and the climate data of 1981-2010 and RCP4.5 scenario data. The results showed that under the background of the future climate change, the climatic suitability area of rubber plantation would have a trend of expansion to the north in 2041-2060, 2061-2080. The climatic suitability areas of rubber plantation in 2041-2060 and 2061-2080 increased more obviously than in 1981-2010. The suitable area and optimum area would increase, while the less suitable area would decrease. The climatic suitability might change in some areas, such as the total suitable area would decrease in Yunnan Province, and the suitability grade in both Jinghong and Mengna would change from optimum area to suitable area. However, the optimum area of rubber plantation would increase significantly in Hainan Island and Leizhou Peninsula of Guangdong Province, and a new less suitable area of rubber planting would appear in Taiwan Island due to the climate change.

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients.

BACKGROUND: Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China. METHODS: The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients. RESULTS: The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05). CONCLUSIONS: The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

A randomized trial of Chinese medicine Lirukang Granule combined with psychological intervention for cyclomastopathy and menoxenia.

OBJECTIVE: To observe the influence of therapy with Chinese medicine Lirukang Granule (, LRKG) combined with psychological intervention on anxiety states and sex hormones in patients with cyclomastopathy and menoxenia. METHODS: A total of 470 subjects were randomly assigned to three groups by the net-central randomization system, the treatment group (161 patients, treated with LRKG and psychological intervention), the Chinese medicine group (157 patients, treated with LRKG), and the psychological intervention group (152 patients, treated with psychological intervention). The dose of LRKG was 12 g three times per day; psychological intervention included establishing relations, cognitive intervention and psychological persuasion, 30-40 min per session, once a week. The therapy duration for all groups was three months. The efficacy was compared and anxiety state/State-Trait Anxiety Invertory (STAI) scoring was measured before and after treatment. The serum estradiol (E2), progesterone (P), prolactin (PRL) and follicle stimulating hormone (FSH) levels of 60 patients selected randomly from each group during the luteal phase were measured before and after treatment, and a group of 20 healthy women were evaluated for comparison. A follow-up was arranged for one year after treatment. RESULTS: Thirty subjects were lost to follow-up. (1) Comparison of efficacy: the markedly effective rate and the total effective rate of the treatment group were 86.67% (131/150) and 98.00% (147/150), respectively; of the Chinese medicine group, 64.58% (93/144) and 90.27% (130/144), respectively; and of the psychological intervention group, 0% (0/146) and 3.42% (5/146), respectively. The markedly effective rate and the total effective rate in the treatment group were significantly higher than those in the Chinese medicine and psychological intervention groups (P < 0.05). (2) Comparison of STAI scoring: STAI scoring was decreased dramatically in the treatment group after treatment compared with that of the Chinese medicine group (P < 0.01), but there was no significant difference compared with the psychological intervention group. (3) Comparison of levels of sex hormones: E2, P, PRL and FSH of the three patient groups were disordered before treatment, and significantly different from healthy women (P < 0.01). After treatment, the levels of P and FSH of the treatment group were significantly increased (P < 0.01), E2 and PRL were significantly reduced, which were also significantly decreased compared with the psychological intervention groups (P < 0.01). (4) FOLLOW-UP: the markedly effective rate and the total effective rate of the treatment group remained higher than those of the other two groups after one year of treatment (P < 0.05). (5) Adverse reactions: no obvious adverse reactions were found among the three groups. CONCLUSIONS: Therapy with Chinese medicine combined with psychological intervention was effective for short-term and long-term treatment of cyclomastopathy and menoxenia. The mechanism might be related to the regulation of sex hormones.

Analysis of early kidney damage in hospitalized patients with chronic kidney disease: a multicenter study.

BACKGROUND: To identify the risk factors for early kidney damage in hospitalized Chinese patients with chronic kidney disease (CKD). METHODS: A total of 12 multicenter cross-sectional studies were conducted between January 2005 and January 2006 in Chinese CKD patients with estimated glomerular filtration rate (eGFR) equal to or more than 30 mL/min/1.73 m2 in Shanghai. CKD was defined according to the K/DOQI guideline. GFR was estimated by the simplified modification of diet in renal disease equation. The demographic, clinical, and laboratory data were collected through a questionnaire and analyzed among eligible patients stratified by three different CKD groups (CKD stages 1, 2, and 3). The relevant clinical and laboratory risk factors for early kidney damage with a GFR < 90 mL/min/1.73 m2 were determined by logistic regression. RESULTS: A total of 822 CKD patients were enrolled in this study. There were significant differences in age and gender among patients with CKD stages 1, 2, and 3. The prevalence of hypertension, cardiovascular disease, cerebral vascular disease, anemia, and hyperuricemia increases when the eGFR declines. Logistic analysis showed that age, hypertension, anemia, and hyperuricemia were independently associated with early kidney damage. CONCLUSIONS: In CKD patients, we have identified only age, hypertension, anemia, and hyperuricemia as the risk factors for early kidney damage. Risk factors should be managed to prevent accelerated kidney damage in CKD patients.

[Surgical treatment of non-traumatic aneurysm in ilio-femoral arterial region].

OBJECTIVE: To summarize the surgical experiences of treating 61 cases of non-traumatic aneurysms in ilio-femoral arterial region. METHODS: The clinical data of 61 consecutive patients with non-traumatic aneurysms in ilio-femoral arterial region between January 1985 and November 2010 were retrospectively reviewed. RESULTS: There were a total of 76 non-traumatic aneurysms in ilio-femoral arterial region, including solitary iliac aneurysms (n = 29) and femoral aneurysms (n = 32). Seventeen (27.9%) patients had multiple aneurysms, 8 (13.1%) patients ruptured aneurysms and 4 (6.6%) patients coexistent peripheral vascular occlusive disease. Fifty patients underwent electively aneurysm excision and graft (or autogenous vein) replacement. Seven patients with ruptured aneurysms received emergency treatment. And one with multiple aneurysms died intra-operatively from ruptured iliac aneurysm. One patient with common iliac aneurysm underwent endovascular repair without endoleak and 1 with internal iliac aneurysm received embolization. There was no perioperative mortality. But one with femoral aneurysm underwent amputation due to acute thrombosis. Seven patients died during the follow-up period and the survivors remained stable and had a good graft patency without new aneurysm formation. CONCLUSION: Early management of aneurysms in ilio-femoral arterial region is rather important and multiple aneurysms should be considered. Aneurysm excision and arterial reconstruction yield an excellent outcome. Close and long-term follow-up is mandatory for the detection of new aneurysm formation.

[A multi-center survey of hypertension and its treatment in patients with maintenance hemodialysis in Shanghai].

OBJECTIVE: To study the prevalence, treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control. METHODS: We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female. Hypertension was defined as systolic blood pressure (SBP)≥140 and/or diastolic blood pressure (DBP)≥90 mm Hg (1 mm Hg=0.133 kPa). Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey. Hypertension control was defined as blood pressure<140/90 mm Hg before each dialysis session. RESULTS: The prevalence of hypertension in the hemodialysis patients was 86.3%. The treatment rate and control rate in those patients were 96.8% and 25.5% respectively. More than half (50.4%) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more. Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin II receptor blockers (56.4%), centrally acting anti-hypertensive agent (26.4%), beta blockers and alpha, beta-blockers (14.0%). The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease. The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension. The hypertension control rate elevated significantly with the adequate hemodialysis. CONCLUSIONS: There is a very high prevalence of hypertension in maintenance hemodialysis patients. Although the treatment rate is high, the control rate is unsatisfactory. So the control of hypertension in hemodialysis patient is still a clinical challenge. Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.

[Speciation analysis and toxicity of arsenic in realgar bioleaching solution].

OBJECTIVE: To analyze speciation and toxicity of arsenic in realgar bioleaching solution, and to explore its possible relation between speciation and toxicity. METHODS: Capillary zone electrophoresis (CZE) can be used quickly and simply onto the simultaneous separation and quantitative determination of the speciation of arsenic in realgar bioleaching solution. The effects of three different realgar bioleaching liquids on the acute toxicity level of rat were also investigated as well. Parallel experiments with traditional processing realgar via gastric irrigation were conducted for comparison. RESULTS: There are three different arsenic species in realgar bioleaching solution (iAs(III), iAs(V) MMA(V)), and the processing method largely affected speciation and toxicity of arsenic of it. It was found that the toxicity level was decreased through increasing the amount of MMA(V). CONCLUSION: These results indicate that the species of arsenic may be tightly relationship to its toxicity in realgar bioleaching solution.

[Pharmacokinetics of bacteria bioleaching solution of realgar in rat].

The paper is to report the preparation of realgar bioleaching solution (RBS) by bacteria and the comparison of pharmacokinetics of RBS and H3AsO3 (ATO), and the study of its possible change of absorption and distribution of soluble arsenic in rat. The experiment was carried out on Wistar rats given peritoneal injection of RBS at a dose of 0.3 mg x kg(-1) (soluble arsenic content, 0.3 mg x kg(-1)), and rats given ATO at the dose of 0.3 mg x kg(-1) (soluble arsenic content, 0.3 mg x kg(-1)). The arsenic concentrations in many tissues including heart, liver, spleen, lung, renal and brain were determined. The changes of pharmacokinetic parameters and arsenic distribution in different tissues were detected and compared in these two groups of rats. The pharmacokinetic parameters of RBS and ATO are very similar. There is very few distribution of arsenic in the tissues in RBS group, compared with the ATO group. There is significant difference in the content of arsenic between two groups statistically (P < 0.01). It is feasible that we select the bacteria bioleaching solution as a candidate drug, which may be employed for primary change of arsenic compounds including dissolved inorganic arsenic and organic arsenic, in order to improve bioavailability and decrease the amount of arsenic accumulation in animal tissues. In addition, there is significant difference in the change of arsenic compounds between two groups. It can be concluded that, the investigation on application of microbial technology may provide a basis for exploratory research of realgar.

[Dilingdan Decoction prevents renal interstitial fibrosis in a rat model of unilateral ureteral obstruction].

OBJECTIVE: To investigate the preventive and therapeutic effects and the possible mechanisms of Dilingdan Decoction (DLDD), a compound Chinese herbal medicine, on rats with renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHODS: Sixty SD rats were randomly divided into sham-operated group, untreated group, enalapril-treated group and DLDD-treated group. Blood urea nitrogen (BUN), serum creatinine (SCr), urine protein quantization in 24 hours and pathological changes of the obstructed kidney were observed. The expressions of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), fibronectin (FN) and laminin (LN) were detected by immunohistochemical method and colored-multimedia pathological image analysis system. RESULTS: Massive inflammatory infiltrates and collagen expression in renal interstitial in the untreated group were observed on the 7th day. Compared with the sham-operated group, percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions in the untreated group were markedly increased (P<0.05), while the percentage of area of interstitial fibrosis was decreased in the DLDD-treated group as compared with the untreated group (P<0.05). On the 14th day, the percentages of area of TGF-beta1, alpha-SMA, FN and LN expressions were declined in two treated groups as compared with the untreated group (P<0.05), but had no statistical difference in biochemical indicators, including BUN, SCr and 24-hour urinary protein. On the 21st day, the level of SCr and the percentage of area of TGF-beta1 expression in the DLDD-treated group were lower than those of the enalapril-treated group (P<0.05). CONCLUSION: DLDD can reduce the excretion of urinary protein and the degree of interstitial fibrosis, and significantly inhibit the expressions of TGF-beta1, alpha-SMA, FN and LN. DLDD is superior to enalapril in protecting renal function after long-time application in rats.

[Effects of adenovirus on vein autografts: experiment with rat].

OBJECTIVE: To assess the effects of transfection of adenovirus on the tunica intima hyperplasia of vein autografts. METHODS: An external branch of the internal jugular vein, 5 mm in length, of a Wistar rat was cut and transplanted to its own common carotid artery by end to end bypass so as to establish a model. Ninety Wistar rats underwent transplantation of vein autografts to their own arteries and then were randomly divided into 3 equal groups: experiment group, undergoing transplantation and adenovirus transfection; experimental control group, undergoing transplantation only; and normal control group. Three, 10, and 30 days later, samples of vessel were obtained. The expression of green fluorescence protein (GFP) was observed so as to measure the transfection rate of adenovirus. Routine HE staining and Verhoeff Van Gieson staining were made to measure the thickness of the vessels with computer-assisted image analyzer. Immunohistochemistry was used to detect the proliferating cell nuclear antigen (PCNA) RT-PCR and Western blotting were used to detect the mRNA and protein expression of intracellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). RESULTS: Three day postoperatively, the expression of GFP reached the peak, (26.4 +/- 3.6)%; decreased to (14.5 +/- 2.1)% 10 day postoperatively; and became very low 30 day postoperatively, at the level of (0.81 +/- 0.2)%. The hyperplasia of venous tunica intima of the control group was obvious 10 day postoperatively, and became less obvious 30 day postoperatively. Proliferation of vascular smooth muscle cells (VSMCs) and sedimentation of extra-cellular matrix in the experimental group were very obvious, compared with the other 2 groups (both P < 0.05). PCNA was very rare in normal vein walls, showing that the VSMCs were in the static phase. PCNA presentation increased obviously in the control group, showing a high proliferation rate of VSMCs. The positive rate of PCNA was associated with the thickness of the tunica intima. mRNA expression and protein expression of ICAM-1 and VCAM-1 could be detected 3 days after the transplantation, peaked 10 days after the transplantation, and remained high 30 days after in the normal group, however, the corresponding expression levels of the normal vein group were all very low (all P < 0.05). The corresponding levels of the experimental group were all higher than those of the experimental control group, however, not significantly different. CONCLUSION: Transfection of adenovirus into the wall of transplanted vein causes inflammation and hyperplasia of tunica intima. However, such affects only a short time.

[Correlation of Her-2 overexpression with endocrine status and response to tamoxifen treatment in patients with breast cancer].

OBJECTIVE: To investigate the correlation of Her-2 overexpression with endocrine status and response to tamoxifen treatment in patients with breast cancer. METHODS: Immunohistochemistry was used to measure the expression of estrogen receptor (ER), progesterone receptor (PR), Her-2, p53, proliferating cell nuclear antigen (PCNA) in 4773 consecutive in-hospitalized patients with primary breast cancer confirmed by pathological examination of the resected specimens, all females, aged 50 (15 - 92), and were followed up for 42 months on average. 1090 if then received tamoxifen (TAM), an anti-estrogen agent, post-operationally. The correlation of Her-2 overexpression with other factors was analyzed. RESULTS: (1) The Her-2 overexpression rate was 26.6%. Her-2 overexpression was significantly negatively correlated with expressions of ER and PR (both P < 0.01). (2) The general 3-year disease-free survival (DFS) rate of those treated with TAM was 92.7%; and the 3-year GFS rate of the subgroup of the TAM-treated patients with Her-1 overexpression was 91.2%, significantly lower than that of those without Her-2 overexpression (93.4%, P = 0.004). (3) The 3-year DFS rate premenopausal patients with Her-2 overexpression was 91.8%, not significantly different from that of those without Her-2 overexpression (92.6%, P > 0.05), however, the 3-year DFS rate of the postmenopausal patients with Her-2 overexpression was 90.4%, significantly lower than that of those without Her-2 overexpression (92.6%, P = 0.010). (4) The 3-year DFS rate of the axillary lymph node-positive patients with Her-2 overexpression was 89.1%, significantly lower than that without Her-2 overexpression (92.3%, P = 0.037). (5) In the premenopausal patients there was no significant difference in the 3-year DFS rate between the lymph node-negative patients with and without Her-2 overexpression (P > 0.05). However, in the postmenopausal lymph node positive patients the 3-year DFS rate of those with Her-2 overexpression was 88.7%, significantly lower than that of those without Her-2 overexpression (92.2%, P = 0.0069). CONCLUSION: ER and PR are independent factors of Her-2 expression. Her-2 overexpression signifies resistance to TAM treatment. The response to TAM is not influenced by the Her-2 expression and axillary lymph node metastasis status in the premenopausal patients, and is not influenced by the Her-2 expression level in the postmenopausal patients.

[Effect on hyperplasia of VSMCS in rat by the plasmid containing the short hairpin RNA of AT1R].

AIM: RNA interference is a new technology that inhibit effectively of the expression the specific genes. The present study was designed to investigate whether the plasmid containing the short hairpin RNA (shRNA) of angiotensin II type 1 receptor (AT1R) can inhibit the hyperplasia of VSMCs in rat. METHODS: The plasmids containing the shRNA of AT1R were constructed, and transfected vascular smooth muscle cell (VSMC) to detect the effect on the AT1R expression by RT-PCR and Western blot, and detect the hyperplasia of VSMCs by trypan blues training and MTT. RESULTS: The plasmids was certified to be in the right rank, and there was significant difference (P < 0.01) in the expression of AT1R mRNA and protein between the plasmid transfected group and the control group. There was significant difference (P < 0.01) in the hyperplasia of VSMCs between the plasmid transfected adding Ang II group and the control group. CONCLUSION: The plasmids containing the shRNA of AT1R have the effect of RNAi, and inhibit the hyperplasia of VSMCs induced by Ang II in rat.

[Inhibition of hyperplasia of vascular smooth muscle cells in rat by the plasmid containing the short hairpin RNA of angiotensin II type 1 receptor].

OBJECTIVE: RNA interference is a new technology that inhibit effectively the expression the specific genes. The current study was designed to investigate whether the plasmid containing the short hairpin RNA (shRNA) of angiotensin II type 1 receptor (AT(1)R) can inhibit the hyperplasia of vascular smooth muscle cells in rat. METHODS: The plasmids containing the shRNA of AT(1)R were constructed, and transfected vascular smooth muscle cell (VSMC) to detect the effect on the AT(1)R expression by RT-PCR and Western blot, observe the shape of VSMCs by the inverted phase contrast microscope, and detect the hyperplasia of VSMCs by trypan blues staining and MTT. RESULTS: The plasmids was certified to be in the right rank. After transfecting cells, there was significant difference (P < 0.01) in the expression of AT(1)R mRNA between the plasmid transfected group (pAT(1)R-shRNA(1) 1.37 +/- 0.15; pAT(1)R-shRNA(2) 1.45 +/- 0.12) and the control group (2.09 +/- 0.26), and there was significant difference (P < 0.01) in the expression of AT(1)R protein between the gene transfected group (pAT(1)R-shRNA1 1.12 +/- 0.04; pAT(1)R-shRNA2 1.20 +/- 0.07) and the control group (3.17 +/- 0.21). It is shown that pAT(1)R-shRNA can decrease the expression of AT(1)R mRNA and protein. There was significant difference (P < 0.01) in the Cell number between the plasmid transfected adding AngII group (pAT(1)R-shRNA1 5.48 +/- 0.44; pAT(1)R-shRNA2 5.55 +/- 0.45) and the AngII control group (8.13 +/- 0.41); there was significant difference (P < 0.01) in the Ratio of light density by MTT between the plasmid transfected adding AngII group (pAT(1)R-shRNA1 0.365 +/- 0.024; pAT(1)R-shRNA2 0.307 +/- 0.025) and the control group (0.485 +/- 0.011); It is shown that that pAT(1)R-shRNA can inhibit the hyperplasia of VSMCs, and matching the result of morphology observation. CONCLUSIONS: The plasmids containing the shRNA of AT(1)R can inhibit the expression of AT(1)R mRNA and protein in VSMCs, and inhibit the hyperplasia of VSMCs induced by AngII in rat.