The Application of the RNA Interference Technologies for KRAS: Current Status, Future Perspective and Associated Challenges.

KRAS is a member of the murine sarcoma virus oncogene-RAS gene family. It plays an important role in the prevention, diagnosis and treatment of tumors during tumor cell growth and angiogenesis. KRAS is the most commonly mutated oncogene in human cancers, such as pancreatic cancers, colon cancers, and lung cancers. Detection of KRAS gene mutation is an important indicator for tracking the status of oncogenes, highlighting the developmental prognosis of various cancers, and the efficacy of radiotherapy and chemotherapy. However, the efficacy of different patients in clinical treatment is not the same. Since RNA interference (RNAi) technologies can specifically eliminate the expression of specific genes, these technologies have been widely used in the field of gene therapy for exploring gene function, infectious diseases and malignant tumors. RNAi refers to the phenomenon of highly specific degradation of homologous mRNA induced by double-stranded RNA (dsRNA), which is highly conserved during evolution. There are three classical RNAi technologies, including siRNA, shRNA and CRISPR-Cas9 system, and a novel synthetic lethal interaction that selectively targets KRAS mutant cancers. Therefore, the implementation of individualized targeted drug therapy has become the best choice for doctors and patients. Thus, this review focuses on the current status, future perspective and associated challenges in silencing of KRAS with RNAi technology.

Comparison of Life-Time Death Probability due to Malignant Tumors in Different Regions of China Based on Chinese Surveillance Sites.

Objective: To estimate and comparably analyze the life-time death probability (LDP) caused by malignant tumors in different regions in 2004 and 2014. Methods: LDP was calculated by a probability additive formula and based on an abridged life table. Data on age-specific mortality was obtained from the National Cause-of- Death Surveillance Dataset in 2014 using surveillance sites in China and data on age-specific mortality was collected from the third retrospective investigation of death cause in China in 2004. Results: LDP caused by malignant tumors, lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal, and anal cancer were 19.2%, 5.6%, 2.8%, 2.8%, 1.7%, 1.3%, respectively. In addition, we calculated LDP caused by malignant tumors in three different regions of China. LDP caused by malignant tumors were 21.2%, 6.1%, 3.1%, 2.8%, 2.0%, and 1.5% in the eastern region, were 18.3%, 5.5%, 2.7%, 3.0%, 1.5%, and 1.1% in the central region, and were 16.7%, 4.6%, 2.3%, 2.8%, 1.6%, and 1.2% in the western region, respectively. Additionally, LDP caused by malignant tumors in 2004 and 2015 were compared. We found that LDPs caused by malignant tumors, lung cancer, and colorectal cancer have increased in the past decade, while LDPs caused by gastric cancer, liver cancer, and esophageal cancer have experienced a decreasing trend. Conclusions: Malignant tumors were still the main cause of death in one's life time, giving rise to LDP. LDP caused by malignant tumours has two divisions. First, traditional upper digestive system cancers related to long-term chronic infection, such as esophageal cancer, gastric cancer, and liver cancer, which has shown a significant downward trend. Second, lung and colorectal cancers related to the environmental factors and lifestyle, which are on the rise.

miR-144 suppresses proliferation and induces apoptosis of osteosarcoma cells via direct regulation of mTOR expression.

Studied as a type of tumor suppressor, microRNA (miR) performs an important role in growth and apoptosis of various human carcinomas. However, the effects of miR-l44 on osteosarcoma growth and apoptosis, as well as possible underlying mechanisms, remain unclear. The present study investigated the expression of miR-144 in osteosarcoma MG-63 and U-2 OS cell lines compared with osteoblast cells. In order to elucidate the effects of miR-144 on osteosarcoma, miR-144 was upregulated in MG-63 and U-2 OS cells by transfecting chemically synthesized miR-144 mimics. Bioinformatics analysis of potential miR-144 target genes was performed using TargetScanHuman 7.0 and confirmed by luciferase assay. This analysis identified mammalian target of rapamycin (mTOR) as a target of miR-144. The present results indicated that the overexpression of miR-144 may significantly inhibit proliferation and promote apoptosis of MG-63 and U-2 cells compared with scramble control. Furthermore, the effects of miR-144 on osteosarcoma were associated with the mTOR signaling pathway via directly targeting the 3' untranslated region of mTOR mRNA, resulting in a decrease in the level of mTOR protein. In summary, miR-144 was demonstrated to act as a tumor suppressor, which inhibits proliferation and promotes apoptosis of osteosarcoma cell lines. In addition, this effect was mediated by direct targeting on mTOR following inhibition of the mTOR signaling pathway. The present study suggested that miR-144 may be a candidate for the gene therapy of osteosarcoma.

Application of microsutures with vascular endothelial growth factor to improve vascular endothelial regeneration after small vessel anastomosis in the rats / 中国组织工程研究

BACKGROUND:The vascular endothelial growth factor (VEGF) plays an important role in the development and formation of blood vessels.Up to now,there are few reports about the treatment of postoperative complications of vascular anastomosis surgery by mcrosutures with VEGF in China.OBJECTIVE:To synthesiize microsutures with VEGF and to evaluate its effect in revascularization following small vessel anastomosis.METHODS:The method of emulsification-diffusion was use to produce biodegradable polymer polylactic acid/glycolic acid (PLGA) copolymer microparticles containing VEGF,and then,the microparticles were added into microsutures to prepare microsutures with VEGF.Ninety Sprague-Dawley rats were enrolled to make animal models of caudal artery anastomosis using microsutures with VEGF in experimental group and microsutures alone in control group.Complications and VEGF level in the peripheral blood were detected and hematoxylin-eosin staining at the anastomotic site was performed at 2,12 hours,1,3,7 days after anastomosis.RESULTS AND CONCLUSION:(1) Postoperative complications:The postoperative incidence of skin necrosis was significantly lower in the experimental group than the control group (P ＜ 0.05).(2) VEGF level:Compared with the control group,the peripheral blood VEGF level was significantly higher in the experimental group at each time point after operation (P ＜ 0.05).(3) Hematoxylin-eosin staining:In the experimental group,proliferated endothelial cells were seen near the anastomotic site at 1 day after anastomosis;there were a large number of proliferated endothelial calls and subcutaneous tissues covering the sutures completely at 3 days after anastomosis;and endothelial cells and internal elastic lamina were completely repaired,smooth muscle cells proliferated further,and the outer membrane returned to normal at 1 week after anastomosis.In the control group,cell degeneration and necrosis were seen near the anastomotic suture,and only adventitial cells infiltrated and exhibited a traumatic proliferative response at 1 day after anastomosis;neonatal endothelial cells appeared in the exfoliated area of the endothelial cells,grew and migrated,and there was a few endothelial cells covering the anastomotic site at 3 days after anastomosis;and newborn endothelial cells got over the anastomotic crack and covered the suture.To conclude,microsutures with sustained-release VEGF microparticles can promote endothelial cell regeneration in rats at the anastomotic site.

Ischemic heart disease deaths, disability-adjusted life years and risk factors in Fujian, China during 1990-2013: Data from the Global Burden of Disease Study 2013.

OBJECTIVES: Ischemic heart disease (IHD) is a large public health problem and is associated with a number of modifiable risk factors. The aim of this study was to estimate the IHD burden and attributable to risk factors in Fujian, China during 1990 to 2013. METHODS: IHD deaths, disability-adjusted life years (DALYs) and attributable to risk factors were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Statistical models were employed to produce comprehensive results of IHD deaths, DALYs and attributable to risk. Means and 95% uncertainty intervals (UIs) were calculated for mortality and DALYs. The median of the percent change and 95% UI were determined for the period between 1990 and 2013. RESULTS: The age-standardized IHD deaths rate increased by 15.3% from 1990 [74.7 (95% UI 62.9-99.1) per 100,000] to 2013 [82.7 (56.5-95.5) per 100,000]. The age-standardized IHD DALYs has slightly decreased 8.8% from 1990 to 2013[from 1356.2 (1134.3-1732.1) to 1202.7 (879.6-1404.6) per 100,000]. All risks combined account for 94.7% (92.9%- 96.0%) of IHD DALYs for all ages in 2013. The five leading risk factors for all ages IHD DALYs were high systolic blood pressure, high total cholesterol, smoking, diet high in sodium, and high fasting plasma glucose. CONCLUSION: Despite decreased age-standardized IHD deaths and DALY rate since 1990, population growth and aging led to a higher global burden of IHD in 2013. Behavioral, environmental, and metabolic risks can explain most of the IHD DALYs providing many opportunities for prevention.

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats.

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor (CaSR) is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ, 40 mg kg-1 ) in Wistar rats. Animals then received GdCl 3 (an agonist of CaSR, 8.67 mg kg-1 ), NPS-2390 (an antagonist of CaSR, 0.20 g kg-1 ), or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde (MDA), lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH 2 -terminal protein kinase (JNK), p38, and extracellular signaling-regulated kinase (ERK) 1/2. The above parameters could be further increased or aggravated by the administration of GdCl 3 , but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

Clinical observations on the treatment of prolapsing hemorrhoids with tissue selecting therapy.

AIM: To compare the effects and postoperative complications between tissue selecting therapy stapler (TST) and Milligan-Morgan hemorrhoidectomy (M-M). METHODS: Four hundred and eighty patients with severe prolapsing hemorrhoids, who were admitted to the Shenyang Coloproctology Hospital between 2009 and 2012, were randomly divided into observation (n=240) and control (n=240) groups. Hemorrhoidectomies were performed with TST in the observation group and with the M-M technique in the control group. The therapeutic effects, operation security, and postoperative complications in the two groups were compared. The immediate and long-term complications were assessed according to corresponding criteria. Pain was assessed on a visual analogue scale. The efficacy was assessed by specialized criteria. The follow-up was conducted one year after the operation. RESULTS: The total effective rates of the observation and control groups were 99.5% (217/218) and 98.6% (218/221) respectively; the difference was not statistically significant (P=0.322). Their were significant differences between observation and control groups in intraoperative blood loss (5.07±1.14 vs 2.45±0.57, P=0.000), pain (12 h after the surgery: 5.08±1.62 vs 7.19±2.01, P=0.000; at first dressing change: 2.64±0.87 vs 4.34±1.15, P=0.000; first defecation: 3.91±1.47 vs 5.63±1.98, P=0.001), urine retention (n=22 vs n=47, P=0.001), anal pendant expansion after the surgery (2.35±0.56 vs 5.16±1.42, P=0.000), operation time (18.3±5.6 min vs 29.5±8.2 min, P=0.000), and the length of hospital stay (5.3±0.6 d vs 11.4±1.8 d, P=0.000). Moreover TST showed significant reductions compared to M-M in the rates of long-term complications such as fecal incontinence (n=3 vs n=16, P=0.003), difficult bowel movement (n=1 vs n=9, P=0.011), intractable pain (n=2 vs n=12, P=0.007), and anal discharge (n=3 vs n=23, P=0.000). CONCLUSION: TST for severe prolapsing hemorrhoids is a satisfactory technique for more rapid recovery, lower complication rates, and higher operation security.

Differences in the levels of gastric cancer risk factors between Nanjing and Minqing counties, China.

OBJECTIVES: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

Calculation of life-time death probability due malignant tumors based on a sampling survey area in China.

PURPOSE: To calculate the probability of one person's life-time death caused by a malignant tumor and provide theoretical basis for cancer prevention. MATERIALS AND METHODS: The probability of one person's death caused by a tumor was calculated by a probability additive formula and based on an abridged life table. All data for age-specific mortality were from the third retrospective investigation of death cause in China. RESULTS: The probability of one person's death caused by malignant tumor was 18.7% calculated by the probability additive formula. On the same way, the life-time death probability caused by lung cancer, gastric cancer, liver cancer, esophageal cancer, colorectal and anal cancer were 4.47%, 3.62%, 3.25%, 2.25%, 1.11%, respectively. CONCLUSIONS: Malignant tumor is still the main cause of death in one's life time and the most common causes of cancer death were lung, gastric, liver, esophageal, colorectal and anal cancers. Targeted forms of cancer prevention and treatment strategies should be worked out to improve people's health and prolong life in China. The probability additive formula is a more scientific and objective method to calculate the probability of one person's life-time death than cumulative death probability .

Differences in the Levels of Gastric Cancer Risk Factors Between Nanjing and Minqing Counties, China / 예방의학회지

OBJECTIVES: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

Differences in the Levels of Gastric Cancer Risk Factors Between Nanjing and Minqing Counties, China / 예방의학회지

OBJECTIVES: In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS: We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS: Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS: The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.

The regulatory mechanism of CCR7 gene expression and its involvement in the metastasis and progression of gastric cancer.

Gastric cancer is the second leading cause of cancer mortality, but the molecular mechanisms underlying its progression and metastasis remain unclear. CCR7 and Dicer 1 protein expression in 80 gastric adenocarcinomas and 40 peritumoral tissues were measured by immunohistochemical staining. The expression of let-7a miRNA in serum, tumor tissues, and peritumoral tissues was measured by real-time PCR. The role of let-7a in CCR7 protein expression, migration, and invasion of gastric cancer cells was tested in vitro. Dicer 1 protein expression was found to be significantly reduced, whereas CCR7 protein expression was significantly increased in gastric adenocarcinomas compared to peritumoral tissues. The let-7a miRNA levels in the serum and tumor tissues of gastric adenocarcinoma patients were significantly lower than in the serum of healthy controls and peritumoral tissues, respectively. Dicer 1 protein positively correlated with let-7a miRNA level, but negatively correlated with CCR7 protein level in gastric adenocarcinoma. Negative Dicer 1 protein and let-7a miRNA expression and positive CCR7 protein expression significantly correlated with lymph node metastasis, depth of invasion, high clinical TNM stage, and larger tumor size. Let-7a transfection significantly inhibited CCR7 protein expression, migration, and invasion of MNK-45 cells in vitro. High expression of CCR7 protein and low expression of Dicer 1 protein and let-7a miRNA are significantly associated with the metastasis and progression of gastric cancer. High CCR7 protein expression may be caused by the loss of Dicer 1 protein expression and reduced let-7a miRNA level in gastric cancer. The serum let-7a level might be a marker for the diagnosis of gastric cancer.

Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents of two cities in china with distinct mortality rates of gastric cancer.

Gastric cancer is one of the most common malignant tumors causing death in Fujian Province, China. However, the mortality of gastric cancer is greatly varied in different areas in Fujian; for example, the mortality in Changle City is 7.4 times higher than that in Fuan City. In this study, we compared the differences in serological parameters, pepsinogen (PG) I, PG II, gastrin-17 (G-17), and Helicobacter pylori (H. pylori) antibody, between the two cities. It has been reported that low serum PG I is correlated with atrophic gastritis, a high-risk condition for developing gastric cancer, while high serum G-17 has been used for serological detection of atrophic corpus gastritis. We recruited 224 healthy subjects in Changle and 229 healthy subjects in Fuan, matched in age and sex. The serum levels of PG II and G-17 were significantly higher in Changle than those in Fuan. Importantly, the frequency of the subjects with low serum PG I (< 25 µg/L) was significantly higher in Changle than in Fuan, although the serum PG I levels were similar between the two cities. Moreover, the percentage of the subjects with high serum G-17 (≥ 2 pmol/L) and the positive rate of serum IgG antibody against H. pylori were significantly higher in Changle than those in Fuan. The detected differences in these serological parameters are consistent with the notion that the prevalence of atrophic gastritis may be higher in Changle than in Fuan, which results in a higher risk condition for developing gastric cancer in Changle.

[Study on the relation between expression of angiotensin II receptor and apoptosis in myocardium in rats of endotoxemia].

OBJECTIVE: To analyze the expression of angiotensin II (ANG II) receptor and apoptosis in myocardium in rats of endotoxemia. METHODS: Model of endotoxemia was induced by intraperitoneal injection with lipopolysaccharide (LPS) 10 mg/kg in male Wistar rats and saline was injected into control group. The rats were killed at 2 h or 6 h after saline (control) or LPS . Expression of the correlation factors related to apoptosis of Bcl-2, Bax, AT1 and AT2 receptor in myocardial tissue were detected with immunohistochemistry (IHC), and changes of myocardial cells apoptosis was detected by the method of TUNEL. The gene expression of AT1 and AT2 receptor was examined by RT-PCR. The pathological changes of myocardial tissue were observed by electron microscope. RESULTS: Compared with control group , the expression of AT1 and AT2 receptor were significantly decreased, especially in 6 h group; and the expression of Bcl-2 and Bax were decreased, the ratio of Bcl-2/Bax had the downtrend as well as the apoptosis of myocardial cells. CONCLUSION: Interfered by LPS, the down regulation of AT1 and AT2 receptor expression has the negative relation with apoptosis of myocardial cells, this result indicated that down regulation of AT1 and AT2 receptor expression maybe related to cardiac functional impairment, which maybe help us to find a new protective path to prevent myocardial damage induced by systemic inflammatory.

Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation.

Chronic kidney disease: an independent risk factor of all-cause mortality for elderly Chinese patients with chronic heart failure.

OBJECTIVE: To evaluate the prognostic value of chronic kidney disease (CKD) in elderly Chinese patients with chronic heart failure (CHF). METHODS: The study consisted of 327 elderly patients with CHF. All-cause mortality was chosen as an endpoint over the median follow-up period of 345 days. Cox regression analysis was used to identify the risk factors of mortality. RESULTS: The median age of the entire cohort was 85 years (60-100 years). The mortality for 168 elderly patients with CHF and CKD (51.4% of entire cohort) was 39.9% (67 deaths), which was higher than the mortality for CHF patients without CKD [25.2% (40/159 deaths)] and the mortality for entire cohort with CHF [32.7% (107/327 deaths)]. The Cox regression analysis showed that old age [hazard ratio (HR): 1.033; 95% confidence interval (95% CI): 1.004-1.064], CKD (HR: 1.705; 95% CI: 1.132-2.567), CHF New York Heart Association (NYHA) class IV (HR: 1.913; 95% CI: 1.284-2.851), acute myocardial infarction (AMI) (HR: 1.696; 95% CI: 1.036-2.777), elevated resting heart rate (HR: 1.021; 95% CI: 1.009-1.033), and decreased plasma albumin (HR: 0.883; 95% CI: 0.843-0.925) were independent risk factors of mortality for elderly patients with CHF. CONCLUSIONS: CKD was an independent risk factor of mortality for elderly Chinese patients with CHF.

Study on the relation between expression of angiotensin II receptor and apoptosis in myocardium in rats of endotoxemia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To analyze the expression of angiotensin II (ANG II) receptor and apoptosis in myocardium in rats of endotoxemia.</p><p><b>METHODS</b>Model of endotoxemia was induced by intraperitoneal injection with lipopolysaccharide (LPS) 10 mg/kg in male Wistar rats and saline was injected into control group. The rats were killed at 2 h or 6 h after saline (control) or LPS . Expression of the correlation factors related to apoptosis of Bcl-2, Bax, AT1 and AT2 receptor in myocardial tissue were detected with immunohistochemistry (IHC), and changes of myocardial cells apoptosis was detected by the method of TUNEL. The gene expression of AT1 and AT2 receptor was examined by RT-PCR. The pathological changes of myocardial tissue were observed by electron microscope.</p><p><b>RESULTS</b>Compared with control group , the expression of AT1 and AT2 receptor were significantly decreased, especially in 6 h group; and the expression of Bcl-2 and Bax were decreased, the ratio of Bcl-2/Bax had the downtrend as well as the apoptosis of myocardial cells.</p><p><b>CONCLUSION</b>Interfered by LPS, the down regulation of AT1 and AT2 receptor expression has the negative relation with apoptosis of myocardial cells, this result indicated that down regulation of AT1 and AT2 receptor expression maybe related to cardiac functional impairment, which maybe help us to find a new protective path to prevent myocardial damage induced by systemic inflammatory.</p>

Effects of omega-3 fatty acid for sudden cardiac death prevention in patients with cardiovascular disease: a contemporary meta-analysis of randomized, controlled trials.

PURPOSE: Experimental and epidemiological studies suggest that omega-3 fatty acids have an antiarrhythmic effect. However, evidence from randomized controlled trials (RCTs) for prevention of sudden cardiac death (SCD) remains controversial. This study sought to evaluate the efficacy of omega-3 fatty acids for secondary prevention of SCD in patients with cardiovascular disease (CVD) in the era of guidelines-based therapy. METHODS: We conducted a PubMed/EMBASE/CENTRAL search for RCTs evaluating omega-3 fatty acids for CVD secondary prevention with at least 6 months follow-up and with data on SCD. Primary outcome was SCD. Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: Ten randomized controlled trials were identified evaluating a total of 33,429 patients with CVD. In patients with guidelines-adjusted therapy, omega-3 fatty acids did not reduce the risk ratio (RR) of SCD (RR:0.96; 95% CI: 0.84-1.10). In patients with non- guidelines-adjusted therapy, omega-3 fatty acids reduced the RR of SCD (RR: 0.64; 95% CI: 0.51-0.80). Overall, RR for cardiac death and all-cause mortality were 0.81 (95% CI: 0.69-0.95) and 0.89 (95% CI: 0.79-1.01), respectively. CONCLUSIONS: In the era of guidelines-adjusted treatment for CVD secondary prevention, omega-3 fatty acids do not appear to reduce SCD.

Activation of anterior cingulate cortex produces inhibitory effects on noxious mechanical and electrical stimuli-evoked responses in rat spinal WDR neurons.

In present study, in vivo electrophysiological techniques were applied to examine the effects of anterior cingulate cortex (ACC) activation on mechanical and electrical stimuli-evoked responses in rat spinal cord wide-dynamic-range (WDR) neurons. We found that bilateral ACC electrical stimulation (100Hz, 20V, 20s) had different effects on neuronal responses to brush, pressure and pinch stimuli (10s). The brush-evoked neuronal responses at baseline, post 1min and post 5min were 60.8±15.0, 59.2±15.4 and 60.0±19.3 spikes/10s, respectively (n=10, P>0.05 vs. baseline). The pressure-evoked neuronal responses at baseline, post 1min and post 5min were 77.8±11.9, 38.0±7.8 and 45.8±7.6 spikes/10s, respectively (n=10, P<0.05 vs. baseline). The pinch-evoked neuronal responses at baseline, post 1min and post 5min were 137.6±16.7, 62.6±17.5 and 68.8±15.0 spikes/10s, respectively (n=10, P<0.05 vs. baseline). Furthermore, ACC stimulation generated distinct effects on the different components of wind-up response. The total numbers of late response (LR) and after-discharge (AD), but not early response (ER), significantly decreased. Collectively, the present study demonstrated that short-term ACC activation could generate long-term inhibitory effects on the responses of WDR neurons to noxious mechanical (pressure and pinch) and electrical stimuli. The results indicated that ACC activation could negatively regulate noxious information ascending from spinal cord with long-term effect, providing potential neuronal substrate for the modulation of ACC activation on nociception.

[Mesenchymal stem cells exist in the compact bones from four species of mammals].

The biological properties of cultured mesenchymal stem cells (MSC) have been intensively investigated, while there is still a paucity of information about the definite in vivo sites that harbor these stem cells due to the lack of specific surface markers. Previous data have demonstrated that human and murine MSC can be isolated from the compact bones. To investigate if it is the case for other species, the femurs from Wistar rats, Beagles, C57 mice and New Zealand rabbits were collected, minced and digested with collagenase type I. The digested bone fragments were seeded into the medium for human bone marrow culture after removal of the suspended cells in the digestion. The results showed that the fibroblast-like cells were observed to migrate from the bone fragments after several days of culture, and they gradually formed an adherent confluent layer. The adherent cells could be passaged and expressed homogenously the mesenchymal cell marker vimentin. Differentiation assays showed that these cells had the capacity to differentiate into osteoblasts and adipocytes. In conclusion, the results here provide new information for the further investigations on the in vivo biological features of MSC in the context of the simplicity of the compact bone structure.