Expression of Glut-1 and HK-II in Pancreatic Cancer and Their Impact on Prognosis and FDG Accumulation.

OBJECTIVE: The purpose of this article is to analyze the expression of Glut-1 and HK-II, the association between their expression and 18F-FDG accumulation in pancreatic cancer. METHODS: Fifty patients with histologically proven pancreatic cancer were included in this preliminary study, all of whom received 18F-FDG PET/CT performance before surgery. Immunohistochemical staining of tumor tissue and adjacent normal tissue was performed for Glut-1 and HK-II. By combining proportions and intensity of immunochemical staining, we obtained the modified immunohistological scores for Glut-1 and HK-II respectively. The relationship between expression of Glut-1, HK-II and series of parameters was analyzed, i.e. clinicopathological characteristics, prognosis of patients and SUVmax of PET-CT. RESULTS: Compared with normal tissue, the Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased (P<.001). There was no correlation between expression of Glut-1, HK-II and age, gender, tumor size, tumor location, tumor histological type, tumor differentiation, the nerve infiltration, vascular invasion, local infiltration, lymph node metastasis or tumor staging in pancreatic cancer (P>.05). During the follow-up period, the survival curves of low Glut-1 group and high Glut-1 group were statistically different (P=.049). Multivariate analysis (Cox regression) revealed that Glut-1 expression was not associated with mortality (P>.05). No statistical difference was found in the survival curves of negative HK-II group and positive HK-II group (P=.545). There was no correlation between 18F-FDG uptake and expression of Glut-1 and HK-II(P>.05). CONCLUSION: The Glut-1 and HK-II expression in pancreatic cancer tissue was significantly increased. There was no correlation between expression of Glut-1, HK-II and clinicopathological characteristics, prognosis and 18F-FDG uptake.

Mucosa-reparing and microbiota-balancing therapeutic effect of Bacillus subtilis alleviates dextrate sulfate sodium-induced ulcerative colitis in mice.

Gut microbiota composition of patients with ulcerative colitis (UC) is markedly altered compared with healthy individuals. There is mounting evidence that probiotic therapy alleviates disease severity in animal models and patients with inflammatory bowel disease (IBD). Bacillus subtilisis, as a probiotic, has also demonstrated a protective effect in IBD. However, the therapeutic mechanism of its action has yet to be elucidated. In the present study, a dextrose sulfate sodium (DSS)-induced UC mouse model was used to investigate the role of B. subtilis in the restoration of gut flora and determine its effective dose. Mucosal damage was assessed by performing alcian blue staining, cytokine levels were analyzed by ELISA and microbiota composition was investigated using 454 pyrosequencing to target hypervariable regions V3-V4 of the bacterial 16S ribosomal RNA gene. The results demonstrated that a higher dose B. subtilisis administration ameliorated DSS-induced dysbiosis and gut inflammation by balancing beneficial and harmful bacteria and associated anti- and pro-inflammatory agents, thereby aiding intestinal mucosa recovery from DSS-induced injuries. These findings indicate that choosing the correct dose of B. subtilis is important for effective UC therapy. The present study also helped to elucidate the mechanisms of B. subtilis action and provided preclinical data for B. subtilis use in UC therapy.

Effect of recombinant Lactobacillus casei expressing interleukin-10 in dextran sulfate sodium-induced colitis mice.

OBJECTIVE: To study the effect of recombinant Lactobacillus casei (L.casei) expressing interleukin (IL)-10 combined with 5-aminosalicylic acid (5-ASA) in dextran sulfate sodium (DSS)-induced colitis mice. METHODS: Recombinant L. casei CECT 5276, which can secrete IL-10, was constructed. The length of colon tissue, disease activity index (DAI) and histological score (HS) of the mice were determined to evaluate the modeling and the effectiveness of L. casei. Real-time polymerase chain reaction (PCR), Western blot and ELISA were used to determine the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor (PPAR)-γ, interferon (IFN)-γ, transforming growth factor (TGF)-ß and IL-10. RESULTS: Recombinant L. casei expressing IL-10 combined with 5-ASA was more effective than L. casei with 5-ASA. Among the three different concentrations of the recombinant L. casei, the highest concentration group (2 × 10(9) colony-forming units/mL) had the best effectiveness. CONCLUSIONS: Recombinant L. casei combined with 5-ASA is effective in the treatment of DSS-induced colitis. The possible mechanism might be the blocking of the excessive activation of NF-κB pathway, thus suppressing the release of inflammation-related factors.

Surgery for left ventricular aneurysm after myocardial infarction: techniques selection and results assessment.

BACKGROUND: The most appropriate surgical approach for patients with post-infarction left ventricular (LV) aneurysm remains undetermined. We compared the efficacy of the linear versus patch repair techniques, and investigated the mid-term changes of LV geometry and cardiac function, for repair of LV aneurysms. METHODS: We reviewed the records of 194 patients who had surgery for a post-infarction LV aneurysm between 1998 and 2010. Short-term and mid-term outcomes, including complications, cardiac function and mortality, were assessed. LV end-diastolic and systolic dimensions (LVEDD and LVESD), LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) and LV ejection fraction (LVEF) were measured on pre-operative and follow-up echocardiography. RESULTS: Overall in-hospital mortality was 4.12%, and major morbidity showed no significant differences between the two groups. Multivariate analysis identified preoperative left ventricular end diastolic pressure > 20 mmHg, low cardiac output and aortic clamping time > 2 hours as risk factors for early mortality. Follow-up revealed that LVEF improved from 37% pre-operation to 45% 12 months post-operation in the patch group (P = 0.008), and from 44% pre-operation to 40% 12 months postoperation in the linear group (P = 0.032). In contrast, the LVEDVI and LVESVI in the linear group were significantly reduced immediately after the operation, and increased again at follow-up. However, in the patch group, the LVEDVI and LVESVI were significantly reduced at follow-up. And there were significant differences in the correct value changes of LVEF and left ventricular remodeling between linear repair and patch groups. CONCLUSIONS: Persistent reduction of LV dimensions after the patch repair procedure seems to be a procedure-related problem. The choice of the technique should be tailored on an individual basis and surgeon's preference. The patch remodeling technique results in a better LVEF improvement, further significant reductions in LV dimensions and volumes than does the linear repair technique. The results suggest that LV patch remodeling is a better surgical choice for patients with post-infarction LV aneurysm.

Osteopontin is required for angiotensin II-induced migration of vascular smooth muscle cells.

Migration and proliferation of vascular smooth muscle cells (VSMCs) play a prominent role in the development of atherosclerotic plaques and restenosis lesions. Angiotensin II (Ang-II) is typically associated with excessive proliferation and migration of VSMCs and vascular remodeling. High levels of osteopontin (OPN) mRNA and protein were reported in human atherosclerotic plaque from the aorta, carotid and coronary arteries. However whether OPN plays a role in VSMCs migration induced by Ang-II is unknown. Here we show that, in primary cultured rat VSMCs, Ang-II exhibits chemotactic effect on cultured VSMCs and induces OPN expression dose-dependently. With a lentiviral shRNA specifically targeting OPN and transwell migration assay, we find that blockade of OPN with shRNA inhibits Ang-II-induced MMP9 upregulation and VSMCs migration. Our results demonstrated that OPN is required for Ang-II to induce VSMCs migration and suggested OPN as a potential target in preventing atherosclerotic development.

Role of osteopontin in the development of neointimal hyperplasia in vein grafts.

OBJECTIVES: Neointimal hyperplasia and superimposed atherosclerosis are central to late vein graft failure following coronary artery bypass grafting. Recent studies on post-injury arterial vessels have suggested a role of osteopontin (OPN) in the process of vascular remodelling. This study was designed to assess the in vivo performance of OPN following vein grafting. METHODS: Bilateral saphenous vein-carotid artery interposition grafting was performed in 16 Large White pigs (35-45 kg). All patent vein grafts were removed and fixed at 1, 2, 4 (n = 8 grafts in each group) and 12 weeks (n = 6 grafts) following surgery. Multiple histological sections from each graft were prepared. The expression of OPN in the vein grafts was determined by immunostaining and western blot assay. Proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Vein graft morphology was assessed using computer-aided planimetry. RESULTS: The expression of OPN remarkably increased in the intima of the vein grafts at the first week postoperatively and then gradually declined from the second postoperative week, although OPN expression remained significantly higher than the baseline level at the end of the 3-month study period. More importantly, the number of PCNA-positive cells and matrix metalloproteinases (MMPs) expression correlated well with the OPN expression. CONCLUSIONS: Early induction of OPN in vein grafts may contribute to the subsequent increase in MMPs activities as well as vascular smooth muscle cell proliferation. Therefore, OPN could play an important role in the development of neointimal hyperplasia in venous conduits after coronary artery bypass grafting.

[Clinical application of extracorporeal membrane oxygenation for severe heart failure during peri-operative period of end-stage cardiopathy].

OBJECTIVE: To summarize the clinical effect and experience of extracorporeal membrane oxygenation (ECMO) support for severe heart failure during peri-operative period of end-stage cardiopathy. METHODS: From June 2007 to July 2010, 6 patients with severe heart failure during peri-operative period of end-stage cardiopathy received ECMO support. The changes in the hemodynamics and outcome of the patients during the use of ECMO were investigated. RESULTS: The duration of ECMO assistance ranged from 23 to 168 hours with a mean of 78 hours. The hemodynamics after using ECMO was much improved than before ECMO [mean arterial pressure (mm Hg, 1 mm Hg=0.133 kPa): 78.13±8.01 vs. 47.75±5.21, central venous pressure ( mm Hg ): 11.03±3.21 vs. 19.36±4.51, cardiac output (L/min): 4.93±1.01 vs. 3.50±0.81, cardiac index (L×min(-1)×m(-2)): 2.71±0.51 vs. 1.91±0.40, pulmonary artery wedge pressure ( mm Hg ): 12.72±6.52 vs. 20.22±6.91, venous oxygen saturation: 0.66±0.13 vs. 0.54±0.07], and the amount of using inotropic drug was significantly reduced compared with that before ECMO [dopamine (µg×kg(-1)×min(-1)): 5.05±0.85 vs. 14.20±5.05, epinephrine (µg×kg(-1) ×min(-1)): 0.05±0.01 vs. 0.24±0.04, all P<0.05]. All patients were successfully weaned from ECMO. After weaning, 3 patients recovered and discharged, and the hospital discharge rate was 50%, while 3 patients died of multiple organ failure (MOF). Major complication was bleeding, disseminated intravascular coagulation, infection, embolism. CONCLUSION: ECMO is an important extracorporeal method to support life. ECMO is an effective measure of treatment for end-stage cardiopathy patients with peri-operative severe heart failure. It is important to properly select patients for ECMO.

[Surgical treatment of post-infarction left ventricular aneurysm: clinical analysis].

OBJECTIVE: To explore the clinical experiences, efficacies and postoperative left ventricular remodeling changes of surgical ventricular reconstruction in the treatment of post-infarction left ventricular aneurysm. METHODS: The investigators reviewed retrospectively the clinical data, operative approaches and follow-up outcomes of consecutive 194 patients with post-infarction left ventricular aneurysm, who underwent surgical ventricular reconstruction between January 1997 and December 2009. There were 54 cases in the linear group and 137 cases in the endoventricular patch plasty group. The changes of ventricular remodeling were measured by peri-operative and follow-up echocardiography. RESULTS: All patients underwent surgery with a mean cardiopulmonary bypass duration of (103 ± 35) min and aortic cross clamp duration of (62 ± 26) min. There were 8 per-operative deaths with a mortality rate of 2.2%. Angina pectoris of other cases disappeared and heart function greatly improved. After operation, the ventricular remodeling results showed that in the linear group, there was not significant difference in the changes of ventricular remodeling of post-op 2 weeks, 6 months, 1 year and 5 years versus pre-operation. However, in the endoventricular patch group, the changes of ventricular remodeling of post-op 2 weeks and follow-up 6 months versus pre-operation were significantly reduced (P < 0.05). End-systolic volume (LVESV) reduced from (129 ± 27) ml to (65 ± 8) ml and end-systolic volume index (LVESVI) decreased from (104 ± 14) ml/m(2) to (44 ± 6) ml/m(2) and the subgroup of LVEF < 35% was the most significant in the changes of LVESV and LVESVI. But LVEF improved significantly at post-operation and follow-up (from preoperation 42% ± 11% to 52% ± 7% during follow-up). CONCLUSIONS: For patients with infarction left ventricular aneurysm, left ventricular reconstruction is quite effective. The choice of operative approaches is determined by the size and range of ventricular aneurysm. Both string suture and endoventricular patch plasty technique can yield similarly satisfactory surgical outcomes. After operation, ventricular volume significantly decreases and cardiac function greatly improves.

Is the use of cardiopulmonary bypass for isolated coronary artery bypass an independent predictor of mortality and morbidity in patients with severe left ventricular dysfunction?

BACKGROUND: Patients presenting with severe left ventricular dysfunction (SLVD) undergoing conventional coronary artery bypass grafting (CCABG) are at an increased risk of perioperative mortality and morbidity. The aim of this study was to assess the risk factors responsible for mortality and morbidity among patients with SLVD by comparing CCABG and off-pump coronary artery bypass surgery (OPCAB). METHODS: We retrospectively evaluated 186 consecutive patients with SLVD who underwent coronary artery bypass grafting (CABG), including 102 by CCABG and 84 by OPCAB. Registry database, medical notes, and charts were studied for preoperative and postoperative data of the patients. Different variables and risk factors (preoperative, intraoperative, and postoperative) were evaluated and compared. The morbidity and mortality outcomes were compared in the two groups. The follow-up results and quality of life were assessed after surgery. RESULTS: The two groups had similar percentage of patients with preoperative high-risk profiles and no significant differences were found between groups in baseline variables such as age or comorbidities. There was a significant difference in the number of grafts used between the two groups. CCABG patients received (3.6 +/- 0.5) grafts per patient, while OPCAB patients had (2.7 +/- 0.6) grafts (P < 0.05). Completeness of revascularization was also significantly different between the two groups (CCABG 91.1% vs OPCAB 73.8%, P < 0.05). The hospital mortality was similar in the two groups (4.8% in OPCAB vs 5.9% in CCABG). The risk-adjusted mortality, according to the calculated propensity score, did not reach statistical significance in the two groups. In this study, OPCAB seemed to have a beneficial effect on reducing reoperation for bleeding, blood transfusion requirement, and the length of stay at ICU. But the incidence of perioperative myocardial infarction was more common in the off-pump group (P < 0.05). The degree of improvement in angina and quality of life did not differ significantly between the two groups. CONCLUSIONS: Using cardiopulmonary bypass is not an independent predictor of mortality and morbidity in patients with SLVD. Isolated CABG can be safely performed in SLVD patients with acceptable postoperative morbidity and mortality in addition to encouraging home discharge rates and higher quality of life. Therefore, CCABG remains a viable option in selected patients with SLVD.

[Stereological study on the myocardial protection in mitral valve replacement with beating heart under mild hypothermia].

OBJECTIVE: To appraise objectively the myocardial protective effect of beating heart with mild hypothermia and cardiopulmonary bypass (CPB) with cardiac arrest by cold cardioplegia perfusion during open-heart operation for mitral valve replacement (MVR). METHODS: Forty patients with rheumatic heart disease were randomly allocated to two groups: (1) beating heart group: 20 cases of MVR with beating heart under mild hypothermia and CPB; (2) heart arrest group: 20 cases of MVR with heart arrest by using cold blood cardioplegia (CBC) and CPB. Samples of myocardium were obtained at 3 times points during CPB, and myocardial ultrastructure was observed and analysed for both groups. RESULTS: There was no difference in ultrastructure of pre-operation specimens between two groups. Dmit and Amit were higher in arrested heart group than those in beating heart group during operation and after operation, but Vmit, Namit and delta mit were significantly lower in cardiac arrest group than those in beating heart group (P<0.05 or P<0.01). There were no significant differences of Vvmyo between preoperative stage and intraoperative stage (both P>0.05) in both groups, while Vvmyo and delta myo of postoperation stage were significantly lower in heart arrest group than beating heart group (P<0.05 and P<0.01). CONCLUSION: Beating heart during open-heart surgery is a good method to protect the myocardium being close to physiological condition, and the protective effect may be attributed to alleviation of ischemia/reperfusion injury.

Comparative study of on-pump and off-pump coronary bypass surgery in patients with triple-vessel coronary artery disease.

BACKGROUND: Studies on selected patients undergoing off-pump versus on-pump coronary artery bypass surgery have produced inconsistent results, especially in patients with multiple coronary artery disease. This study compared the clinical results of on-pump and off-pump coronary bypass surgery in patients with triple-vessel disease. METHODS: A total of 300 consecutive isolated, multiple coronary artery bypass grafting (CABG) patients were assigned to the off-pump coronary artery bypass (OPCAB, n = 150) or CABG with cardiopulmonary bypass (CCABG, n = 150) groups. There were no significant differences regarding degree of angina, history of myocardial infarction or diabetes, and presence of left main coronary artery disease between the two groups. Ejection fraction in the OPCAB group before surgery was lower than in the CCABG group (P < 0.01). In addition, more patients had a history of stroke and abnormal renal function preoperatively in the OPCAB group (P < 0.01). In OPCAB patients, single deep pericardial stay suture with a sling snared down was used to expose the target vessels, along with a stabilizer and a coronary shunt. A Medi-Stim Butterfly Flowmeter was used to measure blood flow through grafts in both groups. RESULTS: No OPCAB patient was converted to the CCABG group. The average numbers of distal anastomoses and the indexes of completeness of revascularization (ICR) were similar in both groups. Postoperative respiratory support time and the volumes of chest tube drainage and of blood transfusions were less in the OPCAB group than in the CCABG group (both P < 0.01). The postoperative incidences of pulmonary dysfunction and renal insufficiency were lower in the OPCAB group than in the CCABG group (both P < 0.05). There were no significant differences between the two groups in mortality and other causes of morbidity (perioperative myocardial infarction, stroke, atrial fibrillation). CONCLUSIONS: OPCAB can be applied to patients with triple-vessel coronary artery disease and can achieve similar completeness of revascularization and similar early surgical results, with shorter respiratory support, reduced transfusion requirement, and fewer cases of pulmonary dysfunction and abnormal renal function.