[Medium- and long-term outcomes of cardiac assist devices after coronary artery bypass grafting in left ventricular dysfunction patients].

Objective: To evaluate the medium-and long-term outcomes of cardiac assist devices after coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction. Methods: From January 2012 to May 2018, a total of 127 patients with low left ventricular ejection fraction (LVEF) value (≤40%) undergoing CABG in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University were selected. Meanwhile, another 2 454 cases with LVEF>55% were also enrolled as controls. Clinical data of intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) application were compared and analyzed. All patients were followed up at the Outpatient Clinic at different time points (3 and 6 months after surgery, then every year). Results: Compared to the control group, IABP usage (10.2% vs 0.8%), ECMO usage (6.3% vs 0.3%) and the mortality (4.7% vs 0.7%) were higher (all P<0.05) in the left ventricular dysfunction group. Additionally, Intensive Care Unit stay [(50±12) h vs (33±10) h] and the hospital stay after surgery [(15±3) d vs (11±4) d] was longer in the left ventricular dysfunction group (all P<0.05). In the left ventricular dysfunction group, LVEF at 3, 6 month and 1 year was (48±8)%, (51±9)%, and (55±9)%, respectively, and then maintained stable. Conclusions: Patients with left ventricular dysfunction who received coronary artery bypass grafting had a high rate of cardiac assist devicesuse, however, optimal perioperative management can save the lives of some patients, whose medium-and long-term outcome are good. Therefore, it is worthy of being recommended in clinical practice.

[Mid-term multi-center outcomes of bilateral radial artery as conduits in coronary artery bypass grafting].

Objective: To evaluate the mid-term outcomes of bilateral radial artery (BRA) grafts in coronary artery bypass grafting (CABG). Methods: All perioperative medical records and follow-up results of CABG with BRA grafts in multi-centers of China were analyzed retrospectively. Results: A total of 211 patients (170 males and 41 females) underwent CABG grafting with BRA conduits between August 2013 and September 2018, with a mean age of (56.5±9.7) years old (rang 41 to 73 years). There were 161 cases of triple-vessel disease and 50 cases of two-vessel disease. Ninety patients had diabetes mellitus (DM), 35 patients with peripheral vascular disease, 4 patients with chronic obstructive pulmonary disease and 11 with heart valve disease. Two patients underwent off-pump CABG and 209 patients accepted on-pump CABG with commitment valve surgery. There were 210 cases of total arterial revascularization and 161 cases using left thoracic artery conduits, with a graft number of 2-4 (2.7±0.9). No operation-related death occurred, atrial fibrillation happened in 12 patients, hemothorax in 7 cases, and forearm hematoma in one case, hypoxemia in 13 cases and pneumonia in one case. The duration of mechanical ventilation was (8.3±4.7) hours and the mean hospital length of stay was (7.1±2.9) days. Follow-up was completed in 191 patients (90.52%) with a duration of 3-59 (35.5±9.3) months. The mean left ventricular ejection fraction at 3 months after operation was significantly improved, compared to that of the pre-operation (61.0%±7.2% vs 47.1%±5.3%, P=0.017). All patients survived, except that one died from brain injury. No major cardiac events occurred, with a cumulative survival rate of 100% at 1 year and 99.53% at 3 year after operation, respectively. It was showed in coronary CT angiography (CTA) examination that all grafts in 132 patients were patent at the mean follow-up duration of (21.5±6.4) months. Conclusions: BRA grafts as arterial conduit in CABG are proved to be safe, easy for total arterial revascularization and have good mid-term clinical results.

LncRNA-NEF inhibits proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating wnt/ß-catenin pathway.

OBJECTIVE: Our study aimed to investigate the role of lncRNA-Neighboring Enhancer of FOXA2 (NEF) in esophageal squamous-cell carcinoma. PATIENTS AND METHODS: Tumor tissues and adjacent tissues were obtained from esophageal squamous-cell carcinoma patients, and blood samples were extracted from both patients with esophageal squamous-cell carcinoma and healthy volunteers. The expression of NEF was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). All patients were followed-up for 5 years and ROC curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic values of serum NEF for esophageal squamous-cell carcinoma. NEF expression vector was transfected into cells of esophageal squamous-cell carcinoma cell lines. Cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay, and transwell invasion assay, respectively. The interaction between NEF and wnt/ß-catenin pathway were explored by Western blot and qRT-PCR. RESULTS: Expression of NEF was significantly downregulated in tumor tissues than in adjacent tissues in most patients. Serum level of NEF was higher in esophageal squamous-cell carcinoma patients than in healthy controls, and was significantly correlated with tumor size and tumor distant tumor metastasis. Serum NEF is a promising diagnostic and prognostic marker for esophageal squamous-cell carcinoma. NEF overexpression inhibited cancer cell proliferation, migration and invasion. NEF overexpression decreased the expression levels of wnt/ß-catenin pathway-related proteins, while Wnt activator showed no significant effects on NEF. However, Wnt inhibitor reduced the effects of NEF overexpression on cell proliferation, migration and invasion. CONCLUSIONS: LncRNA NEF may inhibit the proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating with wnt/ß-catenin pathway.

The expression of MMP-7 in serum and aneurysm tissues of patients with abdominal aortic aneurysm associated with hypertension and the clinical efficacy of endovascular exclusion.

OBJECTIVE: To investigate the expression of matrix metalloproteinase-7 (MMP-7) in abdominal aortic aneurysm (AAA) with hypertension, and the clinical efficacy of endovascular exclusion. PATIENTS AND METHODS: Seventy-two cases of AAA with hypertension were retrospectively analyzed. Patients were divided into the observation group (34 cases) and control group (38 cases). The control group was treated by AAA incision with artificial vascular replacement, while the observation group was treated by endovascular graft exclusion. Over the same period, 72 age- and sex-matched healthy adults and 72 patients with hypertension were selected. MMP-7 expression in patients with hypertension, aneurysm associated with hypertension, and healthy controls were measured by ELISA and immunohistochemical staining. RESULTS: ELISA showed that serum MMP-7 levels of patients with an aneurysm were significantly higher than those of patients with simple hypertension and healthy controls (p<0.05). The operative time, blood loss, and blood transfusion in the observation group were significantly lower than those in the control group (p<0.05). At the 1-month follow-up, the prevalence of pulmonary infection, incision infection, lower limb thrombosis, and lower limb weakness in the observation group were significantly lower than in the control group (p<0.05). The quality of life scores in the observation group after 1 and 3 months was significantly higher than those in the control group (p<0.05). Immunohistochemistry showed that the expression of MMP-7 in aneurysm tissue was significantly higher than in normal tissue. The expression of MMP-7 in the two groups was significantly decreased compared with before surgery (p<0.05). CONCLUSIONS: The detection of MMP-7 expression in hypertensive patients is an early marker of the occurrence of AAA. The use of endovascular exclusion for the treatment of AAA with hypertension is minimally invasive and safe. Furthermore, postoperative vital signs of patients are stable, and the quality of life is improved.

[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].

OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone.

Genistein is the most abundant isoflavone in soybeans. It has exhibited diverse biological activities, among these, its anticancer effects is most noteworthy. Through regulating critical cell cycle genes, genistein can inhibit cancer cell growth in vivo and in vitro. It has been reported that genistein can inhibit activation of NF-κB and Akt signaling pathways to induce cell apopt1osis, both pathways are well known for their function to maintain a balance between cell survival and apoptosis. In order to find out more outstanding anticancer isoflavone agents, against cancers extended synthesis of genistein derivatives has been carried out. Some of these synthetic compounds demonstrated higher anticancer activity with lower doses. Based on these results, genistein and its synthetic derivatives may be an emerging new type of anticancer agents.

Quantification of VEGF-C expression in canine mammary tumours.

BACKGROUND: Tumours release angiogenic factors such as vascular endothelium growth factor (VEGF), which induces growth of a capillary network around the tumour. Elevated concentrations of VEGF have been reported in human mammary gland tumours. METHODS: To evaluate the expression of VEGF-C mRNA in canine mammary tissue, 38 mammary gland tumours (including 15 benign and 23 malignant mammary tumours), and 4 normal mammary glands were investigated by real-time reverse transcriptase quantitative polymerase chain reaction. RESULTS: VEGF-C expression in the malignant mammary tumours was much higher than in the benign mammary tumours or normal mammary tissue (P < 0.001). The expression of VEGF-C in tumours with lymph node metastasis was much higher than in those without (P < 0.01). CONCLUSION: The level of expression of VEGF-C did not correlate with tumour size or the patient's age, but was significantly higher in malignant mammary tumours and related to lymph node metastasis, making it a candidate marker for predicting metastasis of canine mammary cancer.

Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells.

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.

[Mechanism of riboflavin deficiency facilitating carcinogenesis of N-nitrosamine--effect on carcinogen-metabolizing enzymes].

Previous studies have demonstrated the facilitating effect of riboflavin deficiency on the carcinogenesis of the liver of rats induced by N-nitrosamine. However, the mechanism was still not clear. In the present investigation, the alterations of microsomal carcinogen-metabolizing enzymes of rat liver during riboflavin-deficiency with simultaneous administration of nitrosodimethylamine (NDMA) were studied. The results showed that the enzyme activities of hepatic microsomal cytochrome P-450 and NDMA demethylase of riboflavin deficient rats and riboflavin deficient rats receiving NDMA were increased and significantly different from the control rats (P less than 0.05). The enzyme activities of hepatic microsomal NADPH-cytochrome P-450 reductase of riboflavin deficient rats and riboflavin deficient rats receiving NDMA were significantly decreased (P less than 0.01). All the alterations disappeared after supplying riboflavin to the deficient rats. This result indicates that the effect of riboflavin deficiency on carcinogen-metabolizing enzymes of rat liver is reversible.

Bioavailability of selenium to residents in a low-selenium area of China.

For 8 wk 5 groups of 10 men each were given 0.5 g/day DL-methionine, 150 micrograms Se/day as sodium selenite with or without methionine or 150 micrograms Se/day as selenomethionine with or without methionine. Twenty subjects received placebo as controls. Initially plasma Se rose more rapidly than RBC Se. Increases in Se levels were significantly greater with selenomethionine than with the selenite supplement. In the placebo and methionine supplemented groups neither plasma nor RBC Se varied significantly over the course of the study. Supplementation with selenium resulted in marked increases in plasma and RBC GSH-Px within 2 and 4 wk, respectively. Plasma and RBC GSH-Px activity did not differ significantly between Se-supplemented groups. These studies suggest that selenomethionine-Se was more effective in raising plasma and RBC Se than was selenite-Se. Methionine supplements may increase the bioavailability of selenium in severely deficient subjects.

Selenium intake and metabolic balance of 10 men from a low selenium area of China.

Selenium intake and urinary and fecal Se excretion of 10 healthy men from a low Se area in China were determined for three consecutive days, in summer, fall, and winter of 1983, and the spring of 1984 while self-selected diets were being consumed. Mean daily Se intake was 8.8 micrograms/day with a range of 2.3-35.5 micrograms/day, and was far below the recommended range of safe and adequate Se intake of 50-200 micrograms Se/day (National Academy of Sciences/National Research Council). Mean urinary and fecal Se outputs were 3.7 and 3.4 micrograms Se/day, respectively. Mean Se balance during this time was +1.8 micrograms Se/day. Apparent absorption of Se approximated 57%. The low Se intake in this area is a cause for concern since the residents of Molimo may be at risk for Se deficiency diseases.