Effects of high-dose ulinastatin on inflammatory response and pulmonary function in patients with type-A aortic dissection after cardiopulmonary bypass under deep hypothermic circulatory arrest.

OBJECTIVES: To investigate effects of high-dose ulinastatin on the release of proinflammatory cytokines and lung injury in patients with aortic dissection after cardiopulmonary bypass (CPB) under deep hypothermic circulatory arrest (DHCA). DESIGN: A prospective, randomized and double-blinded study. SETTING: A teaching hospital. PARTICIPANTS: Thirty-six patients with acute type-A aortic dissection undergoing cardiac surgery using CPB under DHCA. INTERVENTIONS: These patients randomly were selected to received total doses of 20,000 units/kg of ulinastatin (n = 18) or 0.9% saline (control, n = 18) at 3 time points (after anesthetic induction, before aortic cross-clamp, and after aortic cross-clamp release). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor-alpha, interleukin 6, interleukin 8 and polymorphonuclear neutrophil elastase (PMNE) were measured after anesthetic induction (T0), 30 minutes (T1) after aortic cross-clamp, 3 (T2), 6 (T3) and 9 (T4) hours after weaning from CPB. Except for T1, pulmonary data, such as alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, plateau pressure, static compliance and dynamic compliance, were obtained at the same time points. Concentrations of cytokines and PMNE were significantly lower in the ulinastatin group than the control group from T1 to T4, and peaked at T2 between the 2 groups. Compared with the pulmonary data of the control group at T2~T4, postoperative alveolar-arterial oxygen pressure difference, physiologic deadspace, peak inspiratory pressure, and plateau pressure significantly were lower, and static compliance and dynamic compliance higher in the ulinastatin group. Significantly shorter intubation time and intensive care unit stay were found in the ulinastatin group. CONCLUSIONS: High-dose ulinastatin attenuates the elevation of cytokines and PMNE, reduces the pulmonary injury and improves the pulmonary function after CPB under DHCA. Consequently, it shortens the time of intubation and intensive care unit stay.

Integrated bioinformatics and machine learning algorithms reveal the critical cellular senescence-associated genes and immune infiltration in heart failure due to ischemic cardiomyopathy.

Heart failure (HF) is the final stage of many cardiovascular illnesses and the leading cause of death worldwide. At the same time, ischemic cardiomyopathy has replaced valvular heart disease and hypertension as the primary causes of heart failure. Cellular senescence in heart failure is currently receiving more attention. In this paper, we investigated the correlation between the immunological properties of myocardial tissue and the pathological mechanisms of cellular senescence during ischemic cardiomyopathy leading to heart failure (ICM-HF) using bioinformatics and machine learning methodologies. Our goals were to clarify the pathogenic causes of heart failure and find new treatment options. First, after obtaining GSE5406 from the Gene Expression Omnibus (GEO) database and doing limma analysis, differential genes (DEGs) among the ICM-HF and control groups were identified. We intersected these differential genes with cellular senescence-associated genes (CSAG) via the CellAge database to obtain 39 cellular senescence-associated DEGs (CSA-DEGs). Then, a functional enrichment analysis was performed to elucidate the precise biological processes by which the hub genes control cellular senescence and immunological pathways. Then, the respective key genes were identified by Random Forest (RF) method, LASSO (Least Absolute Shrinkage and Selection Operator) algorithms, and Cytoscape's MCODE plug-in. Three sets of key genes were taken to intersect to obtain three CSA-signature genes (including MYC, MAP2K1, and STAT3), and these three CSA-signature genes were validated in the test gene set (GSE57345), and Nomogram analysis was done. In addition, we assessed the relationship between these three CSA- signature genes and the immunological landscape of heart failure encompassing immunological infiltration expression profiles. This work implies that cellular senescence may have a crucial role in the pathogenesis of ICM-HF, which may be closely tied to its effect on the immune microenvironment. Exploring the molecular underpinnings of cellular senescence during ICM-HF is anticipated to yield significant advances in the disease's diagnosis and therapy.

Evaluation of antioxidant and immunity function of tetramethylpyrazine phosphate tablets in vivo.

The aim of the study was to determine the effect of tetramethylpyrazine phosphate tablets (TPT), a Chinese medicine used for cardiovascular disease, on immunity activity and oxidative injury in rats. Heart failure (HF) was induced by isoproterenol (ISO). After the animal model was established, the rats were administered the TPT by gavage (once a day). The results indicated that TPT improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dP/dt, heart weight/body weight. TPT could decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Furthermore, it also could raise the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but reduce malonyldialdehyde (MDA) level. The results indicated that TPT improved cardiac function and myocardial fibrosis from myocardial injury, and this cardioprotection might be attributed to a reduction of oxidative stress and regulation of inflammation mediators.

Evaluation of the pharmacological function of ulinastatin in experimental animals.

Organ protection is a routine therapy in severe injuries. Our aim was to evaluate the beneficial effects of ulinastatin in experimental rats. Rats were randomly divided into a sham control, a model control and an ulinastatin-treated group. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined. Serum amylase, serum aspartate aminotransaminase (AST), lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CKMD) activities, interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and cardiac troponin I (nTnl) levels were examined. Results showed that ulinastatin decreased MDA levels and ameliorated the down-regulation of SOD activity. In addition, ulinastatin pretreatment may decrease serum AST, LDH and CKMD activities, IL-8, TNF-α, and nTnl levels, and enhance NO level. Our results demonstrated that oxidative injury occurred after IR and that ulinastatin exhibits significant protective effects against these effects.

[Liver transplantation for primary biliary cirrhosis: retrospective analysis of 52 patients in QLTS].

OBJECTIVE: Retrospectively analyzing post-transplant primary biliary cirrhosis patients to document the actual survival time, the cause of post-transplant death, and recurrences after liver transplantation in patients followed up by the Queensland Liver Transplant Service (QLTS). METHODS: The case notes of all post-piggyback liver transplantation patients followed up by QLTS were reviewed. We analyzed the clinical characteristics of the PBC patients, post-transplant actual survival rates, the causes of post-transplant death, and risk factors of recurrence, and compared the survival rates between patients with and without liver transplantation using a European model. RESULTS: Fifty-two post-transplant patients with 54 transplantations were identified with an average age of 53 years and a mean follow-up time of 55 months. The actual survival times of PBC patients with grafts for 1 years, 5 years and 10 years were 88.4%, 80.1%, 76.9% and 80.9%, 65.4%, 19.8%. The causes of death were MOF intra-abdominal bleeding, renal failure, sepsis and cardiovascular diseases. Comparing the survival rates between with and without transplantation, 8.5% of PBC patients have recurrences with an average recurrent time of 34 months. CONCLUSION: (1) Liver transplantation could improve survival rates, but the optimum time for transplantation should be focused on; (2) A long-term and larger follow-up sampling should be done to understand the effects of recurrences on patient's long-term survival; (3) CsA may play a more important role in preventing recurrence of PBC than Tacrolimus

Serum erythropoietin level predicts the prognosis of chronic heart failure with or without anemia.

The aim of this study was to explore the correlation of erythropoietin (EPO) with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hs-CRP) in patients with chronic heart failure (CHF) or CHF complicated with anemia, in addition to its correlation with the prognosis of the patient. A total of 217 CHF patients were enrolled in this study. The patients were graded according to the cardiac function criteria of the New York Heart Association (NYHA). The serum EPO, NT-proBNP and hs-CRP levels of the patients were determined. The patients were followed up for ≥24 months. The EPO expression level in patients with NYHA II-IV CHF was significantly higher compared with that in the control group (P<0.05). EPO expression increased with the aggravation of CHF, exhibiting significant differences amongst the various NYHA graded groups (P<0.05). The EPO expression level increased significantly with an increase in NHA grade in addition to the severity of the anemia in the patients with CHF complicated by anemia (P<0.05). In the patients who succumbed (mortality group), the expression level of EPO was significantly higher and the hemoglobin level was significantly lower compared with those of the survival group (P<0.05). The EPO expression levels were elevated in CHF patients and patients with CHF and anemia. The level of expression correlated positively with the severity of CHF as well as that of anemia. Serum EPO measurements were successful in predicting the mortality and re-hospitalization rates of CHF patients at the end point, within two years of follow-up.

Combined devascularization and proximal splenorenal shunt: is this a better option than either procedure alone?

BACKGROUND/PURPOSE: We aimed to determine the rationality of pericardial devascularization (PCDV) plus proximal splenorenal shunt (PSRS) for cirrhotic patients with portal hypertension with variceal bleeding, using a duplex sonography study of the effects of the different surgical procedures (PCDV, PSRS, and PCDV + PSRS) on the hemodynamics of the portal system. METHODS: Ninety-nine patients with cirrhotic portal hypertension and a history of bleeding esophageal varices were studied. These patients were divided into three groups (PSRS group, PCDV group, and PCDV + PSRS group). The hemodynamic parameters of the portal systems of all patients were measured by Doppler color-flow imaging perioperatively. RESULTS: In the PSRS group, the postoperative portal venous flow (PVF) and free portal pressure (FPP) decreased by 57 +/- 9% and 52 +/- 5%, respectively (P < 0.01). In the PCDV group, the postoperative PVF lessened by 8 +/- 5% (P > 0.05), and the postoperative FPP was reduced by 19 +/- 7% (P < 0.05). In the PCDV + PSRS group, the postoperative PVF and FPP were lowered by 36 +/- 8% and 34 +/- 10%, respectively (P < 0.05). The postoperative decreases of PVF and FPP in the PCDV + PSRS group were between those of the PSRS and PCDV groups. The differences among these groups were statistically significant (P < 0.05). CONCLUSIONS: Combined devascularization and splenorenal shunt (PCDV + PSRS) significantly decreases portal venous flow and portal pressure, as well as maintaining hepatopedal flow, thus entailing fewer complications compared to either PCDV or PSRS. We aimed to determine the rationality of pericardial devascularization (PCDV) plus proximal splenorenal shunt (PSRS) for cirrhotic patients with portal hypertension with variceal bleeding, using a duplex sonography study of the effects of the different surgical procedures (PCDV, PSRS, and PCDV + PSRS) on the hemodynamics of the portal system.