Up-regulation of BTLA expression in myeloid dendritic cells associated with the treatment outcome of neonatal sepsis.

Dentritic cells (DCs) dysfunction has been verified detrimental for sepsis and B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to be associated with DCs dysfunction. However, the role of BTLA expression in myeloid DCs (mDCs) in neonatal sepsis is unknown. In the current study, we found BTLA-expressing mDCs were elevated in neonates with sepsis and the BTLA expression level in mDCs was positively correlated to the severity of sepsis. The presence of BTLA negatively regulated the phagocytosis capacity and bactericidal ability of mDCs as well as the maturation markers expression of mDCs. Our data also showed BTLA+mDCs shifted into an anti-inflammatory phenotype with decreased expression of IL-6, TNF-α and IL-12, but increased IL-10. in addition, we found BTLA expression indeedly altered the mDCs allo-stimulatory capacity. Therefore, BTLA expression in mDCs could be a useful predictive marker for neonatal sepsis and targeting BTLA expression in mDCs may be a new therapeutic strategy.

BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-ß, Favoring Th2 and Foxp3+ Treg Polarization.

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA+ DCs. BTLA+ DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA+ DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA+ DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA+ mDCs produced larger amounts of IL-4 and TGF-ß than BTLA- mDCs in both HCs and APT patients. BTLA+ DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA+ DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3+ Tregs.

MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis.

Regulatory B cells (Bregs) have critical roles as a negative regulator of immunity, mainly due to the fact that it secrets high a level of interleukin 10 (IL-10). Recently, a new subset of Bregs was identified as a key source of IL-35, which is an immunosuppressive cytokine and conventionally thought to be secreted by regulatory T cells (Tregs). Our previous study showed that the level of IL-35 in serum was elevated in the patients with active tuberculosis (ATB). However, none of the studies reported that IL-35 is secreted by B cells in ATB patients. In the current study, we found that the mRNA expressions of the both subunits (p35 and Ebi3) of IL-35 by circulating B cells were increased in ATB patients. By using immunohistochemistry and immunofluorescence staining, we found a subset of B cells infiltrated into the tuberculous granuloma of ATB patients also expressed IL-35. Moreover, Mycobacterium tuberculosis (MTB) lysate stimulation assay also demonstrated higher levels of IL-35 were exerted by MTB lysate within purified B cells from healthy control group (HC). Flow cytometry analysis further showed that the IL-35-producing B cells from ATB patients produced a higher level of IL-10. Taken together, IL-35-producing B cells may play a regulatory role during MTB infection by producing IL-10.

The value of diffusion kurtosis imaging in assessing pathological complete response to neoadjuvant chemoradiation therapy in rectal cancer: a comparison with conventional diffusion-weighted imaging.

OBJECTIVES: The aim of this study is to comprehensively evaluate the advantage of diffusion kurtosis imaging (DKI) in distinguishing pathological complete response (pCR) from non-pCR patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation therapy (CRT) in comparison to conventional diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Fifty-six consecutive patients diagnosed with LARC were prospectively enrolled and underwent pre- and post-CRT MRI on a 3.0 T MRI scanner. Apparent diffusion coefficient (ADC), mean diffusion (MD) and mean kurtosis (MK) values of the tumor were measured in pre- and post-CRT phases and then compared to histopathologic findings after total mesorectal excision (TME). Both Mann-Whitney U-test and Kruskal-Wallis test were used as statistical methods. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: For a total of 56 rectal lesions (pCR, n = 14; non-pCR, n = 42), the MKpre and MKpost values were much lower for the pCR patients (mean±SD, 0.72±0.09 and 0.56±0.06, respectively) than those for the non-pCR patients (0.89±0.11 and 0.68±0.08, respectively) (p < 0.001). The ADCpost and the change ratio of apparent diffusion coefficient (ADCratio) values was significantly higher for the pCR patients (mean±SD, 1.31±0.13 and 0.64±0.34, respectively) than for the non-pCR patients (1.12±0.16 and 0.33±0.27, respectively) (p < 0.001 and p = 0.001, respectively). In addition, the MDpost and the change ratio of mean diffusion (MDratio) (2.45±0.33 vs. 1.95±0.30, p < 0.001; 0.80±0.43 vs. 0.35±0.32, p < 0.001, respectively) also increased, whereas the ADCpre, MDpre and the change ratio of mean kurtosis (MKratio) of the pCR (0.82±0.11, 1.40±0.21, and 0.23±0.010, respectively) exhibited a neglectable difference with that of the non-pCR (p = 0.332, 0.269, and 0.678, respectively). The MKpost showed relatively high sensitivity (92.9%) and high specificity (83.3%) in comparison to other image indices. The area under the receiver operating characteristic curve (AUROC) that is available for the assessment of pCR using MKpost (0.908, cutoff value = 0.6196) were larger than other parameters and the overall accuracy of MKpost (85.7%) was the highest. CONCLUSIONS: Both DKI and conventional DWI hold great potential in predicting treatment response to neoadjuvant chemoradiation therapy in rectal cancer. The DKI parameters, especially MKpost, showed a higher specificity than conventional DWI in assessing pCR and non-pCR in patients with LARC, but the pre-CRT ADC and MD are unreliable.

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis.

Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT. Meanwhile, the number of DCs was associated with the prolonged/complicated TB, ATD treatment effect and lymphocyte immune reactions, as manifested that relapsed APT patients with a higher number of tDC and lower number of pDC compared to newly diagnosed patients. Interestingly, mDC from APT patients displayed high expressions of CD83 and CCR7, but pDC displayed low expressions of CD83 and CCR7. Moreover, DCs from APT patients expressed lower levels of HLA-DR and CD80, but expressed a higher level of CD86 than those from HCs. However, the antigen uptake capacity of DC subsets was not different between APT and HCs, despite the antigen uptake capacity of pDC was much lower than that of mDC in both APT patients and HCs. Our data represent a systematic profile of DC subsets in the blood of APT patients, and would represent a useful biomarker for APT.

Regulatory effects of galanin system on development of several age-related chronic diseases.

Age is a major risk factor for developing chronic diseases, including type 2 diabetes, depression and Alzheimer's disease. The rapidly increase in the morbidity of these age-related chronic diseases is becoming a global problem. Although our understanding of these age-related diseases has tremendously been improved in recent years, certain aspects of their etiology and relative regulatory factors still remain elusive to clinicians and researchers. Emerging evidences suggest that neuropeptide galanin is involved in the pathogenesis of type 2 diabetes, depression and Alzheimer's disease. This article summarized relevant results of our and others studies to highlight the relationship between the galanin system and these age-related chronic diseases. On the one hand, a high galanin expression was found in subjects with type 2 diabetes, depression and Alzheimer's disease. On the other hand, current data suggest that galanin and its agonists (M617, M1145 and M1153) manifest the characters of anti-insulin resistance, anti-Alzheimer's disease and ameliorate or reinforce depression-like behavior. Specially, activation of GAL2 can alleviate those disease features in human and rodent models. These are helpful for us to understand the roles of galanin system in the pathogenesis of these age-related chronic diseases and to provide useful hints for the development of novel approaches to treat these complex diseases.

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation. BTLA-expressing CD11c APCs showed lower antigen uptake capacity, lower CD86 expression, higher HLA-DR expression, and enhanced IL-6 secretion, compared to counterpart BTLA negative CD11c APCs in healthy controls (HC). Interestingly, BTLA-expressing CD11c APCs from ATB patients displayed lower expression of HLA-DR and less IL-6 secretion, but higher expression of CD86 than those from HC volunteers. Mixed lymphocyte reaction suggests that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c APCs stimulatory capacity. This role is impaired in ATB patients manifested by low expression of HLA-DR and low production of IL-6. This previous unappreciated role for BTLA may have implications in the prevention and treatment of patients with ATB.

Tuberculosis-sensitized monocytes sustain immune response of interleukin-37.

Roles of human IL-37 in infections remain poorly characterized. Although plasma IL-37 is elevated in patients with tuberculosis (TB), IL-37 source and immune correlate in TB have not been investigated. It is also unknown whether and how TB can influence the ability of immune cells to mount innate responses of IL-37 and pre-inflammatory cytokines. Here, we demonstrated that IL-37b-producing monocytes coincided with a source of elevated plasma IL-37b in TB patients. While IL-37b production in TB was associated with prolonged/complicated TB, TB burdens and inflammatory reactions, it negatively correlated with immune responses of pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α or IL-10. Interestingly, mycobacterial re-infection of monocytes from TB patients, but not healthy BCG-vaccinated controls, enhanced or sustained IL-37b production by cultured monocytes. TB-sensitized monocytes from TB patients mounted more robust immune responses of IL-37b than those of pre-inflammatory cytokines during mycobacterial re-infection in culture. Our data represent new findings in terms of IL-37b responses, immune correlates and potential mechanisms in TB patients.

Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression. TB infection was associated with expression of p35 or EBI3 protein in CD4(+) but not CD8(+) T cells. Most p35(+)CD4(+) T cells and EBI3(+)CD4(+) T cells expressed Treg-associated marker CD25. Our findings may be important in understanding immune pathogenesis of TB. IL-35 in the blood may potentially serve as a biomarker for immune status and prognosis in TB.

BTLA associates with increased Foxp3 expression in CD4(+) T cells in dextran sulfate sodium-induced colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease, and its pathogenesis involves a variety of genetic, environmental, and immunological factors such as T helper cells and their secreted cytokines. B and T lymphocyte attenuator (BTLA) is an immunoregulatory receptor that has a strong suppressive effect on T-cell function. However the role of BTLA in UC remains poorly understood. Here we demonstrated that the frequency of BTLA-expressing CD3(+) T cells, especially CD4(+) T cells, increased in blood and mucosa in mice with DSS-induced colitis. The frequency of Foxp3-expressing cells in BTLA+ CD4(+) T cell from lamina propria mononuclear cells (LPMCs) was much higher in DSS-treated mice than that in controls. Similarly, the proportion of IL-17+ cells in BTLA+ CD4(+) T cells from LPMCs in DSS-treated mice is much higher than that in controls, while no perceptible difference for the proportion of IFN-γ+ cells in BTLA+ CD4(+) T cells was noted between DSS-treated mice and controls. Treatment of mesalazine, an anti-ulcerative colitis drug, down-regulated Foxp3 and IL-17 expression in BTLA positive T cells along with attenuated severity for colitis. Our findings indicate that BTLA may be involved in the control of inflammatory responses through increasing Foxp3 expression, rather than attenuating IL-17 production, in DSS-induced colitis.

BTLA exhibits immune memory for αß T cells in patients with active pulmonary tuberculosis.

Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αß T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αß T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αß T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLA(high) αß T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αß T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection.

Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles / 药学学报

The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

Effects of betaine, taurine, lycium barbarum polysaccharides in lycium barbarum L. on the pharmacokinetics of β-carotene in beagle dogs / 中国药学杂志

OBJECTIVE: To study the effects of betaine, taurine, lycium barbarum polysaccharides (LBP) in Lycium barbarum L. on the pharmacokinetics of β-carotenes(β-C) in beagle dogs. METHODS: Six Beagle dogs divided into two groups randomly, were given β-carotenes or β-carotenes combined with betaine, taurine or LBP, respectively. The concentrations of β-caro-tenes, retinol and retinol palmitate in dog plasma at different time points were determined by HPLC method. The main pharmacokinetic parameters were processed by the software DAS2.0.1. RESULTS: Compared with β-carotenes group, the t1/2 of β-carotenes was prolonged (P 0.05). CONCLUSION: Other ingredients in Lycium barbarum L. could influence the pharmacokinetic process of in Beagle dogs. The functions of nourishing liver and improving eyesight by Lycium barbarum L. did not result from a single component, but from its multi-ingredients.

Determination of irinotecanand its metabolite SN-38 in nanoparticles by LC-MS/MS in rats whole blood / 中国药学杂志

OBJECTIVE: To develop an LC-MS/MS method for determination of irinotecanin nanoparticles and its metabolite SN-38 in rats whole blood. METHODS: The drugs were using liquid-liquid extraction method in rats of whole blood, with diazepam as an internal standard. The Shim-pack XR-ODS (2.0 mm×100 mm, 2.2 μm) column was used. The gradient mobile phase consisted of 5 mmol·mL-1 ammonium formates solution (A) and Acetonitrile (B) at the flow rate of 0.3 mL·mL-1, the injection volume was 10 μL and the column temperature was 35°C. The total time of the analysis was 4.2 min. Electrospray ionization sourceand selective ion monitoringwere employed. RESULTS: The linear ranges of irinotecan and SN-38 were 1-2000 and 0.5-100 ng·mL-1, respectively; lower limit of quantification (LLOQ) was 1 and 0.5 ng·mL-1, respectively; the intra-batch RSD were less than 9.43% and 11.39%, respectively, the inter-batch RSD were less than 9.73% and 11.79%, respectively. The extraction recoveries were 73.7%-117.4% and 61.7%-75.5%, respectively. CONCLUSION: The method had less interference and is sensitive, accurate for the determination of irinotecan and its metabolite SN-38 in the whole blood of rats.

Assessing the role of IL-35 in colorectal cancer progression and prognosis.

Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.

Pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in Beagle dogs / 药学学报

The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.

Pharmacokinetics and tissue distribution of irinotecan hydrochloride nanoparticles / 药学学报

To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.

[Myocardial protective effect of ulinastatin against ischemia/reperfusion injury during open heart surgery with cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of ulinastatin on myocardium against ischemia-reperfusion injury in open heart surgery with cardiopulmonary bypass (CPB). METHODS: Twenty ASA I-II patients undergoing atrioseptopexy or surgical repair of ventricular septal defect under CPB were randomly divided into two groups of 10 patients. The patients in the ulinastatin group (U), 5 males and 5 females, aged 6.7 +/- 2.6, received ulinastatin 12,000 unit/kg, half of the dose being given intravenously 10 min before aorta cannulation and another half being added into the priming fluid. The patients in the control group (C), 6 males and 4 females, aged 5.9 +/- 2.7, received the same volume of normal saline instead of ulinastatin. Arterial blood samples were taken before CPB (T1), at release of the aortic cross-clamp (T2), 30 min after aortic release (T3), 4 h and 24 h after discontinuation of CPB (T4, T5) for determination of plasma levels of cardiac troponin I (cTnI), creatine phosphokinase (CK) and creatine phosphokinase isoenzyme (CK-MB). RESULTS: The CPB time, aortic cross-clamping time and duration of operation were comparable between these 2 groups. The plasma cTnI level and CK and CK-MB activities were all within normal range before CPB in both groups. In group C the plasma level of cTnI started to increase at T2, peaked at T4 and started to decrease at T5. In group U the plasma levels of cTnI at T3 and T4 were significantly higher than the baseline value (both P<0.01) and returned to the baseline value at T5. The plasma cTnI levels at T(3-5) were significantly lower in group U than in group C (all P<0.01). The plasma CK and CK-MB activities increased significantly at T(2-5) in both groups (all P<0.01). There was no significant difference in plasma CK and CK-MB activity at T(2-4) between the two groups, but at T5 their activities were significantly lower in group U than in group C (P<0.05). The rate of spontaneous recovery of heart beat without defibrillation was higher in group U (8/10) than in group C (4/10) (P<0.05). The drainage volume during the 24 hours after operation was greater in group C than in group U (P<0.05). CONCLUSION: Ulinastatin effectively protects myocardium from ischemia-reperfusion injury during open heart surgery with CPB.