Changes of immune function and mortality in patients with sepsis-induced stress hyperglycemia

AIM: To investigate the role of stress hyperglycemia on condition assessment and predicting prognosis in patients with sepsis. METHODS: The study included 44 patients with sepsis, divided into three groups according to their blood glucose profile within 24 h after admission: patients with stress hyperglycemia (group SH, n=15), diabetes mellitus type 2 (group DM, n=10), and normal glucose levels (group NG, n=19). CD4+/CD8+ ratio, Th1/Th2 ratio and HLA-DR% of the patients were measured within 24 h after admission by flow cytometry as assessment of their immune function. The sepsis-related organ failure assessment (SOFA) scores and acute physiology and chronic health evaluation II (APACHE II) scores of patients were recorded at the same time to analyze whether stress hyperglycemia affects the immune function and the 28 d mortality in patients with sepsis. RESULTS: A higher mortality rate of septic patients with stress hyperglycemia was observed compared to diabetic patients (53.3% vs 10.0%) and group NG (53.3% vs 21.1%). SOFA score and APACHE II score were higher in group SH than those in group DM and group NG while lower levels of human leucocyte antigen DR (HLA-DR) expression and CD4+/CD8+ ratio was found in group SH than those in group DM and group NG. No difference in the levels of Th1/Th2 among the three groups was observed. Non-survivors had higher levels of SOFA score, APACHEⅡ score, Th1/Th2 ratio and HLA-DR%. No difference was detected for CD4+/CD8+ ratio, mean glucose values and age. CONCLUSION: Stress hyperglycemia is associated with decreased immune function and an adverse clinical outcome in patients with sepsis.     

Significance of BNP and APACHE II score on prognosis assessment of critically ill patients

AIM: To evaluate the role of plasma B-type natriuretic peptide (BNP) level and the score of acute physiology and chronic health evaluation II (APACHE II) in the prognosis assessment of critically ill patients. METHODS: Sixty-two critically-ill patients in ICU fo the First Affiliated Hospital of Jinan University were enrolled from October 2009 to February 2010. The APACHE II score was calculated and plasma BNP level was measured within the first 24 h after admission. The correlations between BNP/APACHE II score and length of hospitalization, rate of mechanical ventilation application, duration of ventilation and fatality rate were analyzed.RESULTS: There were 44 survivals and 18 deaths in 62 admissions. The average APACHE II score and plasma BNP level in the survival group were higher than those in death group (P<0.01). Sixty-two patients were divided into 3 groups according to their APACHE II scores. With increased BNP level, APACHE II score, rate of mechanical ventilation application and fatality rate were also increased. CONCLUSION: The increasing level of BNP and APACHE II score have significant implications in prognosis assessment of survival rate, rate of mechanical ventilation application, duration of ventilation and length of hospitalization in critically ill patients.     

The euthyroid sick syndrome in severe SIRS patients

AIM: To assay the pattern of thyroid hormone alternations in systemic inflammatory response syndrome (SIRS) patients. METHODS: 50 SIRS patients were enrolled, divided into two groups as to whether they got MODS. Thyroid hormone measurements were taken, including total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4) and TSH. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) score was calculated according to clinical data. Outcome (recovery or deterioration) was recorded, as well as the length of time from the onset of SIRS to the day when thyroid hormones were measured (the duration of SIRS). RESULTS: Euthyroid sick syndrome (ESS) was presented in 45 cases. TT3 level was negatively correlated with APACHEⅡscore (r＝-0.330, P<0.05), and TT3/TT4 value was negatively correlated with the duration of SIRS (r=-0.316, P<0.05). TT3, TT4 and FT3 levels in the MODS patients were significantly lower than those in the patients without MODS (P<0.05). MODS patients got low TT4 or FT4 levels more frequently than those without MODS (P<0.05). Compared to the normal TSH group, patients with low TSH had lower T3 and T4, higher APACHEⅡscores, higher proportion of MODS, and higher proportion of recovery, but no differences were observed (P>0.05). CONCLUSION: SIRS patients has high possibility to get ESS, which happens more frequently and severely in MODS patients. With the persistence and aggravation of SIRS, there is a progression of thyroid hormone reduction.     

Hydrogen sulfide attenuates urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway

AIM:To explore the effect of hydrogen sulfide (H₂S) on urosepsis-induced acute kidney injury. METHODS:New Zealand white rabbits were randomly divided into control group, sham group, model (sepsis) group, NaHS treatment (NaHS) group, and NaHS combined with TAK-242 (a TLR4 inhibitor) treatment (NaHS+TAK-242) group. After treatment for 72 h, HE staining was used to measure the histopathological changes of rabbit kidney. The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by automatic biochemical analyzer. The serum levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), procalcitonin (PCT), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The TLR4/MyD88/PI3K signaling pathway-related proteins in the kidney were determined by Western blot. RESULTS:Compared with control group, obvious damage was observed in the kidneys of septic rabbits, but the kidneys were markedly improved by treatment with NaHS. The levels of BUN, SCr, NGAL, KIM-1, PCT, IL-1β, IL-6 and TNF-α in the septic rabbits were higher than those in control group, and decreased significantly in NaHS group and NaHS+TAK-242 group. The protein levels of TLR4, MyD88, p-PI3K and p-Akt in septic rabbit kidneys were higher than those in control group. However, NaHS or NaHS+TAK-242 inhibited the activation of TLR4/MyD88/PI3K signaling pathway in the kidneys of septic rabbits. CONCLUSION:H₂S play a protective effect on the rabbits with urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway to inhibit inflammatory response.     

Serum levels of TNF-α, IL-6, IL-10, CRP and D-dimer in patients with multiple organ dysfunction syndrome

AIM: To determine the changes of the serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), IL-10, C reactive protein (CRP) and D-dimer in the patients with multiple organ dysfunction syndrome (MODS) and compare the relationship between the levels of cytokines in early stage and MODS. METHODS: The serum values of TNF-α, IL-6, IL-10, CRP and D-dimer were measured in 27 patients with MODS in 1 d, 3 d and 5 d after undergoing disease, and compared with the adult peripheral blood of 15 normal controls. The levels in the first undergoing day between the lived group (n=19) and died group (n=8) were compared. RESULTS: The serum levels of TNF-α, IL-6, IL-10, CRP and D-dimer in MODS group were higher than that in control (P<0.05). With the development of the MODS, the levels of TNF-α, IL-6, IL-10, CRP and D-dimer were higher gradually. The level of IL-10 was increased at the third day. The levels of TNF-α, IL-6, IL-10, CRP and D-dimer in the first day of MODS in died group were higher than those in lived group, especially IL-6 and D-dimer (P<0.01). CONCLUSION: Determining the serum levels of TNF-α, IL-6, IL-10, CRP and D-dimer in MODS patients is helpful to guide the diagnosis and outcome.     

Serum acute phase reactants sCRP,SAA, IL-6 in acute coronary syndrome and its clinical significance

AIM: To investigate the possible involvement of CRP, SAA, IL-6 and its significance in acute coronary syndrome. METHODS: Serum SAA, IL-6 and sCRP levels in 40 patients with AMI, 40 patients with UAP and 40 controls were measured by means of ELISA. RESULTS: Serum SAA, IL-6 and CRP were significantly higher in ACS group (AMI or UAP) than in control group. In the Spearman correlation analysis , we found a correlation among IL－6, SAA, sCRP, fibrinogen both in the AMI group and UAP group. There was no correlation between CK-MB and serum SAA, IL-6 and sCRP levels either in AMI group or in UAP group. In the AMI group, there was no difference of serum SAA,IL-6 and sCRP levels when divided into ≤6 score group and >6 score group using Wagner's QRS scoring system. CONCLUSIONS: Serum levels of certain inflammatory markers have some diagnostic value for ACS. The high levels of serum SAA, IL-6 and sCRP are not mainly caused by myocardial death, but by the inflammation in the multifocal unstable plague.     

Effects of early enteral nutrition on prognosis of severe acute pancreatitis in obese patients

AIM:To evaluate the efficacy of initiation of early enteral nutrition on the prognosis of severe acute pancreatitis (SAP) in obese patients. METHODS:A prospective randomized control trial including 156 patients with SAP was conducted. The patients were divided into 3 groups according to the nutrition style and the distribution of body mass index. The non-obese patients (group A, n=107) received conventional management and delayed enteral nutrition, whereas the obese patients (body mass index ≥25 kg/m2) were randomized into 2 groups: the patients in group B (n=22) received conventional management and delayed enteral nutrition, and the patients in group C (n=27) received conventional management plus early enteral nutrition. The Ranson score and APACHE-II score of the patients were recorded. The local and systemic complications and case fatality were analyzed. RESULTS:The Ranson score in group B was significantly higher than that in group A (P<0.05), and no significant difference of the Ranson score or APACHE-II score on admission between group B and group C was observed (P>0.05). The rate of the patients developing local complications (pancreatic necrosis, pancreatic infection or abscess) and acute respiratory failure in group B was significantly higher than that in group A (P<0.05). The rate of pancreatic infection or abscess and acute respiratory failure in the patients was greatly reversed by early enternal nutrition in group C (P<0.05). The mortality in group B was significantly higher than that in group A (P<0.05), but it was reversed by early enteral nutrition in group C. The serum levels of CRP and TNF-α in group B were significantly higher than those in group A (P<0.05), and those were reversed by early enteral nutrition in group C. CONCLUSION:Early enteral nutrition in the early stage of SAP (within 48 h after admission) effectively prevents the obese patients from developing pancreatic infection or abscess and acute respiratory failure by reducing the circulating levels of proinflammatory cytokines.     

Effect of ulinastatin plus thymosin-α1 therapy on improving immune function in septic patients

AIM: To investigate the effect of ulinastatin plus thymosin-α1 therapy on improving immune function in septic patients. METHODS: 70 patients were divided into two groups. One group was classical treatment group (CT) with regular therapy and another group was classical treatment plus immunotherapy group (CIT) with ulinastatin plus thymosin-α1 for a week.The immune index before and after treatment on day 0, 1, 3 and 7 was observed, including the clinical and survival data. RESULTS: The most common pathogen of sepsis was bacteria, and infection by fungi was in rare. The common locations of bacteria observed were sputum and abdominal drainage. The level of TNF-α was significant lower in CIT group than that in CT group (P<0.05). IL-10 level was significantly higher in CIT group than that in CT group (P<0.05). IgG level was significant lower in CIT group than that in CT group (P<0.05). No significant difference in the levels of IgA, IgM, C3 and C4 between two groups was observed (P>0.05). CD4+T lymphocytes were significant higher in CIT group than those in CT group (P<0.05). From day 7 to day 28, the lymphocytes and level of HLA-DR in CD14+ monocytes were significant higher in CIT group than those in CT group (P<0.05). The time of mechanical ventilation and vasopressors used in CIT group was shorter than those in CT group (P<0.05). But the length of stay and the cost in ICU showed no significant increase between these two groups (P>0.05). During hospitalization, 20 patients died in the CT group and 13 patients died in CIT group (P<0.05). The long-term survival time in CIT group was longer than that in CT group (P<0.05). CONCLUSION: Immunotherapy in septic patients can decrease TNF-α level and increase IL-10 level. Immunotherapy in septic patients can increase IgG level slightly, CD4+T lymphocyte, and HLA-DR in CD14+ monocytes, which improve the immune paralysis in septic patients. Immunotherapy can shorten the time of mechanical ventilation and vasopressors used, but it doesn’t increase the length of stay and the cost.     

Effect of sedation by infusion of dexmedetomidine on inflammatory factors in patients with severe trauma

AIM: To study the effect of short-term sedation by infusion of dexmedetomidine (DEX) on the inflammatory factors in the patients with severe trauma. METHODS: Sixty patients with severe trauma in ICU were randomly divided into 3 groups: DEX group (n=20), midazolam (MDZ) group (n=20) and control group (without any sedatives, n=20). Dexmedetomidine at an initial loading dose of 1~2 μg/kg was administered intravenously over 10 min to the patients in DEX group before the sedation procedure of continuous infusion at dose of 0.2~0.7 μg·kg^-1·h^-1 by a 50-mL infusion syringe was perform. Midazolam at dose of 0.03~0.3 mg/kg was also administered intravenously immediately before the procedure of a continuous infusion at dose of 0.03~0.2 mg·kg^-1·h^-1. The doses of DEX or MDZ for the patients receiving short-term (48 h) sedation were adjusted according to the Ramsay sedation scale scores. The serum levels of interleukins (IL-1 and IL-6), tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were measured at the time points of the baseline (before the start of the study), 24 h and 48 h of sedative infusion. RESULTS: The levels of TNF-α, IL-1, IL-6 and CRP in the 3 groups of severe traumatic patients at the time when they were admitted to the hospital were significantly higher than those of the normal values. The levels of TNF-α, IL-1, IL-6 and CRP in control group gradually increased at 24 h and 48 h, while those in DEX group and MDZ group significantly declined. No significant difference of TNF-α, IL-1, IL-6 and CRP levels between DEX group and MDZ group was observed at 24 h, but the changes were significantly different at 48 h. CONCLUSION: Dexmedetomidine reduces over-stress responses to a certain extent in the traumatic patients to prevent the further production and release of inflammatory mediators, thus contributing to the stability and recovery of the patients with severe trauma.     

Expression of SAL-like 4 protein in human prostate cancer tissue/cell lines and its relationship with clinical outcome

AIM:To evaluate the expression of SAL-like 4 (SALL4) protein in human prostate cancer cell lines and tissues, and to analyze the relationship between SALL4 expression and the clinicopathological parameters. METHODS:Immunofluorescence, RT-PCR and Western blotting were performed to detect the expression of SALL4 at mRNA and protein levels in 3 common prostate cancer cell lines LNCaP, DU145 and PC-3. The normal prostate epithelial cell line RWPE-1 was used for control. The protein levels of SALL4 in the tissues of benign prostate hyperplasia and prostate cancer tissues were determined by the method of immunohistochemistry. RESULTS:The SALL4 protein was predominantly expressed in the cytoplasm of the cells. The protein levels of SALL4 in 3 common prostate cancer cell lines were significantly higher than that in RWPE-1 cells. However, the mRNA level of SALL4 had no obvious difference among the 4 cell lines. Immunohistochemistry results showed that the expression level of SALL4 in the cancerous tissues was significantly higher than that in noncancerous (benign and normal) prostatic tissues. In addition, we found that the expression level of SALL4 in prostate cancer was significantly correlated with the Gleason score, clinical stage, prognosis estimation and tissue prostate-specific antigen (PSA) expression, but not associated with age, the level of serum total PSA, prostate volume and the expression of androgen receptor in the tissues of the patients. CONCLUSION: The over-expression of SALL4 protein may play an important role in the pathogenesis and progression of prostate cancer, and provides some reference indexes for estimating the malignancy, progression and prognosis of prostate cancer.     

Inhibitory effect of high-dose Xuezhikang on inflammatory response induced by percutaneous coronary intervention in patients with unstable angina

AIM: To study the inhibitory effect of high-dose Xuezhikang,administered before percutaneous coronary intervention (PCI) on inflammatory response induced by PCI in patients with unstable angina (UA).METHODS: All patients with UA in class Ⅲ and ⅡB according to Braunwald classification were considered for inclusion in the present study.Finally,196 patients received Xuezhikang treatment 72 h before coronary angiography and successfully performed PCI with elevated C-reactive protein (CRP) level (>3 mg/L) were randomised to 2 groups: 1.2 g/d of Xuezhikang as group A,or 2.4 g/d of Xuezhikang as group B.The levels of CRP were measured at baseline,after 3 days of therapy (before procedure) and 48 hours after PCI.The patients were followed-up for 6 months for major adverse coronary events and left ventricular ejection fraction.RESULTS: There was no significant difference in the mean CRP level among the two randomized groups (P>0.05),however,after three days of pharmacological treatment,there was significantly reduced CRP content in group A ［(5.44±1.57） mg/L vs （4.04±1.54） mg/L,P<0.05］ and in group B ［(5.42±1.36） mg/L vs （3.60±1.14） mg/L,P<0.05］ compared with admission.Measurements performed 48 hours after the procedure revealed a marked CRP level increase in group A (up to 9.22 mg/L±5.03 mg/L) and an obvious increase in groups B (up to 4.97 mg/L±1.75 mg/L,P<0.05) compared with pre-procedure.The serum level of CRP in B group was distinctly lower than that in A group before (P<0.05) and after the procedure (P<0.05),respectively.Major adverse coronary events during the 6-month clinical follow-up occurred less in group A than that in group B ［21/104 (20.2%) vs 9/92 (9.8%); patients,P<0.05］.Follow-up echocardiography revealed lower left ventricular ejection fraction in group A than that in group B (55.41%±10.93% vs 59.30%±9.99%,P<0.05).CONCLUSION: High-dose Xuezhikang therapy,administered before PCI,has better inhibition effect than low-dose on inflammatory response induced by PCI in patients with UA.Attenuation of inflammatory response may be crucial for the reduction of coronary events following invasive coronary interventions.     

LBP regulates PI3K/Akt/eNOS signaling pathways in ovariectomized rat myocardium to exert antioxidative effect

AIM: To observe the influence of Lycium barbarum polysaccharide (LBP) on the PI3K/Akt/eNOS signaling pathways in ovariectomized rat myocardium. METHODS: Female SD rats (n=30) were divided into sham operation group, ovariectomized group, progynova group, high-dose LBP group and low-dose LBP group. The serum levels of estradiol, lactate dehydrogenase (LDH) and creatine kinase (CK) were measured by ELISA. The myocardial contents of H₂S and oxidative stress injury-related indicators were also detected. The morphological changes of the myocardium were observed with HE staining. The expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium was determined by Western blot. RESULTS: Compared with sham operation group, the serum level of estradiol, the content of H₂S, the activity of GSH-Px, and the expression of eNOS and PI3K/Akt pathway-related proteins in the myocardium in ovariectomized group were all decreased, and the levels of ROS and MDA in the myocardium were increased (P<0.05). The serum levels of LDH and CK were also increased. The arrangement of the myocardial cells was disordered, and the intercellular space was also increased in the ovariectomized group. Compared with ovariectomized group, the serum level of estradiol, the myocardial levels of H₂S and GSH-Px, and the protein levels of eNOS and phosphorylated Akt were all increased in high dose group, while the levels of ROS and MDA in the myocardium were decreased (P<0.05). The serum levels of LDH and CK were also decreased. The morphological changes of the rat myocardium were improved in high dose group. CONCLUSION: LBP prevents and treats postmenopausal cardiovascular lesions through regulating PI3K/Akt/eNOS signaling pathways in ovariectomized rats.     

Significance of soluble CD40 ligand in the vulnerability of coronary atherosclerotic plaque

AIM: To evaluate the significance of serum soluble CD40 ligand (sCD40L) in the vulnerability of coronary atherosclerotic plaque, the relationship between the level of sCD40L and the stenosis degree of the coronary artery by the coronary angiography (CAG), and other inflammatory factors. METHODS: According to WHO diagnostic criterior of coronary heart disease (CHD) and the results of CAG, 84 cases of CHD and 20 cases of non-CHD (NCHD) were included in this study. 84 cases of CHD were divided into three groups: 30 cases in acute myocardial infarction (AMI) group, 30 cases in unstable angina (UA), 24 cases in stable angina (SA). The sera levels of sCD40L in four groups were detected by the enzyme-linked immunosorbent assay (ELISA) and the results were expressed with μg/L. CAG were all conducted in four cases and the results were further evaluated by Jenkins score. ESR and CRP were detected at the same time. RESULTS: The sera levels of sCD40L in four groups were significantly different (P<0.01). The level of sCD40L in AMI group (8.48±4.13) μg/L was higher than that in SA group (4.36±2.68) μg/L, P<0.01 and NCHD group (4.12±1.96) μg/L, P<0.01. The level of sCD40L in UA group (8.72±4.26) μg/L was higher than that in SA group and NCHD group (P<0.01). The level of sCD40L in UA group was slightly higher than that in AMI group, but the difference of two group is not significant (P>0.05). The level of sCD40L in SA group was slightly higher than that in NCHD group, but the difference of two group is not significant (P>0.05). The sera levels of sCD40L in CHD were significantly and positively correlated with Jenkins score (r=0.524, P<0.01). The sera level of sCD40L was positively correlated with the levels of CRP and ESR. CONCLUSION: The sera levels of sCD40L in the patients with various types of CHD are significantly different. The level of sCD40L in the patients with AMI and UA are significantly higher than those in SA and NCHD groups, which may reflect the vulnerability of coronary atherosclerotic plaque. The sera levels of sCD40L is increased with the increasing number of diseased coronary branches and Jenkins score, suggesting that sCD40L promotes atherosclerosis and also can be used as a parameter to predict pathological severity of coronary atherosclerosis. The level of sCD40L is obviously correlated with the levels of CRP and ESR.     

Influence of glycine on LBP mRNA expression induced by LPS in the liver of rats

AIM:To study the influence of glycine(GLY) on lipopolysaccharide-binding protein(LBP) mRNA expression induced by LPS.METHODS:The level of LBP mRNA expression in liver tissues of rats was examined by RT-PCR, and the effects of glycine on LBP mRNA expression in liver tissues of rats induced by LPS were investigated.RESULTS: The level of LBP mRNA expression in hepatic tissue of rats in the LPS group was significantly higher than that in the control group(P＜0.01), the level of LBP mRNA expression in the hepatic tissue of rats in the LPS+GLY group was lower than that in the LPS group(P＜0.01).CONCLUSION:LPS can induce LBP mRNA expression in the hepatic tissue of rats, glycine can inhibit LBP mRNA expression in the hepatic tissue of rats treated by LPS.     

Effects of lipopolysaccharide binding protein on activation of p38 signaling pathway induced by LPS in macrophages

AIM:To investigate the regulatory effects of lipopolysaccharide binding protein(LBP)on activation of p38 signaling pathway induced by lipopolysaccharide(LPS)in alveolar macrophages.METHODS:The LBP from actue phase rat serum was purified by ammonium sulphate precipitation, Bio-Rex70 resin and the MonoQ column. Rat alveolar macrophages were exposed to LPS (0.01 mg/L or 1 mg/L) the various concentrations of LBP(0 mg/L, 0.01 mg/L, 0.1 mg/L, 1 mg/L and 10 mg/L).Western blotting were used to detect phospho-p38 in alveolar macrophages. RESULTS:SDS-PAGE analysis indicated that the purified preparation of rat LBP showed homogeneity and the molecu-lar weight was 60 kD.The binding of lipopolysaccharide to mononuclear cells were enhanced by purified rat LBP.Stimu-lation of rat alveolar macrophages with LPS at concentration of 0.01 mg/L was LBP dependent.LBP at concentrations up to 1 mg/L was able to increase the activation of p38.However, when LBP concentrations were further increased to 10mg/L, the phosphorylation levers of p38 were lower as compared with that in the presence of 1 mg/L.Stimulation of ratalveolar macrophages with LPS at concentrations of 1 mg/L was LBP-independent.CONCLUSION:The activation of p38 induced by LPS at lower concentration(0.01 mg/L) was LBP-dependent, meanwhile, LPS at higher concentration(1 mg/L) was LBP-independent.     

Dynamic changes of mouse cardiac functions in early stage of sepsis induced by CLP

AIM: To detect the changes of cardiac functions of septic mice in the early stage of sepsis. METHODS: Health male Kunming mice were used in the study. The techniques of 2D, M-mode and Doppler echocardiography were applied to evaluate the cardiac functions before cecal ligation and puncture(CLP) as baseline and at time points of 12 h, 24 h, 36 h, 48 h and 168 h after CLP. The mice survived for 168 h(7 d) were considered as survivals. RESULTS: Compared to the baseline at the time point of 24 h after CLP, the blood volumes of heart return decreased significantly in the early stage of sepsis induced by CLP. LVEDV reduced by 46%. Notable compensatory responses of the hearts in septic mice were observed, especially the systolic functions, in which LVEF and LVFS increased by 27% and 39%, respectively. However, the compensatory responses of diastolic function were weaker than the systoles. E/A ratio and EDT decreased by 30% and 25% respectively at the time point of 24 h. CONCLUSION: The strong compensatory cardiac functions are one of the factors for supporting the septic animal to survive. Protection of the cardiac functions especially the diastoles is important in the treatment of septic patients.     

Circulating miRNA-141 as a non-invasive biomarker for prostate cancer detection and prognosis

AIM:To analyze circulating miR-141 in the serum as a non-invasive biomarker in the patients with prostate cancer (PCa) and benign prostate hyperplasia (BPH), and healthy individuals. METHODS:A total of 75 patients with PCa, 52 with BPH and 40 healthy individuals were enrolled into this study. Total RNA was isolated from the serum samples and the circulating levels of miR-141 were determined using quantitative real-time polymerase chain reaction. RESULTS:The serum levels of miR-141 were significantly higher in the patients with PCa compared to the patients with BPH and the healthy controls (P<0.01). The level of miR-141 in PCa group obviously differed from that in BPH group and healthy control group with high diagnosis performance, with areas under the curve of 0.785 and 0.801, respectively. No statistically significant difference of the serum miR-141 levels between the patients with BPH and healthy individuals was observed (P>0.05). The serum miR-141 level was also found to be related to Gleason score, clinical stage and bone metastasis status of the patients with PCa (P<0.05), and the patients with higher Gleason scores had higher serum miR-141 levels. No relationship was detected between miRNA-141 level and the patient’s age, biochemistry recurrence and serum prostate-specific antigen level (P>0.05 for all comparisons). CONCLUSION: Circulating miR-141 could serve as a non-invasive biomarker for prostate cancer diagnosis, staging and prognosis prediction.     

Prolactin induces interleukin-6 expression in PBMCs of rheumatoid arthritis patients

ATM: To investigate the correlation between serum prolactin (PRL) levels and disease activity in rheumatoid arthritis (RA) patients, and the regulatory role of PRL in interleukin-6 (IL-6) release from peripheral blood mononuclear cells (PBMCs), and to explore the MAPK-related mechanism of IL-6 release in PBMCs. METHODS: The clinicopathologic and hematologic parameters of 40 new-onset RA patients in the Department of Rheumatology of our hospital between March and September 2015 were collected. Chemilumineseent immunoassay (CLIA) was used to detect the serum PRL levels in the 40 RA patients and 20 healthy controls. The levels of IL-6 secretion by the PBMCs were evaluated using ELISA. Quantitative real-time PCR was employed to examine the mRNA expression of prolactin receptor (PRLR). MAPK pathway protein p-p38 levels were evaluated by Western blot. RESULTS: Serum PRL level in the RA patients was significantly higher than that in the healthy controls (P<0.01). Serum PRL level in active RA patients was significantly higher than that in inactive RA patients (P<0.01). Serum PRL level was positively correlated with DAS28, ESR and CRP (P<0.01). The expression of PRLR in the PBMCs was markedly increased in the RA patients than that in the healthy samples (P<0.01). Exposure of the PBMCs to PRL in the culture increased the release of IL-6, which was abolished by PRLR gene silencing or blocking the MAPK pathway.CONCLUSION: Serum PRL level is related to DAS28, ESR and CRP of RA patients and could be used as a predictor of disease activity. PRL/PRLR-p38 MAPK-IL-6 pathway may play a central role in the pathogenesis of RA.     

Effects of combination treatment with perindopril and losartan on left ventricular remodeling and cardiac function in patients with myocardial infarction

AIM: Inhibiting the renin-angiotensin-aldosterone system prevents left ventricular (LV) remodeling after myocardial infarction (MI). This study was designed to assess the effects of a combination of perindopril and losartan on LV remodeling, cardiac function and serum procollagen type Ⅲ aminoterminal peptide (PⅢNP) levels in patients with acute MI.METHODS: Patients with anterior MI were divided into 3 groups: MI+perindopril, MI+losartan, and MI+perindopril+losartan. After successful intervention therapy, perindopril 2-4 mg/d or losartan potassium 25-50 mg/d or combination of the both were administered. All patients took aspirin, clopidogrel and statins, while some of the patients were treated with beta-blockers, nitrate and a platelet glycoprotein IIb/Ⅲa receptor antagonist. Three months later, LV dimensions and LV ejection fraction (LVEF) were measured by ultrasonography. Plasma brain natriuretic peptide (BNP), serum C-reactive protein (CRP) and PⅢNP levels were evaluated with ELISA or RIA.RESULTS: Baseline characteristics of the 3 groups were the same. All patients showed decreased CRP, increased BNP and PⅢNP levels, and LV dilation and dysfunction after treatment for three months. Compared with the 2 single therapy groups, patients in the combination group showed significantly lower CRP, BNP and PⅢNP levels, less LV dilation and higher LVEF. Serum PⅢNP level was positively correlated with CRP level and LV end-diastolic volume index(r=0.597 and r=0.543, respectively,both P<0.01), and negatively correlated with LVEF(r=-0.565, P<0.01).CONCLUSION: For patients with AMI, combination of perindopril and losartan significantly inhibited LV remodeling and improved LV function. Inhibition of myocardial interstitial fibrosis might be part of the mechanism.     

Changes of neuropeptides and electrolytes in patients with acute traumatic brain injury

AIM: To investigate the levels of neuropeptides and electrolytes in the patients with acute traumatic brain injury.METHODS: Seventy-eight patients with acute brain injury were divided into mild, moderate and severe groups according to their GCS scores. The serum levels of arginine vasopressin (AVP) and angiotensin II (Ang II) were measured on day 1, 3 and 7 after injury. The serum levels of electrolytes were also measured on day 1. Forty-one subjects who received healthy check-up served as normalcontrols. RESULTS: Compared with normal control group, the serum levels of AVP and Ang II significantly increased in the patients with traumatic brain injury (P<0.01), depending on the severity of brain injury. Both neuropeptides reached the peak on day 3 after injury. The concentrations of serum potassium and calcium decreased in the patients with acute brain injury(P<0.01),also showing a severity-dependent tendency. No significant change of serum sodium in the patients with brain injury was observed. CONCLUSION: The serum levels of arginine vasopressin and angiotensin II canalso be used as the severity indicators of traumatic brain injuries. Decrease in serum potassium and calcium can also be used to evaluate the severity in patients with acute traumatic brain injury.