The pro-inflammatory factors contribute to the EEG microstate abnormalities in patients with major depressive disorder.

Pro-inflammatory factors may be associated with abnormalities in functional brain networks, which may be a mechanism in the pathogenesis of major depressive disorder (MDD). Electroencephalogram (EEG) microstates reflect the functioning of brain networks. However, the relationship between pro-inflammatory factors and the microstate abnormalities in patients with MDD is poorly understood. 24 MDD patients and 24 age-and sex-matched healthy controls (HC) were recruited. Montgomery-Asberg Depression Rating Scale(MADRS) were assessed. Serum (interleukin- 2(IL- 2), tumor necrosis factor-α (TNF-α) and hs-C-reactive protein (CRP)and EEG data were collected. K-means clustering was performed to characterize different microstates. For each microstate, duration, occurrence and coverage were estimated. Four microstates (e.g. A, B, C, D) were characterized, MDD group showed lower duration, occurrence and coverage of microstate B and microstate D, while higher duration of microstate A and microstate C and levels of IL-2, TNF-α, hs-CRP than HC group. The duration, occurrence and coverage of microstate D were negatively correlated with levels of pro-inflammatory factors (IL-2, TNF- α and hs- CRP) (all P < 0.05). Serum pro-inflammatory induced the abnormalities of microstate D. Together, these findings add to the understanding of the pathophysiology of MDD and point to pro-inflammatory factors contribute to EEG microstate abnormalities in patients with MDD.

Value of Magnifying Chromoendoscopy and Magnifying Optical Enhancement Technology in Classifying Colorectal Polyps: A Prospective Controlled Study.

BACKGROUND AND AIMS: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. RESULTS: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. CONCLUSION: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075.

Protective effects of ginsenoside Rb1 on septic rats and its mechanism.

This study aims to observe the protective effects of ginsenoside Rb1 on liver and lung in rats with septic shock and reveal its mechanism. Rats were randomly divided into three groups: sham, cecal ligation and puncture (CLP), and CLP with ginsenoside Rb1. Then, the survival rate, arterial blood pressure, TLR4 mRNA, and TNF-α levels were determined. The liver and lung tissues were stained with hematoxylin-eosin (HE). The overall survival rate of the Rb1 group was significantly higher than that of the CLP group. Mean arterial blood pressure went down in both the CLP and Rb1 groups after CLP, and there was a significant difference both in the sham and Rb1 groups when compared with the CLP group. The Rb1 treatment group had markedly lower TLR4 mRNA expression and TNF-α levels than the CLP group. In the CLP group, pathology showed swelling, degeneration, necrosis, and neutrophil infiltration in the liver and alveolar epithelial cells. However, in the Rb1 group, there was mild degeneration and slight neutrophil infiltration, but no obvious necrosis. Rb1 may improve the survival rate, ameliorate arterial blood pressure, and protect the liver and lung in septic shock rats by downregulating the expression of TLR4 mRNA and inhibiting the production of TNF-α.

[Effects of adrenergic beta-1 antagonists on hemodynamics of severe septic patients].

OBJECTIVE: To explore the effects of adrenergic beta-1 antagonists on hemodynamics of severe septic patients. METHODS: A total of 16 severe septic patients underwent mechanical ventilation from June 2012 to December 2012 at Fourth Affiliated Hospital of Nanchang University. There were 14 males and 2 females with a mean age of (58 ± 6) years (range: 48 - 67 years). Among them, there were multiple trauma (n = 4), acute severe pancreatitis (n = 6) and recent tumorectomy for gastrointestinal cancer (n = 6). The adrenergic beta-1 antagonist esmolol was injected through central venous catheter to reduce heart rate by 20% from baseline. Various indices (heart rate, systolic blood pressure, diastolic blood pressure, cardiac output, cardiac index, central venous pressure, pulmonary artery wedge pressure, pulmonary vascular resistance index, systemic vascular resistance index and stroke volume index) were monitored by a multifunctional and hemodynamic monitor connected to pulmonary artery catheter. And other indices of arterial pressure of carbon dioxide (PaCO2), lactate (Lac) concentration, superior vena cava oxygen saturation (ScvO2), superior vena cava carbon dioxide pressure (PcvO2) and central venous-to-arterial carbon dioxide tension difference (Pcv-aCO2) were measured by a blood-gas-analyzer before 10 minutes and after 3 hours of dosing. RESULTS: Heart rate and cardiac index decreased significantly at 3 hours post-dosing compared with that at pre-dosing ((91 ± 13) vs (114 ± 15) beats per minute, (3.4 ± 0.7) vs (4.2 ± 0.8) L×min(-1)×m(-2), P < 0.05), but systolic blood pressure, diastolic blood pressure, central venous pressure, pulmonary wedge pressure, pulmonary vascular resistance index, systemic vascular resistance index and stroke index showed no significant changes ((100 ± 13) vs (108 ± 14) mm Hg (1 mm Hg = 0.133 kPa), (62 ± 7) vs (64 ± 6) mm Hg, (11.8 ± 2.5) vs (12.1 ± 2.4) mm Hg, (13 ± 5) vs (14 ± 4) mm Hg, (201 ± 72) vs (179 ± 95) dyn×s/(cm(5)×m(2)), (1360 ± 520) vs (1366 ± 538) dyn×s/(cm(5)×m(2)), (40 ± 9) vs (38 ± 6) ml/(beat×m(2)), all P > 0.05). ScvO2, Lac and Pcv-aCO2 also showed no significant change ((72.8 ± 5.3)% vs (70.1 ± 4.0)%, (2.11 ± 0.13) vs (2.31 ± 0.23) mmol/L, (3.9 ± 1.0) vs (4.5 ± 0.8) mm Hg, all P > 0.05). CONCLUSION: Adrenergic beta-1 antagonist may reduce cardiac output in proportion to the percentage decreases in heart rate in severe septic patients without adverse effects upon cardiac function and systemic perfusion.

Phospholamban antisense RNA improves SR Ca2+-ATPase activity and left ventricular function in STZ-induced diabetic rats.

OBJECTIVE: To study the effect of phospholamban antisense RNA (asPLB) on sarcoplasmic reticulum Ca2+-ATPase activity and cardiac function in rats with diabetes mellitus (DM) mediated by recombinant adeno-associated virus (rAAV) vector. METHODS: Six weeks after the induction of DM by streptozotocin injected intraperitoneally, the rats were divided into three groups, namely: DM-rAAV-asPLB group, DM-saline group and DM group (control group). The rats in the DM-rAAV-asPLB group were intramyocardially injected with rAAV-asPLB, the rats in the DM-saline group were injected with saline, and those in the control group did not receive any treatment. Six weeks after gene transfer, the expressions of PLB protein and PLB phosphorylation were detected by Western-blot, while the activity of sarcoplasmic reticulum (SR) Ca2+-ATPase and left ventricular function were measured. RESULTS: The PLB protein expression level was significantly higher whereas the PLB phosphorylation, SR Ca2+-ATPase activity and left ventricular function were significantly lower in the DM-saline group than in the control group. No significant difference was found in PLB protein expression level, PLB phosphorylation or SR Ca2+-ATPase activity between the DM-rAAV-asPLB group and the control group. The left ventricular function in the DM-rAAV-asPLB group was poorer than in the control group and was better than in the DM-saline group. CONCLUSION: rAAV-asPLB can down-regulate PLB protein expression and up-regulate PLB phosphorylation and SR Ca2+-ATPase activity, thus contributing to the improvement of in vivo left ventricular function.

Peripheral pulmonary nodules: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression.

BACKGROUND: The aim of this study is to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules. METHODS: Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated. RESULTS: The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05). CONCLUSION: Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.

The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats.

To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-alpha level, and the nuclear factor-kappaB (NF-kappaB) activation during septic shock, male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty-eight rats were randomly assigned into six equal groups: sham CLP group; CLP group; VGX group was subjected to bilateral cervical vagotomy after CLP; STM group was subjected to bilateral cervical vagotomy after CLP plus the left vagus nerve trunk electrical stimulation; THA group was administered tetrahydroaminoacridine after CLP and bilateral cervical vagotomy; and alpha-BGT group was administered alpha-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-alpha level was measured using enzyme-linked immunosorbent assays. The hepatic NF-kappaB activation was determined by Western blotting. Cecal ligation and puncture produced progressive hypotension. Serum aspartate transaminase and alanine transaminase levels significantly increased after CLP challenge. The plasma TNF-alpha level and the hepatic NF-kappaB activation significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated group. Application of constant voltage pulses to the caudal vagus trunk significantly prevented the development of CLP-induced hypotension, alleviated the hepatic damage, and reduced the plasma TNF-alpha production, but electrical stimulation had no effect on the hepatic NF-kappaB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-alpha response; in addition, it had no effect on the hepatic NF-kappaB activation. alpha-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the hepatic NF-kappaB activation. Our results showed that the cholinergic anti-inflammatory pathway might produce a potential protective effect on polymicrobial sepsis in rats.

[Protective effects of electric stimulation of vagus nerve on acute lung injury in rat with sepsis].

OBJECTIVE: To investigate the protective effect of stimulation of vagus nerve on acute lung injury in rat with sepsis. METHODS: Sepsis was reproduced by cecal ligation and puncture (CLP). Forty male Sprague-Dawley (SD) rats were randomly divided into 4 groups (each n=10): SHAM group received performed sham surgery. In CLP group, CLP was performed. In vagotomy (VGX) group, rats were subjected to bilateral cervical VGX following CLP. In vagus stimulation (STM) group, rats were subjected to bilateral cervical VGX after CLP and the efferent end of the left vagus nerve was stimulated with electric current. The animals were sacrificed at 18 hours after production. Tumor necrosis factor-alpha (TNF-alpha) level in blood was detected, arterial blood lactic acid concentration,pH, partial pressure of oxygen in arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood (PaCO2), base excess (BE) and lung wet/drying (W/D) ratio were determined. The histopathology and ultra-microstructure of the lung were observed. RESULTS: The TNF-alpha and lactic acid concentrations, PaCO2 and W/D ratio were all increased, and pH, PaO2, BE all lowered in CLP group and VGX group compared with those of SHAM group (P<0.05 or P<0.01). Compared with CLP group, TNF-alpha, lactic acid concentration,PaCO2,W/D ratio in STM group were decreased obviously, and pH, PaO2 and BE were all increased (P<0.05 or P<0.01). The lung tissue pathology and ultra-microstructure changes indicated that lung injury was severe in CLP group than in SHAM group and was ameliorated in STM group compared with that of CLP group and VGX group. CONCLUSION: The results suggest that direct electrical stimulation of the efferent end of vagus nerve can protect lung against injury induced by sepsis in rat.

[Protective effect of the cholinergic anti-inflammatory pathway against hemorrhagic shock in rats].

OBJECTIVE: To investigate the effect of the cholinergic anti-inflammatory pathway on hemodynamics in hemorrhaged rats. METHODS: Hemorrhagic shock was induced by modified Wiggers method until mean arterial pressure (MAP) was stabilized within the range of 35 to 40 mm Hg (1 mmHg=0.133 kPa). Thirty male Sprague-Dawley rats were randomly divided into six groups: sham group, hemorrhagic shock (Hem) group, vagotomy (VGX) group, vagus stimulation (STM) group, cholinergic inhibitor (THA) group and N receptor inhibitor (alpha-BGT) group. The distal end of the left vagus nerve trunk was placed on bipolar platinum electrode connected to a stimulation module and controlled by an acquisition system. Stimuli with constant voltage (5 V, 2 ms, 1 Hz) were applied to nerve for 12 minutes, starting 5 minutes after MAP stabilized at a level of 35 to 40 mmHg. Before stimulation a blood pressure transducer was implanted in the common carotid artery for continuous registration of MAP. Blood samples and liver samples were collected from animals of all groups after stimulation. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and liver nuclear factor kappa-B (NF-KappaB) were determined. RESULTS: MAP was markedly lowered at the end of bleeding, and the levels of serum TNF-alpha and liver NF-KappaB markedly increased 45 minutes after the bleeding was discontinued. Bilateral cervical vagotomy did not significantly modify the changes in serum TNF-alpha, but slightly increased liver NF-KappaB activation. Application of constant electric current to the distal end of the vagus trunk significantly reduced serum TNF-alpha and blunted liver NF-KappaB activation. Tetrahydroamino-acridine (THA,1.5 mg/kg, intravenous drip administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNF-alpha and liver NF-KappaB amounts, but alpha-bungarotoxin (1.0 microg/kg intravenous drip) pretreatment reverted the inhibitory effects of vagal stimulation. CONCLUSION: The result suggest that direct electrical stimulation of the vagus nerve and its transmitter can significantly attenuate peak serum TNF-alpha amounts, inhibit the expression of liver NF-KappaB, and prevent the development of hypotension, thus it might produce a potential protective effect on hemorrhaged rats through acetylcholine (Ach) binds NAch receptor alpha 7 subunit which exists in the macrophage.