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Objective:To explore the protective effect of sivelestat (SV) against sepsis-induced acute kidney injury (AKI) and its molecular mechanism.Methods:According to the random number table method, 64 male Wistar rats were divided into sham operation group (Sham group), sepsis due to cecal ligation and puncture group (CLP group), low dose of SV treatment group (SL group, 50 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), and high dose of SV treatment group (SH group, 100 mg/kg SV was injected into the tail vein at 12 hours and 24 hours after CLP), with 16 rats in each group. 48 hours after CLP, the 48-hour survival of rats were recorded, all rats were sacrificed and samples were harvested. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of kidney injury molecule-1 (KIM-1), interleukins (IL-1β, IL-6), tumor necrosis factor-α (TNF-α) and neutrophil elastase (NE). Hematoxylin-eosin (HE) staining was used to observe histopathological changes and assess renal tubule injury score. Masson staining was used to detect the collagen volume fraction (CVF) of kidney tissue. Western blotting was used to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylation PI3K (p-PI3K), protein kinase B (AKT), phosphorylation AKT (p-AKT), nuclear factor-κB p65 (NF-κB p65) and NE. The protein expressions of p-PI3K, p-AKT, NF-κB p65 were detected by immunohistochemistry.Results:Compared with Sham group, the 48-hour survival rate of CLP group was significantly reduced. Histopathological results showed that large tubular epithelial cells and brush margins were shed, tubular casts were formed, some tubular atrophy, glomerular hyperemia, renal interstitial inflammatory cell infiltration and increased renal tubular injury score. Renal interstitial fibrosis was obvious and CVF increased. The levels of KIM-1, IL-1β, IL-6, TNF-α and NE in serum were significantly elevated in the CLP group. The proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly increased in kidney tissue. It suggested that septic rats had renal injury and the PI3K/AKT inflammatory pathway was activated. Compared with CLP group, there was no significant difference in 48-hour survival in SL group and SH group (68.75%, 75.00% vs. 56.25%, both P > 0.05), but kidney injury was significantly relieved. Specifically: renal tubular injury score and CVF significantly decreased [tubular injury score: 2 (1, 2), 1 (1, 1) vs. 2 (2, 3); CVF: (22.36±0.86)%, (18.74±1.05)% vs. (58.38±0.79)%, all P < 0.05]; the serum levels of KIM-1, IL-1β, IL-6, TNF-α and NE also decreased significantly [KIM-1 (ng/L): 145.03±8.88, 117.58±7.02 vs. 158.22±12.00; IL-1β (ng/L): 108.32±9.00, 92.98±8.06 vs. 133.78±8.48; IL-6 (ng/L): 124.33±10.11, 115.42±8.17 vs. 165.19±5.70; TNF-α (ng/L): 321.56±19.29, 289.68±21.57 vs. 424.88±22.76, NE (mol/L): 93.84±9.14, 75.01±10.56 vs. 113.45±6.39, all P < 0.05]; the proteins expression of inflammatory pathway-related p-PI3K/PI3K, p-AKT/AKT, NF-κB p65 and NE were significantly decreased (p-PI3K/PI3K: 0.93±0.06, 0.67±0.04 vs. 1.27±0.08; p-AKT/AKT: 0.78±0.09, 0.47±0.05 vs. 0.96±0.12; NF-κB p65/GAPDH: 1.43±0.13, 0.85±0.08 vs. 1.88±0.17; NE/GAPDH: 1.45±0.06, 0.91±0.04 vs. 1.71±0.08, all P < 0.05), the positive expressions of p-PI3K, p-AKT and NF-κB p65 in kidney tissue were decreased [p-PI3K positive expression area: (13.36±1.84)%, (8.03±1.12)% vs. (21.56±1.20)%; p-AKT positive expression area: (21.57±0.91)%, (15.21±2.76)% vs. (30.81±2.12)%; NF-κB p65 positive expression area: (25.17±1.38)%, (17.07±2.11)% vs. (37.85±2.50)%, all P < 0.05]. Serum inflammatory factor level, and PI3K/AKT pathway related protein, NF-κB p65, NE protein expression level and p-PI3K, p-AKT, NF-κB p65 positive area and other indicators in renal tissue in SH group were further lower than those in SL group (all P < 0.05). Conclusions:SV can ameliorate sepsis-induced AKI. The mechanism may be related to the inhibition of PI3K/AKT pathway, and high dose of SV has better efficacy.
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Sepsis is a life-threatening organ dysfunction caused by dysregulation of the body's response to infection. It is one of the common and serious complications in clinically critical patients with trauma, burn, shock, infection, etc., with high morbidity and mortality. Although the treatment of sepsis has made great achievements in clinical practice, the mortality of patients with sepsis is still increasing due to its secondary complications. Septic cardiomyopathy (SCM) is one of the major complications that threaten septic patient's life. SCM refers to myocardial dysfunction with the aggravation of the primary disease, which is manifested by biventricular dilatation accompanied by a decrease in left ventricular ejection fraction (LVEF). It is one of the major complications that threaten the life of patients with sepsis. The existing research shows that the mechanism of SCM includes myocardial mitochondrial dysfunction, myocardial cell apoptosis, calcium circulation disorder and its treatment including conventional treatment, β 1 receptor blocker treatment and traditional Chinese medicine treatment, etc. This paper reviewed the pathogenesis of SCM and its related, in order to provide references for the rational diagnosis and treatment of SCM.
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Objective:To explore the basic characteristics of various types of intensive care unit (ICU) patients and the predictive value of six common disease severity scores in critically ill patients on the first day on the 28-day death risk.Methods:The general information, disease severity scores [acute physiology score Ⅲ (APSⅢ), Oxford acute disease severity (OASIS) score, Logistic organ dysfunction score (LODS), simplified acute physiology score Ⅱ (SAPSⅡ), systemic inflammatory response syndrome (SIRS) score and sequential organ failure assessment (SOFA) score], prognosis and other indicators of critically ill patients admitted from 2008 to 2019 were extracted from Medical Information Mart for Intensive Care-Ⅳ 2.0 (MIMIC-Ⅳ 2.0). The receiver operator characteristic curve (ROC curve) of six critical illness scores for 28-day death risk of patients in various ICU, and the area under the ROC curve (AUC) was calculated, the optimal Youden index was used to determine the cut-off value, and the AUC of various ICU was verified by Delong method.Results:A total of 53 150 critically ill patients were enrolled, with medical ICU (MICU) accounted for the most (19.25%, n = 10 233), followed by cardiac vascular ICU (CVICU) with 17.78% ( n = 9 450), and neurological ICU (NICU) accounted for the least (6.25%, n = 3 320). The patients in coronary care unit (CCU) were the oldest [years old: 71.79 (60.27, 82.33)]. The length of ICU stay in NICU was the longest [days: 2.84 (1.51, 5.49)] and accounted for the highest proportion of total length of hospital stay [63.51% (34.61%, 97.07%)]. The patients in comprehensive ICU had the shortest length of ICU stay [days: 1.75 (0.99, 3.05)]. The patients in CVICU had the lowest proportion of length of ICU stay to total length of hospital stay [27.69% (18.68%, 45.18%)]. The six scores within the first day of ICU admission in NICU patients were lower than those in the other ICU, while APSⅢ, LODS, OASIS, and SOFA scores in MICU patients were higher than those in the other ICU. SAPⅡ and SIRS scores were both the highest in CVICU, respectively. In terms of prognosis, MICU patients had the highest 28-day mortality (14.14%, 1 447/10 233), while CVICU patients had the lowest (2.88%, 272/9 450). ROC curve analysis of the predictive value of each score on the 28-day death risk of various ICU patients showed that, the predictive value of APSⅢ, LODS, and SAPSⅡ in comprehensive ICU were higher [AUC and 95% confidence interval (95% CI) were 0.84 (0.83-0.85), 0.82 (0.81-0.84), and 0.83 (0.82-0.84), respectively]. The predictive value of OASIS, LODS, and SAPSⅡ in surgical ICU (SICU) were higher [AUC and 95% CI were 0.80 (0.79-0.82), 0.79 (0.78-0.81), and 0.79 (0.77-0.80), respectively]. The predictive value of APSⅢ and SAPSⅡ in MICU were higher [AUC and 95% CI were 0.84 (0.82-0.85) and 0.82 (0.81-0.83), respectively]. The predictive value of APSⅢ and SAPSⅡ in CCU were higher [AUC and 95% CI were 0.86 (0.85-0.88) and 0.85 (0.83-0.86), respectively]. The predictive value of LODS and SAPSⅡ in trauma ICU (TICU) were higher [AUC and 95% CI were 0.83 (0.82-0.83) and 0.83 (0.82-0.84), respectively]. The predictive value of OASIS and SAPSⅡ in NICU were higher [AUC and 95% CI were 0.83 (0.80-0.85) and 0.81 (0.78-0.83), respectively]. The predictive value of APSⅢ, LODS, and SAPSⅡ in CVICU were higher [AUC and 95% CI were 0.84 (0.83-0.85), 0.81 (0.80-0.82), and 0.78 (0.77-0.78), respectively]. Conclusions:For the patients in comprehensive ICU, MICU, CCU, and CVICU, APSⅢ or SAPSⅡ can be applied for predicting 28-day death risk. For the patients in SICU and NICU, OASIS or SAPSⅡ can be applied to predict 28-day death risk. For the patients in TICU, SAPSⅡ or LODS can be applied for predicting 28-day death risk. For CVICU patients, APSⅢ or LODS can be applied to predict 28-day death risk.
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Objective:To investigate the protective effect of β- blocker (esmolol) on myocardia and toll-like receptor 4 (TLR4) inflammatory pathway in septic rats.Methods:Sixty male Wistar rats were randomly (random number) divided into the shame group, sepsis group (CLP group), esmolol group (CLP+ES group) and TLR4 inhibitor group (CLP+TAK-242 group) with 15 rats in each group. Cecal exploration was performed in the shame group, and cecal ligation and perforation (CLP) was performed in the CLP group, CLP+ES group and CLP+TAK-242 group. The CLP+ES group received intraperitoneal injection of esmolol diluent 20 mg/kg 12 h after CLP. The CLP+TAK-242 group was given intraperitoneal injection of TAK-242 3 mg/kg at the same time point as above. The shame group and CLP group were given the same amount of normal saline. Rats in all groups were sacrificed 24 h after operation, and the samples were collected and processed. The pathological changes of myocardium were observed by hematoxylin - eosin staining. The expression of TLR4, myeloid differentiation protein 88 (MyD88) and nuclear factor -κB (NF-κB) in myocardial tissue were observed by immunohistochemistry. Masson staining was used to observe the expression of fibers and inflammatory factors in myocardial tissue. The protein expressions of TLR4, MyD88, NF-κB and aspartic acid specific cysteine protease 1 (caspase-1) were detected by Western blot. Serum levels of cardiac troponin I (cTn-I), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA).Results:Compared with the shame group, myocardial injury, fibrosis and inflammatory cell infiltration were significantly aggravated in the CLP group, and the levels of myocardial injury index cTn-I and inflammatory mediators TNF-α, IL-6 and IL-1β were significantly increased [(8.70±0.22) vs. (4.41±0.31), (445.57±9.13) vs. (219.60±5.52), (165.55±2.18) vs. (93.47±3.37), (124.12±2.59) vs. (67.63±6.04),all P<0.05]. Compared with the CLP group, myocardial injury was significantly reduced in the CLP+ES group and CLP+TAK-242 group, and the levels of inflammatory transmitters were significantly reduced [(5.38±0.18) and (5.37±0.13) vs. (8.70±0.22), (322.73±7.63) and (300.58±17.47) vs. (445.57±9.13), (121.28±5.44) and (120.30±4.95) vs. (165.55±2.18), (102.60±4.09) and (105.08±7.21) vs. (124.12±2.59), all P<0.05]. Western blot analysis showed that the protein expression levels of TLR4, MyD88, NF-κB and caspase-1 in the CLP group were significantly higher than those in the shame group [(1.79±0.15) vs. (1.15±0.04), (4.70±0.30) vs. (3.87±0.10), (0.35±0.04) vs. (0.18±0.02), (2.27±0.29) vs. (1.15±0.07), all P<0.05], while the protein expression levels in the CLP+ES group and CLP+TAK-242 group were significantly lower than those in the CLP group [(1.31±0.16) and (1.18±0.14) vs. (1.79±0.15), (1.50±0.16) and (1.46±0.19) vs. (2.27±0.29), (0.27±0.02) and (0.24±0.01) vs. (0.35±0.04), (1.50±0.16) and (1.46±0.19) vs. (2.27±0.29), all P<0.05]. Conclusions:β-blocker can reduce myocardial injury and inhibit the expression of inflammatory mediators in septic rats by blocking the inflammatory response mediated by TLR4 signaling pathway.
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Objective:To investigate the expression of NOD-like receptor protein 3 (NLRP3) inflammasome in intestinal injury models with different severity of sepsis and the inflammatory response and apoptosis mediated by NLRP3 inflammasome.Methods:Human colorectal adenocarcinoma cells (Caco-2) were cultured in vitro. The logarithmic growth phase cells were divided into blank control group (normal culture in complete medium) and lipopolysaccharide (LPS) 1, 2 and 4 mg/L groups (complete medium containing 1, 2 and 4 mg/L LPS, respectively). The supernatant were collected at 6, 12 and 24 hours, and the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β, IL-18) were detected by enzyme linked immunosorbent assay (ELISA). The apoptotic level of cells was detected by flow cytometry. The cells were harvested, and the real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect the mRNA expressions of NLRP3 and silent information regulator 1 (SIRT1). Western blotting was used to detect the protein expressions of NLRP3, SIRT1, caspase-1 and apoptosis-associated speck-like protein (ASC). Results:ELISA results showed that the levels of IL-6, TNF-α, IL-1β, and IL-18 in cell supernatant of LPS groups increased in a dose-dependent and time-dependent manner as compared with the blank control group during the same intervention period. The increase was most significant in LPS 4 mg/L group at 24 hours [IL-6 (ng/L): 3.55±0.06 vs. 0.67±0.09, TNF-α (ng/L): 15.37±0.19 vs. 5.04±0.14, IL-1β (ng/L): 2.26±0.10 vs. 0.56±0.09, IL-18 (ng/L): 433.92±22.55 vs. 93.55±21.13, all P < 0.05]. The results of the apoptotic test showed that, compared with the blank control group, the apoptotic rate of LPS groups increased in a dose-dependent and time-dependent manner, and the apoptotic rate of LPS 4 mg/L group increased most significantly at 24 hours [(14.83±3.73)% vs. (5.87±1.17)%, P < 0.05]. RT-qPCR results showed that the expression level of NLRP3 mRNA was increased, while the expression level of SIRT1 mRNA was decreased with the increase of LPS intervention dose and the prolonging of intervention time. At 24 hours, there were significant differences between LPS 4 mg/L group and blank control group [NLRP3 mRNA (2 -ΔΔCt): 8.20±2.82 vs. 1.00±0.36, SIRT1 mRNA (2 -ΔΔCt): 0.58±0.01 vs. 1.03±0.06, both P < 0.05]. Western blotting showed that compared with the blank control group, the protein expression levels of NLRP3, caspase-1 and ASC in LPS groups were significantly increased, while the protein expression levels of SIRT1 were significantly decreased. During each intervention period, with the increase of LPS dose, the expressions of NLRP3, caspase-1 and ASC protein increased gradually, while the expression of SIRT1 protein decreased gradually. At 24 hours, the difference between the LPS 4 mg/L group and the blank control group was significant [NLRP3 protein (NLRP3/β-actin): 1.48±0.03 vs. 0.90±0.12, caspase-1 protein (caspase-1/β-actin): 1.18±0.11 vs. 0.72±0.09, ASC protein (ASC/β-actin) : 1.09±0.01 vs. 0.82±0.03, SIRT1 protein (SIRT1/β-actin): 0.48±0.03 vs. 0.76±0.05, all P < 0.05]. Conclusion:In vitro, in the sepsis induced intestinal inflammation model, with the increase of LPS intervention dose and the prolongation of intervention time, intestinal inflammatory response and cell apoptosis showed an increasing trend, which may be related to the up-regulation of NLRP3 inflammasome and its downstream products ASC and caspase-1, and to the down-regulation of SIRT1 expression.
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Objective:To explore whether resveratrol (RSV) could activate silent information regulator 1 (SIRT1) to regulate the activation of NOD-like receptor protein 3 (NLRP3) inflammasome in sepsis induced intestinal injury model, and then reduce intestinal inflammation and cell apoptosis, so as to play a protective role in intestinal barrier function.Methods:① In vitro experiment: human Colorectal adenocarcinoma cells (Caco-2) were cultured, which were divided into normal group (normal culture on complete medium for 48 hours), lipopolysaccharide (LPS) group (normal culture on complete medium for 24 hours, then LPS containing 2 mg/L complete medium intervention for 6 hours), RSV low, medium and high concentration groups and SIRT1 inhibitor (EX-527) group (complete medium normal culture for 24 hours, LPS containing 2 mg/L complete medium intervention for 6 hours, followed by RSV 10, 20, 40 μmol/L or EX-527 10 μmol/L intervention for 6 hours, respectively). The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-18, IL-1β) in the cell supernatant were determined by enzyme linked immunosorbent assay (ELISA). The apoptosis level of the cells was detected by flow cytometry. Western blotting was used to detect the protein levels of NLRP3, SIRT1, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC). ② In vivo experiment: according to random number table method, 24 male Wistar rats were divided into sham operation group (Sham group), cecal ligation and perforation (CLP) 6 hours group (CLP 6 h group), CLP 24 h group and RSV intervention group [RSV (20 mg/kg) was intraperitoneally injected 6 hours and 12 hours after CLP], with 6 rats in each group. The levels of NLRP3, caspase-1 and ASC in the intestine of rats were detected by immunohistochemistry. Results:① Compared with the normal group, the levels of inflammatory factors in the cell supernatant of the LPS group were increased and the expression of SIRT1 protein was decreased, while the protein expressions of NLRP3, caspase-1 and ASC were increased. Compared with LPS group, different concentrations of RSV reduced the level of inflammatory factors, increased the activity of SIRT1, inhibited the expression of NLRP3 inflammasome and its downstream products caspase-1 and ASC, and the effect of high concentration of RSV (40 μmol/L) was the most significant [TNF-α (ng/L): 8.77±0.43 vs. 12.66±0.81, IL-6 (ng/L): 1.35±0.20 vs. 1.93±0.09, IL-1β (ng/L): 1.05±0.04 vs. 1.31±0.07, IL-18 (ng/L): 519.50±11.16 vs. 622.70±30.69, SIRT1/β-actin: 0.80±0.05 vs. 0.58±0.02, caspase-1/β-actin: 0.55±0.06 vs. 0.78±0.06, ASC/β-actin: 0.78±0.08 vs. 1.04±0.15, all P < 0.05], while SIRT1 inhibitor EX-527 had the opposite effects. There was no significant difference in the apoptosis rate among normal group, LPS group, and low, medium and high concentration RSV groups, as well as EX-527 group [(7.03±0.57)%, (9.67±0.55)%, (9.57±0.70)%, (9.30±2.15)%, (9.87±0.97)%, (9.07±0.93)%, F = 2.590, P = 0.082]. ② Immunohistochemical results showed that compared with the Sham group, the expressions of NLRP3 inflammasomes and downstream products caspase-1 and ASC in the intestinal epithelial cells in CLP 6 h group, CLP 24 h group and RSV intervention group were significantly increased. The percentage of ASC-positive area in intestinal epithelium of RSV intervention group was significantly lower than that of CLP 6 h group [(15.22±2.73)% vs. (19.88±2.67)%, P < 0.05], and the expressions of NLRP3 and caspase-1 were significantly lower than those of CLP 24 h group [(9.31±1.37)% vs. (13.19±1.92)%, (19.57±3.92)% vs. (27.28±6.33)%, both P < 0.05]. Conclusion:After sepsis, high concentration of RSV could inhibit the activation of NLRP3 inflammasome by activating SIRT1, thereby reduce the expression of caspase-1 and ASC, and inhibit the secretion of inflammatory factors to reduce the inflammatory response.
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Objective:To explore the damage of the intestinal mucosal barrier of septic rats by the activation of NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasomes and the role of Ulinastatin (UTI) on the expression of intestinal nuclear factor-κB (NF-κB)/NLRP3 inflammasome signaling pathway in septic rats.Methods:According to the random number table method, 64 male Wistar rats were divided into sham operation group (Sham group), cecal ligation and puncture (CLP) group, UTI treatment group (100 kU/kg UTI was intraperitoneally injected 1, 6, 12 and 18 hours after CLP), and UTI pretreatment group (100 kU/kg UTI was given 1 hour before CLP), with 16 rats in each group. The survival of rats was observed after 24 hours, and the blood was collected from abdominal aorta at 24 hours after modeling, then rats were killed and their ileum tissues were taken. Hematoxylin-eosin (HE) staining was used to observe histopathological changes and Chiu score. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and intestinal fatty acid binding protein (I-FABP) in serum were detected by enzyme linked immunosorbent assay (ELISA). The protein expression of NF-κB p65 in intestinal tissue was detected by Western blotting. The expression of intestinal tight junction proteins Claudin-1, Occludin and the inflammasome NLRP3, apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 were detected by immunohistochemistry.Results:Compared with Sham group, the 24-hour survival rate of CLP group was significantly reduced. Histopathological results showed that the CLP group had severe edema of mucosa and submucosal stroma with obvious infiltration of inflammatory cells and disordered villi arrangement. Some glands were incomplete, and the villus structure was severely damaged. The Chiu score was significantly increased. The levels of TNF-α, IL-1β, I-FABP in serum and the protein expression of NF-κB p65 in intestinal tissue were significantly increased. The positive expressions of NLRP3, caspase-1 and ASC were also significantly increased. However, the positive expression of tight junction protein in small intestine tissue such as Occludin and Claudin-1 were significantly reduced. It suggested that when sepsis occurs, small intestinal mucosal barrier dysfunction happens, and mucosal permeability increases, while tight junction protein expression decreases, NLRP3 inflammasome and its upstream molecule NF-κB p65 were activated. After UTI treatment and UTI pretreatment intervention, although there was no significant difference in 24-hour survival compared with CLP group (62.5%, 68.8% vs. 43.8%, both P > 0.05), the intestinal tissue damage of septic rats was significantly improved. Specifically: Chiu score and the levels of TNF-α, IL-1β, I-FABP in serum were significantly decreased [Chiu score: 3.37±0.25, 3.23±0.16 vs. 4.08±0.13, TNF-α (ng/L): 147.62±20.74, 140.71±24.81 vs. 222.82±16.84, IL-1β (ng/L): 80.64±5.68, 78.11±4.75 vs. 133.73±3.92, I-FABP (μg/L): 38.29±3.60, 35.88±4.52 vs. 59.81±4.66, all P < 0.05]; the protein expression of NF-κB p65 was significantly decreased (NF-κB p65/β-actin: 0.65±0.10, 0.69±0.11 vs. 0.99±0.10, both P < 0.05), the positive expressions of Claudin-1 and Occludin in the small intestine tissue were increased [Claudin-1 positive expression area: (19.43±3.08)%, (23.99±6.27)% vs. (7.77±2.03)%; Occludin positive expression area: (19.58±4.75)%, (23.28±3.68)% vs. (11.69±4.30)%, all P < 0.05], while the positive expressions of NLRP3, caspase-1, ASC were decreased [NLRP3 positive expression area: (7.80±3.14)%, (6.86±2.63)% vs. (14.44±3.68)%; caspase-1 positive expression area: (10.62±3.52)%, (9.49±3.09)% vs. (26.69±8.05)%; ASC positive expression area: (9.95±2.81)%, (10.53±3.61)% vs. (24.16±5.48)%, all P < 0.05]. However, there was no significant difference in the improvement effect between UTI treatment group and UTI pretreatment group.Conclusions:Intestinal barrier dysfunction in sepsis may be related to the activation of NLRP3 inflammasomes in the intestinal mucosa. The protective effect of UTI in the intestinal mucosa may be related to inhibiting the activation of NLRP3 inflammasomes in the intestinal mucosa, but UTI pretreatment has no obvious advantage compared with UTI treatment.
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To systematically evaluate the effect of vitamin C on prognosis of critically ill patients. Methods Randomized controlled trials (RCT) about vitamin C treatment for critically ill patients were searched in CNKI, CBM, VIP database, Wanfang database, PubMed, Springer Link, Embase, Web of Science, and Cochrane Library from their inception to May 2019. Patients in the treatment group received ascorbic acid while patients in the control group received placebo or other treatment. Outcome measures included mortality, the length of intensive care unit (ICU) stay, the length of hospital stay, and incidence of atrial fibrillation. Two researchers were responsible for literature screening, data extraction and quality evaluation independently. Meta-analysis was performed with RevMan 5.2 software. The publication bias was analyzed by funnel plot. Results A total of 28 RCTs were enrolled and 4 420 patients were included (2 207 in intervention group and 2 213 in control group). Meta-analysis showed that there was no significant difference in mortality between intervention group and control group [odds ratio (OR) = 0.90, 95% confidence interval (95%CI) = 0.75 to 1.08, P = 0.27]. The length of ICU stay [mean difference (MD) = -0.23, 95%CI = -0.29 to -0.16, P < 0.000 01] and the length of hospital stay (MD = -0.96, 95%CI = -1.21 to -0.70, P < 0.000 01) in intervention group were less than those in control group. Subgroup analysis showed that mortality of patients with sepsis and septic shock in intervention group was lower than that in control group (OR = 0.65, 95%CI = 0.43 to 0.99, P = 0.04). For patients undergoing cardiac surgery, the incidence of postoperative atrial fibrillation in intervention group was lower than that in control group (OR = 0.43, 95%CI = 0.34 to 0.54, P < 0.000 01). It was shown by funnel plot that there was less publication bias among studies. Conclusions Vitamin C does not reduce mortality in critically ill patients, but it can reduce the length of ICU stay and hospital stay. In addition, vitamin C can reduce mortality of patients with sepsis and septic shock and reduce the incidence of atrial fibrillation post operation in patients undergoing cardiac surgery.
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Objective To systematically evaluate the effect of high-flow nasal cannula oxygen (HFNC) on improving the atelectasis and respiratory function in adults after cardiac surgeries.Methods All randomized controlled trials (RCTs) about HFNC therapy for adults after cardiac surgeries published from January 2000 to March 2018 were searched through CNKI, CBM, VIP, Wanfang, PubMed, Springer Link, Embase, Web of Science, Cochrane Library. The references from relevant articles were searched. The experimental group was treated with HFNC while the control group treated with conventional oxygen therapy (COT). The outcome measurements included radiological atelectasis score (RAS), endotracheal reintubation rate and the length of intensive care unit (ICU) stay. Two researchers were responsible for literature screening, data extraction and quality evaluation respectively. Meta-analysis was performed with RevMan 5.2 software. Funnel plot was used to analyze the publication bias.Results A total of 4 RCTs were enrolled and 643 patients were included (325 in experimental group and 318 in control group). Meta-analysis showed that the tracheal reintubation rate in experimental group was lower than that in control group [odds ratio (OR) = 0.26, 95％ confidence interval (95％CI) = 0.09-0.74,P = 0.01], but there was no significant difference in RAS [mean difference (MD) = -0.15, 95％CI = -0.50-0.21,P = 0.41] and the length of ICU stay (MD= 0.09, 95％CI =-0.09-0.26,P = 0.33) between experimental group and control group. Sensitivity analysis was performed in two trials with low risk of bias, which demonstrated that there was no significant difference in RAS between the two groups (MD =0.06, 95％CI = -0.26-0.37,P = 0.73). It was shown by the funnel analysis that there was bias in the study of the length of ICU stay in the literature, while the bias of RAS and tracheal reintubation rate was low.Conclusion Compared with COT, HFNC could reduce the rate of tracheal reintubation in adults after cardiac surgeries, but no difference was found in improving atelectasis or reducing the length of ICU stay.
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Objective To study the computed tomography(CT)manifestations of involvement of bridging septa in the perirenal space(BSPS)during acute pancreatitis(AP)and its correlation with extrapancreatic inflam-mation on abdominal computed tomography(EPICT)score. Methods 106 patients with acute pancreatitis were included in this study. Emphasis was placed on CT findings of BSPS and the EPICT score in all the patients. Results The EPICT score was 4 to 7 in 67 patients,and the EPICT score was 0 to 3 in 39 patients. BSPS involve-ment was shown in all the patients. The left or right BSPS involved in 102 patients and 98 patients,respectively. Thickening of the BSPS was shown as strip shadow with slightly higher density and hazy border;fluid collection of the BSPS was shown as liquid density with hazy border. The involvement of BSPS showed a statistically significant association with the EPICT score in the AP patients(r=0. 703,P<0.01). Conclusion BSPS involved by acute pancreatitis is shown as a strip shadow with slightly higher density or as liquid density with hazy border on CT images, reflecting the severity of the acute pancreatitis.
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Objective To study the computed tomography(CT)manifestations of involvement of bridging septa in the perirenal space(BSPS)during acute pancreatitis(AP)and its correlation with extrapancreatic inflam-mation on abdominal computed tomography(EPICT)score. Methods 106 patients with acute pancreatitis were included in this study. Emphasis was placed on CT findings of BSPS and the EPICT score in all the patients. Results The EPICT score was 4 to 7 in 67 patients,and the EPICT score was 0 to 3 in 39 patients. BSPS involve-ment was shown in all the patients. The left or right BSPS involved in 102 patients and 98 patients,respectively. Thickening of the BSPS was shown as strip shadow with slightly higher density and hazy border;fluid collection of the BSPS was shown as liquid density with hazy border. The involvement of BSPS showed a statistically significant association with the EPICT score in the AP patients(r=0. 703,P<0.01). Conclusion BSPS involved by acute pancreatitis is shown as a strip shadow with slightly higher density or as liquid density with hazy border on CT images, reflecting the severity of the acute pancreatitis.
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Objective To compare the clinical efficacy of video assisted thoracic surgery using two ports and three ports for pulmonary bullae.Methods Clinical data of 120 patients used video assisted thoracic surgery in the treatment of pulmonary bullae were retrospectively analyzed.62 patients with three ports conventional surgery were selected as three ports group,58 patients with two ports method were selected as two ports group.The two groups were followed up after operation,and the operation time,intraoperative bleeding,extubation time,postoperative drainage volume and hospital stay,the pain scores at postoperative 6h,1 day,3 days,1 week and postoperative complications were compared between the two groups.Results There were no significant differences in operative time and blood loss between the two groups(t=-0.845,-1.164,all P>0.05).After operation,the extubation time[(3.2±1.6)d],postoperative thoracic drainage[(270.8±192.4)mL]and hospitalization time[(5.9±2.1)d] of the two ports group were significantly less than those of the three ports group(t=-4.972,-2.637,-4.601,all P<0.05).The two groups had no postoperative complications,all patients recovered and discharged,followed up,there was no recurrence and other complications.6h,1 day,3 days and 1 week after surgery,the VAS scores of the two ports group were significantly lower than those of the three ports group(t=-5.888,-6.682,-4.190,-5.710,all P<0.01).Conclusion The clinical curative effect of video assisted thoracic surgery using two ports is obvious,the safety is high,and it has high popularization and application value.
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Background Pluripotent stem cell-derived retinal pigment epithelial (RPE) cells holds great promise for the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa (RP),but the poor induction efficiency and the according high cost of RPE differentiation hindere its clinical applications.Curcumin is proved to have a promoting effect on the induced differentiation of embryonic stem cells (ESCs).However,the mechanism of curcumin on differentiation of human ESCs into RPE-like cells remains unclear.Objective This study aimed to explore the underlying molecular mechanism of curcumin on directed differentiation of human ESCs into RPE-like cells.Methods Human ESCs strains were cultured in the Matrigel-coated 6-well plate with mTeSRTM 1 medium until over-confluence,and basic fibroblast growth factor was withdrawn there after to induce automatic differentiation.Curcumin at the final concentration 1 μmol/L was added in the first day of differentiation for 24 hours,and the cells without curcumin in the medium served as the control group.Total RNA and protein were extracted at 3 weeks and 5 weeks after induction.RT-PCR,Western blot and immunofluorescence were performed to examine the expressions of the biomarks of stem cells and RPE cells as well as Wnt/β-catenin signaling pathway components.The endocytosis of polystyrene microsphere by induced RPE (iRPE) cells was investigated to verify their function of phagocytosis which features RPE cells.Results Pigmented cells were found from 3 weeks through 5 weeks after induction in the curcumin group,but only less pigmented cells were seen in the fifth week after induction in the control group.In the third and fifth week after induction,the relative expression levels of NANOG mRNA in the iRPE cells were significantly lower than those in the control group (t =13.086,P =0.022;t =34.186,P =0.004),and the relative expression levels of Pax6,RX,CRALBP and RPE65 mRNA were higher in the curcumin group than those of the control group (all at P＜0.01).Western blot assay showed that the expressing bands for CRALBP,RPE65 and MITF enhanced in iRPE cells with a similar appearance in human RPE cells.However,these expressions were all absent in human ESCs.Immunofluorescence staining showed the positive expressions of Pax6,MITF and ZO-1 in cytoplasm of iRPE cells in the curcumin group with a purified efficacy 100％.The fluorescence dye-doped polystyrene microspheres in cytoplasm were obvious in the iRPE cells like positive controls,but the polystyrene microsphere was absent in the negative controls.From 3 weeks through 5 weeks after induced,the relative expression levels of Lef1,MYC and TCF7 mRNA (the dwnstream target genes of Wnt signaling pathway),FZD3 mRNA (Wnt receptor),Wnt2B mRNA (Wnt ligand) and Wnt7B mRNA were significantly reduced in the curcumin group compared with the control group (all at P＜0.01).Conclusions Curcumin promotes the differentiation of human ESCs into RPE-like cells by stimulating the activation of Wnt signaling pathway,and therefore accelerate the differentiation and mature of iRPE cells.
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Objective To evaluate the diagnostic value of 3-dimentional spiral computer tomography (3 D- sCT) in patients with upper urinary tract obstruction. Methods 113 patients with upper urinary tract obstruction were subjected to 3D-sCT. Results The site of urinary tract obstruction and hydronephrosis were distinctly shown in all patients by 3D-sCT. 112 of them were confirmed by ESWL, pathological or operative findings. Conclusions 3D-sCT can exactly show the location, cause and interaction of the upper urinary obstruction, and is especially applied to patients with resultless IVP and unable to retrograde pyelography.