Objective To investigate the effects of sevoflurane preconditioning (SP) on acute lung injury induced by lipopolysaccharide (LPS) in rats.Methods Twenty-four male SD rats weighing 220-250 g were randomly divided into 4 groups (n = 6 each): group Ⅰ control (group C),group Ⅱ LPS,group Ⅲ sevoflurane (group Sev) and group Ⅳ SP + LPS.In group Ⅰ and Ⅱ ,normal saline and LPS 5 mg/kg were given Ⅳ 30 min after ventilation respectively.In group Ⅲ and Ⅳ,the animals inhaled sevoflurane (end-tidal concentration 2.4% ) for 30 min followed by 5 min wash-out,and then received iv injection of normal saline and LPS 5 mg/kg respectively.The animals were killed at 6 h after LPS or normal saline administration.Lungs were removed for determination of W/D lung weight ratio,myeloperoxidase (MPO) activity,cytokine-induced neutrophil chemoattractant-1 (CINC-1) content and expression of CINC-1 and CINC-1 mRNA.The severity of lung injury was evaluated using diffuse alveolar damage (DAD) score.Results Compared with group Ⅰ ,W/D lung weight ratio,DAD score,MPO activity and CINC-1 content were significantly increased,and expression of CINC-1 and CINC-1 mRNA up-regulated in group Ⅱ and Ⅲ,while there was no significant difference in the above indices between group Ⅲ and group Ⅰ .Compared with group Ⅱ ,W/D lung weight ratio,DAD score,MPO activity and CINC-1 content were significantly decreased,and expression of CINC-1 and CINC-1 mRNA down-regulated in group Ⅲ.Conclusion Sevoflurane preconditioning can protect the lungs against LPS-induced acute lung injury by inhibiting inflaunnatory response.

Objective To investigate the prognosis of sepesis patients whose timing of hemopurification therapy was classified according to kidney disease:improving global outcomes acute kidney injury (KDIGO AKI) classification.Methods The clinic data of sepsis patients,who were treated with hemopurification therapy in Xiangya Hospital intensive care unit (ICU) during January 1,2014 to June 1,2014,were retrospectively analyzed.According to KGIDO AKI classification as their timing of hemopurification therapy,103 patients were divided to 2 groups,AKI Ⅰ group (n =34),AKI Ⅱ,Ⅲ group (n =69).Acute physiology and chronic health evaluation Ⅱ (APACHE-Ⅱ),sequential organ failure assessment (SOFA),rate of multiple organ injury 7-,28-,90-days mortality rate of 2 groups were analyzed.For 90 days survivors,the length of ICU stay,hospital stay,the frequency and time of hemopurification were analyzed,respectively.Results APACHE-Ⅱ,SOFA of KDIGO AKI Ⅰ group was less than KDIGO AKI Ⅱ,Ⅲ group.KDIGO AKI I group was less on rate of 3 and ≥4 organ injury than KDIGO AKI Ⅱ,Ⅲ group.7-,28-,90-days mortality rate of KDIGO AKI I group were less than AKI Ⅱ,Ⅲ group.In 90 days survivors,length of ICU stay,hospital stay,frequency and time of hemopurification of KDIGO AKI Ⅰ group were less than AKI Ⅱ,Ⅲ group.Conclusions KDIGO AKI classification is an effective indicator to sepsis patients for hemopurification therapy.Compared to KDIGO AKI Ⅱ,Ⅲ,sepsis patients with KDIGO AKI Ⅰ were less severity and multiple organ injuries.To start hemopurification during AKI Ⅰ,it could decrease mortality rate,length of ICU stay,hospital stay,and frequency and time of hemopurification therapy.

Objective To investigate the effect of 3 concentrations of sevoflurane pretreatment on acute lung injury induced by endotoxin in rats. Methods Thirty-six male SD rats were randomly divided into 6 groups:a control group(Group A), a sevoflurane group(Group B), a 3.6% sevoflurane pretreatment group(Group C), a 2.4% Sevoflurane pretreatment group(Group D), a 1.2% sevo sevoflurane pretreatment group(Group E), and lipopolysaccharide (Group F).The rats were killed 6 h after lipopolysaccharide (LPS) or saline injection.Histological examinations of the lung tissues were performed with light microscope. Lung wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, and intercellular adhesion molecule 1 (ICAM-1) mRNA expression were assayed. Results Introvenous LPS significantly aggravated lung tissue damage,increased lung W/D ratio, MPO activity, and lung ICAM-1 mRNA expression compared with the control group(P＜0.05). Precondition with 2.4% sevoflurane significantly attenuated the above mentioned changes induced by LPS (P＜0.05). The 3.6% LPS (Group C) significantly attenuated lung tissue damage and decreased MPO activity,lung ICAM-1 mRNA expression compared with the Group F (P＜0.05),but no significant change in lung W/D ratio was seen (P＞0.05). MPO activity was significantly decreased in Group E (P＜0.05), but lung W/D ratio and lung ICAM- 1 mRNA expression had no significant changes (P＞0.05).Conclusion Precondition with 2.4% sevoflurane can reduce LPS induced lung injury in rats. Decreased expression of ICAM-1 and less accumulation of neutrophils were participated in its mechanism.

Purpose To investigate the mutations of ID3,TCF3 and MYC genes in Chinese Burkitt lymphoma and discuss their significance.Methods Total DNA was extracted from tumor tissues of 32 patients with Burkitt lymphoma,then the DNA was amplified by polymerase chain reaction (PCR),and the products of PCR were sequenced directly with Sanger sequencing methods.Results The mutation rates of ID3 and TCF3 genes were 35.5％ (11/31) and 18.8％ (6/32) respectively.The mutation rate of MYC was 50％.The mutation rates of MYC exon 1,MYC exon 2 and MYC exon 3 were 3.3％ (1/30),50％ (15/30) and 7.7％ (2/26) respectively.Conclusion Recurrent mutations of the ID3,TCF3 and MYC genes in Chinese Burkitt lymphoma were identified by Sanger sequencing.For TCF3 gene,a novel mutation c.2202G ＞ C p.L569V was found in three cases.In two cases,a novel mutation of c.1070A ＞G p.G182D was found in MYC gene.

OBJECTIVE: To determine whether central venous-to-arterial carbon dioxide tension difference (Pcv-aCO(2)) could still be used as a goal of fluid resuscitation in septic patients who already had ScvO2 greater than 70% after early resuscitation. METHODS: A prospective observational study was performed on 56 septic patients admitted to the Intensive Care Unit (ICU) in a single University Hospital, who already had ScvO2 greater than 70% after early resuscitation. They were divided into two groups, based on whether the patients' initial Pcv-aCO2 was less than 6 mmHg (low gap group) or greater than or equal to 6 mmHg (high gap group). The following data were collected at 0, 12, and 24 hours (T(0), T(12), T(24)) after study inclusion: hemodynamic indices [mean blood pressure (MAP), heart rate (HR), cardiac output (CO), central venous pressure (CVP)], perfusion-related indexes [ScvO(2), Pcv-aCO2, serum lactate (Lac), Lac clearance rate], organ function- related indices [oxygenation index (PaO2/FiO(2)), serum creatinine (SCr), creatine kinase (CK-MB)], APACHE II score, SOFA score, and 24 hours amounts of fluid infusion. RESULTS: Twenty patients (42.9%) with initial Pcv-aCO(2) ≥ 6 mmHg were included in the high gap group and another thirty-two patients were included in the low gap group. At T12 and T24, ScvO(2) and CO were significantly higher, and Lac and SCr were significantly lower in low gap patients than high gap patients (P<0.05). At T(12) and T(24), Lac clearance rate was significantly higher (P<0.05), and 24-hours amounts of fluid infusion was significantly less [(3449.47 ± 695.41) mL vs (4070.66 ± 757.43) mL, P= 0.002] for the low gap group than for the high gap group, as well as the descrease of SOFA score at T(24) (P<0.05). There was no significant difference of APACHE II score between the 2 groups (P<0.05). CO and Pcv-aCO(2) values were inversely correlated (P< 0.05). CONCLUSION Septic patients targeting only ScvO(2) may still have inappropriate tissue perfusion, especially when Pcv-aCO2 ≥6 mmHg, which indicates insufficient resuscitation. When ScvO(2) > 70% has achieved after early resuscitation, Pcv-aCO2 can still be used as a goal of fluid resuscitation in septic patients .
Adult ; Blood Gas Analysis ; Carbon Dioxide ; blood ; Central Venous Pressure ; Female ; Fluid Therapy ; Hemodynamics ; Humans ; Male ; Middle Aged ; Prospective Studies ; Sepsis ; blood ; physiopathology ; therapy ; Severity of Illness Index ; Vena Cava, Superior

Objective:To investigate the clinical efficacy and safety of polymyxin B in the treatment of sepsis caused by extensively-drug resistant (XDR) Gram-negative bacteria.Methods:A retrospective analysis of 39 septic patients with XDR Gram-negative bacterial infection treated with polymyxin B in the department of critical care medicine of Xiangya Hospital of Central South University from June 2018 to September 2019 were enrolled. The clinical characteristics, bacterial culture, the sensitivity antibacterial drugs, types and courses of antibiotics, biochemical indexes, and acute physiology and chronic health evaluationⅡ(APACHEⅡ) before and after polymyxin B treatment were collected, to assess microbial clearance and efficacy, drug related adverse effects, and 28-day mortality in septic patients with XDR.Results:Of the 39 septic patients with XDR, 32 (82.1%) were male, with the mean age of (53.6±12.6) years old. The main infection site was pulmonary infection (51.2%), and the treatment courses of polymyxin B were ≥ 5 days. A total of 66 pathogenic bacteria were detected from 39 patients. Among them, with the high estrate of detecting Acinetobacter baumannii of 51.5% (34/66). After treatment with polymyxin B, the results showed that the clearance rate of microorganisms was 65.2% (43/66), the overall effective rate was 59.0% (23/39), and the 28-day all-cause mortality was 41.0% (16/39). There were no significant differences in clinical efficacy and microbial clearance among patients with different treatment groups of polymyxin B [< 10 days, 10-15 days, and > 15 days groups: effective rates were 56.5% (13/23), 54.5% (6/11), 80.0% (4/5), χ2 = 0.999, P = 0.728; the microbial clearance rates were 43.5% (10/23), 54.5% (6/11), and 80.0% (4/5), χ2 = 2.141, P = 0.393]. The effective and microbial clearance rates of the polymyxin B daily doses of 150 mg and 200 mg groups were significantly higher than those of the daily dose of 100 mg [effectiveness: 85.7% (6/7), 87.5% (7/8) vs. 41.7% (10/24); microbial clearance rate: 71.4% (5/7), 87.5% (7/8) vs. 33.3% (8/24), all P < 0.05], however, there were no significant differences in the length of intensive care unit (ICU) stay and mechanical ventilation time among different daily dose groups. The APACHEⅡscore after polymyxin B administration was significantly lower than before administration (all patients: 16.20±9.24 vs. 24.40±4.73, effective patients: 11.30±4.08 vs. 23.00±4.56, both P < 0.05). Four patients with renal injury had an increase in serum creatinine during the administration of polymyxin B, and recovered after discontinuation of the drug without other adverse reactions. Conclusion:Polymyxin B can be used as an effective treatment option for patients with severe infection of XDR Gram-negative bacteria.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.