【摘要翻译】 一 氧化氮合酶( NOS) -2( NOS-2) 的诱导和一氧化氮产物增加是过敏性气道疾病的共同特征。严重哮喘与气道S-亚硝基硫醇减少相关。S-亚硝基硫醇是NO的生化产物, 可通过促炎症转录因子NF-κB 的S-亚硝基化抑制炎症反应。因此, 重建气道S-亚硝基硫醇对治疗可能有益。我们对此假设在以卵清蛋白诱导的过敏性炎症大鼠模型中进行验证。未使用或使用卵清蛋白致敏的动物均在卵清蛋白激发前于气管内灌注S-亚硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后进行分析。GSNO 给药增加了肺组织S-亚硝基硫醇水平。与对照组比, GSNO 降低了卵清蛋白致敏动物NF-κB 的活性, 但对支气管肺泡灌洗细胞总数、分类计数及杯状细胞化生标记物均无显著影响。GSNO给药也改变了HIF-1 的活性, 导致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我们使用NOS-2基因敲除小鼠来评价内源性一氧化氮合成酶-2 在调节NF-κB和( 或) HIF-1 活性及气道过敏性炎症的作用。尽管在NOS-2 基因敲除小鼠中卵清蛋白诱导的NF-κB 活力轻度增高, 这与支气管肺泡灌洗中性粒细胞轻度增加有关, 其他的过敏性炎症指标和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之间却无明显相差。总体来说, 我们的研究表明GSNO灌注能抑制气道过敏性炎症中NF-κB 活性, 但是并不能显著地影响大部分炎症及杯状细胞化生指标, 这样可能因为对其他信号通道( 比如HIF-1) 的影响而限制了它的治疗价值。【述评】 GSNO 是近年哮喘治疗研究的热点。既往的研究发现GSNO 在哮喘治疗中有一定前景。本研究却发现GSNO 气管内滴注虽能抑制过敏性气道炎症中NF-κB 活性,但并不能显著抑制气道炎症反应及杯状细胞化生这两个哮喘关键病理改变, 可能与GSNO 同时影响了HIF-1 等其他信号通路有关。该研究表明GSNO 对哮喘气道炎症治疗效果有限, 同时表明哮喘气道炎症调控机制较为复杂, 治疗药物的设计需考虑多种信号通路对哮喘气道炎症的影响。
ObjectiveTo evaluate the safety and efficacy of preoperation administration of enteral nutrition enriched ω-3 fatty acids for gastric cancer patients. MethodsA single center randomized controlled clinical trial was performed in 60 cases of gastric cancer in West China Hospital during January 2014 to June 2014, and cases were equally randomized divided into treatment group and control group. Cases of treatment group were given enteral nutrition enriched ω-3 fatty acids which was manufactured by Fresenius Kabi Deutschland GmbH for 5 consecutive days before operation, and cases of control group were given an isocaloric and isonitrogenous homogenized diet for 5 consecutive days before operation. The laboratory indexes of nutritional status and imflammatory factors were observed and compared between 2 groups on admission, preoperative day 1, postoperative day 3, and postoperative day 5. Liver and kidney function indexes which as the safety indexes were detected on admission and preoperative day 1. Vomiting, diarrhea, and infectious complications were recorded in addition. ResultsOn 3 days after operation, levels of interleukin-6 (IL-6) and α-acid glycoprotein (AAG) of treatment group were both lower than those of control group (P<0.05); on 5 days after operation, levels of C-reactive protein (CRP) of treatment group was lower than that of control group too (P<0.05); but at other time points, there were no significant differences in any index between the 2 groups (P>0.05). During the period of enteral nutrition, only 1 case suffered from bloating and 1 case suffered from diarrhea, both in treatment group, and the incidence of adverse reactions didn't differed between treatment group[6.7% (2/30)]and control group[0 (0/30)], P>0.05. Moreover, there were no significant differences between treatment group and control group in incidences of wound infection[3.3% (1/30) vs. 10.0% (3/30)], abdominal infection[0 (0/30) vs. 3.3% (1/30)], urinary infection[0 (0/30) vs. 3.3% (1/30)], and pulmonary infection[0 (0/30) vs. 6.7% (2/30)], but the total incidence of complication was lower in treatment group than that of control group[3.3% (1/30) vs. 23.3% (7/30)], P=0.026. ConclusionEnteral nutrition enriched ω-3 fatty acids can reduce the rate of infection-related complication for patients with gastric cancer, and has a sense of safety.
【Abstract】ObjectiveTo investigate the effect of Salvia Miltiorrhiza (SM) and Shengmai injection （SI） in treating systemic inflammatory response syndrome (SIRS) and their mechanism. Methods The animal model of SIRS was established by injectinglipopolysaccharide(LPS, 1 mg/kg)intraperitoneally. Forty Wistar rats were randomly divided into four groups: control group, SM group, SI group and combined treatment group (SM+SI group), which were treated with normal saline（5 ml/kg） plus LPS（1 mg/kg）, SM（5 ml/kg）plus LPSKG4（1 mg/kg）, SI（5 ml/kg）plus LPS（1 mg/kg）, SM（2.5 ml/kg） plus SI（2.5 ml/kg） and LPS（1 mg/kg） respectively. Six rats of each group were sacrificed for sample collection of blood, liver, lung and kidney 8 hours after LPS injection. Blood routine, serum TNF-α and IL-6 were measured. Specimen of organs were fixed in formalin and sent for routine pathological examination. The survival of other 4 rats of each group were observed untill 48 hours after LPS injection. SPSS 10.0 was used in statistical analysis. Results Two rats in control group died 13 hours and 22 hours after LPS injection respectively, the remaining 2 rats in this group and the rats in other 3 groups survived 48 hours after LPS injection. The white blood cell count of control group was significantly higher than that of other groups. The serum TNF-α and IL-6 of control group were significantly more than those of other groups. Pathological damages were found in all groups, and the most severe ones were in control group. SM and SI could decrease the level of serum TNF-α and IL-6 in the process of LPS-stimulated SIRS, down-regulate the severe inflammatory response, attenuate organ damages of the liver, lung and kidney, and increase forty-eihgt-hour survival rate obviously. Conclusion The experiment provides a theoretical base for clinical use of SM and SI in treatment of SIRS.
ObjectiveTo investigate the feasibility and safety of non-intubation anesthesia in thoracic surgery.MethodsFrom September 2017 to December 2019, 296 patients were operated at department of thoracic surgery in our hospital. There were 167 males and 129 females with an average age of 50.69±12.95 years, ranging from 16 to 76 years. The patients were divided into two groups according to whether they were intubated: 150 patients were in a non-intubation group, including 83 males and 67 females with an average age of 49.91±13.59 years, ranging from 16 to 76 years, and 146 patients were in an intubation group including 84 males and 62 females with an average age of 51.49±12.26 years, ranging from 16 to 74 years. Intraoperative data, postoperative recovery, inflammatory response of the two groups were compared.ResultsThere was no statistical difference between the two groups in operation time, blood loss, the lowest oxygen saturation or other indicators (P>0.05). But the highest partial pressure of carbon dioxide of the non-intubation group was higher than that of the intubation group (P=0.012). The non-intubation group was superior to the intubation group in postoperative recovery and inflammatory response (P<0.05).ConclusionThe non-intubation anesthesia is safe and maneuverable in thoracic surgery, and it has some advantages in accelerating postoperative rehabilitation.
ObjectiveTo investigate clinical efficacy of percutaneous nephroscope in treatment of patients with severe acute pancreatitis (SAP). MethodsEighty-six patients with SAP in this hospital from August 2012 to November 2015 were selected, which were divided into percutaneous nephroscope treatment group (43 cases) and laparotomy treat-ment group (43 cases) according to the difference of therapy modality. The conventional drug therapy was performed for all of them. The postoperative recovery, content of serum C reactive protein (CRP) on day 14 after operation, and post-operative complications were observed in these two groups. Results① The abdominal pain relief time, postoperative bowel sounds recovery time, normal body temperature recovery time, and postoperative hospitalization time in the percu-taneous nephroscope treatment group were significantly shorter than those in the laparotomy treatment group (P<0.05). ② The contents of serum CRP in the percutaneous nephroscope treatment group and in the laparotomy treatment group on day 14 after operation were significantly lower than those on day 1 before operation[(8.35±2.13) mg/L versus (31.44±3.45) mg/L, P<0.05; (16.42±2.44) mg/L versus (32.09±2.98) mg/L, P<0.05]. On day 14 after operation, the content of serum CRP in the percutaneous nephroscope treatment group was significantly lower than that in the laparotomy treat-ment group[(8.35±2.13) mg/L versus (16.42±2.44) mg/L, P<0.05]. ③ The incidence rate of postoperative complications in the percutaneous nephroscope treatment group was significantly lower than that in the laparotomy treatment group[14.0% (6/43) versus 32.6% (14/43), P<0.05]. ConclusionPercutaneous nephroscope in treatment of patients with SAP is effect, it has advantages of shorter hospital stay and early recovery, which could reduce incidence of postoperative complications, and it's mechanism might be related to systemic inflammatory response.
Acute lung injury is a kind of common complication after cardiopulmonary bypass. Acute lung injury is attributed to the ischemia-reperfusion injury and systemic inflammatory response syndrome. Several factors common in cardiac surgery with cardiopulmonary bypass may worsen the risk for acute lung injury including atelectasis, transfusion requirement, older age, heart failure, emergency surgery and prolonged duration of bypass. Targets for prevention of acute lung injury include mechanical, surgical and anesthetic interventions that aim to reduce the contact activation, systemic inflammatory response, leukocyte sequestration and hemodilution associated with cardiopulmonary bypass. We aim to review the etiology, risk factors and lung protective strategies for acute lung injury after cardiopulmonary bypass.
Although great progress has been achieved in the techniques and materials of cardiopulmonary bypass (CPB), cardiac surgery under CPB is still one of the surgeries with the highest complication rate. The systemic inflammatory response is an important cause of complications, mainly characterized by activation of innate immune cells and platelets, and up-regulation of inflammatory cytokines. After activation, a variety of molecules on the membrane surface are up-regulated or down-regulated, which can amplify tissue inflammatory damage by releasing cytoplasmic protease and reactive oxygen species, and activate multiple inflammatory signaling pathways in the cell, ultimately leading to organ dysfunction. Therefore, the expression of these cell membrane activation markers is not only a marker of cell activation, but also plays an important role in the process of vital organ injury after surgery. Identification of these specific activation markers is of great significance to elucidate the mechanisms related to organ injury and to find new prevention and treatment methods. This article will review the relationship between these activated biomarkers in the innate immune cells and vital organ injuries under CPB.
Objective To investigate the feasibility of selenium-methylselenocysteine (SMC) to promote peripheral nerve regeneration and its mechanism of action. Methods Rat Schwann cells RSC96 cells were randomly divided into 5 groups, which were group A (without any treatment, control group), group B (adding 100 μmol/L H2O2), group C (adding 100 μmol/L H2O2+100 μmol/L SMC), group D (adding 100 μmol/L H2O2+200 μmol/L SMC), group E (adding 100 μmol/L H2O2+400 μmol/L SMC); the effect of SMC on cell proliferation was detected by MTT method, and the level of oxidative stress was detected by immunofluorescence for free radicals [reactive oxygen species (ROS)] after determining the appropriate dose group. Thirty-six 4-week-old male Sprague Dawley rats were randomly divided into 3 groups, namely, the sham operation group (Sham group), the sciatic nerve injury group (PNI group), and the SMC treatment group (SMC group), with 12 rats in each group; the rats in the PNI group were fed with food and water normally after modelling operation, and the rats in the SMC group were added 0.75 mg/kg SMC to the drinking water every day. At 4 weeks after operation, the sciatic nerves of rats in each group were sampled for neuroelectrophysiological detection of highest potential of compound muscle action potential (CMAP). The levels of inflammatory factors [interleukin 17 (IL-17), IL-6, IL-10 and oxidative stress factors catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)] were detected by ELISA assay. The luxol fast blue (LFB) staining was used to observe the myelin density, fluorescence intensity of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) was observed by immunofluorescence staining, and myelin morphology was observed by transmission electron microscopy with measurement of axon diameter. Western blot was used to detect the protein expressions of p38 mitogen-activated protein kinases (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). ResultsMTT assay showed that the addition of SMC significantly promoted the proliferation of RSC96 cells, and the low concentration could achieve an effective effect, so the treatment method of group C was selected for the subsequent experiments; ROS immunofluorescence test showed that group B showed a significant increase in the intensity of ROS fluorescence compared with that of group A, and group C showed a significant decrease in the intensity of ROS fluorescence compared with that of group B (P<0.05). Neuroelectrophysiological tests showed that the highest potential of CMAP in SMC group was significantly higher than that in PNI and Sham groups (P<0.05). ELISA assay showed that the levels of IL-6, IL-17, and MDA in PNI group were significantly higher than those in Sham group, and the levels of IL-10, SOD, and CAT were significantly lower; the levels of IL-6, IL-17, and MDA in SMC group were significantly lower than those in PNI group, and the levels of IL-10, SOD, and CAT were significantly higher (P<0.05). LFB staining and transmission electron microscopy showed that the myelin density and the diameter of axons in the SMC group were significantly higher than those of the PNI group and the Sham group (P<0.05). Immunofluorescence staining showed that the fluorescence intensity of GFAP and MBP in the SMC group were significantly stronger than those in the PNI group and Sham group (P<0.05). Western blot showed that the relative expressions of Nrf2 and HO-1 proteins in the SMC group were significantly higher than those in the PNI group and Sham group, and the ratio of p-p38MAPK/p38MAPK proteins was significantly higher in the PNI group than that in the SMC group and Sham group (P<0.05). Conclusion SMC may inhibit oxidative stress and inflammation after nerve injury by up-regulating the Nrf2/HO-1 pathway, and then inhibit the phosphorylation of p38MAPK pathway to promote the proliferation of Schwann cells, which ultimately promotes the formation of myelin sheaths and accelerates the regeneration of peripheral nerves.
Objective To investigate the percentage of CD4+CD25+ Treg in peripheral blood of patients with severe multiple trauma and systemic inflammatory response syndrome（SIRS） and its effects on cellular immunity and secondary infection.Metheds Peripheral blood of 23 patients with severe multiple trauma was collected in 24 h after SIRS was diagnosed，and flow cytometry was used to determine the percentage of CD4+CD25+ Treg and CD4/CD8 ratio.Simultaneously，in order to explore the cell proliferation，silver staining was used to determine Ag-NORs of leukomonocyte in peripheral blood represented by IS%.In order to investigate the infection in patients，sputum and secretion sample were collected for bacteriological examination on 1 and 5 day after SIRS was established.Forty healthy volunteers were enrolled as control.Results Compared with the control，the percentage of CD4+CD25+ Treg was significant higher[（14.21±3.43）% vs（9.53±3.22），Plt;0.01] and the ratio of CD4/CD8 and IS% were significant lower in patients with severe multiple trauma[（5.94±0.66）% vs（6.74±0.95）%，（1.22±0.25）% vs（1.72±0.36）%，respectively，both Plt;0.01].In those patients（n=14） who developed secondary infection，Treg% was significant higher [（18.69±4.21）% vs（12.58±2.49）%，Plt;0.01]，while IS% and CD4/CD8 were significant lower [（5.79±0.68）% vs（6.15±0.57）%，（1.15±0.25）% vs（1.39±0.25）%，both Plt;0.01].compared to the patients without secondary infection Conlusion CD4+CD25+ Treg is valuable to estimate the cellular immunity and predict secondary infection in patients with severe multiple trauma.