Sepsis-induced immunosuppression:mechanisms,diagnosis and current treatment options

Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Incidence, casualties and risk characteristics of civilian explosion blast injury in China: 2000-2017 data from the State Administration of Work Safety

Background: Civilian explosion blast injury is more frequent in developing countries, including China. However, the incidence, casualties, and characteristics of such incidents in China are unknown.Methods: This is a retrospective analysis of the State Administration of Work Safety database. Incidents during a period from January 1, 2000 to April 30, 2017 were included in the analysis. The explosions were classified based on the number of deaths into extraordinarily major, major, serious and ordinary type. Descriptive statistics was used to analyze the incidence and characteristics of the explosions. Correlation analysis was performed to examine the potential correlations among various variables.Results: Data base search identified a total of 2098 explosions from 2000 to 2017, with 29,579 casualties: 15,788 deaths(53.4%), 12,637 injured(42.7%) and 1154 missing(3.9%). Majority of the explosions were serious type(65.4%). The number of deaths(39.5%) was also highest with the serious type(P=0.006). The highest incidence was observed in the fourth quarter of the year(October to December), and at 9:00–11:00 am and 4:00–6:00 pm of the day. The explosions were most frequent in coal-producing provinces(Guizhou and Shanxi Province). Coal mine gas explosions resulted majority of the deaths(9620, 60.9%). The number of explosion accidents closely correlated with economic output(regional economy and national GDP growth rate)(r=–0.372, P=0.040;r=0.629, P=0.028).Conclusions: The incidence and civilian casualties due to explosions remain unacceptable in developing China. Measures that mitigate the risk factors are of urgently required.

Nanomaterials: Applications in the diagnosis and treatment of pancreatic cancer

Pancreatic cancer(PC)remains one of the leading causes of cancer-related death in human sowing to missed early and effective diagnosis.The inability to translate research into clinical trials and to target chemotherapy drugs to tumors is a major obstacle in PC treatment.Compared with traditional cancer detection methods,the method combining existing clinical diagnosis and detection systems with nanoscale components using novel nanomaterials shows higher sensitivity and specificity.Nanomaterials can interact with biological systems to efficiently and accurately detect and monitor biological events during diagnosis and treatment.With the advance of experimental and engineering technology,more nanomaterials will begin the transition to clinical trials for their validation.This paper describes a number of nanomaterials used in the diagnosis and treatment of PC.

Electrotaxis of alveolar epithelial cells in direct-current electric fields

Purpose:This study aims to elucidate the electrotaxis response of alveolar epithelial cells(AECs)in direct-current electric fields(EFs),explore the impact of EFs on the cell fate of AECs,and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.Methods:AECs were extracted from rat lung tissues using magnetic-activated cell sorting.To elucidate the electrotaxis responses of AECs,different voltages of EFs(0,50,100,and 200 mV/mm)were applied to two types of AECs,respectively.Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs.Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration.To further demonstrate the impact of EFs on the pulmonary tissue,the human bronchial epithelial cells transformed with Ad12-SV402B(BEAS-2B cells)were obtained and experimented under the same conditions as AECs.To determine the influence on cell fate,cells underwent electric stimulation were collected to perform Western blot analysis.Results:The successful separation and culturing of AECs were confirmed through immunofluorescence staining.Compared with the control,AECs in EFs demonstrated a significant directionality in a voltage-dependent way.In general,type I alveolar epithelial cells migrated faster than type II alveolar epithelial cells,and under EFs,these two types of cells exhibited different response threshold.For type II alveolar epithelial cells,only EFs at 200 mV/mm resulted a significant difference to the velocity,whereas for,EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference.Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.Conclusion:EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects,which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Value of lung ultrasound score for evaluation of blast lung injury in goats

Purpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided into three groups by different driving pressures:4.0 MPa group(n=4),4.5 MPa group(n=12)and 5.0 MPa group(n=4).The severe blast lung injury model of goats was established using a BST-I bio-shock tube.Vital signs(respiration,heart rate and blood pressure),lung ultrasound score(LUS),PO2/FiO2 and extravascular lung water(EVLW)were measured before injury(0 h)and at 0.5 h,3 h,6 h,9 h,12 h after injury.Computed tomography scan was performed before injury(0 h)and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume.The correlation of LUS with PaO2/FiO2,EVLW,and lung injury ratio(lesion volume/total lung volume*100%)was analyzed.All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination.Statistical analysis was performed by the SPSS 22.0 software.The measurement data were expressed as mean±standard deviation.The means of two samples were compared using independent-sample t-test.Pearson correlation analysis was conducted.Results:(1)At 12 h after injury,the mortality of goats was 0,41.67% and 100%in the 4.0 Mpa,4.5 MPa and 5.0 MPa groups,respectively;the area of pulmonary hemorrhage was 20.00%±13.14% in the 4.0 Mpa group and 42.14%±15.33% in the 4.5 MPa group.A severe lung shock injury model was established under the driving pressure of 4.5 MPa.(2)The respiratory rate,heart rate,LUS and EVLW were significantly increased,while PaO2/FiO2 was significantly reduced immediately after injury,and then they gradually recovered and became stabilized at 3 h after injury.(3)LUS was positively correlated with EVLW(3 h:r=-0.597,6 h:r=-0.698,9 h:r=-0.729;p<0.05)and lung injury ratio(12 h:r=-0.884,p<0.05),negatively correlated with PaO2/FiO2(3 h:r=-0.871,6 h:r=-0.637,9 h:r=-0.658;p<0.05).Conclusion:We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

TNF-α release capacity is suppressed immediately after hemorrhage andresuscitation

ObjectiveTo 在经皮的内视镜的腰部的 discectomy (PELD ) 期间估计类固醇的硬膜上或静脉内的管理的早药品效果 .Methods28 由于在 2014 年 11 月和 2016 年 1 月之间的大腰部的圆盘形成疝经历了 PELD 的连续病人被跟随在上面为 6 个月。这些病人根据他们在 PELD 以后接受了的治疗被划分成二个组。14 个病人(组 A ) 被 PELD 和硬膜上的类固醇对待，当另外的 14 个病人(组 B ) 被 PELD 和静脉内的类固醇对待时。我们由外科手术前、手术后的视觉类似物规模(管) 评估了有效性为背和腿疼痛的分数，和在在经由临床的图表和电话的外科以后的 3 个星期的手术后的 Oswestry 残疾索引(ODI ) 会见。因为 well.ResultsThere 是在管的重要减少，工作的手术后的医院停留和时间回来被调查(回来，腿) ， ODI，和时间回来工作(p < 0.05 ) 。为管(背) ，组 A 在外科以后在 1 天和 1 个星期与组 B 相比显示出重要减少(p = 0.011， p = 0.017 ) 。至于管(腿) ，组 A 在 1 天， 1 个星期， 3 个星期，和 3 月后续考试与组 B 相比显示出重要减少(p = 0.002， p = 0.006， p < 0.001， p < 0.001 ) 。为 ODI，组 A 与组 B 相比显示出著名减少(p < 0.001 ) 。在二个组的手术后的医院停留不是统计上不同的(p = 0.636 ) 。但是在组 A 工作的时间回来在组 B 是比那显著地短的(p = 0.023 ).ConclusionPatients 为大腰部的圆盘形成疝与硬膜上的类固醇管理经历了 PELD 的人，与与静脉内的类固醇管理经历了 PELD 的那些相比显示出有利药品效果。

Continuous purification and culture of rat type 1 and type 2 alveolar epithelial cells by magnetic cell sorting

Purpose:The incidence of acute lung injury(ALI)in severe trauma patients is 48%and the mortality rate following acute respiratory distress syndrome evolved from ALI is up to 68.5%.Alveolar epithelial type 1 cells(AEC1 s)and type 2 cells(AEC2s)are the key cells in the repair of injured lungs as well as fetal lung development.Therefore,the purification and culture of AECls and AEC2s play an important role in the research of repair and regeneration of lung tissue.Methods:Sprague-Dawley rats(3-4 weeks,120-150 g)were purchased for experiment.Dispase and DNase I were jointly used to digest lung tissue to obtain a single-cell suspension of whole lung cells,and then magnetic bead cell sorting was performed to isolate Tla positive cells as AECls from the single-cell suspension by using polyclonal rabbit anti-Tla(a specific AECls membrane protein)antibodies combined with anti-rabbit IgG microbeads.Afterwards,alveolar epithelial cell membrane marker protein EpCAM was designed as a key label to sort AEC2s from the remaining Tla-neg cells by another positive immunomagnetic selection using monoclonal mouse anti-EpCAM antibodies and anti-mouse IgG microbeads.Cell purity was identified by immunofluorescence staining and flow cytometry.Resii沾••The purity of AECls and AEC2s was 88.3%±3.8%and 92.6%±2.7%,respectively.The cell growth was observed as follows:AECls stretched within the 12-16 h,but the cells proliferated slowly;while AEC2s began to stretch after 24 h and proliferated rapidly from the 2nd day and began to differentiate after 3 days.Conclusion:AECls and AEC2s sorted by this method have high purity and good viability.Therefore,our method provides a new approach for the isolation and culture of AECls and AEC2s as well as a new strategy for the research of lung repair and regeneration.