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Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
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Objective:To explore the value of severe ultrasound measurement of internal jugular vein dilation index (ΔIJV) combined with passive leg raising (PLR) in predicting the volume responsiveness of septic shock.Methods:Patients diagnosed with septic shock under complete mechanical ventilation in the ICU of Jinshan Hospital Affiliated to Fudan University from January 2020 to March 2021 were prospectively selected as the research objects. After 500 mL crystals were injected within 30 min, the patients having the "gold standard" left stroke volume (SV) increased by 15% were allocated to the volume response positive group, and patient having an SV increased by less than 15% to the volume response negative group. First, the maximum anterior posterior diameter (IJV max) and the minimum anterior posterior diameter (IJV min) in the respiratory cycle of internal jugular vein were measured by ultrasound, then SV before and after PLR was measured, and finally SV, IJV max and IJV min were measured again after rapid infusion of 500 mL crystals, and ΔIJV=(IJV max-IJV min)/(IJV mean)×100%. The Wilcoxon rank-sum test was used to compare the hemodynamic indexes before and after capacity expansion and PLR. Spearman rank method was used to analyze the change rate of SV (ΔSV) after PLR and the correlation between ΔIJV and ΔSV of the "gold standard". The sensitivity, specificity and relevant cut-off values were obtained by drawing the subject function curve to evaluate the value of ΔIJV and PLR in predicting the volume responsiveness of patients with sepsis. Results:A total of 56 patients were enrolled in the study, and they were divided into two groups: 32 patients in the volume response positive group and 24 patients in the volume response negative group. There was a positive correlation between ΔIJV and ΔSV after capacity expansion ( r=0.778, P<0.01). Taking ΔIJV>17.3% as the threshold, the area under the curve (AUC) was 0.846 (95% CI: 0.716~0.977), the sensitivity was 84.4% and the specificity was 83.3%. PLR was also positively correlated with ΔSV ( r=0.698, P<0.01). Taking ΔSV>15.5% after PLR as the threshold, the AUC was 0.895 (95% CI: 0.796~0.993), the sensitivity was 96.9%, and the specificity was 79.2%. When ΔIJV combined with PLR predicted volume reactivity, the AUC was 0.944 (95% CI: 0.862~1.000), the sensitivity was 99.8% and the specificity was 87.5%. Conclusions:The measurement of internal jugular vein respiratory dilation index by bedside ultrasound is a reliable index to predict volume responsiveness in patients with sepsis. When combined with PLR, the sensitivity and specificity of prediction can be improved.
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Objective:To observe the effect of CoCl2on the cisplatin sensitivity of human ovarian cancer SKOV3cells, and to clarify the possible mechanism.Methods:The SKOV3cells were cultured in vitro and randomly divided into control group, CoCl2 group, cisplatin (DDP) group and CoCl2 combined with DDP (combination) group.The cells in CoCl2group were cultured in normal cell medium for 20hafter cultured in 200μmol·L-1 CoCl2for 4h, the cells in DDP group were cultured in normal cell medium containing 10mg·L-1 DDP for 24h, and the cells in combination group were cultured in 10mg·L-1 DDP for 20hafter cultured in 200μmol·L-1 CoCl2for 4h.The survival rates of SKOV3cells in various groups were detected by MTT method, and the positive expression intensities of hypoxia-inducible factor-1α (HIF-1α) and inducible nitric oxide synthase (iNOS) in the cells in various groups were detected by immunofluorescence method.Rhod 2-AM fluorescence probe was used to observe the levels of Ca2+in mitochondria in the cells in various groups.Western blotting method was used to observe the expression levels of cytochrome C (cyto C) , cysteinyl aspartase 3 (caspase 3) and cleaved cysteinyl aspartase 3 (cleaved caspase 3) .Muse○R apoptosis assay kit was used to detect the apoptotic rates of cells in various groups.Results:Compared with control group, the survival rate of the cells in CoCl2group had no significant change (P＞0.05) , and the survival rates of the cells in DDP and combination groups were decreased (P＜0.05) ;the survival rate in combination group was higher than that in DDP group (P＜0.05) .Compared with control group, the positive expression intensities of HIF-1αin CoCl2and combination groups were increased (P＜0.05) .Compared with control group, the positive expressions of iNOS in DDP and combination groups were increased (P＜0.05) .The Ca2+levels in the cells in DDP group and combination groups were higher than that in control group (P＜0.05) and the Ca2+level in DDP group was higher than that in combination group (P＜0.05) .Compared with control group, the expression levels of cyto C, caspase 3and cleaved caspase 3proteins in the SKOV3cells in CoCl2group had no significant changes (P＞0.05) , and the expression levels of cyto C, caspase 3and cleaved caspase 3in DDP group were increased significantly (P＜0.05) ;compared with DDP group, they were lower than those in combination group (P＜0.05) .Compared with control group, the apoptotic rate of SKOV3cells in DDP group was increased significantly (P＜0.05) ;the apoptotic rate of SKOV3cells in combination group was lower than that in DDP group (P＜0.05) .Conclusion:CoCl2can redece the mitochondrial apoptosis of human ovarian cancer SKOV3cells by inhibiting the DDP-induced enhancement of iNOS expression and decrease the sensitivity of SKOV3cells to cisplatin.
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Objective To investigate the diagnostic value of dynamic-extended focused assessment with sonography for trauma (D-EFAST) in patients with multiple trauma in intensive care unit (ICU). Methods A prospective clinical study was conducted. Eighty patients with multiple trauma admitted to ICU of Anhui Provincial Hospital from September 1st, 2014 to December 31st, 2016 were enrolled. Extended focused assessment with sonography for trauma (E-FAST) check was conducted at first, for those who had positive findings diagnosis was confirmed by immediately CT examination or surgical exploration. If it was negative, the patients received E-FAST every morning for 7 days (defined as D-EFAST), for those with positive findings, immediately CT or surgery was performed to clarify the diagnosis. The final clinical diagnosis was used as the "gold standard" to calculate the diagnostic accordance rate of EFAST and D-EFAST examination technique for pneumothorax, pleural effusion, spleen injury, kidney damage, liver damage, gastrointestinal injury, pericardial effusion, bladder rupture, and pancreatic injury, as well as their sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and missed diagnosis rate, and the difference between EFAST and D-EFAST was compared. Results There were 4 patients excluded because of death and abandoning treatment, and finally 76 patients were included in the study. The total sensitivity of E-FAST examination technique for pneumothorax, pleural effusion, spleen injury, liver damage, gastrointestinal injury, pericardial effusion, and bladder rupture was 75.9% (66/87), and the specificity was 98.3% (587/597), the positive predictive value was 86.8% (66/76), and the negative predictive value was 96.5% (587/608), the accuracy rate was 95.5% (653/684), and the rate of missed diagnosis was 24.1% (21/87). The most of the delayed injury in patients with multiple trauma occurred at 2-7 days after injury with incidence of 4.8% (33/684). The diagnostic sensitivity of D-EFAST for delayed injury was 98.3% (118/120), the specificity was 99.8% (563/564), the positive predictive value was 99.2% (118/119), the negative predictive value was 99.6% (563/565), the diagnostic accuracy rate was 99.6% (681/684), and rate of missed diagnosis was 1.7% (2/120). When the final clinical diagnosis was set as the "gold standard", D-EFAST technology for the detection rate was 98.3% (118/120) for patients with multiple trauma on organ injury while the detection rate of E-FAST was 75.9% (66/87), with statistical significant difference (P < 0.01), indicating that D-EFAST was better than E-FAST in check of multiple trauma patients with organ injury. Conclusion Although the E-FAST technology can quickly diagnose the multiple trauma patients and win the rescue time for critical patients, multiple trauma patients injured after 2-7 days prone to delayed damage and are difficult to detect, and D-EFAST can be used to find delayed damage earlier, and reduce the misdiagnosis rate of multiple trauma patients.
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Objective To investigate the clinical experience and associated factors of extracorporeal membrane oxygenation(ECMO)for adult patients with severe acute respiratory distress syndrome(ARDS).Methods The clinical data of 22 adult patients with severe ARDS,which met the criteria for ECMO,were retrospectively collected and analyzed.The ECMO team all receiving VV-ECMO treatment (Veno-venous extracorporeal membrane oxygenation),data collection including the patients,general data,blood gas analysis,hemodynamics,mechanical ventilation parameter before and after the ECMO treatment and the auxiliary complications,etc.The control group were 14 cases of patients with severe ARDS which receiving conventional treatment;We collected the same data as the research team.Results In the research,8 patients treated with VV-ECMO,There were 5 males and 3 females,with an average age of (46.3 ± 14.1)years.Compared with the factors at the same time point in the control group,those of the ECMO group,except MAP (t =-0.872,P =0.357),Respiratory rate (t =-1.670,P =0.357),Heart rate (t =-1.973,P =0.042),PH (t =-1.432,P =0.033),PaCO2 (t =-2.564,P =0.024),PO2 (t =-4.955,P ＜ 0.001),PO2/FiO2 (t =-3.654,P ＜ 0.01),PEEP (t =-1.382,P =0.031),Pplateau (t =-2.785,P ＜ 0.01),Blood lactate (t =-2.564,P =0.024) were significantly improved after ECMO running 24 hours (all P ＜ 0.05).And also the factors such as the length of ICU stay (t =-2.452,P =0.027),the times of mechanical ventilation (t =-1.478,P =0.038),number of organ failure(t =-1.963,P =0.047),the hospital mortality rates(t =-1.970,P =0.045) and treatment costs(t =-1.667,P =0.035) between the ECMO group and the control group were significantly different (P ＜0.05).In the end,we divided the ECMO group into survival group and death group,and compare the time of Mechanical Ventilation before ECMO(P =0.031) the total time of Mechanical Ventilation(P =0.038),the time of ECMO adjutant (P =0.047),the length of ICU stay (P =0.043) and the cost of treatment (P =0.037) between the two groups;and there were also statistically significant difference (P ＜ 0.05).Conclusion ECMO can significantly improve the patients,oxygenation and respiratory physiology indexes which can not sustain under the conventional mechanical ventilation therapy and win the time for rest and repair of lung.Indexes such as age,time of mechanical ventilation before ECMO therapy,the primary cause of ARDS are the important factors influencing the efficacy of ECMO treatment in the patients with severe ARDS.
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Objective To establish a reliable unstable pelvic fracture model with sacral plexus stretch injury in goats and to detect electrophysiological signals when pelvis is shifted in different orientations and distance.Methods Twenty-four goats were divided into three groups of 8 animals each:pelvic longitudinal displacement was induced in group A,pelvic lateral displacement in group B,and pelvic dorsal displacement in group C.Animal left L6 and S1 nerve root and initial segment of sciatic nerve were exposed to connect stimulating and receiving electrodes respectively.Left pelvis was shifted at the speed of 0.25 mm/s to produce the model of unstable pelvic fracture with sacral plexus stretch injury.Electrophysiological signals of L6 and S1 were recorded when the placement of pelvis was 0,0.5 and 1.0 cm respectively.Results With pelvic displacement,the threshold potential,maximum stimulus potential and incubation period were gradually increased,but the peak-to-peak value became smaller gradually.When the pelvis displaced 0.5 cm at different orientations,group A showed improved threshold potential and incubation period (P ＜0.05),decreased peak-to-peak value (P ＜0.05),and no significant change in maximum stimulus potential(P ＞0.05);group B only showed lowered peak-to-peak value with no significant variations in other electrophysiological signals (P ＜ 0.05);group C had no significant variations in all electrophysiological signals (P ＞ 0.05).When the pelvis displaced 1.0 cm at different orientations,groups A and B showed improved threshold potential,maximum stimulus potential and incubation period (P ＜ 0.05) and lowered peak to peak value (P ＜ 0.05);group C showed higher incubation period with no significant variations in other electrophysiological signals(P ＜0.05).Between groups,the amplitude of variation in electrophysiological signals was the most in group A and the least in group C.Conclusion After unstable pelvis fracture in goats,sacral plexus stretch injury is the most serious in longitudinal displacement of the pelvis.
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People wearing positive pressure biological protective suits might face some potential safety risks when work -ing in a high-risk biological contamination environment .These risks could be effectively prevented by simulation experi-ments.This paper elaborates on the progress in risk studys on positive pressure biological protective suits in terms of dynam -ic detection methods and risk assessment , and points out the problems to be solved and the direction of future development .