Paradoxical systemic toxicity by inhaled paraquat poisoning: A case report

Rationale:Multi-organ failure is a symptom of paraquat poisoning,resulting in high mortality and morbidity rates.Though paraquat is widely available,poisoning through inhalation is rare.Patient’s Concern:A 37-year-old male reported to the emergency department with complaints of vomiting after an alleged history of inhalation of paraquat while at work.Diagnosis:Paraquat poisoning.Interventions:Supportive management along with multiple sessions of hemodialysis.Outcomes:Renal complications caused by paraquat were improved after multiple sessions of hemodialysis.However,the patient developed respiratory complications and later due to persistent hypoxemia and non-responsive to supportive therapy,he succumbed to his illness.Lessons:Acute kidney injury is a complication of paraquat poisoning.However,kidney involvement with the inhalational mode is rare.It is caused by reduction and oxidation cycles,as well as the formation of reactive oxygen species,necessitating hemodialysis as the treatment.Without a clear history,a specific clinical trait,or a diagnostic test,diagnosis can be difficult.Our case thus highlights the inhaled paraquat poisoning,presenting with acute kidney injury with late respiratory impairment as a consequence.

Prognostic value of plasma C-reactive protein in the evaluation of paraquat poisoning patients

Objective: To investigate the prognostic value of plasma C-reactive protein(CRP) level in patients with paraquat poisoning.Methods: This study included 162 patients with paraquat poisoning. The data of plasma paraquat, CRP level and arterial blood gas were analyzed. Cox regression analysis was applied to evaluate the risk factors of prognosis. Receiver operating characteristics curve analysis and area under curve were used to calculate the predictive power of significant variable. Differences in patient survival were determined using the Kaplan–Meier method and a log-rank test.Results: Plasma CRP level was significantly increased in non-survival patients compared with survival patients(P < 0.05), and positively correlated with plasma paraquat level(P < 0.05). Cox regression analysis revealed that plasma CRP level was an independent prognostic marker of mortality within 30 days. The receiver operating characteristics curve analysis indicated that area under curve of plasma CRP level was0.867(95% CI: 0.81–0.93), and the cut-off value was 18 mg/L, and patients with CRP level over this value had a poor survival time compared with those with less than this value.Conclusions: These results suggest that plasma CRP level is distinct increased in patients with paraquat poisoning, and the plasma CRP level may be useful for the prediction of prognosis in paraquat poisoning.

Discernment scheme for paraquat poisoning: A five-year experience in Shiraz, Iran

AIM To evaluate various schemes for paraquat poisoning and different variables that influence the outcome of acute paraquat poisoning.METHODS In a cross-sectional study, the information about all cases of acute paraquat poisoning who were admitted to teaching hospitals affiliated to Shiraz University of Medical Sciences, in a five year period(September 2010 to September 2015) were evaluated. The variables included: Demographic data, medical assessment, therapeutic options, laboratory findings, and the outcomes. Data were analyzed using SPSS, version 22. Significant difference between groups was tested using t-test for continues outcomes and χ~2 test for categorical. The significance level was considered to be P < 0.05. RESULTS A total of 104 patients(66.3% male) were evaluated. The mean age of the female patients was 22.81 ± 9.87 years and the male patients' was 27.21 ± 11.06 years. Ninety seven(93.3%) of all the cases were suicide attempts with mortality rate of 43.2%. Despite the necessity for emergency hemodialysis during the first 6 h of intoxication, none of the patients had dialysis during this time. Immunosuppressive and corticosteroid medications were not administrated in adequate dosage in 31.1% and 60% of the patients, respectively. Ingestion of more than22.5 cc of paraquat and increase in creatinine level were the most important predictors of mortality.CONCLUSION Treatment should start immediately for these patients.Moreover, creating a clinical guideline according to the findings can have an impact on the treatment procedure which seems to be necessary.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Evaluation of gastric lavage efficiency and utility using a rapid quantitative method in a swine paraquat poisoning model

BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.

Serum paraquat concentration detected by spectrophotometry in patients with paraquat poisoning

BACKGROUND：Paraquat （PQ） is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS：The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second- derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student＇s t test or Fisher＇s exact test. RESULTS：The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4-8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer＇s law with r=0.996. The average recovery rates of PQ were within a range of 95.0% to 99.5%, relative standard deviation （RSD） was within 1.35% to 5.41% （n=6）, and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC （r=0.995, P〈0.0001）. The survival rate was 22.2% in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6%, 55.6% and 77.8%, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 pg/mL （P〈0.05）. CONCLUSIONS： For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second- derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 tJg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

Acute lung injury mechanism and therapy induced by paraquat poisoning

Paraquat (PQ, methyl viologen) was widely used in agricultural production throughout the world in 1962 for its efficient herbicidal activity. PQ was also highly toxic drug. About 5 mL medicine including 20% paraquat was life-threatening that can cause poisoning. In 1966, some people died because of PQ poisoning. Most patients had acute respiratory distress syndrome after 2 wk, and 70% of them died due to the lack of effective detoxification drugs. Thus, it was particularly important to understand the pathogenesis of PQ poisoning and give some effective treatments. This article will review the toxicological mechanism and treatment on PQ poisoning of acute lung injury.

Can kissing cause paraquat poisoning: A case report and review of literature

BACKGROUND Paraquat is an effective,broad-spectrum,highly toxic quaternary ammonium herbicide.Paraquat poisoning has been reported frequently in recent years.It has severe lung,kidney,liver,and nervous system toxicity,and there is currently no specific antidote.Paraquat poisoning may follow ingestion,inhalation,and skin contact.There have been no previous reports of paraquat poisoning that resulted from kissing.This rare case provides a new reference for the prevention of paraquat poisoning.CASE SUMMARY A 27-year-old man came to the emergency department complaining that he had come into contact with paraquat by kissing his girlfriend,who had taken 80-120 mL 20%paraquat.After admission,his lung computed tomography(CT)showed increased lung markings.Redness and a burning sensation developed on his tongue,which progressed to painful erosions and coalescent ulcers.The final diagnosis was mild paraquat poisoning.Anti-inflammatory,antioxidant,and symptomatic treatment were initiated and continued for 7 d.Dyspnea did not occur,subsequent lung CT showed no significant changes,and the tongue pain was slightly improved.One month after discharge,the tongue injury was resolved.CONCLUSION This case indicated that the tongue and lung tissues are particularly vulnerable to paraquat toxicity,even after a limited exposure.

Risk factors and optimal predictive scoring system of mortality for children with acute paraquat poisoning

BACKGROUND There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication(APP).AIM To optimize a predictive scoring system for mortality in children with APP.METHODS A total of 113 children with APP from January 1,2010 to January 1,2020 were enrolled in this study.These patients were divided into survivors and nonsurvivors.We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors.The survival rates of patients with different values of the pediatric critical illness score(PCIS)were assessed using kaplan-meier survival analysis.The best scoring system was established by using the area under the receiver operating characteristic curve analysis.RESULTS The overall mortality rate was 23.4%.All non-survivors died within 20 days;48.1%(13/27)died within 3 days,and 70.3%(19/27)died within 7 days.Compared to survivors,the non-survivors were older,had higher white blood cell count,alanine aminotransferase(ALT),aspartate aminotransferase,serum creatinine,blood urea nitrogen,glucose,and pediatric early warning score,and had lower platelet count,albumin,Serum sodium(Na+)and PCIS.ALT and PCIS were the independent prognostic risk factors for children with APP.The survival rate of children classified as extremely critical patients(100%)was lower than that of children classified as critical(60%)or noncritical(6.7%)patients.The specificity of ALT was high(96.51%),but the sensitivity was low(59.26%).The sensitivity and specificity of ALT combined with PCIS were high,92.59%and 87.21%,respectively.The difference in mortality was significantly higher for ALT combined with PCIS(area under the receiver operating characteristic:0.937;95%CI:0.875-0.974;P<0.05).CONCLUSION In our study,ALT and PCIS were independent prognostic risk factors for children with APP.ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP.

Advances in molecular mechanism of lung injury induced by paraquat poisoning

Paraquat is a bipyridine dichloride non-selective herbicide,which was widely used in the world in the last century.Now,paraquat is banned in most countries because of the extremely high lethality and the lack of specific detoxification drugs.However,death due to paraquat poisoning still occurs frequently,thus it is of great clinical significance to explore the molecular mechanism of paraquat poisoning and the detoxification drugs.Paraquat poisoning causes multiple dysfunction of the lung,liver,kidney,heart,and brain through complex molecular mechanisms.About the mechanism there are excessive inflammatory reaction theory,REDOX reaction imbalance theory,oxidative stress free radical damage theory,calcium overload theory,NO molecular damage and cell apoptosis theory,etc.For the treatment of paraquat poisoning,paraquat antibody,pathway target blocker and related factor antibody have been developed in recent years.Although certain effects have been achieved,the treatment efficiency has not been significantly improved.This paper summarized the mechanism of signal transduction pathways involved in lung injury induced by paraquat poisoning in order to provide a theoretical basis for further research.

Effects of ulinastatin combined with hemoperfusion on renal function, fibrosis indexes and oxidative stress indexes of patients with paraquat poisoning

Objective: To study the effects of ulinastatin combined with hemoperfusion on renal function, fibrosis indexes and oxidative stress indexes of patients with paraquat poisoning. Methods:Patients with paraquat poisoning who were treated in Qinghai Provincial People's Hospital between March 2014 and May 2017 were chosen as the research subjects, treated with hemoperfusion and divided into ulinastatin group and control group according to the use of ulinastatin or not in history data. The renal function markers, fibrosis indexes and oxidative stress indexes were measured before treatment and 1 week after treatment. Results: Compared with those of same group before treatment, serum Scr, BUN, Cys-C, β2-MG, TGF-β1, ICAM-1, MMP9, PICP, C-IV and MDA levels as well as peripheral blood Nrf2 and HO-1 expression intensity significantly decreased whereas serum CAT and SOD levels significantly increased after treatment, and serum Scr, BUN, Cys-C, β2-MG, TGF-β1, ICAM-1, MMP9, PICP, C-IV and MDA levels as well as peripheral blood Nrf2 and HO-1 expression intensity of ulinastatin group after treatment were significantly lower than those of control group whereas serum CAT and SOD levels were significantly higher than those of control group. Conclusion:Ulinastatin combined with hemoperfusion can improve the renal function, pulmonary fibrosis and oxidative stress in patients with paraquat poisoning.

Effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning

Objective: To investigate the effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning. Methods: A total of 42 patients with acute paraquat poisoning who were admitted and treated in our hospital between December 2013 and October 2017 were selected as the research subjects, and their therapies were reviewed and used to divide them into the control group (n=20) who received hemoperfusion alone and the combined treatment group (n=22) who received hemoperfusion combined with hemodialysis. The differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were compared between the two groups of patients immediately after admission, after 1 d of treatment and after 3 d of treatment. Results: Immediately after admission, the differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were not statistically significant between the two groups. After 1d of treatment and after 3 d of treatment, kidney function indexes Scr, BUN and β2-MG levels in peripheral blood of combined treatment group were lower than those of control group at corresponding time points respectively;liver function indexes ALT, AST, TB and ALP levels in peripheral blood were lower than those of control group at corresponding time points respectively;lung function indexes PaO2, BE and PCO3- levels in arterial blood were higher than those of control group at corresponding time points respectively whereas PaCO2 levels were lower than those of control group at corresponding time points respectively. Conclusion: Compared with hemoperfusion alone, hemoperfusion combined with hemodialysis is more advantageous in protecting the functions of liver, kidney, lungs and other target organs of patients with acute paraquat poisoning.

百草枯中毒患者外周血对氧磷酯酶1、程序性死亡因子-1、γ干扰素诱导蛋白-10水平检测的意义

目的探讨百草枯中毒患者外周血对氧磷酯酶1(PON1)、程序性死亡因子-1(PD-1)、γ干扰素诱导蛋白-10(IP-10)水平对预后的价值。方法对2017年5月—2023年4月中国人民解放军联勤保障部队第九八〇医院120例百草枯中毒患者进行前瞻性研究,统计百草枯中毒患者30 d内死亡与生存情况,比较不同预后患者临床资料及外周血PON1、PD-1、IP-10水平。采用Pearson相关性分析探讨外周血PON1、PD-1、IP-10水平与中毒剂量、序贯器官衰竭估计(SOFA)评分、急性生理与慢性健康评分系统Ⅱ(APACHEⅡ)评分的相关性;采用受试者工作特征(ROC)曲线评价外周血PON1、PD-1、IP-10水平预测百草枯中毒患者预后的价值。结果随访期间共35例患者死亡(29.17%)。死亡患者中毒剂量、SOFA评分、APACHEⅡ评分及外周血IP-10、PD-1水平均高于生存患者,外周血PON1水平低于生存患者,差异有统计学意义(P<0.05)。相关性分析显示,百草枯中毒患者外周血PON1水平与中毒剂量、APACHEⅡ评分及SOFA评分均呈负相关,PD-1、IP-10水平与中毒剂量、APACHEⅡ评分及SOFA评分均呈正相关(P<0.05);PON1、PD-1、IP-10预测百草枯中毒的曲线下面积(AUC)分别为0.738、0.774、0.770,三者联合预测的AUC为0.922,三者联合预测效能高于各指标单独预测。结论百草枯中毒患者外周血PON1、PD-1、IP-10联合检测对判断患者预后具有较高价值。

Effects of intensive hemoperfusion on the toxin clearance, target organ function and oxidative stress in patient with paraquat poisoning

Objective: To study the effects of intensive hemoperfusion on the toxin clearance, target organ function and oxidative stress in patient with paraquat poisoning. Methods: A total of 56 patients with paraquat poisoning who were treated in the People's Hospital of Hanchuan between November 2013 and January 2017 were reviewed and divided into the control group (n=30) and the intensive hemoperfusion group (n=26). Control group received conventional therapy, and intensive hemoperfusion group received conventional therapy combined with intensive hemoperfusion. The differences in paraquat clearance effect, target organ function and oxidative stress response were compared between the two groups. Results: Serum paraquat level in intensive hemoperfusion group was lower than that in control group, and the paraquat clearance rate was higher than that of control group. Serum pulmonary fibrosis indexes PⅠCP, CⅣ and HA levels in intensive hemoperfusion group were lower than those in control group;serum liver function indexes ALP, STB and ALT levels were lower than those in control group;serum oxidative stress index GSH-Px level was higher than that in control group whereas MDA level was lower than that in control group. Conclusion: Intensive hemoperfusion can significantly improve the paraquat clearance rate, protect the important organ function and suppress the systemic oxidative stress response in patient with paraquat poisoning.

Expression of heat shock protein 70 in lung tissuesof acute paraquat poisoned rats and interventionof ulinastatin

BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.

Edaravone attenuates paraquat-induced lung injury by inhibiting oxidative stress in human type Ⅱalveolar epithelial cells

BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.

百草枯中毒患者血sCD14-T/mCD14水平与病情程度、APACHEⅡ评分有相关性

目的:探讨百草枯中毒患者血可溶性CD14分子亚型(sCD14-T)/膜结合CD14(mCD14)水平变化以及与急性生理与慢性健康状况评估(APACHEⅡ)评分的相关性。方法:选取84例百草枯中毒患者,检测入院时血sCD14-T/mCD14水平、APACHEⅡ评分,根据《急性百草枯中毒诊治专家共识(2013)》,按病情程度,将患者分为轻度17例,中度42例,重度25例。比较不同病情程度患者血sCD14-T/mCD14水平、APACHEⅡ评分,并分析二者相关性,比较不同sCD14-T/mCD14水平、APACHEⅡ评分患者预后情况,分析血sCD14-T/mCD14水平、APACHEⅡ评分与预后的关系。结果:重度患者血sCD14-T、sCD14-T/mCD14水平、APACHEⅡ评分高于中度、轻度患者,且中度患者高于轻度患者,重度患者mCD14水平低于中度、轻度患者,且中度患者低于轻度患者(P均<0.05);以百草枯中毒重度为阳性样本,轻、中度为阴性样本,绘制受试者工作特征(ROC)曲线;外周血sCD14-T/mCD14水平联合APACHEⅡ评分评估重度百草枯中毒的曲线下面积(AUC)为0.898(95%CI:0.824~0.971);百草枯中毒患者sCD14-T/mCD14水平与APACHEⅡ评分呈正相关(P<0.05);sCD14-T/mCD14水平>3.22、APACHEⅡ评分>23分患者的生存率相较于sCD14-T/mCD14水平≤3.22、APACHEⅡ评分≤23分患者更低(P均<0.05);sCD14-T/mCD14水平、APACHEⅡ评分为百草枯中毒患者预后的独立危险因素(P均<0.05)。结论:百草枯中毒患者外周血sCD14-T/mCD14水平随病情加重逐渐升高,与APACHEⅡ评分呈正相关。

Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats

Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)QDS.The PQ+sivelestat group served as the positive control group.The model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/kg.Two hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)QDS.Six rats were selected from each group on the first,third,and seventh days after poisoning and dissected after anesthesia.The PQ content of the kidneys was measured using the sodium disulfite method.Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes.Apelin expression in the renal tissues was detected using immunofluorescence.Western blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ.Twenty-four hours after poisoning,sivelestat and AH_(2)QDS were administered.The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe.Results:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS group.Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group.Vacuolar degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also observed.However,these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH_(2)QDS group(P<0.05).On the third day after poisoning,immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH_(2)QDS group than in the PQ group.Western blotting analysis results showed that IL-6,TNF-α,NF-κB p65,caspase-1,caspase-8,GRP78,and CHOP protein levels in the PQ group were higher than in the PQ+AH_(2)QDS group(P<0.05).The expression of apelin-APJ proteins in the PQ+AH_(2)QDS group was higher than in the PQ+sivelestat and PQ groups(P<0.05);this difference was significant on Day 3 and Day 7.The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH_(2)QDS group and the PQ+sivelestat group was significantly lower than in the PQ group(P<0.05).Conclusions:This study confirms that AH_(2)QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat.The mechanism of the protective effects of AH_(2)QDS may be linked to reduction in cellular oxidative stress,PQ content of renal tissue,inflammatory injury,endoplasmic reticulum stress,and apoptosis.AH_(2)QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

口服敌草快和百草枯中毒患者靶器官损害情况分析

目的 分析敌草快和百草枯中毒患者的靶器官损害特点,为进一步提高临床救治水平提供科学依据。方法 回顾性收集88例单纯经口服敌草快中毒患者(敌草快组)和80例百草枯中毒患者(百草枯组)的临床资料,包括年龄、性别、中毒剂量、中毒到入院时间、中毒催吐导泻情况、中毒到洗胃时间、临床表现、中毒到第一次血液灌流时间、血液灌流次数、住院天数、肝肾功能[丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)、肌酐(Cr)]、凝血功能[凝血酶原时间(PT)]、白细胞计数(WBC)、肺损伤指标[氧合指数(PO2/FiO2)]、心肌损伤指标[肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)]、血乳酸(Lac)、pH值及最终预后等指标。比较敌草快组和百草枯组患者的临床资料差异及不同中毒剂量死亡率与存活率及总体存活率;比较敌草快组和百草枯组死亡患者靶器官功能受损情况;比较死亡患者与存活患者敌草快和和百草枯的中毒剂量。结果 敌草快组年龄最大73岁,最小15岁;百草枯组年龄最大59岁,最小14岁;敌草快组男性34例(38.64%),女性54例(61.36%);百草枯组男37例(46.25%),女43例(53.75%);两组中毒后均以咽喉部疼痛、恶心、呕吐、上腹疼痛为主要临床表现,少部分中毒剂量少的患者可没有任何症状;百草枯组中毒剂量>50 ml的患者出现胸闷气促症状,敌草快组中毒剂量>50 ml的患者出现意识烦躁、嗜睡、谵妄甚至抽搐、昏迷等症状。两组性别、平均年龄、平均中毒剂量、平均中毒到入院时间、中毒催吐导泻率、平均中毒到洗胃时间、平均中毒到第一次血液灌流时间、平均血液灌流次数比较无明显差异(P>0.05);敌草快组的平均住院天数(4.86±1.81)d明显短于百草枯组的(7.85±1.13)d(P<0.05)。中毒剂量21~50 ml和51~100 ml时,敌草快组存活率均高于百草枯组(P<0.05);敌草快组总体存活率78.41%明显高于百草枯组的37.50%(P<0.05)。入院后第3天,敌草快组死亡患者ALT(109.26±63.88)U/L、TBIL(40.29±10.39)μmol/L、PT(12.24±1.56)s、Lac(1.54±1.09)mmol/L及WBC(13.24±3.43)×109/L均低于百草枯组死亡患者的(327.12±127.86)U/L、(68.38±48.55)μmol/L、(17.39±2.73)s、(4.53±1.54)mmol/L、(23.32±4.56)×109/L,Cr(308.44±156.87)μmol/L、PO2/FiO2(207.32±76.10)mm Hg(1 mm Hg=0.133 kPa)、CK(456.56±101.39)U/L、CK-MB(63.29±21.39)U/L、cTnI(11.56±1.31)ng/ml均高于百草枯组死亡患者的(201.93±87.01)μmol/L、(153.25±64.25)mm Hg、(50.29±21.39)U/L、(47.21±12.22)U/L、(4.29±4.21)ng/ml(P<0.05)。死亡患者敌草快和百草枯中毒剂量均明显高于存活患者(P<0.05);死亡患者敌草快中毒剂量大于百草枯(P<0.05);存活患者敌草快和百草枯中毒剂量无明显差异(P>0.05)。结论 敌草快和百草枯中毒患者的年龄以40岁以下中青年女性多见,所有口服中毒患者均出现咽痛、恶心、呕吐等消化道症状;敌草快口服中毒剂量大者会出现意识改变,包括烦躁、嗜睡、抽搐、昏迷等,而百草枯中毒剂量大者会出现胸闷气促等症状;服用同等剂量除草剂,敌草快存活率高于百草枯;敌草快以肾、心肌及神经系统损伤最为显著,且与患者预后密切相关;百草枯中毒以肺、肝和肾脏损伤为主;敌草快中毒患者总体死亡率低于百草枯中毒死亡率。

基于机器学习决策树模型对急性百草枯中毒患者预后的预测价值

目的探讨基于机器学习的决策树模型对急性百草枯(PQ)中毒(APP)患者预后的预测价值。方法采用回顾性研究方法。收集2012年5月至2021年8月沧州市中心医院急诊医学部救治的APP患者的临床数据,包括性别、年龄、服毒至洗胃的时间、血液灌流比例、血PQ浓度、生化指标[白细胞计数(WBC)丙氨酸转氨酶(ALT)血肌酐(SCr)血淀粉酶及血钾]以及血气指标[动脉血乳酸(Lac)、剩余碱和动脉血氧分压(PaO_(2))]。根据中毒后90d预后将患者分为生存组(56例)和死亡组(74例),比较不同预后两组患者临床指标的差异。通过多因素Logistic回归分析影响APP患者预后的危险因素,将危险因素作为变量构建含血PQ浓度及不含血PQ浓度的两种决策树模型。绘制受试者工作特征曲线(ROC曲线)评估决策树模型对APP患者预后的预测价值,通过Hanley&McNeil法对两种决策树模型的ROC曲线下面积(AUC)进行比较。结果患者90d的生存率为43.1%(56/130)。与死亡组比较,生存组WBC[×10^(9)/L:8.9(7.0,11.6)比17.4(11.9,23.1)]、ALT[U/L:25.3(21.2,31.8)比29.3(23.2,40.3)]、SCr[μmol/L:64.0(53.0,74.0)比91.0(72.5,141.5)]、Lac[mmol/L:2.5(1.4,4.0)比7.1(3.7,11.0)]和血PQ浓度[ng/L:0.3(0.10.9)比2.9(1.9,8.1)]均较低,差异均有统计学意义(均P<0.05),剩余碱[mmol/L:-2.5(-4.2,-1.1)比-7.2(-10.9,-4.7)]和血钾[mmol/L:3.7(3.5,4.0)比3.2(2.83.7)]均较高,差异均有统计学意义(均P<0.05),患者更年轻[岁:33.5(26.0,47.8)比42.5(26.0,58.0),P<0.05]。单因素Logistic回归分析结显示,年龄、WBC、ALT、SCr、血钾、Lac、剩余碱和血PQ浓度是影响APP患者90d预后的独立危险因素[优势比(0R)和95%可信区间(95%CI)分别为1.03(1.01~1.05)1.30(1.18~1.44)1.04(1.01~1.07)、1.02(1.01~1.04)、7.59(3.25~17.70)、1.64(1.35~1.99)、1.51(1.29~1.76)、7.00(3.41~14.37),P值分别为0.018、<0.001、0.011、<0.001、<0.001、<0.001、<0.001、<0.001]。含血PQ浓度的多因素Logistic回归分析结果显示,WBC、血钾和血PQ浓度是影响患者90d生存的独立危险因素[OR和95%CI分别为1.17(1.03~1.33)、7.29(1.66~32.01)、5.49(2.48~12.13),P值分别为0.014、0.008、<0.001]。不含血PQ浓度的多因素Logistic回归分析显示,年龄、WBC、血钾和剩余碱是影响患者90d生存的独立危险因素[OR和95%CI分别为1.05(1.01~1.08)、1.20(1.07~1.34)3.12(1.01~9.66)1.41(1.16~1.72),P值分别为0.008、0.002、0.049、0.001]。基于血PQ浓度和血钾决策树模型的AUC为0.94,95%CI为0.89~0.98,敏感度为91.9%,特异度为89.3%,准确率为90.0%。基于WBC、剩余碱和年龄决策树模型的AUC为0.89,95%CI为0.84~0.95,敏感度为86.5%,特异度为91.1%,准确率为88.5%。Hanley&McNeil法比较显示,两种决策树模型的AUC差异无统计学意义(Z=1.34,P=0.180)。结论基于机器学习的决策树模型可为临床早期评估APP患者的预后提供定量、直观的预测工具。