BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Chlorfenapyr,an emerging synthetic pesticide,has been linked to a growing number of poisoning incidents,attributed to heightened human exposure as its application becomes more widespread.However,the toxicokinetics and toxicology of chlorfenapyr remain incompletely understood.Research since the 1990s,including animal experiments,has illuminated the absorption,distribution,excretion,and metabolism of chlorfenapyr.Toxicological investigations have revealed that the primary toxicity of chlorfenapyr is the uncoupling of oxidative phosphorylation.Chlorfenapyr exposure in humans and other animals can lead to various toxic effects,including neurotoxicity,cardiotoxicity,skeletal muscle toxicity,genotoxicity,reproductive and developmental toxicity,renal toxicity,splenic toxicity,and hematotoxicity.This article presents a comprehensive review of the toxicokinetics and toxicology of chlorfenapyr,integrating data from animal experiments,human cell line studies,clinical reports,and human autopsy.Its objective is to raise clinical awareness regarding chlorfenapyr poisoning and offer valuable references for its treatment and management.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective To analyze the problems and solutions in the diagnosis of a patient with occupational radiogenic neoplasms. Methods The dose conversion method was selected in dose estimation. Personal dose equivalent, skin absorbed dose, and reported detection data were converted into red bone marrow absorbed dose. The upper 95% confidence limit of the probability of causation (PC 95%) was calculated. Results The PC 95% of cancer due to radiation in the worker was 66.38%, which suggested occupational radiogenic neoplasms. Personal dose data were missing in dose estimation. The current dose estimation standard lacked bedside radiography and CT operation type, and the dose conversion formula was not perfect. Conclusion In the judgment of occupational radiogenic neoplasms, the estimated dose showed uncertainty. There is an urgent need to formulate and promulgate dose estimation standards that are operational and in line with the current development of radiological diagnosis and treatment technology and equipment.

Objective:To explore the clinical features of acute diquat (DQ) poisoning, and further improve the awareness of acute DQ poisoning.Methods:A retrospective analysis was performed on the clinical data of patients with acute DQ poisoning diagnosed in the emergency department of the Second Hospital of Hebei Medical University from January 1, 2019 to December 31, 2021. The clinical data included age, gender, exposure routes, presence of pesticides (drugs) mixture poisoning, dosage of poison, the time from taking poisoning to admitting in the emergency department, clinical manifestations, laboratory data, treatment, hospital days, prognosis and survival days.Results:The number of cases who firstly complained of acute DQ poisoning in the past three years were 19 cases in 2019, 28 cases in 2020, and 51 cases in 2021. A total of 12 patients were excluded due to being diagnosed paraquat (PQ) poisoning by toxicology detection. Finally, 86 cases of acute DQ poisoning were included, including 80 cases of oral DQ poisoning, 1 case of intramuscular injection, 1 case of binocular contact and 4 cases of dermal exposure. In 80 cases of oral DQ poisoning, there were 70 cases of diquat poisoning alone (42 cases survived, 28 cases died) and 10 cases of pesticide mixture poisoning (6 cases survived, 4 cases died). The time from oral poisoning to admitting in the emergency department was 0.5-96.0 hours, with an average of (8.6±5.8) hours. The time of intramuscular injection poisoning to admitting in the emergency department was 3 hours. The time of dermal exposure to admitting in the emergency department was relatively long, with an average of 66.1 hours. The time from oral simple DQ poisoning to death was 12.0-108.0 hours, and the time from oral mixed DQ poisoning to death was 24.0-576.0 hours. A total of 70 patients with oral diquat poisoning alone presented various degrees of multiple organ injuries. All patients presented gastrointestinal symptoms such as nausea and vomiting. Renal injury and central nervous system injury were the most significant and closely related to the prognosis.Conclusions:Acute oral DQ poisoning can cause to multiple organ injuries, and the clinical manifestations are related to the dose of the poison. In severe cases, acute renal failure and refractory circulatory failure occur within 24 hours after poisoning, and severe central nervous system injury with disturbance of consciousness as the primary manifestation occurs within 36 hours, followed by multiple organ failure until death.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.

Objective:To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning.Methods:In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining.Results:Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant ( P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion:The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.

Objective To investigate the changes and their significance of glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) expressions in glial cells following spinal cord injury (SCI) in adult rats.Methods Twenty-five healthy female adult SD rats were randomly divided into control group (5 rats) and experimental group (20 rats).The contusive spinal cord injury models were prepared at T10 segment in the rats in the experimental group according to the modified Allen's method.At days 1,3,7 and 14 following SCI,five rats were sacrificed by cardiac perfusion and the spinal cord segments adjacent to the epicenter of injury were obtained at each time point after the neurological function of hind limbs was assessed using the modified Tarlov scale.Changes of GLAST and GLT-1 expressions were detected semi-quantitatively using immunofluorescence and computer image analysis system (IPP 6.0).Results (1) Single immunofluorescence:Moderate GLAST expression was found in the control group.The GLAST expression was increased slightly at day 1 after SCI,decreased progressively at days 3 and 7 after SCI,and increased slightly at day 14 after SCI.The GLAST expression in experimental group was significantly lower than those in control group at days 3,7 and 14 after SCI (P ＜ 0.05).Moderate GLT-1 expression was detected in the control group.The expression of GLT-1 was increased slightly at day 1 after SCI,decreased to the lowest at day 3 after SCI,and increased slightly at days 7 and 14 after SCI.The GLT-1 expression in experimental group was significantly lower than those in control group at days 3,7 and 14 after SCI (P ＜0.05).(2) Double immunofluorescence:GLAST expression was found on astrocytes in the control group.The GLAST expression in experimental group was decreased at day 1 after SCI,further decreased progressively at days 3 and 7 after SCI,and started to recover at day 14 after SCI.The coexpressions of GLAST and glial fibrillary acidic protein (GFAP) in experimental group were significantly lower than those in the control group at days 3 and 7 after SCI (P ＜ 0.05).The expression of GLAST was found on microglial cells in the control group.The expression of GLAST in experimental group was increased obviously at day 1 after SCI and increased progressively at days 3-14 after SCI.The coexpressions of GLAST and OX-42 in experimental group were significantly than those in the control group at days 3,7 and 14 after SCI (P ＜ 0.05).(3) Double immunofluorescence:GLT-1 expression was found on astrocytes in the control group.The GLT-1 expression was decreased at day 1 after SCI,further decreased progressively at days 3 and 7 after SCI,and started to recover at day 14 after SCI.The coexpressions of GLT-1 and GFAP were significantly lower than those in the control group at days 3 and 7 after SCI (P ＜ 0.05).The GLT-1 expression was found on microglial cells in the control group.The GLT-1 expression was increased obviously at day 1 after SCI and increased progressively at days 3-14 after SCI.The coexpressions of GLT-1 and OX-42 were significantly higher than those in the control group at days 1,3,7 and 14 after SCI (P ＜ 0.05).Conclusion The glutamate transporters GLAST and GLT-1 show different expression patterns in astrocytes and microglia following SCI in rats,which may be correlated with the roles of different glial cells in repair of spinal cord injury.

Objective To explore the predictive efficacy of XGboost model in predicting risk of relapse and re-admission within 90 d in patients with ischemic stroke,and provide basis for early screening and prevention of high-risk population with ischemic stroke.Methods The clinical data of 6070 primary ischemic stroke patients admitted to our hospital from January 2007 to July 2017 were retrospectively collected.XGboost model and multivariate Logistic regression model were utilized to screen out the influencing factors of relapse and re-admission within 90 d in patients with ischemic stroke.A predictive model was set up.Receiver operating characteristic (ROC) curve was drawn and compared.Sensitivity,specificity and Youden index were calculated and compared to evaluate the prediction performance of XGboost model.Results During the observation period,a total of 520 patients with relapsed ischemic stroke were observed within a period of 90 d,and the incidence density was 8.57％.Multivariate Logistic regression analysis showed that length of first hospital stay,hypertension,pulmonary infection,neutrophil percentage,red blood cell distribution width (variable coefficient),and alkaline phosphatase level were independent influencing factors for re-hospitalization within 90 d of ischemic stroke,(OR=1.016,P=0.000,95％CI:1.008-1.025;OR=4.598,P=0.000,95％CI:3.717-5.687;OR=1.452,P=0.025,95％CI:1.048-2.012;OR=1.013,P=0.006,95％CI:1.004-1.022;OR=1.161,P=0.000,95％CI:1.090-1.237;OR=1.003,P=0.023,95％CI:1.000-1.005).Analysis of importance of risk factors for re-admission of ischemic stroke using XGboost model showed that the top 6 factors were hypertension,red blood cell distribution width,direct bilirubin,length of hospital stay,pulmonary infection,and alkaline phosphatase,and the corresponding importance scores were 32,20,19,18,15 and 14,respectively.ROC curve analysis results indicated that the area under the ROC for re-admission for XGboost model was 0.792 (95％CI:0.717-0.762),which was improved by 5％ as compared with that for multivariate Logistic regression model (0.739 [95％CI:0.764-0.818]).The sensitivity was 89.30％ and the Youden index was 0.444 for XGboost model,which were significantly higher than those for multivariate Logistic regression model (77.3％,0.405).Conclusions XGboost model is superior to multivariate Logistic regression model in predicting recurrence and re-admission of first ischemic stroke patients within 90 d.This model is suitable for prediction and early diagnosis of re-admission of ischemic stroke,which is of great clinical value.

Objective To grasp bilirubin in the quality control serum and calibration items in the same batch the variation law of the designed to ensure that the test quality and the use of reasonable quality control serum and calibration items ,control testing cost .Methods laboratories use The double level quality control serum and calibration items after dilution is divided into five groups ,with automatic biochemical analyzer test for 12 weeks and recorded results of TBIL ,DBIL .use SPSS 17 .0 to calculate the mean ,standard deviation ,coefficient of variation ,Normal distribution analysis and make the results trend line chart to observe any changes .Results RANDOX normal concentration quality control serum TBIL and DBIL values variation RCV% 26 .0% ,48 .2% , more than CLIA bilirubin projects allow 1/3 of the total error value(6 .67% ) .Normal distribution test ,P value was 0 .006 ,0 .012 , less than 0 .05 ,do not obey the normal distribution ,test results line chart is on the decline .LEADMAN high concentration quality control serum and bilirubin calibration items TBIL and DBIL variation RCV% <6 .67% ,normal distribution test all P>0 .05 ,obey the normal distribution ,test results no trend line chart .Conclusion Through the experiment observation to the quality control ser‐um and calibration items bilirubin in the variation law of 12 weeks .Experimenter can be used according to the actual situation to ad‐just ,not only to ensure the quality of the bilirubin test ,and to get the most out of the quality control serum and calibration items use efficiency ,reduce the test cost .