OBJECTIVE: To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ). METHODS: Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated. RESULTS: DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin. CONCLUSIONS The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.
Animals ; Male ; Rats ; Diquat/toxicity* ; Gastrointestinal Diseases ; Intestines ; Poisons ; Rats, Wistar ; Toxicokinetics

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 investigate the current situation of emergency medical service (EMS) system and its effect on treatment of the acute stage and short- and long-term prognosis in patients with acute myocardial infarction in Hebei province.Methods:Totally 2 961 patients with acute myocardial infarction who were admitted to major tertiary and some representative secondary hospitals in Hebei province from January 2016 to December 2016 were collected. According to the pattern of arriving hospital, all the patients were divided into the EMS group and self-transport group. The general conditions, time from onset to treatment, treatment methods, in-hospital mortality rate and 3-year mortality rate were compared between the two groups.Results:Of the included 2 961 patients, 33.13% of them were transported through EMS and 66.87% of them by private transport. Patients with a history of hypertension and ST-segment elevation myocardial infarction were more likely to choose EMS, and the difference was statistically significant ( P<0.05). Moreover, patients in the EMS group were more likely to go to tertiary hospitals for treatment (88.58% vs 85.76%, P=0.033). The time from onset to treatment of the EMS group was significantly shorter than that of the self-transport group (160 min vs 185 min, P<0.01), and the proportion of patients in the EMS group from onset-to-door time in <3 h and 3-6 h was higher than that of the self-transport group (55.76% vs 49.14%, 21.41% vs 19.09%, P<0.01). Compared with the self-transport group, the EMS group has a higher rate of reperfusion therapy (67.48% vs 61.67%, P=0.002). Patients in the EMS group had a higher in-hospital mortality rate in the acute stage (7.03% vs 4.44%, P=0.003), but its 3-year mortality rate was lower than that of the self-transport group (17.31% vs 20.77%, P<0.05). Conclusions:EMS can shorten symptom-onset-to-arrival time, increase the rate of reperfusion therapy and improve long-term prognosis of patients with acute myocardial infarction.

Objective:To investigate the effects of diquat (DQ) on the expression of intestinal pyroptosis-related proteins and tight junction proteins in rats, and to analyze the role of pyroptosis in the intestinal injury of rats with acute DQ poisoning.Methods:A total of 36 Wistar male rats were randomly divided into control group, and 3 hours, 12 hours, 36 hours and 3 days exposure groups, with 6 rats in each group. Each exposure group was given 1/2 median lethal dose (LD50) of 115.5 mg/kg DQ by one-time gavage. The control group was given the same amount of normal saline by gavage. The control group was anesthetized at 3 hours after DQ gavage to take jejunal tissues; each exposure group was anesthetized at 3 hours, 12 hours, 36 hours, and 3 days after DQ gavage to take jejunal tissues, respectively. The general conditions of the rats were recorded. The pathological changes of jejunum tissue were observed by hematoxylin-eosin (HE) staining. The expression of intestinal pyroptosis-related proteins [NOD-like receptor protein 3 (NLRP3), cysteine aspartate-specific protease 1 (caspase-1), Gasdemin D (GSDMD)] in the intestinal tissues was observed by immunohistochemical staining. Western blotting was used to detect the expression of intestinal pyroptosis-related proteins and intestinal tight junction proteins (Occludin and Claudin-1).Results:Light microscopy showed that pathological changes occurred in jejunum tissue at the early stage of exposure (3 hours), and the injury was the most serious in the 12 hours exposure group, with a large number of inflammatory cells infiltrating in the tissue, and the damage was significantly reduced after 3 days exposure. Immunohistochemical results showed that NLRP3, caspase-1 and GSDMD were expressed in the jejunal mucosa of the control group and the exposure groups, and the positive cells in the control group were less expressed with light staining. The expression of the above proteins in the exposed group was increased significantly and the staining was deep. Western blotting results showed that compared with the control group, the expression of NLRP3 protein in jejunum tissues of all groups was increased, with the most significant increase in the 36 hours group (NLRP3/β-actin: 1.47±0.06 vs. 0.43±0.14, P < 0.01). Compared with the control group, the expression of GSDMD protein in the 3 hours, 12 hours and 36 hours exposure groups increased, and the expression of GSDMD protein in the 3 hours and 12 hours exposure groups increased significantly (GSDMD/β-actin: 1.04±0.40, 1.25±0.15 vs. 0.65±0.25, both P < 0.05). The expression of caspase-1 protein was increased in 36 hours exposure group compared with the control group (caspase-1/β-actin: 1.44±0.34 vs. 0.98±0.19, P > 0.05). Compared with the control group, the expression of Occludin and Claudin-1 proteins in each exposure group decreased, and the expression of Occludin proteins was significantly decreased in the 3 hours, 12 hours, and 36 hours exposure groups decreased significantly (Occludin/β-actin: 0.74±0.17, 0.91±0.20, 0.79±0.23 vs. 1.41±0.08, all P < 0.05). Although the protein expression of Claudin-1 decreased in each exposure group, the difference was not statistically significant. Conclusion:The intestinal injury caused by acute DQ poisoning may be related to the activation of pyroptosis pathway of small intestinal cells and the reduction of the density of intercellular junctions.

Objective To analyze the prognosis and influencing factors of patients with acute myocardial infarction(AMI)complicated with cardiogenic shock(CS)under extracorporeal membrane oxygenation(ECMO)support.Methods Retrospective analysis of the clinical data of ECMO supported coronary angiography and percutaneous coronary intervention(PCI)treatment for AMI complicated with CS patients who visited the department of emergency medicine of the Second Hospital of Hebei Medical University from December 2018 to December 2021,including gender,age,body mass index(BMI),past history(smoking history,coronary heart disease,diabetes,hypertension,hyperlipidemia,cerebrovascular disease),acute physiological and chronic health evaluationⅡ(APACHEⅡ),vasoactive-inotropic score(VIS),the worst auxiliary examination indicators within 24 hours before ECMO[arterial lactate acid,white blood cell count(WBC),cardiac troponin I(cTnI),alanine transferase(ALT),total bilirubin(TBil),creatinine(Cr),serum potassium(K+),left ventricular ejection fraction(LVEF)],time from onset to PCI,coronary angiography results(involved anterior descending branch,circumflex branch,right coronary artery,three-vessel lesions,left main artery lesions),whether to use intra aortic-balloon counterpulsation(IABP)and continuous renal replacement therapy(CRRT).Patients were divided into survival and death groups based on the prognosis after 30 days of onset.Univariate analysis was used to compare the differences in the above indicators between the two groups with different prognoses,Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of AMI patients with CS under ECMO support coronary angiography and PCI treatment,and the receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of risk factors on patient prognosis.Results Out of 39 patients,21 cases(53.8%)survived and 18 cases(46.2%)died.Compared with the survival group,the VIS score,lactate acid,time from onset to PCI,involvement of the circumflex artery,three-vessel disease,and left main artery lesions significantly increased in the death group(all P＜0.05).Logistic regression analysis showed that lactate acid and three-vessel lesions were independent risk factors affecting the 30-day prognosis of AMI patients with CS[odds ratio(OR)and 95%confidence interval(95%CI)were 1.845(1.018-3.342)and 107.171(1.307-8 785.901),all P＜0.05].ROC curve analysis showed that lactate acid and three-vessel lesions has predictive value for the prognosis of AMI combined with CS patients undergoing ECMO supported coronary angiography and PCI treatment,the area under the ROC curve(AUC)were 0.756 and 0.752,95%CI were 0.601-0.911 and 0.588-0.916,P value were 0.007 and 0.008.When the cut-off value of lactic acid was 5 mmol/L,the sensitivity and specificity of predicting the prognosis of AMI combined with CS patients undergoing coronary angiography and PCI treatment were 94.1%and 57.1%,respectively.Conclusions The indications for using ECMO in critically ill patients with AMI combined with CS need to be further refined.VIS score,lactate acid,time from onset to PCI,three-vessel lesions,and left main artery lesions are risk factors for patient death.When using ECMO support for high lactate,high VIS score,and three-vessel lesions,caution should be exercised.Early ECMO support can improve the prognosis of appropriate patients by reducing lactate,reducing the use of vasoactive drugs,and shortening the time from onset to PCI.

BACKGROUNDAnterior cruciate ligament reconstruction (ACLR) has developed dramatically in the last century. Now, ACLR has become a reliable and productive procedure. Patients feel satisfied in >90% cases. The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin (ACBCP) used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro.

METHODSThe specimens were provided by the bone banks of the First Affiliated Hospital of People's Liberation Army of General Hospital from September 2011 to June 2012. Fresh deep frozen human allogenetic cortical bone was machined into cross-pins which is 4.0 mm in diameter and 75.0 mm in length. Biomechanical parameters compared with Rigidfix were collected while cross-pins were tested in double-shear test. The load-to-failure test and cycling test were carried out in a goat model to reconstruct anterior cruciate ligament with Achilles tendon autograft on the femoral side fixed by human 4.0 mm ACBCP and 3.3 mm Rigidfix served as control. Maximum failure load, yield load, and stiffness of fixation in single load-to-failure test were compared between the two groups. Cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 were also compared in between.

RESULTSIn double-shear test both maximum failed load and yield load of 4.0 mm human ACBCP were (1 236.998±201.940) N. Maximum failed load and yield load of Rigidfix were (807.929±110.511) N and (592.483±58.821) N. The differences of maximum failed load and yield load were significant between ACBCP and Rigidfix, P < 0.05. The shear strength of ACBCP and Rigidfix were (49.243±8.039) MPa and (34.637±3.439) MPa, respectively, P < 0.05. In the load-to-failure test ex vivo, yield load and maximum failed load of ACBCP fixation complexity ((867.104±132.856)N, (1 032.243±196.281) N) were higher than those of Rigidfix ((640.935±42.836) N, (800.568±64.890) N, P < 0.05). However, stiffness did not differ significantly between ACBCP group ((247.116±31.897)N/mm) and Rigidfix group ((220.413±51.332) N/mm, P > 0.05). In the cycling test, the cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 did not differ significantly between the ACBCP group and Rigidfix group, P > 0.05.

CONCLUSIONSAllogenetic cortical bone cross-pin possesses satisfactory biomechanical profile which is safe for ACLR and suitable for an aggressive rehabilitation program. Animal and clinical tests should be recommended before clinical use to secure the ACBCP could successfully substituted by host new bone in vivo.

Achilles Tendon ; surgery ; Adult ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur ; surgery ; Humans ; Male ; Materials Testing ; Middle Aged ; Orthopedic Fixation Devices

Objective: To determine the value of hyperextension MRI evaluation in determining whether to perform decompression therapy after reduction of reducible atlantoaxial dislocation as well as assess the decompression effect. Methods: A retrospective case series study was conducted to analyze 24 patients with atlantoaxial dislocation admitted to Honghui Hospital affiliated to Xi'an Jiaotong University from May 2015 to May 2017. There were 10 males and 14 females, aged 40-74 years, with an average age of 52 years. There were 14 patients with os odontoideum, four patients with odontoid fracture, and six patients with transverse atlantal ligament rupture. Hyperextension MRI was performed to assess spinal cord compression for all patients. Eight patients with anterior spinal cord compression (Group A) underwent posterior atlantoaxial arch decompression plus atlantoaxial internal fixation reduction and bone graft fusion; 16 patients without anterior compression of the spinal cord (Group B) underwent only atlantoaxial internal fixation reduction and bone graft fusion. Intraoperative and postoperative complications were recorded. Spinal cord compression index and improvement rate of spinal cord decompression were evaluated by routine cervical spine MRI. Japanese Orthopedic Association (JOA) score was used to evaluate the clinical effect. Results: All patients were followed up for 3-24 months, with an average of 9.3 months. There was no nerve or vertebral artery injury during the operation, and no screw loosening occurred after surgery. The spinal cord compression index (0.37±0.18) in Group A at the last follow-up was significantly lower than that before operation (0.73±0.22) (P<0.05), while the index in Group B (0.19±0.20) at the last follow-up was also lower than that before operation (0.61±0.25) (P<0.05). The improvement rate of spinal cord decompression was 67.11% in Group A and 70.61% in Group B. The final JOA score of Group A was (13.29±3.68)points, which was significantly better than the preoperative JOA [(5.61±2.74)points] (P<0.05). The final JOA score in Group B [(14.13±3.45)points] was also significantly better than the preoperative JOA [(7.32±2.90)points] (P<0.05). Improvement rate of JOA was 57.31% in Group A and 59.91% in Group B. Conclusions Hyperextension MRI of cervical vertebra can effectively judge whether the anterior spinal cord is compressed after reduction of atlantoaxial dislocation. It has important clinical significance for decompression treatment during reduction and internal fixation of reducible atlantoaxial dislocation. At the same time, posterior atlantoaxial arch resection and decompression can effectively relieve the compression of the spinal cord after reduction of atlantoaxial dislocation.