OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.

Objective To investigate the anticoagulation status of patients with atrial fibrillation(AF)-related acute ischemic stroke(AIS)after revascularization therapy in the real world.Methods A retrospective study was performed on patients diagnosed as AIS and AF from Jan.2019 to Jan.2022 at The Second Affiliated Hospital of Nanchang University.Patients treated with intravenous thrombolysis(IVT),endovascular thrombectomy(EVT),or both were enrolled.Clinical information,timing of anticoagulation initiation,treatment regimens,and outcomes were documented and statistically analyzed.Additionally,a questionnaire was administered to the primary physicians to understand reasons for delaying or not initiating anticoagulation.Results A total of 189 patients with AF-related AIS met the screening criteria,including 86(45.5%)cases in the IVT group,63(33.3%)cases in the EVT group,and 40(21.2%)cases in the IVT+EVT group.The mean age of 189 patients was(72.90±9.23)years old.There were 93(49.2%)female patients.Anticoagulation was initiated within 14 d after revascularization therapy in 36.0%(68/189)of patients,with the highest rate in the IVT group(58.8%,40/68),followed by the EVT group(22.1%,15/68)and IVT+EVT group(19.1%,13/68).A significant difference was found in the proportion of patients receiving anticoagulation within 14 d among the 3 groups(P=0.020).Univariate analysis was performed on the clinical data of patients who initiated anticoagulation within 14 d after revascularization therapy(68 cases)and those who delayed or did not initiate anticoagulation(121 cases).The results showed that there were significant differences in the stroke history,National Institutes of Health stroke scale(NIHSS)score before revascularization therapy,Alberta Stroke Program early computed tomography score,modified Rankin scale(mRs)score before revascularization therapy,imaging characteristics(lesions near cortex,large infarction,severe stenosis or occlusion of major intracranial arteries),revascularization therapy method,NIHSS score 3 d after revascularization therapy,and intracranial hemorrhagic transformation after revascularization therapy between the 2 groups(all P＜0.05).Multivariate logistic regression analysis indicated that higher NIHSS scores 3 d after revascularization therapy(odds ratio[OR]=1.113,95%confidence interval[CI]1.053-1.176,P＜0.001)and the presence of intracranial hemorrhage after revascularization therapy(OR=6.098,95%CI 2.004-18.193,P=0.001)were significant factors that contraindicated the initiation of anticoagulation.Large infarcts(40.8%),infarct location(35.8%),and hemorrhagic transformation after stroke(40.8%)were the common reasons cited by physicians for not initiating anticoagulation.In the 90-d prognosis of patients with AF-related AIS,6 patients had bleeding events,and 116 patients had a good prognosis(mRS score of 0-2).The 90-d good prognosis rate in the initiated anticoagulation group within 14 d after revascularization therapy(89.7%,61/68)was significantly higher than that in the delayed or non-anticoagulation group(45.5%,55/121;P＜0.001).Conclusion For patients with AF-related AIS who receive IVT,EVT or IVT+EVT,it is safe to initiate anticoagulation early after revascularization therapy,but the timing of anticoagulation in most patients is later than the currently recommended anticoagulation timing.

Objective:To investigate the clinical manifestations of population following COVID-19 by using questionnaires.Methods:COVID-19 among anesthesia workers and the surrounding population was investigated between 11 November 2022 and 31 December 2022 in China.The Tencent electronic questionnaire(ID.11492813) was sent to different WeChat groups of the Association of Anesthesiologists or Society of Anesthesiologists via the WeChat platform of the medical personnel in China. The survey was conducted between January 7 and January 15, 2023. Results:A total of 17 000 questionnaires were issued for this survey, 11 060 valid questionnaires from 31 provinces and autonomous regions were collected all over the country, with a recovery rate of 65.059%.There were 10068 (91.037%) participants diagnosed as having COVID-19, and among of them, 47.606% were male and 52.394% were female. The main post-COVID-19 clinical manifestations included fever (85.777%), cough (83.731%), fatigue (75.338%), parasomnia (64.352%), limb soreness (58.890%), dizziness, headache, tinnitus (38.617%), loss or abnormality of taste (37.763%), and loss or abnormality of smell (30.960%); peripheral neuralgia was usually found within 3 days after positive nucleic acid test or positive antigen test; there were 2 963 cases accompanied with sweating, and among of them, 47.25% were male and 52.75% were female, and 37.80% of these participants continued to sweat after the nucleic acid test or antigen test became negative. There were 1 151 cases with premature heart beats among the study population, and the symptoms aggravated following COVID-19 were found in 34.32% of these patients.Conclusions:In addition to the respiratory system, the central and peripheral nerves of patients are also affected following COVID-19, and the peripheral and central nerve disorders last until several days after negative nucleic acid test or antigen test, suggesting that anesthesiologists should pay more attention to monitoring of various nerve function and impact of surgery and anesthetic drugs on the stress response of the body in such patients.