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 evaluate the cost-effectiveness of omalizumab in the treatment of severe allergic asthma from the perspective of healthcare providers in China. METHODS Based on the data from an international multicenter study of omalizumab in the treatment of severe allergic asthma， the Markov model was constructed according to the progression of severe allergic asthma， with a cycle of 4 weeks. Long-term health outcomes and costs of omalizumab combined with standard of care（SoC） regimen versus SoC regimen in the treatment of severe allergic asthma were simulated by using quality-adjusted life years （QALYs） and incremental cost-effectiveness ratio（ICER） as output indexes. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were performed to test the robustness of the results. RESULTS Compared with the SoC regimen， ICER for the omalizumab combined with SoC regimen was 107 723.05 yuan/QALY， which was less than the willingness-to-pay（WTP） threshold （268 074 yuan/QALY） calculated by three times per capita gross domestic product（GDP） in China in 2023. The one-way sensitivity analysis showed that the baseline serum level of immunoglobulin E had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the omalizumab+SoC regimen had a 93.00% probability of being cost- effective. The scenario analysis showed that in the real world， the billing method of omalizumab based on specifications rather than actual usage may increase ICER. CONCLUSIONS Compared with the SoC regimen， the combination of omalizumab and SoC regimen for treating severe allergic asthma is cost-effective， with a WTP threshold of three times China’s per capita GDP

Objective To compare and analyze the efficacy and risks of percutaneous CT/ultrasound-guided bipolar radiofrequency ablation(RFA)under local anesthesia with robotic-assisted laparoscopic partial nephrectomy(RAPN)for the treatment of sporadic small renal mass.Methods A retrospective study was conducted on 93 consecutive patients with T1a stage small renal mass during Mar.2019 and Oct.2021.Among them,51 underwent RAPN,and 42 underwent RFA.General information,tumor characteristics,perioperative and follow-up data were collected and statistically analyzed.Results There were no significant differences in general information and tumor characteristics between the two groups(P＞0.05).The operation time[(96.0±20.0)min vs.(113.5±24.1)min,P＜0.001],hospital stay[(3.5±0.8)day vs.(6.9±1.8)day,P＜0.001],and hospital costs[(2.4±0.7)ten thousand yuan vs.(6.6±0.4)ten thousand yuan,P＜0.001]were significantly decreased in the RFA group than in the RAPN group.There were no significant differences in the incidence of perioperative complications and long-term disease-free survival rate between the two groups(P＞0.05).However,the difference between one-year postoperative estimated glomerular filtration rate(eGFR)and preoperative eGFR was significantly lower in the RFA group than in the RAPN group[-2.3(-4.7-1.3)mL/(min·1.73 m2)vs.-5.0(-9.1 2.8)mL/(min·1.73 m2),P=0.003],and the reduction of one-year postoperative creatinine and preoperative creatinine was slightly lower in the RFA group than in the RAPN group[4.0(-0.2-5.5)μmol/L vs.4.5(1.8-9.2)μmol/L,P=0.122].Conclusion RFA can achieve comparable disease-free survival rate as RAPN in the treatment of T1a renal tumor,and can effectively preserve renal function,reduce medical costs,save medical resources,and lower the incidence of perioperative complications.

Objective To investigate the clinical efficacy and safety of tirofiban and rt-PA alteplase in the treatment of minor stroke patients.Methods A total of 171 patients with minor stroke ad-mitted to Department of Neurology of Zhengzhou People's Hospital from January 2021 to January 2024 were prospectively and continuously enrolled,and were randomly divided into tirofiban group(84 cases)and rt-PA group(87 cases).The tirofiban group received intravenous infusion of tirofiban but not intravenous thrombolysis therapy.The rt-PA group was treated with intravenous thrombolysis.The 90-day mRS score was observed in all patients.NIHSS was used to score the improvement of neurological function.3-month all-cause death was observed during follow-up.Results The tirofiban group had a significant larger proportion of mRS score of 0-1 at 90 d(92.86％vs 82.76％,P＜0.05),lower NIHSS scores at 24 h and 7 d after treatment and smaller proportion of early neurological deterioration than the rt-PA group(P＜0.05).Larger proportion of mRS score of 0-2 in the 90 day and slightly smaller proportion of the score of 4-6 at 90 d were observed in the tirofiban group than the rt-PA group(P＞0.05).There were no statistical difference in the incidence of 3-month all-cause death between the two groups(P＞0.05).Conclusion Compared with rt-PA,tirofiban can significantly improve the clinical prognosis of pa-tients with minor stroke,reduce the risk of early neurological deterioration,and has higher safety.

Objective:To investigate associations of cerebral perfusion impairment with early neurological deterioration (END) and poor outcome in patients with acute small subcortical infarction (SSI).Methods:Patients with SSI in the perforator artery region admitted to the Department of Neurology, Zhengzhou People's Hospital between January 2020 and November 2022 were prospectively included. END was defined as an increase of ≥2 in the total score of the National Institutes of Health Stroke Scale (NIHSS) or an increase of ≥1 in the motor function score within 72 h after admission. Poor outcome was defined as the modified Rankin Scale score of 2 at 90 d after onset. Cerebral perfusion impairment was defined according to MRI perfusion-weighted imaging parameters. The demographic, baseline clinical and imaging data were collected. Multivariate logistic regression analysis was used to determine associations of cerebral perfusion impairment and END and poor outcome in patients with SSI. Results:A total of 100 patients with SSI were enrolled, including 56 males (56.0%), and aged 69.2±5.8 years. Among them, 19 patients (19.0%) developed END, 27 (27.0%) had poor outcome, and 51 (51.0%) had significant cerebral perfusion impairment. There were statistically significant differences in high sensitivity C-reactive protein, white matter hyperintensities (WMHs) in the basal ganglia, enlarged perivascular space (EPVS) in the basal ganglia, deep cerebral microbleeds (CMBs), and cerebral perfusion impairment between the END group and the non-END group (all P<0.05). Multivariate logistic regression analysis showed that higher diastolic blood pressure (odds ratio [ OR] 1.070, 95% confidence interval [ CI] 1.003-1.141); P=0.040], deep WMHs ( OR 2.271, 95% CI 1.135-4.544; P=0.020), deep CMBs ( OR 5.047, 95% CI 1.240-20.549; P=0.024), and cerebral perfusion impairment ( OR 6.083, 95% CI 1.318-28.080; P=0.021) were independent risk factors for END in patients with SSI. There were statistically significant differences in hypersensitive C-reactive protein, NIHSS score at END, basal ganglia EPVS, END, and cerebral perfusion impairment between the poor outcome group and the good outcome group ( P<0.05). Multivariate logistic regression analysis showed that NIHSS score at END ( OR 1.485, 95% CI 1.034-2.133; P=0.032), basal ganglia EPVS ( OR 3.005, 95% CI 1.224-7.378; P=0.016), and cerebral perfusion impairment ( OR 9.234, 95% CI 1.994-42.765; P=0.004) were independent risk factors for the poor outcome at 90 d in patients with SSI, while anterior circulation infarction ( OR 0.066, 95% CI 0.013-0.334; P=0.001) was independently negatively correlated with the poor outcomes at 90 d after onset. Conclusion:Cerebral perfusion impairment is an independent risk factor for END and poor outcome at 90 d after onset in patients with SSI.

【Objective】 To investigate the clinical efficacy and safety of laparoscopic radical prostatectomy in elderly prostate cancer patients aged ≥80 years in good health. 【Methods】 A total of 18 octogenarian patients who underwent laparoscopic radical prostatectomy during Aug.2016 and Mar.2020 at our hospital were selected for retrospective analysis. 【Results】 The patients were 80 to 86 years old. The preoperative serum PSA was 5.25-101.00 ng/mL. There were 2 cases in stage cT1N0M0,12 in stagec T2N0M0 and 4 in stage cT3N0M. The Gleason score was ≤6 in 4 cases,=7 in 9 cases,and ≥8 in 5 cases. During the follow-up of 22 to 65 months,the rates of urinary incontinence at 1 month,3 months,6 months,and 1 year were 50.00% (9/18),33.33% (6/18),16.67% (3/18) and 5.56 %(1/18),respectively. The postoperative urinary control recovery time was 1 to 220 days. Positive incision margin developed in 3 cases and biochemical recurrence occurred in 3 cases. The IPSS score at 3, 6 months and 1 year after surgery were lower than these before surgery (P<0.05). The overall health score of the FACD-P scale at 6 months after surgery was higher than that before surgery (P<0.05). 【Conclusion】 For well selected octogenarian prostate cancer patients in good condition,laparoscopic radical prostatectomy is a feasible,safe and effective treatment option,but long-term follow-up and prospective clinical studies with large sample size are still needed to confirm its efficacy.

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Objective:To elucidate the phenomenon that epileptic seizure occurs in patients with epilepsy without definite diagnosis when driving a motor vehicle and its hazards.Methods:From January 2020 to June 2022, 7 epileptic patients who experienced traffic accidents caused by seizures were selected from the First Affiliated Hospital of Soochow University, and their demographic data, traffic accident related data and epilepsy diagnosis and treatment data were summarized and analyzed.Results:A total of 7 adult patients with epilepsy were collected, including 6 males, 4 of whom had been driving for more than 10 years. Among them, 1 patient drove a bus, and the other 6 patients drove private cars. Totally 5/7 of the accidents resulted in personal injury, and 3/7 of the accidents resulted in personal death. In 5 patients, video electroencephalogram showed interictal epileptiform discharges. In 2 patients, the imaging findings suggested the presence of cerebral cortical lesions that may lead to seizures. In terms of the form of seizure, 3 patients′ seizure type was focal to bilateral tonic-clonic, and the other 4 patients were very probable to be focal impaired awareness seizure.Conclusions:Undiagnosed epileptic seizures lead to traffic accidents, endanger patients and public safety, which need to attract attention from both doctors and patients, as well as the whole society.

Allergic diseases have continued to increase year by year causing serious physical and mental injury to patients, families and individuals. This increase has been driven by conventional environmental and nutritional changes but is also created by the continual introduction of food additives into the diet and novel interior decoration materials into the living space. The causes of allergic diseases are complex and diverse, and the medical laboratory often is not be able to identify the allergic trigger; this creates a difficult environment to identify the appropriate clinical treatment for disease prevention and control. Physicians must be able to identify these triggers to help patients avoid the underlying allergenic cause of their disease. This can only be done by actively knowing a patient′s medical history, identifying the clinical manifestations of hypersensitivity and utilizing confirmatory testing as an important clinical tool in identifying the allergic source.

Allergic diseases have continued to increase year by year causing serious physical and mental injury to patients, families and individuals. This increase has been driven by conventional environmental and nutritional changes but is also created by the continual introduction of food additives into the diet and novel interior decoration materials into the living space. The causes of allergic diseases are complex and diverse, and the medical laboratory often is not be able to identify the allergic trigger; this creates a difficult environment to identify the appropriate clinical treatment for disease prevention and control. Physicians must be able to identify these triggers to help patients avoid the underlying allergenic cause of their disease. This can only be done by actively knowing a patient′s medical history, identifying the clinical manifestations of hypersensitivity and utilizing confirmatory testing as an important clinical tool in identifying the allergic source.