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 establish a bone knife deformation prediction model for periacetabular osteotomy and quickly and accurately predict bone knife deformation.Methods A finite element numerical model of a pelvic bone knife containing both cortical and cancellous bones was established,and the correlation between nodal strain and deformation was analyzed.The strains of 5 nodes with the strongest integrated correlation were selected as the inputs,and the displacement increments of the nodes on the blade part were established as the outputs.After training the model with the dataset,a deep learning neural network regression model based on the finite element dataset was used to establish a prediction model for the strain deformation of the bone knife.After the model prediction was completed,a binocular visual localization system was used to determine the spatially accurate position of the bone knife during the osteotomy procedure as a means of intraoperative tracking of the bone knife.Results The R2 value of the prediction model was 0.987 81 and the average deformation error after discretizing the bone knife into nodes was 0.07 mm.The prediction model quickly and accurately acquired bone knife deformation and showed great potential for reducing PAO surgical accidents.Conclusions The bone knife deformation prediction model developed in this study rapidly predicted bone knife deformation from strain information.Thus,it can avoid injuring tissues,such as nerves and blood vessels around the tissue,reduce the difficulty and risk of periacetabular osteotomy,and provide theoretical support for clinical application.

Objective To investigate the diagnostic value of detachable string magnetically controlled capsule endoscopy(ds-MCE)in patients with liver cirrhosis.Methods Patients with liver cirrhosis were screened for esophagogastroduodenoscopy(EGD)and ds-MCE examination to assess the accuracy of ds-MCE in identifying gastroesophageal varices,high-risk esophageal varices and portal hypertensive gastropathy using EGD as the gold standard,and evaluate the detection of portal hypertensive enteropathy and the comfort level of patients.Results From May 2021 to July 2022,a total of 53 patients with liver cirrhosis were successfully enrolled.With EGD as the gold standard,ds-MCE detected esophageal varices with 95.45％for sensitivity,100％for specificity and adjusted positive predictive value(PPV),95.65％for adjusted negative predictive value(NPV),and 0.877 for Kappa value(P＜0.001).For detection of gastric varices,ds-MCE had sensitivity,specificity,adjusted PPV,and adjusted NPV of 93.94％,90％,90.38％and 93.69％,and Kappa value of 0.839(P＜0.001).For detection of portal hypertension gastropathy,ds-MCE had sensitivity,specificity,adjusted PPV and adjusted NPV of 80％,90.70％,89.59％and 81.93％,and Kappa value of 0.657(P＜0.001).In differentiating high-risk esophageal varices,the sensitivity,specificity,adjusted PPV,and adjusted NPV were 76％,100％,100％and 77.43％,respectively;Kappa value was 0.770(P＜0.001).Of the patients with liver cirrhosis,26.0％(13/50)were diagnosed with portal hypertensive enteropathy.The main mucosal changes were edema,erythema,and vascular dysplasia.The ds-MCE comfort score of 3(2,4)was higher than that of the traditional EGD 1(0,3)(P＜0.000 1).Conclusion Compared with EGD,ds-MCE is an accurate,safe,feasible and comfortable method for detecting esophagogastric varices and portal hypertensive gastropathy in patients with liver cirrhosis.It is a potential alternative to EGD screening surveillance of gastroesophageal varices in patients with liver cirrhosis.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Purpose: Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). Methods: Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. Results: The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. Conclusions The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.

【Objective】 To evaluate the clinical value of capsule endoscope in the diagnosis of unexplained abdominal pain. 【Methods】 We made a retrospective analysis of 191 patients with unexplained abdominal pain who sought medical help in our hospital and 25 normal controls. Capsule endoscopy was performed in both groups, small bowel lesions were detected, and clinical data were collected for further analysis. 【Results】 The total small bowel lesion detection rate was 52.87% (101/191) in abdominal pain (AP) patients and 20% (5/25) in the control group, respectively. The detection rate of significant findings (ulcers, erosions, polyps, diverticula, parasites, and neoplastic organisms) was only 16.23% (31/191) in AP patients. In the non-significant findings, no statistical difference in the detection rates for vascular malformation, capillary dilation, and lymphoid follicular hyperplasia were found between the two groups, while the detection rate of intestinal lymphangiectasia was significantly higher in the AP patients (23.56% vs. 4%, P<0.05, OR=7.089). 【Conclusion】 Capsule endoscopy can be an optional choice for diagnosis of unexplained abdominal pain, while the relationship between positive findings and abdominal pain should be further investigated.

Purpose To investigate the clinicopathological and histological features of non-small cell lung cancer(NSCLC)patients with high expression of PD-L1 and positive driver muta-tion.Methods The clinical data of 141 patients with PD-L1 high expression and driver mutation-positive NSCLC were col-lected.Immunohistochemical methods,ARMS-PCR,and next-generation sequencing(NGS)were used to detect PD-L1 ex-pression and driver gene mutations.The clinicopathological fea-tures were analyzed and the related literatures were reviewed.Results There were 141 cases NSCLC patients with high ex-pression of PD-L1 in tumor cells,of which 57 cases were≥50％,＜60％;≥60％,＜70％in 18 cases;≥70％,＜80％in 35 cases;≥80％in 31 cases.Among 141 cases NSCLC patients with high PD-L1 expression,53 cases(37.6％)had driver gene mutations,including 4 cases BRAF 15 exon mutations,9 cases MET-associated mutations,17 cases EGFR-associated mutations,16 cases KRAS 2 exon mutations,4 cases EML4-ALK fusion mutations,and 3 cases other rare mu-tations.The high expression of PD-L1 and the occurrence of driver gene mutation were related to the gender,smoking history and pathological type of patients(P＜0.05).MET-related mu-tations and KRAS 2 exon mutations were more common in males than in females.All BRAF 15 exon mutations were female.The mean percentage of PD-L1 expression was highest in patients with MET mutation,KRAS 2 exon mutation,and 3 cases rare mutations.In 33 cases with BRAF 15 exon mutation,MET am-plification or mutation,EGFR-related mutation,and 3 cases oth-er rare mutations,PD-L1 was highly expressed in solid,glandu-lar,and micropapillary tumor cells.In 20 cases with KRAS 2 exon mutation and EML4-ALK fusion mutation,PD-L1 was highly expressed in solid nested tumor cells.Conclusion In NSCLC,high expression of PD-L1 and positive driver gene mu-tation are negatively correlated with the degree of tumor differen-tiation.In the poorly differentiated surgical specimens of lung adenocarcinoma,solid,micropapillary,or glandular tubular tumor tissues should be selected as far as possible for PD-L1 ex-pression and driver gene mutation detection.

Objective:To analyze the incidence and prognosis of epilepsy in frontotemporal lobe glioma.Methods:The clinical data of 208 patients with frontotemporal lobe gliomas in Sanbo Brain Hospital Capital Medical University from 2019 to 2021 were analyzed retrospectively. According to the 2016 World Health Organization (WHO) classification of tumors of the central nervous system, the incidence of epilepsy, Modified Rankin Scale (MRS) score, and Engel Outcome Scale of patients with different grades of tumors were calculated.Results:Among all the patients with frontotemporal lobe gliomas, there was more males than females, and it was more common in the 40 -59 age group. The incidence of epilepsy associated with WHO grade Ⅰand Ⅱ glioma was 100.0% (33/33) and 60.9% (14/23), respectively, while that of WHO grade Ⅳ glioma was 19.0%(19/100). The average follow-up time was (22 ± 9) months. During the follow-up period, the incidence of WHO grade Ⅰ, Ⅱ and Ⅲ glioma-related epilepsy decreased significantly. There was no significant difference in the incidence of glioma-related epilepsy between the total and subtotal resection groups ( P>0.05). There was no statistical correlation between the side of tumor occurrence and the occurrence of epilepsy ( P>0.05), also between the gene phenotype and the occurrence of epilepsy ( P>0.05). There was no significant difference in the Engel Outcome Scale among different grades of gliomas ( P>0.05). The prognosis of patients with Engel Outcome Scale Class 1 was significantly better than that of other grades. Conclusions:The incidence of glioma-related epilepsy is negatively correlated with tumor grade. Age and sex are risk factors for glioma-related epilepsy. The incidence of postoperative epilepsy in patients with low grade glioma is significantly lower than that in patients with high grade glioma, and the prognosis is better. However, there is no significant difference in the Engel Outcome Scale among different grades of gliomas.

Objective: To investigate adolescent haze weather health protection behavior, and to provide scientific basis for behavioral intervention and health guidance for adolescents in haze weather. Methods: From June 2015 to April 2016, 1 025 adolescents were selected from 22 classes in two middle schools of Baoding City, Hebei Province, by stratified cluster sampling method. General information questionnaire and the Brief Haze Weather Health Protection Behavior Assessment Scale Adolescent Version (BHWHPBAS AV) were used. Multiple linear regressions were conducted to explore factors affecting adolescent haze weather health protection behavior. Different models were used to confirm associations between influencing factors and BHWHPBAS AV scores. Results: Adolescents had a low overall score of BHWHPBASAV (45.81±13.16). The score rate of self adjustment after haze weather was the highest (64.54%). The score rate of obtaining relevant knowledge before haze weather was the lowest (50.28%). Compared with adolescents in urban area, rural adolescents had a lower BHWHPBAS AV score ( β=-3.20, P <0.01). Compared with students (living with parents), those living without parents had a lower BHWHPBAS AV score ( β=-4.16, P =0.01). Compared with students never receive physical examination,those had received physical examination during the past years had a higher BHWHPBAS AV score ( β=4.44，5.66，9.04, P <0.01). Compared with students with no knowledge of respiratory system diseases, those with moderate to sufficient knowledge had a higher BHWHPBAS AV score ( β=9.34，12.19，P <0.01). These associations were stable and consistent.Multiple linear regression analysis showed that residence, residence with parents, physical examination and knowledge of respiratory diseases were the relevant factors of BHWHPBAS AV score ( P <0.05). Conclusion Adolescent haze weather health protection behavior level is low and is affected by many factors. Cooperation should be strengthened to conduct behavioral interventions and health guidance on haze health protection for adolescents, so as to promote healthy growth of adolescents.