OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

This study was designed to explore the immune reconstitution efficacy of human thymic slices transplanted into renal capsule,subcutaneous or muscle of nude mice,and further explore the optimal location of heterotopic transplantation.The thymus tissue discarded from congenital heart disease patients was made into 0.5-1 mm thick tissue sections and cultured in vitro to remove immune cells.H&E staining and immunohistochemical staining were used to assess the residual tissue structure and cell types in thymic slices,while quantitative PCR methods were used to assess the function of residual cells in thymic slices.Then thymic slices were transplanted into the renal capsule,subcutaneous or muscle of nude mice,and the immune reconstitution efficacy was compared by flow cytometry and histology.Data showed that after 14 days of culture in vitro,the clearance rate of T lymphocytes in the thymic slices was more than 90%,and the epithelial cell network structure of the tissue was intact,while a large number of macrophages,dendritic cells and endothelial cells remained.Quantitative PCR results showed that the gene expression levels of epithelial cell markers and secreted cytokines in cultured thymic slices could be effectively maintained.Flow cytometry showed that at 16 weeks after transplantation,the proportion of T cells in peripheral blood of mice in different transplantation groups were significantly increased,whereas the proportion of T cells in muscle group was the highest.In situ histological examination showed that the regeneration of thymus tissue was detected at all three transplant sites.In addition,the graft detection rate was 40%in the renal capsule group,60%in the subcutaneous group and 100%in the musclegroup.In conclusion,the human thymic slices cultured in vitro for 14 days retain a complete thymic matrix microenvironment.Transplantation of human thymic slices can effectively reconstruct the ratio of T cells in nude mice,and the muscle is the most effective transplantation site.

ObjectiveTo evaluate the clinical effectiveness and safety of acupuncture with manipulation for lumbar disc herniation in remission period. MethodsOne hundred and four patients with lumbar disc herniation in remission were randomly divided into a treatment group and a control group， with 52 cases in each group. Treatment group applied acupuncture with manipulation of pointing， pulling， and shaking. Acupoints were selected as lumbar Jiaji （EX-B2， bilateral）， Ashi point， Shenshu （BL 23， bilateral）， Huantiao （GB 30， bilateral）， Weizhong （BL 40， opposite side of the affected area）， Chengshan （BL 57， opposite side of the affected area）. The control group applied lumbar traction plus acupoint ultrasonic pulse penetration therapy （acupoints selection same as the treatment group）； 20 minutes each time， 3 times a week， a total of 3 weeks for both groups. The primary outcome was the improvement rate of lumbar disc herniation symptoms and signs， which was calculated at 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up， respectively； the secondary outcome were the Japanese Orthopaedic Association （JOA） scores， Visual Analogue Scale （VAS） scores， and Oswestry Disability Index （ODI） scores （including ODI total scores， sitting scores and standing scores）， which were evaluated before treatment， 1 week of treatment， 3 weeks of treatment， 1 month follow-up， and 3 months follow-up； clinical effectiveness was assessed at 3 months follow-up； and the occurrence of adverse events in the participants， as well as blood routine， urine routine， stool routine， and electrocardiograms before and after the treatment were recorded to evaluate safety. ResultsTwo patients from each group fell out， and 50 patients of each group were included in the outcome analysis ultimately. The scores of lumbar disc herniation symptoms and signs improved more in the treatment group than in the control group at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up （P＜0.01）. The JOA scores of participants in both groups at 1 week of treatment， 3 weeks of treatment， 1 month follow-up and 3 months follow-up were higher than those before treatment in the same group， and the VAS scores， ODI total scores， ODI sitting scores and standing scores were significantly lower than those before treatment in the same group （P＜0.05）， and the JOA scores of patients in the treatment group were higher than those of the control group at all time points， and the VAS scores， ODI total scores， ODI sitting scores and standing score were lower than those of the control group （P＜0.05）. At the 3 months follow-up， the excellent rate of the treatment group was 70.00% （35/50） better than that of the control group， which was 50.00% （25/50） （P＜0.05）. There were no abnormalities in blood， urine， stool routines and electrocardiograms before and after treatment in both groups， and no adverse events occurred. ConclusionAcupuncture with manipulation of pointing， pulling， and shaking for treating patients with lumbar disc herniation in remission has a better safety on pain relief and improving quality of life， and the effectiveness is better than lumbar traction plus acupoint ultrasonic pulse penetration therapy.

Recent studies have found that in the development of epilepsy, cyclic adenosine monophosphate response element binding protein (CREB) may cause recurrent epilepsy by inhibiting the expression of γ-aminobutyric acid, resulting in neuron damage and weakened effect of antiepileptic drug targets. Antiepileptic drugs can not control the extent or frequency of seizures, and then the patients are in a persistent state, hence the development of drug-resistant epilepsy. Therefore, the mechanism of CREB leading to drug-resistant epilepsy was reviewed in this paper, hoping to provide ideas for the treatment of drug-resistant epilepsy patients.

Objective:As a newly emerging thing, the construction and operation management of research wards are still being explored. According to the previous practice, this study summarized and shared the key points of a demonstration research ward in Beijing, and provided a reference for the development of domestic research wards.Methods:Focusing on improving the efficiency and quality of clinical research, this article summarizes and shares the experience of research ward construction. In addition, this study explores how to maintain the high-quality sustainable development of research wards from the aspects of improving core competence, system construction, and talent training.Results:Professional teams, innovative operation modes, as well as intelligence and informatization could improve the quality of clinical research. Besides, the improvement of core competence, talent training, and policy support ensure sustainable development of research wards.Conclusions:As clinical research platforms, the development paths of research wards need to be clarified further. The standardized construction and sustainable development of research wards can effectively improve clinical research capability and promote the transformation of scientific achievements.

Objective:To evaluate the application values of classifications of acute distal occlusion of internal carotid artery and variation of Willis' circle in predicting prognoses of acute ischemic stroke patients after mechanical thrombectomy (MT).Methods:One hundred and fifty-eight patients with acute ischemic stroke, admitted to our hospital from January 2016 to November 2020, were chosen in our study; these patients had conformed imaging diagnosis of acute distal occlusion of internal carotid artery and accepted endovascular MT; the clinical and imaging data of these patients were retrospectively analyzed. The distal occlusion of internal carotid artery was divided into Ia, Ib, L, and T types according to the occlusion positions. Prognoses were evaluated by modified Rankin Scale (mRS) 90 d after treatment. Multivariate Logistic regression was used to determine the independent factors for prognoses.Results:Among these 158 patients, 58 patients achieved good prognosis and 100 had poor prognosis. As compared with patients in the poor prognosis group, patients in the good prognosis group had significantly younger age, significantly lower NIHSS scores at admission, and statistically lower atrial fibrillation ratio ( P<0.05). There were statistical differences in the classifications of acute distal occlusion of internal carotid artery between the two groups ( P<0.05): the proportion of Ia type in patients of good prognosis group was the highest (75.9%), while that of T type was the lowest (3.4%). There was no significant difference in variation of Willis' circle between the two groups ( P>0.05). Multivariate Logistic regression analysis showed that T type of acute distal occlusion of internal carotid artery and atrial fibrillation were independent factors for prognoses of these patients ( OR=0.342, 95%CI: 0.127-0.919, P=0.033; OR=0.066, 95%CI: 0.005-0.803, P=0.033). Conclusion:Patients with T type of acute distal occlusion of internal carotid artery and atrial fibrillation are trend to have poor prognosis.

With the rapid development of network structure, convolutional neural networks (CNN) consolidated its position as a leading machine learning tool in the field of image analysis. Therefore, semantic segmentation based on CNN has also become a key high-level task in medical image understanding. This paper reviews the research progress on CNN-based semantic segmentation in the field of medical image. A variety of classical semantic segmentation methods are reviewed, whose contributions and significance are highlighted. On this basis, their applications in the segmentation of some major physiological and pathological anatomical structures are further summarized and discussed. Finally, the open challenges and potential development direction of semantic segmentation based on CNN in the area of medical image are discussed.

Objective:To investigate the implementation effect of micro-video assisted physiological theory teaching based on functional experiments.Methods:There were 140 clinical undergraduates (control group) from Class 1 and Class 2, and 123 clinical undergraduates (experimental group) from Class3 and Class 4 of Batch 2017 in our university who were involved in this study. The control group adopted traditional teaching method, the experimental group adopted micro-videos to assist traditional teaching in the teaching of selected chapters, and these micro-videos were collected from the recording and editing of functional experiments. After the course, questionnaire survey in terms of course design, implementation and effect, as well as final exanimation performance analysis were conducted to evaluate the teaching effect. SPSS 17.0 was used for t test. Results:The final examination scores of the experimental group were significantly higher than those of the control group [(81.02±9.64) vs. (73.41±11.39)], with significant differences ( t=-5.805, P<0.001). Among them, the scores of Chapter 2 of the two groups were [(8.07±0.94) vs. (6.14±1.05), t=-15.616, P<0.001)], the scores of Chapter 4 were [(16.16±1.79) vs. (10.90±2.23), t=-20.903, P<0.001)], and the scores of Chapter 6 were [(6.04±0.53) vs. (5.82±0.78), t=-2.638, P=0.009)], all with significant differences. 100% of questionnaires were recovered, and more than 90% of students were interested in this teaching method which could strengthen their understanding of the key and difficulties in physiology and was also helpful to cultivate their ability of induction and summarization. Conclusion:Micro-videos based on functional experiments assisted teaching can improve the teaching effect of physiology, and it's worth popularizing.

Objective To explore the mental health status and characteristics of professional degree postgraduates.Methods 326 professional degree postgraduates from 3 universities were selected as subjects by cluster sampling.Symptom checklist 90 (SCL-90) was applied to assess psychological health of the postgraduates in order.Results 1) The positive rate of psychological symptom screening was 11.11％.The detection rate of psychological problems from high to low was:obsessive-compulsion,interpersonal sensitivity,depression,hostility,somatization,paranoid ideation,anxiety,phobic anxiety and psychoticism.2) Excluding the factors of phobic anxiety,there was significant age difference in each factor score and total score of SCL-90 (P＜0.05).The somatization,interpersonal sensitivity,anxiety,hostility,paranoid ideation,psychoticism factor scores and total score of the "≥30 years" group was significantly higher than those of "≤24 years"and the "25-29 years" group (P＜0.05),the depression factor scores of "≥ 30 years" was significantly higher than the "≤24 years" group (P＜0.01).3) The scores of somatizations (P=0.038) and obsessive-compulsive factors (P=0.043) of doctoral students were significantly higher than those of master students.4) In different grades,there were significant differences in the scores of obsessive-compulsives,depression,anxiety,hostility,paranoid ideation factor scores and SCL-90 total score (P＜0.05).The factor scores and total score of the Grade Three were significantly higher than those of the first grade (P＜0.05),and the scores of hostilities,paranoid ideation factors and total score were significantly higher than those of the second grade (P＜0.05).5) Excluding phobic anxiety,the factor scores and total score of SCL-90 in the "peace and tranquility" group were significantly lower than those of "quarrel" group (P＜0.05).6) Except for somatization and paranoia ideation,the factor scores and total score of SCL-90 of caring group were significantly lower than those non-caring group (P＜0.05).Conclusion The psychological health of graduate students of professional degree varies with age,educational level and grade,and is influenced by collective atmosphere and mentor attitude.The differences in the characteristics of the crowd should be taken into full consideration in the mental health education of colleges and universities,and the educational model should be explored,the educational goals,contents and forms should be refined to improve the mental health level of the population.

Computer-aided diagnosis based on computed tomography (CT) image can realize the detection and classification of pulmonary nodules, and improve the survival rate of early lung cancer, which has important clinical significance. In recent years, with the rapid development of medical big data and artificial intelligence technology, the auxiliary diagnosis of lung cancer based on deep learning has gradually become one of the most active research directions in this field. In order to promote the deep learning in the detection and classification of pulmonary nodules, we reviewed the research progress in this field based on the relevant literatures published at domestic and overseas in recent years. This paper begins with a brief introduction of two widely used lung CT image databases: lung image database consortium and image database resource initiative (LIDC-IDRI) and Data Science Bowl 2017. Then, the detection and classification of pulmonary nodules based on different network structures are introduced in detail. Finally, some problems of deep learning in lung CT image nodule detection and classification are discussed and conclusions are given. The development prospect is also forecasted, which provides reference for future application research in this field.
Deep Learning ; Humans ; Lung Neoplasms ; diagnostic imaging ; Radiographic Image Interpretation, Computer-Assisted ; Reproducibility of Results ; Solitary Pulmonary Nodule ; diagnostic imaging ; Tomography, X-Ray Computed