Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To explore the value of fast susceptibility weighted imaging (SWI) generated by a deep learning model in assessment of acute ischemic stroke (AIS).Methods:From January 2019 to January 2021, 118 AIS patients [75 males and 43 females, aged 23-100 (66±14) years] who underwent MR examination and SWI sequence scanning within 24 h of symptom onset in the First Medical Center of PLA General Hospital were retrospectively analyzed. MATLAB ′s randperm function was used to divide 118 patients into a training set of 96 cases and a test set of 22 cases at a ratio of 8∶2. Fourty-seven AIS patients [38 males and 9 females, aged 16-75 (58±12) years] from one center of a multicenter study were selected to build the external validation set. SWI image and filtered phase image were combined into complex value image as full sampling reference image. Undersampled SWI images were obtained by retrospective undersampling of reference fully sampled images, and the undersampling multiple was five times which could save 80% of the scanning time, then the complex-valued convolutional neural network (ComplexNet) was used to develop reconstruct fast SWI. Interclass correlation coefficient (ICC) or Kappa tests were used to compare the consistency of image quality and the diagnostic consistency for the presence of susceptibility vessel sign (SVS), cerebral microbleeds and asymmetry of cerebral deep medullary veins (DMVs) in AIS patient on fully sampled SWI and fast SWI based on ComplexNet.Results:In test set, score of image quality was 4.5±0.6 for fully sampled SWI image and 4.6±0.7 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.86, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.79, P<0.05), microbleeds (Kappa=0.86, P<0.05), and DMVs asymmetry (Kappa=0.82, P<0.05) in AIS patients. In the external validation set, score of image quality was 4.1±1.0 for fully sampled SWI image and 4.0±0.9 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.97, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.74, P<0.05), microbleeds (Kappa=0.83, P<0.05), and DMVs asymmetry (Kappa=0.74, P<0.05) in AIS patients. Conclusions:Deep learning techniques can significantly accelerate the speed of SWI, and the consistency of image quality and detected AIS signs between fast SWI based on ComplexNet and fully sampled SWI is good. The fast SWI based on ComplexNet can be applied to the radiographic assessment of clinical AIS patients

Objective:To investigate and analyze the basic occupational situation of Chinese radiotherapists and to provide references for the development and construction of the radiation therapist team in China.Methods:Between May 7, 2021 and June 15, 2021, this survey was conducted using a self-designed questionnaire, which was distributed and collected in the form of online survey to conduct a statistical analysis of the basic situation of radiotherapists in 30 provincial-level administrative regions in China.Results:A total of 2 928 valid questionnaires were collected from 30 provincial-level administrative regions. The ratio of male to female and average age of the participants were 69∶31 and 35 years (18-65), respectively. According to the survey result, 84.7% of the participants came from Tertiary A-level hospitals. In terms of educational background, the participants with doctoral, master, undergraduate, junior-college, and technical-secondary degrees accounted for 0.2%, 6.9%, 76.6%, 14.9%, and 1.4%, respectively. In terms of title, full senior technologists, associate senior technologist, technologist-in-charge, technologist, and technician in the participants accounted for 0.5%, 5.8%, 32.5%, 52.2%, and 8.2%, respectively. The participants with years of employment of 0-, 5-, 10-, 20-y accounted for 33.74%, 25.79%, 25.51%, and 14.96%, respectively. The majors of the participants included medical imaging/imaging technology (45.9%), clinical medicine (19.1%), and biomedical engineering (11.9%).Conclusions:Chinese radiotherapists tend to be younger and are rapidly increasing in number. Employers should attach importance to the career planningand continuing education of radiotherapists to improve their technical skills, in order to fully satisfy the demand for radiotherapists in the new era.

Objective To investigate the effect of CYP3A5 and MDR1 gene polymorphisms on blood concentration of tacrolimus and creatinine level in uremic patients during the early phase after kidney transplantation in real clinical practice. Methods 131 patients who underwent kidney transplantation for the first time with triple immunotherapy based on tacrolimus in single-center from 2013 to 2017 were enrolled for retrospective study. Tacrolimus daily dose, blood concentration, blood concentration-to-dose ratio, and serum level were compared according to the various genotypes of CYP3A5 and MDR1 polymorphisms in renal transplantation recipients, respectively. Results The dosage of tacrolimus in CYP3A5*3/*3 (GG) kidney transplantation recipients within 4 weeks after kidney transplantation was lower than those of CYP3A5*1/*1 (AA) and CYP3A5*1/*3 (AG). The serum creatinine levels of patients whose tacrolimus concentration in the range of 10-13 ng/ml were close to the normal value. Conclusion CYP3A5 gene polymorphism affects the blood concentrations of tacrolimus in renal transplant recipients. No association has been found between the blood concentrations of tacrolimus and MDR1 gene polymorphism. Tacrolimus concentration in the range of 10-13 ng/ml might contribute to restore the early kidney graft function.

Objective:To investigate the manpower allocation and scientific research level of radiotherapists in radiotherapy units in mainland China, aiming to provide reference for the construction of radiotherapist teams.Methods:The questionnaire was designed and produced by the organizer, released in the professional committee, professional group and other channels of the radiotherapist industry, and filled out by the technical person in charge of the radiotherapy unit through the online questionnaire survey. The collection time started from mid-May 2021 to mid-June 2021.Results:A total of 558 effective questionnaires filled out by radiotherapy units. The radiotherapy institutions participating in the survey had a total of 5500 radiotherapists, including 3702 males and 1798 females, 3754 with a bachelor's degree, 371 who are currently studying or have obtained a master's degree, 21 who are currently studying or have already obtained a doctoral degree, 3642 with junior or lower titles, 1580 with intermediate titles, and 278 with senior titles. In 2020, radiotherapists from 193 units published articles, those from 81 units received project funding, and those from 56 units obtained patent authorization, and those from 15 units had scientific research transformation. The participating units had a total of 1080 large-scale radiation therapy equipment. In 2020, the daily average number of radiotherapy patients was 47 900, the average daily load of accelerator patients was 44.35, and the average workload index per capita was 8.71. The average daily radiotherapy patients in county-level or below, city-level, and provincial-level institutions were 25.78, 65.68, and 173.76, respectively, and the per capita workload index was 5.22, 8.09, and 10.11.Conclusions:Compared with the 2019 survey, the educational background of radiotherapists in mainland China has been improved, and the title structure has been optimized to a certain extent, and the workload of large-scale radiotherapy units is larger than that of grass-roots units.

OBJECTIVE: To investigate the pre-treatment preventive maintenance and quality control procedure of MRI system and transcranial MRI-guided focused ultrasound (TcMRgFUS) treatment system by monitoring quality control of these two systems. METHODS: The general performance index and image quality control index of MRI system, as well as the quality assurance program of TcMRgFUS EXABLATE 4000 system were tested and recorded. RESULTS: The general performance index and image quality control index of MRI system met requirements. CONCLUSIONS Through system detection, the system performance could be monitored, ensuring the accuracy and safety of surgery.
Hyperthermia, Induced ; Magnetic Resonance Imaging ; Phantoms, Imaging ; Quality Control

Objective:To compare the difference between active breathing coordinator (ABC) technique and free breathing (FB) mode combined with bodyfix stereotactic radiotherapy (SBRT) for chest tumors.Methods:40 thoracic tumor patients receiving SBRT were randomly selected and divided into the ABC technique group and FB model group. After fixation with bodyfix fixing devices in two groups, cone-beam CT (CBCT) scan images before each SBRT were matched with the plan reference images. The setup errors in the left-right (LR), superior-inferior (SI) and anterior-post (AP) directions were obtained. Then, the setup errors were corrected. SBRT was performed and split intra-fraction CBCT was conducted simultaneously, which was repeated until the end of treatment.Results:In the ABC technique group, the setup errors in the LR, SI and AP directions were (0.25±0.21) cm, (0.28±0.21) cm, and (0.21±0.24) cm, significantly less compared with (0.31±0.22) cm, (0.32±0.21) cm and (0.37±0.23) cm in the FB model group (all P<0.05). The V 30Gy of the heart, the V 20Gy and V 30Gy of the lung in the ABC technique group were significantly less than those in the FB model group (0.31%∶7.35%; 24.5%∶32.9%; 19.5%∶25.8%, all P<0.05). Conclusions:ABC technique combined with bodyfix fixation device may be superior to FB mode in SBRT for chest tumors, which remains to be validated by subsequent studies with large samples.

Objective To compare the dosimetric parameters between the use of Tandem and Ring (TR;Nucletron#090.617) or Tandem and Ovoid (TO;Nucletron#189.730) applicators during three-dimensional (3D) high-dose rate (HDR) brachytherapy (BT) for cervical cancer.Methods The records of 40 cervical cancer (ⅡB-ⅣA) patients treated with 3D-image-guided HDR-BT were reviewed.Of these 40 patients, 20 were treated with the TO applicator, and 20 with the TR applicator.The D100% and V150% of the clinical target volume (CTV) and the D2 cc of organs at risk (OAR)(the rectum, bladder, and small intestine) during 3D-HDR-BT using TO and TR were compared using the independent sample t-test.ResultsOverall metrics:CTV volume:66.04±13.86 cm3(TR) vs.65.67±15.08 cm3(TO)(P=0.052);CTV D100:3.71±0.34 Gy (TR) vs.3.37±0.49 Gy (TO)(P=0.016);CTV V150%:0.54±0.02(TR) vs.0.56±0.04(TO)(P=0.034);rectum D2 cc:3.38±0.30 Gy (TR) vs.2.95±0.80 Gy (TO)P=0.037);bladder D2 cc:4.33±0.39 Gy (TR) vs.2.93±1.27 Gy (TO)(P=0.00);and small ntestine D2 cc:3.04±1.02 Gy (TR) vs.3.41±0.57 Gy (TO)(P=0.171).Conclusions TR has better CTV coverage than TO during 3D HDR brachytherapy for cervical cancer.In addition, D2 cc of the rectum and bladder were both igher with TR than with TO, though there is no significant dosimetric difference in the small intestine between the two applicators.Therefore, tumor location, extent of invasion, and vaginal conditions should be considered when selecting the suitable pplicator for the treatment of cervical cancer.

Objective To observethe clinical efficacy of comprehensive acupuncture treatment in treating primary open-angle glaucoma, and to objectively evaluate the therapeutic efficacy.Method Twenty-eight patients (53 eyes) who received acupuncture treatment were recruited. By adopting a self-control design, the changes of intraocular tension, mean defect (MD) of vision field, mean sensitivity (MS), vision, and score of Quality of Life Scale for Patients with Visual Impairment (QLSPVI) were observed after 3-month acupuncture treatment.ResultThe intraocular tension of the 28 patients declined obviously after the treatment (P<0.01); MD, MS and vision didn't show significant improvements after the treatment (P>0.05); the QLSPVI score dropped significantly after the treatment (P<0.01);the total effective rate was 86.8%; the therapeutic efficacy wasn't correlated with age, disease duration, and treatment duration (P>0.05).Conclusion Acupuncture treatment can effectively reduce the intraocular tension, control the deterioration of MD and MS, maintain the level of vision, and enhance the quality of life of patients with primary open-angle glaucoma; with the same disease duration, the longer the treatment, the better the therapeutic efficacy.

[ Abstract] Objective To investigate the clinical efficacy of preoperative three-dimensional radiotherapy (3DRT) with or without concurrent chemotherapy for esophageal carcinoma.Methods We retrospectively analyzed 103 esophageal carcinoma patients who received preoperative 3DRT with or without concurrent chemotherapy from 2004 to 2014 in Cancer Hospital CAMS.The median radiation dose was 40 Gy, and the TP or PF regimen was adopted for concurrent chemotherapy if needed.The overall survival (OS) and disease-free survival ( DFS) were calculated by the Kaplan-Meier method, and the survival difference and univariate prognostic analyses were performed by the log-rank test.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The number of patients followed at 3-years was 54.The 3-year OS and DFS rates were 61.1% and 54.9%, respectively, for all patients.There were no significant differences between the 3DRT and concurrent chemoradiotherapy (CCRT) groups as to OS (P=0.876) and DFS (P=0.521).The rates of complete, partial, and minimal pathologic responses of the primary tumor were 48.0%, 40.2%, and 11.8%, respectively.There were significant differences in OS and DFS between the complete, partial, and minimal pathologic response groups (P=0.037 and 0.003). No significant difference in pathologic response rate was found between the 3DRT and CCRT groups (P=0.953).The lymph node metastasis rate was 26.5%, and this rate for the complete, partial, and minimal pathologic response groups was 14%, 30%, and 67%, respectively, with a significant difference between the three groups (P=0.001).The OS and DFS were significantly higher in patients without lymph node metastasis than in those with lymph node metastasis (P=0.034 and 0.020).The surgery-related mortality was 7.8% in all patients.Compared with the 3DRT group, the CCRT group had significantly higher incidence rates of leukopenia (P=0.002), neutropenia (P=0.023), radiation esophagitis (P=0.008), and radiation esophagitis ( P=0.023).Pathologic response of the primary tumor and weight loss before treatment were independent prognostic factors for OS and DFS (P=0.030,0.024 and P=0.003,0.042). Conclusions Preoperative 3DRT alone or with concurrent chemotherapy can result in a relatively high complete pathologic response rate, hence increasing the survival rate.Further randomized clinical trials are needed to confirm whether preoperative CCRT is better than 3DRT in improving survival without increasing the incidence of adverse reactions.