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 construct a scientific and rational post competency model of human organ donation coordinators. Methods Based on the onion model, the index pool was initially constructed by literature research and behavioral event interview. The index system was screened, modified and improved using Delphi method. The weight of indexes at all levels was determined by analytic hierarchy process. Results The effective response rates of two rounds of Delphi expert inquiries were both 100%, indicating that the expert opinions were highly dependable. The experts' judgment coefficient (Ca), familiarity (Cs) and authoritative coefficient (Cr) were all above 0.7, indicating that the experts' opinions were highly reliable. The expert coordination coefficients (W) were 0.294 and 0.342 (both P<0.001), indicating that experts delivered coordinated opinions and yielded slight difference in understanding the importance of indexes. Finally, according to the "onion model" theory and experts' opinions, a set of coordinator's post competency model including 6 first-level and 55 second-level indexes was established, which comprised an index surface layer, a middle layer and a core layer. Among them, the core layer represented core professional values, the middle layer was personal quality and professional ethics and quality, and the surface layer was interpersonal communication capability, organizational cooperation capability and professional knowledge and lifelong learning capability. Conclusions The post competency model of organ donation coordinators established in this study consists of 6 first-level and 55 second-level indexes, which is highly effective and reliable.

Objective:To compare the histopathological features and treatment efficacy of different methods for metachronous early gastric cancer (MEGC) in the remnant stomach.Methods:A total of 66 patients [38 endoscopic submucosal dissection (ESD) and 28 gastrectomy] with MEGC in the remnant stomach from January 2014 to December 2020 in Drum Tower Hospital were divided into the ESD group and the gastrectomy group. The baseline characteristics, histopathological features, treatment efficacy, and cost differences of the two groups were analyzed.Results:The MEGC in the remnant stomach mostly occurred in elderly male patients, with the mean age of 69.7±8.5 years. The mean interval of the occurrence of MEGC in the remnant stomach was 6 years. As for the tumor location, the gastric body (31.6%) was the main location in the ESD group and gastric cardia (53.6%) in the gastrectomy group with significant difference ( χ2=11.07, P=0.026). The mean operation time, hospital stay, postoperative fasting time, and total treatment cost were 80.0 min, 6.0 d, 1.5 d, ￥19 436 in the ESD group and 215.0 min, 19.0 d, 6.5 d, and ￥68 665 in the gastrectomy group, respectively, with significant differences between the two groups ( P<0.05). The overall survival rate during follow-up was 76.3% in the ESD group and 71.4% in the gastrectomy group with no significant difference between the two groups ( χ2=0.736, P=0.778). In terms of postoperative complications, the incidences of bleeding and infection were 7.9% and 5.3% in the ESD group, and those of obstruction and infection were both 14.3% in the gastrectomy group. There was significant difference in the incidences of postoperative obstruction between the two groups ( P<0.05). Conclusion:ESD is safe and effective for MEGC in the remnant stomach and is better than gastrectomy in terms of the treatment cost and operation time, but the long-term efficacy still needs to be validated by large-scale prospective studies.

Objective:To develop an online interactive cytopathological training program, and to evaluate it for improving the cytopathological diagnostic ability of endoscopists in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreas.Methods:A total of 5 500 cytopathological images were collected from 194 patients with pancreatic solid mass who underwent EUS-FNA in Nanjing Drum Tower Hospital from August 2018 to August 2019. The cell type in each cytopathological picture was labeled by senior cellular pathologists, which was used to build a learning and testing platform for online interactive cytopathological training. Five endoscopists without cytopathological background were invited to participate in this training. Sensitivity, specificity, positive predictive value and negative predictive value of endoscopists in differential diagnosis of cancer and non-cancer before and after training were compared to evaluate the effect of the online interactive cytopathological training program on improving the ability of endoscopists in diagnosis of cytopathology.Results:A cytopathological training platform for endoscopists to learn and take online test was successfully built. Before training, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis of cancer and non-cancer for endoscopists were 0.55 (95% CI: 0.53-0.58), 0.32 (95% CI: 0.30-0.35), 0.43 (95% CI: 0.41-0.45), 0.44 (95% CI: 0.41-0.47) and 0.43 (95% CI: 0.42-0.45), respectively. After training, the above indicators were 0.96 (95% CI: 0.95-0.97), 0.70 (95% CI: 0.68-0.73), 0.74 (95% CI: 0.72-0.76), 0.95 (95% CI: 0.94-0.96) and 0.81 (95% CI: 0.80-0.83), respectively, which were significantly improved compared with those before ( P<0.001). Conclusion:The online interactive cytopathological training program can improve the understanding and diagnostic ability of endoscopists in pancreatic cytopathology, help to implement rapid on-site evaluation in the process of EUS-FNA, and improve the diagnostic efficiency of EUS-FNA.

Objective:To explore the application effect of scenario simulation exercise in standardized training of newly recruited nurses.Methods:Using the convenient sampling method, the newly recruited nurses in Henan Provincial People's Hospital from 2019 to 2020 were selected as the research objects. A total of 50 newly recruited nurses in 2019 were set as the control group, while 50 newly recruited nurses in 2020 were set as the observation group. The newly recruited nurses in the control group adopted traditional training methods, while the observation group added scenario simulation exercise teaching on the basis of the control group. The theoretical assessment and practical operation scores and Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) scores of the two groups were compared, and the training satisfaction was evaluated.Results:The theoretical assessment and practical operation scores, all dimensions scores of CTDI-CV and total satisfaction of training of the newly recruited nurses in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:In the standardized training of newly recruited nurses, the use of scenario simulation exercise can improve the theoretical and practical mastery of new nurses, promote the improvement of critical thinking ability of nurses and improve training satisfaction.

Objective:To investigate the clinical characteristics of elderly patients with coronavirus disease 2019(COVID-19), in order to provide scientific evidence for the diagnosis and treatment of COVID-19 in elderly patients.Methods:Clinical data of 102 patients with COVID-19 admitted to the B11 East Ward of the Zhongfaxincheng campus and the E1-3 ward of the Guanggu Campus of Tongji Hospital affiliated to Huazhong University of Science and Technology in Wuhan from 1 February 2020 to 28 February 2020 were retrospectively collected and analyzed.Patients were categorized into 2 groups: the elderly group(≥60 years old)and the young and middle-aged group(<60 years old). Differences in epidemiological features, demographics, clinical symptoms, laboratory results and imaging findings between the two groups were retrospectively analyzed.Results:Among 102 patients with COVID-19, 58 were in the elderly group(≥60 years old), with a median age of 67.0(63.8, 71.0)years old, and 44 in the young and middle-aged group(<60 years old), with a median age of 47.5(38.0, 51.8)years old.There was no significant difference in gender ratio between the two groups( χ2=0.033, P=0.855). Of 102 patients, 42.0%(21/50)had close contact with an infected person, 14.0%(7/50)were from infection clusters, and 18.0%(9/50)had suspected hospital-acquired infections.Fever and cough remained the most common symptoms, but gastrointestinal symptoms such as nausea, poor appetite, diarrhea and muscle cramps were also warning signs.Fatigue and cough were the most common presenting symptoms in elderly male patients.Bilateral patchy infiltrates(57.9%, 22/38)and ground-glass opacities(42.1%, 16/38)were the main imaging features and 42.1%(16/38)patients had multiple areas of the lungs involved.Over 50% patients had increased levels of blood glucose, D-dimer, fibrinogen, C-reactive protein, procalcitonin, multiple cytokines and neutrophil-to-lymphocyte ratio, as well as decreased levels of albumin, hemoglobin, hematocrit, lymphocytes and serum calcium.Compared with the young and middle-aged group, the elderly group had higher rates of abnormality in levels of D-dimer and serum calcium( χ2=7.067 and 4.166, P=0.008 and 0.041). Conclusions:Fever and cough are the most common symptoms in elderly patients with COVID-19.Elderly patients with COVID-19 have multiple abnormalities in clinical laboratory test results, which show a certain level of specificity compared with young and middle-aged patients.

Objective: To evaluate the feasibility and safety of magnetic tracer technique for preoperative endoscopic marking in laparoscopic surgery. Methods: In the preliminary study, a total of 8 patients with gastric (n=3) or colorectal (n=5) tumors underwent endoscopic magnetic marking before laparoscopic surgery from April to June in 2019. First, a magnet was attached to the lesion by 2 titanium clips under the endoscope. Second, during the subsequent laparoscopic operations, the other magnet was sent to the vicinity of the lesion through the laparoscopic tunnel. The magnet in the abdominal cavity was quickly attracted to the one in the gastrointestinal tract to successfully locate the lesions. Data of preoperative marking and operations of 8 patients were reviewed. Results: All 8 lesions were marked successfully, rapid and accurate intraoperative positioning was achieved. The mean time of endoscopic marking was 5.75±2.45 minutes, and the mean time of intraoperative localization was 1.94±0.56 minutes. All patients underwent laparoscopic tumor resections with accurate localization. The mean proximal and distal resection margins of colorectal tumors were 105 mm and 74 mm respectively. No complications occurred. Conclusion Magnetic tracer technique for laparoscopic localization, simple, safe and accurate for gastrointestinal lesions, can be performed without additional equipment or endoscopic procedures involved.

Objective Explore Colaizzi′s 7-step analysis in patients with senile cataract surgery subjective feelings and provide a basis for formulating targeted interventions. Methods It was a phenomenological study,and a total of 21 cases were recruited and conducted with semi-structural interviews. Results Five themes were found including fear,discomfort,insecurity,eager to communicate,a strong sense of family support. Conclusions Importance to subjective feelings, after entering the operating room to strengthen communication with the patient, increase opponents cognition, is an important measure to reduce the psychological burden of patients. And evidence-based, and scenario training before the increase,using a variety of forms of education,help to reduce patient anxiety and fear and promote patient safety.

Objective To investigate the clinical significance of neutrophil parameters Neut‐X and Neut‐Y in the diagnosis of blood stream infection(BSI) .Methods The data in106 patients with blood stream infection and 51 cases in the healthy control group were retrospectively analyzed .The results of WBC ,neutrophil percentage ,Neut‐X ,Neut‐Y and procaclitonin (PCT ) were compared .Results Neut‐X and Neut‐Y in the BSI group were 1 393 .5 ± 33 .4 and 416 .2 ± 30 .0 respectively ,which were signifi‐cantly higher than 1 371 .9 ± 32 .7 and 391 .7 ± 23 .7 in bacterial culture negative group and 1 347 .2 ± 26 .2 and 371 .9 ± 21 .5 in the healthy control group ,the differences were statistically significant (P<0 .05) .Neut‐X and Neut‐Y had good correlation with PCT . Neut‐X and Neut‐Y levels in the Gram‐negative bacterial group were higher than those in the Gram‐positive bacterial group .Conclu‐sion Neut‐X and Neut‐Y parameters in the patients with BSI are significantly increased and can be used as the assistant diagnosis parameters of blood stream infection .

3' Untranslated Regions ; Animals ; Antagomirs ; metabolism ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Mice ; MicroRNAs ; antagonists & inhibitors ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Rats ; Sequence Alignment ; Snail Family Transcription Factors ; antagonists & inhibitors ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; pathology