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 investigate the effect of oral immunotherapy with donor human milk on feeding tolerance in premature infants with very low birth weight.Methods:A total of 94 extremely low birth weight preterm infants admitted to the neonatal Intensive Care Unit of Cangzhou People's Hospital from August 2022 to February 2024 were selected, These infants were randomized at 1:1 into 2 groups (47 cases each) using random number method. The control group were given oral 0.9% sodium chloride (oral drip), while the experimental group were given donor human milk (oral drip). General information were collected, including gender, delivery method, twins or not, small for gestational age or not, birth weight, gestational age, intestinal feeding of dairy products, and so on. Total intestinal feeding time, length of hospital stay and feeding intolerance were compared between groups.Results:The total intestinal feeding time and length of hospital stay were significantly shorter in the experimental group compared with the control group ( P<0.05). The incidence of feeding intolerance in the experimental group was also lower than that in the control group ( P<0.05). Conclusion:Oral immunotherapy with donor human milk can improve the feeding tolerance in premature infants with very low birth weight and shorten the hospital stay.

Objective To observe the clinical efficacy of Tongfengke Granules combined with external treatment of TCM in acute gouty arthritis(AGA)with damp-heat accumulation type.Methods A total of 96 patients with AGA were divided into the experimental group and the control group according to random number table method,with 48 patients in each group.The control group received meloxicam treatment.On this basis,the experimental group was treated with Tongfengke Granules(1 bag at a time,three times a day,orally)combined with external therapy of TCM(once a day),and mobile continuing care.The treatment for both groups lasted for 2 weeks.The clinical efficacy of both groups was observed.Before and after the treatment,pain visual analogue scale(VAS),TCM syndrome scores,major symptom scores,and levels of serum uric acid(UA),interleukin-6(IL-6),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),platelet/lymphocyte ratio(PLR),as well as engagement in self-care ability scale(ESCA),general self-efficacy scale(GSES),negative psychological condition[self-rating depression scale(SDS),self-rating anxiety scale(SAS)]were measured.The adverse reactions in both groups were monitored.Results Totally 45 and 47 patients in the experimental group and control group were finally included respectively in the analysis.The total effective rate of the experimental group was 75.6%(34/45),while that of the control group was 63.8%(30/47),with statistical significance(P<0.05).Compared with before treatment,the VAS score and TCM syndrome score in the experimental group decreased significantly(P<0.05);after treatment,the VAS score and TCM syndrome score of the experimental group were lower than those of the control group(P<0.05).Compared with before treatment,the joint pain,joint tenderness,joint swelling,and joint mobility limitation scores in both groups were significantly decreased after treatment(P<0.05,P<0.01);after treatment,the scores of joint pain,joint tenderness,and joint swelling in the experimental group were lower than those in the control group(P<0.01).Compared with before treatment,the levels of UA,ESR,CRP and PLR in both groups decreased significantly after treatment(P<0.01);after treatment,the levels of UA,ESR,CRP and PLR in the experimental group were lower than those in the control group(P<0.05,P<0.01).Compared with before treatment,the experimental group showed significant improvement in ESCA,GSES and SAS after treatment(P<0.05,P<0.01),while the control group showed significant improvement in ESCA(P<0.01);after treatment,the ESCA and GSES of the experimental group were better than those of the control group(P<0.05,P<0.01).There was no statistical significance in safety indicators and incidence of adverse reactions between the two groups(P>0.05).Conclusion Tongfengke Granules combined with external treatment of TCM can significantly improve the clinical efficacy of AGA,reduces UA levels,significantly improves inflammatory response,and has anti-inflammatory,anti-inflammatory,and analgesic effects.

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 evaluate the long-term efficacy of endoscopic transluminal drainage(ETD) for acute pancreatitis complicated with walled-off necrosis (WON) or pancreatic pseudocyst (PPC).Methods:A total of 79 patients who were diagnosed as having WON or PPC by abdominal CT or ultrasound and treated with ETD in Nanjing Drum Tower Hospital were enrolled. Past medical records and follow-up by phone call after discharge were analyzed for long-term outcomes including endocrine and exocrine functions and long-term quality of life.Results:A total of 50 patients were enrolled, including 31 patients with infected WON/PPC and 19 patients with uninfected WON/PPC. Seventeen patients (54.84%) in the infected WON/PPC group and 11 patients (57.89%) in the uninfected WON/PPC group lost 5% or more of their weight. There were no significant differences in the proportion of cases of weight loss of 5% or more ( P=0.833), or the weight loss between the two groups (12.59±8.89 kg VS 10.91±2.47 kg, P=0.522). Only one patient in the infected WON/PPC group had chronic abdominal pain. There was no significant difference in the Izbicki score between the two groups (23.79±6.74 VS 22.03±3.21, P=0.295). None of the patients developed steatorrhea after discharge. Five patients (16.67%, 5/30) in the infected WON/PPC group and 6 patients (40.00%, 6/15) in the uninfected WON/PPC group developed endocrine insufficiency with no significant difference ( P=0.140). Greater risk of secondary diabetes resulted from higher low-density lipoprotein cholesterol ( HR=1.9, 95% CI: 1.0-3.4, P=0.044)and triglycerides ( HR=1.2, 95% CI: 1.0-1.3, P =0.029). Conclusion:ETD is safe and effective for WON and PPC. But there is possibility that patients develop secondary diabetes. Additionally, greater risk of secondary diabetes results from higher low-density lipoprotein cholesterol and triglycerides.

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 clinicopathological features of gastric adenocarcinoma of fundic gland type (GA-FG).Methods:A total of 12 patients, including 7 cases treated with endoscopic submucosal dissection (ESD), were diagnosed as having GA-FG in Nanjing Drum Tower Hospital from January 2018 to August 2019. Morphological changes were analyzed by reviewing endoscopic and pathological results. Patients were followed up after definitive diagnosis.Results:The clinical symptoms of patients with GA-FG were nonspecific. No Helicobacter pylori infection was identified. The lesions were found in the non-atrophic gastric mucosa of the upper 1/3 portion in 10 cases and middle 1/3 portion in 2 cases. Endoscopically, the most common features were whitish color (9 cases), and all lesions diameter≤1 cm. Their macroscopic types were classified as 0-Ⅰ (2 cases), 0-Ⅱa (9 cases) and 0-Ⅱc (1 case) respectively. All lesions had sharp boundary, with branching dilated blood vessels on the surface. Five in 7 cases who were treated with ESD showed submucosal invasion. Immunohistochemically, 9 cases were classified as the chief cell type , 3 as the mixed type, 11 MUC6 positive, 4 MUC5AC positive, 2 MUC2 positive, and 3 CD10 positive. P53 was detected in all 12 cases, and 9 cases had low Ki-67 staining index (<10%). The mean time of follow-up was 11 months, and 11 patients survived. Conclusion:GA-FG should be taken into consideration when the polyps are found in the upper part of the stomach, with whitish color, and branch dilated blood vessels on the surface. Excellent clinical outcomes can be achieved for GA-FG patients with ESD.

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) represents the most common mode by which children acquire HBV infection. For pregnant women with high viral load and positive hepatitis B e antigen (HBeAg), antiviral therapy during late pregnancy combined with timely and standardized inoculation of neonatal hepatitis B immunoglobulin and hepatitis B vaccine can minimize the possibility of MTCT of HBV. This review focuses on using and withdrawing antiviral drugs during pregnancy, managing postpartum hepatitis, and breastfeeding issues to further optimize the combined immunization and antiviral treatment strategies and seek the optimal solution to preventing MTCT of HBV.

Objective:To compare the efficacy and safety of endoscopic submucosal excavation (ESE) and endoscopic full-thickness resection (EFR) for intraluminal gastric stromal tumors.Methods:Data of 441 patients diagnosed as having gastric stromal tumors in Nanjing Drum Tower Hospital from June 2009 to June 2020 were retrospectively analyzed. A total of 241 patients underwent ESE (ESE group) and 200 EFR (EFR group). Epidemiological data (gender, age and body mass index), tumor size, procedure related parameters, complications, hospital stay, cost and follow-up were compared between the two groups.Results:There were no significant differences between the two groups in gender, age, body mass index, tumor size, National Institutes of Health risk grade, complete resection rate, or block resection rate ( P>0.05). Compared with the EFR group, the ESE group required less titanium clips to close defects in the stomach wall [6.0 (4.0, 6.0) VS 6.0 (5.0, 8.0), U=18 424.0. P<0.001], shorter time of first postoperative fluid intake [2.0 (1.0, 2.0) days VS 2.0 (2.0, 3.0) days, U=17 420.0, P<0.001] and hospital stay [6.0 (5.0, 8.0) days VS 7.0 (6.0, 9.0) days, U=18 906.0, P<0.001], and lower total cost [18.9 (16.4, 21.4) thousand yuan VS 20.9 (18.1, 23.8) thousand yuan, U=17 956.0, P<0.001]. Moreover, the total incidence of complications of the ESE group was lower than that of the EFR group [5.8% (14/241) VS 11.5% (23/200), χ2=4.605, P=0.032]. Patients were followed up with the median period of 45.0 months. The disease recurrence rate was 0.45% (2/441), and there were no disease-related deaths. Conclusion:The efficacy is comparable between ESE and EFR for treating intraluminal gastric stromal tumors, but ESE shows a lower incidence of complications, and requires a shorter hospital stay and lower cost.

Objective:To explore the effect of group-based exercise on physical and psychological symptom cluster in children with acute lymphoblastic leukemia during chemotherapy.Methods:32 children with acute lymphoblastic leukemia treated in the Second Hospital of Anhui Medical University were selected as study group, matched by age, gender, diagnosis, 32 acute lymphoblastic leukemia children in other tertiary hospital were included as control group. The control group were given routine care, children in the control group were carried out group-based exercise. The physical and psychological symptom status were measured by Memorial Symptom Asssessment Scale (MSAS) before and after intervention.Results:After intervention, children in the study group showed a decreased scores in pain, lack of appetite, weight loss and total physical symptom compared to the control group (1.45±0.31, 1.72±0.23, 0.56±0.11, 1.19±0.23, 1.35±0.09 vs 1.81±0.44, 1.96±0.29, 0.77±0.16, 1.66±0.39, 1.52±0.10), the differences was statically significant ( t value was 3.467-6.963, all P<0.05). After intervention, children in the study group showed a decreased scores in difficult concentrating, sad, irritable and total psychological symptom compared to the control group (1.26±0.23, 0.66±0.13, 2.11±0.33, 1.35±0.12 vs. 1.74±0.29, 0.90±0.20, 2.38±0.31, 1.51±0.13), the differences was statically significant ( t value was 3.260-7.070, all P<0.05). Conclusion:Group-based exercise can alleviate physical and psychological symptom distress in children with acute lymphoblastic leukemia during chemotherapy.