ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

Objective:To predict the molecular mechanism of Biminkang Granules in the treatment of allergic rhinitis using network pharmacological methods combined with animal experiments.Methods:Active component targets and allergic rhinitis targets were screened from TCMSP, OMIM, GeneCards, TTD, DrugBank and PharmGKB databases; R language software was used to map the intersection of drug and disease targets; Cytoscape software and String platform were used to construct intersection target PPI network and conduct network topology analysis; DAVID platform was used to perform GO enrichment and KEGG pathway analysis, and perform molecular docking verification on the main active components and key targets. 32 rats were divided into a blank group of 8 and a model group of 24 using a random number table method. Model rats were induced by ovalbumin to establish an allergic rhinitis model. 24 SD rats that were successfully modeled and were randomly divided into model group, Western medicine group, and Biminkang Granules group using a random number table method, with 8 rats in each group. The Western medicine group was gavaged with 1 mg/kg of loratadine solution, the Biminkang Granules group was gavaged with 4.1 g/kg of Biminkang Granules solution, and the blank group and model group rats were gavaged with the same volume of physiological saline once a day for 2 consecutive weeks. The symptoms of rhinitis in each group of rats for 30 minutes were observed and recorded, and the pathological changes of the rat nasal mucosa were observed using HE staining. ELISA method was used to detect the levels of IL-17 and IL-6 in rat serum, and Western blot method was used to determine the expressions of TNF and STAT3 proteins in rat tissues.Results:A total of 41 target proteins of BiMinKang Dranule in the treatment of allergic rhinitis were predicted, and TNF, STAT3 and other core target proteins were obtained by PPI network topology analysis. The biological process of GO involved drug response, inflammatory response, cytokine response, etc.KEGG enrichment is involved in Th17 cell differentiation, lipid and atherosclerosis, IL-17, toll-like receptor and other pathways. Molecular docking results indicated that the main active components had good binding activity to key target proteins.Animal experiments showed that BiMinKang Dranule could improve the inflammatory symptoms of allergic rhinitis rats, down-regulate the expression of IL-17 and IL-6 in blood, and inhibit the expression of TNF and STAT3 proteins.Conclusion:Biminkang Granules can treat allergic rhinitis through multiple active components, multiple target proteins and multiple pathways, and the mechanism may be related to the regulation of Th17 cell differentiation pathway related proteins.

Objective:To develop serious games for pediatrics and to explore the effect of cultivating the clinical reasoning and reflection ability of pediatric trainee nurses.Methods:This was a non-randomized controlled trial study. The convenience sampling method was used to select 88 pediatric trainee nurses in the Second Xiangya Hospital of Central South University from April 2021 to January 2022. They were divided into the control group and the experimental group with 44 cases in each group by the method of random sampling. The control group was given clinical practice teaching in pediatrics according to the practice syllabus. Based on the teaching events of Gagne, the teaching links of serious games were designed, and teaching was carried out to the experimental group. The clinical reasoning and reflection ability, learning satisfaction and self-confidence of the two groups of pediatric trainee nurses before and after teaching were evaluated by the Self-Assessment of Clinical Reasoning and Reflection, Student Learning Satisfaction and Self-Confidence Scale, and examination scores of the two groups of pediatric trainee nurses were evaluated.Results:There was no significant difference in the clinical reasoning and reflection ability, learning satisfaction and self-confidence before teaching between the two groups( P>0.05). The total score of clinical reasoning and reflection evaluation after teaching was (101.13±6.69) points in the experimental group, which was higher than that in the control group (94.57 ± 8.86) points, the difference was statistically significant ( t=-3.92, P<0.05). The learning satisfaction and self-confidence scores after teaching were (20.82 ± 2.16), (33.20 ± 1.47) points in the experimental group, which were higher than those in the control group (19.52 ± 2.30), (31.89 ± 2.44) points, the differences were statistically significant ( t=-2.33, -3.07, both P<0.05). The scores on the theory and skill examination in the experimental group were also better than those in the control group, the differences were statistically significant ( t values were -2.59--2.14, all P<0.05). Conclusions:The serious game teaching method can effectively improve the clinical reasoning and reflection ability, practical learning satisfaction, self-confidence, and graduation performance of pediatric nursing interns, which can provide a reference for the reform of pediatric nursing practice teaching.

Objective To evaluate the clinical application of female orthotopic ileal neobladder.Methods Modified radical cysteetomy plus orthotopic ileal neobladder was performed on 19 female pa-tients with bladder cancer from June 1999 to January 2008.The mean age of the patients was 52(45-66) years,mean course of disease was 4.4 months (16 days-1.9 years).Of all the patients,there were 10 cases with grade 1,7 cases with grade 2 and 2 cases grade 3.According to the UICC stage system,5 patients were T1 stage,12 T2 and 2 T3a.All the patients received modified radical cystecto-my without resection of uterus and anterior vagina,meanwhile the nerves around urethra were protec-ted.0.8-1.2 cm proximal end of the urethra was excised and 30 cm distal ileum was used for the re-construction of the neobladder.Results Sixteen cases were followed up for 6-102 months,mean 71 months.Fifteen patients survived without disease recurrence,1 patient died of myocardial infarc-tion 17 months postoperation.The daytime and night continent rate was 100$,93% at 9 months postoperative.The average voiding volume of the 15 patients was 519.0 ml.The average residual vol-ume was 29.2 ml,and Qmax was 18.6 ml/s.The average filling and voiding pressure was 16.7 cm H2O and 53.0 cm H2O.Intravenous urography showed slight hydronephrosis in 1 case.Conclusion Female orthotopic ileal neobladder could be a good choice because of the continence,fewer complica-tions,lower pressure and enough bladder capacity.