Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective:To investigate microbial ecology in restored milk (RM) -donor human milk (DHM) supplemented with mother's own milk (MOM)-under varying MOM ratios, incubation temperatures, and durations. Methods:This in vitro controlled study utilized breast milk samples collected from mothers of preterm infants (<37 weeks) admitted to the Neonatal Intensive Care Unit of Chongqing Health Center for Women and Children between December 2024 and March 2025, including five MOM samples and one DHM sample. Each MOM sample was mixed with DHM at 10% (RM-10 group) or 30% (RM-30 group) volume ratios. Samples were incubated at room temperature (23-26 ℃) and 37 ℃ for 1 h and 4 h, followed by collection. Microbial α-diversity (Chao/Shannon indices), β-diversity (principal co-ordinates analysis), and taxonomic composition (phylum/genus) were analyzed via high-throughput sequencing. Statistical analysis included analysis of variance and the Kruskal-Wallis H test. Results:No statistically significant differences in the Chao index or Shannon index were observed between the RM-10 and RM-30 groups across different incubation times and temperatures ( H or F values=7.61 and 93.20, respectively; both P>0.05). At 37 ℃, the microbial composition of the RM-30 group at both 1 h and 4 h showed no significant difference compared to the initial MOM samples ( R=－0.018, P=0.540), with Firmicutes abundance restored to 65%-90% of the initial MOM level. At room temperature, incubation of the RM-30 group partially restored microbial communities (50%-60%), but induced overgrowth of Proteobacteria (e.g., Pseudomonas, Acinetobacter). Incubation of the RM-10 group at 37 ℃ for 1 h and 4 h also showed no significant difference in microbial composition compared to the initial MOM ( R=－0.004, P=0.442). However, at room temperature, Proteobacteria consistently increased in the RM-10 group samples, and significant differences in microbial composition compared to initial MOM were observed at both 1 h and 4 h ( R=0.179, P=0.027). Conclusion:Under the experimental conditions of this study, preliminary evidence suggests that incubating a blend of DHM and 30% MOM at 37 ℃ for 1 h or 4 h may modulate the microbial composition toward a potentially beneficial profile.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To investigate microbial ecology in restored milk (RM) -donor human milk (DHM) supplemented with mother's own milk (MOM)-under varying MOM ratios, incubation temperatures, and durations. Methods:This in vitro controlled study utilized breast milk samples collected from mothers of preterm infants (<37 weeks) admitted to the Neonatal Intensive Care Unit of Chongqing Health Center for Women and Children between December 2024 and March 2025, including five MOM samples and one DHM sample. Each MOM sample was mixed with DHM at 10% (RM-10 group) or 30% (RM-30 group) volume ratios. Samples were incubated at room temperature (23-26 ℃) and 37 ℃ for 1 h and 4 h, followed by collection. Microbial α-diversity (Chao/Shannon indices), β-diversity (principal co-ordinates analysis), and taxonomic composition (phylum/genus) were analyzed via high-throughput sequencing. Statistical analysis included analysis of variance and the Kruskal-Wallis H test. Results:No statistically significant differences in the Chao index or Shannon index were observed between the RM-10 and RM-30 groups across different incubation times and temperatures ( H or F values=7.61 and 93.20, respectively; both P>0.05). At 37 ℃, the microbial composition of the RM-30 group at both 1 h and 4 h showed no significant difference compared to the initial MOM samples ( R=－0.018, P=0.540), with Firmicutes abundance restored to 65%-90% of the initial MOM level. At room temperature, incubation of the RM-30 group partially restored microbial communities (50%-60%), but induced overgrowth of Proteobacteria (e.g., Pseudomonas, Acinetobacter). Incubation of the RM-10 group at 37 ℃ for 1 h and 4 h also showed no significant difference in microbial composition compared to the initial MOM ( R=－0.004, P=0.442). However, at room temperature, Proteobacteria consistently increased in the RM-10 group samples, and significant differences in microbial composition compared to initial MOM were observed at both 1 h and 4 h ( R=0.179, P=0.027). Conclusion:Under the experimental conditions of this study, preliminary evidence suggests that incubating a blend of DHM and 30% MOM at 37 ℃ for 1 h or 4 h may modulate the microbial composition toward a potentially beneficial profile.

Objective:To explore the current status and training needs of nurses' knowledge, belief, and behavior regarding the good limb positioning in stroke patients with hemiplegia.Methods:From November to December 2023, convenience sampling was used to select 1 708 nurses from 30 ClassⅢ hospitals in 17 provinces across the country, who worked in departments such as Neurology and Rehabilitation. The self-designed General Information Questionnaire, Knowledge, Belief and Behavior Questionnaire for Putting Good Limb Position in Clinical Nurses, and self-designed Training Status and Needs Questionnaire for Good Limb Positioning were used for online surveys. Multiple linear regression was used to analyze the influencing factors of nurses' knowledge, belief, and behavior in good limb positioning.Results:A total of 1 622 valid questionnaires were collected. Nurses scored (135.64±25.93) on the Knowledge, Belief and Behavior Questionnaire for Putting Good Limb Position in Clinical Nurses, with the lowest score rate of 65.65% in the knowledge subscale and the highest score rate of 88.16% in the belief subscale. Multiple linear regression analysis showed that education level, working years, department, and whether they received training were the influencing factors of nurses' knowledge, belief, and behavior in good limb positioning ( P<0.05). 92.23% (1 496/1 622) of nurses were willing to receive training on good limb positioning, and 70.10% (1 137/1 622) of nurses participated in training on good limb positioning. Conclusions:Nurses generally have a moderate level of knowledge, belief, and behavior towards the good limb positioning, with room for improvement in their knowledge and behavior. However, their belief is relatively positive. Nursing managers should actively carry out training on good limb positioning based on the different characteristics and needs of nurses, improve their ability to good limb positioning.

Objective:To analyze the clinical characteristics of pediatric patients with Beh?et′s disease.Methods:The clinical characteristics of 86 newly diagnosed children with Beh?et′s disease admitted to the rheumatology department of Beijing Children′s Hospital from July 2015 to December 2020 were analyzed retrospectively. Statistical product and service solutions (SPSS) 26 was used for statistical analysis. The normal distribution of measurement data is expressed in Mean± SD, and the non normaldistribution of measurement data was expressed in median(minimum, maximum). The counting data was expressed in frequency (cases) and percentage. Results:There was no gender difference in the incidence of Beh?et′s disease in 86 children.The age of onset was 0.1~15.9 years, with an average of (7±4) years, and the age of diagnosis was 1.3~16.6 years, with an average of (10±4) years.The course of disease from onset to diagnosis was 0.5~168 months, with a median course of 21 months. Among 86 cases, 52 cases (60.5%) showed the most common oral ulcer at the onset, followed by 19 cases (22.1%) with fever. In terms of clinical manifestations: the most common clinical manifestation was oral ulcer in 82 cases (95.3%), followed by fever in 58 cases (67.4%), and gastrointestinal symptoms in 44 cases (51.2%). The common manifestation of digestive system involvement was abdominal pain and diarrhea. Ten cases (11.6%) had ocular symptoms, 13 cases (15.3%) had vascular involvement, and 3 cases (3.5%) had pulmonary involvement. Fourteen cases (16.2%) had family history. Fourty seven patients (54.7%) had elevated leukocyte, 65 patients (75.6%) had elevated CRP and 72 patients (83.7%) had elevated ESR.Conclusion:Beh?et′s disease in children is usually insidious in onset and infants may suffer from this disease. Oral ulcer is the most common clinical manifestation, followed by fever. For patients with fever of unknown cause, Beh?et′s disease should be noted. In terms of involvement of important organs, digestive tract involvement is more common in childhood, followed by large blood vessels and eyes.