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 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 analyze the effects of nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection on inflammatory markers in peripheral blood of sinonasal inverted papilloma(SINP)and their correlations with recurrence.Methods A retrospective analysis was performed on 60 SINP patients admitted to Chengdu First People's Hospital from May 2021 to May 2023,all of whom were treated with endoscopic low temperature plasma ablation and nasal dynamical system-assisted resection;and another 60 healthy persons who underwent physical examination in the same period were enrolled and set as control group.The changes of peripheral blood inflammatory markers before and at various time points after operation were compared between control group and SINP patients.General data of patients were collected by self-made scales.The recurrence was recorded,and its influence factors were analyzed for further exploring and the correlation between recurrence and levels of peripheral blood inflammatory factors.Results Statistically significant differences between control group and SINP group were found in serum tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),eosinophilic cationic protein(ECP)and eosinophilic granulocytes(EOS)before operation,3 days and 1 month after operation(all P<0.001).Univariate analysis identified that TNF-α,CRP,IL-6,IL-8,mitotic counts,atypical hyperplasia and course of disease were associated with postoperative recurrence in SINP patients.Spearman correlation analysis showed that the postoperative recurrence in SINP patients showed no correlation with IL-6 level(P>0.05),but positively correlated with TNF-α,CRP and IL-8 levels(P<0.05).Conclusion Nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection is effective for SINP,with a low postoperative recurrence rate.Moreover,peripheral blood inflammatory markers are closely related to the occurrence and development of SINP,which may be involved in the recurrence,and there is a synergistic effect.

Objective To analyze the effects of nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection on inflammatory markers in peripheral blood of sinonasal inverted papilloma(SINP)and their correlations with recurrence.Methods A retrospective analysis was performed on 60 SINP patients admitted to Chengdu First People's Hospital from May 2021 to May 2023,all of whom were treated with endoscopic low temperature plasma ablation and nasal dynamical system-assisted resection;and another 60 healthy persons who underwent physical examination in the same period were enrolled and set as control group.The changes of peripheral blood inflammatory markers before and at various time points after operation were compared between control group and SINP patients.General data of patients were collected by self-made scales.The recurrence was recorded,and its influence factors were analyzed for further exploring and the correlation between recurrence and levels of peripheral blood inflammatory factors.Results Statistically significant differences between control group and SINP group were found in serum tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),interleukin-8(IL-8),eosinophilic cationic protein(ECP)and eosinophilic granulocytes(EOS)before operation,3 days and 1 month after operation(all P<0.001).Univariate analysis identified that TNF-α,CRP,IL-6,IL-8,mitotic counts,atypical hyperplasia and course of disease were associated with postoperative recurrence in SINP patients.Spearman correlation analysis showed that the postoperative recurrence in SINP patients showed no correlation with IL-6 level(P>0.05),but positively correlated with TNF-α,CRP and IL-8 levels(P<0.05).Conclusion Nasal endoscopic low temperature plasma ablation combined with nasal dynamical system-assisted resection is effective for SINP,with a low postoperative recurrence rate.Moreover,peripheral blood inflammatory markers are closely related to the occurrence and development of SINP,which may be involved in the recurrence,and there is a synergistic effect.

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.