BACKGROUND:Bone remodeling is the biological basis of orthodontic tooth movement.Type 2 diabetes mellitus leads to metabolic changes in the jaw and alveolar bone,so it is hypothesized that tooth mobility characteristics may be altered in a high-sugar environment.OBJECTIVE:To explore the impact of type 2 diabetes mellitus on orthodontic tooth movement in rats within one tooth movement cycle.METHODS:Seventy-two Sprague-Dawley rats were selected.Forty rats were randomly chosen and fed with a high-fat diet to construct a type 2 diabetes mellitus model.Thirty-two rats that were successfully modeled were randomly divided into a type 2 diabetes mellitus group(n=16)and a diabetic orthodontic group(n=16).The remaining 32 rats were randomly divided into a control group(n=16)and an orthodontic group(n=16).The rats in the orthodontic group and the diabetic orthodontic group were equipped with nickel-titanium coil spring orthodontic force application devices to move the unilateral maxillary first molars mesially with a force of 50 g.The rats were anesthetized and sacrificed on the 3rd,7th,14th,and 21st days after orthodontic treatment,and Micro-CT was used to measure the mesial displacement of the first molars and detect the changes in the bone microstructure parameters on the tension side.RESULTS AND CONCLUSION:There were significant differences in the tooth movement distances among the four groups of rats on the 3rd,7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were significant differences in bone mineral density,bone volume fraction and trabecular bone separation on the tension side among the four groups on the 7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were differences in the trabecular thickness among the four groups on the 3rd and 14th days of orthodontic treatment(P＜0.05).The diabetic orthodontic group had the smallest tension-side alveolar bone mineral density,bone volume fraction,and trabecular thickness,and the largest tooth movement distance and trabecular separation on the 21st day of orthodontic treatment.The above results indicate that type 2 diabetes mellitus adversely affects bone microstructural parameters on the tension side in orthodontic tooth movement in rats,suggesting the occurrence of an osteoporotic state.

BACKGROUND:Bone remodeling is the biological basis of orthodontic tooth movement.Type 2 diabetes mellitus leads to metabolic changes in the jaw and alveolar bone,so it is hypothesized that tooth mobility characteristics may be altered in a high-sugar environment.OBJECTIVE:To explore the impact of type 2 diabetes mellitus on orthodontic tooth movement in rats within one tooth movement cycle.METHODS:Seventy-two Sprague-Dawley rats were selected.Forty rats were randomly chosen and fed with a high-fat diet to construct a type 2 diabetes mellitus model.Thirty-two rats that were successfully modeled were randomly divided into a type 2 diabetes mellitus group(n=16)and a diabetic orthodontic group(n=16).The remaining 32 rats were randomly divided into a control group(n=16)and an orthodontic group(n=16).The rats in the orthodontic group and the diabetic orthodontic group were equipped with nickel-titanium coil spring orthodontic force application devices to move the unilateral maxillary first molars mesially with a force of 50 g.The rats were anesthetized and sacrificed on the 3rd,7th,14th,and 21st days after orthodontic treatment,and Micro-CT was used to measure the mesial displacement of the first molars and detect the changes in the bone microstructure parameters on the tension side.RESULTS AND CONCLUSION:There were significant differences in the tooth movement distances among the four groups of rats on the 3rd,7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were significant differences in bone mineral density,bone volume fraction and trabecular bone separation on the tension side among the four groups on the 7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were differences in the trabecular thickness among the four groups on the 3rd and 14th days of orthodontic treatment(P＜0.05).The diabetic orthodontic group had the smallest tension-side alveolar bone mineral density,bone volume fraction,and trabecular thickness,and the largest tooth movement distance and trabecular separation on the 21st day of orthodontic treatment.The above results indicate that type 2 diabetes mellitus adversely affects bone microstructural parameters on the tension side in orthodontic tooth movement in rats,suggesting the occurrence of an osteoporotic state.

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 the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

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 investigate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer.Methods:A retrospective case series study was conducted. The clinical data of 38 breast cancer patients with metastasis in other parts who received T-DXd treatment in Xi'an International Medical Center Hospital from August 2021 to August 2024 were analyzed. The clinical efficacy and incidence of adverse reactions in patients were recorded, comparison of clinical efficacy in stratified patients based on clinical characteristics was performed, and the progression-free survival (PFS) was analyzed using Kaplan-Meier method.Results:All 38 patients were female, with a median age [ M ( Q1, Q3)] of 55 (42, 60) years; according to the guidelines of the American Society of Clinical Oncology/College of American Pathologists, 13 cases (34.2%) were positive for human epidermal growth factor receptor 2 (HER2) and 25 cases (65.8%) were low in HER2 expression; the Eastern Cooperative Oncology Group (ECOG) physical status scores of 23 cases (60.5%) were 0-2 points and 15 cases (39.5%) were 3-4 points; the median number of T-DXd treatment lines was 4 (2,16) lines. According to the Response Evaluation Criteria in Solid Tumors 1.1, the objective response rate (ORR) of T-DXd treatment was 34.2% (13/38), and the disease control rate (DCR) was 78.9% (30/38); the ORR of patients aged ≤ 50 years old was higher than that of patients aged >50 years old [56.3% (9/16) vs. 18.2% (4/22)], patients with HER2 positive was lower than that of patients with low HER2 expression [100.0 (13/13) vs. 68.0% (17/25)], patients with previous tyrosine kinase inhibitor (TKI) treatment was higher than that of patients without TKI treatment [100.0% (12/12) vs. 69.2% (18/26)], and the DCR of patients with T-DXd treatment for ≥ 4 cycles was higher than that of patients with T-DXd treatment for 1-3 cycles [100.0% (25/25) vs. 38.5% (5/13)], and the differences were statistically significant (all P < 0.05). Among the 38 patients, 19 (50.0%) stopped medication due to disease progression, 11 (28.9%) stopped medication due to economic reasons, 1 (0.8%) stopped medication due to grade 3 nausea and vomiting, and 1 (0.8%) stopped medication due to grade 2 interstitial lung disease (ILD), while the remaining 6 (15.8%) were undergoing T-DXd treatment. The median follow-up time was 9.5 (3.9, 17.8) months, and 16 cases (42.1%) progressed and died; the median PFS time was 5.9 months (95% CI: 3.1-8.7 months). Adverse reactions were mostly grade 1-2; common hematological adverse reactions included leukopenia [18 cases (47.3%)], neutropenia [16 cases (42.1%)], thrombocytopenia [11 cases (28.9%)], and anemia [15 cases (39.5%)]. Non-hematological adverse reactions included nausea [28 cases (73.7%)], vomiting [15 cases (39.5%)], decreased appetite [20 cases (52.6%)], fatigue [22 cases (57.9%)], alopecia [22 cases (57.5%)], elevated aspartate aminotransferase [20 cases (52.6%)], and elevated alanine aminotransferase [15 cases (39.5%)] were more common. Two cases developed interstitial lung disease (ILD), classified as grade 1 and grade 2, respectively. After discontinuation of medication and treatment with methylprednisolone, they returned to normal. Conclusions:T-DXd ≥ 2 line therapy has good efficacy and safety in the treatment of HER2 positive or low expression metastatic breast cancer. Bone marrow suppression and gastrointestinal adverse reactions are the most common, and the occurrence of ILD should be noted in the treatment.

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.