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.

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Objective To explore the application value of Xuanbai Chengqi Decoction combined with enteral nutrition support in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)guided by the theory of simultaneous treatment of lung and intestine.Methods A total of 92 patients with AECOPD were randomly divided into an observation group and a control group,46 cases in each group.Both groups were given routine symptomatic treatment.In addition,the control group was given enteral nutrition support intervention,and the observation group was given Xuanbai Chengqi Decoction combined with enteral nutrition support intervention.The course of treatment lasted for two weeks.The changes in the nutritional parameters such as serum albumin(ALB),prealbumin(PA),and transferrin(TF),and in the distribution of intestinal flora of the two groups were observed before and after treatment.After treatment,the clinical efficacy and the incidence of adverse reactions were compared between the two groups.Results(1)After two weeks of treatment,the total effective rate of the observation group was 97.83％(45/46),and that of the control group was 82.61％(38/46).The comparison between the two groups(tested by chi-square test)showed that the therapeutic efficacy of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the serum levels of nutritional parameters of ALB,PA and TF in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of serum ALB,PA and TF levels in the observation group was significantly superior to that in the control group,the differences being statistically significant(P＜0.05 or P＜0.01).(3)After treatment,the number of Lactobacillus and Bifidobacterium strains of intestinal flora in the two groups was significantly higher than that before treatment(P＜0.05),and the number of Enterococcus strain was significantly lower than that before treatment(P＜0.05).The increase in the number of Lactobacillus and Bifidobacterium strains and the decrease in the number of Enterococcus strains in the observation group were significantly superior to those in the control group,and the differences were statistically significant(P＜0.05 or P＜0.01).(4)The incidence of adverse reactions in the observation group was 4.35％(2/46),which was significantly lower than that in the control group(19.57％,9/46).The difference between the two groups was statistically significant(P＜0.05).Conclusion Significant clinical efficacy has been achieved after the application of Xuanbai Chengqi Decoction combined with enteral nutrition support in treating AECOPD patients with lung heat and bowel excess syndrome guided by the theory of simultaneous treatment of lung and intestine.The combined therapy is effective on improving the nutritional status and intestinal flora imbalance of patients,and reducing the incidence of adverse reactions.

Objective To explore the mechanism of'Wenyang Tongmai'(warming yang to unblock meridians)moxibustion in preventing and treating atherosclerosis.Methods Ten C57BL/6J mice fed with normal diet were set as blank group.Thirty ApoE-/-mice were fed with high-fat diet to establish atherosclerosis model,and were randomly divided into model group,Simvastatin group and moxibustion group,with 10 mice in each group.The intervention began on the first day of modeling.The mice in the moxibustion group were given moxibustion at Danzhong(RN17),Shenque(RN8),Neiguan(PC6),Xuehai(SP10)points,and the Simvastatin group was given Simvastatin distilled water suspension by gavage for 12 weeks.After administration,the pathological structure of thoracic aorta in mice was observed by hematoxylin-eosin(HE)staining method.The ultrastructure of thoracic aortic endothelial cells in mice was observed by transmission electron microscopy.The levels of serum tumor necrosis factor α(TNF-α),intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)in mice were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of silent information regulator 1(SIRT1)and forkhead box O3a(FOXO3a)in thoracic aorta were detected by real-time quantitative polymerase chain reaction(qRT-PCR).The protein expression levels of SIRT1 and FOXO3a in thoracic aorta were detected by Western Blot.Results Compared with the blank group,the pathological changes of thoracic aorta and vascular endothelial cells in the model group were obvious,the levels of serum inflammatory factor TNF-α,ICAM-1 and VCAM-1 were increased(P＜0.05 or P＜0.01),the mRNA and protein expressions of SIRT1 in thoracic aorta were decreased(P＜0.01),and the mRNA and protein expressions of FOXO3a had no significant difference(P＞0.05).Compared with the model group,the thoracic aorta and vascular endothelial cell structure of the mice in the Simvastatin group and the moxibustion group were obviously improved,the levels of serum TNF-α,ICAM-1 and VCAM-1 were decreased(P＜0.05),the mRNA and protein expressions of SIRT1 in the thoracic aorta were increased(P＜0.05 or P＜0.01),and the mRNA and protein expressions of FOXO3a had no significant difference(P＞0.05).There was no significant difference in the above indexes between the Simvastatin group and the moxibustion group(P＞0.05).Conclusion'Wenyang Tongmai'moxibustion can prevent and treat atherosclerotic in rats via regulating and controlling SIRT1/FOXO3a signaling pathway to reduce inflammatory response.