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 the association between famine exposure in different life cycles and the risk of central obesity. Methods A total of 2234 spermanent residents were recruited to participate in the China Multi-Ethnic Cohort (CMEC) Study ,they were grouped into four birth cohorts of fetal-exposed (born between January 1,1959, and December 31,1961,95 cases), childhood-exposed (born between January 11,949, and December 31,1958,533 cases), adolescence/adult-exposed (born between January 1,1931, and December 31,1948,256 cases),unexposed cohorts（born after January 1, 1975，871 cases).we used logistic regression model to assess the effect of famine exposure on central obesity in adulthood. Results After adjusting for confounding factors, females in the fetal/infant exposure group（OR=3.283,95%CI：1.472～7.321,P＜0.001）、childhood- exposed group (OR=3.557,95%CI：2.374～5.313,P＜0.001) and adolescence/adult-exposed group (OR=5.785，95%CI：3.536～9.492，P＜0.001) had a higher risk of adult central obesity than the control group.After excluding the subjects with coronary heart disease、cancer、diabetes、stroke or obesity, sensitivity analysis was carried out. The risk of central obesity increased in the female / fetal、childhood、adolescent / adult exposure group,which was unfound in males. Conclusion Severe famine exposure in fetal/infant、childhood and adolescence/adulthood can increase the risk of central obesity in adulthood in females. Therefore, the prevention and control of central obesity in female should start from the early life.

Epilepsy is a common chronic neurological disease, and its comorbidity has attracted more attention.The proportion of epileptic children with mental disorders is also increasing year by year.Among them, children with epilepsy have more depression and anxiety disorders.Repeated seizures can easily cause depression and anxiety, and depression and anxiety can also induce epilepsy, thus the two affect each other.The assessment, screening, diagnosis and intervention of comorbid depression and anxiety in children with epilepsy have become an important part of clinical practice.This review summarized the relationship between epilepsy and depression and anxiety disorders in children, and its research progress on pathogenesis, clinical diagnosis, evaluation and treatment.

Abstract OBJECTIVE To establish an efficient and simple HPLC-MS/MS method for determination of flucloxacillin in newborn plasma, and to investigate the interaction between ambroxol and flucloxacillin in newborns. METHODS The samples were analyzed by API4000 HPLC-MS/MS. Ultimate XB-C18 column(2.1 mm×100 mm, 5 μm) were carried out. The mobile phase was composed of water-0.1% formic acid(A) and acetonitrile-0.1% formic acid(B). The quantitative analysis of the ion transitions were monitored at m/z 452.6→284.2 for flucloxacillin and m/z 821.4→397.3 for rifampicin(internal standard). RESULTS The linear range of flucloxacillin under this analysis method was 0.20-80 ng·mL-1, and the lower limit of quantification was 0.20 ng·mL-1; The intra-day and inter-day precision of flucloxacillin were both less than 8.23%; The extraction recovery was in the range of 85.3%-89.2%, and the matrix effect was between 89.3%-92.3%; The stability of plasma samples was good under conditions of 12 h at room temperature, 4 h at room temperature after treatment, repeated freeze-thaw for 3 times, and -20 ℃ freezing for 30 d. The results of clinical samples indicated that the combination of ambroxol could significantly increase the blood concentration of flucloxacillin. CONCLUSION The established HPLC-MS/MS method is accurate, sensitive and can be used for the determination of flucloxacillin concentration in neonatal plasma. The results of clinical samples indicate that ambroxol can significantly increase the blood concentration of flucloxacillin. There are drug interactions between ambroxol and flucloxacillin.

Objective:To summarize the clinical and laboratory characteristics of infectious mononucleosis (IM) in children.Methods:Clinical features and laboratory results of 270 cases with IM admitted to the Department of Pediatrics in Strategic Support Force Medical Center of People′s Liberation Army from January 2012 to December 2020 were retrospectively analyzed. χ2 test was used for comparison between groups. Results:IM mainly occurred in children aged 5 months to 18 years old in autumn and spring.The highest incidence rate (105 cases, 38.9%) was 3-<6 years old (preschoolers). There were 253 cases (93.7%) with fever, 266 cases (98.5%) with adenopharyngitis, 196 cases (72.6%) with tonsil pseudomembrane or exudation, 248 cases (91.9%) with cervical lymphadenopathy, 92 cases (34.1%) with eyelid edema, 202 cases (74.8%) with nasal obstruction, 124 cases (45.9%) with nasal obstruction and snoring, 24 cases (8.9%) with rash, and 112 cases (41.5%) with splenomegaly.A total of 225 cases (83.3%) presented with typical triplets of IM (fever, adenopharyngitis and cervical lymphadenopathy). Sixty-two IM patients were complicated with pulmonary infections and 3 cases with diarrhea.The main co-infection pathogens in children with IM were Mycoplasma pneumonia (MP) (79 cases, 29.3%), influenza A or B virus (34 cases, 12.6%), Streptococcus pneumonia (SP) (18 cases, 6.7%), adenovirus (22 cases, 8.1%) and cytomegalovirus (3 cases, 1.11%). A total of 46 cases (17.0%) had multiple infections.Laboratory test results suggested that absolute lymphocyte count ≥5.0×10 9/L was found in 199 cases (73.7%), and abnormal lymphocyte ratio >0.10 was found in 225 cases (83.3%). Some children had elevated transaminase levels.Epstein-Barr virus capsid antigen-immunoglobulin M (EBV-VCA-IgM) was positive in 249 cases (92.2%), Epstein-Barr virus capsid antigen-immunoglobulin G (EBV-VCA-IgG) was positive in 238 cases (88.1%), and Epstein-Barr virus nuclear antigen-immunoglobulin G (EBV-NA-IgG) was negative in all cases.EBV-VCA-IgG showed low affinity in all cases (<40%). EBV DNA tests of peripheral blood plasma were carried in 153 cases, of which 118 cases (77.1%) were positive. Conclusions:EBV related IM mainly attacks preschoolers.Most patients are presented with typical triplets of IM.Eyelid edema, nasal obstruction, snoring, splenomegaly and elevated transaminase levels are prevalent in IM children.Most cases have a favorable prognosis.

Objective:To investigate the efficacy and safety of plasma exchange(PE) in the treatment of autoimmune hemolytic anemia in children.Methods:The data from 8 hospitals in China during November 2014 to April 2017 were collected, and the clinical characteristics of PE in children with AHA were analyzed retrospectively.Results:A total of 21 children with AHA were included in the study, including 17 cases from PICU and 4 cases from pediatric kidney ward, with 11 boys and 10 girls, and the median age was 3.64(0.25, 11.10)years old, and median hospital stay was 12(4, 45)days.There were 15 cases(71.4%) with infection, 2 cases(9.5%)with autoimmune diseases, 4 cases(19.0%) with unknown.Consciousness disturbance occurred in 4 patients before replacement and recovered to normal after PE.The volume of blood decreased in two cases(9.5%) and completely relieved.There were 20 cases of anemia (95.2%), 15 cases were normal after PE, and 5 cases were improved.Jaundice occurred in 18 cases (85.7%), 12 cases were normal after PE, 6 cases were improved.Hepatosplenomegaly was found in 11 cases, 10 cases were normal after PE, 1 case was improved.After PE, the hemoglobin and red blood cell count increased, while the total bilirubin, indirect bilirubin, urea nitrogen and lactate dehydrogenase decreased, there were significant differences between pre-and post-replacement ( P<0.05). Only 1 case had allergic reaction, which was improved after symptomatic treatment, and PE was continued.After PE, 2 cases (9.5%) had complete remission, 16 cases (76.2%) had partial remission and 3 cases (14.3%) had been discharged. Conclusion:PE therapy can obviously improve the clinical symptoms and laboratory indexes of children with AHA who have failed to respond to conservative treatment.It can be used as a treatment measure for children with severe AHA and has a good safety.

Objective:To evaluate the effect of orexin A on morphine-induced gastrointestinal dysfunction in mice.Methods:Forty SPF C57B/6 mice, aged 6-8 weeks, half male and half female, weighing 18-22 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), morphine group (group M) and morphine + different doses of orexin A groups (MOH, MOM and MOL groups). Normal saline 8 ml/kg was subcutaneously injected daily in group C, morphine 6 mg/kg was subcutaneously injected daily in the other four groups, and orexin A 75, 50 and 25 μg/kg were subcutaneously injected daily for 10 days at the same time in MOH, MOM and MOL groups.The fetal water content was calculated and averaged daily.After the last administration, the mice were gavaged with black nutrient paste, and the gastric emptying rate and small intestinal propulsion rate were detected 30 min later.Blood samples were collected from the orbit, and the concentration of serum gastrin (GAS) was detected by enzyme-linked immunosorbent assay.The mice were then sacrificed, and colon tissues were removed for determination of c-kit positive cell area (by immunohistochemistry) and expression of c-kit, substance P (SP) and neural nitric oxide synthase (nNOS) in colon tissues (by Western blot). Results:Compared with group C, the rate of fecal water content, gastric emptying rate, small intestinal propulsion rate and serum GAS concentration were significantly decreased, the area of c-kit positive cells was decreased, and the expression of c-kit and SP was down-regulated, and the expression of nNOS was up-regulated in group M ( P<0.05). Compared with group M, the small intestinal propulsive rate and serum GAS concentration were significantly increased, and the area of c-kit positive cells was increased, and the expression of c-kit was up-regulated in group MOH, the rate of fecal water content, gastric emptying rate, small intestinal propulsion rate and serum GAS concentration were significantly increased, the area of c-kit positive cells was increased, and the expression of c-kit and SP was up-regulated, and the expression of nNOS was down-regulated in group MOM, and the serum GAS concentration and c-kit positive cell area were significantly increased in group MOL ( P<0.05). Conclusions:Orexin A 50 μg/kg can effectively alleviate the gastrointestinal dysfunction induced by morphine in mice, and the mechanism may be related to promotion of GAS secretion, interstitial cells of Cajal growth and SP release and inhibition of NO release.