Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

Objective To evaluate the intravascular volume at different levels of edema and disease course by the fractional excretion of filtered sodium(FeNa)of children with primary nephrotic syndrome(PNS).Methods A total of 172 children with newly diagnosed PNS who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from September 2022 to September 2024 were selected and divided into non-e-dema group(n=51),mild edema group(n=43),moderate edema group(n=46)and severe edema group(n=32)according to the degree of edema at the time of admission.A total of 40 healthy children who underwent physical examination during the same period were selected as the healthy control group.Serum creatinine,ser-um sodium were detected before and after treatment.Urine samples were collected to detect urine creatinine,urine sodium,FeNa was calculated and compared according to the results,and the degree of edema was recor-ded.24 h urine samples were collected on the same day to detect 24 h urine protein quantification and 24 h u-rine volume.Results On day 1 to 2 of the course of the disease,about 12%of the PNS children had FeNa<0.2%,indicating insufficient intravascular volume,which was mainly concentrated in the severe edema group.The moderate,severe edema group had a significantly lower FeNa level than the non-edema group,mild edema group,and healthy control group(P<0.01).The moderate edema group had a significant increase in FeNa on days 6 to 7 of the course of the disease,and the severe edema group had a significant increase in Fena on days 11 to 12 of the course of the disease(P<0.01).Conclusion Intravascular volume of PNS children with mod-erate to severe edema is often reduced,and intravascular volume may be insufficient in severe edema.PNS chil-dren with moderate to severe edema have increased intravascular volume with the extension of the course of disease and the improvement of the condition.

Objective To explore the change of nucleoplasm distribution of glucocorticoid receptor alpha(GRα)in peripheral blood of children with primary nephrotic syndrome(PNS)during the course of the disease,aiming at evaluating the correlation between nuclear transport abnormality and different GC responses.Methods A total of 45 children with PNS were enrolled as subjects in this prospective study,and divided into steroid-sensitive nephrotic syndrome(SSNS,n=36)and steroid-resistant nephrotic syndrome(SRNS,n=9)groups,according to their response to GC.The SSNS group was further subclassified into non-frequently relapsing nephrotic syndrome(NFRNS,n=21)and frequently relapsing nephrotic syndrome(FRNS,n=15)based on relapse frequency during 12-month follow-up.Peripheral blood samples were collected before GC treatment,6-week and 6-month after GC treatment.GRα nuclear localization was detected by immunofluorescence assay,and their correlations with clinical-laboratory indicators were analyzed.Results Before the GC treatment,the average fluorescence intensity showed no significantly difference among different groups(P＞0.05),the GRαin the three groups were localized mainly in cytoplasm,and the nucleocytoplasmic ratio showed no significantly difference among the three groups(P＞0.05).6-week after the GC treatment,the average fluorescence intensity showed no significantly difference among the three groups(P＞0.05),the GRα in SSNS group were localized mainly in nucleus,while those in SRNS group were localized mainly in cytoplasm.Furthermore,nucleocytoplasmic ratio in NFRNS group and SRNS group demonstrated significant differences,while those in NFRNS group and FRNS group showed no significant difference(P＞0.05).6-month after the GC treatment,the average fluorescence intensity in NFRNS group and FRNS group showed no significant difference(P＞0.05),GRα in the two groups were localized mainly in nucleus,and their nucleocytoplasmic ratio had significantly differences(P＜0.05).The GRα nucleocytoplasmic ratio in children with PNS was negatively correlated with 24-hour urine protein(24 h-UTP),TNF-α,while positively correlated with serum albumin(Alb).Conclusion There are differences in nuclear transport ability among PNS children of SRNS,NFRNS and FRNS groups,and these differences are correlated with the differency of GC responses.

Objective To observe the distribution of atypical memory B cells in peripheral blood of children with frequently relapsing nephrotic syndrome(FRNS).Methods A total of 60 children with primary ne-phrotic syndrome(PNS)admitted to the hospital from October 2020 to March 2023 were selected as the re-search objects.According to the response to glucocorticoid(GC),they were divided into non-frequently relap-sing nephrotic syndrome(NFRNS)group(25 cases)and FRNS group(35 cases).A total of 20 age-and gen-der-matched healthy children were enrolled as the control group.The changes of atypical memory B cells in each group before and after GC treatment were compared,and the correlation between the changes and clinical data was analyzed.Results Before GC treatment,The percentages of total B cells(CD19+CD20+),total memory B cells(CD19+CD20+CD27+),resting memory B cells(CD19+CD20+CD21+CD27+)and atypical memory B cells(CD19+CD20+CD21-CD27-)in FRNS group and NFRNS group were significantly higher than those in control group.And the FRNS group was significantly higher than the NFRNS group(P＜0.05).After GC treatment,the percentages of total B cells,total memory B cells,resting memory B cells,acti-vated memory B cells(CD19+CD20+CD21-CD27+)and atypical memory B cells in FRNS group and NFRNS group were lower than those before GC treatment(P＜0.05).The FRNS group had a significantly higher pro-portion of atypical memory B cells than the NFRNS group and the control group(P＜0.05).Before GC treat-ment,the 24 h urinary protein in FRNS group and NFRNS group were higher than those in control group,and the levels of immunoglobulin G and albumin were lower than those in control group.The 24 h urinary protein in FRNS group was significantly higher than that in NFRNS group(P＜0.05).Before GC treatment,there was a positive correlation between 24 h urinary protein and the proportion of atypical memory B cells in FRNS group(P＜0.05).Conclusion There is abnormal distribution of atypical memory B cells in peripheral blood of FRNS children.The increase of atypical memory B cells can be used as a marker of recurrence of FRNS af-ter GC treatment.

Objective To investigate the efficacy of total glucosides of paeony ( TGP ) in the treatment of hematuria and proteinuria purpura nephritis ( HSPN ) and serum interleukin?6 ( IL?6 ), interleukin?1 beta (IL?1 beta) and interleukin?18 (IL?18).Methods From June 2017 to December 2018, 64 cases of children with primary hematuria and proteinuria purpura nephritis admitted to the department of pediatrics affiliated hospital of Xuzhou medical university were selected as study subjects,and were divided into control group (33 cases) and observation group (31 cases) according to random number method.The children in the control group were given oral administration of poniasone acetate,and the observation group was treated with TGP on the basis of the control group.Both groups received continuous treatment for 4 weeks.Two groups′ before and after treatment expression level of serum interleukin?6, interleukin?1β and interleukin?18,and level of clinic indicator such as Urinary red biood cell (URBC),24 hour urinary protein quantity, urinary immune globulin G ( IGU ), micro?albuminuria ( urinary microalbumin, MAU ), α?Microglobulin (α1?MG) and urinary transferrin ( TFRU) is made a comparison.Results After 4weeks of treatment,the total clinical effective rate of the observation group (93.5%(29／31)) was significantly higher than that of the control group (72.7%(24／33)),and the difference between the two groups was statistically significant (χ2＝4.868,P＜0.05).Before treatment,difference between serum interleukin?6,interleukin?1β and interleukin?18 from two groups and each clinic indicators level has no statistic significance (all P＞0.05) .After treatment,in the observation group,Serum IL?6 ( (16.68±6.83) ng／L and (32.24±6.99) ng／L,t＝12.373),IL?1β((63.83 ±8.97)ng／L and (85.59±9.42) ng／L,t＝9.758),IL?18((64.52±5.46) ng／L and (88.50±5.54) ng／Ll,t＝18.899),24 h urinary protein quantification ( 0.3 (0.21,0.36) g／24 h and 1.0 (0.65,1.23) g／24 h,Z＝－4.861),URBC (15.30 (3.80,36.80)×106／L and 168.9 (58.4, 324.0)×106／L,Z＝－4.840),were lower than before treatment ( all P＜0.05); After treatment, in the control group,Serum IL?6 ((23.62±5.95) pg／ml and (33.44±4.68) pg／ml,t＝9.149),IL?1β ((68.67 ±6.31) pg／ml and (86.59±8.71) pg／ml,t＝10.617),IL?18((71.25±9.69) pg／ml and (89.87±6.68) pg／ml,t＝11.506),24 h urinary protein quantification (0.42 (0.33,0.56) g／24 h and 0.94 (0.74,1.25) g／24 h,Z＝－5.013),URBC ( 57.00 ( 39.25,77.50)×106／L and 145.60 ( 58.20,360.85)×106／L,Z＝－4.762),were lower than before treatment ( all P＜0.05).The difference between the two groups was statistically significant (P＜0.05).Conclusion The adjuvant effect of total glucoside of white peony root on hematuria and proteinuria purpura nephritis is significant, which can reduce the level of hematuria and proteinuria and improve the renal symptoms of children.Its mechanism of action may be to reduce renal inflammation and protect the kidney by down?regulating the expression of serum IL?6,IL?1 and IL?18.

Objective To study the clinical features and treatments of childhood systemic lupus erythematosus (SLE) complicated with macrophage activation syndrome (MAS). Methods Clinical data of a patient with SLE complicated with MAS were retrospectively analyzed, and relevant literatures were reviewed. Results An eight-year-old girl diagnosed as SLE two years ago was admitted to the hospital with complaint of high fever for over one week. Peripheral blood cytopenia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia and hepatolienomegaly occurred after admission gradually. Thus the child was diagnosed definitely as MAS. Conclusions SLE complicated with MAS is not rare. The disease progresses very rapidly and can be life-threatening, while early diagnosis is very difficult. The key to improve prognosis is early diagnosis and treatment.

Objective To explore the protective role of lipoxin A4 (LXA4) during early process of atherosclerosis formation in rats with juvenile metabolic syndrome (MS).Methods Rat models of juvenile MS were established with 3-week Sprague-Dawley (SD) rats fed on high-carbonhydrates and high-fat diet for 6 weeks.The other qualified ones were randomly grouped into model group,LXA4 low-dose group,LXA4 middle-dose group,and LXA4high dose group,and a control group fed with normal forage.The low,middle,high-dose groups were injected different doses of LXA4 daily,while the model group and control group were injected with the same dose of isotonic NaCl solution for 2 consecutive weeks.After 2-week medication,the visceral adipose tissue were isolated by laparotomy and heart blood collected by thoracotomy under anesthesia,followed the fixation of thoracic and abdominal aortas in the immobilized rats.The mRNA expression level of inflammation cytokines interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),C-reactive protein (CRP) in the adipose tissue were determined by semi-quantitative reverse transcription PCR (RT-PCR),respectively.Secretions of IL-6,and TNF-α in serum were determined by enzyme linked immunosorbent assay (ELISA).Immunocytochemistry was used to label endomembrane and middle-membrane of thoracic aorta,and endothelial cell layer in each group and the ratios of thickness of endomembrane and middle-membrane were compared.Results Compared with the control group,weight,body length and abdominal circumference of juvenile MS rats increased significantly (all P ＜ 0.05),and levels of fasting plasma glucose (FPG),triglyceride (TG),high density lipoprotein cholesterol (HDL-C) and insulin in models increased significantly (P ＜ 0.05).RT-PCR showed that the mRNA expressions of inflammatory cytokines IL-6,TNF-α and CRP in adipose tissue in model rats were upexpressed (all P ＜ 0.05).Compared with model rats,mRNA of IL-6,TNF-oα,and CRP in mid,high-dose rats were downexpressed (all P ＜ 0.05),mRNA of TNF-α in low-dose rat downexpressed (all P ＜ 0.05),and there were no significant differences between mRNA expressions of IL-6,CRP in low-dose and model rats according to statistics (all P ＞0.05).Compared with control group,inflammatory cytokines IL-6,TNF-α secreted in serum of model rats were increased significantly (all P ＜ 0.05),and inflammatory cytokines secreted in serum of intervention rats were decreased significantly compared with model rats (P ＜ 0.05).Pathological changes were as follows:HE staining:compared to model group,aortic tunica intima of model rats were remarkably thickened and endothelial cell layer was fragmented and incomplete,which was attenuated in each intervention group.The ratios of endomembrane and middle-membrane in rats:at the end of consecutive medication for 2 weeks,the ratios of endomembrane and middle-membrane in model rats were significantly greater than those of control group (P ＜ O.05),and the ratios of endomembrane and middle-membrane in high-dose intervention rats were significantly smaller than those of the model group (P ＜ 0.05),but still greater than control group,while there were no statistical differences between the ratios in low,middle-dose intervention rats and model rats (P ＞ 0.05).Conclusions The increasing inflammatory cytokines are involved in early process of atherosclerosis formation in rats with juvenile MS.LXA4 by reducing the expression of inflammatory factor level in adipose tissue,thereby reducing the inflammatory cytokines in serum,alleviate the damage of arterial wall.

Objective To study effect and its possible mechanism of total glucosides of paeony ( TGP ) on adriamycin-induced nephropathy rats.Methods Thirty male SD rats were randomly divided into normal group ( CON) , adriamycin-induced nephropathy group ( ADRN) and TGP-treated ADRN group (TGP).The rat nephropathy model was established by adriamycin injection.At the end of the 8th week after treatment, ELISA was used to detect the level of Cr and BUN.The values of 24 urine protein was determined by urinary protein kit.Masson staining was used to observe the fibrosis.RT-PCR was used to detect the mRNA levels of TLR4/NF-κB/TGF-β1 .Immunohistochemical method was used to detect the content of TLR4/NF-κB/TGF-β1.ResuIts Compared with the CON group, the level of Cr, BUN, 24 urine protein of ADRN group rised(P<0.01), the degree of fibrosis of ADRN group were aggravated(P<0.01), and the expressions of TLR4/NF-κB/TGF-β1 of ADRN group increased significantly.However, compared with ADRN group, the(P<0.01) level of Cr, BUN, 24 urine protein of TGP-treated rats reduced(P<0.01), the degree of fibrosis of TGP-treated rats eased(P<0.05), and the expressions of TLR4/NF-κB/TGF-β1 of TGP-treated rats decreased significantly.ConcIusion TGP retards the process of fibrosis and reduces the pathological damage in adriamycin-induced rats by down-regulating the expression of TLR4/NF-κB/TGF-β1 signaling.