A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Lupus podocytopathy and antiphospholipid syndrome in a child with SLE: A case report and literature review.

Lupus podocytopathy is a glomerular lesion in systemic lupus erythematosus (SLE) characterized by diffuse podocyte foot process effacement (FPE) without immune complex (IC) deposition or with only mesangial IC deposition. It is rarely seen in children with SLE. A 13-year-old girl met the 2019 European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) Classification Criteria for SLE based on positive ANA; facial rash; thrombocytopenia; proteinuria; and positive antiphospholipid (aPL) antibodies, including lupus anticoagulant (LAC), anti-ß2 glycoprotein-I antibody (anti-ß2GPI), and anti-cardiolipin antibody (aCL). The renal lesion was characterized by 3+ proteinuria, a 4.2 mg/mg spot (random) urine protein to creatinine ratio, and hypoalbuminemia (26.2 g/l) at the beginning of the disease. Kidney biopsy findings displayed negative immunofluorescence (IF) for immunoglobulin A (IgA), IgM, fibrinogen (Fb), C3, and C1q, except faint IgG; a normal glomerular appearance under a light microscope; and diffuse podocyte foot process effacement (FPE) in the absence of subepithelial or subendothelial deposition by electron microscopy (EM). Histopathology of the epidermis and dermis of the pinna revealed a hyaline thrombus in small vessels. The patient met the APS classification criteria based on microvascular thrombogenesis and persistently positive aPL antibodies. She responded to a combination of glucocorticoids and immunosuppressive agents. Our study reinforces the need to consider the potential cooccurrence of LP and APS. Clinicians should be aware of the potential presence of APS in patients with a diagnosis of LP presenting with NS and positivity for aPL antibodies, especially triple aPL antibodies (LCA, anti-ß2GPI, and aCL).

Erchen Decoction Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats.

Objective: Brown adipose tissue (BAT) dissipates chemical energy to protect against obesity. In the present study, we aimed to determine the effects of Erchen decoction on the lipolysis and thermogenesis function of BAT in high-fat diet-fed rats. Methods: Sprague-Dawley rats were randomly divided into four groups, which were fed a control diet (C) or a high-fat diet (HF), and the latter was administered with high and low doses of Erchen decoction by gavage once a day, for 12 weeks. Body weight, the serum lipid profile, serum glucose, and insulin levels of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ coactivator- (PGC-) 1α, and uncoupling protein 1 (UCP-1) in BAT were measured by immunoblotting and RT-PCR. Results: Erchen decoction administration decreased body weight gain and ameliorated the abnormal lipid profile and insulin resistance index of the high-fat diet-fed rats. In addition, the expression of p-AMPK and ATGL in the BAT was significantly increased by Erchen decoction. Erchen decoction also increased the protein and mRNA expression of PGC-1α and UCP-1 in BAT. Conclusion: Erchen decoction ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of lipolysis and thermogenesis in BAT.

The ß3 Adrenergic Receptor Agonist CL316243 Ameliorates the Metabolic Abnormalities of High-Fat Diet-Fed Rats by Activating AMPK/PGC-1α Signaling in Skeletal Muscle.

PURPOSE: Skeletal muscle has a major influence on whole-body metabolic homeostasis. In the present study, we aimed to determine the metabolic effects of the ß3 adrenergic receptor agonist CL316243 (CL) in the skeletal muscle of high-fat diet-fed rats. METHODS: Sprague-Dawley rats were randomly allocated to three groups, which were fed a control diet (C) or a high-fat diet (HF), and half of the latter were administered 1 mg/kg CL by gavage once weekly (HF+CL), for 12 weeks. At the end of this period, the serum lipid profile and glucose tolerance of the rats were evaluated. In addition, the phosphorylation and protein and mRNA expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator (PGC)-1α, and carnitine palmitoyl transferase (CPT)-1b in skeletal muscle were measured by Western blot analysis and qPCR. The direct effects of CL on the phosphorylation (p-) and expression of AMPK, PGC-1α, and CPT-1b were also evaluated by Western blotting and immunofluorescence in L6 myotubes. RESULTS: CL administration ameliorated the abnormal lipid profile and glucose tolerance of the high-fat diet-fed rats. In addition, the expression of p-AMPK, PGC-1α, and CPT-1b in the soleus muscle was significantly increased by CL. CL (1 µM) also increased the protein expression of p-AMPK, PGC-1α, and CPT-1b in L6 myotubes. However, the effect of CL on PGC-1α protein expression was blocked by the AMPK antagonist compound C, which suggests that CL increases PGC-1α protein expression via AMPK. CONCLUSION: Activation of the ß3 adrenergic receptor in skeletal muscle ameliorates the metabolic abnormalities of high-fat diet-fed rats, at least in part via activation of the AMPK/PGC-1α pathway.

Phenotypic variability in a child with Felty's syndrome: a case report.

BACKGROUND: Felty's syndrome (FS) is characterized by the triad of rheumatoid arthritis (RA), splenomegaly and neutropenia. The arthritis is typically severe and virtually always associated with high-titer rheumatoid factor. The presence of persistent neutropenia is generally required to make the diagnosis. Most patients diagnosed with FS are aged 50-70 years and have had RA for more than 10 years. It is rarely seen in patients with juvenile idiopathic arthritis (JIA), with only five cases having been reported throughout the world. CASE PRESENTATION: The present study describes the case of a 14-year-old female with a seven-year history of polyarticular JIA, presenting with splenomegaly, hepatomegaly, cholestasis and thrombocytopenia. However, she occasionally developed neutropenia. Titers of rheumatoid factor and anti-CCP were persistently high, and the antinuclear antibody titer was 1:320, while the antibody results for anti-dsDNA and anti-Sm were negative. Serum levels of IgA, IgG, IgM and IgE were all persistently elevated, and the ratio of CD19+ lymphocytes in the subgroups of lymphocytes was persistently high. The level of complements was normal. No STAT3 and STAT5B mutations were found by next-generation sequencing. The patient did not respond to methotrexate, prednisolone, hydroxychloroquine (HCQ), sulfasalazine and etanercept but was responsive to rituximab. CONCLUSIONS: JIA, thrombocytopenia and splenomegaly are the most common and important features in six children with FS, while persistent neutropenia is not seen in all these patients. No complement deficiency has been found in children with FS so far. Manifestations of FS without neutropenia may be extremely rare. There are differences between adults and children in the clinical and laboratory features of FS.

Dural sinus thrombosis and giant pulmonary artery aneurysm in paediatric Behçet's disease.

Paediatric Behçet's disease (BD) accounts for only 2-5% of all patients with BD. Neurological and vascular involvement account for only 3.6% and 1.8% of paediatric BD in China, but both are lethal complications. We report the case of a 12-year-old Chinese boy presenting with recurrent oral ulcers, extensive thrombosis, cerebral sinus vein thrombosis and bilateral inferior pulmonary artery aneurysm. With treatment that included oral prednisone, a monthly pulse of cyclophosphamide followed by mycophenolate mofetil, and anticoagulant therapy, the patient became symptom free, his C-reactive protein and erythrocyte sedimentation rate remained normal, and the right inferior pulmonary artery aneurysm was reduced to normal. However, the left inferior pulmonary artery aneurysm progressively expanded to 64.9 mm×36.2 mm×44 mm. Eventually, the patient underwent left pulmonary aneurysm resection and a left inferior lobectomy. The post-operative maintenance treatment included oral prednisone, mycophenolate mofetil and low-dose aspirin, and the patient was followed for 2 years without recurrence. Additionally, we retrospectively analysed the clinical characteristics of 23 paediatric BD patients from our medical centre and briefly reviewed the literature on paediatric BD.

Expanding the spectrum of A20 haploinsufficiency in two Chinese families: cases report.

BACKGROUND: The association between mutations in the TNFAIP3 gene and a new autoinflammatory disease (called A20 haploinsufficiency, HA20) has recently been recognized. Here, we describe four patients with HA20 from two unrelated Chinese families. CASE PRESENTATION: A total of four patients from two families were included. The average age at onset was 5.9 years. All patients had no signs of eye or skin problems, such as uveitis, rash, folliculitis and dermal abscess. Prior to the recognition of HA20, P1 was diagnosed with SLE, liver fibrosis and hypothyroidism. She also had no oral, genital or perineal ulcers. P2 was diagnosed with Crohn's disease and inflammatory bowel disease-related arthritis (IBD-RA). He had a perianal abscess but no oral or genital ulcers. P3, the father of P1 and P2, only had mild oral ulcers, arthralgia, and archosyrinx. P4 was diagnosed with polyarticular juvenile idiopathic arthritis (JIA), macrophage activation syndrome (MAS) and interstitial lung disease (ILD). Whole exome sequencing (WES) was performed in two families. WES revealed heterozygous c.559C > T in the TNFAIP3 gene in P1, P2 and P3, while the c.259C > T mutation in the TNFAIP3 gene was identified in P4. The c.259C > T mutations is novel. CONCLUSION: HA20 had a different phenotype between families and even between family members with the same mutation. Liver fibrosis, hypothyroidism, ILD and MAS in the patients with HA20 were first reported in this study. Our results expanded the phenotype and genotype spectrum of A20 haploinsufficiency.

Icariin induces irisin/FNDC5 expression in C2C12 cells via the AMPK pathway.

Backgroud Icariin, a major bioactive pharmaceutical component of the Chinese herbal medicine Epimedii Herba, has demonstrated lipid-lowering and anti-obesity effects. Irisin/ fibronectin type III domain-containing 5 (FNDC5) protects against obesity by inducing browning in white adipose tissue. Objectives This study investigated the effects of icariin on irisin/FNDC5 expression in C2C12 myotubes. Method Cultured murine C2C12 myocytes were used to study the effects of icariin on irisin/FNDC5 expressions by Western-blot, qPCR, Elisa and Immunofluorescence. We also investigated FNDC5 expression in icariin-treated intact mice. Results Icariin increased irisin/FNDC5 protein levels. mRNA levels of irisin/FNDC5 were also increased in C2C12 myocytes after treatment with icariin. Icariin increased peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1α) protein and mRNA levels. Additionally, icariin exposure resulted in phosphorylation of AMP-activated protein kinase (AMPK) in a dose-dependent manner. The regulatory effect of icariin on FNDC5 protein expression was blocked by the AMPK antagonist compound C or silencing of AMPK, suggesting that icariin increased FNDC5 protein expression via the AMPK pathway. In vivo, icariin decreased body weight gain in C57BL/6 mice and increased FNDC5, PGC-1α, and p-AMPK expression levels in skeletal muscle. Conclusions Taken together, our results indicated that icariin induces irisin/FNDC5 expression via the AMPK pathway, indicating that icariin may be promising as an anti-obesity drug.

A mutation in PIK3CD gene causing pediatric systemic lupus erythematosus: A case report.

RATIONALE: Gain of function (GOF) mutations in PIK3CD gene encoding PI3K p110δ were recently associated with a novel combined immune deficiency characterized by recurrent sinopulmonary infections, CD4 lymphopenia, reduced class-switched memory B cells, lymphadenopathy, cytomegalovirus and/or epstein-Barr virus (EBV) viremia, and EBV-related lymphoma. A subset of affected patients also had elevated serum IgM. PATIENT CONCERNS: We report a patient who was diagnosed with systemic lupus erythematosus (SLE) at a young age and was recently found to carry heterozygous mutations in PIK3CD. The patient not only presented with recurrent sinopulmonary infections, CD4 lymphopenia, lymphadenopathy, EBV viremia, and elevated serum IgM, but also met classification criteria of SLE based on persistent proteinuria and hematuria, leukopenia and anemia, low level of serum complement, and positive autoantibody for antinuclear antibodies. DIAGNOSES: Activated PI3Kδ syndrome. INTERVENTIONS: Oral prednisolone and hydroxychloroquine combined with mycophenolate mofetil was given to the patient. He was currently receiving intravenous immunoglobulin per month in association with hydroxychloroquine, low-dose prednisolone, and mycophenolate mofetil. OUTCOMES: At present, the level of complement restored to normal, hematuria and proteinuria disappeared, and liver function returned to normal. LESSONS: SLE may be a novel phenotype of GOF mutation in PI3CKD gene (GOF PIK3CD).

Gene mutation analysis in 12 Chinese children with congenital nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome (CNS) is characterised by increased proteinuria, hypoproteinemia, and edema beginning in the first 3 months of life. Recently, molecular genetic studies have identified several genes involved in the pathogenesis of CNS. A systematic investigation of the genes for CNS in China has never been performed; therefore, we conducted a mutational analysis in 12 children with CNS,with the children coming from 10 provinces and autonomous regions in China. METHODS: Twelve children with CNS were enrolled from 2009 to 2016. A mutational analysis was performed in six children by Sanger sequencing in eight genes (NPHS1, NPHS2, PLCE1, WT1, LAMB2, LMXIB, COQ6 and COQ2) before 2014, and whole-exome sequencing was used from 2014 to 2016 in another six children. Significant variants that were detected by next generation sequencing were confirmed by conventional Sanger sequencing in the patients' families. RESULTS: Of the 12 children, eight patients had a compound heterozygous NPHS1 mutation, one patient had a de novo mutation in the WT1 gene, and another patient with extrarenal symptoms had a homozygous mutation in the COQ6 gene. No mutations were detected in genes NPHS2, PLCE1, LAMB2, LMXIB, and COQ2 in the 12 patients. CONCLUSIONS: This study demonstrates that the majority of CNS cases (67%, 8/12 patients) are caused by genetic defects, and the NPHS1 mutation is the most common cause of CNS in Chinese patients. A mutational analysis of NPHS1 should be recommended in Chinese patients with CNS in all exons of NPHS1 and in the intron-exon boundaries.

Browning of Abdominal Aorta Perivascular Adipose Tissue Inhibits Adipose Tissue Inflammation.

BACKGROUND: Perivascular adipose tissue (PVAT) can regulate vascular homeostasis by secreting various adipokines. This study investigated the effects of PVAT browning on its endocrine function. METHODS: In the first section of our study, male Sprague-Dawley rats were randomly divided into cold exposure (8°C) and 24°C acclimation groups. After cold exposure for 7 days, interscapular brown adipose tissue (iBAT), subcutaneous white adipose tissue, thoracic aortic PVAT, and abdominal aortic PVAT (aPVAT) were harvested for histological and brown marker gene expression analysis. In the second part, male rats were fed a high fat diet (HFD) for 10 weeks. In the 11th week, the rats were treated with or without cold exposure. After 14-day cold exposure, aPVAT was collected for histological, gene, and protein expression analysis. RESULTS: Cold exposure had a browning effect on aPVAT by increasing UCP-1 and PGC-1α expression levels. After HFD feeding for 10 weeks, 14-day cold exposure was still able to induce aPVAT browning. Compared with thermoneutrality acclimation rats, TNF-α, IL-6, and p-p65 expression levels were significantly lower in aPVAT from HFD-fed rats with cold exposure. In contrast, p-AMPK expression levels were increased in aPVAT from HFD-fed rats with cold exposure. CONCLUSIONS: Our study demonstrated that browning of aPVAT in HFD-fed rats lowered the pro-inflammatory adipokine expression levels and activated AMPK.

Initial Benchmarking of the Quality of Medical Care in Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To assess the quality of medical care in childhood-onset systemic lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured by observance of SLE quality indicators (SLE-QIs). METHODS: International consensus has been achieved for childhood-onset SLE-QIs capturing medical care provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmologic surveillance, transition, pregnancy, and vaccination. Using medical record information, the level of performance of these childhood-onset SLE-QIs was assessed in childhood-onset SLE populations treated at 4 tertiary pediatric rheumatology centers in the US, 2 in Brazil, and 1 center in India. RESULTS: A total of 483 childhood-onset SLE patients were assessed. Care for the 310 US patients differed markedly for childhood-onset SLE-QIs addressing LN, bone health, vaccinations, education on CV risk, and transition planning. Performance of safety blood testing for medications was high at all centers. Despite often similar performance on the childhood-onset SLE-QI, access to kidney biopsies was lower in Brazil than in the US. Irrespective of the country of practice, larger centers tended to meet the childhood-onset SLE-QIs more often than smaller centers. CONCLUSION: The childhood-onset SLE-QIs, evidence-based minimum standards of medical care, are not consistently met in the US or some other countries outside the US. This has the potential to contribute to suboptimal childhood-onset SLE outcomes.

Brain­derived neurotrophic factor gene polymorphisms are associated with coronary artery disease­related depression and antidepressant response.

Depression is a well­established risk factor for cardiac morbidity and mortality in patients with coronary artery disease (CAD). Previous studies have demonstrated that the level of brain­derived neurotrophic factor (BDNF) is decreased in depressed patients and this depletion may be reversed by antidepressants. Several recent studies have suggested that BDNF is involved in the pathogenesis of CAD. The aim of the present study was to investigate the possible association between seven single nucleotide polymorphisms (SNPs) of the BDNF gene (SNPs; rs16917204, rs6265, rs7103873, rs16917237, rs56164415, rs13306221 and rs10767664) and coronary artery disease­related depression (CAD­D). In the present study, 616 CAD patients without depression (CAD­nD) and 155 patients with CAD­D were recruited, and the response to an eight week sertraline antidepressant treatment regimen was also evaluated. The results demonstrated that a significant association existed between the SNP rs6265, located in exon 4 of the BDNF gene, and CAD­D [χ2=9.634, P=0.002, odds ratio (OR)=1.486, 95% confidence interval (CI)=1.156­1.910]. Another potential association was observed for rs13306221 (χ2=5.194, P=0.023, OR=2.139, 95% CI=1.096­4.175) in the promoter region of the BDNF gene. Strong linkage disequilibrium was observed in block 1 (rs16917204, rs6265; D'>0.9). However, there was no evidence of a significant linkage disequilibrium between the seven SNPs in our sample population. Additionally, carriers of the A allele of rs6265 exhibited improved responses to the sertraline treatment (χ2=8.942, P=0.003, OR=2.136, 95% CI=1.293­3.528). To the best of our knowledge, these results demonstrate, for the first time, the presence of a significant association between BDNF rs6265 and CAD­D, the identification of which may facilitate early diagnosis of CAD­D in the future.

Mutational analysis of AGXT in two Chinese families with primary hyperoxaluria type 1.

BACKGROUND: Primary hyperoxaluria type 1 is a rare autosomal recessive disease of glyoxylate metabolism caused by a defect in the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) that leads to hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. METHODS: Two unrelated patients with recurrent urolithiasis, along with members of their families, exhibited mutations in the AGXT gene by PCR direct sequencing. RESULTS: Two heterozygous mutations that predict truncated proteins, p.S81X and p.S275delinsRAfs, were identified in one patient. The p.S81X mutation is novel. Two heterozygous missense mutations, p.M1T and p.I202N, were detected in another patient but were not identified in her sibling. These four mutations were confirmed to be of paternal and maternal origin. CONCLUSIONS: These are the first cases of primary hyperoxaluria type 1 to be diagnosed by clinical manifestations and AGXT gene mutations in mainland China. The novel p.S81X and p.I202N mutations detected in our study extend the spectrum of known AGXT gene mutations.

Efficacy of rituximab therapy in children with refractory nephrotic syndrome: a prospective observational study in Shanghai.

BACKGROUND: Idiopathic nephrotic syndrome is the most common glomerular disease in children. This study was undertaken to observe the efficacy and side-effects of rituximab (RTX) in treating children with different types of refractory primary nephrotic syndrome. METHODS: Twelve patients with steroid dependent nephrotic syndrome (SDNS), frequently relapsing nephritic syndrome (FRNS), and steroid resistant nephrotic syndrome (SRNS) were enrolled in our study. There were obvious drug side-effects, and proteinuria remained difficult to control. RTX was administered at a dose of 375 mg/m(2) body surface area, once or twice weekly. RESULTS: The male to female ratio was 3:1, and the onset age was 1.6-8.9 years. There were 9 patients with steroid sensitive nephrotic syndrome (SDNS or FRNS), and 3 patients with SRNS. There were 7 patients with minimal change disease (MCD), 3 patients with focal segmental glomerular sclerosis (FSGS), 1 with focal proliferative glomerulonephritis, and 1 without renal biopsy. The total effective treatment rate of RTX was 91.67%, and for 77.78% of the patients, steroid dosage could be reduced. Six months before and after RTX infusion, the mean steroid dosage was significantly decreased (P=0.014) and the recurrence number was significantly reduced (P<0.001). The results were better in MCD patients than in FSGS patients (P=0.045). There was no significant difference between FRNS/SDNS and SRNS patients (P=0.175). During RTX administration, 3 patients developed skin rashes, 1 developed hypotension, and 1 developed a fever. One patient experienced a persistent decrease in serum immunoglobulin level but without serious infection. CONCLUSION: RTX was effective in the treatment of refractory nephrotic syndrome, and it could significantly reduce the use of steroid and immunosuppressants.

Morphine treatment enhances extracellular ATP enzymolysis and adenosine generation in rat astrocytes.

Recent studies have shown that astrocytes play important roles in ATP degradation and adenosine (a well known analgesic molecule) generation, which are closely related to pain signaling pathway. The aim of this study was to investigate whether morphine, a well known analgesic drug, could affect the speeds of ATP enzymolysis and adenosine generation in rat astrocytes. Intracellular calcium concentration ([Ca(2+)](i)) of astrocyte was measured by flow cytometry, and the time points that morphine exerted notable effects were determined for subsequent experiments. Cultured astrocytes were pre-incubated with morphine (1 µmol/L) and then were incubated with substrates, ATP and AMP, for 30 min. The speeds of ATP enzymolysis and adenosine generation were measured by high performance liquid chromatography (HPLC). The results showed that both 1.5 and 48 h of morphine pre-incubation induced maximal ATP enzymolysis speed in astrocytes among all the time points, and there was no statistical difference of ATP enzymolysis speed between morphine treatments for 1.5 and 48 h. As to adenosine, morphine pre-incubation for 1.5 h statistically increased adenosine generation, which was degraded from AMP, in cultured astrocytes compared with control group. However, no difference of adenosine generation was observed after 48 h of morphine pre-incubation. These results indicate that treatment of morphine in vitro dynamically changes the concentrations of ATP and adenosine in extracellular milieu of astrocytic cells. In addition, astrocyte can be regarded as at least one of the target cells of morphine to induce changes of ATP and adenosine levels in central nervous system.

Intrauterine growth restriction and postnatal high-protein diet affect the kidneys in adult rats.

OBJECTIVE: Intrauterine growth restriction (IUGR) is associated with hypertension and chronic kidney disease in adulthood. Postnatal overnutrition after IUGR may be of pathogenic importance for the development of diabetes and cardiovascular disease. This study was to identify the effects of IUGR and a postnatal high-protein diet on the kidneys in adult rats. METHODS: Intrauterine growth restriction was induced in Sprague-Dawley rats by isocaloric protein restriction in pregnant dams. IUGR pups were divided into two groups that were a standard-protein diet (IUGR group) or a high-protein diet (HP group). A comparative proteomic method was used to study the differences of protein expression profiles between normal adult rats and adult rats with IUGR and the effects of a postnatal high-protein diet on the protein expression profiles of the kidneys. RESULTS: The IUGR adults had higher urinary excretion of protein and blood pressure than controls and the HP diet caused more severe hypertension and proteinuria than IUGR itself. The differential proteomic expression analysis found 12 proteins that had significantly differential expression between the IUGR and control groups, which were transcription regulators and structural molecules. The differential proteomic expression analysis between the HP and control groups found 13 proteins that had significantly differential expression and were involved primarily in body metabolism, oxidation reduction, and apoptosis regulation. CONCLUSION: An HP diet intervention after IUGR worsens the severity of hypertension and proteinuria, and this study may provide valuable experimental evidence of proteins involved in the pathogenesis of kidney disease in IUGR and the effect of postnatal overnutrition.

[Long-term follow-up of 101 cases with pediatric lupus nephritis in a single center in Shanghai].

OBJECTIVE: To deeply understand prognosis of pediatric cases with lupus nephritis (LN) treated in our hospital and analyze the prognostic factors. METHOD: One hundred and one patients were enrolled, who were diagnosed as lupus nephritis in our hospital during the period from Jan. 1996 to Dec. 2007. Clinical data were retrospectively analyzed; the observation was ended on 31(st) Dec. 2009. Patients were divided into renal biopsy group and non renal biopsy group; group A (type I + II LN), group B (type III + IV LN) and group C (type V LN); CTX group (cyclophosphamide) and MMF group (mycophenolate mofetil); remission group (complete remission and partial remission) and ineffective group (treatment failure and death). Medication non-compliance means (1) the interval of CTX pulse was more than 45 days or treatment course less than 6 times; (2) patients discontinued MMF or other immunosuppressant on themselves more than a week ago. SPSS 11.0 software Life-Tables method was used to analyze cumulative survival rates. RESULT: (1) Three and five years' patient survival rates were 93.59% and 87.80% respectively. Three and five years' kidney survival rates were 100% and 91.12% respectively. (2) Univariate analysis showed that induction remission were related to five factors, including whether received renal biopsy (χ(2) = 9.023, P = 0.003), different pathological types (χ(2) = 9.437, P = 0.009), different induction drug (χ(2) = 4.610, P = 0.032), treatment compliance (χ(2) = 18.716, P = 0.000) and proteinuria amount (χ(2) = 8.013, P = 0.046), and maintenance remission were related to the former four factors (χ(2) = 10.209, P = 0.001;χ(2) = 7.757, P = 0.021;χ(2) = 4.206, P = 0.04;χ(2) = 24.571, P = 0.000). (3) Multivariate analysis showed that maintenance remission was mainly related to medication-compliance (χ(2) = 9.818, P = 0.002). Poor medication compliance mainly occurred in non renal biopsy group (χ(2) = 9.569, P = 0.002). (4) In renal biopsy group, 15 cases showed a small amount proteinuria, 4 of them were proved as severe pathological type LN (2 cases type III, 1 case type IV and 1 case type V). (5) In group B, no medication non-compliance occurred, and the efficacy of MMF and CTX had no significant difference (P = 0.405). CONCLUSION: The main affecting factor of remission rate was medication compliance. In type III and IV lupus nephritis, the efficacy of MMF and CTX were no significant difference. The poor outcome of non-renal biopsy group may be due to unclear pathological classification and poor medication compliance. We strongly recommend that SLE patients with mild abnormal results of urinalysis should receive renal biopsy.

A comparative proteomic study of nephrogenesis in intrauterine growth restriction.

Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. The aim of this study was to test the hypothesis that IUGR affects expression of key proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR was induced in Sprague-Dawley (SD) rats by isocaloric protein restriction in pregnant dams. A series of methods, including two-dimensional gel electrophoresis (2-DE), silver staining, mass spectrometry and database searching was used. After silver staining, 2-DE image analysis detected an average 730 + or - 58 spots in the IUGR group and 711 + or - 73 spots in the control group. The average matched rate was 86% and 81%, respectively. The differential proteomic expression analysis found that 11 protein spots were expressed only in the IUGR group and one in the control group. Seven protein spots were up-regulated more than fivefold and two were down-regulated more than fivefold in the IUGR group compared with those in control group. These 21 protein spots were preliminarily identified and were structural molecules, including vimentin, perlecan, gamma-actin and cytokeratin 10, transcription regulators, transporter proteins, enzymes, and so on. These proteins were involved primarily in energy metabolism, oxidation and reduction, signal transduction, cell proliferation and apoptosis. Data from this study may provide, at least partly, evidence that abnormality of metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and cell proliferation may be the major mechanisms responsible for abnormal nephrogenesis in IUGR.

[Clinical analysis of 139 cases of primary vesicoureteric reflux in children].

OBJECTIVE: To analyze the clinical features, renal damage and prognosis of primary vesicoureteric reflux (VUR) in children, hoping to give more attention to early recognition and treatment of the disease. METHODS: Between June 1995 and December 2006, 974 patient were admitted in our hospital because of urinary tract infection (UTI), 139 primary VUR children were enrolled in the retrospective study. VUR grades, renal scar development, renal ultrasound and urinalysis were evaluated. RESULTS: The incidence of VUR in UTI children was 14.3% (139/974), however, the incidence in infants and toddlers (younger than two years of age) was 17.2% (79/458), which was greatly higher than that in school children. Of the 139 children, 79(56.8%) were younger than two years and the number of boys was much larger than that of girls (P = 0.001). Bilateral reflux was found in 69 cases, unilateral in 70 cases; the percentages of mild reflux (grade I-II) was 19.7% (41/208), moderate reflux (grade III) was 35.6% (74/208), severe reflux (grade IV-V) was 44.7% (93/208). Dimercaptosuccinic acid (DMSA) scanning was performed for 135 patients, and renal scar was found in 37% (50/135), and the rate of scar in infants was the highest (42.4%), and 30 (60%) patients with renal scar were younger than two years of age. Among them five patients were found to have renal scar during the follow up period, four of them were younger than two years. The rate of renal scar in moderate and severe reflux was much higher than that in mild reflux cases, the risk of occurring renal scar would increase with its severity of reflux (P < 0.001). The sensitivity and specificity of renal ultrasound in suggesting VUR were 24.8% and 94.3%, respectively. The positive outcome of urinary N-acetyl-beta-glucosaminidase was a bit high, but there were no associations between renal scar and urinary microprotein (P > 0.05). Thirty-one cases were followed up for long time (> 1 year); and 90% of urinary infection was controlled and in 44.4% of patients VUR disappeared with medical treatment. No child had decreasing renal function in follow-up period. CONCLUSION: Children with primary VUR need early diagnosis and treatment. Insisting on normal therapy and long-term follow-up will protect renal function effectively.