Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study.

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.

Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay. Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

Mycophenolate Mofetil in the Treatment of Steroid-Dependent or Frequently Relapsing Nephrotic Syndrome in Children: A Meta-Analysis.

Objectives: This meta-analysis aims to evaluate the efficacy and safety of the mycophenolate mofetil (MMF) in the treatment of steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS) in children. Methods: We searched for the studies especially the randomized controlled trials in PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wan Fang database. The data were analyzed by Review Manager 5.3 software. We used the GRADE pro-Guideline Development Tool online software to evaluate the quality of evidence. Results: Finally, we identified 620 studies, of which we included five randomized controlled trials and one prospective cohort study with 447 children. The results showed the following: (1) the relapse-free survival rate within 1 year-the MMF group was superior to the levamisole group [ratio difference (RD) = 0.13, 95% CI (0.02, 0.24), P = 0.02] but not to the calcineurin inhibitors (CNIs) group [RD = -0.27, 95%CI (-0.40, -0.14), P < 0.0001]; (2) the number of relapses within 1 year-the MMF group was less than that in the CNIs and levamisole group [mean difference (MD) = -0.26, 95%CI (-0.45, -0.08), P = 0.005]; (3) the cumulative prednisone dosage-the MMF group was lower than that in the control group [standardized mean difference (SMD) = -0.32, 95%CI (-0.53, -0.11), P = 0.003]; (4) incidence of adverse reactions-there was no significant difference between the MMF group and the control group [RD = 0.02, 95%CI (-0.04, 0.09), P = 0.46]. Conclusion: The therapy of mycophenolate mofetil in the treatment of SDNS or FRNS in children has a certain advantage in reducing the number of relapses and cumulative prednisone dosage within 1 year when compared with the CNIs and levamisole. However, due to the limited quantity and quality of the included studies, the conclusions above need to be confirmed by more high-quality randomized controlled trials.