Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology.

BACKGROUND: Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP. METHODS: Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking. RESULTS: A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was "Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai)." Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway. CONCLUSION: This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.

Diagnostic efficacy and influence factors of urinary protein/creatinine ratio replacing 24-h urine protein as an evaluator of proteinuria in children.

PURPOSE: The aim was to investigate the diagnostic efficacy of urinary protein/creatinine ratio (UPCR) and factors influencing its substitutability of 24-h urine protein (24hUP) in children with proteinuria. METHODS: A total of 356 children were recruited, including 149 with non-nephrotic-range proteinuria and 207 with nephrotic-range proteinuria which were further divided into Henoch-Schönlein purpura nephritis (HSPN), lupus nephritis (LN), and primary nephrotic syndrome (PNS). The urine protein and creatinine were measured by routine methods. Bland-Altman analysis was used to test the agreement. Spearman correlation was performed to evaluate the relevance. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of UPCR. RESULTS: Bland-Altman analysis showed there was an excellent agreement between UPCR and 24hUP in each group. Correlations between UPCR and 24hUP were strong in 356 children (r = 0.869) and in the non-nephrotic-range proteinuria group (r = 0.806), but moderate in nephrotic-range proteinuria group (r = 0.586). With the increase of nephrotic-range proteinuria, the correlations between UPCR and 24hUP were decreased further, however, after UPCR was adjusted by 24-h urine creatinine (24hUCr), the correlation coefficient was improved (r = 0.682). In three subgroups with nephrotic-range proteinuria, high correlation coefficient (r = 0.731) was observed in HSPN, but not in LN (r = 0.552) and PNS (r = 0.563). The sensitivity and specificity of UPCR for diagnosing nephrotic-range proteinuria were 89.9 % and 92.2%. CONCLUSIONS: UPCR is competent in evaluating proteinuria. The degree of proteinuria, 24hUCr and the underlying pathological types of renal disease may be the important influencing factors in the correlation between UPCR and 24hUP in children with nephrotic-range proteinuria.

Correlation of urine protein/creatinine ratios to 24-h urinary protein for quantitating proteinuria in children.

BACKGROUND: The purpose of this study was to evaluate the correlation and consistency between urine protein/creatinine ratio (UPCR) and 24-h urine protein (24HUPr) in children, and to determine cutoff values of UPCR relative to 24HUPr at 100 mg/m2/d (≥ 100 mg/m2/d as pathological proteinuria) and 1000 mg/m2/d (≥ 1000 mg/m2/d as nephrotic-range proteinuria). METHODS: Three hundred sixty-six children were enrolled, including 81 controls, 109 with Henoch-Schönlein purpura nephritis, 167 with nephrotic syndrome, 5 with IgA nephropathy, and 4 with lupus nephritis. Patients were divided into three groups: normal group; non-nephrotic-range proteinuria group; nephrotic-range proteinuria group. The cutoff values of UPCR in predicting the different levels of proteinuria were determined using ROC curve analysis. RESULTS: UPCR was positively correlated with 24HUPr (r = 0.915, p < 0.01). Bland-Altman diagrams showed that UPCR and 24HUPr had good consistency, and > 95% spots of UPCR and 24HUPr were within 95% confidence intervals. Relative to 24HUPr at 100 mg/m2/d, the cutoff value of UPCR (0.18 g/g Cr) had the highest sensitivity (94%) and specificity (98.8%) which is close to 0.2 g/g Cr as proposed by the American College of Rheumatology. Relative to 24HUPr at 1000 mg/m2/d, the cutoff value of UPCR (2.09 g/g Cr) had the highest sensitivity (92.1%) and specificity (92.1%) which is close to the 2.0 g/g Cr proposed in KDIGO guidelines. CONCLUSIONS: UPCR showed strong correlation and consistency with 24HUPr for evaluating levels of proteinuria in children. UPCR < 0.2 g/g Cr can be considered a criterion for normal-range proteinuria. Instead of 24HUPr ≥ 1000 mg/m2/d, UPCR ≥ 2.0 g/g Cr can be considered a criterion for nephrotic-range proteinuria or nephrotic syndrome in children.