Pediatric central precocious puberty (CPP) is driven by premature activation of the hypothalamic-pituitary-gonadal (HPG) axis, along with immune-inflammatory imbalance, metabolic dysfunction, obesity, and gut microbiota-derived signals. According to traditional Chinese medicine (TCM) principles, kidney yin deficiency with hyperactive ministerial fire and spleen deficiency with phlegm-dampness form the basis for central pubertal activation and peripheral metabolic-inflammatory burden, thus supporting a combined approach for obesity-related or mixed-pattern CPP. Representative prescriptions include modified Zhibai Dihuang pills with Liujunzi decoction and modified Danzhi Xiaoyao powder with Erchen decoction, which integrate kidney yin-nourishment and ministerial fire-clearance with spleen qi-strengthening and phlegm resolution. Available clinical evidence suggests potential benefits in controlling secondary sexual characteristics, reducing gonadotropin and sex-steroid levels, and slowing bone-age advancement. Mechanistic studies indicate possible regulation of kisspeptin/GPR54/GnRH and LH/FSH-sex-steroid signaling, Th1/Th2/Treg homeostasis, NF-κB/NLRP3 pathways, adipokine imbalance, insulin resistance, hypothalamic inflammation, and gut microbiota-associated metabolism. However, most mechanistic links remain indirect, comparative trials are scarce, and direct correction of pathogenic MKRN3 or DLK1 variants has not been demonstrated. In this review, we have discussed the role of kidney and spleen dysfunction in CPP and explored the underlying mechanisms – particularly in the context of the neuro-endocrine-immune network that links central neuroendocrine activation with peripheral immune-metabolic signals. In addition, the application of TCM in the management of CPP, and the translational challenges of applying TCM as an adjunct to established CPP management have also been explored. Future research should prioritize CPP-specific pathway validation, identification of syndrome biomarkers, multi-omics-based stratification, multicenter trials, and long-term pediatric safety monitoring.
Yu-Jun Luo, Chao-Jie Huang, Yanbing Lu et al.· Frontiers in Immunology· 0 citations
Background Neuropathic pain (NP) frequently co-occurs with sleep disorders, yet the causal relationship between the two remain unclear, necessitating further investigation to elucidate their intrinsic connection. Methods We conducted linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), multivariable mendelian randomization (MVMR) and causal analysis using summary effect estimates (CAUSE) analyses based on genome-wide association study summary statistics of six NP subtypes (FinnGen R12) and six sleep traits (UK Biobank) to verify causal associations. Multi-method combined gene prioritization screening genes, with comprehensive sensitivity analyses and bias correction performed. Results Our analyses revealed that among all NP subtypes, only insomnia exerted a stable potential causal effect on sciatica. LDSC analysis revealed a significant positive genetic correlation between insomnia and sciatica (rg = 0.395, P < 0.0017). MR analyses demonstrated that insomnia significantly increased the risk of sciatica (OR = 3.15, 95% CI: 2.20–4.51, PIVW = 3.48E-10), with robust results confirmed by multiple sensitivity analyses. CAUSE further validated a positive causal association between insomnia and sciatica (OR = 3.899, 95% CI: 1.823–8.339, P = 0.003). MVMR proved the causal association remained significant after adjustment for psychiatric disorders (PIVW < 0.05). Heritability enrichment analysis indicated that the heritability of insomnia was mainly enriched in the central nervous system. And six potential pathogenic genes were screened via multiple integrated analytical methods. Among these candidates, EIF3KP1 and PPIP5K2 showed the strongest genetic evidence and were validated in the FinnGen database. Conclusion We identified a potential causal effect of insomnia on sciatica. The comorbidity of the two conditions may be regulated by genetic mechanisms associated with the central nervous system. EIF3KP1 and PPIP5K2 were prioritized as candidate genes, and further cellular and animal experiments are required to validate their potential as molecular targets for intervening in this comorbidity.
Shuyan Li, Xianmei Chen, Haiwen Cen et al.· Journal of Pain Research· 0 citations
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