Jingtong Granules is a widely used Chinese patent medicine approved by China’s National Medical Products Administration for cervical spondylotic radiculopathy, but its systems-level mechanism remains insufficiently defined. This study investigated its potential mechanisms in cervical degeneration using a staged integrative framework. Candidate targets were screened and evaluated using transcriptomic, genetic, and structural evidence. Intersecting compound targets from four databases with cervical-spondylosis-associated genes identified 40 multi-source-supported drug–disease targets and 17 hub genes. The hub module was dominated by inflammatory cytokines, matrix-remodeling molecules, and central signaling regulators, with enrichment concentrated in PI3K-Akt, TNF, IL-17, and AGE-RAGE signaling. MMP9 showed the strongest pathway association, exploratory blood-discriminative potential, and nominal genetic support for spondylosis risk. AKT1 was the highest-degree signaling hub, and molecular dynamics simulations supported the stability of its quercetin and kaempferol complexes. Single-cell analysis placed the hub module in relevant disc-cell populations. However, these findings may be confounded by age because patient and control age ranges did not overlap. Overall, this study prioritizes an AKT1/MMP9-centered inflammatory and extracellular-matrix-remodeling module as a patient-grounded candidate mechanism of Jingtong Granules in cervical degeneration. Experimental validation in adequately powered disease-specific cohorts is warranted.
Endometriosis (EMs) pain severely reduces patients’ quality of life, but its underlying mechanisms are not fully understood. Mast cells and C-C motif chemokine ligand 2 (CCL2) are highly abundant in EMs lesions, yet their roles in neural sensitization remain unclear. Bioinformatics analysis of a public scRNA-seq dataset (GSE179640) was performed to define CCL2 expression across EMs cell types and its enrichment in mast cells. We collected ectopic and eutopic endometrial tissues from EMs patients and normal endometrial tissues from controls. CCL2, C-C chemokine receptor type 4 (CCR4) expression, mast cell numbers, and protein gene product 9.5-positive nerve fibers were measured and correlated with pain. In vitro coculture models of endometrial stromal cells, mast cells, and neurons were established, and related functions were examined. An in vivo EMs rat model was used to assess pain thresholds and nerve fiber density. CCL2 was significantly upregulated in EMs and positively correlated with pain, mast cell infiltration, and sensory nerves. Stromal cell–mast cell coculture increased CCL2. CCL2 knockdown in mast cells inhibited degranulation and migration but promoted neurite outgrowth, nerve growth factor expression, and calcium influx in neurons. Inhibiting CCR4 relieved hyperalgesia and reduced lesion nerve fibers in rats. Mast cell–derived CCL2 promotes neural sensitization by activating neuronal CCR4, which contributes to EMs pain. Targeting CCL2/CCR4 may serve as a new therapeutic approach for EMs pain.
This study aimed to explore the characteristics of tongue microbiota in children with geographic tongue (GT) and provide microecological evidence for elucidating the occurrence and progression mechanism of GT. 16S rDNA high-throughput sequencing combined with bioinformatic analysis was adopted to compare the species differences of tongue microbial communities between children with GT and healthy children. The microbial richness of tongue coating in children with GT was markedly lower than that in healthy children (p < 0.05). Species analysis revealed that the dominant genera in healthy children's tongue coating were Prevotella, Veillonella, and Actinomyces, while the tongue coating of children with GT was predominated by Neisseria, Pasteurellaceae, and Streptococcus. Kyoto Encyclopedia of Genes and Genomes functional pathway enrichment analysis demonstrated an overall downregulation trend of metabolic functions in tongue coating microbiota of children with GT, with main differential pathways in histidine metabolism and teichoic acid biosynthesis. These results indicate that the onset of GT is highly correlated with abnormal enrichment of Neisseria, Pasteurellaceae, and Streptococcus. Imbalance of the tongue coating microbial communities may be involved in the development of GT.
Matched single-cell analyses may reveal glioblastoma recurrence changes obscured by pooled comparisons. We reanalyzed tumor-classified cells from 9 Wang primary-recurrent pairs and 59 paired CARE patients using recurrent-minus-primary program vectors. Five of nine Wang pairs were assigned an astrocytic-like (AC-like) route, but its exact 95% proportion interval was 21-86%, and an exact paired sign-flip test did not establish an excess of this route (p = 0.227). Continuous positive-program contributions indicated mixed trajectories. A 10-gene candidate expression module selected from 5 Wang AC-like pairs increased in all 11 CARE AC-like patients in the original sample-level analysis (median T2-T1 score +0.277), versus 13 of 48 other patients (median -0.125). In the CARE authors' copy-number-informed malignant-cell table, 242,702 cells from paired T1/T2 samples were scored; the mean paired score change was +0.412 in AC-like patients and -0.158 in others (between-group difference +0.570, 95% confidence interval 0.321-0.820). Enrichment implicated glutamate transport but does not establish a single pathway or EGFR/NFIA causality. These findings support a recurrence-associated candidate module in an independent cohort while leaving discovery-route frequency, mechanistic function, and spatial localization unresolved.
Public mucosal transcriptomic datasets provide an opportunity to examine whether experimental epithelial barrier biology is reflected in human inflammatory bowel disease (IBD) endpoints. We constructed a prespecified barrier-injury transcriptomic score from an inositol polyphosphate multikinase-histone deacetylase 3-matrix metalloproteinase (MMP) barrier-biology gene set and epithelial junctional genes, then evaluated it across 10 public IBD mucosal transcriptomic cohorts (2172 scored biopsies) and an independent prospective adult cohort (GSE193677; 1162 participants). Adult cohorts were analyzed for mucosal healing, clinical remission, or treatment response; pediatric and early onset cohorts were analyzed separately. In UNIFI (GSE206285), a higher baseline score was inversely associated with week 8 mucosal healing (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.45-0.71, p < 0.001). In GSE193677, the score was associated with IBD compared with control status (OR: 1.71, 95% CI: 1.45-2.02) and with endoscopic and histologic activity. The association was directionally consistent across biopsy-selection analyses and exceeded expression- and variance-matched random-gene estimates (empirical p = 0.034), while MMP and inflammatory comparators were at least as strong. Single-cell data localized the MMP module predominantly to stromal cells. These findings support retrospective transcriptomic stratification of mucosal injury states and define a barrier biology-motivated bulk mucosal readout shaped by stromal inflammatory remodeling in human tissue.
