Xiyuan Hospital of China Academy of Chinese Medical Sciences

Globally, there are over 3 million severe cases of influenza each year, leading to up to half a million deaths. This study provides a comprehensive analysis of the current status of children's influenza vaccine research over the past 20 years and explores potential future research trends, including improvements in vaccine coverage and strategies to address vaccine hesitancy. We extracted all research data on children's influenza vaccines from 2004 to 2024 using the Web of Science Core Collection (WOSCC). The contributions of various countries/regions, institutions, authors, and journals in this field were assessed, and research hotspots as well as promising future trends were predicted through keyword analysis using CiteSpace and VOSviewer. A total of 2,598 related publications from 2004 to 2024 were identified and collected for analysis. The United States (USA) and England emerged as the leading contributors with the highest number of published papers. AstraZeneca was identified as a key leader among research institutions, and Ambrose Christopher S was recognized as the most productive author in this field. The journals Vaccine and Human Vaccines & Immunotherapeutics stood out as the most prominent publications in this area. The keyword analysis highlighted that international research collaboration maybe a promising strategy for bridging global gaps; Addressing vaccine hesitancy could potentially increase vaccination coverage; Live attenuated vaccines, intranasal administration and universal vaccines are promising directions for future development. These insights highlight potential avenues for improving influenza vaccine coverage and inform strategies to mitigate vaccine hesitancy, crucial for protecting children and enhancing public health.

Although neferine exhibits obvious therapeutic effects against hypertension, its effects on cardiac protection remain unknown.

This study aimed to investigate its potential cardioprotective effects and associated mechanisms.

Spontaneously hypertensive rats (SHRs) were randomly divided into four groups, namely SHR, SHR + Neferine-L (2.5 mg/kg/day), SHR + Neferine-M (5 mg/kg/day), and SHR + Neferine-H (10 mg/kg/day). Wistar Kyoto rats were used as control. Various concentrations of neferine or double distilled water were then administered intragastrically for 10 weeks. Thereafter, cardiac function, pathological changes, cell apoptosis, and reactive oxygen species (ROS) accumulation, as well as their underlying mechanisms, were evaluated in SHRs and/or hypoxia-induced H9c2 cells.

Neferine treatment significantly mitigated the decrease in left ventricular ejection fraction and fractional shortening and increase in left ventricular mass, end-systolic volume, and cardiac injury in SHRs. In SHR cardiac tissues, neferine treatment reversed 154 upregulated and 108 and downregulated transcripts. Pathway enrichment analysis found that multiple pathways were commonly enriched, including the apoptosis, PI3K-Akt, MAPK, and HIF-1 pathways. Consistently, neferine treatment significantly mitigated cardiomyocyte apoptosis, restored mitochondrial membrane depolarization, and reduced ROS accumulation. Mechanistically, neferine treatment significantly decreased the phosphorylation of ERK, p38 MAPK, and JNK; the Bax/Bcl-2 ratio; and the expression of HIF-1α, NADPH oxidase 4, and cleaved caspases-3 and -9 but increased the phosphorylation of PI3K and Akt and the expression of CD31.

Neferine treatment effectively mitigated hypertensive cardiomyocyte apoptosis and attenuated the abnormal activation of multiple signaling pathways, including the PI3K/Akt, MAPK, and HIF-1 pathways.

Polygonum capitatum Buch.-Ham. ex D. Don (Pc, DB52/YC141-2003), a traditional herbal medicine utilized by the Miao nationality, is acknowledged for its therapeutic potential and efficacy in treating various urologic disorders, notably chronic bacterial prostatitis (CBP). Experimental and clinical studies have demonstrated that the combination of Pc with Ciprofloxacin (CIP) effectively alleviates the urinary symptoms in CBP patients,offering superior outcomes compared to monotherapy. However, the underlying mechanisms and specific constituents responsible for this synergistic effect remain poorly understood, which hinders its broader clinical application..

This study aims to elucidate the potential synergistic mechanism of Pc and CIP in ameliorating CBP and to identify the major active ingredient of Pc that contributed most significantly to the therapeutic efficacy when combined with CIP.

A rat model of CBP was induced in rats by prostate bilateral injections of Escherichia coli (E. coli.), followed by therapeutic intervention with a combination of Pc and CIP. The therapeutic effect of this combination was assessed by quantifying the Prostate viscera coefficient (PVC) and bacterial colonization. Histopathological changes in the prostate were observed using HE staining. The expressions of inflammatory mediators was quantified using Western blotting (WB), qRT-PCR, and immunohistochemical staining (IHC). To elucidate the molecular mechanisms underlying the synergism of the combination therapy, transcriptomic profiling was performed using RNA sequencing (RNA-seq). Differentially expressed genes were analyzed via Ingenuity Pathway Analysis (IPA) to identify regulated pathways, with critical targets further validated by qRT-PCR and WB. For direct drug target identification, Tissue-thermal proteome profiling (Tissue-TPP) was implemented, incorporating differential temperature heat treatment, data-independent acquisition (DIA) quantitative proteomics, and thermal shift curve analysis to characterize interaction targets of the Pc-CIP combination in prostate tissue. Binding affinity between the drug combination and identified targets was further confirmed through thermal shift assays. Finally, molecular docking simulations were conducted to characterize the predominant bioactive constituents of Pc that contributed synergistically to therapeutic outcomes when co-administered with CIP.

The results indicated that the combination of Pc and CIP significantly reduced the PVC and bacterial concentration, restored the prostate gland structure, and inhibited the mRNA and protein expression of pro-inflammatory factors (TNF-α and IL-1β) in CBP rats. RNA-Seq combined with IPA analysis showed that Pc combined with CIP significantly inhibited inflammatory signaling pathway in CBP rats, especially the NF-κB/IL-6/JAK2/STAT3 pathway. Moreover, Tissue-TPP revealed that Pik3cb is a direct target of Pc combined with CIP. Molecular docking studies showed that GA, a predominant component of Pc, can directly bind to Pik3cb. Finally, it was also found that the combination of GA and CIP significantly improved CBP.

The results suggest that Pc combined with CIP can mitigate CBP by targeting Pik3cb to inhibit the NF-κB/IL-6/JAK2/STAT3 signaling pathway, and GA may be a potential pharmacodynamic substance of Pc.