Ruifang Wu

Objectives: This bibliometric analysis systematically evaluated the research landscape, emerging trends, and key focus areas in adenomyosis to guide future research directions. Design: Performance analysis combined with scientific mapping of global adenomyosis research literature. Data sources: Web of Science Core Collection (1980–2024). Data extraction and synthesis: Articles were manually screened. Bibliometrix (R 4.3.0), VOSviewer, and CiteSpace analyzed productivity, collaboration, citation patterns, and research trends. Derived data and analysis scripts are deposited in the Open Science Framework (OSF) under a citable DOI. Results: Among 3100 included publications, China led output (752, 24.26%, full-counted), followed by the United States (414, 13.35%), Japan (350, 11.29%), Italy (215, 6.94%), and South Korea (128, 4.13%). In the 2 adenomyosis-specific corpora, however, the United States ranked first. The US had the highest citations and international collaboration, though international co-authorship among top-producing countries remained low (16.14%). Leading institutions were Fudan University (89), Shandong University (52), and University of Tokyo (49). Top journals by volume: Fertility and Sterility, Human Reproduction, and Journal of Minimally Invasive Gynecology. Research focus shifted from hysterectomy and uterine artery embolization toward high-intensity focused ultrasound (HIFU), and from endothelial nitric oxide synthase/induced adenomyosis toward ectopic endometrium. Eight keyword clusters emerged; the 4 largest (#0 EMT, #1 HIFU, #2 endometrial cancer, #3 pregnancy outcomes) form the present focus. Burst analysis identified “consensus” (2020–2024), “pathogenesis” (2022–2024), and “pregnancy outcome” (2022–2024) as recent and currently active hotspots. Conclusions: Current adenomyosis research centers on ectopic endometrium and EMT in pathogenesis, fertility outcomes, long-term efficacy of HIFU and fertility-sparing surgery, links to endometrial cancer, and adverse pregnancy outcomes. Beyond deepening pathogenesis and pregnancy-outcome research, key future directions include enhancing international collaboration and developing internationally agreed, evidence-based standardized terminology, diagnostic criteria, and classification systems for adenomyosis.

Human papillomavirus (HPV) persistence and progression to high-grade squamous intraepithelial lesions (HSIL) involves complex interactions between the cervicovaginal microbiome, metabolome, and host immune responses. While Lactobacillus crispatus has been associated with the risk of cervical lesion progression, the underlying molecular mechanisms remain poorly understood. We conducted a cross-sectional study of 74 HPV-positive Chinese women diagnosed with low-grade SIL (LSIL) or HSIL. Cervicovaginal swabs were analyzed using 16S rRNA sequencing and untargeted LC-MS metabolomics, while cervical exfoliated cells underwent RNA-sequencing. Community state types (CSTs) were determined by hierarchical clustering, and differentially expressed genes were identified across CSTs and SIL grades. Bayesian network analysis was employed to model molecular interactions between CVM compositions, metabolites, host gene expression, and HSIL status. Key findings were validated through in vitro experiments using HPV16-infected cervical epithelial cells (Ect1/E6E7) co-cultured with Lactobacillus supernatants and D-lactic acid. L. crispatus-dominated communities (CST_I) were significantly enriched in LSIL compared to HSIL patients (16.22% vs 2.70%, p < 0.05). CST_I exhibited 2.2–2.8-fold higher D-lactic acid levels compared to L. iners-dominated (CST_III) and non-Lactobacillus-dominated (CST_IV) communities. Transcriptomic analysis identified 116 DEGs varying across both CSTs and SIL grades, with functional enrichment revealing HSIL-associated genes involved in axonogenesis and pattern specification, while LSIL-associated genes were linked to immune responses. Bayesian network modeling suggested that CST_I-derived D-lactic acid inhibits FOXD1 expression, which directly correlates with HSIL status. In vitro validation confirmed that L. crispatus supernatant and D-lactic acid significantly reduced FOXD1 expression (p < 0.05), decreased HPV16 viral load, and inhibited Ect1/E6E7 cell growth. This study elucidates a novel protective mechanism whereby L. crispatus-derived D-lactic acid modulates cervical gene expression, particularly through FOXD1 downregulation, conferring negative links to precancerous cervical lesions. These findings provide mechanistic insights into microbiome-mediated cervical cancer prevention and suggest potential therapeutic targets for intervention strategies aimed at reducing HSIL progression. The online version contains supplementary material available at 10.1186/s12967-026-07982-w.

Therapeutic elimination of high-grade cervical intraepithelial neoplasia (CIN) is widely implemented for cervical cancer prevention. Despite the demonstrated dysbiosis of vaginal microenvironment in high-grade CIN, its post-therapy restorations remain to be poorly understood, especially in functional aspects. This study aimed to characterize temporal changes in both vaginal microbiota (VM) and metabolome (VMeta) following therapeutic elimination of high-grade CIN. We conducted a longitudinal study of 32 HPV-positive women with high-grade CIN who underwent therapeutic procedures. Vaginal swabs were collected at baseline (pre-therapy) and at 6- and 12-month follow-up visits for integrated VM and VMeta analysis. We observed a gradual restoration of Lactobacillus crispatus levels from baseline to 12 months ( P < 0.05). Concurrently, we detected significant decreases in dysbiosis-associated bacteria, including Prevotella bivia , Ureaplasma parvum , and Peptoniphilus sp. 6 months post-therapy compared to the baseline. VMeta analysis revealed distinct metabolic shifts across the follow-up periods. The early post-therapy phase (baseline to 6 months) was characterized by enrichment of glycerophospholipids and depletion of nucleotide metabolites, while the later phase (6–12 months) showed increases in flavonoids, lysophospholipids, bioactive amides, and amino acid metabolism. Integration of correlation and dynamic Bayesian network analysis indicated potential regulatory relationships and time-lag effects involving HPV infection, L. crispatus , Bifidobacterium sp., Streptococcus anginosus , Megasphaera sp., U. parvum, and those metabolites. This study enhances our understanding of a sequential restoration process post-therapy in the vaginal microenvironment. IMPORTANCE: Therapeutic elimination of high-grade CIN is routine, yet functional recovery of the vaginal ecosystem is poorly defined. In a 12-month longitudinal multi-omics study of 32 women, we show stepwise restoration: progressive L. crispatus dominance with sustained decreases in dysbiosis-associated taxa ( P. bivia, U. parvum, Peptoniphilus ). Metabolically, an early rise in glycerophospholipids and fall in nucleotide metabolites is followed by later enrichment of flavonoids, lysophospholipids, bioactive amides, and amino acid derivatives. Correlation and dynamic Bayesian network analyses reveal putative regulatory links, time-lag effects, and downstream impacts of HPV clearance. These findings deliver a functional roadmap of post-therapy recovery, nominate measurable microbial–metabolite milestones and candidate biomarkers for monitoring, and suggest targets for adjunct interventions to accelerate re-establishment of protective states. This work informs precision follow-up in cervical cancer prevention programs.

Endometriosis (EMs) and adenomyosis (AD) are prevalent gynecological disorders with overlapping symptoms but potentially distinct pathophysiology. This study was to understand different gene expression patterns of eutopic endometrium between EMs and AD in Chinese populations. This study investigated transcriptomic profiles of eutopic endometrium in Chinese women with EMs (n = 25), AD (n = 22), and controls (n = 18) to identify shared and disease-specific gene expression patterns. RNA sequencing and bioinformatic analyses revealed 370 differentially expressed genes (DEGs) between EMs and controls, as well as 309 DEGs between AD and controls. Both conditions showed significant downregulation of immune-related pathways compared to controls, though with disease-specific immune signatures. We identified 115 shared DEGs between EMs and AD, primarily involved in inflammatory processes, while disease-specific DEGs highlighted unique pathophysiological mechanisms: antibacterial responses in EMs and neutrophil activation in AD. Direct comparison between EMs and AD revealed 46 DEGs, with EMs-upregulated genes enriched in mucosal immunity. In addition, EMs-enriched pathways included oxidative phosphorylation, ribosome biogenesis, and arachidonic acid metabolism, while AD-enriched pathways involved Wnt signaling and epithelial proliferation. This study identified shared inflammatory processes of eutopic endometrium for EMs and AD in a Chinese population. EMs-enriched and AD-enriched pathways also inform distinct diagnostic and therapeutic strategies between EMs and AD.

Currently, there is no relevant literature specifically discussing the human papillomavirus (HPV) negative conversion rate following Hiporfin photodynamic therapy (PDT) in HPV-associated high-grade squamous intraepithelial lesion (HSIL) of the female lower reproductive tract. Our study aims to fill this gap. Prospective study of 91 patients aged 37.4 ± 13.2 years old with HSIL in the female lower reproductive tract (cervical HSIL: 55, vaginal HSIL: 25, cervical HSIL combined with vaginal HSIL: 8, cervical HSIL combined with vulvar HSIL: 1, vaginal HSIL combined with vulvar HSIL: 2). Hiporfin^® (2 mg/kg) was administered intravenously, and 48–72 h later, 630-nm laser irradiation was applied to the lesions. The median follow-up period was 36 months. Before treatment, all patients (91/91, 100%) tested positive for HPV, and only 6 patients (6/91, 6.6%) had been previously vaccinated against HPV. The HPV negative conversion rates were 74.5% (41/55), 89.1% (49/55), 89.8% (44/49) and 95.8% (23/24) at 3–6 months, 12 months, 24 months and 36 months respectively after PDT in treating cervical HSIL. For vaginal HSIL, the negative conversion rates were 28.0% (7/25) at 3–6 months, 52.0% (13/25) at 12 months, 60.9% (14/23) at 24 months, and 64.7% (11/17) at 36 months. In cases of multiple sites of female lower genital tract HSIL, the negative conversion rates were 18.2% (2/11), 45.5% (5/11), 60.0% (6/10), and 62.5% (5/8) at 3–6, 12, 24, and 36 months, respectively. Hiporfin-PDT was most effective in achieving HPV negative conversion for treating cervical HSIL, followed by vaginal HSIL, and finally for multisite female lower genital tract HSIL.

Vaginal microbiota (VM) links to the risk of persistent HPV infection and the progression of cervical intraepithelial neoplasia (CIN). However, a comprehensive understanding of concurrent alterations in VM and metabolome associated with that risk remains elusive in population-based studies, particularly among Chinese women. This study conducted an extensive analysis of VM and metabolome profiles in a cohort of 56 Chinese women, classified into HPV_C (natural clearance of HPV, n = 18) and HPV_PH(persistent HPV infection accompanied by high-grade CIN, n = 38), based on the result of 3–6 months follow-up visits. Our analysis revealed a higher prevalence of Lactobacillus-dominated samples in the HPV_C cohort. Notably, the vaginal metabolome exhibited a significant interaction with VM, with Lactobacillus emerging as a pivotal influencer. We identified 386 metabolites that significantly differentiated between HPV_C and HPV_PH groups, of which 364 were associated with VM components such as Lactobacillus, Hoylesella, Fannyhessea and Megasphaera. Further examination showed that 66 of these 364 metabolites positively correlated with Lactobacillus, including citric acid, DL-beta-Leucine, Xanoic acid and Norcholic acid. Conversely, 19 metabolites, including HPV_PH enriched maltotriose and N-Acetyl-L-aspartic acid, negatively correlated with Lactobacillus. Further analysis suggested potential bi-directional modulation between VM and persistent HPV infection accompanied by high-grade, being partially mediated by vaginal metabolites. This study provides additional insights into the correlations between concurrent alterations in VM and metabolome associated with persistent HPV infection accompanied by high-grade CIN.