Liang Wen’s research while affiliated with 307 Hospital of the Chinese People's Liberation Army and other places

Background Cervical cancer remains a significant global health concern, necessitating effective screening strategies. Traditional methods, such as liquid-based cytology (LBC) and high-risk human papillomavirus (HR-HPV) testing, have limitations in sensitivity and specificity. This study aimed to evaluate the diagnostic performance of p16, Ki-67, and minichromosome maintenance protein 2 (MCM2) as biomarkers in cervical cancer screening, both as standalone methods and in combination, to improve early detection and risk stratification. Methods This prospective study included 344 women who underwent LBC and HR-HPV testing, followed by the gold standard of colposcopy and biopsy. Immunocytochemical (ICC) staining for p16, Ki-67, and MCM2 was performed. The sensitivity, specificity, and Youden index were calculated to compare the efficacy of the single and combined screening methods. Results LBC alone demonstrated suboptimal sensitivity, while HR-HPV testing exhibited low specificity. Among the single methods, dual staining of p16 paired with MCM2 (p16/MCM2) when using a high-risk threshold achieved the highest Youden index (0.55). The combination of LBC with p16/MCM2 yielded superior sensitivity (96.3%) and moderate specificity (42.6%), outperforming the combination of HR-HPV with dual staining of p16/MCM2. Importantly, all missed diagnoses were high-grade squamous intraepithelial lesion (HSIL) with cervical intraepithelial neoplasia (CIN) grades 2–3, and no cases of cervical cancer were missed. Conclusions HR-HPV-based primary screening with p16/Ki-67 triage may offer a viable strategy for cervical cancer detection. Combining LBC with p16/MCM2 dual staining demonstrated improved sensitivity and specificity compared to conventional methods. Notably, p16/MCM2 as a standalone assay achieved the highest Youden index when using a high-risk threshold. Further validation through multicenter studies is essential to confirm its generalizability.

Objective Recurrent implantation failure (RIF) is a significant challenge in assisted reproductive technology (ART), affecting many women undergoing in vitro fertilization (IVF). This study aims to compare the efficacy of various intrauterine infusion treatments, including granulocyte colony-stimulating factor (G-CSF), platelet-rich plasma (PRP), human chorionic gonadotropin (HCG), and peripheral blood mononuclear cells (PBMCs), in improving clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR) in women with RIF. Methods A comprehensive search was conducted in multiple databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Web of Science, and China National Knowledge Internet (CNKI), to identify randomized controlled trials (RCTs) evaluating the efficacy of intrauterine infusion treatments for RIF. Data extraction and quality assessment were performed independently by two reviewers. Network meta-analysis was conducted using a random-effects model to compare the outcomes of different treatments. Results A total of 25 RCTs involving 3035 patients were included in the network meta-analysis. The treatments involved G-CSF, PRP, HCG, PBMCs, placebo, and blank control. The results of the network meta-analysis for CPR and LBR were statistically significant among treatments, but there was no statistical significance in MR. The surface under cumulative ranking curve (SUCRA) ranking of CPR and LBR showed that intrauterine infusion treatments of G-CSF, PRP, HCG, and PBMCs were much better than placebo and blank. The SUCRA values of CPR were ranked probabilistically from high to low as follows: PRP (84.5%) > PBMCs (76.5%) > G-CSF (65.7%) > HCG (52.5%) > placebo (20.8%) > blank (0.1%). The SUCRA values of LBR were ranked probabilistically from high to low as follows: PRP (81.4%) > PBMCs (64.6%) > G-CSF (58.0%) > HCG (48.7%) > placebo (42.4%) > blank (4.9%). Conclusion All these findings confirmed that intrauterine infusions of PRP and PBMCs significantly improve pregnancy outcomes in women with RIF. PRP emerged as the most effective treatment. However, to establish the most effective approach for managing patients with RIF, future research should prioritize direct and robust comparisons between PRP and other therapeutic strategies, ensuring a comprehensive evaluation of their relative efficacy.

The formation of immune synapses (ISs) between cytotoxic T cells and tumor cells is crucial for effective tumor elimination. However, the role of ISs in immune evasion and resistance to immune checkpoint blockades (ICBs) remains unclear. We demonstrate that ICAM-1, a key IS molecule activating LFA-1 signaling in T and natural killer (NK) cells, is often expressed at low levels in cancers. The absence of ICAM-1 leads to significant resistance to T and NK cell-mediated anti-tumor immunity. Using a CRISPR screen, we show that ICAM-1 is epigenetically regulated by the DNA methylation pathway involving UHRF1 and DNMT1. Furthermore, we engineer an antibody-based therapeutic agent, “LFA-1 engager,” to enhance T cell-mediated anti-tumor immunity by reconstituting LFA-1 signaling. Treatment with LFA-1 engagers substantially enhances immune-mediated cytotoxicity, potentiates anti-tumor immunity, and synergizes with ICB in mouse models of ICAM-1-deficient tumors. Our data provide promising therapeutic strategies for re-engaging immune stimulatory signals in cancer immunotherapy.

Background: Despite breakthroughs in treatment, ovarian cancer (OC) remains one of the most lethal gynecological malignancies, with an increasing age-standardized mortality rate. This underscores an urgent need for novel biomarkers and therapeutic targets. Although growth factor receptor-bound protein 7 (GRB7) is implicated in cell signaling and tumorigenesis, its expression pattern and clinical implications in OC remain poorly characterized. Methods: To systematically investigate GRB7’s expression in OC, our study utilized extensive datasets from TCGA, GTEx, CCLE, and GEO. The prognostic significance of GRB7 was evaluated by means of Kaplan–Meier and Cox regression analyses. Using a correlation analysis and gene set enrichment analysis, relationships between GRB7’s expression and gene networks, immune cell infiltration and immunotherapy response were investigated. In vitro experiments were conducted to confirm GRB7’s function in the biology of OC. Results: Compared to normal tissues, OC tissues exhibited a substantial upregulation of GRB7. Reduced overall survival, disease-specific survival, and disease-free interval were all connected with high GRB7 mRNA levels. The network study demonstrated that GRB7 is involved in pathways relevant to the course of OC and has a positive connection with several key driver genes. Notably, GRB7’s expression was linked to the infiltration of M2 macrophage and altered response to immunotherapy. Data from single-cell RNA sequencing data across multiple cancer types indicated GRB7’s predominant expression in malignant cells. Moreover, OC cells with GRB7 deletion showed decreased proliferation and migration, as well as increased susceptibility to T cell-mediated cytotoxicity. Conclusion: With respect to OC, our results validated GRB7 as a viable prognostic biomarker and a promising therapeutic target, providing information about its function in tumorigenesis and immune modulation. GRB7’s preferential expression in malignant cells highlights its significance in the biology of cancer and bolsters the possibility that it could be useful in enhancing the effectiveness of immunotherapy.