Cationic nanogels represent an alternative yet promising class of polymeric vectors for siRNA delivery. However, their intrinsic surface charges inevitably lead to the formation of a protein corona, which often compromises delivery efficiency. In this study, we propose a regulated PEGylation strategy to address this obstacle. Based on a recently developed electrostatic templated polymerization (ETP) method, we prepared cationic nanogels with precisely regulated PEG length and density, and thoroughly investigated their impact on protein corona resistance and siRNA delivery efficiency. The identified structure-property relationship between PEGylation and delivery performance enabled the optimization of the shell PEG, ideally with a block length of 113 units and a fraction of 1 %, which eliminated the protein corona and simultaneously promoted the delivery capability. The nanogel core consisted of cationic poly(N-(4-Vinylbenzyl)-N, N-Dimethylamine) (PVBDMA) chains cross-linked by a reduction-responsive linker. This design facilitated siRNA endocytosis and endosomal escape while enabling cytoplasmic release through the dissociation of the nanogels triggered by intracellular GSH. We clarify that, the engineered PEGylated nanogel integrate multiple essential functions for efficient siRNA delivery, leading to significant gene silencing both in vitro and in an orthotopic ovarian tumor model. We believe that the proposed PEGylation strategy further enhances the delivery capacity of cationic nanogel vectors, thereby boosting their potential applications in the delivery of biotherapeutics.

The occurrence and progression of tumors are linked to the process of pyroptosis. However, the precise involvement of pyroptosis-associated genes (PRGs) in endometrial cancer (EC) remains uncertain. 29 PRGs were identified as being either up-regulated or down-regulated in EC. PRGs subgroup analysis demonstrated distinct survival outcomes and diverse responses to chemotherapy and immune checkpoint blockade therapy. A higher expression of GPX4 and NOD2, coupled with lower levels of CASP6, PRKACA, and NLRP2, were found to be significantly associated with higher overall survival (OS) rates (p < 0.05). Conversely, lower expression of NOD2 was linked to lower progression-free survival (p = 0.021) and advanced tumor stage(p = 0.0024). NOD2, NLRP2, and TNM stages were identified as independent prognostic factors (p < 0.001). The LASSO prognostic model exhibited a notable decrease in OS among EC patients in the high-risk score group (ROC-AUC10-years: 0.799, p = 0.00644). Furthermore, NOD2 displayed a positive correlation with the infiltration of immune cells and the expression of immune checkpoints (p < 0.001). GPX4 and CASP6 are significantly associated with TMB and MSI (RTMB = 0.39; RMSI = 0.23). Additionally, a substantial upregulation of NOD2 was confirmed in both EC cells and tissue, indicating a positive relationship between advanced TNM stage (p < 0.0001) and infiltration of M1 phenotype macrophages. Nonetheless, its impact on patient OS did not reach statistical significance (p = 0.141). Our findings have contributed to the advancement of a prognostic model for EC patients. NOD2 receptor-mediated pyroptosis mechanism potentially regulates tumor immunity and promotes the transformation of macrophages from the M2 phenotype to the M1 phenotype, which significantly impacts the progression of EC.

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.

Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole-slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease-free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP-12. In conclusion, this study identified PACAP was associated with PNI in cervical cancer and suggested that tumour-derived PACAP reversed myelin differentiation of SCs to aid PNI.

Cervical cancer is considered one of the diseases with the highest mortality among women and with limited treatment options. Hydrogen (H-2) inhalation has been reported to have a variety of tumor-suppressive effects, but the exact mechanism remains unclear. In the present study, HeLa cervical cancer cells and HaCaT keratinocytes treated with H-2, and a HeLa xenograft mouse model subjected to H-2 inhalation were established. TUNEL, Cell Counting Kit-8 and Ki67 staining assays were used to detect cell apoptosis and proliferation. Oxidative stress was determined according to the levels of reactive oxygen species, malondialdehyde and superoxide dismutase. Tumor growth was recorded every 3 days, and the excised tumors were stained with hematoxylin and eosin. High-throughput RNA sequencing and subsequent Gene Ontology (GO) enrichment analysis were performed in HeLa-treated and un-treated HeLa cells. The expression of hypoxia-inducible factor (HIF)-1 alpha and NF-kappa B p65 was verified by western blotting, immunohistochemistry and reverse transcription-quantitative PCR. The results revealed an increased apoptosis rate, and reduced cell proliferation and oxidative stress in H-2-treated HeLa cells but not in HaCaT cells. Similarly, decreased tumor growth and cell proliferation, and enhanced cell apoptosis were observed in H-2-treated HeLa tumors. RNA sequencing and GO analysis suggest that downregulated HIF1A (HIF-1 alpha mRNA) and RelA (NF-kappa B p65) levels, and reduced NF-kappa B signaling were associated with the antitumor effect of H-2. Finally, decreased HIF-1 alpha and NF-kappa B p65 expression both at the transcriptional and translational levels were observed in H-2-treated HeLa cells and in HeLa-derived tumors. In conclusion, the present study reveals a novel mechanism of H-2 against cervical cancer, which may serve as a potential therapeutic target in clinical practice.

Long non-coding RNA (lncRNA) has increasingly been identified as a key regulator in pathologies such as cancer. Multiple platforms were used for comprehensive analysis of ovarian cancer to identify molecular subgroups. However, lncRNA and its role in mapping the ovarian cancer subpopulation are still largely unknown. RNA-sequencing and clinical characteristics of ovarian cancer were acquired from The Cancer Genome Atlas database (TCGA). A total of 52 lncRNAs were identified as aberrant immune lncRNAs specific to ovarian cancer. We redefined two different molecular subtypes, C1(188) and C2(184 samples), in "iClusterPlus" R package, among which C2 grouped ovarian cancer samples have higher survival probability and longer median survival time (P <0.05) with activated IFN-gamma response, Wound Healing and Cytotoxic lymphocytes signal; 456 differentially expressed genes were acquired in C1 and C2 subtypes using limma (3.40.6) package, among which 419 were up-regulated and 37 were down-regulated, in TCGA dataset. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed that these genes were actively involved in ECM-receptor interaction, PI3K-Akt signaling pathway interaction KEGG pathway. Compared with the existing immune subtype, the Cluster2 sample showed a substantial increase in the proportion of the existing C2 immune subtype, accounting for 81.37%, which was associated with good prognosis. Our C1 subtype contains only 56.49% of the existing immune C1 and C4, which also explains the poor prognosis of C1. Furthermore, 52 immune-related lncRNAs were used to divide the TCGA-endometrial cancer and cervical cancer samples into two categories, and C2 had a good prognosis. The differentially expressed genes were highly correlated with immune-cell-related pathways. Based on lncRNA, two molecular subtypes of ovarian cancer were identified and had significant prognostic differences and immunological characteristics.

PURPOSE:To compare perioperative outcomes between robotic single-site surgical technique and conventional laparoendoscopic single-site surgical technique.METHODS:This was a retrospective cohort study involving 67 patients who received robotic single-site surgery or laparoendoscopic single-site surgery for the treatment of stage IB1 cervical squamous carcinoma. The robotic single-site radical hysterectomy technique combined with pelvic lymph node dissections were performed in 32 patients while the laparoendoscopic single-site radical hysterectomy technique combined with pelvic lymph node dissections were performed in 35 patients.RESULTS:The enrolled patients had been diagnosed with stage IB1 cervical squamous carcinoma. The perioperative outcomes were mean age (51.63±8.32 years in the lymph node dissection (RSS group) and 53.14±8.14 years in the lymph node dissection (LESS group), p=0.453); BMIs (23.76±2.72 in the RSS group and 23.46±2.28 in the LESS group, p=0.629); shorter operative times (223.56±15.43 min in the RSS group and 248.61±20.89 min in the LESS group, p<0.01) and less estimated blood loss (217.25±16.77 mL in the RSS group and 294.74±24.00 mL in the LESS group, p<0.01). None of the study participants exhibited postoperative pain. There were no statistically significant differences in the length of hospital stay (p=0.865), perioperative complications (p=0.602), duration of closure and removal of catheter (p=0.518) as well as in pathological diagnoses between the two groups.CONCLUSION:Robotic single-site surgery can be used in the treatment of early stage cervical cancer as it exhibits acceptable operative times and perioperative outcomes. This surgical technique is feasible and safe.

OBJECTIVES:The accuracy of robotic surgery has been recognized by many doctors, but traditional robotic surgery requires 4-5 puncture holes in the operating area. With the popularization and application of single port laparoscopic surgery, the aesthetic of abdominal incision of robotic surgery has been challenged. How to use the single-site platform to complete robot operation is a new field worthy of our exploration. Here we introduce a kind of technology innovation of robot-assisted single-site laparoscopic surgery through common robotic equipment and LAGIS single-site port. METHODS:From November 2018 to March 2019, 20 patients with cervical cancer or endometrial cancer admitted to the minimally invasive gynecological group were included. Single-hole robotic surgery was successfully performed in all 20 patients, with no additional assisted puncture and no conversion to laparotomy. The operation time of patients, intraoperative bleeding volume and hospitalization time were recorded and compared. Besides, the Intraoperative complications were observed and analyzed. RESULTS AND CONCLUSIONS:By comparison, we can find that the effect of this innovative single-hole robotic surgery is significantly better than that of traditional single-hole laparoscopy.