Yan Chen

Association between the quantitative characteristics of dual-energy spectral CT and cytoreduction surgery outcome in patients with advanced epithelial ovarian cancers: A prospective observational study

This study aimed to explore the association between the quantitative characteristics of dual-energy spectral CT and cytoreduction surgery outcome in patients with advanced epithelial ovarian carcinoma (EOC). In this prospective observational study, patients with advanced EOC (federation of gynecology and obstetrics stage III–IV) treated in the Department of Gynecological Oncology at our Hospital between June 2021 and March 2022 were enrolled. All participants underwent dual-energy spectral computed tomography (DECT) scanning 2 weeks before cytoreductive surgery. The quantitative data included peritoneal cancer index (PCI) determined by DECT, CT value at 70 keV, normalized iodine concentration, normalized water concentration, effective atomic number (effective-Z), and slopes of the spectral attenuation curves (slope λ Hounsfield unit). Fifty-five participants were included. The patients were 57.2 ± 9.8 years of age, and 72.7% were menopausal. The maximal diameter of tumors was 8.6 (range, 2.9–19.7) cm, and 76.4% were high-grade serous carcinomas. Optimal cytoreduction was achieved in 43 patients (78.2%). Compared with the optimal cytoreductive group, the suboptimal cytoreductive group showed a higher PCI (median, 21 vs 6, P < .001), higher 70 keV CT value (69.5 ± 16.6 vs 57.1 ± 13.0, P = .008), and higher slope λ Hounsfield unit (1.89 ± 0.66 vs 1.39 ± 0.60, P = .015). The multivariable analysis showed that the PCI (OR = 1.74, 95%CI: 1.24–2.44, P = .001) and 70 keV CT value (OR = 1.07, 95%CI: 1.01–1.13, P = .023) were independently associated with a suboptimal cytoreductive surgery. The area under the receiver operating characteristics curve of PCI and 70 keV CT value was 0.903 (95%CI: 0.805–1.000, P = .000) and 0.740 (95%CI: 0.581–0.899, P = .012), respectively. High PCI and 70 keV CT value are independently associated with suboptimal cytoreductive surgery in patients with advanced EOC. The PCI determined by DECT might be a better predictor for suboptimal cytoreduction.

Analysis of the correlation between vaginal microbiota and high-risk human papillomavirus infection and cervical lesions

The aim of this study was to evaluate changes in the vaginal microbiota and biomarkers among high-risk human papillomavirus (hrHPV)-positive women, those with hrHPV accompanied by mucositis, and patients with cervical intraepithelial neoplasia (CIN) and to establish a novel predictive model. Vaginal samples from 102 women were categorized into four groups: control group (n = 26), hrHPV-positive group (n = 22), hrHPV-positive with mucositis group (n = 26), and CIN group (n = 28). Microbiota analysis was performed using the PacBio platform with full-length 16S rDNA gene sequencing. The vaginal microbiota in the hrHPV-positive, hrHPV-positive with mucositis, and CIN groups showed significant differences compared with the healthy control group. The microbial richness in the hrHPV-positive group was significantly different from both the CIN group and healthy controls. Compared with the control group, the hrHPV-positive group exhibited significantly increased relative abundances of Bifidobacterium , Escherichia-Shigella , Hoylesella and nominally increased abundances of Gardnerella , Prevotella , along with a significant decrease in Lactobacillus . No statistically significant differences were retained between the hrHPV-positive group and the hrHPV-positive with mucositis group after FDR correction for the top 10 genera. Compared with the hrHPV-positive with mucositis group, the CIN group demonstrated significantly reduced levels of Pseudomonas, nominally decreased levels of Bifidobacterium and Faecalibacterium , whereas Glutamicibacter and Sporosarcina were nominally enriched. A random forest model was constructed to predict risk across groups and demonstrated good predictive performance, suggesting that vaginal microbiota may serve as valuable indicators for predicting cervical lesion risk. During hrHPV infection, significant alterations occur in the vaginal microecology, primarily characterized by an increase in pathogenic bacteria and a reduction in beneficial bacterial populations.

Independent predictive value of blood inflammatory composite markers in ovarian cancer: recent clinical evidence and perspective focusing on NLR and PLR

AbstractOvarian cancer (OC) is one of the deadliest malignant tumors affecting women worldwide. The predictive value of some blood inflammatory composite markers in OC has been extensively reported. They can be used for early detection and differential diagnosis of OC and can be used for predicting survival, treatment response, and recurrence in the affected patients. Here, we reviewed the predictive values of composite inflammatory markers based on complete blood count, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, and systemic inflammation index and markers based on blood protein, namely C-reactive protein-to-albumin ratio and prognostic nutritional index in OC, with a focus on NLR and PLR. We referred to the clinical studies on these six markers, reviewed the patient population, and summarized the marker cut-off values, significance, and limitations of these studies. All these studies were retrospective and most of them were single-center clinical studies with small sample sizes. We found that the cut-off values of these markers have not been unified, and methods used to determine these values varied among studies. The predictive value of these markers on survival was mainly reflected in the postoperative patients of multiple subtypes of ovarian cancer including epithelial OC, high-grade serous ovarian carcinoma, and ovarian clear cell carcinoma. We focused on NLR and PLR and calculated their pooled hazard ratios. NLR and PLR were reliable in predicting overall and progression-free survivals in patients with OC. Therefore, it is necessary to adjust important confounding factors and conduct a long-term follow-up prospective cohort study to further clarify the cut-off values of NLR and PLR and their clinical applications.

CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation

AbstractOvarian tumor family deubiquitinase 4 (OTUD4), a member of the OTU deubiquitinating enzyme, is implicated to decrease in cancer to regulate cell apoptosis. However, the role of OTUD4 in cigarette smoke induced epithelial cell apoptosis and its mechanism have not been elucidated. In this study, we showed that OTUD4 protein reduced in CSE treated mice and airway epithelial cells. OTUD4 silence aggravated cell apoptosis and emphysematous change in the lung tissue of cigarette smoke extract (CSE) treated mice. Additionally, restoration of OTUD4 in the lung of mice alleviated CSE induced apoptosis and emphysematous morphology change. The effect of OTUD4 on cell apoptosis was also confirmed in vitro. Through protein profile screening, we identified that OTUD4 may interact with plasminogen activator inhibitor 1(PAI-1). We further confirmed that OTUD4 interacted with PAI-1 for de-ubiquitination and inhibiting CSE induced PAI-1 degradation. Furthermore, the protective role of OTUD4 in airway epithelial cells apoptosis was blocked by PAI-1 deactivation. Taken together, our data suggest that OTUD4 regulates cigarette smoke (CS)-triggered airway epithelial cell apoptosis via modulating PAI-1 degradation. Targeting OUTD4/PAI-1 signaling might potentially provide a therapeutic target against the lung cell apoptosis in cigarette smoke (CS)-induced emphysema.

Retracted: Reduced levels of miR‐485‐5p in HPV‐infected cervical cancer promote cell proliferation and enhance invasion ability

Cervical cancer (CC) is the most common gynecological malignancy, with high incidence and mortality rates in China. The microRNA miR‐485‐5p has previously been reported to serve as a negative regulator of tumorigenesis in breast cancer and hepatocellular carcinoma, and miR‐485‐5p has been observed to be differentially expressed between CC and normal control tissue. Here, we confirmed that miR‐485‐5p expression is lower in CC than in adjacent normal tissue and proceeded to investigate the effects of miR‐485 on tumor behavior in CC cell lines. We report that miR‐485‐5p transcription is decreased in HPV‐infected CC tissue, and levels of miR‐485 in clinical samples are positively correlated with the 5‐year overall survival rate. The Transwell assay showed that miR‐485‐5p inhibited cell invasion and migration but had no influence on apoptosis and cell proliferation. Using a luciferase reporter assay, we demonstrated that miR‐485‐5p partially abrogated cell migration and proliferation by targeting FLOT‐1 mRNA. Transfection of HPV‐infected cervical carcinoma cells with an adenovirus vector encoding human FLOT‐1 partially diminished the inhibitory effects of miR‐485 on cell invasion. Taken, together, these data demonstrated that miR‐485‐5p suppresses the invasion of cancer cells by targeting FLOT‐1 in HPV‐infected cervical carcinoma cells.