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Cervical cancer is one of the most common gynecological malignancies, and it has become a crucial public health problem. In the present study, the expression profiles of cervical cancer and normal cervical tissues were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Subsequently, the dysregulated long non-coding RNAs (lncRNAs) in cervical cancer were identified using R software Differentially expressed lncRNAs in cervical cancer that were associated with glucose-regulated protein 78 (GRP78) were screened out and the results demonstrated that eight lncRNAs were strongly positively correlated with GRP78. In order to confirm the relationship between GRP78 and candidate lncRNAs, GRP78 small interfering RNA (siRNA) was transfected into HeLa cells. The target lncRNAs that were regulated by GRP78 were then identified by reverse transcription-quantitative PCR and it was revealed that LINC00294 was significantly downregulated following GRP78-knockdown. Subsequently, Gene Set Enrichment Analysis demonstrated that LINC00294 was mainly enriched in regulating the cell cycle and the Hedgehog pathway. Following transfection of HeLa and SiHa cells with LINC00294 siRNA, the cell cycle was arrested at the G0/G1 phase. Western blotting suggested that LINC00294-knockdown downregulated the expression of cell cycle-associated factors (cyclin D, cyclin E and cyclin Dependent kinase 4) and upregulated cell cycle inhibitory factors (p16 and p21). The Hedgehog pathway was inhibited following knockdown of LINC00294 in HeLa and SiHa cells. In summary, LINC00294 induced by GRP78 promoted the progression of cervical cancer by regulating the cell cycle via Hedgehog pathway.

Objectives This study aimed to identify the magnetic resonance imaging (MRI)-based radiomics phenotypes of intermediate-to-high-risk endometrial cancers (ECs), explore their association with histopathologic features, and compare their prognostic ability with the International Federation of Gynecology and Obstetrics (FIGO) stage. Methods This study retrospectively recruited 355 patients with pathologically confirmed EC from 01/2016 to 06/2023. 166(46.8%) were classified as intermediate-to-high-risk ECs according to the European Society for Medical Oncology guidelines. Radiomics clustering analysis was performed on preoperative MRI to identify the radiomics phenotype of intermediate-to-high-risk ECs. The association between the radiomics phenotypes and the clinicopathologic information was explored, and the added value in predicting the recurrence was also evaluated using concordance index (C-index). Results Of the included 166 patients (average age 56.83 ± 9.25 years), 23 were recurrent patients. The corresponding tumors in various clusters were assigned to phenotypes 1 and 2. Larger tumor diameter ( P  < .01), cervical mucosa invasion [30(36.15%) vs 15(18.07%), P  = .01], deep myometrial infiltration [51(61.45%) vs 31(37.35%), P  = .00], and histologic subtype [17(20.48%) vs 5(6.02%), P  = .01] were associated with subtype 1. The risk of recurrence ( P  = .01) was higher in phenotype 1, and the FIGO stage could further differentiate higher recurrence risk in phenotype 1 ( P  < .01). The C-index was 0.66 for the radiomics phenotype model, 0.69 for the FIGO stage model, and 0.72 for the combined model. Conclusions MRI-based radiomics consensus clustering enabled the identification of associations between radiomics features and histopathologic features in intermediate-to-high-risk EC. The FIGO stage could further elevate the prediction ability of recurrence risk.

ObjectiveTo investigate the influence of two types of tumor-associated macrophages (TAMs) on the biological function of human ovarian cell lines in vitro.Methods(1) M2 macrophage release was induced by IL-4, and M1 macrophage release by phorbol myristate acetate (PMA) in vitro. Flow cytometry was used to distinguish these two types; (2) transwell culture system was used to establish a non-contact co-culture model of macrophage and ovarian cancer cells (SKOV3, HEY, HO8910 and A2780) in vitro. The microenvironment of ovarian cancer was simulated in vitro. (3) The proliferation, apoptosis, migration and invasion of ovarian cancer cells SKOV3, HEY, HO8910 and A2780 were analyzed after co-culture. Their proliferation was detected by CCK8 method, apoptosis by flow cytometry, Annexin V-FITC/PI double staining, invasion by Transwell assay, and migration by wound healing test.Results(1) IL-4-induced macrophages (M2) overexpressed CD163, and PMA-induced macrophages (M1) overexpressed HLA-DR. After co-culturing primary macrophages with ovarian cancer cells (SKOV3, HEY, HO8910, A2780), macrophage CD163 was highly expressed. (2) Proliferation and apoptosis of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the proliferation of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the apoptosis of ovarian cancer cells in M2 co-culture group decreased compared to that in M1 co-culture group and primary co-culture group (p < 0.05). (3) Migration and invasion of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the invasion of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the migration of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and the primary co-culture group (p < 0.05).ConclusionIn the simulated in vitro tumor microenvironment, co-cultured ovarian cancer cells polarized macrophages to the M2 phenotype. Furthermore, M2 macrophages enhanced the proliferation, invasion and migration, and inhibited the apoptosis of ovarian cancer cells.

Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.

With the acceleration of human economic activities and dramatic changes in climate, the validity of the stationarity assumption of flood time series frequency analysis has been questioned. In this study, a framework for flood frequency analysis is developed on the basis of a tool, namely, the Generalized Additive Models for Location, Scale, and Shape (GAMLSS). We introduced this model to construct a non-stationary model with time and climate factor as covariates for the 50-year snowmelt flood time series in the Kenswat Reservoir control basin of the Manas River. The study shows that there are clear non-stationarities in the flood regime, and the characteristic series of snowmelt flood shows an increasing trend with the passing of time. The parameters of the flood distributions are modelled as functions of climate indices (temperature and rainfall). The physical mechanism was incorporated into the study, and the simulation results are similar to the actual flood conditions, which can better describe the dynamic process of snowmelt flood characteristic series. Compared with the design flood results of Kenswat Reservoir approved by the China Renewable Energy Engineering Institute in December 2008, the design value of the GAMLSS non-stationary model considers that the impact of climate factors create a design risk in dry years by underestimating the risk.

Background Ovarian granulosa cell tumors (OGCTs) feature low incidence, indolent growth and late recurrence. Treatment for recurrent OGCTs is challenging. Methods The present study was designed to explore the prognostic factors and establish a nomogram to predict cancer‐specific survival (CSS) for OGCTs patients. Enrolled in the study were 1459 eligible patients in the Surveillance, Epidemiology, and End Results (SEER) database, who were randomized to the training (n = 1021) or testing set (n = 438) at a ratio of 7:3. Univariate and multivariate Cox regression analyses were employed to screen the prognostic factors. The predictors were determined by using the Least absolute shrinkage and selection operator (LASSO) regression analysis. The model was constructed via the Cox proportional hazards risk regression analysis. The performance and clinical value of the nomograms was assessed with C‐index, calibration plots, and decision curve analysis. Results Age, pTNM stage, tumor size, surgery of the primary tumor, surgery of regional lymph nodes (LNs), residual disease after surgery, and chemotherapy were considered as significant predictive factors for CSS in OGCTs patients. After screening, the prognostic factors except surgery of regional LNs and chemotherapy were employed to build the nomogram. With desirable discrimination and calibration, the nomogram was more powerful in predicting CSS than the American Joint Committee on Cancer staging system in clinical use. Conclusion This novel prognostic nomogram, which comprises a stationary nomogram and a web‐based calculator, offers convenience for clinicians in personalized decision‐making including optimal treatment plans and prognosis assessments for OGCTs patients.

Lymph node metastasis significantly impacts prognosis and treatment in locally advanced cervical cancer (LACC). Surgical staging offers precise information on node involvement, though its survival benefit is debated. We pooled data from 9 cohort studies involving 2553 patients to evaluate the benefit of pre‐treatment surgical staging in patients with locally advanced cervical cancer. Fixed effects models or random effects models were used to calculate the pooled hazard ratios (HRs). The overall pooled results showed no difference in PFS (HR 0.94, 95% CI 0.73–1.22, p = 0.65) or OS (HR 1.00, 95% CI 0.74–1.35, p = 0.99) between the two approaches of lymph node staging. However, the subgroup analyses found the PFS superiority of surgical staging in patients with FIGO stage II (HR 0.68, 95% CI 0.49–0.95, p = 0.02). Additionally, for the patients with no evidence of lymph node metastasis on imaging, surgical staging was associated with significantly improved PFS (HR 0.69, 95% CI 0.56–0.86, p = 0.001) and OS (HR 0.56, 95% CI 0.36–0.87, p = 0.01). In the subgroup of patients with suspicious bulky nodes on imaging, lymph node debulking‐based surgical staging did not significantly improve either PFS (HR 0.97, 95% CI 0.72–1.31, p = 0.31) or OS (HR 1.16, 95% CI 0.68–1.99, p = 0.59) in comparison with imaging staging. Surgical staging may not be applicable to all patients with LACC. However, for the patients with FIGO II disease or those without suspicious lymph node involvement on imaging, node surgery staging could afford a survival benefit. Trial Registration: PROSPERO ID: CRD42024543768 The negative pooled result in the overall population indicated that surgical staging may not be applicable to all LACC patients. However, it is worth noting in our subgroup analysis that in patients with stage II disease or those who had only radiographic exclusion of PALN metastases, node staging surgery affords a survival benefit.

Background Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus. 1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. Methods CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig.  1 ). Results The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig.  2 . The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion, 2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1 ). Conclusions This study details the skills of CLRS for CSC, especially space development and the ‘no-look, no-touch’ tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis

The incidence and mortality of cervical cancer (CC) rank fourth among those of all gynecological malignancies. Long noncoding RNAs (lncRNAs) serve important roles in the development of various types of cancer. The aim of the present study was to explore the role of lncRNAs in the pathogenesis of CC and to identify novel therapeutic targets. LINC01012 was identified to be associated with an unfavorable prognosis in patients with CC based on bioinformatics analyses. Upregulated LINC01012 expression was further verified in CC samples and in cervical intraepithelial neoplasia grade 3 tissues compared with healthy tissues using reverse transcription-quantitative PCR. Functionally, following transfection with LINC01012 short hairpin RNA (sh-LINC01012), the proliferation and migration of CC cell lines were examined using 5-ethynyl-2′-deoxyuridine staining, colony formation and Transwell assays, which demonstrated that knockdown of LINC01012 in CC cells suppressed cell proliferation and migration in vitro and tumor growth in an in vivo xenograft model. The potential mechanisms of LINC01012 were further explored. A negative association between LINC01012 and cyclin dependent kinase inhibitor 2D (CDKN2D) was also identified based on The Cancer Genome Atlas data and this was confirmed using western blotting and rescue experiments. Consistently, knockdown of LINC01012 in CC cells upregulated CDKN2D expression. The inhibition of proliferation and migration of CC cells following transfection with sh-LINC01012 was reversed following co-transfection of sh-LINC01012 and CDKN2D short hairpin RNA. These findings suggested that upregulated LINC01012 expression in CC may stimulate the proliferation and migration of cancer cells, thus promoting CC progression via downregulation of CDKN2D.