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Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC)., Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone. The primary endpoint was the objective response rate (ORR). Pivotal secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety., Findings: 205 patients were randomized to receive IBI310-sintilimab (n = 103) or placebo-sintilimab (n = 102). The ORR difference between the IBI310-sintilimab arm (32.3%, 95% confidence interval [CI]: 23.3%-42.5%) and the placebo-sintilimab arm (23.5%, 95% CI: 15.5%-33.1%) was not significant (p = 0.17). IBI310-sintilimab and placebo-sintilimab exhibited median PFS values of 3.6 (95% CI: 2.7-6.3) and 4.2 months (95% CI: 2.8-6.2), respectively (hazard ratio [HR] = 0.91, 95% CI: 0.65-1.27; p = 0.58). The median OSs were 13.9 months (95% CI: 11.5-25.6) in the IBI310-sintilimab arm and 17.2 months (95% CI: 13.7-25.9) in the placebo-sintilimab arm (HR = 1.12, 95% CI: 0.79-1.58; p = 0.54). Adding IBI310 to sintilimab increased the incidence of grade ≥3 treatment-related adverse events (55% versus 19%)., Conclusions: Compared to single-agent PD-1/PD-L1 blockade, dual blockade of CTLA-4 and PD-1/PD-L1 did not significantly improve clinical outcomes in R/M CC., Funding: This work was funded by Innovent Biologics (Suzhou)., Competing Interests: Declaration of interests S.W., L. Li, and H. Zhou are employees of Innovent Biologics (Suzhou), Co., Ltd., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The "Healthy China" initiative, along with advancements in technology for cancer diagnosis and treatment, has significantly enhanced outcomes for patients with gynecologic tumors. The trends of late marriage and delayed childbirth have led to an increasing number of women diagnosed with gynecologic cancers who are seeking fertility preservation in China. This issue is critical yet often overlooked in clinical practice. This review aims to synthesize the existing research on fertility preservation within the field of gynecologic oncology, emphasizing both clinical explorations and expert guidelines., Methods: We conducted a comprehensive literature review on fertility preservation in the context of gynecologic tumors, examining treatment approaches, commonly employed tumor management technologies, and specific techniques for preserving fertility., Results: This extensive review highlights the importance of integrating fertility preservation strategies into treatment plans for gynecologic tumors. It explores various methods to safeguard fertility during chemotherapy, radiation therapy, and surgical interventions. For patients with early-stage cervical cancer, surgical options are available; however, these may result in obstetric complications. Neoadjuvant chemotherapy is currently under investigation as an alternative approach. Endometrial cancer can be managed through hysteroscopic resection combined with hormonal therapy. The feasibility of fertility preservation in ovarian cancer varies based on tumor type and patient age. In cases of vulvar and vaginal cancers, partial excision may be considered following a thorough evaluation. Chemotherapy for gestational trophoblastic tumors has proven effective and typically preserves fertility despite potential decreases in AMH levels., Conclusion: This review provides a comprehensive and current synthesis of the latest evidence and clinical practice guidelines regarding fertility preservation in gynecologic cancers. Its aim is to assist clinicians and researchers in addressing the urgent and increasing demand for effective fertility preservation strategies for their patients., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Increasing evidence links exposure to ambient particulate matter with a diameter less than 2.5 μm (PM 2.5 ) with reduced survival in cancer survivors, but little was known about the association between PM 2.5 exposure and cervical cancer survival. We analyzed data from 5144 cervical cancer patients diagnosed between January 2014 and December 2020, who completed recommended treatments. Exposure levels were determined by the monthly average concentration of ambient PM 2.5 and its five constituents, obtained from Tracking Air Pollution in China (TAP) based on individual residential addresses. Log-rank tests and multivariate Cox Proportional Hazardous regression were performed to examine the impacts of PM 2.5 and its constituents on overall survival (OS) of cervical cancer patients. We observed that for every increase of 1 μg/m 3 in average individual exposure, the hazard ratios (95%CI) for ambient PM 2.5 , sulfate (SO 4 2- ), ammonium (NH 4 + ), and nitrates (NO 3 - ) were 1.078(1.069-1.086), 6.755(5.707-7.996), 2.123(1.935-2.329), and 3.717(3.237-4.267), respectively. Subgroups with longer OS had larger HRs of PM 2.5 and its constituents, which might attributed to more cumulative exposure. No evidence of a threshold for the hazardous effects of PM 2.5 on the OS of cervical cancer patients was identified. Furthermore, long-term exposure to PM 2.5 was negatively associated with pretreatment counts of monocytes, neutrophils, and lymphocytes in peripheral blood of cervical cancer patients. In conclusion, elevated levels of PM 2.5 mass, SO 4 2- , NH 4 + , and NO 3 - in ambient PM 2.5 exposure were associated with reduced OS among cervical cancer patients. There may be no discernible threshold effect of PM 2.5 on the risk for cervical cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pro-viral Insertion site for the Moloney Murine Leukemia virus 1 (PIM-1) is widely involved in various biological processes and diseases, which is based on its structure and functional sites. However, the relationship between active sites and function of PIM-1 kinase remains unclear due to the lack of effective study approaches in live cells. Herein, to visualize the effect of different active sites in PIM-1 protein on its function activity and relation with PI3K/Akt/mTOR pathway, three mutant probes of EPHY which was developed previously based on fluorescence resonance energy transfer (FRET) technology to detect PIM-1 kinase activity in living cells were further constructed and transfected into cells followed by treating with PIM-1 inhibitors, ATP and PI3K inhibitor, respectively. The results showed that Lys67 is related to substrate binding and catalytic activity of PIM-1 kinase, thereby directly regulating PI3K/Akt/mTOR signaling pathway. Pro81/Asn82 are primarily participated in PIM-1 binding to ATP, thus also involving in the modulation on PI3K/Akt/mTOR signaling pathway, but play less role in the interaction between PIM-1 protein and its substrate. Asp167 has few effects on both the catalytic function activity of PIM-1 and PI3K/AKT/mTOR pathway, even though the binding ability of PIM-1 protein to its substrate is dramatically inhibited by D167A mutation. Altogether, the mutant probes works well as visualization tools to unearth the function of active sites in PIM-1 kinase, not only facilitating the further clarification of molecular mechanism underlying PIM-1 related signaling pathways, but also shedding light on drug development and disease therapy targeting PIM-1 protein., (© 2024 Wiley‐VCH GmbH.)

Research Question: Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway?, Design: The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo., Results: The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05)., Conclusion: The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/β-catenin, Notch, NF-κB, MAPK, TGF-β, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cardiovascular disease stemmed from atherosclerosis (AS) is well recognized to be the predominant cause of global death. To comprehensively clarify the pathogenesis of AS, exploit effective drugs, as well as develop therapeutic solutions, various atherosclerotic models were constructed in vitro and widely utilized by the scientific community. Compared with animal models, the in vitro atherosclerotic models play a prominent role not only in the targeted research of single pathological factor related to AS in the human derived system, but also in the combined study on multipathological factors leading to AS, thereby contributing tremendously to the in-depth elucidation of atherosclerotic pathological process. In the current review, a variety of pathological factors incorporated into the existing atherosclerotic models in vitro are broadly elaborated, including the pathological mechanism, in vitro simulation approaches, and the desired improvement perspectives for reproducing each pathological factor. In addition, this review also summarizes the advantages and disadvantages of current atherosclerotic models as well as their potential functionality. Finally, the promising aspects for future atherosclerotic models in vitro with potential advances are also discussed.

Background: In the general population, primary human papillomavirus (HPV) testing is advocated for cervical cancer (CC) screening. HPV E6/E7 mRNA (Aptima HPV, AHPV) assays have garnered considerable traction due to their higher specificity when compared with HPV DNA assays. Here, we investigated age-specific primary AHPV screening assays and different triage strategies versus cytology to identify the best approach., Methods: Between April 2018 and December 2021, we recruited female participants from 34 communities across Liaoning province and Qingdao City, China. Primary cervical screening protocols included liquid-based cytology (LBC) and AHPV assays, with females positive for any assays undergoing colposcopy. Genotyping (AHPV-GT) was conducted on all HPV-positive samples. Our primary outcomes were the identification of age-specific detection rates, colposcopy referral rates, and sensitivity and specificity values for high-grade squamous intraepithelial lesions or worse (HSIL+). AHPV and different triage strategy performances were also examined across different age cohorts., Results: Our investigation included 9911 eligible females. Age-specific abnormal cytology rates were in the 6.1%-8.0% range, and were highest in 45-54-year olds. When compared with 35-44-or 45-54-year olds, HPV prevalence was highest in 55-64-year olds (12.2% or 11.6% vs.14.1%, P = 0.048 and P = 0.002, respectively). In 35-44-year olds, AHPV sensitivity for detecting HSIL+ was 96.6 (95% confidence interval [CI]: 89.7-100) - significantly higher than LBC sensitivity (65.5 [95% CI: 48.3-82.8], P < 0.001). When compared with LBC, HSIL+ detection rates by AHPV-GT using reflex LBC triage increased by 31.5% (9.6‰ vs. 7.3‰), and colposcopy referral rates decreased by 16.4% (5.1% vs. 6.1%). In 45-54-year olds, HSIL+ detection rates for AHPV-GT using reflex LBC triage were lower than LBC rates (6.2‰ vs. 6.6‰). In 55-64-year olds, AHPV sensitivity (97.2 [95% CI: 91.7-100.0]) was higher than LBC sensitivity (66.7 [95% CI: 50.0-80.6], P = 0.003). The area under the curve (AUC) value was not significantly different between AHPV-GT with reflex LBC triage and LBC (0.845 [95% CI: 0.771-0.920] vs. 0.812 [95% CI: 0.734-0.891], P = 0.236)., Conclusions: Primary AHPV screening using different triage strategies were different across different age cohorts. Thus, AHPV may be an appropriate primary screening method for 35-44 and 55-64 year old females, while AHPV-GT with reflex LBC triage may be more apt for 35-44 year old females., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Yang, Cui, Wang, Wang and Piao.)

Background: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy., Methods: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS)., Results: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]., Conclusions: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2., Trial Registration: NCT03534453. Registered at May 23, 2018., (© 2024. The Author(s).)

Background: Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (g BRCA m) status, in NORA. This analysis reports final data on overall survival (OS)., Methods: This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with g BRCA m) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by g BRCA m status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200 mg/day for patients with bodyweight <77 kg and/or platelet count <150 × 10 3 /μL at baseline and 300 mg/day otherwise. OS was a secondary endpoint., Findings: Totally, 265 patients were randomised to receive niraparib (n = 177) or placebo (n = 88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with g BRCA m; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients., Interpretation: Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of g BRCA m status., Funding: Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019]., Competing Interests: ZH, JD, CZ, and JMH report employment with and hold shares and stock options in Zai Lab. MRM is a member of board of directors and holds stocks/shares of Karyopharm Therapeutics and Sera Prognostics and has participated in advisory boards for Allarity Therapeutics, AstraZeneca, Biocad, Biontech, Boehringer Ingelheim, Clovis, Daiichi-Sankyo, Eisai, Genmab, GSK, Immunogen, Incyte, Karyopharm, Merck/MSD, Mersana, Novartis, Regeneron, Roche, SeaGen, Takeda, Tesaro, and Zai Lab. All other authors declare no competing interest., (© 2024 The Authors.)

Hydrogen-bonded organic frameworks (HOFs) are porous crystalline materials. The pores in HOFs are usually non-covalent extrinsic pores constructed through the formation of the framework. Supramolecular macrocycles with intrinsic pores in their structures are good candidates for constructing HOFs with intrinsic pores from the macrocycles themselves, thus leading to hierarchically porous structures. Combining the macrocycle and HOFs will endow these hierarchically porous materials with enhanced properties and special functionalities. This review summarizes recent advances in macrocycle-based HOFs, including the macrocycles used for constructing HOFs, the hierarchically porous structures of the HOFs, and the applications induced by the hierarchically HOFs porous structures. This review provides insights for future research on macrocycle-based hierarchically porous HOFs and the appropriate applications of the unique structures., (© 2023 Wiley-VCH GmbH.)

The purpose of this perspective cohort study was to evaluate the effectiveness of low-dose computed tomography (LDCT) screening for lung cancer in China. This study was conducted under the China Urban Cancer Screening Program (CanSPUC). The analysis was based on participants aged 40 to 74 years from 2012 to 2019. A total of 255 569 eligible participants were recruited in the study. Among the 58 136 participants at high risk of lung cancer, 20 346 (35.00%) had a single LDCT scan (defined as the screened group) and 37 790 (65.00%) not (defined as the non-screened group). Overall, 1162 participants were diagnosed with lung cancer at median follow-up time of 5.25 years. The screened group had the highest cumulative incidence of lung cancer and the non-screened group had the highest cumulative lung cancer mortality and all-cause cumulative mortality. We performed inverse probability weighting (IPW) to account for potential imbalances, and Cox proportional hazards model to estimate the weighted association between mortality and LDCT scans. After IPW adjusted with baseline characteristics, the lung cancer incidence density was significantly increased (37.0% increase) (HR1.37 [95%CI 1.12-1.69]), lung cancer mortality was decreased (31.0% decrease) (HR0.69 [95%CI 0.49-0.97]), and the all-cause mortality was significantly decreased (23.0% lower) (HR0.77 [95% CI 0.68-0.87]) in the screened group. In summary, a single LDCT for lung cancer screening will reduce the mortality of lung cancer and all-cause mortality in China., (© 2023 UICC.)

A nitrogen-rich graphdiyne (HATN-GDY) material containing electrochemical active hexaazatrinaphthylene units was successfully prepared. HATN-GDY exhibits a superior specific capacity of 2139 mA h g -1 and firm long-term stability due to the unique 2D π-conjugated structure and the large in-plane N-cavities.

Cervical cancer (CC) is one of the most common malignant tumors in gynecology. Immunotherapy and targeted therapy are two particularly effective treatments. In this study, weighted gene co-expression network analysis and CIBERSORT algorithm that quantifies the composition of immune cells were used to analyze CC expression data based on the GEO database and identify modules related to T cells. Five candidate hub genes were identified by tumor-infiltrating immune cells estimation and Kaplan-Meier survival analysis according to CC data from The Cancer Genome Atlas (TCGA). Chemotherapeutic response, methylation, and gene mutation analyses were implemented so that the five candidate hub genes identified may be the potential biomarkers and therapeutic targets which were related to T cell infiltration. Moreover, the results of RT-qPCR revealed that CD48 was a tumor suppressor gene, which was negatively correlated with CC stages, lymph node metastasis, and differentiation. Furthermore, the functional study verified that the interference of CD48 was able to boost the proliferation and migration ability in vitro and the growth of transplanted tumors in vivo. Overall, we identified molecular targets related to immune infiltration and prognosis, regarded CD48 as a key molecule involved in the progression of CC, thus providing new insights into the development of molecular therapy and immunotherapeutics against CC., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The main aim of this study was to establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis., Methods: Clinicopathological and follow-up data of 174 patients with clear cell and endometrial ovarian cancer were retrospectively extracted. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer for comparative analysis of clinicopathological characteristics and prognosis., Results: Average age and post-menopausal rate in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P < 0.05). Body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA19.9, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1β and Napsin A were not significantly different between the groups (P > 0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05)., Conclusion: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy., (© 2023. The Author(s).)

A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C 60 molecule inside of the cavity and significantly improve the water-solubility of the C 60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C 60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C 60 and verifies the important role of C 60 in preventing oxidative stress-related cardiovascular disease injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria., Methods: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study., Results: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup., Conclusions: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma., (© 2023 Japan Society of Obstetrics and Gynecology.)

A highly rigid amine-linked 3D COF was constructed from two orthogonal building blocks (spirobifluorene and bicarbazole) through a post-synthetic chemical reduction. The rigid 3D framework decreased the conformational flexibility of the amine linkages, and thus showed a fully preserved crystallinity and porosity. The amine moieties in the 3D COF afforded abundant chemisorptive sites for selectively capturing CO 2 .

Two imine-based 2D covalent organic frameworks (COFs) with slight differences in their core structures are presented. The COF containing benzotrithiophene moieties with better planarity and π-conjugation ( BTTh-TZ-COF ) shows much better photocatalytic activity than the COF with trithienylbenzene cores ( TThB-TZ-COF ). Further photoelectrochemical study reveals the catalytic mechanism in more detail. Since other factors such as crystallinity, porosity, and optical bandgaps are equal, the different structures of the cores in the two similar COFs are the major contributors to the significantly different photocatalytic performance. The better electron delocalization of the planar trithiophene-based core and the enhanced D-A interactions between the triazine and trithiophene units in BTTh-TZ-COF create efficient charge separation and transfer, thus leading to superior photocatalytic hydrogen evolution activity. A new strategy for preparing high-performance organic photocatalysts for solar-energy conversion is revealed by this study.

Background: Cervical cancer (CC) screening is currently recognized as an effective intervention for CC. Previous studies found that the proportion of screening was low in China, especially in Liaoning. Therefore, we performed a population-based cross-sectional survey to investigate the situation of cervical cancer screening and analyze their related factors for providing a decision-making basis for sustainable and effective development of cervical cancer screening., Methods: This population-based cross-sectional study involved aged 30 to 69 years in nine counties/districts in Liaoning from 2018 to 2019. Data were collected using the quantitative data collection methods, and analyzed in SPSS version 22.0., Results: Overall, only 22.37% of 5334 respondents reported having ever been screened for cervical cancer in past 3 years, and 38.41% of respondents reported having the willingness for cervical cancer screening in next 3 years. In the rate of CC screening, multilevel analysis indicated that age, marital status, education level, type of occupation, medical insurance, family income, place of residence and regional economic level had a significant impact on proportion of screening. In the rate of CC screening willingness, multilevel analysis indicated that age, family income, health status, place of residence, regional economic level and CC screening still had a significant impact, but marital status, education level and medical insurance type had no significant impact. There was no significant difference in marital status, education level and medical insurance type after the factors of CC screening were added in the model., Conclusion: Our study found both proportion of screening and willingness were at a low level, and age, economic and regional factors were the main factors for implementation of CC screening in China. In the future, targeted policies should be formulated according to the characteristics of different groups of people, and reduce the gap in the current health service capacity between different regions., (© 2023. The Author(s).)

A weak CH/O hydrogen-bonded organic framework (HOF) with both rigidity and flexibility that could easily and reversibly switch from a non-crystalline to a crystalline phase was constructed. The specific solvent molecule acts as a "key" to control the crystallinity, while the highly rigid triangle macrocycle as the building block is the "lock". The introduction and removal of the "key" could influence the local flexibility of the whole framework and lead to switchable crystallinity. Furthermore, the obtained HOF exhibits excellent separation efficiency for benzene and cyclohexane (94.4 %)., (© 2023 Wiley-VCH GmbH.)

Introduction: Natural orifice specimen extraction (NOSE) laparoscopic surgery is emerging as a new and promising technique, especially in gastric cancer (GC)., Aim: To analyze the difference between transvaginal and transumbilical specimen extraction following totally laparoscopic gastrectomy (TLG)., Material and Methods: Between January 2016 and July 2021, 37 consecutive female patients with GC who underwent either natural orifice specimen extraction surgery (NOSES) or TLG at our center were included and analyzed., Results: In total, 12 patients underwent NOSES, and 25 patients underwent TLG. The NOSES group had a shorter operative time (239.3 ±21.5 vs. 256.1 ±21.2 min, p = 0.031) and shorter specimen extraction time (17.0 ±4.2 vs. 30.8 ±4.3 min, p < 0.01). No significant difference was observed in the comparison of the radical validity including estimated blood loss, the number of harvested LNs and the comparisons of distal and proximal margin. In the postoperative recovery comparisons, the NOSES group had a shorter time to first fluids (3.9 ±0.5 vs. 5.6 ±1.2 days, p < 0.01), and time to starting a soft diet (5.6 ±0.7 vs. 7.7 ±1.7 days, p < 0.01). Postoperative pain in the NOSES group was significantly less. Postoperative hospital stay days in the NOSES group were fewer (10.2 ±2.2 vs. 12.4 ±2.9 days, p = 0.030). Overall, the postoperative complications were similar between the two groups (p = 0.438). When more cases were included, the results were similar. NOSES reduced hospital costs for GC patients, and it also applied to the premenopausal patients., Conclusions: NOSES was a safer and more reliable method as compared to transumbilical specimen extraction., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Fundacja Videochirurgii.)

This study aimed to build a comprehensive model for predicting the overall survival (OS) of cervical cancer patients who received standard treatments and to build a series of new stages based on the International Federation of Gynecologists and Obstetricians (FIGO) stages for better such predictions. We collected the cervical cancer patients diagnosed since the year 2000 from the Surveillance, Epidemiology, and End Results (SEER) database. Cervical cancer patients who received radiotherapy or surgery were included. Log-rank tests and Cox regression were used to identify potential factors of OS. Bayesian networks (BNs) were built to predict 3- and 5-year survival. We also grouped the patients into new stages by clustering their 5-year survival probabilities based on FIGO stage, age, and tumor differentiation. Cox regression suggested black ethnicity, adenocarcinoma, and single status as risks for poorer prognosis, in addition to age and stage. A total of 43,749 and 39,333 cases were finally eligible for the 3- and 5-year BNs, respectively, with 11 variables included. Cluster analysis and Kaplan-Meier curves indicated that it was best to divide the patients into nine modified stages. The BNs had excellent performance, with area under the curve and maximum accuracy of 0.855 and 0.804 for 3-year survival, and 0.851 and 0.787 for 5-year survival, respectively. Thus, BNs are excellent candidates for predicting cervical cancer survival. It is necessary to consider age and tumor differentiation when estimating the prognosis of cervical cancer using FIGO stages., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients., Methods: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial., Results: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002)., Conclusions: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments., Trial Registration: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017., (© 2022. The Author(s).)

Purpose: This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer., Patients and Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. The primary endpoints of the dose-expansion phase were safety and the objective response rate (ORR) of the 5 mg/kg dose. Efficacy was assessed by the third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)., Results: 104 patients were successfully enrolled into the study. Twelve patients were included in the dose-escalation phase, with one complete response and two partial responses in the 5 mg/kg treatment group. Ninety-two patients (5 mg/kg) were enrolled in the dose-expansion phase. Fifty-four patients (59.3%) had baseline PD-L1-positive tumor expression (combined positive score ≥1). ORR was 15.4% [95% confidence interval (CI), 8.7%-24.5%]. Median PFS was 4.44 months (95% CI, 2.37-5.75 months), and the median OS was 14.72 months (95% CI, 9.59-NE months). ORR of PD-L1-positive patients was 16.7%, and the ORR of PD-L1-negative patients was 17.9%. No treatment-related deaths occurred., Conclusions: Our study demonstrates that socazolimab has durable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti-PD-1/PD-L1 mAbs., (©2022 American Association for Cancer Research.)

Particulate matter with a diameter of 2.5 μm or less (PM 2.5 ) has frequently been reported to be associated with an increased incidence of cancer, but few studies have explored the association between PM 2.5 exposure and cancer survival. We retrospectively analyzed the association between PM 2.5 exposure and the overall survival (OS) of cervical cancer patients residing in 14 urban areas of Liaoning Province, northeastern China, during January 2014-October 2021. Patients from urban areas who completed the recommended treatments with complete follow-up information were included. The PM 2.5 monitoring data of each urban area of Liaoning Province were retrieved, and individual exposure to PM 2.5 after diagnosis was calculated as the average daily concentration in the city of residence from the date of discharge to the date of death or the last follow-up. Log-rank tests and Cox regression were performed to examine the relationship between PM 2.5 exposure and cervical cancer survival. A total of 1753 cervical cancer patients were finally included, among whom 804 (45.9%) were from Shenyang City, the capital of Liaoning Province. The median average daily concentration of PM 2.5 to which the patients were exposed was 45.0 (interquartile range 38.2-50.0) μg/m 3 . Both log-rank tests (grouped by quartiles, p < 0.001) and Cox regression (continuous, HR = 1.06, 95% CI 1.04-1.08) indicated that PM 2.5 was significantly associated with shorter OS. Sensitivity analysis also confirmed the robustness of our findings. From the subgroup analysis, only the OS of stage II and stage III patients was associated with PM exposure. Our findings provide the insight that PM 2.5 exposure might be associated with shorter OS of cervical cancer patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a facile strategy to prepare a large amount of ultrathin graphdiyne (GDY) with good crystallinity in the mixture of oil-water systems. By simply mixing the solution of GDY monomer in CHCl 3 and the copper acetate solution as a catalyst in water and stirring at room temperature, ultrathin GDY films with a thickness of ∼4 nm were obtained in a yield of 95 %. This work provides a feasible path for the substantial preparation of GDY films and may pave the way to the development of substantial preparation of the GDY materials., (© 2022 Wiley-VCH GmbH.)

Purpose: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer., Patients and Methods: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453)., Results: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs., Conclusions: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201., (©2022 The Authors; Published by the American Association for Cancer Research.)

Accurate labeling is essential for supervised deep learning methods. However, it is almost impossible to accurately and manually annotate thousands of images, which results in many labeling errors for most datasets. We proposes a local label point correction (LLPC) method to improve annotation quality for edge detection and image segmentation tasks. Our algorithm contains three steps: gradient-guided point correction, point interpolation, and local point smoothing. We correct the labels of object contours by moving the annotated points to the pixel gradient peaks. This can improve the edge localization accuracy, but it also causes unsmooth contours due to the interference of image noise. Therefore, we design a point smoothing method based on local linear fitting to smooth the corrected edge. To verify the effectiveness of our LLPC, we construct a largest overlapping cervical cell edge detection dataset (CCEDD) with higher precision label corrected by our label correction method. Our LLPC only needs to set three parameters, but yields 30-40% average precision improvement on multiple networks. The qualitative and quantitative experimental results show that our LLPC can improve the quality of manual labels and the accuracy of overlapping cell edge detection. We hope that our study will give a strong boost to the development of the label correction for edge detection and image segmentation. We will release the dataset and code at: https://github.com/nachifur/LLPC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Fan, Wang, Li, Tang, Wang, Zhou and Chen.)

Background: This study aimed to compare the survival outcomes between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix after radical radiotherapy and chemotherapy., Methods: Propensity score matching (1:4) was used to compare overall survival (OS) and disease-free survival (DFS) in cervical cancer patients with SCC and AC/ASC in China., Results: Five thousand four hundred sixty-six patients were enrolled according to the criteria. The 5-year OS and DFS in the SCC group (n = 5251) were higher than those in the AC/ASC group (n = 215). After PSM (1:4), the 5-year OS and DFS in the SCC group were higher than those in the AC/ASC group (72.2% vs 56.9%, p < 0.001, HR = 1.895; 67.6% vs 47.8%, p < 0.001, HR = 2.056). In stage I-IIA2 patients, after PSM (1:4), there was no significant difference in 5-year OS between the SCC group (n = 143) and the AC/ASC group (n = 34) (68.5% vs 67.8%, P = 0.175). However, the 5-year DFS in the SCC group was higher than that in the AC/ASC group (71.0% vs 55.7%, P = 0.045; HR = 2.037, P = 0.033). In stage IIB-IV patients, after PSM (1:4), the 5-year OS and DFS in the SCC group (n = 690) were higher than those in the AC/ASC group (n = 173) (70.7% vs 54.3% P < 0.001 vs 1.940%, P < 0.001 vs 45.8%, p < 0.001)., Conclusions: For stage I-IIA2, there was no significant difference in 5-year survival time, but patients with AC/ASC were more likely to relapse. In the more advanced IIB-IV stage, the oncological outcome of radical radiotherapy and chemotherapy of cervical AC/ASC was worse than that of SCC., (© 2022. The Author(s).)

An interlocked covalent organic molecular cage with a trigonal-prismatic structure based on anthracene units and imine bonds was synthesized by a template-free and one-pot reaction in a relatively good yield. By comparing the single-crystal structures of the interlocked cage and two additional monomeric cages as reference compounds, a cause of weak supramolecular interaction-induced synthesis was proposed; π···π interactions induce the triphenylbenzene units as the core and anthracenes as side parts close to each other, which provides a possibility of the preorganization for the formation of the interlocked structure.

Purpose: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer., Patients and Methods: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1., Results: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34-79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2-21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3-74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6-56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count., Conclusions: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: With the continuous progress of medical imaging technology, evaluation of cervical cancer is increasingly dependent on imaging methods. Diffusion-weighted imaging (DWI) plays an important role, and apparent diffusion coefficient (ADC) value is a unique quantitative parameter in the research of cervical cancer., Methods: In this prospective study, a total of 273 patients diagnosed with stage IB1 to IIIC1 cervical cancer based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging guidelines who underwent pelvic 3.0T magnetic resonance imaging (MRI), including MRI and DWI, were enrolled, and the diagnostic value of preoperative staging of cervical cancer was compared between the MRI and DWI groups. The DWI group was used to explore the potential association of mean ADC (ADC mean ) with different pathological characteristics and receiver operating characteristic (ROC) curves of ADC mean generated to predict the appropriate postoperative supplementary therapy., Results: The diagnostic coincidence rate of DWI was higher than that of MRI in preoperative staging of cervical cancer (χ 2 , P<0.05) and determined as stages IB1 + IB2 + IIA1 (90.91%), IB3 + IIA2 (93.48%), and IIIC1p (95.16%). The DWI staging results were consistent with postoperative pathological staging (Kappa value =0.865, P<0.001). We observed significant differences in ADC mean values in relation to pathological type, histological grade, depth of stromal infiltration, tumor diameter, lymphovascular invasion, and pelvic lymph node metastasis of cervical cancer (all P<0.05). The area under the ROC curve (AUC) was 0.815, with the best predictive value for postoperative supplementary therapy in cervical cancer (sensitivity 80.0%, specificity 74.0%) at ADC mean of 0.910×10 -3 mm 2 /s., Conclusions: The DWI is a useful tool for preoperative evaluation of cervical cancer. In local cervical lesions, ADC mean varies in relation to different clinicopathological characteristics and a reference index of <0.910×10 -3 mm 2 /s can be effectively applied to predict the need for postoperative supplementary therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-5319/coif). The series “New Progress and Challenge in Gynecological Cancer” was commissioned by the editorial office without any funding or sponsorship. DW served as the unpaid Guest Editor of the series. YL reports that this work was supported by National Public Welfare Industry Research Fund (No. 201402020 to YL). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Research Question: What is the mechanism of hypermethylation of runt-related transcription factor 3 (RUNX3) in the eutopic endometrium of endometriosis as biomarker in the malignant transformation of endometriosis?, Design: Methylation-specific polymerase chain reaction was used to analyse the methylation status of RUNX3 in endometriosis-associated ovarian cancer (EAOC). Primary eutopic endometrial stromal cells (ESC) were isolated from the uteri of patients with ovarian endometriosis. After RUNX3 knockdown by RNA interference technology or ESC treated with oestradiol, the proliferation and invasion ability were evaluated in ESC by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell assays., Results: The frequency of methylation of RUNX3 in neoplastic tissue in the EAOC group was significantly higher than that in the ectopic endometrium of the endometriosis group (P < 0.001), and the frequency of methylation of RUNX3 in the eutopic endometrium of the EAOC group was significantly higher than that in the endometriosis group (P < 0.001). However, there was no significant difference in the eutopic endometrium when compared between the endometriosis group and the control endometrium group (P = 0.233). Silencing RUNX3 promoted the proliferation and invasion of ESC (P < 0.001 and P < 0.001). Following intervention with oestrogen, it was observed that the oestradiol group showed higher levels of RUNX3 methylation (P < 0.001) and DNA methyltransferase 1 (DNMT1) mRNA and protein expression (P < 0.001 and P < 0.001), and lower RUNX3 mRNA and protein expression when compared with the ESC group (P < 0.001 and P < 0.001)., Conclusion: This study demonstrated that hypermethylation of the RUNX3 was related to the malignant transformation of endometriosis and that this process was related to corresponding changes in the eutopic endometrium. Furthermore, the 'oestrogen-DNMT1' signalling pathway may induce the hypermethylation of RUNX3 to promote the malignant transformation of endometriosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To investigate the survival outcomes of abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy (LRH), and vaginal-assisted laparoscopic radical hysterectomy (VALRH) in the treatment of cervical cancer patients., Methods: This was a retrospective study. We collected the clinical data of 654 patients with cervical cancer (406 ARH, 172 LRH, and 76 VALRH), then compared the effects of different surgical methods on recurrence and survival., Results: Total overall survival (OS) were no significant differences in three groups (P>0.05). Total disease-free survival (DFS) was significantly higher in ARH group than in LRH group [hazard ratio (HR) =2.8, 95% confidence interval (CI): 1.199-3.607, P=0.004]; however, there were no significant differences between the VALRH (94.7%) and ARH (93.3%) groups. Subgroup stratification analysis showed that the overall recurrence rate in LRH group was significantly higher than that of the ARH groups for patients with a tumor size from ≥2 to <4 cm, negative postoperative lymph nodes, and no postoperative adjuvant therapy (all P<0.05). However, in the subgroup with tumor sizes of ≥2, <4, and ≥4 cm, no matter whether the lymph nodes were positive or not, and those with no postoperative supplementary adjuvant therapy, LRH was associated with a significantly higher local pelvic recurrence rate than ARH (all P<0.05). No significant differences between VALRH and ARH in any of the subgroup analyses (all P>0.05). A Cox analysis indicated that LRH increased the risk of overall and local pelvic recurrence after surgery compared with ARH (HR =2.338, 95% CI: 1.186-4.661, P=0.014; HR =10.313, 95% CI: 2.839-37.460, P<0.001); however, no significant difference between VALRH and ARH (all P>0.05). Sensitivity analysis of surgeons did not change the conclusions., Conclusions: Our analyses showed that the local pelvic recurrence rates and overall recurrence rates of LRH were significantly higher than ARH. VALRH could avoid tumor intraperitoneal exposure and achieve the same tumor prognosis as open surgery. By improving the standardization of minimally invasive surgery for early cervical cancer and paying close attention to the tumor-free concept, minimally invasive radical hysterectomy may achieve the same tumor outcome as open surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6450/coif). The series “New Progress and Challenge in Gynecological Cancer” was commissioned by the editorial office without any funding or sponsorship. DW served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Objective: To compare the 5-year overall survival (OS) and disease-free survival (DFS) of patients with cervical cancer who received neoadjuvant chemotherapy followed by surgery (NACT) with those who received abdominal radical hysterectomy alone (ARH)., Methods: We retrospectively compared the oncological outcomes of 1410 patients with stage IB3 cervical cancer who received NACT (n=583) or ARH (n=827). The patients in the NACT group were divided into an NACT-sensitive group and an NACT-insensitive group according to their response to chemotherapy., Results: The 5-year oncological outcomes were significantly better in the NACT group than in the ARH group (OS: 96.2% vs. 91.2%, respectively, p =0.002; DFS: 92.2% vs. 87.5%, respectively, p =0.016). Cox multivariate analysis suggested that NACT was independently associated with a better 5-year OS (HR=0.496; 95% CI, 0.281-0.875; p =0.015), but it was not an independent factor for 5-year DFS (HR=0.760; 95% CI, 0.505-1.145; p =0.189). After matching, the 5-year oncological outcomes of the NACT group were better than those of the ARH group. Cox multivariate analysis suggested that NACT was still an independent protective factor for 5-year OS (HR=0.503; 95% CI, 0.275-0.918; p =0.025). The proportion of patients in the NACT group who received postoperative radiotherapy was significantly lower than that in the ARH group ( p <0.001). Compared to the ARH group, the NACT-sensitive group had similar results as the NACT group. The NACT-insensitive group and the ARH group had similar 5-year oncological outcomes and proportions of patients receiving postoperative radiotherapy., Conclusion: Among patients with stage IB3 cervical cancer, NACT improved 5-year OS and was associated with a reduction in the proportion of patients receiving postoperative radiotherapy. These findings suggest that patients with stage IB3 cervical cancer, especially those who are sensitive to chemotherapy, might consider NACT followed by surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Zhang, Sun, Wang, Cui, Zhao, Wang, Zhang, Guo, Yang, Wang, Bin, Lang, Liu and Chen.)

Background: Multicentric intraepithelial lesions of the lower genital tract (multicentric lesions) were defined as intraepithelial lesions of two or three sites within cervix, vagina, and vulva occurring synchronously or sequentially. The characteristics of multicentric lesions has been poorly understood. This study aimed to evaluate the risk factors for multicentric lesions, including specific HPV genotypes., Methods: A retrospective case-control study was performed involving patients histologically diagnosed with multicentric lesions between January 2018 and October 2019. Controls were patients histologically diagnosed with single cervical intraepithelial neoplasia (CIN) and admitted during the same period. Univariable and multivariable analyses were used to assess the risk factors for multicentric lesions., Results: Of 307 patients with multicentric lesions, the median age was 50 years (interquartile range: 43-55.5), and they were older than patients with single CIN (median age: 43 years, interquartile range: 36-50). In the multicentric lesion group, the proportions of cytologic abnormalities, HPV positivity, and multiple HPV infections were 68.9, 97.0, and 36.5%, respectively. In the multivariable analysis, menopause, a history of malignant tumors beyond the lower genital tract and multiple HPV infections were associated with the incidence of multicentric lesions (Odd ratio (OR) = 3.14, 95% confidence interval (CI) 2.24-4.41; OR = 9.58, 95% CI 1.02-89.84; OR = 1.47, 95% CI 1.03-2.10). The common HPV genotypes were HPV16, HPV53, HPV58, HPV52, HPV51, HPV56 and HPV18 in patients with multicentric lesions. The proportion of HPV16 infection was higher in high-grade lesions group than that in low-grade lesions group (OR = 2.54, 95% CI 1.34-4.83). The OR for multicentric lesions, adjusted for menopause, smoking, gravidity, parity, a history of malignant tumor beyond the lower genital tract and multiple HPV infection, was 1.97 (95% CI 1.04-3.75) in patients with HPV51 infection., Conclusions: Multicentric lesions were associated with menopause, a history of malignant tumors and multiple HPV infections. HPV16 was the most common genotype, especially in high grade multicentric lesions and HPV51 infection was found to be a risk factor for detecting multicentric lesions.

Inspired by the tessellation or tiling process in daily life, a rigid triangular macrocyclic molecule containing anthracene as a photo-active moiety was synthesized to realize pre-organization through π-π interactions. The successful preparation of a 2D polymer monolayer at the air/water interface was achieved through [4+4]-photocycloaddition.

Background: As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown., Methods: We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa&#95;circ&#95;0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR., Results: Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation., Conclusion: Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

Graphdiyne (GDY), as a new carbon allotrope, possessing both sp- and sp 2 -hybridized carbon atoms, has attracted extensive attention due to great application potentials in various fields. To realize a fundamental understanding of the intrinsic properties of GDY, the controllable synthesis of ultrathin and highly crystalline GDY is necessary and challenging. Herein, a confined interfacial synthetic strategy towards highly crystalline ultrathin GDY at the water/oil/organogel interface, with greatly improved control over GDY structures, is reported. The morphology and chemical composition of GDY was characterized accordingly. After loading with gold, the as-prepared hydrophobic Au/GDY system showed excellent performance in the nitrogen reduction reaction, reaching the highest yield of 4.15 μg cm -2  h -1 with a Faraday efficiency of 1.95 %., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting cervical cancer and its precursors. This study aimed to analyze the prevalence of high-risk HPV genotypes and evaluate the role of HPV genotyping triage for detecting high-grade squamous intraepithelial lesions, adenocarcinoma in situ and cervical cancer (HSIL+) in HPV-positive women with normal cytology., Methods: A retrospective study was performed in women who had undergone co-screening at the China Medical University-affiliated Shengjing Hospital between 2012 and 2014., Results: Of the 34,587 women, 2665 HPV-positive women with normal cytology who had received colposcopy were eligible for analysis. In HSIL+ groups of 204 women, the common genotypes were HPV16, HPV52, HPV58, HPV33, HPV31 and HPV18 in order of prevalence. The proportion of histological HSIL+ in women infected with HPV33 or HPV31 was not significantly different compared to women infected with HPV16 (P = 0.30, P = 0.19, respectively). The odds ratios for histological HSIL+ were 3.26 (95% confidence interval [CI]: 2.41-4.40) in women with HPV16/18, 4.21 (95% CI: 2.99-5.93) in those with HPV16/18/31/33, and 5.73 (95% CI: 3.30-9.97) in those with HPV16/18/31/33/52/58. Including HPV31/33 genotyping together with HPV16/18 significantly increased the proportion of HSIL+ detection from 63.2 to 77.5% (P = 0.002) without significantly increasing the colposcopy per HSIL+ detection ratio (7.7 to 8.1, P = 0.66)., Conclusions: HPV genotyping played an important role in managing HPV-positive women with normal cytology. Genotyping for HPV31/33 should be added to the previously recommended HPV16/18 genotyping in triaging HPV-positive women in northeastern China.

A co-crystal was obtained based on donor-acceptor interactions. The obvious charge transfer from the linear donor to the triangular acceptor units results in a quasi-two-dimensional CT complex with excellent near-infrared photothermal conversion efficiency. The co-crystals further acted as an excellent photothermal material in seawater desalination.

Objective: To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients with elevated CA125 levels., Methods: The levels and positive expression rate of HE4 were compared between 371 patients with elevated CA125 levels and benign ovarian disease, and 132 patients with epithelial ovarian cancer to determine the diagnostic value of HE4., Results: The level and positive expression rate of HE4 differed significantly between the benign and malignant groups, in that, there was no significant difference in HE4 expression between CA125 low- and high-level groups within the benign ovarian disease group, with levels of HE4 being in the normal range in both groups. However, the positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups. ROC curve analysis showed that optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03 pmol/L and 119.70 pmol/L before and after menopause, respectively., Conclusions: Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels. The high specificity of HE4 was superior in identifying benign ovarian disease. We recommend increasing the cutoff values of HE4 in premenopausal patients and decreasing the cutoff values in postmenopausal patients for increased accuracy in the differential diagnosis of patients with elevated CA125 levels.

Drug resistance is a major problem in the treatment of advanced cervical cancer. The oncogenic microRNA-21 (miR-21) is involved in drug resistance in various cancers. However, the regulatory role of miR-21 and its target, Smad7 in drug resistance of cervical cancer remains to be elucidated. We compared miR-21 and Smad7 levels in human samples from chemoradiotherapy-resistance cervical cancer (resistant group) and chemoradiotherapy-sensitive cervical cancer (sensitive group) patients. Then, the miR-21 level was manipulated in HeLa and SiHa cervical cancer cells and the Smad7 level was determined by PCR and western blot. We also manipulated miR-21, Smad7 or both in cells, and measured cell viability using cell counting kit-8 method and epithelial-mesenchymal transition (EMT) biomarkers using Western blot. In human samples, resistant group has significantly higher miR-21 and lower Smad7 levels than sensitive group. In-vitro analysis demonstrated downregulated Smad7 after transfection with miR-21 mimics. When cells were transfected with Smad7 inhibitor, we observed increased drug resistance and changed levels of EMT-biomarkers after chemoradiotherapy, suggesting that downregulation of Smad7 decreased the sensitivity through EMT. When the cells were transfected with miR-21 inhibitor alone, we found increased sensitivity to chemoradiotherapy through EMT. However, such effects were attenuated when Smad7 was also downregulated after cotransfection. In summary, we provided clinical and experimental evidence that decreased miR-21 may improve drug resistance through EMT by direct targeting Smad7 in cervical cancer. Our data suggest that miR-21/Smad7 pathway may be an effective target for drug resistance in cervical cancer treatment.

We evaluated the ability of our two laparotomy-based models to predict optimal primary debulking surgery (PDS) and long-term outcomes of stage IIIC epithelial ovarian cancer (EOC). Data of 400 IIIC EOC patients who underwent laparotomy were retrospectively analyzed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated for 10 parameters. The parameters with a specificity ≥75%, PPV ≥50%, and NPV ≥50% were included in the final predictive index value (PIV) model. Peritoneal cancer index (PCI) was calculated summarizing lesion size scores (LSSs) of 13 regions. Receiver operating characteristic (ROC) curve was used to assessed the predictive value of PIV and PCI for optimal PDS. Univariate and multivariate analyses were performed to assess the prognostic value of PIV and PCI. After PDS, 223 (55.8%) patients with RD ≤1 cm had longer progression-free survival (PFS) and overall survival (OS) than patients with RD >1 cm (PFS: 22.4 vs. 15.4 months, respectively; P < 0.001 and OS: 48.6 vs. 35.6 months; P < 0.001). PCI better predicted optimal PDS than PIV (The area under the curve of ROC: PCI 0.79 vs. PIV 0.75). The predictive value of PIV and PCI models was verified using another cohort of 77 patients. And PIV and PCI models were demonstrated to be more powerful than the published laparoscopy-based predictive index (LPS-PI) model. Patients with a PIV ≥14 were more likely to undergo suboptimal PDS with a specificity of 100%. The median PFS and OS of patients with PIV < 3 were significantly longer than patients with PIV > 3 (PFS: 19.5 vs. 16.3 months, P = 0.007; OS: 46.1 vs. 37.0 months, P = 0.009). The median PFS and OS of patients with the PCI < 17.5 were significantly longer than patients with the PCI > 17.5 (PFS: 22.9 vs. 14.5 months, P < 0.001; OS: 54.3 vs. 31.5 months, P < 0.001). PCI could better predict optimal PDS compared with PIV. PCI was an independent prognostic factor for long-term outcome of IIIC EOC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Long non-coding RNA (lncRNA) microarray screening previously identified that HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) was significantly upregulated in type I endometrial cancer (EC). The present study aimed to determine the potential role of HOTAIRM1 and its sense transcript HOXA1 in the development and progression of type I EC., Methods: We detected the expression levels of HOTAIRM1 and HOXA1 in type I EC tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting and analyzed associated clinical data. Gain- or loss-of-function experiments were used to investigate the biological function of HOTAIRM1 and HOXA1 in type I EC, both in vitro and in vivo., Results: The expression levels of HOTAIRM1 and HOXA1 were significantly upregulated in type I EC tissues. Furthermore, the expression of HOTAIRM1 and HOXA1 were both significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. The expression of HOTAIRM1 was significantly correlated with that of HOXA1. Knockdown of HOTAIRM1 significantly inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro, while the over-expression of HOTAIRM1 led to the opposite effects. Moreover, we identified that HOTAIRM1 acts as a regulator for the expression of the HOXA1 gene in type I EC cells. As an oncogene, HOXA1 silencing also caused suppressive effects on tumors by inhibiting cell proliferation, migration and invasion. In addition, we also confirmed the role of HOTAIRM1 and HOXA1 in promoting tumor growth in vivo., Conclusion: Our findings are the first to identify that HOTAIRM1 functions as an oncogene to promote cell proliferation, migration and invasion by regulating HOXA1 in type I EC. Therefore, the HOTAIRM1/HOXA1 axis is a novel potential prognostic biomarker and new potential therapeutic target for type I EC., Competing Interests: The author reports no conflicts of interest in this work., (© 2019 Li et al.)

Endometriosis is an estrogen-dependent gynecological disease; however, the mechanism by which estradiol promotes the development of endometriosis, including invasion and proliferation, remains unclear. Estradiol is involved in cell invasion and proliferation by regulating the cytoskeleton. The abnormally high expression of cytoskeletal regulators (LIM kinase 1 [LIMK1] and cofilin1) is closely related to increased invasiveness and proliferation of eutopic endometrial stromal cells from endometriosis patients compared to normal eutopic endometrial cells. The aim of this study was to analyze the role of estradiol during invasion and proliferation through the LIMK1/cofilin1 pathway in the endometrium of women with endometriosis. To address this, primary eutopic endometrial stromal cells were isolated from the uteri of patients with endometriosis and cultured without estradiol. The phosphorylation of cofilin1 was analyzed by western blotting. Cell invasiveness and proliferation were evaluated following LIMK1 knockdown by RNA interference technology. We found that, before LIMK1silencing, the phosphorylation levels of cofilin1 and LIMK1 of eutopic endometrial stromal cells from endometriosis patients treated with estradiol were higher than cells not treated with estradiol ( P < .05 and P < .01, respectively). The total levels of cofilin1 and LIMK1 protein did not change ( P > .05 and P > .05, respectively). After LIMK1 silencing, the phosphorylation of cofilin1 by estradiol was significantly reduced, and invasiveness and proliferation were clearly and concurrently decreased ( P < .05 and P < .05, respectively). Thus, the phosphorylation of cofilin1 by estradiol is mediated by LIMK1, and estradiol is involved in regulating cell invasion and proliferation in endometriotic patients through the LIMK1/cofilin1 pathway.

Purpose: Endometriosis (EMs) is an estrogen-dependent multifactorial disease. Inhibition of estrogen in endometrial cells contributes to their failure to form lesions in ectopic sites. However, whether reducing or suppressing the inhibitory effect of estrogen results in the establishment of ectopic lesions remains unclear. The BCAR3 gene induces estrogen resistance in estrogen-dependent breast cancer cells and promotes cell migration, invasion, and epithelial-mesenchymal transition (EMT). However, the expression of BCAR3 in endometriosis and its effect on endometrial cell function and the anti-estrogen effect of endometriosis have not been reported. These issues are addressed in the present study., Methods: The study included 32 cases of ectopic endometrium and eutopic endometrium in patients with endometriosis and 31 cases of normal endometrium as controls. The expression of BCAR3 and microRNA (miR)-126-5p was detected by real-time PCR, immunohistochemistry, and western blotting. The effects of BCAR3 and miR-126-5p on the morphology and biological behavior of eutopic endometrial cells were verified using lentivirus overexpression and a vector knockdown model, the CCK-8 assay, Transwell experiments, and estrogen intervention experiments using primary cultures of epithelial and stromal cells., Results: The BCAR3 gene was highly expressed in ectopic endometrium and the eutopic endometrium of patients with endometriosis, and the expression level was higher in stage III-IV patients than in stage I-II patients. In vitro cell experiments showed that miR-126-5p negatively regulated the expression of BCAR3 and its effect on the migration and invasion of stromal cells. Low expression of miR-126-5p and high expression of BCAR3 promoted endometriosis stromal cell migration and invasion. Assessment of EMT in endometriosis compared with eutopic endometrium showed that the expression of vimentin was significantly increased and the expression of E-cadherin was significantly decreased in ectopic endometrium. Estrogen promoted EMT in eutopic endometrial epithelial cells and this effect was reversed by estrogen inhibitors. BCAR3 had no direct effect on EMT and did not act synergistically with estrogen on promoting EMT., Conclusion: miR-126-5p negatively regulated BCAR3 expression in eutopic endometriosis, enhanced the migration and invasion of endometrial cells, and promoted the occurrence of endometriosis. BCAR3 did not induce EMT and had no synergistic effect with estrogen, but its inhibition of anti-estrogen function may provide new insight into the mechanism of local estrogen action in endometriosis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Previous lncRNA microarray screening found that the AC002454.1 gene was highly expressed in endometriosis (EMS), and these expression levels were highly correlated with cyclin-dependent kinase-6 (CDK6). This study investigated the expression level and correlation between AC002454.1 and CDK6 in endometrium tissues and the influence of these changes in expression upon the biological behavior of eutopic endometrial cells. We confirmed AC002454.1 and CDK6 mRNA and protein were highly expressed in ectopic and eutopic endometrial tissue from patients with EMS and were clearly correlated. In vitro, both AC002454.1 and CDK6 positively regulated the proliferation, migration and invasion ability of eutopic endometrial cells and could promote the transformation of cells from G0/G1 phase to S phase. AC002454.1 and CDK6 may have synergistic effects, thereby affecting the biological behavior of endometrial cells, and thus promote the progression of EMS.