Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study.

OBJECTIVE: To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. METHODS: Patients with BOTs younger than 20 years who underwent FSS were included in this study. RESULTS: A total of 34 patients were included, with a median patient age of 17 (range, 3-19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8-40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10-148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. CONCLUSIONS: Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Modulation of evapotranspiration and stream runoff by weathered bedrock in arid and semi-arid mountains.

Earth's Critical Zone exhibits remarkable heterogeneity and complexity. Hence, further investigation is required to examine the composition of Earth's Critical Zone as well as the diverse eco-hydrological patterns they exhibit under varying climatic and geological circumstances. This exploration should primarily be conducted through the investigation and experiments of the hillslope unit, where the topography and weathered bedrock are representative, with particular emphasis on semi-arid regions where water resources serve as the primary limiting factor. Here, we have determined that the structure of the weathering profile displays systematic variation across the topography and heterogeneous landscape on uninterrupted slopes. Differences in the structure of the subsurface critical zone led to differences in its water storage capacity at the same time. Runoff in alpine shrubs and forests was dominated by subsurface runoff, and grassland was dominated by surface runoff. In the alpine shrub immediately adjacent to the watershed, an estimated quantity of 129 mm of water is stored within the unsaturated zone of the soil, serving as exchange water to replenish moisture in the underlying bedrock. In contrast to alpine shrubs, an estimated quantity of 62.7 mm of water originates from the unsaturated zone of soil and weathered bedrock in the forest. However, approximately 21.1 mm of moisture is unavailable to plants. The soil water storage in grasslands exhibits a decline throughout the growing season, with a subsequent augmentation occurring solely after substantial precipitation events exceeding 20 mm. In wet years, dynamic storage predominantly manifests as groundwater saturation throughout the entire ground and high subsurface runoff. In dry years, the limited runoff response indicates that the catchment's dynamic water storage primarily comprises "indirect" water storage, which predominantly resides within the soil, saprolite, and weathered rock below the "field capacity", subsequently being released into the atmosphere through evapotranspiration.

SERS-based AI diagnosis of lung and gastric cancer via exhaled breath.

Distinct diagnosis between Lung cancer (LC) and gastric cancer (GC) according to the same biomarkers (e.g. aldehydes) in exhaled breath based on surface-enhanced Raman spectroscopy (SERS) remains a challenge in current studies. Here, an accurate diagnosis of LC and GC is demonstrated, using artificial intelligence technologies (AI) based on SERS spectrum of exhaled breath in plasmonic metal organic frameworks nanoparticle (PMN) film. In the PMN film with optimal structure parameters, 1780 SERS spectra are collected, in which 940 spectra come from healthy people (n = 49), another 440 come from LC patients (n = 22) and the rest 400 come from GC patients (n = 8). The SERS spectra are trained through artificial neural network (ANN) model with the deep learning (DL) algorithm, and the result exhibits a good identification accuracy of LC and GC with an accuracy over 89 %. Furthermore, combined with information of SERS peaks, the data mining in ANN model is successfully employed to explore the subtle compositional difference in exhaled breath from healthy people (H) and L/GC patients. This work achieves excellent noninvasive diagnosis of multiple cancer diseases in breath analysis and provides a new avenue to explore the feature of disease based on SERS spectrum.

Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs.

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.

Intra-Articular Injection of Interleukin-8 Neutralizing Monoclonal Antibody Effectively Attenuates Osteoarthritis Progression in Rabbits.

OBJECTIVE: Cytokines are implicated in the pathogenesis of osteoarthritis (OA), and this study aims to assess the therapeutic potential of an IL-8 neutralizing monoclonal antibody (mAb) for OA intervention. DESIGN: The study employed a rabbit model of OA induced by anterior cruciate ligament transection (ACLT) surgery to investigate the effects of an interleukin (IL)-8 neutralizing mAb, with hyaluronic acid (HA) used as a positive control. Primary outcomes assessed in the rabbits included cartilage repair, synovitis, joint effusion, changes in footprints, and lower limb loading conditions. RESULTS: Compared to HA, intra-articular injection of the IL-8 neutralizing mAb demonstrated a more pronounced attenuation of OA progression and enhancement of cartilage repair. We observed a reduction in synovitis and joint effusion, indications of bone marrow edema, as well as improvements in lower limb function. In knees treated with the neutralizing IL-8 mAb, there was a significant decrease in IL-8 levels within the synovial tissues. CONCLUSIONS: The IL-8 neutralizing mAb exhibits promising therapeutic potential in the management of OA by attenuating inflammation and facilitating cartilage repair. However, further investigations are warranted to comprehensively elucidate the underlying mechanisms, optimize treatment protocols, and ensure the long-term safety and efficacy of this innovative therapeutic approach.

The association between ferroptosis and autophagy in cardiovascular diseases.

Autophagy is a process in which cells degrade intracellular substances and play a variety of roles in cells, such as maintaining intracellular homeostasis, preventing cell overgrowth, and removing pathogens. It is highly conserved during the evolution of eukaryotic cells. So far, the study of autophagy is still a hot topic in the field of cytology. Ferroptosis is an iron-dependent form of cell death, accompanied by the accumulation of reactive oxygen species and lipid peroxides. With the deepening of research, it has been found that ferroptosis, like autophagy, is involved in the occurrence and development of cardiovascular diseases. The relationship between autophagy and ferroptosis is complex, and the association between the two in cardiovascular disease remains to be clarified. This article reviews the mechanism of autophagy and ferroptosis and their correlation, and discusses the relationship between them in cardiovascular diseases, which is expected to provide new and important treatment strategies for cardiovascular diseases.

Corrigendum: LASSO-derived prognostic model predicts cancer-specific survival in advanced pancreatic ductal adenocarcinoma over 50 years of age: a retrospective study of SEER database research.

[This corrects the article DOI: 10.3389/fonc.2023.1336251.].

Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia.

BACKGROUND: Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. METHODS: Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. RESULTS: We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. CONCLUSIONS: Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

One-step stromal vascular fraction therapy in osteoarthritis with tropoelastin-enhanced autologous stromal vascular fraction gel.

Background: Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE). Methods: We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The in vivo therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes. Results: Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the in vivo OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments. Discussion: The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.

Macrophage migration inhibitory factor reversed senescent phenotype in human chondrocytes in vitro.

BACKGROUND: The senescence of chondrocytes, which is closely linked to the development of osteoarthritis (OA), has been found to be influenced by the inflammatory environment of joint cavity. However, there remains a lack of comprehensive understanding regarding the specific mechanisms through which cytokine impacts chondrocytes senescence. PURPOSE: To investigate the effects of MIF on the chondrocytes senescence and explore the underlying mechanism. METHODS: Human cytokine array and ELISA were used for the level of MIF in synovium fluid. CCK-8 was used for chondrocytes viability. IF, WB, SA-ß-gal staining and flow cytometry were used for the chondrogenic, apoptotic and senescent phenotype of chondrocytes. RESULTS: The level of MIF was significantly increased in OA patients. MIF significantly reversed the senescent phenotype induced by LPS pretreatment in human chondrocytes. MIF significantly enhanced the expression of Col II, SOX9, and ACAN in LPS pre-treated human chondrocytes. Furthermore, MIF significantly inhibited the apoptosis of LPS-induced senescent chondrocytes. CONCLUSION: Increased level of MIF in osteoarthritic joint cavity might effectively suppress the senescent phenotype and simultaneously improve the chondrogenic phenotype in chondrocytes, the underlying mechanism was likely to be independent of apoptosis.

Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-ß in Giant Cell Tumor of Bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. OBJECTIVE: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. METHODS: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. RESULTS: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-ß II receptor to ligand Activin A. CONCLUSION: HCG restrained the Smad signaling pathway by antagonizing TGF-ß signaling in GCTB. HCG may serve as a useful patent to treat GCTB.

Magnetic resonance imaging and deoxyribonucleic acid methylation-based radiogenomic models for survival risk stratification of glioblastoma.

Glioblastoma multiforme (GBM) is one of the deadliest tumours. This study aimed to construct radiogenomic prognostic models of glioblastoma overall survival (OS) based on magnetic resonance imaging (MRI) Gd-T1WI images and deoxyribonucleic acid (DNA) methylation-seq and to understand the related biological pathways. The ResNet3D-18 model was used to extract radiomic features, and Lasso-Cox regression analysis was utilized to establish the prognostic models. A nomogram was constructed by combining the radiogenomic features and clinicopathological variables. The DeLong test was performed to compare the area under the curve (AUC) of the models. We screened differentially expressed genes (DEGs) with original ribonucleic acid (RNA)-seq in risk stratification and used Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotations for functional enrichment analysis. For the 1-year OS models, the AUCs of the radiogenomic set, methylation set and deep learning set in the training cohort were 0.864, 0.804 and 0.787, and those in the validation cohort were 0.835, 0.768 and 0.651, respectively. The AUCs of the 0.5-, 1- and 2-year nomograms in the training cohort were 0.943, 0.861 and 0.871, and those in the validation cohort were 0.864, 0.885 and 0.805, respectively. A total of 245 DEGs were screened; functional enrichment analysis showed that these DEGs were associated with cell immunity. The survival risk-stratifying radiogenomic models for glioblastoma OS had high predictability and were associated with biological pathways related to cell immunity.

The association between sleep duration and lung cancer: a meta-analysis.

PURPOSE: The link between sleep duration and lung cancer risk has been suggested by some epidemiological studies. This meta-analysis was performed to further understand this relationship. METHODS: MEDLINE and EMBASE entries up to December 2022 were searched for eligible publications. A random effects model was used to calculate pooled relative risks (RRs) with 95% confidence intervals (95% CIs). Publication bias was estimated using Begg's and Egger's regression asymmetry test. RESULTS: The meta-analysis included 11 studies (including 10 cohort studies and 1 case-control study). The pooled adjusted RRs were 1.13 (95% CI: 1.03-1.24) for short sleep duration and 1.21 (95% CI: 1.07-1.37) for long sleep duration. CONCLUSION: The findings of this meta-analysis suggested that both short and long sleep duration are associated with an increase in lung cancer risk. These findings need to be corroborated through large-scale prospective studies.

Elevated ADAR expression is significantly linked to shorter overall survival and immune infiltration in patients with lung adenocarcinoma.

To date, few studies have investigated whether the RNA-editing enzymes adenosine deaminases acting on RNA (ADARs) influence RNA functioning in lung adenocarcinoma (LUAD). To investigate the role of ADAR in lung cancer, we leveraged the advantages of The Cancer Genome Atlas (TCGA) database, from which we obtained transcriptome data and clinical information from 539 patients with LUAD. First, we compared ARAR expression levels in LUAD tissues with those in normal lung tissues using paired and unpaired analyses. Next, we evaluated the influence of ADARs on multiple prognostic indicators, including overall survival at 1, 3 and 5 years, as well as disease-specific survival and progression-free interval, in patients with LUAD. We also used Kaplan-Meier survival curves to estimate overall survival and Cox regression analysis to assess covariates associated with prognosis. A nomogram was constructed to validate the impact of the ADARs and clinicopathological factors on patient survival probabilities. The volcano plot and heat map revealed the differentially expressed genes associated with ADARs in LUAD. Finally, we examined ADAR expression versus immune cell infiltration in LUAD using Spearman's analysis. Using the Gene Expression Profiling Interactive Analysis (GEPIA2) database, we identified the top 100 genes most significantly correlated with ADAR expression, constructed a protein-protein interaction network and performed a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis on these genes. Our results demonstrate that ADARs are overexpressed in LUAD and correlated with poor patient prognosis. ADARs markedly increase the infiltration of T central memory, T helper 2 and T helper cells, while reducing the infiltration of immature dendritic, dendritic and mast cells. Most immune response markers, including T cells, tumor-associated macrophages, T cell exhaustion, mast cells, macrophages, monocytes and dendritic cells, are closely correlated with ADAR expression in LUAD.

Are people living with HIV have a low vulnerability to omicron variant infection: results from a cross-sectional study in China.

BACKGROUND: A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. METHODS: A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. RESULTS: In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42-0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96-0.99; aOR 0.59, 95%CI 0.36-0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08-0.25). CONCLUSIONS: Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.

Oncological and Reproductive Outcomes after Fertility-Sparing Surgery in Patients with Advanced-Stage Serous Borderline Ovarian Tumor: A Single-Center Retrospective Study.

Our study aimed to analyze the prognosis and reproductive outcomes of patients with advanced-stage serous borderline ovarian tumors (SBOTs) who underwent fertility-sparing surgery (FSS). This study included patients aged ≤ 45 years diagnosed with advanced-stage (International Federation of Gynecology and Obstetrics II and III) SBOTs who were treated with FSS. Conservative surgeries were performed in 65 patients with advanced-stage SBOT with a median age of 28 years (range, 16-44 years). Nine patients had invasive implants. The median follow-up was 81.7 months. Forty-six patients (70.8%) had a relapse (median time to first recurrence, 22.8 months). Thirteen patients subsequently developed recurrence as an invasive disease, and two died due to disease progression. After multivariate analysis, age < 30 years and incomplete cytoreduction were independent risk factors for recurrence. Invasive implants and postoperative residual tumors were significantly associated with shorter disease-free survival. Of 35 patients attempting to conceive, 12 underwent assisted reproductive technology. Additionally, 19 pregnancies, including 15 full-term births, were documented. FSS provides a good chance of reproductive success in women with advanced-stage SBOT who desire fertility preservation, but it has a high recurrence rate and risk of malignancy transformation. Patients with invasive implants should be strictly selected for FSS.

Comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for low-risk gestational trophoblastic neoplasia (FIGO Score 0-4): study protocol for a prospective, multicentre, randomized trial.

BACKGROUND: Single-agent chemotherapy using methotrexate or actinomycin D is the first-line treatment for patients with low-risk gestational trophoblastic neoplasia. Various methotrexate-based and actinomycin D-based single-agent regimens can be used. However, there is insufficient evidence to determine the superior regimen. To guide doctors in selecting a single-agent chemotherapy regimen for patients with low-risk gestational trophoblastic neoplasia, we will compare two regimens. METHODS: We will conduct a multicentre, randomized, prospective clinical trial. Selected low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4) will be randomized 1:1 to a biweekly single-dose actinomycin D group or a multiday methotrexate therapy group. The actinomycin D group will receive IV pulse actinomycin D (1.25 mg/m2) every 14 days, and the methotrexate group will receive methotrexate (50 mg) intramuscularly on days 1, 3, 5, and 7 (4 doses per cycle) and leucovorin (15 mg) intramuscularly on days 2, 4, 6, and 8. This process will be repeated every 14 days. The primary endpoints will include the complete remission rate by single-agent therapy and the overall complete remission rate. The secondary endpoints will include the duration needed to achieve complete remission after single-agent chemotherapy, number of courses needed to achieve complete remission after single-agent chemotherapy, incidence and severity of adverse effects, effects on menstrual conditions and ovarian function based on the anti-Mullerian hormone level, and patient-reported quality of life. DISCUSSION: Previous clinical trials comparing biweekly single-dose actinomycin D with multiday methotrexate therapy for treating low-risk gestational trophoblastic neoplasia patients failed to meet the expected case number. Through this multicentre study, the complete remission ratio and efficacy difference between biweekly single-dose actinomycin D and multiday methotrexate therapy will be obtained. This study will also provide the basis for formulating a preferred regimen for treating patients with low-risk gestational trophoblastic neoplasia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04562558, Registered on 13 September 2020 (Protocol version 2020-9-24, version 1.0).

The Triaging Effect of the Human Papillomavirus 16/18 E7 Oncoprotein Assay in HPV 16/18-Positive Patients for High-Grade Cervical Intraepithelial Neoplasia Screening: A Cross-Sectional Study.

Objective: To investigate the triaging efficacy of the human papillomavirus (HPV) 16/18 E7 oncoprotein assay for high-grade cervical intraepithelial neoplasia (CIN2+) screening in HPV 16/18-positive patients in a tertiary hospital in China. Methods: We collected 476 cervical cell samples from women who tested positive for HPV 16/18 in the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2022 and analyzed them by the HPV 16/18 E7 oncoprotein assay before colposcopy and biopsy. The study assessed the triaging efficacy of the HPV 16/18 E7 oncoprotein assay in HPV 16/18-positive patients by analyzing its performance against the gold standard of histologically confirmed CIN2+. Results: The positive rate of the HPV 16/18 E7 oncoprotein assay was 41.0% (114/278) in the negative for intraepithelial lesions and malignancy/CIN1 group and 80.3% (159/198) in the CIN2+ group. For triage of women with a positive HPV 16/18 test for CIN2+ detection, the HPV 16/18 E7 oncoprotein assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 80.3%, 59.4%, 58.5%, and 80.9%, respectively. Furthermore, longitudinal follow-up of five patients showed a good correlation between the expression of the HPV 16/18 E7 oncoprotein and cervical lesion grades. Conclusions: As a triage method for HPV 16/18-positive patients, the HPV 16/18 E7 oncoprotein assay improves the specificity, reduces the colposcopy referral rate, and has the potential for long-term monitoring of high-grade CIN.

Early-stage oral cancer diagnosis by artificial intelligence-based SERS using Ag NWs@ZIF core-shell nanochains.

Surface-enhanced Raman spectroscopy (SERS) has great potential in the early diagnosis of diseases by detecting the changes of volatile biomarkers in exhaled breath, because of its high sensitivity, rich chemical molecular fingerprint information, and immunity to humidity. Here, an accurate diagnosis of oral cancer (OC) is demonstrated using artificial intelligence (AI)-based SERS of exhaled breath in plasmonic-metal organic framework (MOF) nanoparticles. These plasmonic-MOF nanoparticles were prepared using a zeolitic imidazolate framework coated on Ag nanowires (Ag NWs@ZIF), which offers Raman enhancement from the plasmonic nanowires and gas enrichment from the ZIF shells. Then, the core-shell nanochains of Ag NWs@ZIF prepared with 0.5 mL Ag NWs were selected to capture gaseous methanethiol, which is a tumor biomarker, from the exhalation of OC patients. The substrate was used to collect a total of 400 SERS spectra of exhaled breath of simulated healthy people and simulated OC patients. The artificial neural network (ANN) model in the AI algorithm was trained with these SERS spectra and could classify them with an accuracy of 99%. Notably, the model predicted OC with an area under the curve (AUC) of 0.996 for the simulated OC breath samples. This work suggests the great potential of the combination of breath analysis and AI as a method for the early-stage diagnosis of oral cancer.