The Influence of Online and Offline Mixed Teaching Mode Based on TPACK on the Theoretical Knowledge and Comprehensive Ability Level of Tumor Gynecology Postgraduates.

Aim: To explore the influence of online and offline mixed teaching modes based on TPACK on theoretical knowledge and comprehensive ability of tumor gynecology postgraduates. Methods: In this study, a prospective randomized controlled study model was used to select 60 masters of oncology and gynecology who were interned in the Affiliated Hospital of the First Affiliated Hospital of Bengbu Medical College from September 2019 to April 2022 as the research objects. They were divided into a study group and a control group by random number table, with 30 cases in each group. The control group adopted the traditional teaching mode, while the study group adopted the mixed online and offline teaching mode based on TPACK to implement the teaching. The knowledge mastery, problem analysis ability and total ability of the two groups were compared before and after the practice. Results: After the practice, the scores of theoretical knowledge, clinical operation skills and case analysis ability of both groups were improved compared with those before the practice, and the scores of the study group were higher than those of the control group (P < .05). After practice, the scores of problem analysis and clinical work competence in both groups were significantly higher than those before practice, and the study group was higher than the control group (P < .05). After practice, the scores of professional technical knowledge, doctor-patient communication ability, clinical operation skill, disease observation ability and clinical first-aid ability of both groups were improved compared with those before practice, and the scores of the study group were higher than those of the control group (P < .05). Conclusion: In clinical teaching, the online and offline mixed teaching mode based on TPACK has obvious effects on improving the theoretical and clinical operation level of tumor gynecology postgraduates and the total ability of medical staff.

Prediction of lymph node status in patients with early-stage cervical cancer based on radiomic features of magnetic resonance imaging (MRI) images.

BACKGROUND: Lymph node metastasis is an important factor affecting the treatment and prognosis of patients with cervical cancer. However, the comparison of different algorithms and features to predict lymph node metastasis is not well understood. This study aimed to construct a non-invasive model for predicting lymph node metastasis in patients with cervical cancer based on clinical features combined with the radiomic features of magnetic resonance imaging (MRI) images. METHODS: A total of 180 cervical cancer patients were divided into the training set (n = 126) and testing set (n = 54). In this cross-sectional study, radiomic features of MRI images and clinical features of patients were collected. The least absolute shrinkage and selection operator (LASSO) regression was used to filter the features. Seven machine learning methods, including eXtreme Gradient Boosting (XGBoost), Logistic Regression, Multinomial Naive Bayes (MNB), Support Vector Machine (SVM), Decision Tree, Random Forest, and Gradient Boosting Decision Tree (GBDT) are used to build the models. Receiver operating characteristics (ROC) curve and area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to assess the performance of the models. RESULTS: Of these 180 patients, 49 (27.22%) patients had lymph node metastases. Five of the 122 radiomic features and 3 clinical features were used to build predictive models. Compared with other models, the MNB model was the most robust, with its AUC, specificity, and accuracy on the testing set of 0.745 (95%CI: 0.740-0.750), 0.900 (95%CI: 0.807-0.993), and 0.778 (95%CI: 0.667-0.889), respectively. Furthermore, the AUCs of the MNB models with clinical features only, radiomic features only, and combined features were 0.698 (95%CI: 0.692-0.704), 0.632 (95%CI: 0.627-0.637), and 0.745 (95%CI: 0.740-0.750), respectively. CONCLUSION: The MNB model, which combines the radiomic features of MRI images with the clinical features of the patient, can be used as a non-invasive tool for the preoperative assessment of lymph node metastasis.

Identification of a prognostic model based on immune and hypoxia-related gene expressions in cervical cancer.

BACKGROUND: Tumour immune microenvironment (TIME) has long been a key direction of tumour research. Understanding the occurrence, metastasis and other processes of cervical cancer (CC) is of great significance in the diagnosis and prognosis of tumours. METHODS: Here, this study applied the univariate Cox regression model to determine the prognostic association of immune and hypoxia signature genes in CC, and used Least Absolute Shrinkage and Selection Operator (LASSO) Cox method to build immune and hypoxia related risk score model to uncover the immune signature of the TIME of CC. Moreover, we used in vitro experiment to validate the expression level of signature genes. Notably, we assessed the predictive effect of anti-PD1/PDL1 immunotherapy using risk score model. RESULTS: Through the LASSO Cox regression model, we obtained 12 characteristic genes associated with the prognosis of CC, and also associated with immunity and hypoxia. Interestingly, the high-risk group had the properties of high hypoxia and low immunity, while the low-risk group had the properties of low hypoxia and high immunity. In the low-risk group, patients lived longer and had a significant therapeutic advantage of anti-PD-1 immunotherapy. CONCLUSIONS: Established risk scores model can help predict response to anti-PD-1 immunotherapy of CC.

The survival rate of cervical cancer (CC) is still low. A prognostic model for CC is urgently needed to improve the prognosis and survival. This study constructed a risk scoring models based on 12 characteristic gene related to hypoxia and immunity, including CX3CL1, CXCL3, GHSR, DLL4, FGFR2, PDF, KLRK1, MAP3K14, RETNLB, PRDX2, P4HA1 and PGK1, which can help predict the prognosis of PD-1 immunotherapy in CC patients. The high-risk group may have the properties of high hypoxia and low immunity, while the low-risk group patients live longer and have obvious therapeutic advantages in anti-PD-1 immunotherapy. Our findings suggest a potential link between hypoxia, immunity, prognosis, tumour immune microenvironment and response to immunotherapy in CC patients.

Different dominant transitions in holmium and ytterbium codoped oxyfluoride glass and glass ceramics originating from varying phonon energy environments.

Transparent oxyfluoride glass and glass ceramics doped with 0.5% Ho3+ and 1.0% Yb3+ ions have been prepared. X-ray diffraction and transmission electron microscopy demonstrated the formation of NaYF4 nanocrystals during the heat treatment process. Raman spectra indicated the variation of glass structure brought about by the formation of NaYF4 nanocrystals. XRD curves and Judd-Ofelt intensity parameters confirmed the incorporation of Ho3+ into NaYF4 nanocrystals. Significantly enhanced visible upconversion and 2.85 µm emissions were achieved in glass ceramic under 980 nm laser diode pumping. A broadband spectrum with a full-width at half-maximum close to 132 nm was obtained in the glass ceramic. Besides, the calculated peak emission cross section was 0.6 × 10-20 cm2, suggesting that the glass ceramic is a promising gain material that can be applied to broadband amplifiers in the mid-infrared region. Furthermore, energy transfer mechanisms in glass and glass ceramics were proposed based on visible to mid-infrared emission spectra. It was found that the change in the photon energy environment around rare earth ions induced different dominant transitions in glass and glass ceramic. Finally, the influence of phonon energy on the transition processes was further quantitatively investigated, which may provide useful guidance for obtaining highly efficient 2.85 µm emission of holmium.

The relationship of C-Reactive Protein to Albumin Ratio and interval debulking surgery outcome after neoadjuvant chemotherapy in ovarian cancer patients.

OBJECTIVE: To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients. METHODS: A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state. RESULTS: The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause. CONCLUSION: CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

[Oxidative damage effect of the serum of severe preeclamptic patients on human umbilical vein endothelial cell].

OBJECTIVE: To investigate oxidative damage effect of the serum of severe preeclamptic patients on human umbilical vein endothelial cells (HUVEC). METHODS: (1) HUVEC were randomly divided into 4 groups according to the following: blank group as control, normal group added 20% normal sera of pregnant women, group PE added 20% sera of severe preeclamptic patients, and group PE + Cat added 20% sera of severe preeclamptic patients plus 3×10(3) U/ml catalase. After cultured for 24 hours, the injury morphology and APO2.7 expression of HUVEC were detected by transmission electron microscopy and flow cytometry respectively. (2) Under the real-time scanning by laser scanning confocal microscopy, HUVEC were randomly divided into 4 groups according to the following: control group added 100 µmol/L H2O2 as positive control, normal group, group PE, and group PE + Cat. HUVEC of each group was scanned for 120 seconds to determine levels of reactive oxidative species (ROS), calcium homeostasis, and mitochondria membrane potential. RESULTS: (1) Obvious injury morphology of HUVEC was observed in group PE, and it was obviously improved by catalase in group PE + Cat. Percentage of HUVEC expressed APO2.7 was (37.8 ± 1.1)% in group PE, which was significantly higher than (13.4 ± 1.1)% in blank group or (13.5 ± 1.5)% in normal group, but significantly lower than (19.2 ± 1.6)% in group PE + Cat (all P < 0.01). (2) The fluorescence intensity curves of intracellular ROS and calcium showed slowly rising in group PE, but no obvious changes in normal group and PE + Cat. The values of ROS and calcium in group PE (12.0 ± 1.3, 4.1 ± 0.7) were higher than those in normal group (1.1 ± 0.4, 0.6 ± 0.4), but lower than those in group PE + Cat (1.5 ± 0.5, 0.9 ± 0.5; all P < 0.01). CONCLUSION: The serum of severe preeclamptic patients caused oxidative damage on HUVEC by increasing intracellular ROS generation, calcium overload, and decreasing mitochondrial membrane potential.

CISD2 transcriptional activated by transcription factor E2F7 promotes the malignant progression of cervical cancer.

Cervical cancer (CC) is the second most common type of cancer in women, and presents a serious threat to public health. We aimed to investigate the regulatory impacts of CDGSH iron-sulfur domain-containing protein 2 (CISD2) in CC and to discuss its relationship with E2F transcription factor 7 (E2F7). With the employment of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the expression of CISD2 and E2F7 in SiHa cells before or after transfection was estimated. Cell counting kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay, wound healing and transwell were used to detect the proliferation, apoptosis, migration and invasion of SiHa cells. The activity of CISD2 was detected using luciferase report assay and chromatin immunoprecipitation (ChIP) assay was used to confirm the binding of E2F7 and CISD2 promoter. The contents of proliferation- and apoptosis-related proteins were detected using western blot. Results revealed that CISD2 expression was greatly enhanced in CC cell lines. CISD2 depletion inhibited the proliferation, migration and invasion of SiHa cells but promoted the cell apoptosis. It was also found that E2F7 was remarkably elevated in SiHa cells. According to JASPAR database, the binding sites of E2F7 and CISD2 were predicted and ChIP confirmed the binding of E2F7 and CISD2 promoter. Results obtained from luciferase report assay indicated that E2F7 overexpression increased the activity of CISD2 promoter region. Furthermore, further functional experiments demonstrated that the impacts of E2F7 interference on the proliferation, migration, invasion and apoptosis of SiHa cells were reversed by CISD2 overexpression. In summary, CISD2 silence could alleviate the malignant progression of CC and could be transcribed by E2F7.

RNA methylation-related genes of m6A, m5C, and m1A predict prognosis and immunotherapy response in cervical cancer.

PURPOSE: To investigate the prognostic value of N6-methyladenosine (m6A)-, 5-methylcytosine (m5C)-, and N1-methyladenosine (m1A)-related genes in cervical cancer (CESC) and predicting immunotherapy response. METHODS: We downloaded cervical cancer mRNA expression profiles, clinical data, and m6A, m5C, m1A-related genes from public databases, and subjected them to serial bioinformatics analysis and clinical sample validation. RESULTS: Differential analysis revealed 106 methylation-related differential genes (MEDs), including 44 differentially downregulated and 62 upregulated genes. We then obtained methylation models containing 10 genes by univariate and multifactorial COX analysis. High risk genes with HR > 1 include IQGAP3, PTBP1, STAC3, CUX1, SLC2A1, and CA2, and low risk genes with HR < 1 include IGBP1, DUOX1, CHAF1A, and STAC3. We verified the accuracy of the model from inside TCGA and outside GSE39001 (AUC = 0.729). K-M analysis showed shorter survival times in the High-risk group, and Immunocytic infiltration analysis showed model genes closely associated with six immune cells. The high-risk group may benefit more effectively from immunosuppressive therapy, especially anti-CTLA-4 therapy (p < .05). We also screened nine drugs for potential treatment and verified the expression of three key genes SLC2A1, CUX1, and CA2 using immunohistochemistry and RT-qPCR experiments with clinical samples. CONCLUSION: We identified a prognostic model using m6A/m5C/m1A-related genes in cervical cancer, which can predict survival time and correlate with immune cell infiltration. Additionally, anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer.KEY MESSAGESCervical cancer still has a high mortality rate, we aim to establish a strong prognostic index and new treatment goals for improving patient survival.The role of three types of RNA methylation modifications, m6A, m5C, and m1A, in cervical cancer, remains unknown. Therefore, it is essential to explore the potential molecular mechanisms of m6A, m5C, and m1A methylation regulation in cervical cancer.We also screened nine drugs for potential treatment and anti-CTLA-4 may be used as an immunotherapeutic agent for cervical cancer. We verified the expression of three key genes SLC2A1, CUX1, and CA2.

A fast forward algorithm of azimuthal gamma imaging logging while drilling.

Logging while drilling (LWD) technology can evaluate the formation interface and stratigraphic properties around the borehole in real time, so as to adjust the drilling trajectory and effectively improve the reservoir encounter rate. Fast forward algorithm can be used with LWD, by comparing the fast forward results with the actual gamma LWD results, it can distinguish the formation interface more accurately. Fast forward algorithm also can provide a theoretical basis for geosteering and azimuthal gamma logging interpretation. In this paper, based on the spatial distribution law of gamma rays and The Monte Carlo N-particle code (MCNP)-driven spatial sensitivity function, a 3D fast forward method of gamma ray LWD is proposed. Compared with the traditional algorithms, the new method can realize the fast simulations of gamma ray logging in four sectors, which enables fast azimuthal imaging. The comparison shows that whether in vertical wells or high-angle wells, the results of the proposed method are in high agreement with the MCNP fine simulations. In addition, the new method improves the calculation speed by tens of thousands of times with comparable accuracy. Finally, the gamma logging-while-drilling data of a highly deviated well in a field case verifies the accuracy and applicability of the method. The algorithm can meet the requirements of LWD for fast forward modeling of azimuthal natural gamma ray logging, which is expected to be applied to geosteering and logging interpretation of high angle and horizontal wells.

Stearoyl-CoA desaturase 1 regulates malignant progression of cervical cancer cells.

The primary regulatory gene for fatty acid synthesis, stearoyl-CoA desaturase 1 (SCD1), has been linked to the progression of several malignancies. Its role in cervical cancer remains unclear till now. This paper aimed to explore the role and mechanism of SCD1 in cervical cancer. The GEPIA database was used to perform a bioinformatics analysis of the role of SCD1 in cervical cancer staging and prognosis. The influences of SCD1 knockdown on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress were then investigated. Following transcription factor Kruppel like factor 9 (KLF9) was discovered to be negatively correlated with SCD1, the regulatory role of KLF9 in the effects of SCD1 on cervical cancer cells and the signaling pathway was evaluated. According to the GEPIA database, SCD1 level was associated with the cervical cancer stage, the overall survival level, and the disease-free survival level. Cell proliferation, migration, invasion, and EMT progress were all hindered when its expression was knocked down. Novelty, KLF9 reversed the effects of SCD1 on cells, as well as the Akt/glycogen synthase kinase 3ß (GSK3ß) signaling pathway. Together, SCD1 was negatively regulated by KLF9 and it activated the Akt/GSK3ß signaling pathway to promote the malignant progression of cervical cancer cells. Developing SCD1 inhibitors offers novel ideas for the biological treatment of cervical cancer.

PGE2 inhibits neutrophil phagocytosis through the EP2R-cAMP-PTEN pathway.

Prostaglandin E2 (PGE2) is a potent lipid mediator of inflammation that modulates immune cell function by binding to unique G protein-coupled receptors (EP receptors). PGE2 production increases during microbial infection and inflammation. In this study, we assessed the effect of PGE2 on the phagocytosis of bacteria by neutrophils, which are key players during infection and inflammation. We also looked for specific EP receptor signaling pathways that contributed to the neutrophil phagocytic activity. PGE2 (50-1000 ng/ml) inhibited the phagocytosis of Escherichia coli by HL-60 human neutrophils in a concentration-dependent manner. Inhibition of neutrophil phagocytosis by PGE2 correlated with increased intracellular cyclic adenosine monophosphate (cAMP) production, and forskolin, an adenosyl cyclase agonist, confirmed the inhibitory effect of cAMP stimulation on neutrophil phagocytosis. The expression of EP2 receptors by HL-60 cells was confirmed by western blot analysis, and selective agonism of EP2 receptors mimicked the inhibition of phagocytosis by PGE2. The EP2 receptor antagonist AH-6089 partially blocked the inhibition of neutrophil phagocytosis PGE2. Specific inhibition of phosphatase and tensin homolog (PTEN) enzyme attenuated the inhibition of neutrophil phagocytosis by PGE2, and both PGE2 and increased intracellular cAMP increased neutrophil PTEN activity, which was associated with decreased PTEN phosphorylation. The results support negative regulation of the antimicrobial activity of neutrophils (i.e., phagocytosis), which has important implications for the future management of bacterial infections.

Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer.

We aimed to study the function and mechanism of endothelial cell-specific molecule 1 (ESM1) in endometrial cancer (EC). The binding relationship between SPI1 and ESM1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter assay. The expressions and effects of SPI1 and ESM1 were determined using quantitative real-time PCR, immunohistochemistry, Western blot, and functional experiments. ESM1 was highly expressed in EC and was associated with the poor prognosis of patients. ESM1 silencing suppressed the viability, proliferation, invasion, and angiogenesis of EC cells, down-regulated expressions of PCNA, N-cadherin, Vimentin, VEGFR-1, VEGFR2, and EGFR, but upregulated E-cadherin level, while ESM1 overexpression did oppositely. Moreover, SPI1 bound to ESM1. Overexpressed SPI1 promoted the expression of ESM1 and induced malignant phenotype (viability, proliferation, and invasion), which were countervailed by ESM1 silencing. Collectively, ESM1 induced by SPI1 promotes the malignant phenotype of EC.

Human neonatal neutrophils are resistant to apoptosis with lower caspase-3 activity.

The incidence of neonatal inflammatory diseases remains high despite improved strategies for dealing with infection. Neutrophils are believed to play a significant role in neonatal inflammatory diseases due to their secretion of harmful mediators. Neutrophils rapidly undergo apoptosis following activation; dysregulation of the neutrophil apoptotic pathway may be an underlying mechanism of neonatal inflammatory disorders. In this study, we determined whether neonatal neutrophils are intrinsically resistant to apoptosis relative to their adult counterparts. Twelve healthy full-term newborn infants and 12 healthy adult volunteers, aged 20 to 45 years, were enrolled in this study. Neutrophils were isolated from umbilical cord blood or fresh venous peripheral blood, and neutrophils of each subject were cultured for up to 48 hours. Flow cytometric analysis revealed that spontaneous apoptosis of adult neutrophils increased with culture time (23% ± 2% at 12 h, 49% ± 4% at 24 h and 76% ± 3% at 48 h), whereas the frequency of apoptosis was significantly lower in neutrophils from neonates (9% ± 2% at 12 h, 30% ± 4% at 24 h and 49% ± 3% at 48 h) (p < 0.01 for each time point). Importantly, the expression levels of caspase-3 mRNA and a precursor form of caspase-3 protein were lower in neonatal neutrophils than adult neutrophils, as judged by RT-PCR and Western blot analyses. Moreover, caspase-3 activity was lower in neonatal neutrophils, compared to adult neutrophils. These findings suggest that neonatal neutrophils are intrinsically apoptosis-resistant, which may be due to the low expression of caspase-3.

Fucoxanthin may inhibit cervical cancer cell proliferation via downregulation of HIST1H3D.

OBJECTIVE: To investigate the role of fucoxanthin, reported to have significant anticancer effects, and histone Cluster 1 H3 Family Member D (HIST1H3D; implicated in tumorigenesis) in cervical cancer. METHODS: The half maximal inhibitory concentration (IC50) of fucoxanthin against HeLa and SiHa cervical cancer cells was determined. Differentially expressed genes (DEGs) in SiHa cells treated with IC50 fucoxanthin were screened by high-throughput techniques and subjected to signal enrichment. Following identification of HIST1H3D as a candidate gene, HIST1H3D-knockdown models were created via transfection with a short hairpin HIST1H3D payload. Impacts on cell proliferation, cell-cycle distribution, colony formation, and apoptosis were studied. RESULTS: The fucoxanthin IC50 was 1 445 and 1 641 µM (Hela and SiHa cells, respectively). Chip results revealed 2 255 DEGs, including 943 upregulated and 1 312 downregulated genes, in fucoxanthin-treated versus untreated SiHa cells. Disease and function analysis indicated that these DEGs are primarily associated with cancer and organismal injuries and abnormalities, and online integrated pathway analysis showed that the DEGs were mainly enriched in p53 signalling. HIST1H3D was significantly downregulated in response to fucoxanthin. Inhibition of HIST1H3D mRNA significantly reduced cell proliferation and colony formation, significantly augmented the percentage of apoptotic HeLa and SiHa cells, and cells were arrested in G0/G1 cell cycle phase. CONCLUSION: The results suggest that HIST1H3D may be an oncogene in cervical carcinogenesis and a potential fucoxanthin target in treating cervical cancer.

Hydrogen peroxide promotes the activation of preeclampsia peripheral T cells.

Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients with PE exhibit systemic high oxidative stress status and inflammatory immune activation. This study aims to define the role of H2O2 in the activation of neutrophils and T lymphocytes in PE patients. CD3+/HLA-DR+ cells in blood from PE patients are remarkably increased compared with those of normal non-pregnancies or normal pregnancies, while the percentage of CD3+/CD62L+ cells is significantly reduced in PE patients compared to normal pregnancies. Furthermore, CD62L levels in granulocytes of periphery blood of PE patients are significantly higher than non-pregnancies, but significantly lower than normal pregnancies. To characterize the effects of intracellular reactive oxygen species (ROS) on T lymphocyte activation in PE patients, PBMCs from normal pregnancies were challenged with H2O2, and intracellular ROS levels in neutrophil granulocytes, as well as T cell surface marker levels, have been determined. We confirm that H2O2 exposure increases intracellular ROS levels in neutrophil granulocytes, and increases the proportion of CD3+/HLA-DR+ cells, but does not alter the percentage of CD3+/CD62L+ cells in PBMCs. Our study has confirmed dysregulated CD3+/HLA-DR+ and CD3+/CD62L+ T lymphocytes in PE patient peripheral blood, and the dysregulative effects of H2O2 on T lymphocyte activation, suggesting a novel mechanism of immune activation in PE.