Ovarian cancer (OC) is a lethal malignancy with limited treatment options. While p53-associated cellular protein-testes derived (PACT) has been implicated in cellular stress responses, its role in OC progression and the regulation of ferroptosis remains unclear. The functional role of PACT was examined in A2780 and OVCAR-3 cells through siRNA-mediated knockdown and overexpression. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay was used to detect cell migration and invasion. Ferroptosis was assessed by measuring cell death, iron content, malondialdehyde (MDA), reactive oxygen species (ROS), and the expression of key proteins (SLC7A11, GPX4). Molecular mechanisms were investigated via co-immunoprecipitation (Co-IP), ubiquitination assays, and analysis of subcellular localization. In vivo validation was conducted using a xenograft model in BALB/c nude mice. The results showed that PACT knockdown significantly inhibited the proliferation, migration, and invasion of OC cells. It also promoted ferroptosis, as indicated by elevated iron accumulation, lipid peroxidation, and ROS levels, along with reduced SLC7A11 and GPX4 expression-effects that were reversed by ferrostatin-1. PACT was found to enhance TERT expression and telomerase activity via the Keap1-Nrf2 pathway by facilitating Keap1 ubiquitination and degradation, which promoted Nrf2 nuclear translocation. Importantly, Nrf2 knockdown abolished PACT-mediated TERT upregulation. In vivo, PACT silencing suppressed tumor growth and induced ferroptosis. In conclusion, PACT promotes OC progression by suppressing ferroptosis and enhancing malignant phenotypes through the Keap1-Nrf2-TERT axis. These findings suggest that targeting PACT may represent a promising therapeutic strategy for OC.

Although the maternal microbiome is recognized as a critical regulator of offspring physiology, its role in heart development and the pathogenesis of heart failure remains largely unclear. Using a germ-free (GF) mouse model, we demonstrated that maternal microbiota depletion leads to spontaneous heart failure with preserved ejection fraction (HFpEF) in adult female offspring, recapitulating the phenotypes of human diastolic dysfunction. Integrated transcriptomic and proteomic profiling of fetal hearts revealed impaired structural cardiomyocyte maturation in GF offspring, characterized by suppressed sarcomere assembly. Metabolomic analysis revealed that acetate was concurrently downregulated in maternal serum and fetal cardiomyocytes. Importantly, prenatal acetate supplementation and fecal microbiota transplantation rescued fetal cardiomyocyte maturation defects and prevented the onset of HFpEF in adult female offspring. Mechanistically, maternal microbe-derived acetate regulates fetal cardiomyocyte maturation by enhancing the levels of H3K9ac and H3K27ac in the MYL2 promoter region, thereby promoting the transcriptional enhancement of MYL2. This developmental reprogramming provides lifelong protection against diastolic dysfunction. In addition, the concentration of acetate in pregnant women's serum was positively correlated with myocardial thickness in the left ventricle of the fetus. Our findings establish maternal microbial metabolites as determinants of cardiac maturation and suggest prenatal acetate supplementation as a novel preventive intervention for developmental diastolic dysfunction.

Background Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a common but preventable complication in hospitalized patients. However, VTE prophylaxis remains underutilized. This study aims to explore physicians’ knowledge, attitudes, practices (KAP) regarding VTE prevention in Chinese public hospitals and their interrelationships to inform improvement strategies. Methods A cross-sectional, multicenter online survey was conducted using a KAP-based questionnaire distributed to physicians in Chinese public hospitals. Data analysis integrated descriptive statistics, Pearson correlations, and structural equation modeling (SEM). Results Among 787 valid responses, KAP scores were positive (Knowledge: 4.00 ± 0.81; Attitude: 4.38 ± 0.78; Practice: 4.38 ± 0.82). Scores on knowledge of intermittent pneumatic compression usage (3.40 ± 1.24) and VTE risk assessment tools (3.98 ± 1.08) were relatively low, while only 23% and 40% of physicians reported being very familiar with them, respectively. About half strongly agreed on performing dynamic VTE/bleeding risk assessments and tailoring prophylactic measures accordingly. Poor patient awareness and adherence also hindered VTE prevention. Positive correlations were observed among KAP domains ( r = 0.35 – 0.59, P < 0.001). SEM demonstrated knowledge directly influenced practice ( β = 0.50, P < 0.05), while attitude facilitated knowledge-to-practice translation ( β = 0.25, P < 0.05). Conclusions Knowledge is pivotal for VTE prophylaxis implementation. Future targeted training should focus on addressing physicians’ knowledge deficiencies, enhancing awareness of dynamic risk assessment and improving patient education to strengthen institutional VTE prevention capabilities. Given the predominance of tertiary public hospital respondents, the generalizability of these findings should be interpreted with caution.

BACKGROUND:The paracrine crosstalk between macrophages and granulosa cells, forming a "macrophage M1 polarization-inflammation-pyroptosis" vicious cycle in the ovarian immune microenvironment, promotes premature ovarian insufficiency (POI) progression. This study aimed to investigate the therapeutic potential of metformin-capped silver nanoparticles (Met-AgNPs) in disrupting pathological paracrine signaling axis and restoring ovarian function. METHODS:Met-AgNPs and control AgNPs were synthesized and physicochemically characterized. Dynamic light scattering (DLS) was conducted to evaluate the hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the nanoparticles in different dispersion media (deionized H2O, PBS, DMEM). The in vitro release kinetics and in vivo biodistribution were also evaluated. THP-1-derived macrophages were induced to M1 polarization and treated with Met-AgNPs, AgNPs, or metformin, followed by assessment of macrophage polarization states. The conditioned medium (CM) from these macrophages was then applied to human granulosa KGN cells to evaluate its effects on NLRP3 inflammasome activation and pyroptosis. A cyclophosphamide (CTX)-induced POI rat model was established and treated with Met-AgNPs, AgNPs, or metformin. Ovarian function was evaluated via estrous cycle, hormone levels, follicle counting, and fertility assessment. Ovarian histopathology, macrophage polarization, inflammation, and NLRP3-driven pyroptosis were assessed. RESULTS:Met-AgNPs exhibited a spherical morphology, smaller hydrodynamic diameter, and enhanced colloidal stability compared to AgNPs. Crucially, Met-AgNPs demonstrated sustained drug release and achieved targeted accumulation with localized retention in inflamed ovaries. In vitro, treatment with Met-AgNPs, AgNPs, or metformin all reprogrammed M1 macrophages towards M2 phenotype, accompanied by decreased pro-inflammatory cytokine secretion and increased anti-inflammatory cytokine secretion. The CM from all treated macrophages inhibited NLRP3 inflammasome activation and pyroptosis in KGN cells. Notably, Met-AgNPs demonstrated superior efficacy among all treatment groups. In POI rats, Met-AgNPs treatment restored estrous cycles, serum hormone levels, and healthy follicle count, and improved fertility. These improvements were mechanistically associated with the inhibition of M1 macrophage infiltration and NLRP3-driven pyroptosis within the ovarian tissues. CONCLUSION:Met-AgNPs ameliorated POI by reprogramming macrophage polarization from M1 to M2 phenotype and then inhibiting NLRP3-dependent pyroptosis in granulosa cells. Our findings propose Met-AgNPs as a promising nanotherapeutic strategy for alleviating ovarian inflammation and restoring fertility in POI.

BACKGROUND:Although miR-216a-5p is linked to tumour progression and chemoresistance, its mechanistic contributions to gastric cancer (GC) remain undefined. This study sought to clarify the role of miR-216a-5p in GC progression and its impact on oxaliplatin (OXA) resistance. METHODS:MiR-216a-5p expression in GC specimens and cell lines was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics and dual-luciferase reporter assays were employed to identify and, subsequently, validate ZBTB2 as a direct target of miR-216a-5p, which was further confirmed through RNA immunoprecipitation, Western blot, and qRT-PCR analyses. In vitro functional assays, including proliferation, migration, and drug sensitivity assays, assessed the effects of miR-216a-5p and ZBTB2 on GC cells. Rescue experiments further elucidated the miR-216a-5p/ZBTB2 regulatory axis. Additionally, in vivo experiments substantiated these findings. RESULTS:Quantitative analyses revealed substantial downregulation of miR-216a-5p in both clinical GC samples and cellular models relative to matched non-neoplastic mucosal tissues and normal epithelial controls. Functional assays demonstrated that miR-216a-5p inhibited GC cell proliferation and migration while enhancing their sensitivity to OXA. Mechanistically, miR-216a-5p directly targeted and downregulated ZBTB2, thereby modulating GC cell growth and chemoresistance. Rescue experiments confirmed that ZBTB2 overexpression partially reversed the effects of miR-216a-5p on GC cells. In vivo studies further supported the tumour-suppressive role of miR-216a-5p and its regulation of ZBTB2. CONCLUSION:This study demonstrated that miR-216a-5p suppresses GC by inhibiting cell proliferation, migration, and OXA resistance through the downregulation of ZBTB2. Our findings underscored miR-216a-5p's role as a potential molecular target for improving chemotherapy efficacy against GC.

Background: Ovarian cancer (OC) ranks among the most lethal gynecological malignancies. Research has highlighted long noncoding RNAs (lncRNAs) as promising novel molecular targets for cancer therapy. This study endeavors to identify novel lncRNAs, elucidate their specific roles, and unravel their regulatory mechanism in OC development. Methods: Utilizing LncRNA Microarray technology, we screened for differentially expressed RNAs, ultimately selecting THAP7-AS1 for in-depth investigation. RNA pull-down, luciferase assays and FISH were performed to validate the interaction among THAP7-AS1, miR-92b-5p and FA2H. qRT-PCR was conducted to assess the expression of THAP7-AS1, miR-92b-5p and FA2H in OC tissues and cell lines. Cellular biological effects were examined using proliferation CCK-8 and EdU assays, chamber Transwell migration assays, and flow cytometer for apoptosis analysis. Additionally, nude mice xenograft models were established to evaluate the in vivo effect of THAP7-AS1 on tumor growth. Results: Our findings revealed a downregulation of THAP7-AS1 in OC tissues and cells. Overexpression of THAP7-AS1 inhibited cell proliferation, migration, and induced apoptosis. miR-92b-5p was identified as a sponge target of THAP7-AS1, with its expression upregulated in OC tissues and cells. Forced expression of miR-92b-5p exhibited cellular effects opposite to those of THAP7-AS1 overexpression. Additionally, FA2H was confirmed as a direct target of miR-92b-5p Silencing FA2H suppressed apoptosis, promoted proliferation and migration. In vivo experiments showed overexpression of THAP7-AS1 significantly reduced tumor volume and weight. Conclusion: THAP7-AS1 is firstly reported as a tumor suppressor in OC by targeting the miR-92b-5p/FA2H axis. Our findings suggest that THAP7-AS1 holds potential as therapeutic target in OC treatment.

Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. Proliferation, migration and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. A xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis in nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and western blot assays were conducted. FAM64A was upregulated in ovarian cancer tissues and cells and was demonstrated to promote the proliferation, migration and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assays indicated that FAM64A could regulate the EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the knockdown of FAM64A inhibited tumor growth in xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogenic function by regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.

Cervical cancer (CC) is an important public health problem for women, gene expression patterns which were governed by epigenetic modifications can result in CC, CC-chemokine receptor 4 (CCR4) interacts with C-C-motif ligand 22 (CCL22) is associated with tumor progression or metastasis. A previous study by the present authors revealed the levels of chemokine CCL22 and its receptor CCR4 are increased in CC tissues, nevertheless, the regulatory mechanisms governing its expression remain poorly understood. The present study aimed to investigate the potential role of enhancer of zeste homolog 2 (EZH2)-induced epigenetic activation of CCL22/CCR4 and caused epithelial-to-mesenchymal transition (EMT) remodeling in CC. CCL22 and CCR4 were significantly up-regulated in CC samples compared with normal cervix tissues, and obvious induction of promoter DNA methylation levels of CCL22 and CCR4 was found in CC tissues. Demethylation reactivated the transcription of CCL22 and CCR4. DNA methyltransferase 3A (DNMT3A) was found to directly bind to the CCL22 and CCR4 promoter regions in vitro. Downregulation of the expression of EZH2 in CC cell lines altered DNMT3A expression and induced CCL22 and CCR4 promoters' methylation levels, while CCL22 and CCR4 mRNA expression decreased. An in vivo assay showed that EZH2 regulated the expression of CCL22/CCR4 components through DNMT3A, consistent with the in vitro results. In EZH2-silenced CC cells, migration was reduced, levels of EMT-related markers, including vimentin, slug, snail and β-catenin, were all reduced and zona occludens 1 (ZO-1) increased. In DNMT3A-silenced CC cells, migration was induced, vimentin, slug, snail and β-catenin were all induced and ZO-1 was reduced. Inhibition of CCL22 protein significantly decreased migration of CC cells and vimentin, slug, snail and β-catenin levels, while ZO-1 increased. In conclusion, EZH2 appears to regulate CCL22/CCR4 expression via epigenetic activation, causing EMT process remodeling in CC progression.

With the development of immunotherapy research, the role of immune checkpoint blockade (ICB) in the treatment of cervical cancer has been emphasized, but many patients still can’t receive long-term benefits from ICB. Poly ADP ribose polymerase inhibitor (PARPi) has been proved to exert significant antitumor effects in multiple solid tumors. Whether cervical cancer patients obtain better benefits from the treatment regimen of PARPi combined with ICB remains unclear. The alteration of PD-L1 expression induced by niraparib in cervical cancer cells and its underlying mechanism were assessed by western blot and immunofluorescence and quantitative real-time polymerase chain reaction (qRT–PCR).The regulation of PTEN by KDM5A was confirmed using Chromatin immunoprecipitation (ChIP) assay and RNA interference. Analyzing the relationship between PD-L1 and immune effector molecules through searching online databases. Therapeutic efficacy of niraparib, PD-L1 blockade or combination was assessed in syngeneic tumor model. The changes of immune cells and cytokines in vivo was detected by immunohistochemistry (IHC) and qRT–PCR. We found that niraparib upregulated PD-L1 expression and potentiated the antitumor effects of PD-L1 blockade in a murine cervical cancer model. Niraparib inhibited the Pten expression by increasing the abundance of KDM5A, which expanded PD-L1 abundance through activating the PI3K-AKT-S6K1 pathway. PD-L1 was positively correlated with immune effector molecules including TNF-α, IFN-γ, granzyme A and granzyme B based on biological information analysis. Niraparib increased the infiltration of CD8+ T cells and the level of IFN-γ, granzyme B in vivo. Our findings demonstrates the regulation of niraparib on local immune microenvironment of cervical cancer, and provides theoretical basis for supporting the combination of PARPi and PD-L1 blockade as a potential treatment for cervical cancer.

Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.

Myeloid-derived suppressor cells (MDSCs) contribute to tumor immune evasion, and have been identified as immunosuppressive cells in cervical cancer. The effect of TMPRSS11D (transmembrane serine protease 11D) in some cancers has been reported, but its role in immune escape of cervical cancer is still unclear. This study aims to elucidate the regulatory mechanism of TMPRSS11D on the immunosuppressive function of MDSCs in cervical cancer. Our data showed that the proportion of polymorphonucleoid MDSCs (PMN-MDSCs), the contents of immunosuppressive factors (including INOS, IDO, and ARG-1) secreted by MDSCs, and TMPRSS11D mRNA level in peripheral blood mononuclear cells (PBMCs) of malignant cervical cancer patients was significantly higher than that of benign tumor patients. Next, CD3+ T cells from PBMCs of cervical cancer patients were stimulated with anti-CD3 and anti-CD28, and then co-cultured with PMN-MDSCs from the same donors at a ratio of 1:2 for 3 days. PMN-MDSCs from malignant tumors produced more ROS, while TMPRSS11D knockdown blocked ROS production. PMN-MDSCs inhibited T cell proliferation and IFN-& gamma; production, while silencing TMPRSS11D in PMN-MDSCs hindered the immunosuppressive effect of PMN-MDSCs. Mechanistically, TMPRSS11D bound to ALR (Augmenter of liver regeneration) and negatively regulated ALR expression, inducing ER stress in PMNMDSCs, thereby enhancing the immunosuppressive effect of PMN-MDSCs on T cells. Additionally, mouse xenograft tumor assay was conducted to assess the role of TMPRSS11D in tumor growth and MDSC accumulation in vivo. Silencing TMPRSS11D impeded the growth of cervical cancer xenografts and reduced the accumulation of MDSCs in tumor tissues. In conclusion, TMPRSS11D induced ER stress in MDSCs through negative regulation of ALR, thus enhancing the immunosuppressive effect of MDSCs on T cells, so as to promote the growth of cervical cancer tumors.

Abstract Background: Our previous study revealed the chemokine CCL22 and its receptor CCR4 are elevated in cervical cancer (CC) tissues. The present study aimed to investigate the potential role of EZH2-induced epigenetic activation of CCL22/CCR4 and caused EMT remodeling in CC. Methods: We evaluated whether CCL22-CCR4 expression levels could be regulated by EZH2 and subsequently evaluated the mechanism of EZH2 on the CCL22-CCR4. The animal model supported the experimental findings. Results: CCL22 and CCR4 were significant up-regulated in CC samples compared with normal cervix tissues, and obvious induction of promoter DNA methylation levels of CCL22and CCR4 was shown in CC tissues. Demethylation reactivated the transcription of CCL22 and CCR4. DNMT3A was found to directly bind to the CCL22and CCR4 promoter regions in vitro. Downregulation of the expression of EZH2 in CC cell lines altered DNMT3A expression, induced CCL22and CCR4 promoters’ methylation level as well, and decreased CCL22and CCR4 mRNA expression. An in vivo assay showed that, EZH2 regulated the expression of CCL22/CCR4 components through DNMT3A, consistent with the in vitro results. In EZH2-silenced CC cells, migration was reduced, levels of EMT related markers, including vimentin, slug, snail and β-catenin, were all reduced, and ZO-1 increased. In DNMT3A-silenced CC cells, migration was induced and vimentin, slug, snail and β-catenin were all induced, ZO-1 reduced. Inhibition of CCL22 protein significantly decreased migration of CC cells and vimentin, slug, snail and β-catenin, increased ZO-1. Conclusions: Overall, EZH2 thus appears to regulate CCL22/CCR4 expression via epigenetic activation, causing EMT process remodeling in CC progression.

Pachymic acid has various pharmacological effects, including anti-inflammatory, antioxidant, immunomodulatory, and antitumor. However, the role of pachymic acid in cervical cancer remains unclear. So, we investigated the effects of pachymic acid in cervical cancer and elucidated the underlying mechanisms. We treated HeLa cells and normal cervical epithelial cells (HUCECs) with pachymic acid (0, 10, 20, 40, 80, or 160 μM) for 72 h, and found the cell activity was decreased in cells treated with 160 μM pachymic acid for 48 h or 80 μM pachymic acid for 72 h, while HUCECs viability without effect. Next, we observed that endoplasmic reticulum (ER) related gene expression, mitochondrial membrane potential (MMP) changes, ATP depletion, reactive oxygen species (ROS) generation and apoptosis were increased. Moreover, we observed that cytochrome C (Cytc) expression was increased and apoptosis-inducing factor (AIF) was decreased in the cytoplasm of pachymic acid-treated HeLa cells. Tauroursodeoxycholic acid (TUDCA) of ER stress inhibitor reversed the effects of pachymic acid on HeLa cells. Phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) of the AMPK pathway key protein was upregulated in pachymic acid-induced HeLa cells. Finally, we subcutaneously implanted HeLa cells into female nude mice and treated them with pachymic acid (50 mg/kg) for 3 weeks (5 days/week), and observed in pachymic acid induced xenograft mice, tumor growth was suppressed, cell apoptosis, ER-related gene expression, and ROS levels in tumor tissues were increased. Therefore, these findings demonstrated that pachymic acid plays an anti-tumor activity in cervical cancer through inducing ER stress, mitochondrial dysfunction, and activating the AMPK pathway.

Background: High-risk human papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the risk of cervical cancer among Asian populations. Objective: This study aimed to determine whether the HPV58 E7 T20I (C632T) variant promotes the malignant behavior of cervical cancer cells and the underlying mechanism of the HR-HPV E7 oncoprotein involved in the development of cervical cancer. Methods: CCK-8 and clone formation assays were used to detect cell proliferation ability. Transwell assays and cell wound healing assays were used to evaluate cell migration ability. Targeted knockdown of E2F1 expression using specific siRNA, RT-qPCR and Western blot were performed to assess gene expression changes. A chromatin immunoprecipitation assay was used to verify that E2F1 interacted with the TOP2A promoter region. Results: HPV58 E7 and HPV58 E7M oncoproteins increased the proliferation and migration ability of cervical cancer cells. However, the HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. HPV E7 and E7M oncoproteins increased the expression of TOP2A, BIRC5 and E2F1, and knockdown of HPV E7 decreased their expression. Low E2F1 expression reduced the expression of TOP2A and BIRC5 and inhibited the proliferation and migration ability of cervical cancer cells. E2F1 interacted with the TOP2A gene promoter region to promote its transcriptional expression. Conclusion: The HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. The HR-HPV E7 oncoprotein enhanced the proliferation and migration of cervical cancer cells, which was considered to be due to the HPV E7 oncoprotein, increasing the expression of BIRC5 and TOP2A by upregulating the transcription factor E2F1.

高校作为人才培育的"基地",在夯实本科专业理论知识的同时,如何支持并鼓励学生进行实习实践活动,提供实践交流平台,使学生全面发展,以此提升高校人才就业率以及人才就业竞争能力,是当下高校教育工作研究的重要课题.高校艺术类人才提升就业竞争力,首先要科学分析艺术类人才自身应具备的能力,其次从学校培养艺术人才工作的角度来探索提升就业竞争力的具体途径,包括在打牢专业技能基础上还应重视多方位发展,学习新技能,提高自己的就业优势,还要注重加强自身的政治思想修养,牢固树立为实现中华民族伟大复兴无私奉献的精神.

Family with sequence similarity 83, member A (FAM83A) is a tumor-exclusive gene that has a vital role in numerous tumors. However, its role in tumorigenesis remains controversial. This work is dedicated to the study of the role of FAM83A in ovarian cancer. We observed elevated levels of FAM83A in ovarian cancer specimens and cells. Kaplan-Meier survival curves revealed that elevated FAM83A levels predicted a worse overall survival in ovarian cancer patients. The inhibition of FAM83A caused remarkable suppressive effects on the proliferation and invasion of ovarian cancer cells, and enhanced their chemosensitivity. On the contrary, the upregulation of FAM83A had opposite effects. Mechanistically, FAM83A had an effect on the Akt and Wnt/β-catenin pathways in ovarian cancer cells. The repression of Akt could cancel the regulatory effect of FAM83A overexpression on the Wnt/β-catenin pathway. Moreover, reactivation of the Wnt/β-catenin pathway abolished FAM83A-inhibition-evoked antitumor effects. Additionally, FAM83A inhibition weakened the tumorigenic potential of ovarian cancer in vivo. Taken together, this work shows that FAM83A exerts a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/β-catenin pathway and proposes FAM83A as an effective and possible treatment target for ovarian cancer.

音乐是人类的精神需求中的娱乐需求,而大学生要树立正确的理想信念,这需要培养大学生的思想政治修养.通过把我国思政教育和音乐进行有机结合,可以把复杂的知识变得通俗易懂,让学生对枯燥乏味的思政课程产生兴趣,该文通过阐述音乐与人的基本思想作为分析,深入认识音乐教育和思想政治之间的联系和影响,为提升当代大学生思想政治的方法提出切实可行的办法.

目的:检测免疫抑制细胞Foxp3+Treg和免疫蛋白IDO在不同病变宫颈组织中的表达情况.方法:采用免疫细胞化学及蛋白印记(Western blot)检测Foxp3蛋白及IDO蛋白在宫颈癌细胞系HeLa、SiHa及C33A中的表达与分布;采用免疫组织化学法检测Foxp3和IDO在20例正常宫颈组织及45例不同程度宫颈病变组织中的表达情况.结果:Foxp3蛋白在HeLa、SiHa及C33A中无表达;IDO蛋白在HeLa、SiHa及C33A细胞的胞浆中均有表达.Foxp3蛋白在宫颈组织中表达于Treg,IDO蛋白在宫颈组织中表达于APC和/或异常细胞.宫颈病变组织中的Foxp3+Treg(H=43.211,P=0.000)和IDO蛋白的表达均明显高于正常组织(χ2=20.028,P=0.00;Z=226.600,P=0.00).随着病理级别升高,Foxp3+Treg的侵袭性(H=28.307,P=0.000)增加,Foxp3+Treg与IDO+APC的数目显著正相关(rs=0.550,P=0.003)统计学正相关(rs=0.550,P=0.000).结论:在宫颈癌进展的不同病理阶段,局部微环境中Foxp3+Treg数目随宫颈细胞恶性转化的进程而增多,IDO+APC细胞在早期宫颈病变组织中表达多于晚期病变.

目的 探讨精细化管理护理新理念应用于消毒供应中心管理中的作用.方法 将在本院消毒供应中心工作的50名工作者根据护理新理念应用前后分成常规管理组25名和精细化管理组25名,对比两组护理人员知识掌握率和患者院内感染发生率及其对护理工作的满意率.结果 常规管理组护理人员知识掌握率为76.00％,精细化管理组为100.00％;患者院内感染发生率常规管理组为31.67％,精细化管理组为8.33％;常规管理组患者对护理工作总满意率是76.67％,精细化管理组是98.33％,相比有统计学意义,P＜0.05.结论 在消毒

Objective:To explore the teaching effect of individualized teaching based on problem-based learning (PBL) that applied in gynecology practice teaching under the background of conflicts between postgraduate examination preparation and clinical internship for medical undergraduates.Methods:A total of 157 medical students of the five-year program who started gynecology internship and meanwhile prepared for the postgraduate entrance examination in 2018 were enrolled in the study and divided into two groups randomly. One group received traditional teaching (control group), and the other group received individualized teaching mode based on PBL (observation group). After the internship, the two groups of students were assessed for their theoretical and clinical skills, and the students' evaluation of the teaching effect was acquired through a questionnaire survey. SPSS 22.0 was used to perform chi-square test.Results:The students in observation group had statistically significant higher scores in theory and skill tests than those in the control group ( P<0.001). The evaluation of boosting their enthusiasm for internship, advancing self-learning ability, conducing to improving learning methods in the future, and enhancing clinical skills and thinking ability in the observation group was significantly better than that in the control group ( P<0.05). Conclusion:The individualized teaching model based on PBL could efficiently alleviate the conflicts between internship and postgraduate entrance examination preparation and improve the effect of gynecology practice teaching.