Background Spermidine (SPD) dysregulation is common in multiple cancers and is associated with reduced survival of cervical cancer (CC) cells. However, the mechanisms underlying SPD's role in CC progression remain poorly understood. This study aimed to investigate how SPD metabolism influences ferroptosis in cervical cancer. Methods Using bioinformatics analysis of public databases and immunohistochemistry on clinical specimens, we assessed the expression of SPD metabolic enzymes. In vitro experiments were conducted using HeLa and SiHa cervical cancer cell lines. Cell viability was measured by CCK-8 assay, mitochondrial morphology was observed via transmission electron microscopy, and protein expression was analyzed by Western blot. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels were quantified using fluorescent probes and biochemical assays. Statistical significance was determined using Student’s t-test or one-way ANOVA. Results We identified elevated expression of the rate-limiting SPD metabolic enzyme SAT1 in cervical cancer tissues. SPD treatment induced ferroptosis in CC cells, as demonstrated by decreased Glutathione Peroxidase 4 (GPX4) expression, increased ROS and MDA levels, and characteristic mitochondrial alterations. Overexpression of SAT1 or supplementation with its downstream metabolite N 1 -acetylspermidine enhanced ferroptosis. Importantly, both SPD and N 1 -acetylspermidine attenuated the ferroptosis resistance caused by SAT1 inhibition. Conclusion Our findings reveal that enhanced SAT1-mediated SPD metabolism promotes ferroptosis in cervical cancer, suggesting that targeting this metabolic pathway could represent a novel therapeutic strategy for CC treatment.

Objective To determine the relationship between local microenvironment and cervical cancer (CC). Discovering differential florae and metabolites associating with CC. Design Observational study. Participants 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls were enrolled in our study. Methods We performed 16S rDNA sequencing and metabolomic analysis in the cervicovaginal fluid to reveal the differential florae and metabolites during cervical carcinogenesis. Results Carcinogenesis was associated with alterations in microbiome diversity, individual taxa, and functions. Bacterial diversity was increased and the composition was changed by the influence of cervical cancer carcinogensis. Lactobacillus was significantly reduced in LSIL and CC patients. On the contrary, the relative abundance of Prevotella was significantly elevated in LSIL patients. Lipids were significantly declined in LSIL and HSIL patients compared to HC participants, and significantly elevated in CC compared to LSIL and HSIL patients. Pathway enrichment analysis found phenylalanine, tyrosine and tryptophan biosynthesis pathway was crucial in cervical carcinogenesis. Conclusions These results showed that microbic and metabolomic profiling are capable of distinguishing CC from precancer and highlighted potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites expected to become a potential tool to assist in the diagnosis of cervical cancer. Funding We would like to thank Development & Demonstration Program of Wuxi (N20192004), Key Research & Development Program of Jiangsu Province (BE2015617), The 5th Phase of “Project 333” of Jiangsu (BRA2019024) and Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (KYCX19_1182) for their support.

目的 探讨青海省海东市育龄期女性生殖道感染知识、健康信念及健康行为现状,并分析其影响因素.方法 采用调查问卷对海东市第二人民医院妇科门诊 722 名育龄期女性进行调查,采用t检验、方差分析、多重线性回归分析.结果 海东市育龄期女性生殖道感染知识维度得分为(14.48±5.08)分,信念维度得分为(72.13±9.09)分,行为维度得分为(34.49±5.64)分;知识维度和信念维度得分与居住地、文化程度、职业、家庭收入、丈夫文化程度与职业、生殖健康知识获取时间及途径相关(P<0.05);行为维度得分与居住地、文化程度、婚姻状况、家庭收入、丈夫文化程度与职业有关(P<0.05).结论 海东市育龄期女性生殖道感染知识、行为、态度得分均较低,相关部门应结合其影响因素对育龄期女性采取针对性的健康教育措施,进而提高当地女性的自我保健意识.

Cervical cancer (CC) continues to be one of the most common cancers among females worldwide. It takes a few years or even decades for CC to arise in a minority of women with cervical precancers. An increasing corpus of studies today indicates that local microecology and carcinogenesis are intimately related. To investigate the changes in cericovaginal microecology with the development of cervical cancer, we performed 16S rDNA sequencing and metabolomic analysis in cericovaginal fluid from 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls to reveal the differential flora and metabolites during cervical carcinogenesis. Carcinogenesis is associated with alterations in microbiome diversity, individual taxa, and functions with notable changes in Lactobacillus, Prevotella and Aquabacterium, as well as in cervicovaginal metabolites that correlate with cervicovaginal microbial patterns. Increased bacterial diversity and a decline in the relative abundance of Lactobacillus, the dominant species in the cericovaginal flora, are observed when cervical lesions advance. According to KEGG pathway enrichment analysis, lipids and organic acids change as cervical cancer progresses, and the phenylalanine, tyrosine, and tryptophan biosynthesis pathway is essential for the development of cervical cancer. Our results reveal that microbic and metabolomic profiling is capable of distinguishing CC from precancer and highlights potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites are expected to become a potential tool to assist in the diagnosis of cervical cancer.

Cervical cancer(CC)continues to be the second leading cause of cancer death in women aged 20 to 39[1].Recent research has shown that the cervical microbiota differs in different stages of cervical carcinogenesis[2].It has been reported that the gut microbiota is linked to host metabolism,which influences the progression of the disease[3].The role of cervicovaginal flora in affecting host metabolism,thereby causing the progression of cervical cancer,requires further research.In this direction,metabolomics has been implemented to detect small molecular differential metabolites in cancer progression.Metabolomics is the study of the thousands of low-molecular-weight molecules found in biological fluids and tissues of different individuals,whether normal or afflicted with disease,and it reflects reasonable changes in biological functions.

Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1β and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.

质子泵抑制剂(proton pump inhibitors,PPIs),也称为H+/K+-ATP酶抑制剂,由于其抑制胃酸分泌导致胃内pH值升高,阻碍药物溶解及吸收,从而影响药物的有效性和安全性.口服靶向抗肿瘤药物是肿瘤一线治疗手段之一.由于部分肿瘤患者同时服用PPIs和靶向抗肿瘤药物,研究PPIs对口服靶向抗肿瘤药物吸收的影响,对于实现有效和安全的癌症治疗具有特别重要的意义.本文对相关文献进行检索并整理,总结PPIs对口服靶向抗肿瘤药物吸收的影响,以期为临床用药提供参考,促进合理用药,提高临床疗效.

Toll样受体(Toll Like Receptor,TLR)是一种模式识别受体( pattern recognition receptor , PRR) ,微生物及其代谢产物入侵人体是通过识别PRR,激活固有免疫从而激活抗原特异性获得性免疫系统[1-2].TLRs是一个膜受体家族,在感知包括细菌、真菌和病毒在内的多种入侵病原体方面发挥着关键作用[3-4].TLR4是人类发现的第一个TLR,是介导信号转导的重要PRR,而且是唯一可以经髓样分化因子88 ( myeloid differ-entiation primary response protein 88 , MyD88 )依赖型和β干扰素TIR结构域衔接蛋白( TIR domain-containing adaptor indu-cing interferon-β,TRIF)依赖型两条信号通路的TLR家族成员.TLR4具有多种不同结构的配体,如植物二萜紫杉醇、呼吸道合胞病毒的融合蛋白、纤连蛋白和热休克蛋白,其中最重要的配体是脂多糖[1].脂多糖是革兰阴性菌外膜的重要成分,有强大的免疫刺激活性,TLR4通过识别脂多糖激活下游信号通路,在机体的细菌感染和免疫反应中起着重要作用.

Background Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. Methods we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. Results Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increasedFTH1andGPX4mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. Conclusions These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.

PURPOSE:Therapy for triple-negative breast cancer (TNBC) is a global problem due to lack of specific targets for treatment selection. Cancer stem cells (CSCs) are responsible for tumor formation and recurrence but also offer a promising target for TNBC-targeted therapy. Here, zirconium-89 (89Zr)-labelled multifunctional liposomes (MLPs) surface-decorated with chitosan (CS) were fabricated to specifically target and trace cluster of differentiation 44+ (CD44+) TNBC CSCs specifically.PATIENTS AND METHODS:The biological basis of CS targeting CD44 for cancer therapy was investigated by detecting the expression of CD44 in TNBC CSCs and TNBC tissues. Molecular docking and dynamics simulations were performed to investigate the molecular basis of CS targeting CD44 for cancer therapy. Gambogic acid (GA)-loaded, 89Zr@CS-MLPs (89Zr-CS-GA-MLPs) were prepared, and their uptake and biodistribution were observed. The anti-tumor efficacy of 89Zr@CS-GA-MLPs was investigated in vivo.RESULTS:CD44 is overexpressed in TNBC CSCs and tissues. Molecular docking and dynamics simulations showed that CS could be stably docked into the active site of CD44 in a reasonable conformation. Furthermore, 89Zr@CS-GA-MLPs were able to bind specifically to CD44+ TNBC stem-like cells and accumulated in tumors of xenograft-bearing mice with excellent radiochemical stability. 89Zr@CS-GA-MLPs loaded with GA showed remarkable anti-tumor efficacy in vivo.CONCLUSION:The GA-loaded, 89Zr-labelled, CS-decorated MLPs developed in this study represent a novel strategy for TNBC imaging and therapy.

目的:分析血清抗苗勒管激素(AMH)和促卵泡激素(FSH)水平对多囊卵巢综合征(PCOS)的诊断价值.方法:106例PCOS患者作为PCOS组、同期92例健康妇女作为对照组,检测2组妇女月经周期血清AMH及FSH水平、PCOS组内不同症状患者血清AMH及FSH水平;建立AMH、FSH单一及联合检测对PCOS患者预测的受试者工作特征曲线(ROC)下面积(AUC),分析AMH、FSH单一指标检测及联合检测预测PCOS的诊断价值.结果:PCOS组患者血清AMH水平明显高于对照组、FSH明显低于对照组,差异有统计学意义(P<0.05);PCOS组中稀少或无排卵、高雄激素血症(HA)、卵巢多囊样改变(PCOM)者基础血清AMH水平明显高于无症状者,FSH水平明显低于无症状者,差异有统计学意义(P<0.05);ROC曲线显示基础血清AMH、FSH单一指标检测及联合检测均对PCOS均具有预测价值,血清AMH对PCOS的临床价值较高,其预测PCOS的最佳临界值为5.5μg/L,此时敏感度和特异度分别为84.5％、70.1％,AUC为0.843,AMH与FSH联合检测PCOS的敏感性和特异度分别为89.8％、72.7％,AUC为0.906.结论:PCOS患者体内AMH、FSH分泌异常,患者血清AMH和FSH水平可作为预测PCOS的指标,两项指标联合检测的价值更高.

Background Drowning-induced acute lung injury (ALI) has been a major cause of accidental death worldwide. Severe oxidative stress injury is the key factor in drowning-induced ALI. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress Ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 attenuates drowning-induced ALI via inhibiting ferroptosis. Methods In this study, we employed Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the beneficial roles of Nrf2 on drowning-induced ALI and the underlying mechanisms. Results In this study, we firstly showed that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential. However, ML385 promoted cell death and lipid ROS production. Furthermore, Nrf2 knockout aggravated seawater drowning-induced ALI in mice. Conclusions In summary, these results suggest that Nrf2 alleviate drowning-induced ALI in MLE-12 cells and mice through inhibiting ferroptosis.

卵巢癌是女性常见的恶性肿瘤之一,其死亡率居妇科恶性肿瘤之首.患者就诊时通常已处于晚期,治疗效果差且易产生耐药性.故阐明卵巢癌发病的分子机制对于促进早期诊断和发现新的治疗方法至关重要.外泌体是一种携带多种物质的细胞外囊泡,包裹在外泌体中的miRNA广泛参与卵巢癌肿瘤微环境的形成、肿瘤的发生发展以及耐药性的产生,并在卵巢癌的诊治中具有较大的应用价值.本文就外泌体源miRNA在卵巢癌的发生和诊治中的研究进展进行综述.

BackgroundHypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors. Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes. Therefore, Hy may be attractive compound applicable to hypoxia-related diseases.PurposeThis study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism.Study Design and MethodsA549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot.ResultsWe showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia.ConclusionTaken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.

•Curcumin treatment reduced BDL-induced hepatic chronic inflammation in mice.•Curcumin enhanced the expression and activity of HO-1, and induced HO-1 nuclear translocation.•Curcumin ameliorated the BDL-induced lipid metabolic disturbance.•HO-1 inhibitor, Zinc protoporphyrin, abolished the curative effects of curcumin on BDL mice.

Recurrent spontaneous abortions (RSA) are defined as aborting three or more times within 20 gestational weeks with the same sexual partner. The occurrence of RSA exhibits an upward trend in modern society. The NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome, which is an important component of innate immunity, serves a role in the immune response and in disease occurrence. In the present study, it was demonstrated that the disordered regulation of the NLRP3 inflammasome may induce the occurrence of RSA. The results of the present study demonstrated that caspase‑1 activity, interleukin (IL)‑1β and IL‑18 were upregulated in patients with RSA compared with healthy controls. Further investigation was performed to elucidate the mechanism of activation of the NLRP3 inflammasome in patients with RSA. The inhibition of the NLRP3 inflammasome in a RSA mouse model was able to decrease the rate of abortions. Finally, the present study demonstrated that the activated NLRP3 inflammasome was involved in the pathogenesis of RSA through regulation of the Th17 and regulatory T cell imbalance. The present study provides a potential future therapeutic target for RSA via the NLRP3 inflammasome.

目的 调查社区妇科门诊育龄妇女人乳头瘤病毒(HPV)感染情况,探讨其在宫颈癌早期筛查中的作用.方法 选择2017年在该院妇科门诊接受免费宫颈癌筛查的无锡市滨湖区育龄妇女共5 240名,统计其一般临床资料并行HPV基因分型检测,HPV检测阳性者由上级医院进一步行液基薄层细胞学检查(TCT)、阴道镜检查及宫颈组织病理学检查.结果 5 240名育龄妇女HPV阳性率为12.04％,其中地区、年龄、职业与HPV检出率密切相关(均P＜0.05),而妊娠次数及分娩方式不同组间比较,差异无统计学意义(P＞0.05),但妊娠次数＞3次组及阴道分娩组较相对应组HPV感染率略升高.在亚型分布上,本区HPV感染亚型前6位为HPV 52、16、58、68、18、31.631例HPV阳性者经TCT检查,阳性者占HPV阳性患者的69.57％,占总调查人群的8.38％.细胞学异常或可疑者行阴道镜检查,共发现宫颈上皮内瘤变(CIN) Ⅰ～Ⅲ期278例,占HPV阳性者的44.06％,占总调查人数的5.30％.结论 高危型HPV检测是筛查宫颈癌及其癌前病变的理想指标,是一种值得在广大基层医院推广应用的筛查措施.