Recently, RNA editing, as a natural modification process of RNA molecules, has aroused extensive interest in the scientific community. This study elaborated the role and process of A-to-I RNA edited miR-3167 in lung adenocarcinoma (LUAD). RT-qPCR and Western blot analysis were employed for the detection of miRNA and gene expressions. The function of miRNA was investigated through Transwell, CCK-8 and flow cytometry assays. Dual-luciferase reporter assay was conducted to assess the link between gene and miRNA. The level of A-to-I RNA editing for miR-3167 was declined in LUAD tissues, which was linked to adverse clinical outcomes and prognosis in LUAD patients. In LUAD, ADAR2 enzyme is responsible for mediating the A-to-I RNA editing of miR-3167. Functionally, LUAD cell viability and metastasis were scarcely influenced by wt-miR-3167, while miR-3167 displayed antitumor activity in LUAD post A-to-I RNA editing. Mechanically, SSR2 is directly targeted by ed-miR-3167 in LUAD, but not wt-miR-3167. SSR2 served as a tumor promoter in LUAD progression by inactivating Hippo signaling and hindering immune infiltration. Ed-miR-3167 exerted tumor inhibitory effect in LUAD by weakening the carcinogenesis of SSR2. A-to-I RNA edited miR-3167 curbs malignant behaviors of LUAD by activating Hippo signaling through downregulating SSR2, indicating that edited miR-3167 has the potential as a therapeutic target for LUAD.
This paper presents an innovative framework for the automated diagnosis of gastric cancer using artificial intelligence. The proposed approach utilizes a customized deep learning model called MobileNetV2, which is optimized using a Dynamic variant of the Pelican Optimization Algorithm (DPOA). By combining these advanced techniques, it is feasible to achieve highly accurate results when applied to a dataset of endoscopic gastric images. To evaluate the performance of the model based on the benchmark, its data is divided into training (80%) and testing (20%) sets. The MobileNetV2/DPOA model demonstrated an impressive accuracy of 97.73%, precision of 97.88%, specificity of 97.72%, sensitivity of 96.35%, Matthews Correlation Coefficient (MCC) of 96.58%, and F1-score of 98.41%. These results surpassed those obtained by other well-known models, such as Convolutional Neural Networks (CNN), Mask Region-Based Convolutional Neural Networks (Mask R-CNN), U-Net, Deep Stacked Sparse Autoencoder Neural Networks (SANNs), and DeepLab v3+, in terms of most quantitative metrics. Despite the promising outcomes, it is important to note that further research is needed. Specifically, larger and more diverse datasets as well as exhaustive clinical validation are necessary to validate the effectiveness of the proposed method. By implementing this innovative approach in the detection of gastric cancer, it is possible to enhance the speed and accuracy of diagnosis, leading to improved patient care and better allocation of healthcare resources.
Our work aimed to investigate the interactive roles of transforming growth factor β1 (TGF-β1), ubiquitin-specific-processing protease 7 (USP7), and Yes-associated protein (YAP) in ferroptosis during sepsis-secondary acute lung injury (ALI). Our study demonstrated that ferroptosis was aggravated by TGF-β1 in both cellular and animal models of acute lung injury. Additionally, YAP upregulated glutathione peroxidase 4 (GPX4) and SLC7A11 by regulating the binding of TEAD4 to GPX4/SLC7A11 promoters. Furthermore, large tumor suppressor kinase 1 (LATS1) knockdown resulted in YAP expression stimulation, while USP7 downregulated YAP via deubiquitinating and stabilizing LATS1/2. YAP overexpression or USP7/LATS1 silencing reduced ferroptosis process, which regulated YAP through a feedback loop. However, TGF-β1 annulled the repression of ferroptosis by YAP overexpression or LATS1/USP7 knockdown. By elucidating the molecular interactions between TGF-β1, USP7, LATS1/2, and YAP, we identified a new regulatory axis of ferroptosis in sepsis-secondary ALI. Our study sheds light on the pathophysiology of ferroptosis and proposes a potential therapeutic approach for sepsis-induced ALI.
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the cell invasion assays in Figs. 4D and 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 3933‑3940, 2019; DOI: 10.3892/mmr.2019.9990].
Background: Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression. Methods: The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation. Results: CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2. Conclusions: CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.
目的 探讨两种不同类型的肋骨接骨板治疗多发性肋骨骨折的临床疗效.方法 回顾性分析2019年3月—2020年9月上海交通大学医学院附属第九人民医院胸外科收治的92例切开复位内固定术的多发性肋骨骨折患者资料,按照不同的内固定手术方式分为观察组和对照组,每组46例.观察组采用形状记忆环抱接骨板治疗,男性28例,女性18例;年龄21~65岁,平均42.1岁;撞伤23例,跌伤21例,其他2例;骨折数量3~8根,平均4.2根.对照组采用肋骨锁定接骨板治疗,男性30例,女性16例;年龄20~66岁,平均45.4岁;撞伤20例,跌伤23例,其他3例;骨折数量3~6根,平均3.5根.观察并记录两组患者的手术时间、术中出血量、胸管引流量、拔除引流管时间、住院时间等围术期指标,比较两组胸痛缓解时间以及术后并发症(包括伤口感染、肺部感染、肺不张、骨折延迟愈合等)的情况.结果 经手术治疗后,观察组较对照组手术时间更短[(58.11±13.43)minvs.(75.31±10.56)min,P<0.05].两组患者术中出血量[(50.45±9.78)mLvs.(51.36±8.90)mL]、拔除引流管时间[(5.15±1.32)dvs.(5.24±1.08)d]、胸腔引流量[(330.24±150.78)mLvs.(348.53±148.29)mL]及住院时间[(7.45±2.01)dvs.(8.02±1.76)d]比较差异无统计学意义(P>0.05);两组在治疗24h和48h后VAS均有所降低,且观察组明显低于对照组[(7.85±0.55)分vs.(8.53±0.62)分,(7.01±0.27)分vs.(7.89±0.18)分,P<0.05];观察组患者术后并发症发生率更低(8.7%vs.21.7%,P<0.05).结论 采用形状记忆环抱接骨板进行肋骨骨折固定较肋骨锁定接骨板可以有效缩短手术时间,患者术后疼痛程度较轻,并发症发生率低,值得临床广泛应用.
Non-small cell lung cancer (NSCLC) is still a threat to people worldwide. In the current study, we aimed to investigate the effect of folic acid (FA) and Adriamycin on NSCLC. Our work modified Adriamycin with microRNA (miR)-128-3p-loaded FA-mesoporous silica nanoparticles (MSN) (Adriamycin/miR/MSN-FA) or with Adriamycin/miR/MSN. The synthesized nanoparticles’ in vitro drug release and hydrodynamic characteristics were detected. Then Adriamycin and nanoparticles were applied to treat NSCLC cells followed by analysis of cell proliferation by MTT, cytometry and clone formation assay, apoptosis-related proteins by Western blot, and in vitro absorption by Rhodamine B staining. Animal model was set up to detect in vivo impact of nanoparticles. Adriamycin/miR/MSN-FA nanoparticles released Adriamycin in a controlled manner, inhibited colony formation and cell proliferation. Besides, nanoparticles promoted cell apoptosis and upregulated cleaved Caspase-3 and PARP. Moreover, Adriamycin/miR/MSN-FA significantly aggregated in tumor with high concentration of Adriamycin, thereby inhibiting NSCLC tumor progression with low toxicity and side effects. Adriamycin/miR/MSN-FA nanoparticles could effectively inhibit the progression of NSCLC with low toxicity and side effects.
MicroRNA (miRNA/miR)‑92a has been identified as being significantly downregulated in non‑small cell lung cancer (NSCLC) tissues using a miRNA array. However, its biological function and molecular mechanisms in NSCLC have not been fully elucidated. The aim of the present study was to determine the role of miR‑92a in NSCLC and the mechanisms by which it affects NSCLC cells. The expression levels of miR‑92a in NSCLC tissues and cell lines were analyzed using reverse transcription‑quantitative PCR. Cell viability and cell apoptosis were determined using an MTT assay and flow cytometry, respectively. It was observed that miR‑92a was significantly upregulated in NSCLC tissues and cell lines. Inhibition of miR‑92a significantly suppressed viability of NSCLC cells, with concomitant downregulation of key proliferative genes, such as proliferating cell nuclear antigen and Ki‑67. miR‑92a downregulation induced apoptosis of NSCLC cells, as evidenced by flow cytometry and apoptosis‑related protein detection. Luciferase assays confirmed that miR‑92a could directly bind to the 3'‑untranslated region of tumor suppressor F‑box/WD repeat‑containing protein 7 (FBXW7) and suppress its translation. Furthermore, small interfering RNA‑mediated FBXW7 inhibition partially attenuated the tumor suppressive effect of an miR‑92a inhibitor on NSCLC cells. Collectively, these findings demonstrated that miR‑92a might function as an oncogene in NSCLC by regulating FBXW7. In conclusion, miR‑92a could serve as a potential therapeutic target in NSCLC treatment.
目的 探讨乙醇脱氢酶1B (alcohol dehydrogenase 1B,ADH1B)-rs1229984位点基因单核苷酸多态性(single nucleotide polymorphism,SNP)对食管癌患者临床病理特征及预后的影响.方法 132例食管癌患者为食管癌组,108例体检健康者为对照组,采集2组外周静脉血提取血液基因组DNA,采用二对引物-PCR法检测ADH1B-rs1229984基因SNP;比较2组ADH1B-rs1229984基因型和等位基因频率,分析ADH1B-rs1229984基因型与患者临床病理特征的关系;比较不同基因型食管癌患者的生存期;采用Cox比例风险回归模型分析影响食管癌患者预后的危险因素.结果 ADH1B在rs1229984存在SNP,分别为野生型纯合子GG型、突变杂合子AG型、突变纯合子AA型;2组ADH1B-rs1229984位点基因型分布频率比较差异有统计学意义(P<0.05),食管癌组G等位基因频率(51.52%)明显高于对照组(42.13%)(P<0.05);GG+AG基因型食管癌患者TNM分期Ⅲ期(89.47%)、低分化(93.48%)、浸润程度T4期(93.33%)和淋巴结转移(88.89%)比率高于AA基因型(10.53%、6.52%、6.67%、11.11%)(P<0.05),年龄、性别比例、肿瘤直径、肿瘤部位与AA基因型比较差异均无统计学意义(P>0.05);AG+GG基因型食管癌患者中位生存期[(17.31±2.89)个月]短于AA基因型[(26.75±4.45)个月](P<0.05),1、2、3 a生存率(61.86%、19.59%、9.28%)低于AA基因型(97.14%、74.29%、37.14%)(P<0.05);淋巴结转移与ADH1B-rs1229984 GG基因型为影响食管癌患者预后的危险因素(OR=1.852,95%CI:1.339~2.561,P=0.026;OR=2.171,95%CI:1.675~2.815,P=0.013).结论 ADH1B-rs1229984基因SNP与食管癌患者临床病理特征有关,且该基因位点GG基因型预示患者预后不良.
Dysregulated microRNAs (miRNAs/miRs) directly modulate the biological functions of non-small cell lung cancer (NSCLC) cells and contribute to the initiation and progression of NSCLC; however, the specific roles and underlying mechanisms of the dysregulated miRNAs in NSCLC require further investigation. The present study reported that miRNA-629-5p (miR-629) was upregulated in NSCLC tissues and cell lines. High miR-629 expression levels were significantly associated with tumour size, clinical stage and lymph node metastasis in patients with NSCLC. Functional experiments indicated that miR-629 inhibition suppressed the viability and invasion NSCLC cells in vitro. Furthermore, bioinformatics prediction, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that runt-related transcription factor 3 (RUNX3) was a direct target gene of miR-629 in NSCLC. Restoration of RUNX3 expression suppressed the effects of miR-629 inhibition in NSCLC cells. Rescue experiments revealed that RUNX3 knockdown partially abrogated the effects of miR-629 inhibition on NSCLC cells. In summary, miR-629 directly targeted RUNX3 to inhibit the progression of NSCLC, suggesting that this miRNA may be considered as a diagnostic and therapeutic target for patients with NSCLC.
目的 观察分析胸腹腔镜联合手术治疗上段食管癌的临床效果.方法 选取2016年1月~2017年12月上海交通大学医学院附属第九人民医院北院及上海交通大学医学院附属仁济医院宝山分院收治的86例上段食管癌患者作为研究对象,随机分为观察组和对照组,每组各43例.观察组进行胸腹腔镜联合手术,对照组进行传统的开放式手术.比较两组的淋巴结清扫数、术后的疼痛程度[视觉模拟量表(VAS)评分]、术中出血量、住院治疗时间以及并发症发生的情况.结果 两组患者的淋巴结清扫数比较,差异无统计学意义(P>0.05);观察组术中出血量少于对照组,手术及住院时间均短于对照组,差异有统计学意义(P<0.05);观察组患者术后12、24、36 h的VAS评分低于对照组,差异有统计学意义(P<0.05);观察组患者的并发症总发生率低于对照组,差异有统计学意义(P<0.05).结论 胸腹腔镜联合手术对治疗上段食管癌效果显著,能够有效地减轻患者的疼痛程度,减少术中出血量,缩短手术及住院治疗的时间,且并发症发生率低,具有很大的临床推广价值.
目的:研究手术在胃食管反流病(GERD)合并食管裂孔疝的疗效.方法:选择2016年1月至2017年6月上海交通大学医学院附属第九人民医院收治的80例GERD合并食管裂孔疝患者作为研究对象,并采用电脑随机法将患者分为两组.其中,观察组实施腹腔镜下抗反流手术治疗,对照组实施开腹手术.观察分析比较两组患者治疗效果.结果:两组患者治疗后观察组反流性疾病问卷评分(RDQ评分)、并发症发生率均低于对照组,差异均具有统计学意义(P<0.05).结论:腹腔镜下抗反流手术治疗GERD合并食管裂孔疝的疗效显著,且安全性高.
目的 检测食管癌患者手术前后血清p53抗体的水平,以同期体检健康人为对照,探讨其临床意义.方法 选取食管癌患者48例为食管癌组,以同期体检健康人48例作为对照组,食管癌组在手术前后采用酶联免疫吸附法测定p53水平,分析手术前后p53抗体水平变化及其与相应临床参数的关系,评估其临床意义.结果 食管癌患者术前1天血清p53抗体浓度为(332.62±106.08)ng/L,对照组为(36.50±68.32)ng/L,差异有显著性(t=4.612,P=0.001).食管癌组患者手术前1天,术后7、30、90、180天p53抗体浓度分别为(332.62±106.08)ng/L、(114.80±56.42)ng/L、(34.60±102.04)ng/L、(18.62±102.04)ng/L、(0.62±102.04)ng/L,术后与术前比较,差异有显著性(t=2.12,P=0.039;t=2.23,P=0.030;t=1.26,P=0.021;t=2.56,P=0.013).食管癌患者48例,术前1天血清p53抗体阳性18例(37.5%),对照组无阳性病例.将食管癌组患者根据p53抗体是否阳性分为p53抗体阳性组18例和p53抗体阴性组30例,比较两组患者间性别、年龄、肿瘤体积、肿瘤分化程度等临床参数的相关性,结果提示p53抗体阳性率与患者的吸烟量、肿瘤分化程度、TNM分期呈正相关性(P<0.05),而与患者的性别、年龄以及肿瘤大小无明显相关性(P>0.05).结论 测定血清p53抗体对于明确诊断具有较高的特异性,对患者是否发生复发及转移和预后有一定的评估价值.
Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model. We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm2) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.
Objective: To explore the effects of oxygen concentrations on malondialdehyde (MDA) and superox-ide dismutase (SOD) in secondary brain injury (SBI) rat model of post-traumatic axonal injury (TAI) with hypoxia. Methods: A total of 48 SD rats were divided into groups of sham (A, n=8), TAI with hypoxia (B, n=8) and ventilat-ing (C, n=32). According to the different concentrations of oxygen, group C was divided into four subgroups (21%, 50%, 75% and 100%). TAI and systemic hypoxia were induced by an impact-acceleration & rotation device and ventilating rats with 10% oxygen for 30 min, respectively. After that, the rats were given different concentrations of oxygen gas mixture for 1 hour. The MDA and SOD levels among those groups were systemically assessed and compared. Results: Compared to the group A, the MDA levels in the groups B and C were increased obviously, then returned to normal after one week. In the group C, the higher oxygen led to a higher MDA level. The SOD level dismutase in the groups B and C were decreased significantly, compared to that in the group A (P<0.05). Compared with that in the group B, the level of SOD in the subgroup ventilating with 21% oxygen in group C was significantly increased (P<0.05). In addition, while ventilating 100% oxygen, the SOD level decreased significantly (P<0.05). With the increase of ventilationg oxygen in group C, the level of SOD dramatically decreased. Conclu-sion: Appropriately ventilating oxygen can ameliorate hypoxemia in brain tissue. The level of MDA increases with ventilating higher concentration of oxygen, while the level of SOD decreases with increasing oxygen concentration.
目的 在创伤性轴索损伤(traumatic axonal injury,TAI)合并低氧血症性二次脑损伤(secondary brain injury,SBI)大鼠模型基础上进一步探讨不同氧浓度复苏对大鼠脑组织病理学的影响.方法 应用自制TAI致伤装置,大鼠伤后给予10%浓度氧吸入30min制成低氧血症性SBI模型,随后给予大鼠不同氧浓度混合气体1h,复苏后不同时间点(24h、1周)进行免疫组化染色.结果 脑干ROI的β-APP免疫组化染色显示,24h时TAI合并缺氧组的阳性染色明显强于各复苏组,50%氧浓度时的阳性染色最弱;各组阳性染色随时间而减弱,1周时各组阳性染色明显弱于24h,此时TAI合并缺氧组的阳性染色仍明显强于各复苏组,50%氧浓度时的阳性染色最弱.染色阳性的神经轴索半定量分析显示,24h时TAI合并缺氧组明显高于各复苏组,50%氧浓度时的值最低;各组数值随时间而降低,1周时各组值明显低于24h,此时TAI合并缺氧组的值仍高于各复苏组,50%氧浓度的值仍为最低.结论 给氧治疗可以显著减低轴索损伤,起到神经保护作用;对于当前的TAI合并缺氧动物模型的最佳复苏氧浓度为50%.
Objective To explore the effects of different oxygen concentrations on the blood gases in the hypoxia-induced secondary brain injury(SBI) rat subjected to traumatic axonal injury(TAI). Methods TAI and systemic hypoxia was induced by an impact-acceleration&rotation device and ventilating rats with 10%oxygen in nitrogen 30 min, respectively. Adult Sprague-Dawley rats were randomly separated into four groups:A(21%O2), B(50%O2), C(75%O2), D(100%O2). After that the rats were given different concentrations of oxygen gas mixture 1 hour. Blood gas parameters (SpO2, PO2 and PCO2) among those groups were systemically assessed and compared. Results Given different oxygen concentrations gas, the PO2 and SPO2 of the rats were significantly increased compared with post-traumatic hypoxia. After resuscitation, the PO2 and SPO2 of A(21% O2) group consistent with before injury;While compared to before injury and A(21%O2) group, after resuscitation, the PO2 of B(50% O2), C(75% O2), D(100% O2) groups were significantly increased and the SPO2 increased with no statistically significant difference; the PO2 of B(50% O2), C(75% O2), D(100% O2) groups were gradually significantly increased. Conclusion Oxygen therapy can significantly improve the PO2 and SPO2 of the post-traumatic hypoxic rats, and with the increase of oxygen concentration, the PO2 was gradually increased.
Objective: To investigate the value of fractional anisotropy(FA) of diffusion tensor imaging(DTI) in severity assessment and prognosis prediction of diffuse axonal injury(DAI).Methods: Twenty-eight patients with DAI(DAI group) and 10 healthy control volunteers(control group) were recruited for the study.Glasgow coma scale(GCS) was used to assess the consciousness of DAI patients at admission.Patients received MR inspection within two weeks after onset and the data of DTI were collected.Glasgow outcome score(GOS) was used to evaluate the patients 6 months later.The fractional anisotropy(FA) values in different regions of interest(ROI) were measured and compared.The correlation between FA values in different ROIs and GCS,GOS scores were analyzed.Results: When compared with the control group,the FA value was significantly decreased in each ROI of DAI group(P0.01).In DAI group,FA values were significantly lower in the visualized lesions than in the homologous ones in contralateral hemisphere(P0.01).The FA values in the brainstem(midbrain,pons and medulla oblongata) were positively correlated with GCS and GOS scores(P0.01).The FA values in the corpus callosum were positively correlated with GCS scores(P0.01).Conclusion: DTI is a potentially useful imaging modality to detect DAI lesions.Changes of FA value in ROIs help to assess the severity and the outcome of DAI.