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BACKGROUND: Lower extremity arteriosclerosis obliterans (ASO) is the most common occlusive disease of the peripheral blood vessels. OBJECTIVE: To explore the application effect of symptom management-based rehabilitation strategy in postoperative functional exercises in patients with lower extremity ASO. METHODS: The researchers selected 136 patients that underwent lower extremity ASO surgery for the first time in their department from January to September 2020. Patients were divided into a control group (n= 68) and an experimental group (n= 68). The control group implemented routine discharge rehabilitation education and continuous nursing. On this basis, the experimental group applied the symptom management theory to the rehabilitation management strategy to compare the degree of pain, the ankle-brachial index, self-care ability and quality of life between the two groups before and after the intervention. RESULTS: Three months (P= 0.045) and six months (P=0.013) after discharge, the experimental group’s degree of pain was significantly lower than that of the control group. At one month (P= 0.019), three months (P= 0.003) and six months (P= 0.000) after discharge, the experimental group recovered significantly better than the control group. At six months after discharge, the self-care ability, mood status and physical pain of the experimental group were significantly higher than in the control group (P< 0.05). CONCLUSION: The rehabilitation management strategy, which is based on symptom management theory, can effectively improve the symptoms, quality of life and self-efficacy of ASO patients in continuous care. This nursing strategy is worthy of clinical promotion.

Affected by traditional gender inequality consciousness, China’s progress on gender equality in education was relatively backward, which led to the primary stage of gender equality perception of people and postponed the agenda of gender equality. Gender equality education, as an ideal and effective way, is able to promote the implementation of the gender equality procedure. To this end, the research probes into the status quo of gender equality in education around the world, including America, South Korea and Taiwan. Some lessons are extracted from these three cases, which could be utilized to improve China’s development of gender equality education. Also, this paper proposes suggestions from three aspects, the government’s role in the establishment of women’s universities and legal support as well as the school’s responsibility for teachers’ development and teaching material improvement. By these multiple measures mentioned above, it would be easier and more efficient to achieve the goal of gender equality in modern China.

Although azoxystrobin has been widely applied on various crops, little is known about the bioavailability of azoxystrobin in the soil-vegetable system. In this study, the uptake, accumulation and translocation of azoxystrobin as affected by soil characteristics and plant species were respectively investigated. The accumulation amount of azoxystrobin in pakchoi increased as soil adsorption decreased and was positively associated with its concentration in pore water (C

Breast cancer is a malignancy harmful to physical and mental health in women, with quite high mortality. Copy number variations (CNVs) are vital factors affecting the progression of breast cancer. Detecting CNV in breast cancer to predict the prognosis of patients has become a promising accurate treatment in recent years. The differential analysis was performed on CNV of lncRNAs as well as the expression of lncRNAs, miRNAs and mRNAs in the normal tissue and breast tumor tissue based on The Cancer Genome Atlas (TCGA) database. And the CNV-driven lncRNAs were identified by Kruskal-Wallis test. Meanwhile, a competitive endogenous RNA (ceRNA) network regulated by CNV-driven lncRNA was constructed. As the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed, the mRNAs in the dysregulated ceRNA network were mainly enriched in the biological functions and signaling pathways including Focal Adhesion-PI3K-Akt-mTOR-signaling pathway, Neuronal System, Metapathway biotransformation Phase I and II and blood circulation, etc. The relationship between CNVs of 5 lncRNAs and their gene expression in the ceRNA network was analyzed via Chi-square test, which confirmed that except LINC00243, the expression of 4 lncRNAs was notably correlated with CNVs. The survival analysis revealed that only copy number gain of LINC00536 was evidently related to poor prognosis of patients. CIBERSORT algorithm showed that 5 lncRNAs were correlated with the abundance of immune cell infiltration and immune checkpoints. In a word, by analyzing CNV-driven lncRNAs and the ceRNA network regulated by these lncRNAs, this study explored the mechanism of breast cancer and provided novel insights into new biomarkers.

Exosomes are cell-derived extracellular vesicles of 40-160 nm diameter, which carry numerous biomolecules and transmit information between cells. They are used as functional nanomaterials with great potential in biomedical areas, such as active agents and delivery systems for advanced drug delivery and disease therapy. In recent years, potential applications of exosomes in tissue engineering have attracted significant attention, and some critical progress has been made. This review gives a complete picture of exosomes and their applications in the regeneration of various tissues, such as the central nervous systems, kidney, bone, cartilage, heart, and endodontium. Approaches employed for modifying exosomes to equip them with excellent targeting capacity are summarized. Furthermore, current concerns and future outlook of exosomes in tissue engineering are discussed.

Background The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented burden on the delivery of intensive care services worldwide. Research Question What is the global point estimate of deaths and risk factors for patients who are admitted to ICUs with severe COVID-19? Study Design and Methods In this systematic review and meta-analysis Medline, Embase, and the Cochrane library were searched up to August 1, 2020. Pooled prevalence of participant characteristics, clinical features, and outcome data was calculated with the use of random effects models. Subgroup analyses were based on geographic distribution, study type, quality assessment, sample size, end date, and patient disposition. Studies that reported in-hospital mortality rate of adult patients (age >18 years) with confirmed COVID-19 admitted to an ICU met study eligibility criteria. Critical evaluation was performed with the Newcastle Ottawa Scale for nonrandomized studies. Results Forty-five studies with 16,561 patients from 17 countries across four continents were included. Patients with COVID-19 who were admitted to ICUs had a mean age of 62.6 years (95% CI, 60.4-64.7). Common comorbidities included hypertension (49.5%; 95% CI, 44.9-54.0) and diabetes mellitus (26.6%; 95% CI, 22.7-30.8). More than three-quarters of cases experienced the development of ARDS (76.1%; 95% CI, 65.7-85.2). Invasive mechanical ventilation was required in 67.7% (95% CI, 59.1-75.7) of case, vasopressor support in 65.9% (95% CI, 52.4-78.4) of cases, renal replacement therapy in 16.9% (95% CI, 12.1-22.2) of cases, and extracorporeal membrane oxygenation in 6.4% (95% CI, 4.1-9.1) of cases. The duration of ICU and hospital admission was 10.8 days (95% CI, 9.3-18.4) and 19.1 days (95% CI, 16.3-21.9), respectively, with in-hospital mortality rate of 28.1% (95% CI, 23.4-33.0; I2 = 96%). No significant subgroup effect was observed. Interpretation Critically ill patients with COVID-19 who are admitted to the ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global death from severe COVID-19 is

Realistic modelling of human soft tissue is very important in medical applications. This paper proposes a novel method by dynamically incorporating soft tissue characterisation in the process of soft tissue modelling to increase the modelling fidelity. This method defines nonlinear tissue deformation with unknown mechanical properties as a problem of nonlinear filtering identification to dynamically identify mechanical properties and further estimate nonlinear deformation behaviour of soft tissue. It combines maximum likelihood theory, nonlinear filtering and nonlinear finite element method (NFEM) for modelling of nonlinear tissue deformation behaviour based on dynamic identification of homogeneous tissue properties. On the basis of hyperelasticity, a nonlinear state-space equation is established by discretizing tissue deformation through NFEM for dynamic filtering. A maximum likelihood algorithm is also established to dynamically identify tissue mechanical properties during the deformation process. Upon above, a maximum likelihood-based extended Kalman filter is further developed for dynamically estimating tissue nonlinear deformation based on dynamic identification of tissue mechanical properties. Simulation and experimental analyses reveal that the proposed method not only overcomes the NFEM limitation of expensive computations, but also absorbs the NFEM merit of high accuracy for modelling of homogeneous tissue deformation. Further, the proposed method also effectively identifies tissue mechanical properties during the deformation modelling process.

Elaborating the environmental behavior of mefentrifluconazole, a novel triazole fungicide, in stereoselective level is of paramount importance for the application of the pesticide in agriculture. In this study, the enantioselective bioactivity, acute toxicity and stereoselective bioaccumulation of mefentrifluconazole in earthworm (Eisenia fetida) were investigated. Bioactivity tests against four pathogens revealed that R-(-)-mefentrifluconazole exhibited approximately 11-113 times higher bioactivity than its S-(+)-mefentrifluconazole. However, the LC

Prediction of COVID-19 spread plays a significant role in the epidemiology study and government battles against the epidemic. However, the existing studies on COVID-19 prediction are dominated by constant model parameters, unable to reflect the actual situation of COVID-19 spread. This paper presents a new method for dynamic prediction of COVID-19 spread by considering time-dependent model parameters. This method discretises the susceptible-exposed-infected-recovered-dead (SEIRD) epidemiological model in time domain to construct the nonlinear state-space equation for dynamic estimation of COVID-19 spread. A maximum likelihood estimation theory is established to online estimate time-dependent model parameters. Subsequently, an extended Kalman filter is developed to estimate dynamic COVID-19 spread based on the online estimated model parameters. The proposed method is applied to simulate and analyse the COVID-19 pandemics in China and the United States based on daily reported cases, demonstrating its efficacy in modelling and prediction of COVID-19 spread.

The coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented burden on the delivery of intensive care services worldwide.What is the global point estimate of deaths and risk factors for patients who are admitted to ICUs with severe COVID-19?In this systematic review and meta-analysis Medline, Embase, and the Cochrane library were searched up to August 1, 2020. Pooled prevalence of participant characteristics, clinical features, and outcome data was calculated with the use of random effects models. Subgroup analyses were based on geographic distribution, study type, quality assessment, sample size, end date, and patient disposition. Studies that reported in-hospital mortality rate of adult patients (age18 years) with confirmed COVID-19 admitted to an ICU met study eligibility criteria. Critical evaluation was performed with the Newcastle Ottawa Scale for nonrandomized studies.Forty-five studies with 16,561 patients from 17 countries across four continents were included. Patients with COVID-19 who were admitted to ICUs had a mean age of 62.6 years (95% CI, 60.4-64.7). Common comorbidities included hypertension (49.5%; 95% CI, 44.9-54.0) and diabetes mellitus (26.6%; 95% CI, 22.7-30.8). More than three-quarters of cases experienced the development of ARDS (76.1%; 95% CI, 65.7-85.2). Invasive mechanical ventilation was required in 67.7% (95% CI, 59.1-75.7) of case, vasopressor support in 65.9% (95% CI, 52.4-78.4) of cases, renal replacement therapy in 16.9% (95% CI, 12.1-22.2) of cases, and extracorporeal membrane oxygenation in 6.4% (95% CI, 4.1-9.1) of cases. The duration of ICU and hospital admission was 10.8 days (95% CI, 9.3-18.4) and 19.1 days (95% CI, 16.3-21.9), respectively, with in-hospital mortality rate of 28.1% (95% CI, 23.4-33.0; ICritically ill patients with COVID-19 who are admitted to the ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global death from severe COVID-19 is 1 in 3.

Background and Objective: Soft tissue modelling is crucial to surgery simulation. This paper introduces an innovative approach to realistic simulation of nonlinear deformation behaviours of biological soft tissues in real time. Methods: This approach combines the traditional nonlinear finite-element method (NFEM) and nonlinear Kalman filtering to address both physical fidelity and real-time performance for soft tissue modelling. It defines tissue mechanical deformation as a nonlinear filtering process for dynamic estimation of nonlinear deformation behaviours of biological tissues. Tissue mechanical deformation is discretized in space using NFEM in accordance with nonlinear elastic theory and in time using the central difference scheme to establish the nonlinear state-space models for dynamic filtering. Results: An extended Kalman filter is established to dynamically estimate nonlinear mechanical deformation of biological tissues. Interactive deformation of biological soft tissues with haptic feedback is accomplished as well for surgery simulation. Conclusions: The proposed approach conquers the NFEM limitation of step computation but without trading off the modelling accuracy. It not only has a similar level of accuracy as NFEM, but also meets the real-time requirement for soft tissue modelling.

Modelling of soft tissue deformation is a key issue in surgical simulation. Despite extensive research studies on this issue, accurate modelling of soft tissue deformation in run time still remains challenging. This paper proposes a new reduced-order nonlinear Kalman filter to emulate nonlinear behaviors of biological deformable tissues. This approach defines the deformable modelling problem as a reduced-order filtering problem to accurately calculate soft tissue deformation in real time. Soft tissue deformation is discretized in space using nonlinear finite element method based on hyperelasticity and further formulated as a nonlinear state-space equation for filtering estimation. Subsequently, the order of this nonlinear state-space equation is reduced using proper orthogonal decomposition to reduce the computational cost. Upon this reduced-order state-space equation, an extended Kalman filter is constructed to online calculate nonlinear behaviors of tissue physical deformation. Simulation results and comparison analysis prove the effectiveness of the suggested method for accurate simulation of tissue physical deformation in real time.

© 2018 Elsevier B.V. Highly hydrophobic thermosetting polyurethane (TSU) surfaces with micro-nano hierarchical structures were developed by a simple process combined with sandpaper templates and nano-silica embellishment. Sandpapers with grit sizes varying from 240 to 7000 grit were used to obtain micro-scale roughness on an intrinsic hydrophilic TSU surface. The surface wettability was investigated by contact angle measurement. It was found that the largest contact angle of the TSU surface without nanoparticles at 102 ± 3° was obtained when the template was 240-grit sandpaper and the molding progress started after 45 min curing of TSU. Silica nanoparticles modified with polydimethylsiloxane were scattered onto the surfaces of both the polymer and the template to construct the desirable nanostructures. The influences of the morphology, surface composition and the silica content on the TSU surface wettability were studied by scanning electron microscopy (SEM), attenuated total reflection (ATR) infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The surface of the TSU/SiO 2 nanocomposites containing 4 wt% silica nanoparticles exhibited a distinctive dual-scale structure and excellent hydrophobicity with the contact angle above 150°. The mechanism of wettability was also discussed by Wenzel model and Cassie-Baxter model.

Triazole-resistance in Aspergillus fumigatus has been frequently found in agricultural soils. We determined if triazole-resistance in A. fumigatus can be acquired in soil and earthworm guts after exposure to environmentally relevant concentrations of formulated propiconazole (FPRO) and difenoconazole (FDIF). Acquired triazole-resistance was found in two strains of A. fumigatus after exposure to 2.5 mg/L of FPRO and three strains of A. fumigatus after induction by 0.1–2.5 mg/L of FDIF for 40 d in liquid medium. Resistance development depended upon exposure time and substrate concentration. There were one, three, and two resistant strains of A. fumigatus in soils receiving FPRO, FDIF, and their combination, respectively. Resistance was identified in two strains of A. fumigatus isolated from the guts of earthworms exposed in soils contaminated by FDIF and two strains of A. fumigatus isolated from the guts of earthworms exposed to the combination of FDIF and FPRO. We conclude that normal applications of FPRO, FDIF, and their combination are likely to induce triazole-resistance in A. fumigatus in agricultural fields. Earthworms may act as disseminators of triazole-resistant A. fumigatus.

This research work proposes a novel method for realistic and real-time modelling of deformable biological tissues by the combination of the traditional finite element method (FEM) with constrained Kalman filtering. This methodology transforms the problem of deformation modelling into a problem of constrained filtering to estimate physical tissue deformation online. It discretises the deformation of biological tissues in 3D space according to linear elasticity using FEM. On the basis of this, a constrained Kalman filter is derived to dynamically compute mechanical deformation of biological tissues by minimizing the error between estimated reaction forces and applied mechanical load. The proposed method solves the disadvantage of costly computation in FEM while inheriting the superiority of physical fidelity.

MicroRNAs (miRNAs/miRs) are 19–25 nucleotide-long, non-coding RNAs that regulate the expression of target genes at the post-transcriptional level. In the present study, the role of miR-340 in breast cancer (BC) was investigated. The overexpression of miR-340 significantly inhibited the proliferation, migration and invasion of human breast MDA-MB-231 cancer cells in vitro. The Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) gene was identified as a target of miR-340; its expression was downregulated by overexpression of miR-340 by binding to its 3′-untranslated region. The short interfering RNA-mediated silencing of ROCK1 was also performed, which phenocopied the effects of miR-340 overexpression. An inhibitor of miR-340 was used to suppress miR-340 expression, which led to increased expression of ROCK1, thus improving the proliferation, migration and invasion of MDA-MB-231 cells. Data from the present study suggest that miR-340 inhibits MDA-MB-231 cell growth and its downregulation may lead to the progression and metastasis of BC. Thus, miR340 may act as a tumor-suppressor agent that could serve a key role in the diagnosis and therapy of BC.

Pancreatic cancer is a disease of the elderly. Surgical resection is usually offered to patients in early stage disease; however, pancreatic resection in the elderly is controversial.MEDLINE, EMBASE and Cochrane Library, were searched for studies comparing short- and long-term outcomes of elderly (above the age of 70) with non-elderly patients (below the age of 70) following pancreatic resection for pancreatic adenocarcinoma over the period from the inception of electronic database to 2017. Twelve articles documenting 4860 patients were included. A meta-analysis of data on patient characteristics, operative techniques, and perioperative outcomes were analysed. Our primary endpoint was postoperative mortality, defined as 30-day mortality or in-hospitalisation mortality.There were 919 patients in the elderly group and 3941 patients in the non-elderly group. Elderly patients had worse ASA scores (p 0.001) and more cardiovascular comorbidities (p = 0.002). Tumour size, T-stage, N-stage and tumour grade were similar between the elderly and non-elderly group (p 0.05). Fewer elderly patients received a concomitant venous resection with their pancreatectomy (RR0.80, p = 0.003, I2 = 0%), achieved a negative margin status (RR0.76, p = 0.02, I2 = 28%) and underwent adjuvant chemotherapy treatment (RR0.69, p 0.001, I2 = 42%). Overall complication (RR1.15, p 0.001, I2 = 47%), in particular, respiratory complications (RR2.33, p = 0.004, I2 = 39%), was higher in the elderly group. There was no difference in postoperative pancreatic fistula formation, postoperative haemorrhage, intraabdominal abscess and length of hospital stay between both groups (p 0.05). Postoperative mortality was similar between both groups (p = 0.17). Subgroup analysis according to the time of enrolment (2000, ≥2000) showed a significant subgroup effect (Chi2 = 3.44, p = 0.06, I2 = 70.9%) and revealed that postoperative mortality in the elderly group improved over time (Before 2000: n = 1654, subtotal RR2.27, p = 0.02, I2 = 0%; From 2000 onwards: n = 3206, subtotal RR1.00, p = 0.99, I2 = 0%).Fewer elderly patients received chemotherapy and portal vein resection to achieve a clear margin. Pancreatic resection of pancreatic adenocarcinoma can be performed safely on elderly patients with acceptable risks in experienced centres by specialist hepatobiliary surgeons. Age alone should not be the only determinant for the selection of patients for surgical treatment of pancreatic adenocarcinoma.

As the distinctions of formation structure between Chinese and Western languages, learners take more effort in grasping correct formation structure and pronunciation when they are studying Chinese character. Various Chinese character learning systems have already been proposed in order to help the learners recognize the character, but ignore its handwriting and cultural background. We here present a learning system for learners to study Chinese character better. To increase the effectiveness in learning Chinese character, we combine pronunciation and character writing with the integrated use of computer, projector and camera in this design. This system eases the learners to understand the meaning, cultural background and formation structure of character by using the morphological and phonetic animation projection and handwriting instruction. In comparison with screen-writing systems, this system provides a more authentic learning experience for learners through simulating the learning process of writing on real paper. We anticipate our system to be a starting point to explore the instruction in Chinese character in the field of its formation structure, pronunciation and handwriting, and to be used in the classroom or at home in the future.

Numerous studies have demonstrated that microRNAs (miRNAs) play vital roles in papillary thyroid carcinoma (PTC). The aim of the present study was to examine the expression levels of miR-183 in PTC and investigate whether its potential roles involved targeting the programmed cell death 4 (PDCD4). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to examine the expression levels of miR-183 in 38 PTC specimens and 4 PTC cell lines. MTT, colony formation, wound-healing and Transwell invasion assays, and flow cytometry were conducted to explore the potential functions of miR-183 in human TPC1 papillary thyroid carcinoma cells. The dual-luciferase reporter assay was performed to validate whether PDCD4 was a direct target of miR-183. The effects of modulating miR-183 on endogenous levels of PDCD4 were subsequently confirmed via RT-qPCR and western blotting. Functional assays were used to indicate the roles of endogenous PDCD4 in TPC1. The results showed the miR-183 expression levels were significantly upregulated in PTC specimens and cell lines (P

RAB1A acts as an oncogene in various cancers, and emerging evidence has verified that RAB1A is an mTORC1 activator in hepatocellular and colorectal cancer, but the role of RAB1A in breast cancer remains unclear. In this investigation, RAB1A siRNA was successfully transfected in MDA-MB-231 and BT-549 human triple-negative breast cancer cells, and verified by real‑time quantitative polymerase chain reaction and western blotting. Then, MTT cell proliferation, colony formation, cell invasion and wound healing assays were performed to characterize the function of RAB1A in the breast cancer cell lines. Downregulation of RAB1A inhibited cellular growth, cell migration, cell invasion and cell epithelial-mesenchymal transition. Furthermore, compared with NC siRNA transfected cells, RAB1A siRNA transfected breast cancer cells inhibited the phosphorylation of S6K1, the effector molecular of mTORC1. Collectively, our data suggested that RAB1A acts as an oncogene by regulating cellular proliferation, growth, invasion and metastasis via activation of mTORC1 pathway in triple-negative breast cancer.

Dysregulation of microRNAs (miRNAs) plays a critical role in cancer progression. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-135b in breast cancer and to validate whether miR-135b could regulate proliferation of breast cancer cells by effecting specific targets in the Hippo pathway. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to quantify the expression levels of miR-135b in both breast cancer tissues and cell lines. To characterize the function of miR-135b, MTT assays, colony formation assays, cell migration assays, cell invasion assays, and cell cycle assays were used. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-135b, in corroboration with western blot assays. Finally, we verified the changes of cellular function after transfection of LATS2-siRNA. Our experiments indicate that expression of miR-135b was commonly upregulated in breast cancer specimens and breast cancer cells when compared with that in adjacent normal tissues and non-malignant breast epithelial cells. Enforced expression of miR-135b can regulate cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-135b directly bound to the 3'-untranslated region (3'-UTR) of LATS2 (large tumor suppressor kinase 2), a critical gene in the Hippo pathway. Western blot analysis verified that miR-135b regulated the expression of LATS2 at protein levels. Further study demonstrated that the downstream gene of LATS2 in the Hippo pathway, such as cyclin-dependent kinase 2 (CDK2) and Phospho-Yes-associated protein (p-YAP), can also be regulated by miR-135b and LATS2 axis. Knockdown of endogenous LATS2 can mimic the result of miR-135b up-regulation in breast cancer. Taken together, our findings reveal that the miR-135b and LATS2 axis may be a potential therapeutic target for breast cancer in the future.

MicroRNAs (miRNAs) are small, non-coding RNAs that modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression of microRNA-145 (miR-145) in human papillary thyroid cancer and its potential function. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-145 in ten papillary thyroid cancer and adjacent normal specimens. The function of miR-145 overexpression on the proliferation of human TPC1 thyroid cancer cells was conducted by MTT assays and by colony-formation assays. Western blot was used to validate the impact of miR-145 on the protein expression of the target gene. Luciferase reporter assays were employed to validate a putative target of miR-145. MiR-145 expression was relatively decreased in papillary thyroid cancer specimens compared with adjacent normal tissues (P

Many studies have demonstrated that microRNAs (miRNAs) may play vital roles in the development of breast cancer. The aim of this study was to examine the expression levels of miR-497 in human breast cancer and investigate whether its potential roles involved targeting Bcl-2. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to examine the expression levels of miR-497 in 48 breast cancer specimens and six breast cancer cell lines. MTT assay, colony formation assay, and flow cytometry were conducted to explore the potential functions of miR-497 in human MDA-MB-231 breast cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether Bcl-2 was a direct target of miR-497. The effects of modulating miR-497 on endogenous levels of Bcl-2 were subsequently confirmed via qRT-PCR and western blot. MTT assay, colony formation assay and flow cytometry were used to indicate the roles of endogenous Bcl-2 in breast cancer cells. miR-497 expression levels were significantly decreased in human breast cancer specimens and cell lines (P

Hong-ming Song,* Jia-lu Song,* Deng-feng Li, Kai-yao Hua, Bing-kun Zhao, Lin Fang Department of Breast and Thyroid Surgery, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally tothis work Abstract: Forkhead box protein O1 (FOXO1) is a multifunctional transcription factor of the forkhead family. It may function as a tumor suppressor through its ability to regulate cellular events, including cell proliferation, apoptosis, and cell cycle control. As reported, FOXO1 is downregulated in papillary thyroid carcinoma (PTC). However, the function of FOXO1 in human PTC remains unclear. In this study, we investigated the function and underlying regulatory mechanisms of FOXO1 in PTC cells. PTC cell lines K1 and TPC1 were transiently transfected with FOXO1 small interfering RNA (siRNA) and negative control RNA. Successful transfection was confirmed by RT-qPCR and Western blot analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays, colony formation assays, apoptosis, and cell cycle assays were used to explore the potential function of FOXO1 in the PTC cell lines. We found that downregulation of FOXO1 promoted cellular proliferation, enhanced clonogenesis, and inhibited cellular apoptosis. However, the cell cycle was not markedly affected by FOXO1 siRNA. Furthermore, Bim, a downstream target of the Akt/FOXO1 signaling pathway, was downregulated at both mRNA and protein levels in cells transfected with FOXO1 siRNA. Collectively, these results indicate that FOXO1 may play an important role in inhibiting PTC development by regulating cellular proliferation, growth, and apoptosis. FOXO1 expression is a potentially useful biomarker for human PTC. Moreover, tumorigenesis of PTC may be associated with repression of the Akt/FOXO1/Bim signaling pathway. Keywords: siRNA, FOXO1, Akt/FOXO1/Bim pathway, papillary thyroid carcinoma, proliferation, apoptosis