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Ehm2/1, an Ehm2 transcript variant, regulates the cytoskeleton by binding to plasma membrane proteins. However, the role of Ehm2/1 in breast cancer development remains poorly understood. This study shows that, the expression of Ehm2/1 was decreased in breast cancer and that patients with low Ehm2/1 expression had a significantly poorer prognosis than those with high expression of Ehm2/1. Overexpression of Ehm2/1 in MCF-7 breast cancer cells inhibited cell migration and invasion. Ehm2/1 markedly increased the stability and half-life of E-cadherin. Moreover, Ehm2/1 was collocated with E-cadherin in the plasma membrane of MCF-7 cells. Furthermore, downregulation of Ehm2/1 promoted ubiquitination of E-cadherin, whereas overexpression of Ehm2/1 inhibited ubiquitination of E-cadherin. These results suggest that Ehm2/1 could suppress the migration and invasion of breast cancer cells by increasing E-cadherin stability.

A novel doxorubicin hydrochloride liposome injection was prepared to reduce toxicity and side effects, as well as extend plasma half-life in the treatment of breast cancer. In this study, a rapid and sensitive bioanalytical method was developed and validated to characterize the pharmacokinetic profile of total and free doxorubicin in plasma of 3 Chinese patients after intravenous infusion of this injection. Plasma samples were prepared by protein precipitation for the determination of total doxorubicin, while solid phase extraction was used to determine free doxorubicin. After plasma sample pre-treatment, total and free concentrations were quantified individually using a validated LC-MS/MS method. The calibration curves were found to be linear in the range of 0.20–500.0 ng mL−1 for total doxorubicin and in the range of 1.00–1,000 ng mL−1 for free doxorubicin. The free concentrations in plasma were only one sixth to one quarter of the total levels. Liposomal doxorubicin had a longer apparent half-life (>50 h) than the non-targeted drug (

To explore the effect of circRHOT1 on breast cancer progression and the underlying mechanism. Significantly, our data revealed that the depletion of circRHOT1 was able to repress the proliferation and induce the apoptosis of breast cancer cells. CircRHOT1 knockdown could remarkably inhibit the invasion and migration in the breast cancer cells. Meanwhile, the depletion of circRHOT1 enhanced the erastin-induced inhibition effect on cell growth of breast cancer cells. The circRHOT1 knockdown notably increased the levels of reactive oxygen species (ROS), iron, and Fe2+ in breast cancer cells. Mechanically, circRHOT1 was able to sponge microRNA-106a-5p (miR-106a-5p) and inhibited ferroptosis by down-regulating miR-106a-5p in breast cancer cells. Besides, miR-106a-5p induced ferroptosis by targeting signal transducer and activator of transcription 3 (STAT3) in the system. Moreover, the overexpression of STAT3 and miR-106a-5p inhibitor could reverse circRHOT1 knockdown-mediated breast cancer progression. Functionally, circRHOT1 promoted the tumor growth of breast cancer in vivo. In conclusion, we discovered that circRHOT1 contributed to malignant progression and attenuated ferroptosis in breast cancer by the miR-106a-5p/STAT3 axis. Our finding provides new insights into the mechanism by which circRHOT1 promotes the development of breast cancer. CircRHOT1 and miR-106a-5p may serve as potential targets for breast cancer therapy.

SODA (Simple Ocean Data Assimilation) is one of the ocean reanalysis data widely used in oceanographic research. The SODA3 dataset provides multiple ocean reanalysis data sets driven by different atmospheric forcing fields. The differences between their arctic sea ice simulations are assessed and compared with observational data from different sources. We find that in the simulation of arctic sea ice concentration, the differences between SODA3 reanalysis data sets driven by different forcing fields are small, showing a low concentration of thick ice and a high concentration of thin ice. In terms of sea ice extent, different forced field model data can well simulate the decline trend of observed data, but the overall arctic sea ice extent is overestimated, which is related to more simulated sea ice in the sea ice margin. In terms of the simulation of arctic sea ice thickness, the results of different forcing fields show that the simulation of arctic sea ice thickness by SODA data set is relatively thin on the whole, especially in the thick ice region. The results of different models differ greatly in the Beaufort Sea, the Fram Strait, and the Central Arctic Sea. The above differences may be related to the differences between the model-driven field and the actual wind field, which leads to the inaccurate simulation of arctic sea ice transport and ultimately to the different thickness distribution simulation. In addition, differences in heat flux may also lead to differences in arctic sea ice between models and observations. In this paper, the differences between the results of arctic sea ice driven by different SODA3 forcing fields are studied, which provides a reference for the use of SODA3 data in the study of arctic sea ice and guidance for the selection of SODA data in the study of sea ice in different arctic seas.

Focused on the issue that density peaks clustering algorithm will make mistakes when facing data sets allocation with complex structures, a kind of density peaks clustering with optimized allocation strategy (ODPC) is proposed in this paper. Firstly, the parameter product [γ] is introduced into the new algorithm to expand the selection of cluster centers. Then, it proposes an improved allocation strategy for data points, which redistributes points of data sets with similarity index [MS,] and further optimizes the allocation of points. Finally, [dc] nearest neighbor method is used to optimally identify the noise points of data sets. The experiments on artificial and UCI real data sets show that the new algorithm can improve the accuracy of complex manifold data sets allocation while opti-mizing noise recognition, and achieves better clustering results than DPC (clustering by fast search and find of den-sity peaks), DenPEHC (density peak based efficient hierarchical clustering) and GDPC (density peaks clustering algorithm with gird-division strategy) algorithms.

GIS plays an important role in power system,so when there is a failure in GIS,it will affect the stable operation of the whole power system, and even threaten the security issues,partial discharge is a common fault in GIS, and it can be caused by many reasons.The insulation fault can be predicted in advance by live detection or on-line monitoring of partial discharge. However, due to the low efficiency of the current equipment condition based maintenance, there is a lack of effective intelligent diagnosis algorithm. In view of this situation, an intelligent diagnosis and recognition technology of GIS partial discharge data atlas based on deep learning is proposed. Firstly, on the basis of deep learning neural network and data fusion theory, combined with the application of AI Artificial Intelligence Algorithm in UHF and ultrasonic partial discharge defect diagnosis of GIS equipment, the intelligent diagnosis model of UHF and ultrasonic partial discharge data Atlas of GIS equipment based on deep learning is constructed, and then the intelligent diagnosis and analysis system of GIS partial discharge data based on artificial intelligence is developed, Finally, the intelligent diagnosis and recognition of partial discharge data Atlas of GIS equipment are realized. The experimental results show that the data intelligent analysis system has excellent data classification and judgment performance in the face of multimodal data. In general, deep learning greatly improves its computational efficiency by using neural network pre training algorithm. In addition, its high efficiency in data fitting and classification makes it show great industrial application potential and commercial application value in the social production and life with the rapid development of information technology and the continuous expansion of data scale and complexity.

To compare the clinical efficacy and aesthetic perspectives between single-port gasless laparoscopic breast-conserving surgery (SGL-BCS) and traditional breast-conserving surgery (T-BCS) in early-stage breast cancer. A total of 70 patients who were diagnosed with stage I or stage II breast cancer participated in this study, which 35 patients underwent SGL-BCS, while others underwent T-BCS. There were no death or severe intraoperative complications, and none of the patients exhibited regional recurrence, distant metastases, or any critical complications after 2 years follow-up. SGL-BCS is feasible and safe surgery, and has advantages in terms of a single, shorter, hidden incision, high-satisficed aesthetic outcome and less intraoperative blood loss.

DLG1-AS1 and PBX3 have been identified as acting as an oncogene in cervical cancer. However, they have not been well explored in triple-negative breast cancer (TNBC). As TNBC is one of the malignancies causing increasing death throughout the world, this study aimed to probe into the regulatory relationship between DLG1-AS1 and PBX3 in TNBC cells. In this study, real-time quantitative PCR (qRT-PCR) and western blot experiments were conducted to investigate the RNA and protein levels of genes of interest in TNBC cells. Functional experiments were implemented, such as 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays, to assess the changes in TNBC cell phenotype. Chromatin immunoprecipitation, luciferase reporter, RNA binding protein immunoprecipitation, and RNA pull-down assays were conducted to investigate the binding relationships among subject genes. The results show that DLG1-AS1 and PBX3 displayed high expression in TNBC cells, and PBX3 worked as the transcriptional activator of DLG1-AS1. Also, DLG1-AS1 served as an oncogene in TNBC cells and as a sponge for miR-16-5p to up-regulate JARID2. Meanwhile, JARID2 and PBX3 exerted oncogenic effects on TNBC cell growth. In conclusion, PBX3-activated DLG1-AS1 can promote the proliferation, invasion, and migration of TNBC cells by sponging miR-16-5p and elevating JARID2 expression.

The influence of Ta on the intermediate temperature creep behavior and deformation mechanism in a Ni-based single crystal superalloy has been investigated at 760 oC and 750 MPa. The results indicate that there is a significant increasing of creep rupture life after the addition of Ta. Lattice misfit between γ and γ′ phase at 760 oC increases in the Ta-containing alloy. Microstructure showed that the formation of stacking faults in the γ matrix and denser dislocation network at the γ/γ′ interfaces caused by Ta addition are found during the primary creep stage. And a large amount of stacking fault locks which act as an important pattern in the strengthening generate in the γ′ precipitates, resulting in a lower steady state creep rate and longer steady state creep life in Ta-containing alloy. And possible formation mechanism of the stacking fault locks is also discussed.

Background and Objectives To evaluate efficacy and aesthetic outcome for combined endoscopic subcutaneous mastectomy (E-SM) and endoscopic sentinel lymph node biopsy (E-SLNB) in early stage breast cancer patients. Methods Combined E-SM+E-SLNB was compared to modified radical resection in a cohort of Chinese patients (n = 49) with stages I and II breast cancer. Patient satisfaction with the aesthetic results was assessed 1 year after surgery with a 5-item-by-4-step scoring system for evaluating cosmetic outcomes. Results All patients were alive 1 year following surgery with no locoregional recurrence or distant metastases and without any critical complications. The average length of incision was less in patients receiving E-SM+E-SLNB (4.4 vs. 19.4 cm; P

Ehm2, which belongs to the FERM superfamily, is a metastasis-associated protein. However, its function in cancer metastasis and the associated molecular mechanism is not definitely clear. Alternative splicing is an important biological step during mRNA processing and has been reported to be related with many diseases including cancers. Ehm2 has two transcript variants. Transcript variant 1(Ehm2/1) encodes isoform 1 of 518 amino acids, while transcript variant 2(Ehm2/2) encodes isoform 2 of 913 amino acids. In this study, we found that Ehm2/1 was the main transcript variant in the MCF-7 breast cancer cell line. Forced expression of Ehm2/1 upregulated the total protein amount but had no effect on the mRNA levels of β-catenin. The increased β-catenin was found to be dominantly located at the cell membrane. Meanwhile, knockdown of Ehm2/1 in MCF-7 cells decreased the total protein amount but not the mRNA levels of β-catenin. Further results showed that Ehm2/1 interacted with β-catenin and colocalized with it at the cell membrane. E-cadherin, a partner of β-catenin in cadherin-catenin complexes, was also upregulated by the overexpression of Ehm2/1 and also colocalized with it at the cell membrane. Meanwhile, overexpression of Ehm2/1 inhibited the migration ability of MCF-7 cells. These results suggested that Ehm2/1 may render β-catenin at the cell membrane by interacting with β-catenin and E-cadherin.

Rationale: Complete small intestinal volvulus is a rare entity in adults, unlike partial intestinal volvulus. Although prompt surgical intervention is the mainstay of treatment, attention should also be paid to recovery of intestinal function postoperatively. Ignoring this issue during the postoperative recovery process can have serious consequences. We report the case of an 82-year-old woman with complete small intestinal volvulus at the root of the superior mesenteric vessel. Patients concerns: The patient was admitted for acute onset (22 hours) of abdominal pain and distention. Nausea and vomiting also developed during this period. Diagnoses: Abdominal physical examination was suspicious for peritoneal irritation. Computed tomography scan showed anticlockwise swirl of the mesenteric vessels at the lower margin of the pancreas with distension of the entire small intestine. A complete small intestinal volvulus was diagnosed. Interventions: Laparotomy and detorsion of the volvulus were performed after early diagnosis. Outcomes: The patient developed intestinal wall edema because of ischemic–reperfusion damage. She exhibited severe abdominal distention and absent intestinal motility. Two days later, she went into septic shock; she died 19 days after surgical intervention. Lessons: Because complete small intestinal volvulus involves the entire intestine, ischemic–reperfusion intestinal damage after detorsion may be severe and can predict prognosis.

Death receptor-3 (DR3) plays controversial roles in cancer. Currently, DR3 is known to be a functional receptor of vascular endothelial growth inhibitor (VEGI). The role of DR3 in breast cancer remains unclear. The present study investigated DR3 expression in a clinical cohort of breast cancer patients and its role in breast cancer cells in vitro. The expression of DR3 was examined in a breast cancer cohort using quantitative PCR (Q-PCR) and immunohistochemistry (IHC) in comparison to the patients' data. In vitro function of DR3 was examined through the targeting of this molecule in MCF7 and MDA-MB-231 breast cancer cells using ribozyme transgene technology. Decreased DR3 expression was noted in breast cancer tissues compared to normal tissues and decreased expression of DR3 was generally associated with a poorer prognosis as well as a significantly shorter long-term survival (p=0.038). Targeting of DR3 in vitro in breast cancer cell lines resulted in impaired migratory rates compared to respective control cells. Collectively, these data suggest a complex role for DR3 in breast cancer development and progression.

A simple and rapid liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sunitinib and its two metabolites in plasma of Chinese patients with metastatic renal cell carcinoma (mRCC). After simple one-step protein precipitation with methanol–acetonitrile (1:1, v/v), all three analytes were separated on an Agilent Zorbax SB-C18 column using a gradient mobile phase consisting of water (0.1% formic acid)–acetonitrile (0.1% formic acid) at a flow rate of 0.50 mL/min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 399.0 → 326.2, m/z 371.0 → 283.1, m/z 343.0 → 283.1 and m/z 386.3 → 122.2 for sunitinib, M1, M2 and buspirone, respectively. The method was linear over the range of 0.10–100 ng/mL for all three analytes using only 50 μL of plasma and the lower limit of quantifications for the three analytes were all 0.10 ng/mL. The intra-day and inter-day precisions were all less than 15% and the accuracies were within the range of ±15%; recoveries were between 85.0 and 115%. The validated method was successfully applied to an explorative pharmacokinetic study of sunitinib in Chinese patients with mRCC following multi-dose oral administration. Copyright © 2012 John Wiley & Sons, Ltd.

The expression of taxol resistance gene 1 and thrombospondin 1 remains unknown in human breast cancer tissues. In the current study, we sought to measure the mRNA expression levels of taxol resistance gene 1 and thrombospondin 1 in breast cancer tissue and adjacent normal tissue specimens and further analyzed their expression according to the molecular subtypes and age of breast cancer patients who had received taxane-containing regimens. Archived breast cancer and adjacent non-tumor tissue specimens were obtained at Beijing Friendship Hospital, Beijing, China. The mRNA transcript levels of taxol resistance gene 1, thrombospondin 1 and multi-drug resistance 1 were determined by quantitative RT-PCR . Taxol resistance gene 1 and multi-drug resistance 1 protein levels were measured by immunoblotting assays. Forty-nine archived breast cancer tissue specimens were included. The majority of the specimens (65.3%) were of the molecular subtype A followed by triple negative breast cancer (14.3%). The mRNA transcript levels of taxol resistance gene 1 , thrombospondin 1 and multi-drug resistance 1 in breast cancer tissues were higher than those of adjacent normal tissues. The mRNA expression of TXR1 in the HER2 subtype (4.513 ± 0.810) was the highest and in the Luminal B subtype was the lowest (3.103 ± 0.417) among the four molecular subtypes. The HER2 subtype also had the highest mRNA expression of thrombospondin 1(4.827 ± 0.927) and the Luminal B subtype had the lowest TSP1 mRNA level (3.197 ± 0.565) among the four molecular subtypes. Our study represents the first attempt in delineating taxol resistance gene 1 and thrombospondin 1 expression in breast cancer and we demonstrate that taxol resistance gene 1 and thrombospondin 1 expression may vary according to the molecular subtypes of breast cancer.

Breast cancer is one of the most common malignant female diseases worldwide. It is a significant threat to every woman's health. Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells. According to previous literature, overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models, but there has been limited research on the significance of VEGI in the breast cancer.In our study, cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed. The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo. The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting. The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth, invasion, adhesion, and migration assay with subcutaneous tumor-bearing nude mice models. Then the growth curves of the subcutaneous tumors were studied. Expressions of VEGI, CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI. As can be seen in the invasion, adhesion and migration assay, the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration, adhesion and invasion. The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups. Immunohistochemistry analysis of the tumor biopsies clearly showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly. In vitro and in vivo, the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Taken together, recombinant lentivirus that were successfully constructed, demonstrated up-regulated VEGI gene expression in breast cancer cells. Lentivirus-mediated over-expression of VEGI weakened the ability of the breast cancer cell migration, adhesion and invasion. Over-expression of VEGI diminished the tumorigenic capacity of breast cancer cells in vivo. Up-regulation of VEGI gene expression however inhibited breast cancer MDA-MB-231 cell in the early apoptosis.

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of sunitinib and its two metabolites in plasma of Chinese patients with metastatic renal cell carcinoma (mRCC). After simple one-step protein precipitation with methanol-acetonitrile (1:1, v/v), all three analytes were separated on an Agilent Zorbax SB-C(18) column using a gradient mobile phase consisting of water (0.1% formic acid)-acetonitrile (0.1% formic acid) at a flow rate of 0.50 mL/min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 399.0 → 326.2, m/z 371.0 → 283.1, m/z 343.0 → 283.1 and m/z 386.3 → 122.2 for sunitinib, M1, M2 and buspirone, respectively. The method was linear over the range of 0.10-100 ng/mL for all three analytes using only 50 μL of plasma and the lower limit of quantifications for the three analytes were all 0.10 ng/mL. The intra-day and inter-day precisions were all less than 15% and the accuracies were within the range of ±15%; recoveries were between 85.0 and 115%. The validated method was successfully applied to an explorative pharmacokinetic study of sunitinib in Chinese patients with mRCC following multi-dose oral administration.

Death Decoy Receptor-3 (DcR3), otherwise known as tumour necrosis factor receptor superfamily member 6b, is suggested to be involved in the progression and immune evasion of malignant tumours. Its ligands include FASL and LIGHT (Tumour necrosis factor ligand superfamily member 14). DcR3 has been found to be amplified in certain solid tumours. However, its role in breast tumours remains unclear. In the present study, we examined the role played by DcR3 in MCF7 and MDA-MB-231 cell lines.The expression of DcR3 was examined in MCF7 and MDA-MB-231 cell lines using immunocytochemical staining and RT-PCR. Anti-DcR3 hammerhead ribozyme transgenes were constructed and transfected into cells to create DcR3 knock-down cell sublines. The biological impact of modifying DcR3 expression in breast cancer cells was evaluated using a variety of in vitro assays, including growth, adhesion, migration and invasion models.MCF7 and MDA-MB-231 cells, usually expressing DcR3, were transfected with the anti-DcR3 ribozyme transgene. Stable transfectants containing the DcR3 ribozyme transgene (MCF7DcR3KO, MDA-MB-231DcR3KO) displayed a reduction of DcR3 expression at mRNA and protein levels. DcR3 knockdown in MCF7 cells was found to significantly reduce invasive capacity compared to pEF6 control cell lines (30.78 +/- 6.40 vs.151.67 +/- 17.67 P0.001). The rate of migration in MCF7DcR3KO was significantly lower than MCF7pEF6 (P0.001). In contrast, no such significant differences was seen between MDA-MB-231DcR3KO and MDA-MB-231pEF6.Suppressing DcR3 expression was found to have an inhibitory effect on cellular invasion and migration in MCF7 breast cancer cells. This suggests that the invasion and migration capacity of this breast cancer cell line may, at least partly, depend on DcR3. DcR3 may be regarded as a negative regulator for aggressiveness during the development and progression of certain types of breast cancer.