Search

Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease. The lack of targeted therapies and poor patient outcome have fostered efforts to discover new molecular targets to treat patients with TNBC. Here, we showed that baculoviral IAP repeat containing 6 (BIRC6) is overexpressed and positively correlated with epidermal growth factor (EGF) receptor (EGFR) in TNBC cells and tissues and that BIRC6 overexpression is associated with poor patient survival. Mechanistic studies revealed that BIRC6 stability is increased by EGF-JNK signaling, which prevents ubiquitination and degradation of BIRC6 mediated by the E3 ubiquitin ligase HECTD1. BIRC6 in turn decreases SMAC expression by inducing the ubiquitin-proteasome pathway, thereby antagonizing apoptosis and promoting the proliferation, colony formation, tumorsphere formation, and tumor growth capacity of TNBC cells. Therapeutically, the PEGylated cationic lipid nanoparticle (pCLN)-assisted delivery of BIRC6 small interfering RNA (siRNA) efficiently silences BIRC6 expression in TNBC cells, thus suppressing TNBC cell growth in vitro and in vivo, and its antitumor activity is significantly superior to that of the EGFR inhibitor gefitinib. Our findings identify an important regulatory mechanism of BIRC6 overexpression and provide a potential therapeutic option for treating TNBC., Graphical abstract, TNBC is the most aggressive subtype of breast cancer, and discovery of new targeted therapies is required. Our findings show that EGF-JNK-HECTD1 signaling can drive the overexpression of BIRC6 in TNBC. Targeting BIRC6 with lipid nanoparticle-coated siRNA represents a very promising approach for treating TNBC.

Introduction Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy outcomes in mothers and infants. The aim was to evaluate the sensitivity and specificity of biochemical detection of ICP by ROC curve and to determine the threshold of more reliable experimental indicators. Materials and Methods 305 patients and 305 healthy pregnant women were enrolled in the study. Results The average levels of TBA, ALT, and AST in the ICP group were much higher than those in the control group (P Conclusions This study did not find any single specificity and sensitivity markers that could be used to reliably diagnose ICP. In the future, we will pay more attention to the correlation between sensitive biochemical indicators and adverse pregnancy outcomes.

Yupeng Liu,1 Suhuan Dai,1 Lijuan Wen,1,2 Yun Zhu,3 Yanan Tan,3 Guoxi Qiu,1 Tingting Meng,1 Fangying Yu,1 Hong Yuan,1 Fuqiang Hu1 1College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, People’s Republic of China; 2National Engineering Research Center for Modernization of Traditional Chinese Medicine - Hakka Medical Resources Branch, School of Pharmacy, Gannan Medical University, Ganzhou 342700, People’s Republic of China; 3Ocean College, Zhejiang University, Zhoushan 316021, Republic of ChinaCorrespondence: Fuqiang HuCollege of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People’s Republic of ChinaTel/Fax +86-571-88208439Email hufq@zju.edu.cnBackground: Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis.Methods: In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dualeffect of PDT/PTT with NIR irradiation.Results: In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation.Conclusion: The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.Keywords: angiogenesis, dual-targeting, glycolipid-like micelles, phototherapy, glioblastoma

Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.

Background CYB5D2 is a member of the membrane-associated progesterone receptors (MAPRs) family and plays essential roles in regulating nerve development. CYB5D2 is associated with tumor suppression in breast cancer. Despite the potential implication of CYB5D2 in cancer progression, its level and clinical significance in cervical cancer tissues has not been investigated yet. Via this study, we aimed to investigate the possible role played by CYB5D2 in epithelial–mesenchymal transition (EMT) in cervical cancer and correlate its level with clinical outcomes. Methods The expressions of CYB5D2 and the EMT marker E-cadherin in different groups of cervical samples were compared using immunofluorescence. Furthermore, co-localization of CYB5D2 and E-cadherin was analyzed in different cervical tissue samples via confocal laser scanning microscopy. The relationship between CYB5D2/E-cadherin and the progression and clinicopathological features of cervical cancer were analyzed, and the prognostic value of CYB5D2 mRNA expression was evaluated in various tumors using the Kaplan-Meier plotter database. Results CYB5D2 and E-cadherin were downregulated in cervical cancer (P0.05). Higher expression levels of CYB5D2 mRNA were predicted to be associated with a better relapse-free survival (RFS) in patients with cervical cancer. E-cadherin expression was associated with invasive tumors, tumor grade, and FIGO stage (P0.05). There was a positive correlation between CYB5D2 and E-cadherin expression in cervical cancer (P

Objective: To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. Methods: The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. Results: Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and β-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. Conclusions: The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing.

Background This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC. Methods Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC. Results Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC. Conclusion miRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.

Background Some Western medicine schools in China established standardized patient (SP) programs for medical education. However, SP programs are rarely applied to the education of traditional Chinese medicine (TCM). In this study, we evaluated the effectiveness of using standardized patient traditional Chinese medicine (SP-TCM) to improve clinical competency among TCM medical students. Methods This study was a prospective, 2-group, parallel-training randomized trial over the course of 5 years. Data were collected from September 2016 to December 2020. Participants in each year were randomly allocated into the traditional-method training group or the SP-TCM training group (1:1) for a 3-month curriculum. Measurement of clinical competency among all trainees was based on a standardized examination composed of scores of medical record documentation, scores of TCM syndrome differentiation and therapeutic regimen, and checklist assessment from both SP-TCMs and TCM professionals. Feedback was collected using semi-constructive questionnaires from both groups. Results Compared with those assigned to traditional-method training, those assigned to SP-TCM training demonstrated significantly greater post-training improvement in medical record documentation and TCM syndrome differentiation and therapeutic regimen. Moreover, SP-TCM trainees outscored those assigned to traditional training in the assessment for encounter performance given by independent SP-TCMs and TCM professionals. The SP-TCM method gained higher satisfaction of training efficacy and test performance than the traditional method. Conclusion This SP-TCM program demonstrated great benefits for improving clinical competency among TCM medical students.

The emergence of energy spectrum CT provides greater diagnostic value for clinical practice. Its advantage is that it can provide more functional imaging parameters and accurate image information for clinical practice, which represents a mainstream direction of CT technology development at present. This paper mainly studies the clinical trial of CAMPO Precision128 Max ENERGY spectrum CT combined with multiple parameters to evaluate the benign and malignant pleural effusion. This paper analyzes the principle and key performance parameters of energy spectrum CT imaging, the etiology of pleural effusion, and its conventional diagnostic methods and uses energy spectrum CT to detect the benign and malignant pleural effusion. In this paper, two groups of patients with different types of pleural effusions were scanned by line spectrum chest CT scans, and energy spectrum analysis software was used to measure and calculate the CT values of conventional mixed energy values of ROI of patients with pleural effusions. For the CT value and energy curve slope measurement value of different single energy keV, independent sample t-test was used to analyze and compare the two sets of data, and finally it has been found out that the two sets of data were similar. According to the experimental results, the curves of energy spectrum of the two groups of data are similar in the descending curve of bow-back. The slope of energy spectrum curve in the leakage group was lower than that in the exudate group, showing statistical significance ( P < 0.05 ). The slope of energy spectrum curve K in the malignant pleural effusion group was significantly higher than that in the benign pleural effusion group, and the difference was statistically significant ( P < 0.05 ). The trend of energy spectrum curves of the two is roughly the same, while at the high energy level, part of the energy spectrum curves of the two are overlapped. The above conclusion indicates that energy spectrum CT plays a certain role in the differential diagnosis of pleural effusion. At the same time, energy spectrum CT also provides a noninvasive and rapid examination method for clinical differentiation of pleural effusion, which has certain clinical application value and prospect.

Background The study was a retrospective cohort analysis based on the results of noninvasive prenatal screening (NIPS), complete blood count, thyroxin test and Down’s syndrome screening in first or second trimester from 14043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction of cell free DNA (with FF lower than 10th percentile) through individual and laboratory information. Performance of the model was evaluated and compared to prediction using maternal weight.To investigate factors associated with lower FF in the NIPS and to develop a new predictive method for low FF before NIPS. Results Of 14043 cases, maternal weight, RBC, HGB and free T3 were significantly negative correlated with FF while gestation age, free T4, PAPP-A, AFP, uE3 and β-hCG were significantly positive correlated with FF. Compared to prediction using maternal weight as isolated parameter, the model has a higher area under curve(AUC) of Receiver Operating Characteristic (ROC) and overall accuracy. Conclusions The comprehensive predictive method based on combined multiple factors was more effective than single-factor model in low FF status prediction. This method can provide more information for clinical choice and pre-test quality control of NIPS.

Recent studies have revealed that artesunate (ART) has clear anti-tumor activity, suggesting that it could be a good candidate chemotherapeutic agent. In this study, we researched the inhibitory effect of ART on MCF7 cells and explored the possible mechanisms. MTT assay was used to detect the effect of ART on the proliferation of MCF7 cells. Crystal violet staining was used to observe morphological and quantitative changes. Flow cytometry was used to detect the cell cycle of the drug-acting MCF7 cells. In addition, western blotting was used to detect the drug influence on expression of the ATM, phospho-ATM(S1981), H2AX, γH2AX(S139), CHK2 and phospho-CHK2(T68), cdc25C, and phospho-cdc25C(S216). In the experimental groups, the proliferation of MCF7 cells was inhibited in a dose-dependent manner and the original cell morphology was lost. The number of G2/M phase cells in the experimental groups increased significantly, and the expression of DNA damage response-associated proteins was significantly increased, such as phospho-ATM(S1981), γH2AX(S139), phospho-CHK2(T68), and phospho-cdc25C(S216). ART can inhibit cell proliferation and promote G2/M arrest in MCF7 cells through ATM activation and the ensuing “ATM-Chk2-Cdc25C” pathway, thus implicating ART as a novel candidate for breast cancer chemotherapy.

Glioblastoma (GBM) is one of the malignant tumors with high mortality, and the presence of the blood brain barrier (BBB) severely limits the penetration and tissue accumulation of therapeutic agents in the lesion of GBM. Active targeting nanotechnologies can achieve efficient drug delivery in the brain, while still have a very low success rate. Here we revealed a previously unexplored phenomenon that chemotherapy with active targeting nanotechnologies causes pathological BBB functional recovery through VEGF-PI3K-AKT signaling pathway inhibition, accompanied with up-regulated expression of Claudin-5 and Occludin. Seriously, pathological BBB functional recovery induces a significant decrease of intracerebral active targeting nanotechnologies transport during GBM multiple administration, leading to chemotherapy failure in GBM therapeutics. To address this issue, we chose AKT agonist SC79 to transiently re-open functional recovering pathological BBB for continuously intracerebral delivery of brain targeted nanotherapeutics, finally producing an observable anti-GBM effect in vivo, which may offer new sight for other CNS disease treatment.

Usage of combination therapies to deliver multiple therapeutics to increase treatment efficacy has shown promising results in the clinic. In an effort to maximize the synergistic effect of co-delivery of a drug and siRNA, we have developed a time-dependent sequential drug delivery system (DDS) based on a disulfide-linked chitosan-based nanocarrier (CS-ss-SA) for the co-delivery of paclitaxel (PTX) and Bcl-2 specific siRNA (siBcl-2). This CS-ss-SA nanocarrier is able to transport both drug and siRNA by entrapment of PTX and adsorption of siRNA on the shell by electrostatic attraction. We show that this nanocarrier transports siRNA into tumor cells via its glycolipid-like spatial structure and releases a hydrophobic model drug, Nile Red 8-11 h later. Next, when siRNA and the hydrophobic drug PTX were co-delivered to tumor cells, a synergistic effect was observed in both cell cycle arrest and cell viability. Ultimately, the co-delivery of PTX and siBcl-2 by CS-ss-SA may prove to be more efficacious and may even help overcome drug resistance.

// Tingting Meng 1 , Jingwen Liu 1 , Lijuan Wen 1 , Ming Yuan 1 , Bolin Cheng 1 , Yingwen Hu 1 , Yun Zhu 1 , Xuan Liu 1 , Hong Yuan 1 , Fuqiang Hu 1 1 Institute of Pharmaceutics, College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China Correspondence to: Fuqiang Hu, email: hufq@zju.edu.cn Keywords: multi-cycle chemotherapy, tumor repopulation, drug delivery, cancer stem cell, microenvironment Received: April 05, 2016 Accepted: September 13, 2016 Published: September 21, 2016 ABSTRACT Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro , on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo , the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What’s more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.

Rupture of abdominal aortic aneurysm (AAA) is a devastating event that can be prevented by inhibiting the growth of small aneurysms. Therapeutic strategies targeting certain events that promote the development of AAA must be developed, in order to alter the course of AAA. Chronic inflammation of the aortic mural is a major characteristic of AAA and is related to AAA formation, development and rupture. Daphnetin (DAP) is a coumarin derivative with anti-inflammatory properties that is extracted from Daphne odora var. However, the effect of DAP on AAA development remains unclear. The present study investigated the effect of DAP on the formation and development of experimental AAAs and its potential underlying mechanisms. A mice AAA model was established by intra-aortic infusion of porcine pancreatic elastase (PPE), and mice were intraperitoneally injected with DAP immediately after PPE infusion. The maximum diameter of the abdominal aorta was measured by ultrasound system, and aortic mural changes were investigated by Elastica van Gieson (EVG) staining and immunohistochemical staining. The results demonstrated that DAP significantly suppressed PPE-induced AAA formation and attenuated the depletion of aortic medial elastin and smooth muscle cells in the media of the aorta. Furthermore, the density of mural macrophages, T cells and B cells were significantly attenuated in DAP-treated AAA mice. In addition, treatment with DAP resulted in a significant reduction in mural neovessels. These findings indicated that DAP may limit the formation and progression of experimental aneurysms by inhibiting mural inflammation and angiogenesis. These data confirmed the translational potential of DAP inclinical AAA inhibition strategies.

This chapter examines the impacts of climate variability on selected socio-ecological settings in South Asia. A transdisciplinary conceptual framework is presented that blends multilevel interactions in a social-ecological-climate nexus. The overarching objective is to draw on empirical experience to build capacity to make use of climate data for societal needs, i.e., to facilitate climate change adaptation planning. The chapter has two modules. The first module, Climate Change Monitoring (CCM), details the operating structure of real-time climate data and its practical use. The second module, Climate Change Assessment (CCA), examines impacts and adaptation options using a case study approach. Focusing on the analytical process, the authors examine three socio-ecological subsystems, i.e., marine fisheries, a rice agroecosystem, and human migration, using a mixed "tool box" of meteorological data, remote sensing images, primary and secondary socioeconomic information, and a variety of software programs. The results indicate that (1) spatial indicators are useful in explaining a decline in marine ecosystem productivity; (2) local-level temperature variability is closely related to agroecosystem transitions; and (3) climatic variability, especially increased frequency of extreme events, triggers human migration. The case studies highlight the need to employ real-time climate data in the design of adaptation strategies and the requirement for a transdisciplinary approach.

In this paper, in order to precisely extract video objects from complex background, a new video objects extraction algorithm based on fusion of temporal segmentation and spatial segmentation is proposed. The method can extract moving objects effectively under complex background and overcome the drawback of integrity of the extracted moving objects in the condition of similarity of the foreground color and background color. First, in temporal space, the paper adopted the background model and improved background difference method to extract complete moving objects area. Subsequently, in spatial space, to get precise segmented edge image, the paper used the algorithm of adaptive meanshift for color image segmentation. Finally, the author made some improvement in the fusion operation of the extracted moving objects area and the segmented edge image, the method extracted video objects with precise edge. Experimental results show the proposed algorithm above can segment the accurate and complete video objects in video sequence with complex background.

In order to extract the accurate depth map which accords with human vision, a new depth extraction method based on fusion of motion information and geometry information was proposed in the paper. First, to extract the stationary background image from the video sequence with stationary background and moving foreground, the gaussian mixture model algorithm was adopted, then the paper adopted background difference method with adaptive threshold to extract complete moving objects area. Furthermore, the depth map of background image was computed based on geometry information, similarly, the depth map of moving foreground was computed based on motion information. Finally, the complete and precise depth map was obtained using the method based on fusion of the depth map of background image and the depth map of moving foreground.

Nowadays the Web is being increasingly deepened by a large group of online databases. How to map a uniform query to corresponding online database exactly is a critical problem to integrate the deep Web databases in the same domain. The same attribute may have different ranges in different forms, which means mapping it becomes the bottle-neck to solve the form mapping problem. We use fuzzy synthetic evaluation to solve this problem. Firstly, we analyze the form mapping issue, point that the data range mapping is the key problem, and we transfer it to a fuzzy synthetic function problem and compute the membership function in different ranges. Then we use it to select the optimal mapping result. To validate its effectiveness we developed ldquoEasy Auto Searcherrdquo, an deep web integration system of auto, and conduct experiments. The result shows that it is effective.

Alpine regions are changing rapidly due to loss of snow and ice in response to ongoing climate change. While studies have documented ecological responses in alpine lakes and streams to these changes, our ability to predict such outcomes is limited. We propose that the application of fundamental rules of life can help develop necessary predictive frameworks. We focus on four key rules of life and their interactions: the temperature dependence of biotic processes from enzymes to evolution; the wavelength dependence of the effects of solar radiation on biological and ecological processes; the ramifications of the non-arbitrary elemental stoichiometry of life; and maximization of limiting resource use efficiency across scales. As the cryosphere melts and thaws, alpine lakes and streams will experience major changes in temperature regimes, absolute and relative inputs of solar radiation in ultraviolet and photosynthetically active radiation, and relative supplies of resources (e.g., carbon, nitrogen, and phosphorus), leading to nonlinear and interactive effects on particular biota, as well as on community and ecosystem properties. We propose that applying these key rules of life to cryosphere-influenced ecosystems will reduce uncertainties about the impacts of global change and help develop an integrated global view of rapidly changing alpine environments. However, doing so will require intensive interdisciplinary collaboration and international cooperation. More broadly, the alpine cryosphere is an example of a system where improving our understanding of mechanistic underpinnings of living systems might transform our ability to predict and mitigate the impacts of ongoing global change across the daunting scope of diversity in Earth's biota and environments.