Evaluation of the presence and severity of spontaneous splenorenal or gastrorenal shunts via four-dimensional flow magnetic resonance imaging: a preliminary study.

Background: Four-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) is a relatively new type of MRI acquisition technique that provides a unique and comprehensive set of information within a single acquisition, including hemodynamic and anatomical information. This study was designed to noninvasively evaluate the correlation between the presence and severity of spontaneous splenorenal shunt (SRS) or gastrorenal shunt (GRS) and 4D flow MRI-derived parameters. Methods: This retrospective case-control study enrolled 70 patients who were diagnosed with hepatocirrhosis portal hypertension and admitted to the Second Affiliated Hospital of Chongqing Medical University. Patients were divided into three groups according to the diameter of the SRS and GRS. 4D flow MRI-derived parameters, including the turbulent kinetic energy, total volume (TV), flow velocity, blood flow volume (BFV), maximum flow (MF), wall shear stress, and relative pressure, were obtained for eight cut planes: proximal to the splenomesenteric confluence and liver hilum of the portal vein (PV1/PV2); the left/right branch of the bifurcation of the PV (LPV/RPV), at the mesosplenic confluence of the splenic vein (SV1), at the splenic hilum of the SV (SV2); at the proximal to the splenomesenteric confluence of the superior mesenteric vein (SMV1), and 5 cm from the splenomesenteric confluence of the SMV (SMV2). Comparisons among the three groups were based on one-way analysis of variance (ANOVA). Logistic regression was used to identify the risk factors for small SRS/GRS (S-SRS/GRS) and for large SRS/GRS (L-SRS/GRS). Receiver operating characteristic curves were used to evaluate the diagnostic performance of the independent risk factors for SRS and GRS. The associations between the clinical data and the 4D flow MRI-derived parameters of GRS and SRS were assessed via Spearman correlation coefficient analysis. Results: The presence of SRS or GRS was correlated with TVLPV (r=-0.302; P=0.035), TVPV1 (r=-0.385; P=0.001), TVPV2 (r=-0.301; P=0.013), BFVPV1 (r=-0.360; P=0.010), BFVSMV2 (r=0.371; P=0.008), MFPV1 (r=-0.341; P=0.004), and MFPV2 (r=-0.291; P=0.017). Meanwhile, the severity of the SRS or GRS was correlated with alanine aminotransferase level (r=-0.535; P<0.001), BFVLPV (r=-0.560; P=0.008), aspartate aminotransferase level (r=-0.321; P=0.038), and model for end-stage liver disease score (r=0.323; P=0.039). TVPV1, TVPV2, BFVPV1, BFVPV2, and MFSMV2 were found to be independent risk factors for L-SRS/GRS, with intermediate diagnostic efficacy, with the area under the curve (AUC)TV PV1=0.706 [95% confidence interval (CI): 0.519-0.853; sensitivity, 61.54%; specificity, 80.77%; P=0.018], AUCBFV PV1 =0.694 (95% CI: 0.507-0.844; sensitivity, 95.00%; specificity, 63.16%; P=0.035), AUCTV PV2 =0.729 (95% CI: 0.544-0.870; sensitivity, 77.78%; specificity, 66.67%; P=0.016), AUCBFV PV2 =0.718 (95% CI: 0.531-0.862; sensitivity, 60.00%; specificity, 82.35%; P=0.017), and AUCMF SMV2 =0.788 (95% CI: 0.608-0.912; sensitivity, 44.00%; specificity, 84.46%; P=0.005), respectively. As the TV of PV1 and PV2 and the BFV of PV1 and PV2 decreased, the risk of L-SRS/GRS increased. As the MF of SMV2 increased, the risk of the presence of L-SRS/GRS increased. Conclusions: 4D flow MRI-derived parameters correlated with the presence and severity of SRS or GRS. Meanwhile, the independent risk factors for the presence of L-SRS/GRS were the TV of LPV, PV1, and PV2; the BFV of PV1 and SMV2; and the MF of PV1 and PV2.

Quality control of elbow joint radiography using a YOLOv8-based artificial intelligence technology.

BACKGROUND: To explore an artificial intelligence (AI) technology employing YOLOv8 for quality control (QC) on elbow joint radiographs. METHODS: From January 2022 to August 2023, 2643 consecutive elbow radiographs were collected and randomly assigned to the training, validation, and test sets in a 6:2:2 ratio. We proposed the anteroposterior (AP) and lateral (LAT) models to identify target detection boxes and key points on elbow radiographs using YOLOv8. These identifications were transformed into five quality standards: (1) AP elbow positioning coordinates (XA and YA); (2) olecranon fossa positioning distance parameters (S17 and S27); (3) key points of joint space (Y3, Y4, Y5 and Y6); (4) LAT elbow positioning coordinates (X2 and Y2); and (5) flexion angle. Models were trained and validated using 2,120 radiographs. A test set of 523 radiographs was used for assessing the agreement between AI and physician and to evaluate clinical efficiency of models. RESULTS: The AP and LAT models demonstrated high precision, recall, and mean average precision for identifying boxes and points. AI and physicians showed high intraclass correlation coefficient (ICC) in evaluating: AP coordinates XA (0.987) and YA (0.991); olecranon fossa parameters S17 (0.964) and S27 (0.951); key points Y3 (0.998), Y4 (0.997), Y5 (0.998) and Y6 (0.959); LAT coordinates X2 (0.994) and Y2 (0.986); and flexion angle (0.865). Compared to manual methods, using AI, QC time was reduced by 43% for AP images and 45% for LAT images (p < 0.001). CONCLUSION: YOLOv8-based AI technology is feasible for QC of elbow radiography with high performance. RELEVANCE STATEMENT: This study proposed and validated a YOLOv8-based AI model for automated quality control in elbow radiography, obtaining high efficiency in clinical settings. KEY POINTS: QC of elbow joint radiography is important for detecting diseases. Models based on YOLOv8 are proposed and perform well in image QC. Models offer objective and efficient solutions for QC in elbow joint radiographs.

Mono+ algorithm assessment of the diagnostic value of dual-energy CT for high-risk factors for colorectal cancer: a preliminary study.

Background: Risk factors for colorectal cancer (CRC) affect the way patients are subsequently treated and their prognosis. Dual-energy computerized tomography (DECT) is an advanced imaging technique that enables the quantitative evaluation of lesions. This study aimed to evaluate the quality of DECT images based on the Mono+ algorithm in CRC, and based on this, to assess the value of DECT in the diagnosis of CRC risk factors. Methods: This prospective study was performed from 2021 to 2023. A dual-phase DECT protocol was established for consecutive patients with primary CRC. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), overall image quality, lesion delineation, and image noise of the dual-phase DECT images were assessed. Next, the optimal energy-level image was selected to analyze the iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number, electron density, dual-energy index (DEI), and slope of the energy spectrum curve within the tumor for the high- and low-risk CRC groups. A multifactor binary logistic regression analysis was used to construct a differential diagnostic regression model for high- and low-risk CRC, receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to assess the diagnostic value of the model. Results: A total of 74 patients were enrolled in this study, of whom 41 had high-risk factors and 33 had low-risk factors. The SNR and CNR were best at 40 keV virtual monoenergetic imaging (VMI) based on the Mono+ algorithm (VMI+) (SNR 8.79±1.27, P<0.001; CNR 14.89±1.77, P=0.027). The overall image quality and lesion contours were best at 60 keV VMI+ and 40 keV VMI+, respectively (P=0.001). Among all the DECT parameters, the arterial phase (AP)-IC, NIC, DEI, energy spectrum curve, and venous phase-NIC differed significantly between the two groups. The AP-IC was the optimal DECT parameter for predicting high- and low-risk CRC with AUC, sensitivity, specificity, and cut-off values of 0.96, 97.06%, 87.80%, and 2.94, respectively, and the 95% confidence interval (CI) of the AUC was 0.88-0.99. Integrating the clinical factors and DECT parameters, the AUC, sensitivity, specificity, and predictive accuracy of the model were 0.99, 100.00%, 92.68%, and 94.67%, respectively, and the 95% CI of the AUC was 0.93-1.00. Conclusions: The DECT parameters based on 40 keV noise-optimized VMI+ reconstruction images depicted the CRC tumors best, and the clinical DECT model may have significant implications for the preoperative prediction of high-risk factors in CRC patients.

Mode coupling characteristics investigation on a tapered seven-core fiber sensor.

In this work, we analytically derive the transmission spectra of the seven-core fiber (SCF) with a phase mismatch between the center core and outer cores based on the mode coupling theory. We also establish the wavelength shift as a function of temperature and ambient refractive index (RI) using approximations and differentiation techniques. Our results reveal the opposite effects of temperature and ambient RI on the wavelength shift of the SCF transmission spectrum. The theoretical conclusions are confirmed by our experiments on the behavior of SCF transmission spectra under various temperature and ambient RI conditions.

Silencing TRPM2 enhanced erastin- and RSL3-induced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins.

Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. Cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival. Our bioinformatic analysis revealed that TRPM2 is associated with cellular responses to chemical stimulus and oxidative stress, implying the potential role of TRPM2 in ferroptosis. Gastric cancer cells were treated with the ferroptosis-inducer, Erastin and RSL3. siRNA transfection was used to silence TRPM2. The levels of GSH, Fe2+, ROS and lipid peroxidation, and the activity of GPx activity were evaluated by flow cytometry and spectrophotometer. The effect of TRPM2 on ubiquitination of HIF-1α and Nrf2 were evaluated by co-immunoprecipitation. Erastin and RSL3 induced the up-regulation of TRPM2 in gastric cancer cell lines, especially in SGC7901 and MGC803. These two cells also showed stronger resistance to Erastin and RSL3 than the other cell lines. TRPM2 knockdown reduced the concentration of GSH and GPx activity, but enhanced the concentration of Fe2+, ROS and lipid peroxidation, which are significant indicators of ferroptosis. Importantly, silencing TRPM2 enhanced the inhibitory effects of Erastin and RSL3 on gastric cancer cell viability, migration, and invasion. TRPM2 stabilized and finally elevated the abundance of HIF-1α and Nrf2 in SGC7901 and MGC803 cells upon Erastin and RSL3. Activation of HIF-1α impaired Erastin- and RSL3-induced ferroptosis after TRPM2 knockdown. Collectively, silencing TRPM2 enhanced Erastin- and RSL3-induced ferroptosis in gastric cancer cells through destabilizing HIF-1α and Nrf2 proteins. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00545-z.

The prevalence of human papillomavirus among women in northern Guangdong Province of China.

Globally, cervical cancer, whose etiologic factor is Human papillomavirus (HPV), is the third most common cancer among women. In cervical cancer screening, HPV testing is important. However, the prevalence of HPV in northern Guangdong Province has not been conclusively determined. A total of 100,994 women attending Yuebei People's Hospital Affiliated to Shantou University Medical College between 2012 and 2020 were recruited. HPV was tested by a polymerase chain reaction (PCR)-based hybridization gene chip assay. The prevalence of HPV among these women was established to be19.04%. Peak prevalence was observed in women aged 40-49 (7.29%). Besides, the prevalence of single-type HPV infection (14.46%) was significantly high, compared to multiple-type infection (4.58%) (p < 0.01), while the prevalence of high-risk HPV infection (19.97%) was significantly higher than that of low-risk genotypes (5.48%) (p < 0.01). The most prevalent high-risk genotypes were HPV52 (4.16%), HPV16 (2.98%), HPV58 (2.15%), HPV53 (1.58%) and HPV68 (1.34%). HPV co-infection with up to 10 genotypes was reported for the first time. Our findings suggested a high burden of HPV infections among women in northern Guangdong. Establishing the prevalence and genotype distribution characteristics of HPV infections in the region can contribute to cervical cancer prevention through HPV vaccination.

Understanding the experiences of older caregivers of patients with lung cancer during palliative chemotherapy in China: a qualitative study.

PURPOSE: Although there has been an increase in research on caregivers of patients with cancer, there has been little focus on the specific experiences of older caregivers of patients with lung cancer and the effect of their cultural backgrounds on their experiences. This study explored the caregiver experience among the ageing population in China. METHODS: Older caregivers of patients with lung cancer undergoing palliative chemotherapy were recruited. Data were collected using a qualitative descriptive design involving semi-structured interviews, which were recorded, transcribed verbatim and analysed qualitatively using inductive content analysis. RESULTS: Eighteen caregivers aged 61-81 years completed the interviews. The following four themes were identified: physical difficulty, living with ambivalence, perception of role and role-related behaviour changes. These themes enabled a greater understanding of role-related behaviours in older caregivers and their challenges in addressing biological and psychosocial challenges related to older age. CONCLUSION: The present study highlighted the vulnerability and perceived challenges of the role of older caregivers. These findings help lay the foundation for interventions to improve the care provided to caregivers and their health outcomes, especially caregivers with chronic conditions.

A deep-learning model for identifying fresh vertebral compression fractures on digital radiography.

OBJECTIVES: To develop a deep-learning (DL) model for identifying fresh VCFs from digital radiography (DR), with magnetic resonance imaging (MRI) as the reference standard. METHODS: Patients with lumbar VCFs were retrospectively enrolled from January 2011 to May 2020. All patients underwent DR and MRI scanning. VCFs were categorized as fresh or old according to MRI results, and the VCF grade and type were assessed. The raw DR data were sent to InferScholar Center for annotation. A DL-based prediction model was built, and its diagnostic performance was evaluated. The DeLong test was applied to assess differences in ROC curves between different models. RESULTS: A total of 1877 VCFs in 1099 patients were included in our study and randomly divided into development (n = 824 patients) and test (n = 275 patients) datasets. The ensemble model identified fresh and old VCFs, reaching an AUC of 0.80 (95% confidence interval [CI], 0.77-0.83), an accuracy of 74% (95% CI, 72-77%), a sensitivity of 80% (95% CI, 77-83%), and a specificity of 68% (95% CI, 63-72%). Lateral (AUC, 0.83) views exhibited better performance than anteroposterior views (AUC, 0.77), and the best performance among respective subgroupings was obtained for grade 3 (AUC, 0.89) and crush-type (AUC, 0.87) subgroups. CONCLUSION: The proposed DL model achieved adequate performance in identifying fresh VCFs from DR. KEY POINTS: • The ensemble deep-learning model identified fresh VCFs from DR, reaching an AUC of 0.80, an accuracy of 74%, a sensitivity of 80%, and a specificity of 68% with the reference standard of MRI. • The lateral views (AUC, 0.83) exhibited better performance than anteroposterior views (AUC, 0.77). • The grade 3 (AUC, 0.89) and crush-type (AUC, 0.87) subgroups showed the best performance among their respective subgroupings.

Diagnostic value of multi-slice spiral CT scan in lung compression ratio of patients with pulmonary contusion complicated by pneumothorax or hydropneumothorax.

OBJECTIVE: This study was designed to explore the diagnostic value of multi-slice spiral CT (MSCT) scanning in lung compression ratio of patients with pulmonary contusion complicated by pneumothorax or hydropneumothorax. METHODS: Seventy-eight patients with pulmonary contusions complicated by pneumothorax or hydropneumothorax treated in the Department of Emergency Surgery of our hospital were examined by CT and X-ray, and the diagnostic value of these two methods was observed. The correlation of lung compression ratio measured by multiplanar reconstruction (MPR) and volume rendering (VR) with W/D ratio was studied, and the formula between VR-measured lung compression ratio and W/D ratio was constructed using a one-variable linear regression equation. RESULTS: The diagnostic rate of pulmonary contusions complicated by pneumothorax or hydropneumothorax measured by CT was higher than that by X-ray (P<0.05). Among the patients with pulmonary contusion diagnosed by CT, 45 were localized and 33 were extensive, and there were statistically significant differences in the incidence of comorbid rib fractures (P<0.05). The correlation of lung compression ratio measured by VR with W/D ratio measured by CT was analyzed, and the regression equation of the two was obtained by one-variable linear regression equation analysis: lung compression ratio =1.159* W/D -1.034. VR-measured lung compression ratio measured was positively correlated with W/D ratio (r=0.936, P<0.001). CONCLUSION: CT is superior to X-ray in the diagnosis of pulmonary contusions complicated by pneumothorax or hydropneumothorax. The calculation of lung compression ratio using the formula of lung compression ratio =1.159* W/D -1.034 has certain clinical value and can improve clinical work efficiency.

Regulation of GSK3ß/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer.

Ferroptosis is a newly discovered form of regulated cell death and characterized by an iron-dependent accumulation of lethal lipid reactive oxygen species (ROS), ferroptosis may exhibit a novel spectrum of clinical activity for cancer therapy. However, the significance of ferroptosis in the context of carcinoma biology is still emerging. Glycogen synthase kinase-3ß (GSK-3ß) has been found to be a fundamental element in weaking antioxidant cell defense by adjusting the nuclear factor erythroid 2-related factor 2 (Nrf2). In our study, decreased expression of GSK-3ß was observed in the cancer tissues of breast cancer patients, results of immunohistochemistry indicated that Nrf2 was highly expressed in low-GSK-3ß-expressed breast cancer tissues. The contributions of aberrant expression of GSK-3ß and Nrf2 to the erastin-induced ferroptosis in breast cancer were further assessed, silence of GSK-3ß blocked erastin-induced ferroptosis with less production of ROS and malondialdehyde (MDA) via upregulation of GPX4 and downregulation of arachidonate 15-lipoxygenase (Alox15), overexpression of GSK-3ß enhanced erastin-triggered ferroptosis with elevated ROS and MDA. Enhanced erastin-induced ferroptosis by overexpression of GSK-3ß was blocked by activating Nrf2. We further confirmed that overexpression of GSK-3ß strengthened erastin-induced tumor growth inhibition in breast cancer xenograft models in vivo. In summary, our findings conclude that modulation the balance between GSK-3ß/Nrf2 is a promising therapeutic approach and probably will be important targets to enhance the effect of erastin-induced ferroptosis in breast cancer.

The lncRNA NORAD/miR-520a-3p Facilitates Malignancy in Non-Small Cell Lung Cancer via PI3k/Akt/mTOR Signaling Pathway.

BACKGROUND/AIMS: The effects of lncRNA-NORAD/mir-520a-3p on proliferation and invasion of non-small cell lung cancer (NSCLC) were studied, and its potential molecular mechanism was discussed. METHODS: qRT-PCR was used to detect the expression of lncRNA NORAD and miR-520a-3p in non-small cell lung cancer tissues and cell lines. CCK-8 method and Transwell test were used to identify the effects of lncRNA NORAD on the proliferation and invasion in NSCLC. Target gene prediction and screening and luciferase reporter assay was used to verify downstream target genes of lncRNA NORAD. The expressions of PI3K, AKT, and mTOR proteins were detected by Western blot. RESULTS: Compared with normal tissues and cells, the expressions of lncRNA NORAD in cancer tissues and cells were significantly higher. Compared with normal cells, the expression of miR-520a-3p in cells was considerably lower. LncRNA NORAD could accelerate the growth and metastasis of NSCLC in vitro and in vivo. Luciferase reporter assay results indicated that miR-520a-3p was a downstream target gene of lncRNA NORAD. Further findings showed that lncRNA NORAD might bind to miR-520a-3p, thereby affecting the PI3k/Akt/mTOR signaling pathway. CONCLUSION: LncRNA NORAD can regulate the proliferation of NSCLC by regulating miR-520a-3p/PI3k/Akt/mTOR signaling pathway, thus promoting the occurrence and development of NSCLC.

Highly sensitive optical fiber curvature sensor based on a seven-core fiber with a twisted structure.

A highly sensitive Mach-Zehnder interferometer based on a twisted structure in seven-core fiber (SCF) for curvature measurement is investigated both theoretically and experimentally. The device is fabricated by splicing a segment of a twisted SCF with single-mode fibers by the over fusion method. An interference pattern of the straight sensor appears in the transmission spectra. When the sensor is bent, the wavelength shift of the interference pattern is induced, which may be used for curvature measurement through wavelength shift. In the experiment, SCFs with and without the twisted structure are tested, and the results are compared with wavelength-based sensitivities. The proposed twisted-SCF sensor offers a maximum curvature sensitivity of $ - {25.16}\,\,{{\rm nm/m}^{ - 1}}$-25.16nm/m-1 within the measurement range of ${0.5201 - 1.0071}\,\,{{\rm m}^{ - 1}}$0.5201-1.0071m-1, which is a 37-fold improvement compared with the previous works. The results also indicate that this highly sensitive all-fiber sensor offers great potential for realization of curvature measurement in the field of structural health monitoring.

Thalidomide induce response in patients with corticosteroid-resistant or relapsed ITP by upregulating Neuropilin-1 expression.

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. METHODS: 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. RESULTS: Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. CONCLUSIONS: Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.

Protective efficacy of inhaled quercetin for radiation pneumonitis.

Radiation pneumonitis is a clinical problem with a high incidence. Once the onset of radiation pneumonitis has occurred, the administration of antioxidants and anti-inflammatory agents is the most commonly used method of clinical treatment. Quercetin (Que) is a common flavonoid, with potent anti-inflammatory and anti-oxidant activities. In the present study, the therapeutic effect of inhaled Que on radiation-induced radiation pneumonitis in rats was investigated. Treatment with Que via inhalation was shown to increase the number of leukocytes and erythrocytes in the blood, and reduce the number of inflammatory cells in bronchoalveolar lavage fluid. Histological examination of lung tissue indicated that inhaled Que reduced hemorrhaging and the infiltration of inflammatory cells, and suppressed the expression of the proinflammatory cytokines transforming growth factor-ß1 and interleukin-6. These results indicated that treatment with Que via inhalation ameliorates radiation pneumonitis by reducing the number of inflammatory cells, and attenuating the inflammatory response and pathological changes. This suggests that administration of Que via inhalation has the potential to become a novel treatment for radiation pneumonitis.

Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery.

High drug resistance, poor water solubility, short half-life, and low local drug concentration are obstacles for successful delivery of chemotherapeutic drugs for lung cancer. A new method involving the use of nanoparticles (NPs) for pulmonary delivery is proposed. However, use of NPs is limited by the particle size range for pulmonary drug delivery considering that NPs cannot be deposited directly into the lungs. NPs polymerized into microspheres (polymeric microspheres, PMs) will result in suitable particle sizes and retain the advantages of nanodrugs after redispersion when applied in pulmonary delivery. We report the development of novel NPs in the form of PMs loaded with paclitaxel (PTX) and quercetin (QUE) double drugs based on the synthesis of oleic acid-conjugated chitosan (OA-CTS) for pulmonary delivery. This approach is aimed toward prolonging PTX retention time in the presence of QUE and bypassing P-glycoprotein drug efflux pumps. NPs loaded with PTX or QUE were prepared with 11% substitution degree using OA-CTS as the carrier by ionic cross-linking method, which NPs loaded with PTX or QUE were used in the preparation of PMs by spray-drying. The diameters of the PMs ranged from 1 to 5 µm which had uniform size range. Scanning electron microscopy showed that PMs were polymers formed by a large number of NPs and readily redispersed (after redispersion, size of NPs ranged between 250 and 350 nm) in water within 1 h. PMs displayed slow-release characteristics at pH 4.5 and 7.4. The in vivo pharmacokinetic and biodistribution studies suggested that PMs exhibit prolonged circulation time and a markedly high accumulation in the lung. The obtained results indicate that PMs can serve as a promising pulmonary delivery system for combined pharmacotherapy using hydrophobic anticancer drugs.

Amplification and the clinical significance of circulating cell-free DNA of PVT1 in breast cancer.

Duplication in the chromosome 8q24 region is a frequent occurrence in carcinomas. The PVT1 oncogene (PVT1), a long non-coding RNA, is found in this locus. PVT1 amplification is a frequent event in cancers, such as in lymphomas, serous ovarian, colorectal and breast cancers. Ectopic PVT1 expression is related with reduced survival duration in cancer patients. in the present study, we proved that PVT1 is markedly augmented in breast cancer tissues compared with adjacent non-tumorous tissues. Thus, PVT1 is an independent prognostic factor for the survival duration of breast cancer patients. Furthermore, PVT1 is pivotal in regulating p21 expression. In addition, we detected PVT1 DNA in serum and found that circulating PVT1 DNA significantly increased in the serum of breast cancer patients. Compared with PVT1 RNA, DNA is the main form of the PVT1-derived segment. These relevant findings collectively demonstrate that PVT1 plays a pivotal role in breast cancer and is a possible target for novel breast cancer therapies. The detection of circulating PVT1 DNA fragments may be a convenient means to predict the prognosis of breast cancer patients.

miR-199a-5p regulates ß1 integrin through Ets-1 to suppress invasion in breast cancer.

Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of ß1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of ß1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.

Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer.

Therapeutic resistance to trastuzumab caused by dysregulation of long noncoding RNAs (lncRNAs) is a major obstacle to clinical management of HER2-positive breast cancer. To investigate which lncRNAs contribute to trastuzumab resistance, we screened a microarray of lncRNAs involved in the malignant phenotype of trastuzumab-resistant SKBR-3/Tr cells. Expression of the lncRNA GAS5 was decreased in SKBR-3/Tr cells and in breast cancer tissue from trastuzumab-treated patients. Inhibition of GAS5 promoted SKBR-3 cell proliferation, and GAS5 knockdown partially reversed lapatinib-induced inhibition of SKBR-3/Tr cell proliferation. GAS5 suppresses cancer proliferation by acting as a molecular sponge for miR-21, leading to the de-repression of phosphatase and tensin homologs (PTEN), the endogenous target of miR-21. Moreover, mTOR activation associated with reduced GAS5 expression was required to suppress PTEN. This work identifies GAS5 as a novel prognostic marker and candidate drug target for HER2-positive breast cancer.

Synthesis and evaluation of perfluorooctylbromide nanoparticles modified with a folate receptor for targeting ovarian cancer: in vitro and in vivo experiments.

BACKGROUND: Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. However, detecting ovarian cancer at an early stage remains challenging. In this work, we aimed to synthesize a folate-receptor-targeting perfluorooctylbromide nanoparticle (FR-TPNP) as a targeted computed tomography (CT) contrast agent for the early detection of ovarian cancer. METHODS: Perfluorooctylbromide (PFOB) was encapsulated in Poly (lactic-co-glycolic acid) (PLGA) by a two-step emulsion technique to construct the nanoparticles. Folate-poly (ethylene glycol)-carboxylic acid (Fol-PEG-COOH) was introduced to modify the surface of the nanoparticles through attachment to the PLGA. The effects of different volume ratios of PFOB to PLGA on the characteristics of the FR-TPNP emulsions were compared. The size distribution and potential of the FR-TPNPs were assessed with a laser particle size analyzer system. The in vitro targeting ability of the FR-TPNPs was observed with a confocal laser scanning microscope (CLSM), and the in vivo transportation of the FR-TPNPs was evaluated with CT. RESULTS: The sizes of the FR-TPNP emulsion with different volume ratios varied from 302.67 ± 27.83 nm to 563.68 ± 47.29 nm, and the mean CT value ranged from 233 ± 20.59 HU to 587.66 ± 159.51 HU. Both the size and mean CT value increased with the volume ratio. The FR-TPNPs showed greater cell affinity and targeting efficiency to SKOV3 cells than the control group and folic acid interference group in vitro, as observed by CLSM. A significant CT enhancement of ovarian cancer xenografts in the targeted group of a nude mice model was observed 2 h post-injection; it increased to a peak at 12 h and had a duration of 48 h. The mean CT value of the tumor in the targeted group was considerably higher than those in the non-targeted and other groups 6 h post-injection. CONCLUSION: The synthesized FR-TPNP emulsion was an effective CT contrast agent with highly efficient targeting ability and a long circulation time, thus representing a potential strategy for the earlier detection of ovarian cancer.