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To investigate the effectiveness of dynamic susceptibility contrast-perfusion weighted imaging (DSCPWI) in predicting the progression-free survival (PFS) and chemotherapeutic responsiveness of primary central nervous system lymphoma (PCNSL) before high-dose methotrexate-based chemotherapy. DSCPWI was used to analyze 35 patients who had pathology-confirmed PCNSL. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP) were measured on parameter maps. The 5th, 50th and 95th percentile values of every parameter were recorded for enhanced tumors and compared with the parameters of the normally contralateral hemisphere. The ratio of each PWI parameter (rrCBV, rrCBF, rrMTT, rrTTP) was obtained. The influence of parameters on responsiveness and PFS was investigated by univariate Kaplan-Meier analysis and logistic regression and Cox regression for multivariate analysis with a stepwise method. Differences in PWI parameters between the higher and lower vascular endothelial growth factor (VEGF) groups were assessed by the Mann-Whitney U test. Eighteen patients achieved a complete response (CR

Monitoring the levels of cancer biomarkers is essential for cancer diagnosis and evaluation. In this study, a novel sandwich type sensing platform based on surface-enhanced Raman scattering (SERS) technology was developed for the detection of carcinoembryonic antigen (CEA), with a limit of detection (LOD) of 0.258 ng/mL. In order to achieve sensitive detection of CEA in complex samples, gold nanoparticle monolayer modified with CEA antibodies and with aptamer-functionalized probes was fabricated to target CEA. Two gold layers were integrated into the SERS platform, which greatly enhanced the signal of the probe by generating tremendous “hot spots”. Meanwhile, the intensity ratio of Raman probes and the second-order peak of the silicon wafer was used to achieve dynamic calibration of the Raman probe signal. Excitingly, this sensing platform was capable of distinguishing cancer patients from healthy individuals via CEA concentrations in blood samples with the accuracy of 100%. This sandwich structure SERS sensing platform presented promising potential to be an alternative tool for clinical biomarker detection in the field of cancer diagnosis.

Follicular thyroid carcinoma (FTC) is an indolent carcinoma. The cumulative incidence of death from patients with FTC and the nomogram built based on the competing risks model have not been described. The data from patients diagnosed with primary FTC were identified and extracted from the surveillance, epidemiology, and end results (SEER) program (1988–2015). The cumulative incidence function was utilized to calculate the likelihood of death resulting from thyroid cancer and other causes, respectively. Gray’s test was used to examine the difference in the cumulative incidence of death between the groups. A tenfold cross-validation was applied to assess the discrimination and calibration of the model. A total of 9210 patients diagnosed with primary FTC were included. The median follow-up time was 92 months (1–347 months). The 5-year, 10-year, and 20-year probabilities of death from FTC were 2.84%, 5.23%, and 8.61%, respectively. The age at diagnosis, sex, tumor size, pathological subtypes, tumor extension, lymph node involvement, as well as surgical and radiotherapy methods used, were related to the cumulative incidence of death. Multivariate analysis identified several risk factors for patient survival. The model behaved well in terms of performance. A nomogram based on the model allowed the prediction of the probability of death among patients with FTC. The prognosis of FTC is excellent. The likelihood of death caused by thyroid cancer increases with age. Male sex, tumors larger than 4 cm, invasion, extrathyroidal extension, lymph node involvement, and distant metastases increase the risk of dying of thyroid carcinoma. The nomogram constructed on the basis of the model is potentially useful for both clinicians and patients.

BACKGROUND AND OBJECTIVES Although the significance of Delphian lymph nodes (DLNs) in patients with papillary thyroid carcinoma (PTC) has been reported, all studies have been based on a small sample size and lack a direct statement concerning prognosis. METHODS A total of 904 consecutive patients were enrolled in the current study, and all patients were divided into two groups (DLN-positive and DLN-negative) according to the presence of DLN metastasis. RESULTS DLN was detected in 687 patients (76.0%), and 123 (17.9%) had DLN metastasis. Compared to those in the DLN-negative group, the proportion of other central lymph node (CLN) metastases, mean number of metastatic CLNs, and mean metastatic CLN ratio were higher in the DLN-positive group (86.2 vs. 50.2%, 6.70 ± 5.19 vs. 1.60 ± 2.37, and 0.54 ± 0.25 vs. 0.18 ± 0.26, respectively; p

Breast cancer is a malignant tumor of breast epithelial tissue. Early diagnosis and postoperative evaluation of breast cancer are critical to improve the survival rate. The current main screening methods are mammography and computerized tomography (CT), however, these methods suffer from false positives, over-diagnosis and radiation risk. Herein, unlabeled surface-enhanced Raman spectroscopy (SERS) technology combined with silver nanoparticles that was used to measure and analyze peripheral serum protein samples from patients of breast cancer for preoperation, postoperation and normal subjects. Results showed that there were significant differences in the serum protein SERS spectra among three groups due to changes in certain biochemical compositions related to breast cancer transformation. Moreover, diagnostic sensitivity, based on principal component analysis combined with linear discriminant analysis (PCA-LDA) for pre-surgery versus post-surgery, post-surgery versus normal and pre-surgery versus normal were 96.7%, 53.3%, and 100%, respectively, and the diagnostic specificities were 96.7%, 46.7%, and 96.7%, respectively. Therefore, serum protein SERS combined with PCA-LDA analysis holds promising potential as a novel strategy for early screening and postoperative evaluation of breast cancer.

Mammography, a standard screening method for breast cancer, is effective for reducing the rate of death; however, it suffers from frequent false positive alarm and radiation risk. Besides, surgery treatment has a vital impact on the clinical outcomes of breast cancer, offering enormous benefits for breast cancer care and management. In this work, we analyzed the peripheral blood sample from breast cancer patients with pre- and post-surgery and healthy volunteers using label-free surface-enhanced Raman spectroscopy technology based on silver nanoparticles. Results showed that distinct patterns of blood belonging to specific subjects could be profiled, and corresponding accuracies of 95% and 100% were achieved by multivariate diagnostic algorithm for pre-surgery vs. post-surgery and pre-surgery vs. normal groups, respectively, providing a unique blood analysis method for surgery evaluation as well as tumor screening in breast cancer. Graphical abstract.

Objective: Preoperative evaluation of vessels and nerves will help surgeons to understand and design the intermuscular approach individually. The aim of this study is to analyze the ability of computed tomography (CT) and magnetic resonance imaging (MRI) to display the vessels and nerves for paraspinal intermuscular approach to lumbar spine. Methods: A total of 18 healthy volunteers were examined by CT angiography (CTA) and MRI (sagittal, transverse T2WI and coronary nerve imaging) respectively. The vessels and nerve surrounding the paraspinal intermuscular space (Wiltse, Watkins and Weaver space) was observed. Results: In CTA, the blood supply of lumbar spine were originated from the lumbar artery. All the lumbar artery coursed between the upper and the lower pedicle of vertebral arch, and no vessels were found in the lateral sides of pedicle. In the lateral border of L1–S1, lumbar arteries sent branches into Wiltse space. All levels showed no obvious vessels into Weaver space. Slightly below the transverse process at L1–L3 levels, the lumbar arteries sent a branch into the Watkins space, and finally into the erector spinae. In the MR sagittal T2WI phase, lumbar artery were visible by the blank empty signal. The course of artery was similar with CT. Coronal nerve imaging can clearly show the ventral root and dorsal root, spinal ganglia, and spinal nerve. The relationship between spinal nerve and intermuscular space was failed to show. In the transverse T2WI, the vessel were visible in the Wiltse and Watkins space which similar with CT. Conclusion: Preoperative imaging analysis of vessels and nerves surrounding paraspinal muscle is beneficial to the design of paraspinal intermuscular approach to lumbar spine.

Papillary thyroid cancer (PTC) is the main histological type of thyroid cancer and accounts for almost all increased cases worldwide. Patients with PTC exhibit a favorable prognosis, but the fact that PTC is often accompanied by a high prevalence of lymph node metastasis (LNM) means that the overall recurrence-free survival rate in PTC patients is relatively low. Herein, we identified that ID3 expression is subdued in PTC tissues and closely associated with LNM and a poor disease-free survival outcome in PTC patients. The main contributor to this gene repression is the hypermethylation of the CpG island at the promoter of ID3. Besides, we uncovered that a loss of ID3 promotes invasion and migration of PTC cells, while an ectopic overexpression of ID3 inhibits invasion and migration. Mechanistically, ID3 exhibits tumor suppressor functions in PTC cells by interacting with E47 to form heterodimers that prevent E47 binding to CDH1 promoter and maintaining CDH1 transcription and epithelial phenotype in PTC cells. Taken together, our study demonstrates that ID3 plays a tumor suppressor role in PTC and impedes metastasis by inhibiting E47-mediated epithelial to mesenchymal transition.

Background Breast cancer is one of the most common tumors for women globally. Various miRNAs have been reported to play a crucial role in breast cancer, however the clinical significance of miR-1908-3p in breast cancer remains unclear. The present study aimed to explore the role of miR-1908-3p in breast cancer. Methods The expression of miR-1908-3p was detected in 50 pairs of breast cancer tissues and adjacent normal tissues, 60 breast cancer patient serum and 60 healthy volunteer serum. The functional roles of miR-1908-3p in breast cancer cells such as proliferation, migration and invasion were evaluated using CCK8, SRB, wound healing and transwell chambers. In addition, bioinformatics tools were used to identify potential targets of miR-1908-3p. Results The results showed that the expression of miR-1908-3p were increased in breast cancer tissues and serum compared with normal breast tissues and serum of healthy volunteers respectively. Furthermore, the young breast cancer patients and HER2-positive patients had a higher level of tissues’ miR-1908-3p than elder breast cancer patients and HER2-negative patients, respectively. The young breast cancer patients had a higher level of serum miR-1908-3p than elder breast cancer patients, ROC analysis suggested that miR-1908-3p had the potential as a promising serum diagnostic biomarker of breast cancer. Up-regulation of miR-1908-3p promoted the cells proliferation, migration and invasion while knockdown of miR-1908-3p inhibited these processes in breast cancer cell MCF-7 and MDA-MB-231. The potential target genes of miR-1908-3p in breast cancer included ID4, LTBP4, GPM6B, RGMA, EFCAB1, ALX4, OSR1 and PPARA. Higher expression of these eight genes correlated with a better prognosis for breast cancer patients. Conclusions These results suggest that miR-1908-3p may exert its oncogenic functions via suppression of these eight genes in breast cancer.

Additional file 2. The expression of eight genes in breast cancer. The expression of ID4 (A), LTBP4 (B), GPM6B (C), RGMA (D), EFCAB1 (E), ALX4 (F), OSR1 (G) and PPARA (H) in breast cancer based on GSE33447.

Additional file 1. Primer sequence used in RT-qPCR.

Breast cancer is one of the most common malignancies in women worldwide. In breast cancer, the cell proliferation rate is known to influence the cancer malignancy. Recent studies have shown that DNA replication initiation/licensing factors are involved in cancer cell proliferation as well as cancer cell migration and invasion. Licensing factors have also been reported as important prognostic markers in lung, prostrate, and bladder cancers. Here, we studied the role of MCM10, a novel licensing factor, in breast cancer progression. From the public database, NCBI, we investigated six independent breast cancer patient cohorts, totaling 1283 patients. We observed a significant association between high MCM10 mRNA expression with tumor grading and patients&rsquo, survival time. Most importantly, using breast cancer cohorts with available treatment information, we also demonstrated that a high level of MCM10 is associated with a better response to conventional treatment. Similarly, in in vitro studies, the expression level of MCM10 in breast cancer cell lines is significantly higher compared to paired normal breast epithelium cells. Knockdown of MCM10 expression in the cancer cell line showed significantly decreased tumorigenic properties such as cell proliferation, migration and anchorage independence. The MCF7 breast cancer cell line, after MCM10 expression knockdown, showed significantly decreased tumorigenic properties such as cell proliferation, migration, and anchorage independent growth. Mechanistically, MCM10 expression is observed to be regulated by an Estrogen Receptor (ER) signaling pathway, where its expression is suppressed by the inhibition of the ER or serum withdrawal. Our results suggest that MCM10 plays an important role in breast cancer progression and is a potential prognostic/predictive biomarker and therapeutic target for breast cancer patients.

The influence of Toll-like receptor (TLR)4/myeloid differentiation factor (MyD)88 signaling on the invasion and metastasis of cancer cells has been previously reported. The purpose of the present study was to determine the role of TLR4/MyD88 in breast cancer cell migration and invasion, and to discover novel therapeutic targets for breast cancer treatment. TLR4, MyD88 and high mobility group box 1 (HMGB1) mRNA expression levels were assessed in highly invasive human MDA-MB-231 breast cancer cells, breast cancer cells with a low rate of invasion (MCF-7) and normal human MDA-Kb2 mammary gland cells by reverse transcription-quantitative polymerase chain reaction. The protein expression levels of these markers were detected by western blotting and immunofluorescence. Randomly selected breast cancer and paracarcinoma tissues were used to measure TLR4 and MyD88 protein expression levels by immunohistochemistry. The mRNA and protein expression levels of TLR4 and MyD88 were significantly higher in MDA-MB-231 cells compared with either MCF-7 cells or MDA-Kb2 cells. The mRNA and protein expression levels of HMGB1 were comparable in the two breast cancer cell lines, with no statistical difference (P>0.05). TLR4 and MyD88 protein expression levels were also significantly higher in breast cancer tissues compared with paracarcinoma tissues (P

This study aims to evaluate the difference of central lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) associated with or without Hashimoto's thyroiditis (HT) in predicting lateral node metastasis. A retrospective case control study was performed. Patients (1276) with PTC who underwent a total or near-total thyroidectomy with at least one lymph node dissection in our institution were retrospectively reviewed. All patients were divided into two groups (HT-group and non-HT group) according to the pathological diagnosis. In HT-group, the incidence of both central and lateral LNM was lower compared with non-HT group. The average of central metastatic lymph node radio (LNR) was also lower than that in Non-HT group. The multivariate analysis showed that the number of metastatic central LNs (HT ≥ 4, Non-HT ≥ 2) and the central LNR (HT ≥ 0.4, Non-HT ≥ 0.6) were independently associated with lateral LNM. Patients with HT need larger primary tumor size, more positive central LN and higher LNR to predict the presence of lateral LNM. HT may protect against central and lateral LNM in PTC. The number of positive central LNs and central LNR in PTC could be used to determine the presence of lateral LNM and inform postoperative follow-up.

Background Distinguishing the involved lymph nodes from other tissues during surgery is critical for lymph node dissection. The purpose of this study was to assess the feasibility by using carbon nanoparticles as guidance for lymph node dissection in patients with papillary thyroid carcinoma (PTC). Methods Eighty-one patients were injected with carbon nanoparticles (carbon nanoparticle group), whereas the other 81 patients were not (control group). Routine pathological examination was performed. Results The lymph node dissection and metastatic lymph node dissection rates of the carbon nanoparticle group were significantly higher than that of the control group. In the carbon nanoparticle group, the number of mistakenly dissected parathyroid gland, the case number of postoperative hypocalcemia, the case number of postoperative hypoparathyroidism, and the recovery time from hypocalcemia were 4, 6, 8, and 2.33 ± 0.58 weeks, respectively, significantly less than 14, 17, 20, 3, and 3.8 ± 0.92 weeks in the control group (p

The dynamic processes of formatting long-term memory traces in the cortex are poorly understood. The investigation of these processes requires measurements of task-evoked neuronal activities from large numbers of neurons over many days. Here, we present a two-photon imaging-based system to track event-related neuronal activity in thousands of neurons through the quantitative measurement of EGFP proteins expressed under the control of the EGR1 gene promoter. A recognition algorithm was developed to detect GFP-positive neurons in multiple cortical volumes and thereby to allow the reproducible tracking of 4,000 neurons in each volume for 2 mo. The analysis revealed a context-specific response in sparse layer II neurons. The context-evoked response gradually increased during several days of training and was maintained 1 mo later. The formed traces were specifically activated by the training context and were linearly correlated with the behavioral response. Neuronal assemblies that responded to specific contexts were largely separated, indicating the sparse coding of memory-related traces in the layer II cortical circuit.

BackgroundDeath-associated protein kinase 1 (DAPK) is an important tumor suppressor kinase involved in the regulation of multiple cellular activities such as apoptosis and autophagy. DNA methylation of DAPK gene was found in various types of cancers and often correlated with the clinicopathological characteristics. However, the mRNA and protein expression of DAPK in the same sample was rarely measured. Thus, it was unclear if the correlation between DAPK gene methylation and clinicopathological parameters was due to the loss of DAPK expression.MethodsIn this study, the DNA methylation rate, mRNA and protein expression of DAPK was quantitatively detected in 15 pairs of breast cancer patient samples including tumor (T) and adjacent non-tumor (N) tissues.ResultsThe correlation between DNA methylation rate and mRNA expression, together with the correlation between mRNA and protein expression, was calculated. No correlation was observed between any levels using either the measurement value of each sample or the T/N ratio of each pair.DiscussionThese data suggested that the DNA methylation status of DAPK did not correlate well with its mRNA or protein expression. Extra caution is needed when interpreting the DNA methylation data of DAPK gene in clinical studies.

Death associated protein kinase 1 (DAPK1) is a notable serine/threonine kinase involved in the regulation of multiple cellular pathways, including apoptosis and autophagy. Although DAPK1 is usually considered to be a tumor suppressor, it was previously reported to promote the viability of p53 mutant cancer cell lines and possess physiological oncogenic functions in breast cancer. However, the ability of endogenous DAPK1 to suppress breast cancer cell mobility has not been assessed. In the present study, the prognostic function of DAPK1 in a Chinese patient cohort was evaluated, and no significant association was observed between DAPK1 expression and patient survival or lymph node metastasis. In order to investigate the physiological function of endogenous DAPK1, stable inducible DAPK1 knockdown MCF7 and MDA-MB-231 cell lines were established. Consistent with previous studies, endogenous DAPK1 only regulated cell viability in p53 mutant MDA-MB-231 cells. However, knockdown of DAPK1 did not significantly affect cell motility of either MCF7 or MDA-MB-231 cells. Altogether, these results further explored the function of endogenous DAPK1 in breast cancer and may shed light in understanding the molecular signaling pathways regulating the physiological function of DAPK1.

A variety of problems in nonlinear time-evolution systems such as communication networks, computer networks, manufacturing, traffic management, etc., can be modelled as min–max-plus systems in which operations of min, max and addition appear simultaneously. Systems with only maximum (or minimum) constraints can be modelled as max-plus system and handled by max-plus algebra which changes the original nonlinear system in the traditional sense into linear system in this framework. Min-max-plus systems are extensions of max-plus systems and nonlinear even in the max-plus algebra view. Output feedback stabilization for min–max-plus systems with min–max-plus inputs and max-plus outputs is considered in this paper. Max-plus projection representation for the closed-loop system with min–max-plus output feedback is introduced and the formula to calculate the cycle time is presented. Stabilization of reachable systems with at least one observable state and a further result for reachable and observable systems are worked out, during which max-plus output feedbacks are used to stabilize the systems. The method based on the max-plus algebra is constructive in nature.

Background Double injection of blood into cisterna magna using a rabbit model results in cerebral vasospasm. An unacceptably high mortality rate tends to limit the application of model. Ultrasound guided puncture can provide real-time imaging guidance for operation. The aim of this paper is to establish a safe and effective rabbit model of cerebral vasospasm after subarachnoid hemorrhage with the assistance of ultrasound medical imaging. Methods A total of 160 New Zealand white rabbits were randomly divided into four groups of 40 each: (1) manual control group, (2) manual model group, (3) ultrasound guided control group, and (4) ultrasound guided model group. The subarachnoid hemorrhage was intentionally caused by double injection of blood into their cisterna magna. Then, basilar artery diameters were measured using magnetic resonance angiography before modeling and 5 days after modeling. Results The depth of needle entering into cisterna magna was determined during the process of ultrasound guided puncture. The mortality rates in manual control group and model group were 15 and 23 %, respectively. No rabbits were sacrificed in those two ultrasound guided groups. We found that the mortality rate in ultrasound guided groups decreased significantly compared to manual groups. Compared with diameters before modeling, the basilar artery diameters after modeling were significantly lower in manual and ultrasound guided model groups. The vasospasm aggravated and the proportion of severe vasospasms was greater in ultrasound guided model group than that of manual group. In manual model group, no vasospasm was found in 8 % of rabbits. Conclusions The ultrasound guided double injection of blood into cisterna magna is a safe and effective rabbit model for treatment of cerebral vasospasm.

Background Recognition of the intermuscular spaces within lumbar paraspinal muscles is critically important for using the paramedian muscle-splitting approach to the lumbar spine. As such, it is important to determine the intermuscular spaces within the lumbar paraspinal muscles by utilizing modern medical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). Methods A total of 30 adult cadavers were studied by sectional anatomic dissection, and 60 patients were examined using CT (16 slices, 3-mm thickness, 3-mm intersection gap, n = 30) and MRI (3.0T, T2-WI, 5-mm thickness, 1-mm intersection gap, n = 30). The distances between the midline and the superficial points of the intermuscular spaces at different intervertebral disc levels were measured. Results Based on study of our cadavers, the mean distances from the midline to the intermuscular space between multifidus and longissimus, from intervertebral disc levels L1–L2 to L5–S1, were 0.9, 1.1, 1.7, 3.0, and 3.5 cm, respectively. Compared with the upper levels (L1–L3), the superficial location at the lower level (L4–S1) is more laterally to the midline (P

Objective: To investigate the expression of TLR4/MyD88 in breast cancer, and explore the relationship between their expression and breast cancer tumor growth and invasion. Methods: We examined the protein expression of TLR4 and MyD88 in 60 cases of histologically confirmed breast cancer. The relationship of their protein expressions with clinical features including age at diagnosis, tumor size and stage, lymph node metastasis and distant metastasis were analyzed. Results: The IHC results showed that TLR4 and MyD88 were expressed in 63.3% (38/60) and 58.3% (35/60) of malignant breast tumors respectively. TLR4 expression in breast cancer were significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissues (n = 2, 10.0%) (P < 0.001). MyD88 expression in breast cancer were also significantly higher than in fibroadenoma (n = 4, 20.0%) and adjacent normal tissue (n = 3, 15.0%) (P < 0.001). The gene expressions of TLR4 and MyD88 were significantly higher in breast cancer than in fibroadenoma and adjacent normal tissues (P < 0.05). The protein expressions of TLR4 and MyD88 were also significantly associated with poor clinical features (P < 0.05). Conclusion: TLR4 and MyD88 expression might be associated with breast cancer growth and regional and distant metastases.

Distinguishing the involved lymph nodes from other tissues during surgery is critical for lymph node dissection. The purpose of this study was to assess the feasibility by using carbon nanoparticles as guidance for lymph node dissection in patients with papillary thyroid carcinoma (PTC).Eighty-one patients were injected with carbon nanoparticles (carbon nanoparticle group), whereas the other 81 patients were not (control group). Routine pathological examination was performed.The lymph node dissection and metastatic lymph node dissection rates of the carbon nanoparticle group were significantly higher than that of the control group. In the carbon nanoparticle group, the number of mistakenly dissected parathyroid gland, the case number of postoperative hypocalcemia, the case number of postoperative hypoparathyroidism, and the recovery time from hypocalcemia were 4, 6, 8, and 2.33 ± 0.58 weeks, respectively, significantly less than 14, 17, 20, 3, and 3.8 ± 0.92 weeks in the control group (p .05).Carbon nanoparticles can be applied to more accurately guide the dissection of lymph nodes during thyroidectomy in patients with PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: 840-845, 2016.

The supervisory software has widely been applied in various areas for many years. This paper introduces the design of supervisory software which is a part of a practical implementation platform for the ethernet-based control systems. The software architecture is presented in which a client/server structure is constructed to deal with the case where there are many users who want to access the system information and even change system parameters online and dynamically, an access control module is designed to make this process controllable and safe, friendly human machine interface (HMI) makes it very easy to configure signals and parameters that need to be monitored or controlled according to the users' demands.