Supplementation of a High-Fat Diet with Pentadecylresorcinol Increases the Representation of Akkermansia muciniphila in the Mouse Small and Large Intestines and May Protect against Complications Caused by Imbalanced Nutrition.

Imbalanced nutrition, such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to change significantly in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) were investigated in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that C15 supplementation in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum in both the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

Ten-year retrospect of the investigation of proximal limbs metastasis in cancer: a multi-center study on survival outcome, limb function status and surgical procedures analysis.

BACKGROUND: The aim of study was to evaluate survival outcome and limb function in cancer patients with proximal limbs metastasis. Associated factors on survival outcome and limb function were identified. The comparative analysis between intramedullary nailing and prosthesis surgery in cancer patients with proximal limb metastasis was performed. METHODS: In this five-center retrospective study, patients diagnosed with limbs metastasis were collected. Descriptive statistics was used and log-rank test was performed to analyze the survival in subgroups. The Cox proportional hazards regression analysis was performed to identify the independent prognostic factors. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate limb function after surgery, and t test or analysis of variance (ANOVA) was utilized in subgroup analysis. RESULTS: A total of 316 patients with limb metastasis were included with mean age at 61.0 years. The most common primary tumor was breast, followed by renal cancer and lung cancer. The median overall survival was 24.0 months and the 1-, 3- and 5-year survival rates were 86.9%, 34.7% and 6.8%, respectively. Primary tumor type, visceral metastasis and chemotherapy were proved to be the independent prognostic factors. The mean Musculoskeletal Tumor Society (MSTS) score was 20.5, significant difference was observed in subgroup of solitary/multiple bone metastasis, with/without pathological fracture, and type of surgery. CONCLUSION: The present study concluded that primary tumor type, visceral metastasis and chemotherapy were three factors affecting the survival of patients. Compared with intramedullary nailing, the patients underwent prosthesis surgery showed better limb function, this procedure should be encouraged in patients with indication.

Clinicomics-guided distant metastasis prediction in breast cancer via artificial intelligence.

BACKGROUND: Breast cancer has become the most common malignant tumour worldwide. Distant metastasis is one of the leading causes of breast cancer-related death. To verify the performance of clinicomics-guided distant metastasis risk prediction for breast cancer via artificial intelligence and to investigate the accuracy of the created prediction models for metachronous distant metastasis, bone metastasis and visceral metastasis. METHODS: We retrospectively enrolled 6703 breast cancer patients from 2011 to 2016 in our hospital. The figures of magnetic resonance imaging scanning and ultrasound were collected, and the figures features of distant metastasis in breast cancer were detected. Clinicomics-guided nomogram was proven to be with significant better ability on distant metastasis prediction than the nomogram constructed by only clinical or radiographic data. RESULTS: Three clinicomics-guided prediction nomograms on distant metastasis, bone metastasis and visceral metastasis were created and validated. These models can potentially guide metachronous distant metastasis screening and lead to the implementation of individualized prophylactic therapy for breast cancer patients. CONCLUSION: Our study is the first study to make cliniomics a reality. Such cliniomics strategy possesses the development potential in artificial intelligence medicine.

Analysis of Single Biomacromolecules and Viruses: Is It a Myth or Reality?

The beginning of the twenty-first century witnessed novel breakthrough research directions in the life sciences, such as genomics, transcriptomics, translatomics, proteomics, metabolomics, and bioinformatics. A newly developed single-molecule approach addresses the physical and chemical properties and the functional activity of single (individual) biomacromolecules and viral particles. Within the alternative approach, the combination of "single-molecule approaches" is opposed to "omics approaches". This new approach is fundamentally unique in terms of its research object (a single biomacromolecule). Most studies are currently performed using postgenomic technologies that allow the properties of several hundreds of millions or even billions of biomacromolecules to be analyzed. This paper discusses the relevance and theoretical, methodological, and practical issues related to the development potential of a single-molecule approach using methods based on molecular detectors.

Therapeutic Efficiency of Proteins Secreted by Glial Progenitor Cells in a Rat Model of Traumatic Brain Injury.

Traumatic brain injuries account for 30-50% of all physical traumas and are the most common pathological diseases of the brain. Mechanical damage of brain tissue leads to the disruption of the blood-brain barrier and the massive death of neuronal, glial, and endothelial cells. These events trigger a neuroinflammatory response and neurodegenerative processes locally and in distant parts of the brain and promote cognitive impairment. Effective instruments to restore neural tissue in traumatic brain injury are lacking. Glial cells are the main auxiliary cells of the nervous system, supporting homeostasis and ensuring the protection of neurons through contact and paracrine mechanisms. The glial cells' secretome may be considered as a means to support the regeneration of nervous tissue. Consequently, this study focused on the therapeutic efficiency of composite proteins with a molecular weight of 5-100 kDa secreted by glial progenitor cells in a rat model of traumatic brain injury. The characterization of proteins below 100 kDa secreted by glial progenitor cells was evaluated by proteomic analysis. Therapeutic effects were assessed by neurological outcomes, measurement of the damage volume by MRI, and an evaluation of the neurodegenerative, apoptotic, and inflammation markers in different areas of the brain. Intranasal infusions of the composite protein product facilitated the functional recovery of the experimental animals by decreasing the inflammation and apoptotic processes, preventing neurodegenerative processes by reducing the amounts of phosphorylated Tau isoforms Ser396 and Thr205. Consistently, our findings support the further consideration of glial secretomes for clinical use in TBI, notably in such aspects as dose-dependent effects and standardization.

Survival Estimation, Prognostic Factors Evaluation, and Prognostic Prediction Nomogram Construction of Breast Cancer Patients with Bone Metastasis in the Department of Bone and Soft Tissue Tumor: A Single Center Experience of 8 Years in Tianjin, China.

Purpose: Bone metastasis in breast cancer remains globally concerned. Accurate survival estimation would be beneficial for clinical decision-making, especially for the patients with potential indications of surgery. Based on a retrospective cohort from China, the study aimed to construct a prognostic prediction nomogram for breast cancer patients with bone metastasis. Methods: Breast cancer patients with bone metastasis diagnosed between 2009 and 2017 in our department were retrospectively selected. The total cohort was divided into construction and validation cohorts (ratio 7 : 3). A nomogram was constructed to predict the probability of survival, and the performance of model was validated. Results: A total of 343 patients were enrolled with 243 and 100 patients in construction and validation cohorts, respectively. The median overall survival for the total cohort was 63.2 (95% CI: 52.4-74.0) months. Elevated ALP (HR = 1.71, 95% CI: 1.16-2.51; P=0.006), no surgery for breast cancer (HR = 2.19, 95% CI: 1.30-3.70; P=0.003), synchronous bone metastasis (HR = 1.98, 95% CI: 1.22-3.22; P=0.006), and liver metastasis (HR = 1.68, 95% CI: 1.20-2.37; P=0.003) were independent prognostic factors for worse survival. The independent predictors and other five factors (including age at diagnosis, ER status, PR status, Her-2 status, and the performance of bisphosphonate) were incorporated to construct the nomogram. The C-index was 0.714 (95% CI: 0.636-0.792) and 0.705 (95% CI: 0.705) in the construction cohort and validation cohort, respectively. All the calibration curves were close to the 45-degree line, which indicated satisfactory calibration. Conclusion: A retrospective study aiming at prognostic estimation of breast cancer patients with bone metastasis was designed. Four independent prognostic factors were identified and a prognostic nomogram was constructed with satisfactory discrimination and calibration. The model could be used in survival estimation and individualized treatment planning.

Racial disparities in bone metastasis patterns and targeted screening and treatment strategies in newly diagnosed lung cancer patients.

Objective: Race disparities exist in bone metastasis (BM) development and survival in lung cancer (LC) patients. The Surveillance, Epidemiology, and End Results (SEER) database was used to investigate different patterns of BM development and survival in different races.Design: LC patients with BM were identified from the database from 2010 to 2014. Risk factors were investigated by univariable and multivariable logistic regression. Potential factors for prognosis were evaluated by univariable and multivariable Cox regression.Results: Asian and Pacific Islander (API) patients presented the highest prevalence of BM (24.6%), followed by white (20.7%) and black patients (19.9%) (χ2 = 78.74; p < .001). After adjusting for the demographic and clinical factors, API race was independently associated with a high risk of BM development. The median survival times for the API, white and black LC patients with BM were 16 months (95% CI: 15.2-16.8), 11 months (95% CI: 10.9-11.1) and 10 months (95% CI: 9.7-10.3), respectively, with significant differences (p < .001). Multivariable Cox regression showed that API race was positively associated with greater overall survival compared with white and black patients. Male gender, larger tumor size, lymph node involvement, lower tumor differentiated grade, and the presence of lung, liver and brain metastases were independently associated with a high risk of developing BM and worse survival with LC across all races. Age, income, insurance and histological types had different impacts on BM among different races.Conclusion: Homogeneous and heterogeneous associated factors for BM were revealed among different races. Individualized screening and treatment should be performed race-specifically.

Synchronous bone metastasis in lung cancer: retrospective study of a single center of 15,716 patients from Tianjin, China.

BACKGROUND: This study aimed to describe the incidence, clinical characteristics, and prognosis of lung cancer patients with synchronous bone metastasis (SBM) and to analyze the prognostic factors of the lung cancer patients with SBM. METHODS: A total of 15,716 lung cancer patients who were diagnosed between 2009 to 2018 in the Tianjin Medical University Cancer Institute and Hospital were retrospectively reviewed. Among them, patients with SBM were checked. Both the demographic and clinical characteristics were included as follows: age, gender, marital status, history of smoking, alcohol consumption, family history of tumor, Karnofsky score, lymph node metastasis, histological type. Besides, laboratory data such as alkaline phosphatase, lactate dehydrogenase, carcinoembryonic antigen, squamous cell carcinoma antigen, cytokeratin-19 fragment, and neuron specific enolase were also included. The log-rank test and multivariate Cox regression analysis were employed to reveal the potential prognostic predictors. A further analysis using the Kaplan-Meier was employed to demonstrate the difference on the prognosis of LC patients between adenocarcinoma and non-adenocarcinoma. RESULTS: Among the included patients, 2738 patients (17.42%) were diagnosed with SBM. A total of 938 patients (34.3%) with SBM were successfully followed and the median survival was 11.53 months (95%CI: 10.57-12.49 months), and the 1-, 2-, and 5-year overall survival rate was 51, 17, and 8%, respectively. Multivariable Cox regression results showed history of smoking and high level of NSE were associated with the poor prognosis, while adenocarcinoma histological type was associated with better survival. CONCLUSION: The prevalence of SBM in lung cancer is relatively high with poor survival. The lung cancer patients with SBM showed diverse prognosis. Among all the pathological types, the division of adenocarcinoma suggested different prognosis of the lung cancer patients with SBM. The present study emphasized the importance of pathological diagnosis on prognostic determinants in lung cancer patients with SBM.

Nomogram for predicting overall survival in colorectal cancer with distant metastasis.

BACKGROUND: Colorectal cancer (CRC) is a major cancer burden, and prognosis is determined by many demographic and clinicopathologic factors. The present study aimed to construct a prognostic nomogram for colorectal cancer patients with distant metastasis. METHODS: Colorectal cancer patients with distant metastasis diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was used to identify independent prognostic factors. A nomogram was constructed to predict survival, and validation was performed. RESULTS: A total of 7099 stage IV colorectal cancer patients were enrolled in the construction cohort. The median overall survival was 20.0 (95% CI 19.3-20.7) months. Age at diagnosis, marital status, race, primary tumour site, tumour grade, CEA level, T stage, N stage, presence of bone, brain, liver and lung metastasis, surgery for primary site and performance of chemotherapy were independent prognostic factors. The nomogram was constructed and the calibration curve showed satisfactory agreement. The C-index was 0.742 (95% CI 0.726-0.758). In the validation cohort (7098 patients), the nomogram showed satisfactory discrimination and calibration with a C-index of 0.746 (95% CI 0.730-0.762). CONCLUSION: A series of factors associated with the survival of CRC patients with distant metastasis were found. Based on the identified factors, a nomogram was generated to predict the survival of stage IV colorectal cancer patients. The predictive model showed satisfactory discrimination and calibration, which can provide a reference for survival estimation and individualized treatment decisions.

Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM. METHODS: Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors. RESULTS: Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1-9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival. CONCLUSIONS: The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.

A Novel Phenylpyrrolidine Derivative: Synthesis and Effect on Cognitive Functions in Rats with Experimental Ishemic Stroke.

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood-brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions.

Early Death Incidence and Prediction in Stage IV Breast Cancer.

BACKGROUND The early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors. MATERIAL AND METHODS Based on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ≤1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed. RESULTS A total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7-78.9%), 75.8% (75.1-76.4%), and 72.3% (71.6-72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5-75.4%), 73.5% (72.0-74.9%), and 68.6% (67.0-70.1%), respectively. CONCLUSIONS Nomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

Bacterial Metabolites of Human Gut Microbiota Correlating with Depression.

Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.

Female sex is associated with a lower risk of bone metastases and favourable prognosis in non-sex-specific cancers.

BACKGROUND: The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM. METHODS: Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis. RESULTS: The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6-3.2%) and 1.8% (95% CI: 1.2-2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11-40 years old, plateaued for patients aged 41-90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75-0.84; p < .001) and a favourable prognosis for respiratory system cancers (pooled HR = 0.81; 95% CI: 0.71-0.92; p < .001). However, no significant associations existed for other cancers. Male non-sex-specific cancer patients and those with male-leaning genetic variations or hormonal status have a greater likelihood of developing BM than female patients. CONCLUSIONS: Female sex was associated with fewer BM in various non-sex-specific cancers, and the effect was constant with changes in age. Female sex showed a protective effect exclusively on the prognosis of respiratory system cancers.

The incidence, associated factors, and predictive nomogram for early death in stage IV colorectal cancer.

PURPOSE: The purpose of the present study was to investigate the incidence and associated factors for early death in stage IV colorectal cancer (CRC) and to construct the predictive nomogram. METHODS: Patients with stage IV CRC, who had been diagnosed between 2010 and 2014 in the Surveillance, Epidemiology, and End Results datasets, were eligible for this retrospective cohort study. The univariable and multivariable logistic regression models were conducted to determine the associated factors for early death (survival time ≤ 3 months). The predictive nomogram was constructed and the internal validation was performed. RESULTS: Ten thousand two hundred sixty-three out of 36,461 (28.1%) eligible patients resulted in all causes of early death (25.8% for cancer-specific early death and 2.3% for non-cancer early death). Advanced age, marital status, right colon, poor differentiation, higher N stage, and bone metastasis were positively associated with all causes of early death, cancer-specific early death, and non-cancer early death, while higher T stage, positive carcinoembryonic antigen, and distant metastases (bone, lung, liver, and brain) were only positively associated with all causes of early death and cancer-specific early death. The calibration curve for all causes of early death, cancer-specific early death, and non-cancer early death showed the prediction curve closely approximated at the 45° line and the areas under the curve were 75.7% (95% CI, 74.9-76.4%), 75.9% (95% CI, 75.1-76.6%), and 76.9% (95% CI, 76.3-77.6%), respectively. CONCLUSIONS: The nomogram was calibrated to predict all causes of early death development, cancer-specific early death development, and non-cancer early death development. These findings can be utilized in early screening and to tailor targeted treatment regimens for stage IV CRC patients.

Epidemiology, tumor characteristics and survival in patients with angiosarcoma in the United States: a population-based study of 4537 cases.

OBJECTIVE: Limited by sample size, angiosarcoma was rarely studied. We aimed to investigate the characteristics and prognosis of angiosarcoma in the National Cancer Institute's Surveillance, Epidemiology and End Results database. METHODS: Patients who were diagnosed with primary angiosarcoma from 1973 to 2014 were extracted from the Surveillance, Epidemiology and End Results database. Kaplan-Meier analysis was used to estimate the overall survival, and the difference between groups was tested by the log-rank test. Multivariate Cox regression analyses were employed to identify prognostic factors for primary angiosarcoma. RESULTS: A total of 4537 patients with angiosarcoma were included with the median age of 69 years. The median overall survival was 82.1 (95% confidence interval: 76.5-87.7) months. Overall 1-, 2- and 5-year survival rates were 55.2 ± 0.7, 41.0 ± 0.7 and 26.3 ± 0.7%, respectively. In the univariate analysis, age, gender, marital status, race, primary site, tumor grade, tumor size, Surveillance, Epidemiology and End Results historic stage and the surgery of primary site were significantly associated with overall survival. Multivariate Cox regression showed that factors including the patients older than 69 years, male, unmarried status, other primary sites, grades (III and IV), tumor size ≥ 5 cm, regional and distant stage and non-surgery were independently associated with poor survival. The results were consistent after excluding the patients in IV stages. CONCLUSIONS: This large population-based study comprehensively described the survival rate and prognostic factors for angiosarcoma in the United States. Age, gender, marital status, primary sites, tumor grade and size and historic stage were determinants of survival, and surgery can improve the prognosis of patients with angiosarcoma.

Advanced Hepatocellular Carcinoma with Bone Metastases: Prevalence, Associated Factors, and Survival Estimation.

BACKGROUND The objective of the present research was to explore the prevalence, risk, and prognostic factors associated with bone metastases (BM) in newly diagnosed hepatocellular carcinoma (HCC) patients. MATERIAL AND METHODS From 36 507 HCC patients who were registered in Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 1263 with BM at the initial diagnosis of HCC from 2010 to 2014. Kaplan-Meier curves and log-rank tests were used to estimate overall survival for different subgroups. Univariate and multivariate logistic and Cox regression analyses were performed to identify risk factors and independent prognostic factors for BM. RESULTS A total of 1567 (4.29%) HCC patients were detected with BM at initial diagnosis. Male sex, unmarried status, higher T stage, lymph node involvement, intrahepatic metastases, and extrahepatic metastases (lung or brain) were positively associated with BM. The median survival of the patients was 3.00 months (95% CI: 2.77-3.24 months). Marital status and primary tumor surgery were independently associated with the better survival. CONCLUSIONS A list of factors associated with BM occurrence and the prognosis of the advanced HCC patients with BM were found. These associated factors may provide a reference for BM screening in HCC and guide prophylactic treatment in clinical settings.

Circulating tumor cells and their advances to promote cancer metastasis and relapse, with focus on glioblastoma multiforme.

In the late stages of their development, cancers can form metastases. Formation of metastases was found to be associated with the capacity of cancer cells to quit the tumor mass and journey through the circulation to distant organs. This cell population is called circulating tumor cells (CTCs). They exhibit several advanced properties such as epithelial-to-mesenchymal transition (EMT) and dormancy that are essential for supporting their survival in the bloodstream, radio- and chemoresistance, their escape from the anti-cancer immune response, and metastasis initiation. CTCs, and especially dormant tumor cells, are responsible for post-surgery tumor recurrence. CTCs were detected in the blood of patients affected with glioblastoma multiforme (GBM)-the most frequent, invasive, and deadly neoplasm among primary brain tumors. The identification of glioblastoma CTCs might have a promising clinical potential for early tumor diagnosis and prognosis. A variety of CTC enrichment and detection techniques have been developed to date. For several epithelial cancers, especially for breast carcinoma, a prognostic value of CTCs was reported. Similar efforts should be performed for GBM to evaluate clinical the significance of CTCs.

Toxicity of iron oxide nanoparticles: Size and coating effects.

Toxicological research of novel nanomaterials is a major developmental step of their clinical approval. Since iron oxide magnetic nanoparticles have a great potential in cancer treatment and diagnostics, the investigation of their toxic properties is very topical. In this paper we synthesized bovine serum albumin-coated iron oxide nanoparticles with different sizes and their polyethylene glycol derivative. To prove high biocompatibility of obtained nanoparticles the number of in vitro toxicological tests on human fibroblasts and U251 glioblastoma cells was performed. It was shown that albumin nanoparticles' coating provides a stable and biocompatible shell and prevents cytotoxicity of magnetite core. On long exposure times (48 hours), cytotoxicity of iron oxide nanoparticles takes place due to free radical production, but this toxic effect may be neutralized by using polyethylene glycol modification.

Diffusion Tensor Imaging in Diagnosis of Post-Traumatic Syringomyelia in Spinal Cord Injury in Rats.

BACKGROUND Post-traumatic syringomyelia (PTS) is a common disease after spinal cord injury (SCI). The present study was performed to evaluate the advantages of diffusion tensor imaging (DTI) in estimating SCI and prognosing PTS in SCI rats. MATERIAL AND METHODS Forty rats were divided into 3 groups based on the extent of the individual SCI and PTS: a control group (n=10), a PTS group (n=8), and an SCI group (n=22). BBB tests were performed preoperatively and postoperatively at (1 d, 3 d, 5 d, 1 w, 2 w, 1 w, 2 w, 3 w, 4 w, 5 w, and 6 w). MRI T2 scanning was conducted postoperatively at (1 w, 2 w, 3 w, 4 w, 5 w, 6 w). DTI and diffusion tensor tractography were used for analyzing neuro-fiber changes after SCI. RESULTS BBB scoring showed no differences between the PTS group and SCI group (P<0.05). PTS was found in 8 rats after SCI. MRI showed PTS formation in 3 rats at 2 w after SCI, and 5 rats showed PTS formation at postoperative 3w after SCI. Compared with the control group, ADC showed significant increase in both the PTS group (P<0.05) and the SCI group (P<0.05), FA showed significant decreases in the PTS (P<0.05) and SCI (P<0.05) groups. Compared with the SCI group, the PTS group showed an increase in ADC, but no statistical difference was found in ADC (P>0.05). The PTS group showed a significant increase in FA (P<0.05). CONCLUSIONS The combination of diffusion tensor imaging and diffusion tensor tractography has characteristics of high-sensitivity and quantitation for PTS prognosis. FA is predictive in the prognosis of PTS formation after SCI.