Interoperable Nanoparticle Sensor Capable of Strain and Vibration Measurement for Rotor Blade Monitoring.

Recent advances in nanomaterials technology create the new possibility to fabricate high performance sensors. However, there has been limitations in terms of multivariate measurable and interoperable sensors. In this study, we fabricated an interoperable silver nanoparticle sensor fabricated by an aerodynamically focused nanomaterial (AFN) printing system which is a direct printing technique for inorganic nanomaterials onto a flexible substrate. The printed sensor exhibited the maximum measurable frequency of 850 Hz, and a gauge factor of 290.62. Using a fabricated sensor, we evaluated the sensing performance and demonstrated the measurement independency of strain and vibration sensing. Furthermore, using the proposed signal separation algorithm based on the Kalman filter, strain and vibration were each measured in real time. Finally, we applied the printed sensor to quadrotor condition monitoring to predict the motion of a quadrotor.

Evaluation of the Impacts of Formulation Parameters on the Pharmacokinetics and Bioequivalence of Risperidone Orodispersible Film: a Physiologically Based Pharmacokinetic Modeling Approach.

The purpose of this study was to investigate the impacts of the formulation parameters on the pharmacokinetics and bioequivalence of risperidone orodispersible film (ODF) using physiologically based pharmacokinetic model. The pharmacokinetic profiles of two risperidone ODFs, which exhibit different in vitro dissolution, were examined in Beagle dogs after supralingual administration. Subsequently, a physiologically based pharmacokinetic (PBPK) model was constructed to evaluate the in vivo performance of risperidone ODF. The parameter sensitivity analysis (PSA) was used to access the impacts of formulation parameters on the pharmacokinetics of risperidone. Moreover, the validated PBPK model was applied to predict human pharmacokinetic profiles and examine the bioequivalence of these two ODFs. These two ODFs displayed similar risperidone pharmacokinetic profiles in dogs. The parameter sensitivity analysis indicated that the changes in the solubility, particle size, particle density, and diffusion coefficient did not have obvious influence on the in vivo properties of risperidone ODF. Alternation of the in vitro complete dissolution time in water from 15 to 30 min led to a 30% decrease in Cmax and 20% of increase in Tmax. AUC0-∞ would be decreased if risperidone was not fully released within 1 h. As both ODFs completely released risperidone within 15 min, the difference in the extent of in vivo absorption, intestinal regional absorption location, and plasma concentration-time curves between these two ODFs was almost negligible. Consequently, a bioequivalence was foreseen in humans. The in vitro cumulative dissolution percentage in water at 15 min was found to be the major determinant on the in vivo properties of risperidone ODF. PBPK modeling appears to be an innovative strategy to guide the development of risperidone ODF.

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway.

BACKGROUND: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. METHODS: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. RESULTS: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. CONCLUSION: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

Comparison of laparoscopic versus open gastrectomy for advanced gastric cancer: an updated meta-analysis.

BACKGROUND: Laparoscopic gastrectomy (LG) has been used as an alternative to open gastrectomy (OG) to treat early gastric cancer. However, the use of LG for advanced gastric cancer (AGC) has been in debate. METHODS: Literature retrieval was performed by searching PubMed, EMBASE, and the Cochrane library up to July 2014. Potential studies comparing the surgical effects between LG with OG were evaluated and data were extracted accordingly. Meta-analysis was carried out using RevMan. The pooled risk ratio and weighted mean difference (WMD) with 95 % confidence interval (95 % CI) were calculated. RESULTS: Overall, 26 studies were included in this meta-analysis. LG had some advantages over OG, including shorter hospitalization (WMD, -3.63, 95 % CI, -4.66 to -2.60; P < 0.01), less blood loss (WMD, -161.37, 95 % CI, -192.55 to -130.18; P < 0.01), faster bowel recovery (WMD, -0.78, 95 % CI, -1.05 to -0.50; P < 0.01), and earlier ambulation (WMD, -0.95, 95 % CI, -1.47 to -0.44; P < 0.01). In terms of surgical and oncological safety, LG could achieve similar lymph nodes (WMD, -0.49, 95 % CI, -1.78 to 0.81; P = 0.46), a lower complication rate [odds ratio (OR), 0.71, 95 % CI, 0.59 to 0.87; P < 0.01], and overall survival (OS) and disease-free survival (DFS) comparable to OG. CONCLUSIONS: For AGCs, LG appeared comparable with OG in short- and long-term results. Although more time was needed to perform LG, it had some advantages over OG in achieving faster postoperative recovery. Ongoing trials and future studies could help to clarify this controversial issue.

[Expression and clinical significance of GRHL2 in colorectal cancer].

OBJECTIVE: The purpose of this study was to detect the expression of GRHL2 in colorectal cancer (CRC) tissues, and to assess the relationship between GRHL2 expression and clinicopathological features. METHODS: Immunohistochemistry was used to examine GRHL2 in 75 CRC tissues. GRHL2 mRNA and protein levels in the CRC tissues were also analyzed by qRT-PCR and Western blot. The relationship between GRHL2 and clinicopathological features was assessed by Pearson's chi-square (χ(2)) test. RESULTS: Positive immunoreactivity for GRHL2 was detected in the nuclei of CRC cells. GRHL2 expression was increased in CRC tissues compared withthat in the paired non-tumor tissues (61.3% vs. 44.0%, P<0.01). Moreover, qRT-PCR results showed that the relative expression level of GRHL2 mRNA in the colorectal cancer tissue was (2.64±0.35), significantly higher than that of normal mucosa tissue (1.19±0.23, P<0.001). The expression level of GRHL2 mRNA was higher in stage III-IV patients (2.84±0.36) than that of stage I-II cases (2.31±0.32, P<0.05). Western blot results also showed that the expression level of GRHL2 protein in the colorectal carcinoma tissue was significantly higher than that in the normal mucosa (P<0.05). GRHL2 expression was positively correlated with tumor size, TNM stage and Ki-67 (P<0.05, respectively). CONCLUSION: Taking together, our findings demonstrate that GRHL2 is overexpressed in CRC, and plays an important role in the progression of CRC.

miR-320a suppresses colorectal cancer progression by targeting Rac1.

MicroRNAs (miRNAs) have emerged as critical epigenetic regulators involved in cancer progression. miR-320a has been identified to be a novel tumour suppressive miRNA in colorectal cancer (CRC). However, the detailed molecular mechanisms are not fully understood. Here, we reported that miR-320a inversely associated with CRC aggressiveness in both cell lines and clinical specimens. Functional studies demonstrated that miR-320a significantly decreased the capability of cell migration/invasion and induced G0/G1 growth arrest in vitro and in vivo. Furthermore, Rac1 was identified as one of the direct downstream targets of miR-320a and miR-320a specifically binds to the conserved 8-mer at position 1140-1147 of Rac1 3'-untranslated region to regulate Rac1 protein expression. Over-expression of miR-320a in SW620 cells inhibited Rac1 expression, whereas reduction of miR-320a by anti-miR-320a in SW480 cells enhanced Rac1 expression. Re-expression of Rac1 in the SW620/miR-320a cells restored the cell migration/invasion inhibited by miR-320a, whereas knockdown of Rac1 in the SW480/anti-miR-320a cells repressed these cellular functions elevated by anti-miR-320a. Conclusively, our results demonstrate that miR-320a functions as a tumour-suppressive miRNA through targeting Rac1 in CRC.

Oncological superiority of extralevator abdominoperineal resection over conventional abdominoperineal resection: a meta-analysis.

PURPOSE: The oncological superiority, i.e., lower circumferential resection margin (CRM) involvement, lower intraoperative perforation (IOP), and local recurrence (LR) rates, of extralevator abdominoperineal resection (EAPR) over conventional abdominoperineal resection (APR) for rectal cancer is inconclusive. This meta-analysis systematically compared the rates of CRM involvement, IOP, and LR of rectal cancer patients treated by EAPR and APR, respectively. METHODS: An electronic literature search of MEDLINE, EMBASE, and Cochrane Library through May 2013 was performed by two investigators independently to identify studies evaluating the CRM involvement, IOP, and LR rates of EAPR and APR, and search results were cross-checked to reach a consensus. Data was extracted accordingly. A Mantel-Haenszel random effects model was used to calculate the odds ratio (OR) with 95 % confidence intervals (95 % CI). RESULTS: Six studies with a total of 881 patients were included. Meta-analysis of CRM involvement and IOP data from all six studies demonstrated significant lower CRM involvement (OR, 0.36; 95%CI, 0.23-0.58; P < 0.0001) and IOP (OR, 0.31; 95%CI, 0.12-0.80; P = 0.02) rates of EAPR. Data from four studies also showed that EAPR was associated with a lower LR rate than APR (OR, 0.27; 95%CI, 0.08-0.95; P = 0.04). No differences of between-study heterogeneity or publication bias were seen in any of the meta-analyses. CONCLUSIONS: Extralevator abdominoperineal resection could achieve better CRM involvement outcome and lower IOP and LR rates, demonstrating an oncological superiority over conventional abdominoperineal resection.

E2A suppresses invasion and migration by targeting YAP in colorectal cancer cells.

BACKGROUND: E2A gene, which encodes two basic helix-loop-helix (bHLH) transcription factors E12 and E47, has been identified as regulator of B lymphoid hematopoiesis and suppressor of lymphoma. E47 protein was found to decrease E-cadherin expression and induce epithelial-mesenchymal transition (EMT). However, the role of E2A in colorectal cancer (CRC) metastasis is still elusive. METHODS: qRT-PCR and semi-qRT-PCR were performed to determine mRNA level of E2A in CRC specimens and colorectal cancer cells. RNAi was employed to downregulate E2A expression and subsequent protein level change was evaluated by immunoblot. Cell invasion and migration capacity were detected by transwell assay using cell culture inserts with or without basement membrane matrix, respectively. RESULTS: E2A expression was decreased in metastatic CRC tissues. Invasion and migration assays showed downregulation of E2A increased metastatic capacity of CRC cells while forced expression of E12 or E47 could offset this effect. Both E12 and E47 suppressed EMT induced by E2A downregulation. Moreover, Yes-Associated Protein (YAP) was a downstream target of E2A and suppression of YAP inhibited the pro-migration/invasion of E2A deficiency. CONCLUSION: Our results suggest that E2A suppresses CRC cell metastasis, at least partially if not all, by inhibiting YAP expression.

AL360181.1 promotes proliferation and invasion in colon cancer and is one of ten m6A-related lncRNAs that predict overall survival.

Background: N6-methyladenosine (m6A) exerted a pivotal role in colon cancer. Nevertheless, the long non-coding RNAs (lncRNAs) associated with this process have yet to be elucidated. Methods: The open-access data used for analysis was downloaded from The Cancer Genome Atlas (TCGA) database for analysis, employing the R software for computational evaluations. The RNA level of specific molecules was assessed using the quantitative real-time PCR. CCK8, colony formation and transwell assay were used to evaluate the proliferation, invasion and migration ability of colon cancer cells. Results: Here, we identified the m6A regulators from TCGA data and subsequently pinpointed lncRNAs with a -Cor- > 0.3 and P < 0.05, categorizing them as m6A-associated lncRNAs. Moreover, we formulated a prognosis signature rooted in ten m6A-related lncRNAs, consisting of AL360181.1, PCAT6, SNHG26, AC016876.1, AC104667.2, AL114730.3, LINC02257, AC147067.1, AP006621.3 and AC009237.14. This signature exhibited notable predictive accuracy in gauging patient survival. Immune-related evaluations revealed varied immune cell infiltration patterns across different risk groups, with our findings suggesting superior immunotherapy response in low-risk patients. Biological enrichment analysis indicated that the high-risk patients had a higher activity of multiple carcinogenic pathways, including glycolysis. The previously unreported lncRNA, AL360181.1, displayed a connection to glycolytic activity and diminished survival rates, warranting further investigation. The result indicated that AL360181.1 was correlated with more aggressive clinical characteristics. Immune infiltration assessments found AL360181.1 to have a positive correlation with Tcm infiltration, but an inverse relationship with entities like Th2 cells, T cells, neutrophils and macrophages. Biological enrichment analysis indicated that the pathways of WNT/ß-catenin, pancreas beta cells, hedgehog signaling and some metabolism pathways were upregulated in high AL360181.1 patients. In vitro experiments showed that AL360181.1 was upregulated in the colon cancer cells. Moreover, AL360181.1 significantly promotes the proliferation, invasion and migration of colon cancer cells. Conclusions: Our results can provide direction for future studies on m6A-related lncRNA in colon cancer.

Effect of fiber entanglement in chopped glass fiber reinforced composite manufactured via long fiber spray-up molding.

Long Fiber Spray-up Molding (LFSM) deviates from the conventional approach in liquid composite molding (LCM) processes by utilizing extremely long chopped strands of fibers as the primary reinforcement material in its fabrication process. In LFSM, chopped fibers are impregnated with resin that is sprayed vertically downwards before reaching the mold surface. The spraying mechanism is mounted on an actuator, which is capable of spraying freely in any specified pattern or direction. Under LFSM, it is extremely difficult to fabricate a composite part with uniformly distributed fiber content throughout its volume. The consequences of the non-uniform fiber volume distribution arise from the fiber entanglement as the length of the fiber reaches up to 100 mm in LFSM. In this study, the effect of fiber entanglement during LFSM was analyzed through various approaches. This included measuring the coefficient of friction between fibers in contact and examining the correlation between fiber lengths and the number of intersections. Furthermore, the viscoelastic properties of the uncured composite part were assessed by experimenting with the influence of viscosity on fiber length during compression molding. The results were then computed, modeled, and visualized in MATLAB, considering variations in viscosity and fiber length, both before and after compression molding.

Genomic and immunological features of microsatellite instability in colon cancer.

Microsatellite instability (MSI) is closely related to the prognosis and therapy response of colon cancer. Colon cancer patients with MSI show resistance to 5-Fluorouracil (5-FU) but sensitivity to immunosuppressive checkpoint inhibitors (ICIs). The relevant mechanism behind the opposite response remains unclear. Multi-omics research data of colon cancer patients were acquired from The Cancer Genome Atlas (TCGA) database, GEO database, and DAFI dataset. Transcriptome data were normalized to gene expression data through the R software package "Limma". Somatic mutations data were analyzed and visualized through the R software package "maftools". CIBERSORT algorithm was used to estimate the relative proportion of 22 infiltrating immune cell types. We demonstrated MSI patients showed both overexpressed immune checkpoints (mRNA level) and activated tumor-infiltrating lymphocytes (TILs), which may explain the satisfying response of ICIs. The additionally, we also demonstrated MSI promoted the mRNA expression of thymidylate synthase (TYMS) through regulating its copy number variation. As a main target of 5-FU, overexpressed TYMS promoted the resistance of 5-FU. Furthermore, we demonstrated MSI patients showed significantly increased somatic mutations compared with microsatellite stability (MSS) patients, except APC, TP53, and KRAS mutations. The substitutions and location of somatic mutations in different genes were at variance between MSS and MSI patients. In conclusion, our research determined mechanisms of MSI associated treatment response, and may provide potential value for improving the survival of colon cancer patients.

Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy.

Autophagy plays a key role in colorectal cancer (CRC) development and reduces the sensitivity of CRC cells to treatment. The present study reported a novel tumor­suppressive role for autophagy, which was demonstrated to be regulated through the novel oncogene neurotrophin­4 (NTF4). NTF4 was significantly overexpressed in tumor tissue compared with non­tumor mucosa, and the upregulation of NTF4 in CRC was associated with poor overall survival and advanced TNM stage. The genetic knockdown of NTF4 using short hairpin RNA in CRC cells prevented epithelial­to­mesenchymal transition and activated autophagy; this was regulated through the interaction between autophagy­associated gene 5 (Atg5) and the mitogen­activated protein kinase pathway. In addition, the knockdown of NTF4 inhibited cell invasion, migration, proliferation and colony formation, and promoted cell cycle arrest. Treatment of the cells with the autophagy inhibitor chloroquine (CQ) rescued these functions and promoted cell invasion, migration, proliferation and colony formation. Finally, the knockdown of NTF4 inhibited the growth of subcutaneous xenografts in Balb/c­nu mice. In conclusion, these findings suggested that NTF4 may be a diagnostic marker associated with the overall survival and progression of patients with CRC. NTF4 was found to promote tumorigenesis and CRC development through autophagy regulation.

Interleukin 1ß/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy.

Interleukin (IL)­1ß is a member of the IL­1 family of proteins. IL­1 receptor antagonist (IL­1RA) is an agent that binds to the IL­1 receptor, preventing IL­1 from transmitting signals to cells. The present study aimed to identify the role of the IL­1ß/1RA axis in epithelial­mesenchymal transition (EMT), cell invasion, migration, proliferation and clone formation in colorectal cancer (CRC) and to determine its underlying mechanisms of action. Significantly increased expression of both IL­1ß and IL­1RA was identified in CRC patient data uploaded in The Cancer Genome Atlas database, and in tumor tissues when compared with matched control tissue. High expression of IL­1ß was associated with an increased rate of overall survival and recurrence­free survival. Further research revealed that the IL­1ß gene was co­expressed with the IL­1RA gene in tumors of CRC patients. It was additionally determined that recombinant human (rh)IL­1ß suppressed autophagy as well as EMT in HCT­116 cells compared with control­treated cells, whereas rhIL­1RA exhibited the opposite effect. In addition, autophagy activator rapamycin (RAPA) rescued the inhibition of EMT in rhIL­1ß­treated HCT­116 cells. Moreover, rhIL­1ß inhibited cell invasion, migration, proliferation and colony­formation ability, when compared with a control treatment. Compared with a control treatment rhIL­1RA promoted cell invasion, migration, proliferation, but had no effect on clone formation ability. Furthermore, both rhIL­1RA and RAPA rescued inhibition of cell invasion, migration and clone formation ability in rhIL­1ß­treated HCT­116 cells. RAPA, but not rhIL­1RA, rescue inhibited proliferation in rhIL­1ß­treated HCT­116 cells compared with controls. In addition, it was confirmed that rhIL­1ß inhibited the growth of subcutaneous xenografts in nude mice, when compared with control treatments. These results indicated that upregulation of the IL­1ß/1RA axis in CRC regulated EMT, cell invasion and migration, proliferation and clone formation via autophagy.

Stretchable Biaxial and Shear Strain Sensors Using Diffractive Structural Colors.

Structural colors that can be changed dynamically, using either plasmonic nanostructures or photonic crystals, are rapidly emerging research areas for stretchable sensors. Despite the wide applications of various techniques to achieve strain-responsive structural colors, important factors in the feasibility of strain sensors-such as their sensing mechanism, stability, and reproducibility-have not yet been explored. Here, we introduce a stretchable, diffractive, color-based wireless strain sensor that can measure strain using the entire visible spectrum, based on an array of cone-shaped nanostructures on the surface of an elastomeric substrate. By stretching or compressing the substrate, the diffractive color can be tuned according to the changing grating pitch. Using the proposed method, we designed three types of strain-sensing modes: large-deformation (maximum 100%) tensile strain, biaxial 2D strain, and shear strain (maximum 78%). The strain sensors were fabricated, and applicability to strain-sensing was evaluated.

Upregulation of interleukin­17F in colorectal cancer promotes tumor invasion by inducing epithelial­mesenchymal transition.

Interleukin­17F (IL­17F) is a member of the IL­17 family of proteins. Previous studies concerning IL­17F have mainly focused on its proinflammatory responses, whereas the present study explored its role as an oncogene in colorectal cancer (CRC). The present study investigated the expression of IL­17F in 69 patients with CRC. IL­17F was significantly overexpressed in tumor mucosa compared with that in the paired non­tumor mucosa. Furthermore, several studies from Gene Expression Omnibus (GEO) databases were analyzed to assess the association between IL­17F and overall survival and relapse­free survival time. Recombinant human IL­17F protein (rhIL­17F) and anti­IL­17F antibody were used to study the effect of IL­17F on the CRC cell line HCT­116 in vitro. According to the results of Transwell and wound healing assays, rhIL­17F promoted HCT­116 cell migration and invasion which was mediated by inducing epithelial­mesenchymal transition (EMT), whereas anti­IL­17F inhibited EMT.

GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition.

Our previous study has demonstrated that knockdown of Grainyhead-like 2(GRHL2) in colorectal cancer (CRC) cells inhibited cell proliferation by targeting ZEB1. This study aimed at researching whether knockdown of GRHL2 promoted CRC progression and metastasis via inducing epithelial-mesenchymal transition (EMT). GRHL2-upregulated SW-620/GRHL2+ and GRHL2-knockdown HCT116/GRHL2-KD, HT29/GRHL2-KD cells and their control cells were generated. The morphological changes after overexpression and knockdown GRHL2 were observed. qRT-PCR, Western blotting, and Immunofluorescence were used to detect EMT markers: E-cadherin, Vimentin, p-catein, ZO-1 and ZEB1 expression. Then, sh-ZEB1 was transfected to GRHL2 knockdown cells to research the relationship between GRHL2 and ZEB1. Transwell and wound healing assays were further performed to detect the impact of GRHL2 on invasion and migration in vitro. CRC cells were injected into mice tail vein to verify the impact of GRHL2 on CRC metastasis. Morphological change of mesenchymal-epithelial transition (MET) could be observed in SW620/GRHL2+ cell. The expression of epithelial markers: E-cadherin, ß-catenin, ZO-1 were up-regulated, while mesenchymal markers: Vimentin was decreased. Meanwhile, opposite EMT morphological change could be observed in HCT116/GRHL2-KD cell, accompanied by reverse change of E-cadherin, ß-catenin, ZO-1, and Vimentin. The expression level of GRHL2 and ZEB1 was found negative in both SW620/GRHL2+ and HCT116/GRHL2-KD cells. Knockdown of ZEB1 by siRNA in HCT116/GRHL2-KD and HT29/GRHL2-KD could upregulate expression of E-cadherin and GRHL2. GRHL2 knockdown also promoted migration, invasion in vitro and CRC metastasis in mice model. In conclusion, GRHL2/ZEB1 axis inhibits CRC progression and metastasis via oppressing EMT.

Analysis of risk factors for colon cancer progression.

Purpose: This study aimed to find risk factors for colon cancer progression with bioinformatics methods, and validated by clinical patients. Methods: Differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were extracted from The Cancer Genome Atlas (TCGA) database using R software, amounted to 8,051. DEGs between pathologic stage I+II and stage III+IV amounted to 373, and were compared with DEGs of cancer/normal analyzed above to get the intersection of both. Ninety-six intersected DEGs were identified and defined as progressive DEGs of colon cancer. Then these 96 progressive DEGs were studied by Gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis using the DAVID database and visualizing by R software. A protein-protein interaction (PPI) network and functional modules were established using the STRING database. Further, an overall survival (OS) curve was drawn via the GEPIA website based on the CGA database and six progressive DEGs were found to be involved with OS of colon cancer patients. The Linkedomics website was used for detailed analysis of specific subsets of TNM. Results: Pregnancy specific glycoprotein (PSG), vitamin digestion, and absorption were confirmed to promote the progression of colon cancer. Furthermore, NTF4 was found to be associated with both OS and each subset of TNM; therefore, defined as a key risk factor for colon cancer progression. Further analysis of NTF4 expression using clinical data showed it acted as a key risk factor and diagnosis marker for colon cancer progression. Conclusion: NTF4 is a risk factor contributing to colon cancer progression and associated with overall survival.

Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film.

OBJECTIVE: The aim of the present study was to investigate the absorption routes as well as the potential application of the oral transmucosal delivery of risperidone orodispersible film (ODF) using physiologically based pharmacokinetic modeling. METHODS: The pharmacokinetic study after intragastric (i.g.), supralingual, and sublingual administration of risperidone ODF was conducted in Beagle dogs. Then a mechanic absorption model which combined Oral Cavity Compartment Absorption and Transit (OCCAT) model with Advanced Compartment Absorption and Transit (ACAT) model for predicting the absorption routes of risperidone ODF in vivo was constructed using GastroPlus™. A sensitivity analysis was performed to investigate the impact of oral residence time on the in vivo absorption of risperidone ODF. Based on the fraction of intraoral absorption, the potential of the oral transmucosal delivery of risperidone were predicted. RESULTS: There were no statistical differences in the AUC0-t (P = 0.4327), AUC0-∞ (P = 0.3278), Cmax (P = 0.0531), and Tmax (P = 0.2775) values among i.g., supralingual, and sublingual administration of risperidone ODF in Beagle dogs. The predicted absorption percentage via oral mucosa at oral residence time of 2 min, 5 min, and 10 min was 7.0%, 11.4%, and 19.5%, respectively. No obvious difference was observed for the bioavailability of risperidone ODF within 10 min of oral residence time. The PBPK absorption model for risperidone could be simplified to include ACAT model solely. CONCLUSION: The main absorption route for risperidone ODF was the gastrointestine. The absorption percentage via oral mucosa was almost negligible due to the physicochemical properties of risperidone although ODF dissolved completely in the oral cavity of Beagle dogs within 2 min.

[Assessment of energy expenditure and body composition in cancer patients].

OBJECTIVE: To demonstrate the changes of resting energy expenditure (REE), substrate metabolism and body composition in cancer patients. METHODS: From September 2004 to March 2008, REE, carbohydrate oxidation (CO) and fat oxidation (FO) in 936 cancer patients and 840 control subjects were measured by indirect calorimetry. Bioelectrical impedance appliance was applied to assess intracellular fluid, extracellular fluid, fat mass (FM) and fat free mass (FFM) in the two groups. RESULTS: No difference in REE was found between the cancer patients and non-cancer patients [(1452.2 +/- 196.4) kcal/d vs. (1429.5 +/- 182.6) kcal/d, P = 0.136]. But REE/FFM and REE/pREE were elevated in cancer patients than in controls (all P < 0.05). Of the cancer patients, 48.6% were hypermetabolic, 42.9% normal and 8.5% hypometabolic, while those were 22.5%, 58.5% and 19.0% in controls. Cancer patients had higher FO [(77.8 +/- 11.3) g/min vs. (67.1 +/- 12.1) g/min, P = 0.000], lower CO and npRQ [(68.7 +/- 10.5) g/min vs. (88.8 +/- 12.1) g/min, P = 0.000; 0.782 +/- 0.012 vs. 0.810 +/- 0.014, P = 0.000]. Cancer patients exhibited lower FM and FFM [(14.9 +/- 4.5) kg vs. (18.4 +/- 5.2) kg, P = 0.000; (44.4 +/- 7.2) kg vs. (46.1 +/- 8.1) kg, P = 0.008]. CONCLUSIONS: Elevated REE is common in cancer patients. Substrate metabolism of the cancer patients features in increased FO, decreased CO and npRQ, which is correlated with the elevated REE. FM and FFM loses in proportion in cancer patients.