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Background Radiotherapy is a viable treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, radiation resistance is an issue that needs to be addressed. In this context, cumulative evidence supports the functional roles of a variety of RNA or proteins in radioresistance, and suggests that the modulation of their expression may constitute a novel radiosensitization approach. Here, we investigated the ability of collectrin (CLTRN) to enhance the radiosensitivity in HCC patients for the first time. Methods Transcriptome sequencing technology (RNA-seq technology) was used to analyze the transcription-level changes in the genes from the HepG2 cells before and after X-ray irradiation. Combining the results with the HCC tissue RNA-seq data, we determined the ultimate target gene through bioinformatics analysis and cellular verification. A series of cellular and molecular biology techniques were applied in vitro and in vivo to confirm whether CLTRN can enhance radiosensitivity in HCC cells. Subsequently, the downstream action mechanism, the upstream transcription factor, and the interaction proteins of CLTRN were determined. Results First, we confirmed the association between CLTRN and radiosensitivity. We observed that CLTRN overexpression led to a significant reduction in the proliferation, migration, and invasion potential of X-ray-irradiated HCC cells, whereas no observable effect was exerted on cell cycle and apoptosis. The same results were observed in nude mice in vivo. Investigation of the gene regulatory mechanism revealed that the genes analyzed at transcriptome level after CLTRN overexpression were mostly enriched in the glutathione metabolic pathway. As glutathione metabolism forms a vital link in ferroptosis, we surmised that CLTRN is associated with ferroptosis. This was confirmed through the detection of cellular iron, ROS level determination, transmission electron microscopy, and monitoring of ferroptosis-related protein indicators. Lastly, we investigated whether nuclear respiratory factor 1 (NRF1) is the upstream transcription factor of CLTRN, and whether dihydrolipoamide dehydrogenase (DLD) and members of the RAS oncogene family (RAN) are its interacting proteins. Conclusion Our results indicate that CLTRN is a vital regulator of radiation sensitivity and could serve as a novel therapeutic target or prognostic marker in HCC treatment.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Because of the relatively chemotherapy-refractory nature of HCC and significant potential poor hepatic reserve, chemotherapy has not been used consistently in the treatment of HCC. Effective new drugs for HCC are urgently needed. Teriflunomide, which was approved for the treatment of relapsing forms of multiple sclerosis (MS), has been identified as a potential antineoplastic drug. Long noncoding RNAs (lncRNAs) are a novel class of RNA molecules defined as transcripts longer than 200 nucleotides that lack protein coding potential. In this study, we investigated the ability of teriflunomide to act as an antineoplastic drug by examining the effects of teriflunomide treatment on HCC cells. Teriflunomide strongly inhibited the proliferation of HCC cells, induced cell apoptosis and induced cell accumulation in S phases of the cell cycle. LncRNA and mRNA expression profiles of HCC cells treated with teriflunomide compared with controls were performed by using microarray analysis. For comparison, the differentially expressed mRNAs were annotated by using gene ontology (GO) and pathway analyses. The microarray revealed that 2085 lncRNAs and 1561 mRNAs differed in the cells treated with teriflunomide compared with controls. Several GO terms including protein folding, mitochondrial outer membrane, transmembrane receptor protein phosphatase activity, negative regulation of cellular biosynthetic process, DNA packaging complex, and receptor signaling protein activity were enriched in gene lists, suggesting a potential correlation with the action mechanism of teriflunomide. Pathway analysis then demonstrated that JAK-STAT signaling pathway may play important roles in the cell apoptosis induced by teriflunomide. Co-expression network analysis indicated that a number of lncRNAs and mRNAs were included in the co-expression network, and p34710_v4 is the lncRNA with highest degree. Then the mRNAs associated with those differentially expressed lncRNAs were also annotated by using gene ontology (GO) and pathway analyses. The pathway analyses shows that teriflunomide significantly inhibited cell proliferation and promoted cell apoptosis partly by participating in Wnt signaling pathways. These findings suggest that teriflunomide could be a potential drug for chemotherapy and molecularly targeted therapies of HCC.

Background. Members of the formin-like gene (FMNL) family are required for cytoskeleton-related processes, and their expressions are implicated to the progression of a multitude of malignancies. However, there are insufficient studies on transcription factors and promising prognosis benefit of FMNLs during the genesis of breast cancer (BrCa). Methods. The transcriptional levels of FMNL family members in primary BrCa tissues and their association with intrinsic subclasses were analyzed using the UALCAN database. Then, the prognostic values of FMNLs in BrCa patients were investigated via the Kaplan-Meier plotter. Moreover, the correlations between FMNL expression levels and immune infiltrations were analyzed using the TIMER database. In addition, the expression patterns of FMNLs in BrCa were investigated by single-cell RNA-sequencing (scRNA-seq) analysis and were validated by immunohistochemistry (IHC) staining. Results. The transcriptional level of FMNL1 was shown to be considerably increased in BrCa. It is surprising that the transcriptional quantities of FMNL2 and FMNL3 were substantially reduced. In addition, during the comparison of several BrCa subclasses, FMNL1 and FMNL2 mRNA levels of patients with HER2-positive and triple-negative BrCa subclasses increased, while FMNL3 mRNA levels reduced. With the processions of experimentation, high FMNL1 expression was hopefully linked to well clinical outcome, while high FMNL2 expression predicted poor prognosis. Moreover, FMNL1 was highly expressed in tumor-infiltrating immune cells (TIICs) in tumor tissues. Last but not least, FMNL1 was highly expressed in TIICs and served as a gene marker for TIICs. Conclusions. The fact and result which we analyzed demonstrate FMNL1 as a diagnostic marker for TIICs by comprehensively elucidating the expression patterns and changeable prognostic implications of FMNLs in BrCa clinical applications.

Purpose Evaluating the fitness accuracy and retentive force of cobalt-chrome (Co-Cr) alloy clasps fabricated using the selective laser melting (SLM) technique. Methods Premolar and molar abutment models with a 0.5-mm undercut depth, 1.5-mm-thick occlusal rest seats, and guiding planes were designed and fabricated using a milling machine. On these models, Akers clasps with 0.25- and 0.5-mm undercut depths were designed and fabricated with SLM and a traditional lost wax casting method. Based on the manufacturing methods, abutment types, and undercut depths, the clasps were divided into eight groups (10 per group). The fitness accuracy of the clasps was evaluated by measuring the gap distance between the clasps and abutments using a silicone film method. The initial retentive force and changes in retention up to 7,200 insertion/removal cycles of the clasps were also measured. The data were analyzed using multiple linear regression, paired t-tests, and one-way ANOVA (α=0.05). Results For both the SLM and cast clasps, the fitness accuracy of the rest was greater than that of the clasp tip and shoulder. No significant difference was found in the fitness accuracy between the SLM and cast clasps, regardless of the abutment type and undercut depth before or after insertion/removal cycles (p>0.05). There was also no significant difference in the initial retentive force between the SLM and cast clasps (p>0.05). After 7,200 insertion/removal cycles, the SLM clasp exhibited a greater residual retentive force (p Conclusion The SLM technique for manufacturing the clasps of removable partial dentures has promising clinical applications.

Background Liver ischemia and reperfusion (I/R) is a common but severe clinical problem. Previous studies have revealed that the expression level of β-arrestin2 affects serum deprivation (SD)-induced cell apoptosis and was involved in lipopolysaccharide (LPS) stimulated TLR4 signaling pathway. However, little is known about β-arrestin2 in liver apoptosis and immune response induced by I/R. Methods A non-lethal model of segmental (70%) hepatic ischemia was utilized. Histology examination, cell apoptosis and cytokine levels were measured using H&E staining, TUNEL assay, and ELISA, respectively. Apoptosis-related protein and gene level of cytokines were respectively detected using Western blot and Real-time PCR. Results Our data showed that knockout (KO) of β-arrestin2 gene significantly deteriorated the injury of liver caused by I/R according to liver histology, higher serum liver enzyme, and increased level of cell apoptosis. β-arrestin2 KO could result in increased level of apoptosis related protein and decreased level of Akt phosphorylation. Furthermore, decreased levels of Bcl-2 and Bad phosphorylation, but increased level of Bax were found in β-arrestin2 KO group. In addition, the levels of p-ERK1/2, p-p38MAPKs, and p-NF-κB in β-arrestin2 KO group were significantly higher than that in WT group. Conclusions β-arrestin2 protected liver from I/R injury and this effect may be due to the regulating of Akt pathway, Bcl-2/Bax ratio, MAPKs and NF-κB pathway.

Surgical treatment of gallbladder carcinoma remains challenging, while targeted therapy has been demonstrated to have potential. In the present study, the effect of signal transducer and activator of transcription 3 (STAT3) expression and vasculogenic mimicry (VM) on the occurrence and development of gallbladder carcinoma was evaluated. A total of 72 patients with gallbladder carcinoma and 10 patients with chronic cholecystitis were examined. Immunohistochemical staining was performed to determine the positive expression rates of STAT3. Periodic acid Schiff CD34 double staining was performed to detect VM in the gallbladder carcinoma group. STAT3 expression and VM in gallbladder carcinoma tissues was compared among patients with different clinical characteristics. In postoperative patients with gallbladder cancer, the relationship of the postoperative recurrence time with STAT3 expression and VM was assessed. STAT3 expression in gallbladder carcinoma tissue was significantly higher than that in cholecystitis tissue (P

Numerous efforts have been made to modify the surface topography and chemical composition of biomedical implants in order to enhance the antibacterial ability and the osteointegration between implants and surrounding bone tissue. In the present work, copper-incorporated TiO

It is commonly recognized that aberrant expression of long non-coding RNAs (lncRNAs) is an important cause of cancer progression. The oncogenic property of KCNQ1OT1 has been identified in several malignant tumors. Here, we decided to explore the biological function and molecular mechanism of KCNQ1OT1 in cholangiocarcinoma (CCA). The expression conditions of KCNQ1OT1 in different tissues and cell lines were examined with qRT-PCR analysis. As expected, KCNQ1OT1 was highly expressed in CCA tissues and cell lines. Results of functional assays revealed the oncogenic function of KCNQ1OT in cholangiocarcinoma progression. The positive effect of KCNQ1OT1 on cell proliferation, invasion and epithelial-mesenchymal transition was identified by performing MTT assay, colony formation assay, transwell invasion assay and western blotting. Whereas, the negative effect of KCNQ1OT1 on the cell apoptosis was tested with flow cytometry analysis. Mechanism investigation revealed that KCNQ1OT1 can act as a ceRNA to improve CCA progression by regulating miR-140-5p/SOX4 axis. Recue assays were conducted to demonstrate the actual effects of KCNQ1OT1-miR-140-5p-SOX4 pathway on CCA progression.

Improved insight into the molecular characteristics of hepatocellular carcinoma (HCC) is required to predict prognosis and to develop a new rationale for targeted therapeutic strategy. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information on differentially expressed genes (DEGs). The RNA sequencing data related to HCC in The Cancer Genome Atlas (TCGA) database were analyzed to screen DEGs, which were separately submitted to perform gene enrichment analysis to identify gene sets and signaling pathways, and to construct a protein-protein interaction (PPI) network. Subsequently, hub genes were selected by the core level in the network, and the top hub genes were focused on gene expression analysis and survival analysis. A total of 610 DEGs were identified, including 444 upregulated and 166 downregulated genes. The upregulated DEGs were significantly enriched in the Gene Ontology analysis (GO): Cell division and in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway: Cell cycle, whereas the downregulated DEGs were enriched in GO: Negative regulation of growth and in the KEGG pathway: Retinol metabolism, with significant differences. Cyclin-dependent kinase (CDK)1 was selected as the top hub gene by the PPI network, which exhibited a similar expression trend with the data from the Gene Expression Omnibus (GEO) database. Survival analysis revealed a significantly negative correlation between CDK1 expression level and overall survival in the TCGA group (P

Jing Ke,1,2 Peng Ma,2 Jinpeng Chen,2 Jun Qin,2 Haixin Qian1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China Background: In the present study, we aimed to investigate the role of LGR6 in the progression of gastric cancer (GC) and explore the intrinsic molecular mechanisms.Materials and methods: The lentiviral LGR6 shRNA (sh-LGR6) and lentiviral expression vector of LGR6 gene (OE-LGR6) were used to regulate the LGR6 expression. Furthermore, we performed in vitro experiments to observe whether PI3K/AKT/mTOR pathway was affected by LGR6 and assess the role of LGR6 in the proliferation, apoptosis, migration, and invasion of GC cells.Results: Our data showed that phosphorylated AKT and mTOR were downregulated by sh-LGR6 (P

Background and aims Several studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer. Materials and methods Embase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed. Results Fifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17–1.40, P

This study was expected to reveal the regulatory effects of lncRNA UCA1 on pancreatic cancer cell progression through targeting miR-96/FOXO3. Microarray analysis was carried out on 36 cases of pancreatic cancer tissues and 16 cases of adjacent tissues among them. Expression levels of lncRNA UCA1, miR-96, and FOXO3 in pancreatic cancer tissues and cell lines were determined by qRT-PCR. Expression levels of FOXO3 protein were determined by western blot. Cell viability, cell cycle and apoptosis, cell invasion and migration were detected by CCK-8, flow cytometry, and transwell assay, respectively. The colocalization relationship between lncRNA UCA1 and miR-96 was detected by RNA FISH. Whether UCA1 could target miR-96 and whether miR-96 could target FOXO3 3'UTR were verified by dual-luciferase reporter gene assay. High expression of lncRNA UCA1 and FOXO3 and low expression of miR-96 were shown in pancreatic cancer. Inhibition of UCA1 suppressed pancreatic tumor cell proliferation, colony formation, and metastasis, while inhibition of miR-96 promoted pancreatic cancer cell progression. FOXO3 was the downstream target gene of miR-96 and showed the opposite effects. LncRNA UCA1 promoted cell proliferation, invasion, migration and inhibited cell apoptosis of pancreatic cancer through down-regulating miR-96 and up-regulating FOXO3. © 2018 IUBMB Life, 70(4):276-290, 2018.

Hong Zhou,1,2 HaiXin Qian1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; 2Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Objective: To investigate enteral nutrition’s effect on serum inflammatory factors and the cardiac function of malnourished elderly patients with heart failure.Patients and methods: A total of 105 elderly patients with heart failure were randomly divided into 3 groups: Treatment Group A, Treatment Group B, and the Control Group (Group C), each group having 35 patients and being administered conventional heart failure treatment. Group A was treated with 500 mL·d-1 of enteral nutrition for 1 month. Group B was given the same dose of enteral nutrition for 3 months. The Control Group was given free diet. Nutritional risk screening 2002 was used to assess the nutritional status before and after the treatment for each group. New York Heart Association status was recorded as were left ventricular ejection fraction, plasma B-type natriuretic peptide, inteleukin-6, C-reactive protein, and tumor necrosis factor-α.Results: After the treatment, the body mass index, skinfold thickness of upper arm triceps, muscle circumference of the upper arm, upper arm muscle circumference, total protein, albumin, hemoglobin, and left ventricular ejection fraction in the treatment groups all increased, with relatively obvious relief of symptoms of heart failure. The levels of B-type natriuretic peptide, interleukin-6, tumor necrosis factor-α, and C-reactive protein all rose to different extents (P0.05).Conclusion: The use of enteral nutrition in conventional treatment of elderly patients with heart failure could improve not only patients’ nutritional status and cardiac function, but also their immune function, thus reducing the levels of inflammatory factors. The longer the treatment period is, the more obvious the improvement in patients’ cardiac function and inflammatory factors will be observed. Keywords: enteral nutrition, heart failure, elderly, inflammatory factors, cardiac function

Acidic microenvironment, particularly acid-sensing ion channel 1a (ASIC1a), has been reported to promote carcinoma cell proliferation as well as migration. In this study, we explored the effect of ASIC1a on migration and invasion of gastric carcinoma (GC). ASIC1a expression levels were examined in paired GC and adjacent normal tissues from 16 patients by immunohistochemistry. Reverse transcription real-time PCR and immunoblotting were conducted to assess the ASIC1a expression levels in the GC cell line AGS after transfection with ASIC1a small hairpin RNA (shRNA). Wound healing and transwell invasion assays were utilized to detect metastasis and invasion following ASIC1a silencing. Tumor formation was used to detect the role of ASIC1a in tumorigenicity in vivo. It was found that ASIC1a expression level was significantly higher in GC tissues showing postoperative metastasis compared with non-metastasis and non-tumor tissues. Moreover, silencing of ASIC1a with shRNA significantly down-regulated ASIC1a expression and reduced GC cell migration and invasion. A moderately acidic extracellular environment inhibited GC cell viability. Furthermore, ASIC1a shRNA caused inhibition of tumorigenicity in vivo. Our study is the first report of attenuating the malignant phenotype of GC in vitro and in vivo by suppressing ASIC1a, and suggests a novel approach to study the relationship between ASICs and GC cell migration and invasion.

As demonstrated in previous studies, the phosphorylated form of 4E‑binding protein 1 (p‑4E‑BP1) may be a suitable tumor biomarker. The aim of the current study was to examine the expression status of p‑4E‑BP1 in colorectal cancer (CRC), in order to determine its clinical significance. The present study enrolled 89 patients with CRC that had undergone radical resection. Paired tumor and adjacent normal tissues were evaluated using immunohistochemistry to detect the protein expression of p‑4E‑BP1 and phosphatase and tensin homolog (PTEN). The study identified 53 cases (59.6%) that exhibited moderate or high expression of p‑4E‑BP1 in tumor tissues, compared with little or no expression in the adjacent normal tissues. Conversely, PTEN protein expression was markedly lower in CRC compared with adjacent normal tissues. p‑4E‑BP1 protein upregulation tissues samples was consistent with PTEN downregulation in CRC samples. p‑4E‑BP1 overexpression was predominant in patients with metastasis to the regional lymph nodes. Moderate/high expression of p‑4E‑BP1 protein was significantly associated with adverse overall survival (OS) in patients. Statistical analysis using the Cox proportional hazards model, indicated that p‑4E‑BP1 expression was an independent factor suitable for predicting OS in CRC patients, which was independent of lymph node metastasis. In conclusion, p‑4E‑BP1 protein expression appears to be upregulated in CRC, suggesting that it may be a suitable biomarker for predicting CRC prognosis.

Long non-coding RNA activated by transforming growth factor-β (ATB) was recently reported to be involved in a wide range of physiological and pathological processes. However, the role of ATB in colorectal cancer (CRC) stemness remains unclear. In the present study, the functional role of ATB in maintaining stemness of CRC was determined using colony formation and sphere formation assays, and xenograft models. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed to investigate the mechanisms underlying the effects of ATB. Knockdown of ATB impaired colony formation and sphere formation in CRC cells, accompanied by an inhibition of colon tumor growth. Further results suggested that ATB regulated the transcriptional activity of the β-catenin pathway by inhibiting β-catenin expression. In addition, the results confirmed the role of β-catenin in ATB-mediated regulation of stemness in CRC. Collectively, the results indicated that ATB is a promising therapeutic target for CRC.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors. Identification of diagnostic and therapeutic biomarkers for PDAC is urgently needed. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) has been linked to the progression of various human cancers. Nevertheless, the function and role of TBL1XR1 in pancreatic cancers are unclear. AIM To elucidate the function and potential mechanism of TBL1XR1 in the development of PDAC. METHODS Ninety patients with histologically-confirmed PDAC were included in this study. PDAC tumor samples and cell lines were used to determine the expression of TBL1XR1. CCK-8 assays and colony formation assays were carried out to assess PDAC cell viability. Flow cytometry was performed to measure the changes in the cell cycle and cell apoptosis. Changes in related protein expression were measured by western blot analysis. Animal analysis was conducted to confirm the impact of TBL1XR1 in vivo. RESULTS Patients with TBL1XR1-positive tumors had worse overall survival than those with TBL1XR1-negative tumors. Moreover, we found that TBL1XR1 strongly promoted PDAC cell proliferation and inhibited PDAC cell apoptosis. Moreover, knockdown of TBL1XR1 induced G0/G1 phase arrest. In vivo animal studies confirmed that TBL1XR1 accelerated tumor cell growth. The results of western blot analysis showed that TBL1XR1 might play a key role in regulating PDAC cell proliferation and apoptosis via the PI3K/AKT pathway. CONCLUSION TBL1XR1 promoted PDAC cell progression and might be an effective diagnostic and therapeutic marker for pancreatic cancer.

Gastric cancer (GC) is characterized by unique genetic aberrations. Some of these mutations may be used to predict tumor prognosis or to guide patient therapy. Cell-free circulating tumor DNA (ctDNA) has been considered a promising alternative to biopsy to identify genome aberrations. However, no standardized methods to detect ctDNA variations in patients with GC are currently available. In the present study, the targeted sequencing of 545 genes was used to identify somatic alterations in tissues and matched plasma samples of nine patients with GC. Driver gene mutations were detected in matched tissues and plasma ctDNA. The mutated reads concordance rate of ctDNA in GC tissues with matched tissues was 45%. A true positive copy number gain of human epidermal growth factor receptor 2 in plasma from patients with GC was identified. Furthermore, the ctDNA fraction in plasma cell-free DNA (cfDNA) was positively correlated with metastasis lymph node number and with lactate dehydrogenase level. In conclusion, results from the present study suggested that targeted sequencing of plasma ctDNA may be considered a potential option for the clinical monitoring of GC.

Background: It has been reported that brusatol (BRU) reduces cellular reactive oxygen species (ROS) level under hypoxia; here the protective effect of BRU against oxygen-glucose deprivation/reoxygenation (OGD-R)-induced injury in HepG2 cells and against anoxia/reoxygenation (A/R)-induced injury in rat liver mitochondria was investigated. Materials and Methods: OGD-R-induced HepG2 cell viability loss was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and trypan blue staining. Mitochondrial ROS level in HepG2 cells was measured by MitoSOX staining. The cellular malondialdehyde and adenosine triphosphate level was measured by commercial kits. The mitochondrial membrane potential in HepG2 cells was measured by JC-1 staining. The protein level was detected by Western blotting. Rat liver mitochondria were separated by differential centrifugation. A/R-induced injury in isolated rat liver mitochondria was established by using a Clark oxygen electrode. The ROS generation in isolated mitochondria was evaluated using Amplex red/horseradish peroxidase. Results: BRU reduced mitochondrial ROS level and alleviated oxidative injury in HepG2 cells, thereby significantly inhibited OGD-R-induced cell death. During OGD-R, BRU improved mitochondrial function and inhibited the release of cytochrome c. Furthermore, BRU showed a clear protective effect against A/R-induced injury in isolated rat liver mitochondria. When isolated rat liver mitochondria were pretreated with BRU, A/R-induced ROS generation was significantly decreased, and mitochondrial respiratory dysfunction was ameliorated. Conclusions: BRU pretreatment attenuated OGD-R-induced injury in HepG2 cells and A/R-induced injury in isolated rat liver mitochondria by inhibiting mitochondrial ROS-induced oxidative stress.

In China, breast cancer is the most commonly occurring cancer in women. MicroRNAs (miRs) are a group of endogenous small non-coding RNAs, which serve a role in many biological processes through the regulation of target genes. In the current study, miR-150-5p expression was significantly up-regulated in breast cancer tissues and cell lines. To investigate the cellular function and underlying molecular mechanism of miR-150-5p in breast cancer, TargetScan7.2 was used to identify miR-150-5p target genes. SRC kinase signaling inhibitor 1 (SRCIN1) was identified as a direct target gene of miR-150-5p and the current study demonstrated that SRCIN1 was negatively regulated by miR-150-5p in breast cancer cells. Furthermore, SRCIN1 expression was significantly down-regulated in breast cancer tissues and cell lines. Taken together, these results demonstrated that there was a negative association between miR-150-5p and SRCIN1 in breast cancer. The CCK-8 and Transwell assays were used to examine breast cancer cell viability, invasion and migration ability. The current study demonstrated that over-expression of miR-150-5p enhanced breast cancer cell proliferation, invasion and migration. In addition, miR-150-5p over-expression increased the expression of mesenchymal cell markers (vimentin, N-cadherin and β-catenin) and decreased the expression of epithelial cell markers (E-cadherin and zonula occludens-1). By contrast, miR-150-5p knockdown inhibited breast cancer cell viability, invasion and migration. Additionally, miR-150-5p knockdown decreased the expression of mesenchymal cell markers and increased the expression of epithelial cell markers. Taken together, these results suggest that the miR-150-5p/SRCIN1 axis may be a potential target in the treatment of breast cancer.

Aim. To investigate whether methylene blue-mediated photodynamic therapy (MB-PDT) can affect the “fate” of macrophages in vitro or in periodontitis tissues and to explore the potential mechanism. Methods. For in vitro treatments, THP-1 macrophages were divided into three experimental groups: C/control, no treatment; MB, methylene blue treatment; and MB-PDT, MB and laser irradiation treatment. Then, apoptosis and apoptosis-related proteins were detected in each group. For in vivo treatments, periodontitis was ligature-induced in the first molars of the bilateral maxilla in 12 Sprague Dawley (SD) rats. After six weeks, the ligatures were removed and all the induced molars underwent scaling and root planning (SRP). Then, the rats were divided into three groups according to the following treatments: SRP, saline solution; MB, phenothiazinium dye; and MB-PDT, MB and laser irradiation. Apoptotic macrophages, inflammation levels, and alveolar bone resorption in the periodontal tissues of rats were analyzed in each group. Results. In vitro, flow cytometry analysis demonstrated that 10 μM MB and 40 J/cm2 laser irradiation maximized the apoptosis rate (34.74%) in macrophages. Fluorescence probe and Western blot analyses showed that MB-PDT induced macrophage apoptosis via reactive oxygen species (ROS) and the mitochondrial-dependent apoptotic pathway. Conversely, the addition of exogenous antioxidant glutathione (GSH) and the pan-caspase inhibitor Z-VAD-FMK markedly reduced the apoptotic response in macrophages. In vivo, immunohistochemistry, histology, radiographic, and molecular biology experiments revealed fewer infiltrated macrophages, less bone loss, and lower IL-1β and TNF-α levels in the MB-PDT group than in the SRP and MB groups (P<0.05). Immunohistochemistry analysis also detected apoptotic macrophages in the MB-PDT group. Conclusion. MB-PDT could induce macrophage apoptosis in vitro and in rats with periodontitis. This may be another way for MB-PDT to relieve periodontitis in addition to its antimicrobial effect. Meanwhile, MB-PDT induced apoptosis in THP-1 macrophages via the mitochondrial caspase pathway.

Hong Zhou,1,2 Haixin Qian1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People’s Republic of China Objective: The aim of this study was to develop pH sensitive nanoparticles of budesonide for the treatment of ulcerative colitis.Methods: The NPs system was characterized by the transmission electron microscopy (TEM), particle size, drug loading and encapsulation efficiency. In addition, in vitro drug release properties and pharmacokinetics were also investigated in detail. The optimized formulation was examined for its in-vivo targeting potential using 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in a rat model.Results: Dynamic light-scattering results showed that the particle size of budesonide-Eudragit S100/poly(lactic-co-glycolic acid) nanoparticles was around 110.5 nm, with a polydispersity index of 0.098. Transmission electron microscopy images showed that BUD-ES100/PLGA NPs were spherical with uniform size and relatively smooth surfaces. In vitro release showed that BUD-ES100/PLGA NPs required minimal release of drugs during its transit in the stomach and the upper small intestine to ensure that a maximum dose reached the colon. After the pharmacodynamic treatment, the myeloperoxidase value of BUD-ES100/PLGA NPs was close to the normal group. The histopathological examination of rectum showed that no sign of damages such as epithelial necrosis and sloughing epithelial cells was detected.Conclusion: Our findings suggested that BUD-ES100/PLGA NPs were a promising alternative to single pH-dependent systems for colitis therapy. Keywords: budesonide, nanoparticles, ES100/PLGA, in vitro release, pharmacodynamic

Superior mesenteric artery syndrome (SMAS) is an uncommon cause of vomiting and weight loss due to compression of the third part of the duodenum by the superior mesenteric artery. Small bowel adenocarcinoma is an uncommon tumor, which is frequently delayed in diagnosis as its symptoms and signs are non-specific. The present study describes a case of SMAS occurring in a 51-year-old man, caused by intestinal obstruction secondary to a primary adenocarcinoma of the duodenal-jejunal junction. To the best of our knowledge, the present case is the first report of small bowel adenocarcinoma masquerading as SMAS. The present case highlights the importance of considering the possibility of SMAS in patients with upper bowel obstruction caused by intestinal carcinoma.

Triple-negative breast cancer (TNBC) is a common type of breast malignancy with high a propensity for metastasis and locoregional recurrence. The aim of the present study was to investigate the expression of aquaporin (AQP) 3 and AQP5, analyze their association with clinicopathological parameters and explore their clinical significance in tissue samples from patients with TNBC. Immunohistochemistry was performed to detect the expression patterns of AQP3 and AQP5 in 96 patients with TNBC who underwent surgery between 2007 and 2012. AQP3 and AQP5 were expressed primarily in the membrane and cytoplasm of tumor cells within TNBC tissues. AQP3 and AQP5 expression was notably stronger in carcinoma tissue compared with adjacent normal tissue. Overexpression of AQP3 and AQP5 was significantly associated with tumor size, lymph node status and local relapse/distant metastasis. In addition, aberrant overexpression of AQP5 was observed more frequently in TNBC tissues with higher Ki-67 expression than in those with lower Ki-67 expression. In univariate analysis, patients with TNBC with high AQP3 and AQP5 expression demonstrated poorer 5-year disease-free survival and overall survival compared with patients with low AQP3 and AQP5 expression. In multivariate analysis, the combined expression of AQP3 and AQP5 was an independent prognostic marker in patients with TNBC. The results of the present study suggest that the overexpression of AQP3 and AQP5 may serve as a novel therapeutic marker in patients with TNBC.

BACKGROUND Although bariatric surgery performed for morbid obesity has been shown to significantly improve type 2 diabetes mellitus (T2DM), data on its effectiveness to improve T2DM in nonobese patients are scarce. The present pilot study evaluated the clinical effects of laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) in Chinese T2DM patients with body mass index (BMI) ≤27.5 kg/m. MATERIALS AND METHODS A total of 68 consecutive patients with uncontrolled T2DM underwent LRYGB from May 2010 to March 2012. All patients were subjected to follow-up controls with anthropometric and metabolic indices at 1, 3, 6, and 12 months after surgery. Glycemic control was evaluated. RESULTS One year after the surgery, LRYGB resulted in 69.4%±52.2% excess weight loss percentage (%EWL), remission of T2DM in 80.9% of all the patients. In the group of T2DM patients with BMI≤27.5 kg/m (n=28), 9 (32.1%) cases showed T2DM remission, 10 (35.7%) showed glycemic control, 7 (25%) showed improvement, and 2 (7.1%) were unchanged. The change in BMI, waist circumference, and the plasma levels of FPG, HbA1C, triglycerides, HDL-C, and insulin were statistically significance at 1 year (P

Rationale: Total pancreatectomy (TP) is performed in cases of multifocal and large invasive tumors of the pancreas, and is associated with high rates of mortality and morbidity. Previously, the limitations and unsatisfactory effect of this surgery rendered it rarely performed; however, with improvements in surgical techniques and blood sugar management, TP is now more frequently performed. TP has a similar long-term survival rate as that for pancreatoduodenectomy (PD). However, the application of TP plus total gastrectomy (TG) for the treatment of invasive pancreatic ductal adenocarcinoma has not been reported previously. Patient concerns: The patient was a 64-year-old man with epigastric discomfort. Physical examination showed a hard mass. Preoperative computed tomography and magnetic resonance imaging revealed a solid mass located in the pancreatic body and involving the portal vein and stomach. Diagnosis: Pancreatic cancer. Interventions: The patient was treated with TP combined with TG and portal vein reconstruction. Outcomes: The patient had a smooth post-operative recovery but, regretfully, developed metastases 2 months after discharge. Lessons: Considering the poor outcome of the present case, the validity of the operation should be reevaluated. Although a single case does not elicit a convincing conclusion, the current case might serve as a warning against performing a similar surgery.

Numerous efforts have been made to modify the surface topography and chemical composition of biomedical implants in order to enhance the antibacterial ability and the osteointegration between implants and surrounding bone tissue. In the present work, copper-incorporated TiO2 coatings were fabricated by combining micro-arc oxidation and hydrothermal treatment together to functionalize the surface of Ti implants. The as-prepared surfaces exhibited a hierarchical structure comprising nanoneedles nearly perpendicular to the microrough surface of the TiO2 coating. The Cu-loaded TiO2 coating possessed strong antimicrobial ability against Gram-negative Escherichia coli. In vitro cytocompatibility evaluation suggests that no significant cytotoxicity appeared on the Cu-incorporated TiO2 coating. Furthermore, the addition of the copper element could stimulate the expression of angiogenic genes, including the hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in rat bone marrow stem cells (BMSCs). Moreover, they tended to undergo osteogenic differentiation, indicated by the up-regulation expression of osteogenic markers and the higher level of alkaline phosphatase activity. This study provides insight for the surface modification of biomedical Ti-based implants. To the best of our best knowledge, this is a successful attempt for the first time to combine micro-arc oxidation and hydrothermal treatment to introduce copper nutrient element to functionalize Ti-based implant surfaces with enhanced angiogenesis potential, osteostimulation and antimicrobial properties that can better meet clinical needs.

Hepatocellular carcinoma is one of the most common and lethal cancers worldwide, especially in developing countries. In the present study, we found that the expression of a microRNA, miR-590-5P, was down-regulated and S100A10 was up-regulated in six hepatocellular carcinoma cell lines. The reporter gene assay showed that overexpression of miR-590-5P effectively reduced the activity of luciferase expressed by a vector bearing the 3' untranslated region of S100A10 mRNA. Ectopic miR-590-5P overexpression mediated by lentiviral infection decreased expression of S100A10. Infection of Lv-miR-590-5P inhibited cell growth and induced cell cycle G1 arrest in HepG2 cells. In addition, miR-590-5P expression suppressed the expression of Wnt5a, cMyc and cyclin D1, and increased the phosphorylation of β-catenin and expression of Caspase 3, which may contribute to the inhibitory effect of miR-590-5P on cell growth. Taken together, our data suggest that down-regulation of miR-590-5P is involved in hepatocellular carcinoma and the restoration of miR-590-5P can impair the growth of cancer cells, suggesting that miR-590-5P may be a potential target molecule for the therapy of hepatocellular carcinoma.

The aims of this study were to fabricate a novel titanium/silicon carbide (Ti/SiC) metal matrix nanocomposite (MMNC) by friction stir processing (FSP) and to investigate its microstructure and mechanical properties. In addition, the adhesion, proliferation and osteogenic differentiation of rat bone marrow stromal cells (BMSCs) on the nanocomposite surface were investigated. The MMNC microstructure was observed by both scanning and transmission electron microscopy. Mechanical properties were characterized by nanoindentation and Vickers hardness testing. Integrin β1 immunofluorescence, cell adhesion, and MTT assays were used to evaluate the effects of the nanocomposite on cell adhesion and proliferation. Osteogenic and angiogenic differentiation were evaluated by alkaline phosphatase (ALP) staining, ALP activity, PCR and osteocalcin immunofluorescence. The observed microstructures and mechanical properties clearly indicated that FSP is a very effective technique for modifying Ti/SiC MMNC to contain uniformly distributed nanoparticles. In the interiors of recrystallized grains, characteristics including twins, fine recrystallized grains, and dislocations formed concurrently. Adhesion, proliferation, and osteogenic and angiogenic differentiation of rat BMSCs were all enhanced on the novel Ti/SiC MMNC surface. In conclusion, nanocomposites modified using FSP technology not only have superior mechanical properties under stress-bearing conditions but also provide improved surface and physicochemical properties for cell attachment and osseointegration.

Objectives: Persistent low-grade chronic inflammation is common in type 2 diabetes (T2D) and obesity. To date, the underlying molecular mechanism is not well understood. In this study, we aimed to investigate gut microbiota and the expression of monocyte surface molecules in obese T2D subjects who underwent Roux-en-Y gastric bypass (RYGB) surgery. Methods: Twenty-four T2D patients were enrolled. Gut microbiota was assessed by measuring bacterial DNA. The phenotypes and biological functions of monocytes, and the expression of monocyte surface molecules were examined by flow cytometry. Results: RYGB led to significant alterations in the phenotypes of monocytes. Moreover, the ability of monocyte migration was significantly decreased after RYGB (P

Long non-coding RNAs (lncRNAs) have been proven to serve a critical role in cancer development and progression. The aim of this study was to elucidate clinical significance of lncRNA MALAT1 expression in breast cancer (BC). A total of 78 BC patients treated with radical resection were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction was used to detect MALAT1 expression in tissues and serum samples. The receiver operating characteristics (ROC) curve was constructed to describe diagnostic specificity and sensitivity. Lentivirus-mediated RNA interference was used to knockdown MALAT1 in the MDA-MB-231 cell line, and then cell proliferation and invasion were explored. Results showed that MALAT1 expression was significantly up-regulated in 85.9% (67/78) of cancerous tissues compared with normal counterparts (P0.01). Further, an elevated MALAT1 expression in BC tissue was significantly associated with lymph metastasis (P=0.037) and adverse 5-year disease-free survival (mean 48.5 months vs 62.7 months, P=0.012). Suppression of lncRNA MALAT1 significantly inhibited BC cells proliferation, migration and invasion, induced apoptosis and cell cycle G1 arrest. In addition, serum MALAT1 levels in BC patients were much higher than levels in patients with benign breast disease (P0.001), its diagnostic efficacy was satisfactory, area under the curve (AUC) was 0.833. In conclusion, MALAT1 upregulation plays an important rolein BC development, and serum MALAT1 level may be a potential tumor marker for BC diagnosis.

To explore the optimal pre-sintering temperature for graded glass/zirconia material, glass/zirconia specimens were prepared and pre-sintered at 900, 1,000 and 1,100°C respectively, glass infiltration and densification at 1,450°C. Monolith Y-TZP specimens were sintered at 1,450°C. Nanoindentation was used to test Young's modulus and Hardness. Compressive strength test and cycling fatigue test were conducted. Nanoindentation test showed graded change of Young's modulus in glass/zirconia structure. The compressive strength and the number of cycles to failure of specimens pre-sintered at 1,000°C were significantly higher than those of Y-TZP and the specimens pre-sintered at 900 and 1,000°C (p

Our previous studies have shown that β-arrestin 2 plays an anti-apoptotic effect. However, the mechanisms by which β-arrestin contribute to anti-apoptotic role remain unclear. In this study, we show that a deficiency of either β-arrestin 1 or β-arrestin 2 significantly increases serum deprivation (SD)-induced percentage of apoptotic cells. β-arrestin 2 deficient-induced apoptosis was inhibited by transfection with β-arrestin 2 full-length plasmid, revealing that SD-induced apoptosis is dependent on β-arrestin 2. Furthermore, in the absence of either β-arrestin 1 or β-arrestin 2 significantly enhances SD-induced the level of pro-apoptotic proteins, including cleaved caspase-3, extracellular-signal regulated kinase 1/2 (ERK1/2) and p38, members of mitogen-activated protein kinases (MAPKs). In addition, a deficiency of either β-arrestin 1 or β-arrestin 2 inhibits phosphorylation of Akt. The SD-induced changes in cleaved caspase-3, ERK1/2 and p38 MAPKs, Akt, and apoptotic cell numbers could be blocked by double knockout of β-arrestin 1/2. Our study thus demonstrates that β-arrestin inhibits cell apoptosis through pro-apoptotic ERK1/2 and p38 MAPKs and anti-apoptotic Akt signaling pathways.

Background It has been well recognized that malnutrition causes wounds to heal inadequately and incompletely. Malnutrition is often observed in the elderly, and it appears to be more severe in patients with hip fracture than in the general aging population. Few prospective studies give a detailed account of the identification and classification of nutritional status in the elderly. The objective of this study was to evaluate the effects of different nutritional measurements on wound healing status after hip fracture in the elderly. Methods From September 2002 to December 2007, 207 hip fracture patients older than 60 y treated surgically were reviewed for preoperative nutritional status. There were 81 males and 126 females with an average age of 75.93 y (62–91 y); 131 cases with femoral neck fractures, 76 cases with intertrochanteric fractures. Parameters indicative of nutritional status (serum albumin, serum transferrin, serum pre-albumin, and total lymphocyte count levels) at the time of admission were assessed, along with anthropometric measurements, Rainey MacDonald nutritional index, and MNA tool. Suture removal was performed on postoperative day 14. Results Delayed wound healing complicated 46 (22.2%) of the 207 cases. The preoperative serum transferring total lymphocyte count levels, MNA total score, and Rainey MacDonald nutritional index were significantly lower for patients who subsequently had delayed wound healing. When all variables were subjected to multivariate analysis, only total lymphocyte count levels and MNA total score showed significant value in predicting which patients would have delayed wound healing. Through prophylactic antibiotics and adherence to strict aseptic precautions, on follow-up, wound healing was normal in all patients. Conclusions Patients at risk for delayed wound healing problems after hip fracture can be identified using relatively inexpensive laboratory test such as TLC and MNA tool. The clinician must be aware of the risk values of both measurements. We believe this information is particularly important before planning procedures of hip fractures in the elderly.

Patient A fifty-year-old man received embolization for mandibular hemangioma two years ago, and the surgeon had placed four implants in his mandible and made a removable denture upon the implants. His denture however fractured repeatedly in the past years. After examination and communication with the patient, an implant-assisted overdenture incorporating bar attachment combined ERA attachment and Locator abutment was re-fabricated. A sixteen months follow-up showed acceptable outcome. Discussion There are some guidelines on design of implant over-denture, the site of implant will affect the final result. The unfavorable bone structure of mandibular hemangioma restricts the number and the site of implant, modification of design is essential to improve the final result. Conclusion Multi-disciplinary cooperation should be established for extensive edentulous case. Overlay type prosthesis incorporating several types of attachments can be suitable for complex case because of acceptable results and easy maintenance.

Purpose : To investigate microRNA-383 (miR-383) as a therapeutic target for the management of colon cancer. Methods : Total RNA was isolated using RNeasy RNA isolation kit according to the manufacturer’s instructions. cDNA was synthesized using RevertAid cDNA synthesis kit. Expression analysis was carried out by quantitative real-time polymerase chain reaction (RT-PCR). Cell proliferation was examined using CellTiter 96 AQueous One Solution Cell Proliferation Assay system, while apoptosis was detected by 4',6-diamidino-2-phenylindole (DAPI) and annexin V/PI double staining followed by flow cytometry. The miR-383 target was delimited using TargetScan software. Protein expression analysis was carried out by western blotting. Results : The results indicate that miR-383 was highly expressed in colon cancer cells. Down-regulation of miR-383 inhibited cancer cell proliferation, and promoted apoptosis and cell cycle arrest. Furthermore, in silico analysis revealed caspase-2 gene to be the downstream target of miR-383, a finding that was further confirmed by western blotting. Conclusion : The results reveal that miR-383 may be an important target to tackle the increasing incidence of colon cancer. Thus, drugs that target miR-383 and inhibit its expression can potentially be developed for the treatment of colon cancer. Keywords : MicroRNA, Colon cancer, Cell proliferation, Apoptosis, Protein expression

To explore the relationship between the expression of CXC chemokine receptor 2 (CXCR2) and the clinicopathologic features with prognosis in pancreatic ductal carcinoma (PDAC) tissues.The CXCR2 expression in 161 PDAC tissues were detected with immunohistochemistry using anti-human CXCR2 antibody and tissues microarray.The expression of CXCR2 in PDAC tumor tissues was higher than that in normal pancreatic tissues (χ(2) = 11.437, P = 0.001). The comparison of clinicopathologic characteristics and immunohistochemistry by χ(2) test analysis showed that a high expression of CXCR2 in PDAC was correlated with vascular invasion (χ(2) = 6.489, P = 0.011) and late TNM stage (χ(2) = 6.205, P = 0.013). Kaplan-Meier survival and Cox regression analyses showed that a high expression of CXCR2 (HR: 5.514, P = 0.016) was an independent prognostic factor.A high expression of CXCR2 denotes a poor prognosis in PDAC.

Pancreatic cancer is among the leading causes of cancer-related deaths with extremely poor prognosis. Thus, novel and effective therapies need to be developed to improve the poor survival rates of patients with advanced pancreatic cancer. Pectolinarigenin, a flavonoids compound, has been shown to possess numerous biologic activities such as anti-inflammation and anti-cancer. However, the function and mechanism of pectolinarigenin in pancreatic cancer are still not well understood. We evaluated the antitumor effects of pectolinarigenin, an active component of a medicinal plant. Pectolinarigenin exerted a strong antitumor effect in pancreatic cancer cell lines. Colony formation assay and wound healing assay indicated that pectolinarigenin inhibited cell viability and cell migration. Treatment with pectolinarigenin induced apoptosis and decreased phosphorylation of STAT3. Pectolinarigenin modulates the STAT3 signaling module, thereby inducing cytotoxicity in pancreatic cancer cells. This result verifies the potential use of pectolinarigenin as a new therapeutic agent for the treatment pancreatic cancer.

To determine the influence of Adriamycin (ADM) on the changes in Nanog, Oct4, Sox2, as well as, in ARID1 and Wnt5b expression in liver cancer stem cells.The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study, and were routinely cultured. The 50% lethal dose (LD50) in the cell lines was detected by the MTT assay. Expression changes in liver cancer stem cell related genes (Nanog, Oct-4, Sox2, ARID1, and Wnt5b) were detected by western blot following treatment with ADM (LD50).The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells (0.4123 ± 0.0236 μmol/L vs 0.5259 ± 0.0125 μmol/L, P0.05). Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells, while only Sox2 was expressed in HCCLM3 cells. However, neither ARID1A nor Oct4 was detected in these two cell lines. Genes, related to the stem cells, showed different expression in liver cancer cells with different metastatic potential following treatment with ADM (LD50). Wnt5b protein increased gradually within 4 h of ADM (LD50) treatment, while Nanog decreased (P0.05). After 12 h, Wnt5b decreased gradually, while Nanog increased steadily (P0.05). In addition, only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM (LD50) treatment. The expression of Sox2 increased gradually with ADM (LD50) in HCCLM3 cells (P0.05).ADM increased the death rate of MHCC97-L and HCCLM3 cells, while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Ubiquitin-proteasome system has been shown to play a pivotal role in the pathophysiology of HCC and other malignancies. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and may be involved in the regulation of cancer-related proteins. In this study, we investigated the expression pattern of UBE2Q1 in HCC cell lines and human HCC specimens, and its potential clinical and biological significance in HCC. Western blot and immunohistochemical analyses revealed that UBE2Q1 was significantly upregulated in HCC tumorous tissues compared with the adjacent noncancerous ones. Next, univariate and multivariate survival analyses were performed to determine the prognostic significance of UBE2Q1 in HCC. The results showed that upregulated expression of UBE2Q1 was positively correlated with high histological grades of HCC and predicted poor prognosis. In addition, the expression of UBE2Q1 was progressively increased in serum-refed HCC cells. UBE2Q1 depletion by small interfering RNA inhibited cell proliferation and led to G1 phase arrest in HepG2 and BEL-7404 cells. Furthermore, we showed that cells transfected with UBE2Q1-targeting siRNA resulted in significant increase in the levels of p53, p21 in HepG2 and BEL-7404 cells. These data imply that UBE2Q1 is upregulated in liver cancer cell lines and tumorous samples and may play a role in the development of HCC.

Chemotherapy plays a crucial role in hepatocellular carcinoma (HCC) treatment especially for patients with advanced HCC. Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of HCC. However, acquisition of cisplatin resistance is common in patients with HCC, and the underlying mechanism of such resistance is not fully understood. In the study, we focused on identifying the role of miRNAs in chemotherapy resistance after cisplatin-based combination chemotherapy. We assayed the expression level of miR-182 after cisplatin-based chemotherapy in patients with advanced HCC, and defined the biological functions by real-time PCR analysis and CCK-8 assay. We found that miR-182 levels were significantly increased in HCC patients treated with cisplatin-based chemotherapy. miR-182 levels were also higher in cisplatin-resistant HepG2 (HepG2-R) cells than in HepG2 cells. Upregulated miR-182 significantly increased the cell viability, whereas miR-182 knockdown reduced the cell viability during cisplatin treatment. miR-182 inhibition also partially overcame cisplatin resistance in HepG2-R cell. Furthermore, we found that upregulated miR-182 inhibited the expression of tumor suppressor gene TP53INP1 (tumor protein 53-induced nuclear protein 1) in vitro. In vivo, miR-182 and TP53INP1 expression was negatively correlated. We finally demonstrated that miR-182 increased cisplatin resistance of HCC cell, partly by targeting TP53INP1. These data suggest that miR-182/TP53INP1 signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

To investigate the value of early diagnosis and the effect of surgical treatment of acute superior mesenteric artery occlusion.Forty-eight patients underwent superior mesenteric artery embolectomy. The diagnosis was made by mesenteric angiography in 12 patients, by explorative laparotomy in 15 patients and by abdominal contrast-enhanced CT in 21 patients. The patients were divided into three groups according to the onset of symptoms and operation time. Patients in group I (n = 15) were operated on in the first 6 hours after onset of symptoms; Patients in group II (n = 19) were operated on between 6 and 12 hours after onset; and patients in group III (n = 14) underwent embolectomy after 12 hours.The macroscopic view of the intestine was normal in 24 patients (15 in group I and 9 in group II) 30 minutes after embolectomy and administration of urokinase. Segmental resection was necessary in 8 patients in group II. Extended resection was necessary in 2 patients in group II and 14 patients in group III, and all of the patients died during the early postoperative period.Early diagnosis and prompt surgical treatment can reduce the incident of bowel necrosis and mortality rate of patients with superior mesenteric artery occlusion.

This study investigated upper airway aerodynamic characteristics of patients who underwent maxillectomy using three-dimensional reconstruction and computational fluid dynamics. The results revealed the generation of low-velocity vortices throughout the entire maxillary defect during respiration. The nasal structure on the nonsurgical side changed postsurgically, possibly due to the pressure gradient between the defective and healthy side. The bilateral disturbed airflow patterns are believed to be the cause of common symptoms. The numeric simulation technique could be used as a potential method to understand upper airway morphology changes and respiratory functions, thus guiding the fabrication of prostheses.