Objective To investigate the effects of trifluridine-tipiracil hydrochloride tablets(TAS-102)combined with oxaliplatin(L-OHP)on proliferation,migration,invasion and apoptosis of hepatocellular carcinoma SNU-449 cells and its possible mechanism.Methods SNU-449 cells were divided into control group(without drugs),TAS-102 group(2 μg·mL-1),oxaliplatin group(1.2 μg·mL-1)and combination group(2 μg·mL-1 TAS-102+1.2 μg·mL-1 L-OHP).Cell counting kit-8 assay was used to detect cell proliferation ability;Transwell assay was used to detect cell migration and invasion;the apoptosis rate was analyzed by flow cytometry;the expressions of B-cell lymphoma-2(Bcl-2),Bel-2-associated X(Bax),E-cadherin and Vimentin were detected using Western blotting.Results Survival rate of cells in control group,TAS-102 group,oxaliplatin group and combination group were(100.00±2.98)％,(80.26±5.55)％,(78.49±5.76)％and(47.82±4.26)％,respectively;the number of cell migration were 436.83±27.50,228.17±15.87,171.67±19.49 and 113.83±11.34,respectively;the number of cell invasion were 332.67±19.95,205.33±13.65,219.67±14.49 and 116.83±11.30,respectively;the apoptosis rates were(2.32±0.07)％,(6.74±0.24)％,(6.37±0.18)％and(10.67±0.41)％,respectively;the relative expression levels of Bax protein were 0.28±0.01,0.53±0.03,0.75±0.03 and 1.11±0.03,respectively;the relative expression levels of Bel-2 protein were 0.65±0.03,0.32±0.02,0.23±0.02 and 0.13±0.01,respectively;the relative expression levels of E-cadherin were 0.15±0.01,0.24±0.02,0.35±0.02 and 0.64±0.02,respectively;the relative expression levels of Vimentin were 0.65±0.03,0.27±0.01,0.34±0.02 and 0.18±0.01,respectively.Comparison of each treatment group with the control group and comparison of the combination group with monotherapy group,the above indexes were statistically significant(all P＜0.05).Conclusion The synergistic effect of TAS-102 and oxaliplatin enhanced the inhibitionon proliferation,migration,and invasion,and promoted cell apoptosis of SNU-449 cells,and the mechanism may be related to the promotion of Bax and E-cadherin proteins and the inhibition of Bel-2 and Vimentin proteins.

OBJECTIVETo biomechanically compare the stability of the short and long iliac screw fixation constructs in lumbo-iliac reconstruction.

METHODSSeven adult human embalmed cadavers (L(3)-pelvis) were used. Using posterior spinal fixation system, L(4)-S(1) pedicle screw fixation was performed. This was defined as intact state of the sacroiliac joint. After the intact test, total sacrum resection and L(4)-L(5)-pelvis reconstruction by pedicle screw and iliac screw with different lengths were performed as follow: short screw group (as the length of exceeding 2 mm over ischial notch) and long screw group (as the length of exceeding 2 mm over anterior inferior iliac spine). Using the 858 MTS material testing machine, biomechanical testing was performed under 800 N compression and 7 Nm torsion loading modes. At last, the axial pullout test of two iliac screws was executed. Construct stiffness in compression and torsion test, and maximum pullout force were analyzed.

RESULTSInsertion lengths of the short and long iliac screw were (70 +/- 2) mm and (138 +/- 4) mm respectively. The lumbo-pelvic reconstruction using short and long iliac screw, respectively restored 53.3% +/- 13.6% and 57.6% +/- 16.2% of the initial stiffness in compression testing, and respectively harvested 55.1% +/- 11.9% and 62.5% +/- 9.2% of the initial stiffness in torsion testing. No significant difference was detected between the two reconstructions (P > 0.05), however, the compressive and torsional stiffness of the two techniques were markedly less than the intact condition (P < 0.05). The maximum pullout strength of long iliac screw was significantly higher than short screw (P < 0.05).

CONCLUSIONSUnder the physical loading, lumbo-pelvic fixation construct using the short iliac screw may obtain mechanical stability comparable to that by long iliac screw. The short iliac screw is only the half of the long iliac screw by length, could reduce the implantation risk. However, the long iliac screw behaves greater axial pullout force, should be applied as far as possible in the osteoporosis patient. The lumbo-pelvic reconstruction utilizing any length of iliac screw is difficult to restore the local stability.

Adult ; Aged ; Biomechanical Phenomena ; Bone Screws ; Female ; Humans ; Ilium ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pelvic Bones ; surgery ; Sacrum ; surgery ; Spinal Fusion ; methods

OBJECTIVETo observe Notch1 expression in esophageal squamous cell carcinoma (ESCC) and investigate its relation with microvascular angiogenesis in the tumor.

METHODSTissue slices of 40 cases ESCC (cancer group) and 8 cases normal esophagus tissues (normal group) were obtained to analyze the expression of Notch1 and vascular endothelial growth factor (VEGF) using immunohistochemistry and estimate the microvessel density (MVD) in the tumor.

RESULTSNotch1 expression was significantly lower in the cancer group than in the normal group (P<0.05). In the cancer group, Notch1 expression was higher in highly differentiated than in poorly differentiated tumors (P<0.05) regardless of tumor infiltration or lymph nodes metastasis (P>0.05). VEGF expression and MVD were significantly higher in cancer group than in normal group, and showed significant differences between tumors with different differentiation degrees, infiltration and lymph node metastasis (P<0.05). Correlation analysis showed that Notch1 expression was inversely correlated to VEGF expression.

CONCLUSIONNotch1 may be an anti-oncogene in ESCC and affects cell differentiation in early stage of the malignancy. Abnormally low expression of Notch1 in ESCC may be one of the upstream factors to induce high expression of VEGF and increased MVD. The Notch1 pathway might play a key role in microvascular angiogenesis in ESCC.

Adult ; Aged ; Angiogenesis Inducing Agents ; metabolism ; Capillaries ; growth & development ; Carcinoma, Squamous Cell ; blood supply ; metabolism ; Esophageal Neoplasms ; blood supply ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; Receptor, Notch1 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.
Cell Line, Tumor ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation ; Humans ; Lung Neoplasms ; genetics ; metabolism ; prevention & control ; Neoplasm Metastasis ; Neoplasm Proteins ; biosynthesis ; genetics ; Receptors, Estrogen ; biosynthesis ; genetics

Objective:To observe the efficacy of modified Fangji Huangqitang on early renal damage in hypertension (Qi deficiency and dampness obstruction syndrome) and its effect in resisting inflammation and protecting vascular endothelium. Method:One hundred and forty-four patients were randomly divided into control group and observation group by random number table. Patients in control group got losartan potassium tablets, 50 mg/time, 1 time/day, and nifedipine controlled-release tablets, 30 mg/time, 1 time/day. In addition to the therapy of control group, patients in observation group were alsog given modified Fangji Huangqitang, 1 dose/day. The qualification rate of blood pressure was recorded for every week, and ambulatory blood pressure was detected before and after treatment. Standard deviation of systolic blood pressure for 24 h (24 hSSD), standard deviation of diastolic pressure for 24 h (24 hDSD), mean systolic blood pressure for 24 h (24 hSBP), average diastolic pressure for 24 h (24 hDBP) were recorded, and dynamic pulse pressure index (PPI), dynamic arteriosclerosis index (AASI), and ratio of UmALB and creatinine (CR) were calculated, levels of beta 2 microglobulin (β₂-MG), urinary N-acetyl-beta-glucosaminidase (NAG), serum cystatin C (CysC), urinary microalbumin (UmALB), interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), endothelin-1 (ET-1) were detected, and symptoms and signs were scored. Result:During the 12-week observation period, the qualification rate of blood pressure in observation group was 89.09%, which was higher than 81.52%in control group (χ²=18.776, P<0.01). Levels of 24 hSBP, 24 hDBP, 24 hSSD, 24 h DSD, PPI, AASI, β₂-MG, CysC, NAG, UmALB, UACR, IL-6, IL-1β, TNF-α and ET-1 were lower than those in control group (P<0.01), while level of NO was higher than that in control group (P<0.01). And by rank sum test, the clinical efficacy in observation group was better than that in control group (Z=2.146, P<0.05). Conclusion:In addition of the western medicine therapy, modified Fangji Huangqitang can be added to control blood pressure level, improve blood pressure compliance rate, reduce blood pressure variability, protect renal function, prevent and relieve clinical symptoms, improve the clinical efficacy, inhibit inflammatory reaction and improve endothelial function.

OBJECTIVETo evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery.

METHODSTES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared.

RESULTSSuccess rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969.

CONCLUSIONSThe precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Evoked Potentials, Motor ; physiology ; Evoked Potentials, Somatosensory ; physiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Retrospective Studies ; Sensitivity and Specificity ; Spinal Cord ; physiology ; Spine ; surgery ; Young Adult

Objective To study virulence factors and drug resistance mechanism of linezolid-intermediate Enterococcus faecalis(E.faecalis) isolated from patients with bloodstream infection.Methods Two linezolid-intermediate E.faecalis strains,namely A and B,were isolated from two patients with bloodstream infection,the treatment of two patients was analyzed.The minimum inhibitory concentration (MIC) of linezolid and vancomycin were determined.The virulence genes (esp,asa1,gelE,ace,agg,efaA,cylA,and hyl) and linezolid resistance genes (domain V region of the 23SrRNA,cfr,cfr[B],optrA) were amplified by polymerase chain reaction (PCR).PCR products of domain V region of 23SrRNA gene were sequenced and analyzed.Results Symptoms of two patients who isolated two linezolid-intermediate E.faecalis strains were controlled after accepted linezolid therapy.Strains A and B were both susceptible to vancomycin(MICs were 1μg/mL and 4μg/mL respectively),teicoplain,ampicillin,and nitrofurantoin,while intermediate to linezolid(MIC were both 4μg/mL).Two strains both contained multiple virulence factors,strain A were negative for cylA and hyl,strain B were negative for hyl and esp,but positive for other virulence genes.There was G2621T mutation in domain V region of 23SrRNA in strain A,and no variation was found in strain B.Drug resistance genes of cfr,cfr(B),and optrA were all negative in both strain A and B.Conclusion In the present study,two linezolid-intermediate E.faecalis strains isolated from patients with bloodstream infection were susceptible to vancomycin and ampicillin,although the treatment of linezolid in two patients is effective,the utilization of linezolid therapy in clinical practice still needs to be cautious.The mutation of target site is a significant resistance mechanism,it is necessary for us to pay more attention to these clinical strains which are non-susceptible to such antimicrobial agents,and the treatment strategy needs further study.