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Microgravity has many detrimental impact on brain functions, however the underlying mechanism remain unclear. In present study, 28 days of tail-suspension (30°) was used to simulate microgravity in rats. We showed that oxidative stress in hippocampus was increased after 28 days of simulated microgravity in consideration of the decreased expression of NF-E2-related factor 2 (Nrf2) and the declined activities of total superoxide dismutase (T-SOD), CuZn-SOD, glutathione peroxidase (GSH-PX) and total antioxidant capacity (T-AOC). Using RNA-seq, we further investigated the effect of simulated microgravity on the expression of genes in hippocampus, and 849 genes were found to be differentially expressed. According to pathway analysis, the differentially expressed genes involved in cytoskeleton, metabolism, immunity, transcription regulation, etc. It is interesting to note that the differentially expressed genes were involved in hypoxia-associated pathway. In agreement with this, the expression of hypoxia induced factor-1α (HIF-1α), the master regulator of oxygen homeostasis, was significantly increased. Meanwhile, HIF-2α, a HIF-1α paralog, was elevated compared with the control group. The expression of pyruvate dehydrogenase kinase 1 (PDK1), lactate dehydrogenase A (LDHA) and vascular endothelial growth factor (VEGF), three well-defined downstream targets of HIF-1α, were up-regulated in hippocampus after 28 days of simulated microgravity exposure. Additionally, brain oxygen saturation (SO 2 ) and blood flow analyzed by the tissue oxygen analysis system were also significantly reduced. These findings indicate that simulated microgravity might cause an alteration in oxygen homeostasis, providing novel insight into better understanding of how simulated microgravity affects the function of hippocampus and a new direction to the development of countermeasure for brain dysfunction during spaceflight (actual microgravity)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Clostridium difficile infection (CDI) may lead to poor outcomes in patients with inflammatory bowel disease (IBD). In this study we aimed to investigate the cumulative incidence, risk factors and outcome of CDI in patients with IBD in a single center in China., Methods: The clinical features and endoscopic profiles of consecutive IBD patients admitted to Ruijin Hospital, Shanghai Jiaotong University School of Medicine between January 2013 and December 2015 were retrospectively analyzed. CDI was diagnosed based on a positive polymerase chain reaction (PCR) stool test., Results: A total of 260 patients with IBD were enrolled, including 176 with Crohn's disease (CD) and 84 with ulcerative colitis (UC). Altogether 13 (5.0%) patients were diagnosed with CDI. The incidence of CDI was 4.0% (7/176) in CD and 7.1% (6/84) in UC, respectively. The endoscopic feature of pseudomembrane was found in four (33.3%) IBD-CDI patients, and pseudomembrane and deep ulcers were significantly correlated with CDI (P < 0.001 and P = 0.006, respectively). Hemoglobin (Hb) <100 g/L was found to be associated with CDI (OR 3.48, 95% CI 1.04-11.61, P = 0.043). Patients in the CDI group showed a higher risk of developing abdominal abscesses than those in the non-CDI group (OR 6.09, 95% CI 1.8-15.2, P = 0.003)., Conclusions: PCR-based fecal test for CDI should be performed in these IBD patients. Hb <100 g/L may be an important risk factor for CDI in IBD. For patients with CDI, antibiotics should be administered promptly to prevent abdominal abscess., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aims/introduction: To investigate the effect of telomere shortening and other predictive factors of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus patients in a 6-year prospective cohort study., Materials and Methods: A total of 70 type 2 diabetes mellitus (mean age 57.8 ± 6.7 years) patients without NAFLD were included in the study, and 64 of them were successfully followed up 6 years later, excluding four cases with significant alcohol consumption. NAFLD was diagnosed by the hepatorenal ratio obtained by a quantitative ultrasound method using NIH image analysis software. The 39 individuals that developed NAFLD were allocated to group A, and the 21 individuals that did not develop NAFLD were allocated to group B. Fluorescent real-time quantitative polymerase chain reaction was used to measure telomere length., Results: There was no significant difference between the two groups in baseline telomere length; however, at the end of the 6th year, telomere length had become shorter in group A compared with group B. There were significant differences between these two groups in baseline body mass index, waistline, systolic blood pressure, glycated hemoglobin and fasting C-peptide level. In addition, the estimated indices of baseline insulin resistance increased in group A. Fasting insulin level, body mass index, systolic blood pressure at baseline and the shortening of telomere length were independent risk factors of NAFLD in type 2 diabetes mellitus patients., Conclusions: Telomere length became shorter in type 2 diabetes mellitus patients who developed NAFLD over the course of 6 years. Type 2 diabetes mellitus patients who developed NAFLD had more serious insulin resistance compared with those who did not develop NAFLD a long time ago., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the expression of memory-related antioxidant genes and miRNAs under simulated weightlessness and the regulation of mechano growth factor (MGF) E domain, the peptide preventing nerve damage., Results: Igf-iea and mgf mRNA levels, expression of antioxidant genes sod1 and sod2 and levels of miR-134 and miR-125b-3p increased in rat hippocampus after 14 days tail suspension to simulate weightlessness which was inhibited with intramuscular injection of E domain peptide. Therefore, administration of MGF E domain peptide could reverse increased expressions of memory-related igf-iea, mgf, sod1, sod2, miR-134 and miR-125b-3p in rat hippocampus under simulated weightlessness., Conclusions: MGF may regulate the redox state and miRNA-targeted NR-CREB signaling, and intramuscular injection may be the alternative administration because of its safety, convenience and ability to pass through the blood brain barrier.

The purpose of this study was to elucidate the potential role of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in gemcitabine (Gem)-induced autophagy and apoptosis in breast cancer cells. MDA-MB-231 cells were treated with short hairpin RNA (shRNA) to knockdown Linc-ROR expression in the presence of Gem. Gem treatment alone decreased cell survival and increased both apoptosis and autophagy. Gem treatment also increased the expression of LC3-II, Beclin 1, NOTCH1 and Bcl-2, but decreased expression of p62 and p53. Untreated MDA-MB-231 cell lines strongly expressed linc-ROR, but linc-ROR knockdown decreased cell viability and expression of p62 and p53 while increasing apoptosis. Linc-ROR knockdown also increased LC3-II/β-actin, Beclin 1, NOTCH1, and Bcl-2 expression, as well as the number of autophagic vesicles in MDA-MB-231 cells. Linc-ROR negatively regulated miR-34a expression by inhibiting histone H3 acetylation in the miR-34a promoter. We conclude that linc-ROR suppresses Gem-induced autophagy and apoptosis in breast cancer cells by silencing miR-34a expression.

This study aimed to compare the accuracy of CT and MRI in determining the invasion of thyroid cartilage by and the T staging of laryngeal carcinoma with anterior vocal commissure (AVC) involvement. A total of 26 cases of laryngeal carcinomas with AVC involvement from May 2012 to January 2014 underwent enhanced CT and MRI scan, out of whom 6 patients also underwent diffusion-weighted magnetic resonance imaging(DWI). T staging and thyroid cartilage involvement were evaluated. All the surgical specimens underwent serial section and were reviewed by two senior pathologists independently. When compared with pathologic staging, the accuracy was 88.46% (23/26) of MRI scan (with a 95% confidence interval 37~77%) and 57.69% (15/26) of CT scan (with a 95% confidence interval 70~98%), respectively (P < 0.01). We also reported three cases who were misdiagnosed on CT or MRI about either the thyroid cartilage was involved or not, and one case of preliminary study of DWI. Compared to CT, MRI exhibited a higher accuracy rate on T staging of laryngeal carcinomas with AVC involvement. Combined utility of CT and MRI could help improve the accuracy of assessment of thyroid cartilage involvement and T staging of laryngeal carcinomas with AVC involvement.

We aimed to investigate the role of large intergenic noncoding RNA regulator of reprogramming (linc-ROR) in the chemotherapy resistance of human breast cancer (BC) cells and its mechanism. A total of 142 patients diagnosed with BC in the First Affiliated Hospital, Zhejiang University between January 2012 and January 2014 were enrolled in our study. The BC tissues and the adjacent normal tissues (5 cm away from tumor tissue) of the enrolled patients were selected, and human BC cell lines (MCF10A, SK-BR-3, MCF-7, Bcap-37, MDA-MB-231, and T47D) were also selected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, and Transwell were applied in our study. Expression level of linc-ROR messenger RNA (mRNA) in BC tissues was clearly higher than that in adjacent normal tissues, and significant difference was found between expression level of linc-ROR mRNA and lymph node metastasis (all P < 0.05). Linc-ROR was highly expressed in others BC cell lines compared with that in immortalized mammary epithelial cells (MECs) MCF10A (both P < 0.05), while MDA-MB231 cell presented the higher expression (P < 0.001). Under different concentrations of 5-FU and paclitaxel in MDA-MB231 cell, E-cadherin mRNA and protein expressions increased gradually with the increase of concentrations, and Vimentin and N-cadherin mRNA and protein expressions decreased gradually with the decrease of concentrations (all P < 0.05). Compared with shCtrl group, MDA-MB231 cell in shROR group presented higher sensibility of 5-FU and paclitaxel with increased E-cadherin expression, decreased Vimentin and N-cadherin expression and invasion ability (all P < 0.05). Compared with vector cell, overexpressed linc-ROR cell presented decreased sensibility of 5-FU and paclitaxel with decreased E-cadherin expression, increased Vimentin, N-cadherin expression, and invasion ability (all P < 0.05). Our study demonstrated that linc-ROR is an important marker for multidrug resistance of BC, and its up-regulation is important for chemotherapy tolerance and invasion of BC.

Objective To explore the diagnostic value of contrast-enhanced ultrasound (CEUS)for small focal liver lesions (FLLs). Methods The clinical data,CEUS findings,and pathology of 69 patients with small FLLs were retrospectively analyzed. Patients were grouped according to size of FLLs and the performance of CEUS was compared. Results The accuracy,sensitivity,specificity,positive predictive value,and negative predictive value of CEUS for the 69 FLLs were 94.2%,95.2%,93.8%,87.0%,and 97.8%,respectively. Rate of fast wash-out in portal vein phase was lower in group of diameters ≤2 cm than that in group of diameters>2 cm (P<0.05). Conclusions CEUS has a high diagnostic value for small FLLs.However,the CEUS findings of malignant lesions smaller than 2 cm are not typical in the portal phase and therefore the diagnosis should also be based on clinical features.

Objectives: In the current study, we explored the relationship between glycoprotein Ia (GPIa) C807T polymorphisms and platelet function, and the sensitivity to dual antiplatelet treatment after percutaneous coronary intervention., Materials and Methods: We conducted a case-control study in 220 patients diagnosed with acute coronary syndrome (ACS) and 220 healthy controls. The platelet GPIa C807T genotypes of patients and controls were determined, and platelet aggregation and plasma concentrations of α-granule membrane protein (GMP-140) were assessed following stimulation with arachidonic acid and adenosine diphosphate., Results: The frequency of the GPIa T allele was higher in the ACS group than in controls. In the ACS group, platelet aggregation was significantly higher in individuals with the T allele than in those with the C allele. Dual antiplatelet treatment reduced platelet aggregation in all three genotypes, and patients carrying the CC genotype were more sensitive to antiplatelet treatment than those with the T allele, particularly the ones with the TT genotype. There were no differences in plasma GMP-140 levels., Conclusions: The GPIa C807T polymorphism might be a risk factor for the development and relapse of ACS. The GP Ia T allele may help to identify a group of patients who need more aggressive antithrombotic treatment., (© 2015 S. Karger AG, Basel.)

Environmental factors in space are dramatically different from those on Earth. The spaceflight environment has been known to influence human physiology and behavior on orbital missions. In this study, we investigated alterations in the diurnal rhythms of activity and heart rate of three Chinese astronauts on a space mission. An analysis of the heart rate data showed a significant decrease in heart rate amplitudes during flight in all three subjects. The heart rate amplitudes of all the three astronauts were significantly dampened during flight, and the minimum as well as the maximum value of heart rate increased after flight. A phase shift in heart rate was observed in one of the three astronauts after flight. These results demonstrate the influence of spaceflight on heart physiology and function. In addition, a significant decrease in body trunk activity and rhythmicity occurred during flight, demonstrating that the spaceflight environment disturbs motion adaptation and diurnal activity rhythms., (Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light-dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

Objectives: Chronic kidney disease (CKD), a progressive and irreversible pathological syndrome, is the major cause of renal failure. Renal fibrosis is the principal process underlying the progression of CKD. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness. We evaluated whether the technique could reveal renal tissue fibrosis in CKD patients., Methods: ARFI assessments were performed in 45 patients with CKD referred for renal biopsies to measure cortical shear wave velocity (SWV). During measurement, a standardized method was employed, which aimed to minimize the potential impact of variation of transducer force, sampling error of non-cortical tissue and structural anisotropy of the kidney. Then SWV was compared to patients' CKD stage and pathological fibrosis indicators., Results: ARFI could not predict the different stages of CKD. Spearman correlation analysis showed that SWV did not correlate with any pathological indicators of fibrosis., Conclusion: ARFI assesses tissue stiffness of CKD kidneys by measuring cortical SWV. However, SWV did not show significant correlations with CKD stage and fibrosis indicators despite using standardized measurement methods. We therefore suggest that it would be necessary to evaluate the effect of pathological complexity and tissue perfusion of the kidney on stiffness assessment in future studies., Key Points: • Acoustic radiation force impulse (ARFI) can quantify tissue elasticity of CKD kidney. • Despite standardized measurement, ARFI-estimated elasticity did not correlate with renal fibrosis. • Effects of pathological complexity and tissue perfusion on renal stiffness warrant further study.

For future interplanetary manned spaceflight, mental issues, as well as physiological problems, must inevitably be considered and solved. Mars500 is a high-fidelity ground simulation experiment that involved 520 days of confined isolation for six multinational crewmembers. This experiment provided a good opportunity to perform psycho-physiological and psycho-social researches on such missions. To investigate emotional responses and psychological adaptation over long-term confinement, the International Affective Pictures System (IAPS) was selected as the visual emotional stimuli in this study. Additional data collected and analyzed included the Profile of Mood States (POMS) questionnaire and the levels of four types of plasma hormones: cortisol, 5-hydroxy tryptamine, dopamine, and norepinephrine. The results demonstrated an obvious bias on valence rating for unpleasant stimuli with time (p<0.05), and the correlation between psychological and biochemical data was identified (p<0.05). Overall, we concluded that the confined crew tended to assign positive ratings to negative pictures with time, which might be driven by a defensive system. There was a stage-changing pattern of psychological adaptation of the Mars500 crew, which is similar to the third-quarter phenomenon.

Due to progress in the research of glioma stem cells and the glioma niche, development of an animal model that facilitates the elucidation of the roles of the host tissue and cells is necessary. The aim of the present study was to develop a subcutaneous xenograft green fluorescent protein nude mouse model and use this model to analyze the roles of host cells in tumor necrosis repair. Tumors derived from the human glioma stem/progenitor cell line SU3 were subcutaneously implanted in green fluorescent protein nude mice. The implanted tumors were then passed from animal to animal for 10 generations. Finally, subcutaneous xenografts were assayed with traditional pathology, immunopathological techniques and fluorescence photography. For each generation, the tumorigenicity rate was 100%. Subcutaneous xenografts were rich in blood vessels, and necrotic and hemorrhagic foci, which highly expressed hypoxia-inducible factor-1α, tumor necrosis factor, Ki-67, CD68 and CD11b. In the interstitial tissue, particularly in old hemorrhagic foci, there were numerous cells expressing green fluorescent protein, CD68 and CD11b. Green fluorescent protein nude mouse subcutaneous xenografts not only consistently maintained the high invasiveness and tumorigenicity of glioma stem/progenitor cells, but also consisted of a high concentration of tumor blood vessels and necrotic and hemorrhagic foci. Subcutaneous xenografts also expressed high levels of tumor microenvironment-related proteins and host-derived tumor interstitial molecules. The model has significant potential for further research on tumor tissue remodeling and the tumor microenvironment.

Background: Recent studies have reported that the presence of cancer stem cells (CSCs) has major implications in the treatment of cancer and is responsible for tumor relapse. In the current study, we identified and characterized colon CSC-like side population (SP) cells from colon cancer tissue., Materials and Methods: The colon cancer samples were subjected to fluorescence-activated cell sorting (FACS) based on Hoechst 33342 dye exclusion for the purification of SP cells. The sorted SP cells were subjected to further characterization by immunofluorescence, real-time polymerase chain reaction (RT-PCR), multidrug resistance, and sphere formation assays., Results: We identified a fraction of 3.3% of SP cells in the colon cancer cell samples, which was reduced to 0.6% upon treatment with verapamil. The sorted SP cells showed high positivity with regard to CD133, CD44, CD147, and EpCAM, by fluorescence microscopic analysis. Further, these SP cells were highly resistant to multidrug treatment due to overexpression of the multidrug resistance 1 (MDR1) transporter protein ABCG2., Conclusion: Our findings suggest that the overexpression of ABCG2 and the expression of stem cell surface markers are collectively responsible for chemotherapy failure, tumor recurrence, and invasion in colon cancer., (© 2014 S. Karger GmbH, Freiburg.)

Introduction: Colorectal adenoma is a recognized precancerous lesion that has the potential for malignant transformation. Surgical resection of colorectal adenomas is required for exact diagnosis and treatment. The aim of this study is to assess the safety and therapeutic effect of transanal endoscopic microsurgery for preoperatively diagnosed colorectal adenomas., Methods: From September 2006 to February 2011, 45 patients with preoperatively diagnosed colon and rectal adenomas underwent transanal endoscopic microsurgery. The clinical data of these patients were reviewed., Results: The mean tumor diameter was 2.2 cm, mean operative time was 65 min, and the mean estimated blood loss was less than 10 mL. There was no conversion to transabdominal procedure. The mean tumor distance from the anal verge was 8.2 cm. Four patients had perforation into the peritoneal cavity during full-thickness resection; these were repaired by continuous suturing, and there was no postoperative leakage after 1 week of fasting. The surgical margins of specimens were negative in 44 patients. Complications included rectal bleeding in one patient, acute urinary retention in one patient and pulmonary infection in one patient. The mean postoperative hospital stay was 4.5 days. Only one patient experienced incontinence of hard stool 6 months after surgery. The patients were followed up for a median period of 42 months, with four cases of tumor recurrence observed., Conclusion: Transanal endoscopic microsurgery is a safe and effective technique for excising large adenomas in the mid and upper rectum and in the lower sigmoid colon. It is also an oncologically preferred method for T1 focal carcinomas that develop from villous adenomas., (© 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

SOD2 (superoxide dismutase 2) is one of the endogenous antioxidant enzymes that protect against reactive oxygen species. While explorations of SOD2 expression regulation are mainly focused on transcriptional and post-translational activation, there are few reports about the post-transcriptional regulation of SOD2. MicroRNAs (miRNAs) are 21nt-25nt (nucleotide) small noncoding RNAs that have emerged as indispensable regulators of gene expression. Here we show that miR-146a, a widely expressed miRNA, is up-regulated by H2O2-induced stress. By sequence analysis we found a binding site for miR-146a in the sod2 mRNA 3'UTR, and a luciferase reporter assay confirmed that miR-146a can interact with this sod2 regulatory region. Our results further show that miR-146a could down-regulate the SOD2 protein expression, and antisense-miR-146a could reverse the decrease of both the SOD2 level and cell viability in H2O2 treated PC12 cells. In conclusion, here we have identified a novel function of miR-146a in the post-transcriptional regulation of SOD2 expression.

Background: This study was designed to evaluate the feasibility and safety of total laparoscopic sigmoid and rectal surgery without abdominal incision in combination with transanal endoscopic microsurgery (TEM)., Methods: From May 2010 to October 2011, 34 patients with colon and rectal tumors were treated by total laparoscopic surgery without abdominal incision, and the clinical data of these patients were reviewed., Results: All operations could be successfully accomplished without conversion to open surgery. No diverting ileostomy was created. The average operative time was 151.60 (range, 125-185) minutes. The average blood loss was 200.20 (range, 55-450) ml. All resection margins were negative. Six patients developed postoperative anastomotic leakage. There were no reports of other complications in all patients., Conclusions: This preliminary study indicated that total laparoscopic sigmoid and rectal surgery in combination with TEM was a safe, feasible, and minimally invasive technique. This advanced surgical technique was developed by combining laparoscopy with the concept of natural orifice transluminal endoscopic surgery.

Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.

We extend the linear Radon transform to a nonlinear space and propose a method by applying the nonlinear Radon transform to Zernike moments to extract shape descriptors. These descriptors are obtained by computing Zernike moment on the radial and angular coordinates of the pattern image's nonlinear Radon matrix. Theoretical and experimental results validate the effectiveness and the robustness of the method. The experimental results show the performance of the proposed method in the case of nonlinear space equals or outperforms that in the case of linear Radon.

Objective: To investigate the contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA)., Methods: The sonographic findings and CEUS images of PHA in three patients were retrospectively analyzed., Results: In our study, 3 cases of PHA (2 multiple nodules and 1 solitary mass) showed similar enhancement pattern on CEUS, characterized by remarkable central non-enhancement and peripheral irregular enhancement in the arterial and portal phase, and complete wash-out in the late phase. Furthermore, we unexpectedly found that abundant neoplastic tissues were present in the central area of non-enhancement on pathological evaluation. Based on literature review, we supposed that the unusual finding may be associated with the very low velocity of blood flow in the central region of tumors., Conclusion: CEUS could well depict PHA with some common features, which may provide valuable clues in diagnosis of this rare disease. And non-necrotic tumor tissue of PHA could also demonstrate non-enhancement on CEUS, which warrant further investigations., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the feasibility and short-term outcomes of total laparoscopic sigmoid and rectal surgery combined with transanal endoscopic microsurgery(TEM)., Methods: The clinical data of 26 patients with colorectal carcinoma treated by total laparoscopic surgery with TEM between May 2010 and May 2011 in the Shanghai Ruijin Hospital were retrospectively analyzed., Results: All the 26 operations were successfully accomplished laparoscopically. There was no conversion to open procedure. No diverting ileostomy was made. The mean operative time was (151.6±25.9) min. The mean blood loss was (200.2±114.7) ml. The mean time to first flatus was (2.0±0.5) d. The mean tumor size was (3.0±0.7) cm and all resection margins were negative. The mean number of lymph nodes harvested was (12.9±2.2). Six patients developed postoperative anastomotic leakage, all of who had tumors in the lower rectum. There were no ureteral injury, intestinal obstruction, or pulmonary infection., Conclusions: Total laparoscopic sigmoid and rectal surgery combined with TEM is a safe and feasible minimally invasive surgery. It is an improvement by combining laparoscopic skills with the concept of natural orifice transluminal endoscopic surgery.

In spaceflight human circadian rhythms and sleep patterns are likely subject to change, which consequently disturbs human physiology, cognitive abilities and performance efficiency. However, the influence of microgravity on sleep and circadian clock as well as the underlying mechanisms remain largely unknown. Placing volunteers in a prone position, whereby their heads rest at an angle of -6° below horizontal, mimics the microgravity environment in orbital flight. Such positioning is termed head-down bed rest (HDBR). In this work, we analysed the influence of a 45-day HDBR on physiological diurnal rhythms. We examined urinary electrolyte and hormone excretion, and the results show a dramatic elevation of cortisol levels during HDBR and recovery. Increased diuresis, melatonin and testosterone were observed at certain periods during HDBR. In addition, we investigated the changes in urination and defecation frequencies and found that the rhythmicity of urinary frequency during lights-off during and after HDBR was higher than control. The grouped defecation frequency data exhibits rhythmicity before and during HDBR but not after HDBR. Together, these data demonstrate that HDBR can alter a number of physiological processes associated with diurnal rhythms.

The Peptidyl arginine deiminase, type IV (PADI4) gene has been suggested to have an association with rheumatoid arthritis (RA) in several populations. But its role in Chinese RA is not clarified. We investigated five single-nucleotide polymorphisms (SNPs) of PADI4 as PADI4-89 (rs11203366), PADI4-90 (rs11203367), PADI4-92 (rs874881) PADI4-94 (rs2240340), and PADI4-104 (rs1748033) in Chinese Han population. A total of 378 unrelated RA patients and 204 healthy controls were genotyped for the five SNPs. Individual allele, genotype and haplotype frequencies were compared between patients and controls. No significant differences in the frequency of PADI4 alleles, genotypes and haplotypes were observed between the patients and controls except PADI4-92. These data indicated that PADI4 polymorphisms were unlikely to play an important role in the susceptibility to RA in Chinese Han population.

Zinc ion elevation contributes to acute excitotoxic brain injury and correlates with the severity of dementia in chronic neurodegenerative diseases. Downstream control of zinc-triggered signals is believed to be an efficient countermeasure. In the current study, we examined whether the flavonoid luteolin (Lu) could protect human neuroblastoma SH-SY5Y cells against zinc toxicity. We found that Lu suppressed overproduction of reactive oxygen species and protected against apoptotic cell death induced by zinc. By using specific inhibitors, we found that zinc strongly triggered Akt and ERK1/2 activation via a PI3K-Akt-NF-κB-ERK1/2-dependent pathway. Furthermore, Lu completely blocked this activation. Our study strongly supports the hypothesis that Lu might protect SH-SY5Y cells against ROS-mediated apoptotic cell death induced by zinc in part by inhibiting the PI3K-Akt-NF-κB-ERKs pathway., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To evaluate the safety and outcomes after transanal endoscopic microsurgery (TEM)for rectal adenoma., Methods: Data of 32 patients undergoing TEM for rectal adenoma between September 2006 and February 2010 in the Ruijin Hospital were reviewed., Results: The adenoma diameter ranged from 0.6 to 10.0(2.3±1.2) cm. The mean operative time was 70(range,20-180) min. The estimated blood loss was less than 10 ml. There were no conversions to transabdominal procedure. Twenty-two(68.8%) patients underwent suturing of the wound, of whom 14 had full-thickness resection. Two patients had perforation into peritoneal cavity during full-thickness resection, which were repaired by continuous suturing and no postoperative leak occurred. R0 resection was achieved in 31(96.9%) patients. Postoperative pathology showed 12 simple adenomas, 10 adenomas with low grade intraepithelial neoplasia, 5 adenomas with high grade intraepithelial neoplasia, and 5 T1 focal carcinomas. Complications included rectal bleeding in 1 patient, acute urinary retention in 1 patient, and pulmonary infection in 1 patient. The postoperative stay was 4.5(3-8) days. The patients were followed-up for a period of 23 months(range, 2-43 months). There were 2 tumors recurred., Conclusion: TEM is a safe and effective minimally invasive surgical technique for large rectal adenomas.

Objective: Gastrointestinal stromal tumors (GISTs) occur rarely in the duodenum. The characteristics of duodenal GIST have not been well clarified. The aim of this study is to clarify the characteristics and surgical prognosis of patients with primary duodenal GIST., Methods: Data of patients with surgically treated primary duodenal GIST were retrospectively analyzed. Immunohistochemical expressions of p53, p16, and Ki-67 were evaluated to explain the prognosis., Results: Compared with gastric or small intestinal GISTs in historical studies, duodenal GISTs had a relatively smaller size, lower mitotic count, lower Ki-67 LI, lower p16 loss, and similar p53 expression. The 1- and 3-year recurrence-free survival rates of patients with complete resection were 100 and 95.2%., Conclusion: Patients with completely resected primary duodenal GIST seem to have a more favorable prognosis. This may be related to the different expressions of some immunohistological makers compared with GISTs of other locations.

Foot-and-mouth disease virus (FMDV) is the causative agent of foot-and-mouth disease, a severe, clinically acute, vesicular disease of cloven-hoofed animals. RNA interference (RNAi) is a mechanism for silencing gene expression post-transcriptionally that is being exploited as a rapid antiviral strategy. To identify efficacious small interfering RNAs (siRNAs) to inhibit the replication of FMDV, candidate siRNAs corresponding to FMDV VP1 gene were designed and synthesized in vitro using T7 RNA polymerase. In reporter assays, five siRNAs showed significant sequence-specific silencing effects on the expression of VP1-EGFP fusion protein from plasmid pVP1-EGFP-N1, which was cotransfected with siRNA into 293T cells. Furthermore, using RT-qPCR, viral titration and viability assay, we identified VP1-siRNA517, VP1-siRNA113 and VP1-siRNA519 that transiently acted as potent inhibitors of FMDV replication when BHK-21 cells were infected with FMDV. In addition, variations within multiple regions of the quasispecies of FMDV were retrospectively revealed by sequencing of FMDV genes, and a single nucleotide substitution was identified as the main factor in resistance to RNAi. Our data demonstrated that the three siRNA molecules synthesized with T7 RNA polymerase could have transient inhibitory effects on the replication of FMDV.

The biological mechanism of a recent discovered association of type 2 diabetes with the ACAA-insertion/deletion polymorphism at the 3'UTR of the IGF2R gene has remained unclear. A very recently emerging novel polymorphic control layer by microRNAs (miRNAs) makes it possible to elucidate this issue. In this study, a prediction by web tools MicroInspector and miRanda demonstrated that DNA sequence polymorphism (DSPs) ACAA-insertion/deletion in IGF2R 3'UTR is located within the hsa-miR-657 and hsa-miR-453 binding sites. And luciferase reporter assay revealed that hsa-miR-657 acts directly at the 3'UTR of the IGF2R. Furthermore, ACAA-deletion exerted a further repression compared with ACAA-insertion, indicating that hsa-miR-657 regulates IGF2R gene expression in a polymorphic control manner. Importantly, we also demonstrated that hsa-miR-657 can translationally regulate the IGF2R expression levels in Hep G2 cells. Thus, our findings testify the possibility that the ACAA-insertion/deletion polymorphism may result in the change of IGF2R expression levels at least in part by hsa-miR-657-mediated regulation, contributing to the elucidation for the pathogenesis of type 2 diabetes and raise the possibility that miRNAs or in combination with functional DNA sequence polymorphism may be valuable in the treatment of human type 2 diabetes.

The interest in understanding interaction between the toll-like receptor and the viral infection has increased because of its importance in disease control. Here we have cloned the porcine TLR7 (pTLR7) cDNA encoding for 1050 amino acids. The pTLR7 Exhibits 90, 87, 87, 86, 84 and 78% similarity to TLR7 from cattle, dog, horse, cat, human and mouse, respectively. RT-PCR data suggested that pTLR7 mRNA was mostly synthesized in secondary lymphoid tissues (spleen, lymph node and tonsil) and antigen-presenting cells (macrophage and B cell). The cellular experiments indicated that immunostimulatory RNA oligonucleotides (ORN) found in foot-and-mouth disease virus (FMDV) activated nuclear factor-kB and induced the expression of IFN-alpha via pTLR7. We found that the ORN induced Th1-type cytokines and activated immunocytes in PBMC. The study provides foundation for further investigation in pTLR7 interactions with its ligands and interactions between the porcine immune system and pathogens.

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in tumor necrosis factor alpha (TNFalpha) promoter with rheumatoid arthritis (RA) in Chinese Han population. Six SNPs at positions -238, -244, -308, -376, -857, -863 within TNFalpha promoter were genotyped in 367 unrelated RA patients and 271 healthy controls, using direct DNA sequencing method. Allelic, genotypic, and haplotypic associations of these SNPs with RA were examined. The frequencies of TNFalpha -308A allele and the haplotype GACC (in order of -238, -308, -857, -863) were significantly lower in RA patients when compared with healthy controls (P = 0.0046, P = 0.0045, respectively) but TNFalpha -308 polymorphism was not related to the clinical manifestations of RA patients. These results implied that TNFalpha gene itself or a gene in linkage disequilibrium with it might be associated with RA in Han population of Eastern China.

In order to investigate whether combined DNA vaccines are an ideal way to combine antigens in a single vaccine formulation, we immunized mice with three plasmids (pVSG, pVgD and pVE2), respectively, encoding the antigen of foot-and-mouth disease virus (FMDV), pseudorabies virus (PRV) and classic swine fever virus (CSFV), either alone or in a combined vaccine regimen. We also investigated the immune responses induced by a series of mixtures in which three plasmids were mixed in pairs. Then we further immunized mice with three different plasmids in separate sites and preformed an adoptive transfer experiment. While being given alone, each of the vaccine plasmids induced significant virus-specific antibody responses and splenocytes proliferative activity. But reduced immunogenicity of the pVSG plasmid was found in combined DNA vaccination, no matter whether it was injected in a single or a separate site. Removal single plasmid (pVgD or pVE2) from combined DNA vaccine led to significant increase in the immunogenicity of the pVSG plasmid (P<0.05). And the induction of immune suppression was not mediated by suppressor T cells, as demonstrated by an adoptive transfer experiment. Furthermore, by boosting with whole virus protein of FMDV, mice primed with either pVSG alone or combined DNA vaccine produced statistically significant increase in the FMDV-specific antibody titers (P<0.05). But after boosting, FMDV-specific splenocytes proliferative activity of mice primed with combined DNA vaccine was even lower than that of mice primed with pVSG alone (P<0.05). Taken together, this study reflected the immunogenicity of a single plasmid may be decreased in combined DNA immunization strategy, which still needs to be carefully evaluated before practical application.

Objective: The purpose of this study was to evaluate the accuracy of velocity parameters for the diagnosis of renal artery stenosis (RAS) with color Doppler sonography and to determine the optimal threshold values for these parameters., Methods: The study group was composed of 187 renal arteries, which were examined by color Doppler sonography and angiography. Four Doppler parameters, including the peak systolic velocities (PSVs) in the renal and interlobar arteries, the renal-aortic ratio, and the renal-interlobar ratio (RIR), were measured. Receiver operating characteristic curve analysis was performed to determine the optimal parameter. The sensitivity, specificity, and negative and positive predictive values at various threshold values were calculated., Results: Doppler sonographic examination was technically successful in 96% of renal arteries (180/187). The RIR was determined to be the best parameter. With threshold values of RIR greater than 5, PSV greater than 150 cm/s in the renal artery, renal-aortic ratio greater than 2, and PSV less than 25 cm/s in the interlobar artery, the sensitivity values were 88%, 81%, 70%, and 74%, respectively. An RIR greater than 5 and PSV less than 15 cm/s in the interlobar artery provided the optimal combination of parameters, with sensitivity and specificity of 91% and 87%, respectively., Conclusions: The RIR is the best velocity parameter in the detection of RAS (> or =50%), and its best cutoff is 5. Valuing influencing factors of PSV in the renal artery will help reduce misdiagnosis. The combination of RIR greater than 5 and PSV less than 15 cm/s in the interlobar artery provides the best diagnostic efficiency of RAS.