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Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Mental disorders are thought to affect various clinical outcomes during the perioperative period. Among them, anxiety and depression are 2 of the most common types. However, the impacts of anxiety or depression on propofol requirements remain unclear. This study aimed to investigate the effects of anxiety or depression symptoms on the propofol requirements for sedation in females. This study recruited female patients aged 18 to 65 years, with American Society of Anesthesiologists physical status classification of 1 to 2, who were scheduled for hysteroscopic surgery under propofol-based intravenous anesthesia. The day before surgery, the Hospital Anxiety and Depression Scale (HADS) was used to assess the symptoms of anxiety and depression within the past 6 months. Target-controlled propofol was gradually titrated to achieve 3 desired levels of sedation: Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) score 3, MOAA/S score 1, and MOAA/S score 1 and Narcotrend Index

Reperfusion of the ischemic intestine often leads to drive distant organ injury, especially injuries associated with hepatocellular dysfunction. The precise molecular mechanisms and effective multiple organ protection strategies remain to be developed. In the current study, significant remote liver dysfunction was found after 6 hours of reperfusion according to increased histopathological scores, serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, as well as enhanced bacterial translocation in a rat intestinal ischemia/reperfusion (I/R) injury model. Moreover, receptor-interacting protein kinase 1/3 (RIP1/3) and phosphorylated-MLKL expressions in tissue were greatly elevated, indicating that necroptosis occurred and resulted in acute remote liver function impairment. Inhibiting the necroptotic pathway attenuated HMGB1 cytoplasm translocation and tissue damage. Meanwhile, macrophage-depletion study demonstrated that Kupffer cells (KCs) are responsible for liver damage. Blocking HMGB1 partially restored the liver function via suppressed hepatocyte necroptosis, tissue inflammation, hepatic KCs, and circulating macrophages M1 polarization. What's more, HMGB1 neutralization further protects against intestinal I/R-associated liver damage in microbiota-depleted rats. Therefore, intestinal I/R is likely associated with acute liver damage due to hepatocyte necroptosis, and which could be ameliorated by Nec-1 administration and HMGB1 inhibition with the neutralizing antibody and inhibitor. Necroptosis inhibition and HMGB1 neutralization/inhibition, may emerge as effective pharmacological therapies to minimize intestinal I/R-induced acute remote organ dysfunction.

Fluid resuscitation is the first-line antishock treatment in severe acute pancreatitis (SAP). Currently, although mentions of complications related to aggressive fluid resuscitation are very frequent, a lack of proper handling of complications remains. One of the most important complications is intestinal barrier injury, including intestinal ischemia-reperfusion injury following aggressive fluid resuscitation. Once injured, the intestinal barrier may serve as the source of additional diseases, including systemic inflammatory response syndrome and multiple organ dysfunction syndrome, which aggravate SAP. This study focused on the underlying mechanisms of gut barrier dysfunction in rats induced by aggressive fluid resuscitation in SAP. This study further indicated the important role of necroptosis in intestinal barrier injury which could be relieved by using necroptosis-specific inhibitor Nec-1 before aggressive fluid resuscitation, thus reducing intestinal barrier damage. We also found pancreas damage after intestinal ischemia/reperfusion challenge and indicated the effects of high mobility group protein B1 in the vicious cycle between SAP and intestinal barrier damage.

Intestinal ischemia/reperfusion (I/R) injury is associated with a high morbidity and mortality. Vasopressin is administered to critically ill patients with potential intestinal I/R. However, the impacts of vasopressin on intestinal epithelia under ischemic/anoxic conditions remain unclear. The aim of the present study was to evaluate the effects of terlipressin, a highly selective vasopressin V1 receptor agonist, on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damage in intestinal epithelial cells (IEC-6). IEC-6 cells were subjected to OGD for 4 h, followed by 4 h re-oxygenation. Terlipressin was incubated with cells for 4 h following OGD. Following OGD/R, IEC-6 cell viability, proliferation and apoptosis, as well as cell cycle dynamics, were assessed and the levels of tumor necrosis factor (TNF)-α and 15-F2t-isoprostane in the culture medium were measured. In addition, wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, was administrated to investigate the mechanism of terlipressin action. The results demonstrated that IEC-6 cell viability and proliferation decreased, and cell apoptosis increased, following OGD/R. However, IEC-6 cell cycle dynamics did not significantly change 4 h after OGD. Incubation with 25 nM terlipressin significantly improved cell viability, proliferation and apoptosis. Furthermore, terlipressin inhibited the secretion of TNF-α and 15-F2t-isoprostane from IEC-6 cells following OGD/R. The aforementioned effects of terlipressin were completely abolished following the application of 2 µM wortmannin. Therefore, the current study demonstrated that terlipressin administration following OGD attenuates OGD/R-induced cell damage via the PI3K signaling pathway. These results may help physicians to better understand and more effectively use terlipressin in a clinical setting.

Background Intestinal ischemia-reperfusion (I/R) injury is a common clinical event with high mortality, but its mechanism is elusive. Although long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in I/R damage in other organs, the changes in their expression and potential roles in intestinal I/R remain unclear. Methods The expression profiles of both lncRNAs and mRNAs in mouse intestinal mucosa after intestinal I/R were explored by a microarray approach, and their biological functions were elucidated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Then, some lncRNAs were further verified by qRT-PCR. Based on the coding-noncoding gene coexpression (CNC) network analyses, the role of lncRNA AK089510 in intestinal I/R-induced intestinal mucosa apoptosis was investigated by knockdown assay in vitro. Results A total of 3602 aberrantly expressed lncRNAs (1503 upregulated and 2099 downregulated) and 3158 mRNAs (1528 upregulated and 1630 downregulated) were identified. The dysregulated transcripts were enriched in the lipid metabolic process, apoptotic process, reactive oxygen species metabolic process, MAPK, TNF, ErbB, mTOR, and FoxO signaling pathways, and so on. The overexpression of lncRNA AK089510 was validated by qRT-PCR, and the CNC analysis revealed its target mRNAs. AK089510-siRNA reduced Casp6 and Casp7 expression and suppressed intestinal epithelial cell apoptosis after oxygen-glucose deprivation treatment. Conclusions Our study revealed the lncRNA and mRNA expression patterns in mouse intestinal mucosa after intestinal I/R and predicted their potential functions and pathways. We identified AK089510 as a novel lncRNA involved in the apoptosis of intestinal mucosa, advancing our understanding of the molecular mechanisms of intestinal I/R injury.

Background The debate on lung-protective ventilation strategies for surgical patients is ongoing. Evidence suggests that the use of low tidal volume VT improves clinical outcomes. However, the optimal levels of PEEP and recruitment manoeuvre (RM) strategies incorporated into low VT ventilation remain unclear. Methods Several electronic databases were searched to identify RCTs that focused on comparison between low VT strategy and conventional mechanical ventilation (CMV), or between two different low VT strategies in surgical patients. The primary outcome was postoperative pulmonary complications (PPCs). The secondary outcomes were atelectasis, pneumonia, acute respiratory distress syndrome, and short-term mortality. Bayesian network meta-analyses were performed using WinBUGS. The odds ratios (ORs) and corresponding 95% credible intervals (CrIs) were estimated. Results Compared with CMV, low VT ventilation with moderate-to-high PEEP reduced the risk of PPCs (moderate PEEP [5–8 cm H2O]: OR 0.50 [95% CrI: 0.28, 0.89]; moderate PEEP+RMs: 0.39 [0.19, 0.78]; and high PEEP [≥9 cm H2O]+RMs: 0.34 [0.14, 0.79]). Low VT ventilation with moderate-to-high PEEP and RMs also specifically reduced the risk of atelectasis compared with CMV (moderate PEEP+RMs: OR 0.36 [95% CrI: 0.16, 0.87]; and high PEEP+RMs: 0.41 [0.15, 0.97]), whilst low VT ventilation with moderate PEEP was superior to CMV in reducing the risk of pneumonia (OR 0.46 [95% CrI: 0.15, 0.94]). Conclusions The combination of low VT ventilation and moderate-to-high PEEP (≥5 cm H2O) seems to confer lung protection in surgical patients undergoing general anaesthesia. Clinical trial registration PROSPERO (CRD42019144561)

Cell death is an important biological process that is believed to have a central role in intestinal ischaemia/reperfusion (I/R) injury. While the apoptosis inhibition is pivotal in preventing intestinal I/R, how necrotic cell death is regulated remains unknown. Necroptosis represents a newly discovered form of programmed cell death that combines the features of both apoptosis and necrosis, and it has been implicated in the development of a range of inflammatory diseases. Here, we show that receptor‐interacting protein 1/3 (RIP1/3) kinase and mixed lineage kinase domain‐like protein recruitment mediates necroptosis in a rat model of ischaemic intestinal injury in vivo. Furthermore, necroptosis was specifically blocked by the RIP1 kinase inhibitor necrostatin‐1. In addition, the combined treatment of necrostatin‐1 and the pan‐caspase inhibitor Z‐VAD acted synergistically to protect against intestinal I/R injury, and these two pathways can be converted to one another when one is inhibited. In vitro, necrostatin‐1 pre‐treatment reduced the necroptotic death of oxygen‐glucose deprivation challenged intestinal epithelial cell‐6 cells, which in turn dampened the production of pro‐inflammatory cytokines (tumour necrosis factor‐α and interleukin‐1β), and suppressed high‐mobility group box‐1 (HMGB1) translocation from the nucleus to the cytoplasm and the subsequent release of HMGB1 into the supernatant, thus decreasing the activation of Toll‐like receptor 4 and the receptor for advanced glycation end products. Collectively, our study reveals a robust RIP1/RIP3‐dependent necroptosis pathway in intestinal I/R‐induced intestinal injury in vivo and in vitro and suggests that the HMGB1 signalling is highly involved in this process, making it a novel therapeutic target for acute ischaemic intestinal injury.

BACKGROUND Circulating cardiac troponin levels are powerful predictors of prognosis in many clinical settings, but their association with outcomes after noncardiac surgery is unclear. OBJECTIVES The aim of this systematic review was to summarise current evidence on the association of pre-operative troponin elevation with postoperative major adverse cardiac events (MACE) and mortality in patients undergoing noncardiac surgery. DESIGN Systematic review of observational studies with meta-analysis. DATA SOURCES PubMed, EMBASE and Science Citation Index Expanded (ISI Web of Science) from their inception to 1 October 2017. ELIGIBILITY CRITERIA Observational studies reporting the associations between pre-operative troponin levels and MACE and all-cause mortality after noncardiac surgeries were included. RESULTS Ten studies met the eligibility criteria. The entire body of evidence addressing the research question was based on a total of 10 371 patients: 4.7 to 68.3% (median 23.8%) of patients had elevated troponin levels before surgery. Elevated pre-operative troponin was significantly associated with short-term MACE (seven studies, 5180 patients: odds ratio (OR) 6.92, 95% confidence interval (CI) 3.85 to 12.42), short-term mortality (five studies, 6103 patients: OR 4.23, 95% CI 2.27 to 7.89) and long-term mortality (two studies, 760 patients: OR 2.51, 95% CI 1.47 to 4.29). The associations remained significant when only multivariate-adjusted results were analysed. Overall, the reviewers' certainty about the summary estimates of the associations was very low. CONCLUSION Current evidence suggests that pre-operative high troponin levels are significantly associated with adverse cardiac events and mortality after noncardiac surgery. TRIAL REGISTRATION This systematic review was registered in the International Prospective Register of Systematic Reviews (Centre for Reviews and Dissemination 42017077837).

Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

Objectives Helical tomotherapy (HT) can be applied to treat complex malignant cancer with high-precise radiotherapy, and it can reduce the damage to normal tissues and improve treatment effects. But the procurement of HT must be approved by relevant departments of administration affairs. This study, appointed by the National Health and Family Planning Commission of China and undertook by the National Health Development Research Center and the Chinese Evidence-Based Medicine Centre, was aimed to rapidly assess the effectiveness, safety, costs, and applicability of HT, so as to provide currently available best evidence for decision-makers of health policies. Methods We electronically searched databases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, and other professional websites. Two reviewer independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed quality, and then performed descriptive analysis. Results (i) We finally included 150 studies, encompassing 5 HTAs, 18 CCTs, and 127 observational studies. (ii) The included HTAs were published during 2006–2009, providing fairly less evidence of low quality and the results of 145 primary studies showed that: HT had been used mainly in the treatments of 14 kinds of cancer, with low total toxicity and high survival rates. Although the quality of the included studies was poor, there was much evidence about prostate cancer, head and neck cancer, nasopharynx cancer, cervical cancer, lung cancer and liver cancer, with enough sample and fairly reliable results in HT efficacy and safety. And (iii) a total of 56 clinical trials were registered in Clinicaltrials.gov, most of which were registered by the occident. Among them, 9 were completed but the results had not been published yet. Conclusions The evidence of this study showed that, HT is safe and effective in clinic. But the abovementioned conclusion needs to be verified by conducting more high-quality studies with long-term follow-up. The costs of HT in procurement, maintenance, and application are high; and the skills, training, and qualification of operators are required. We suggest that the procurement of HT should be reduced; it should be allocated rationally and effectively used after comprehensive assessment in China's cancer epidemiology characteristics, health resource allocation, disease burden, medical service level, etc.; and also high-quality studies with long-term follow-up should be financially supported on the basis of establishing projects, so as to provide local evidence and consistently guide and improve scientific decision-making.

Objectives Capsule endoscopy (CE) has been widely used in the diagnosis of small bowel disease (SBD) in the world. To bring CE into the national health insurance directory, and intensify its popularization in primary hospital, the government needs high-quality HTA evidence for decision makers. We were appointed by the National Health and Family Planning Commission of China to evaluate the effectiveness, safety, economy, and applicability of CE in the diagnosis of SBD, to provide the best currently available evidence for decision making. Methods We searched the Cochrane Library (Issue 8, 2013), PubMed, EMbase, INAHTA, VIP, CBM, CNKI and WanFang Data. All confirmed or suspected SBD patients with diagnosis by CE versus other alternative therapies were considered. Health technology assessments (HTAs), systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), guidelines and economic studies were included. Two investigators selected studies, assessed the quality and extracted data independently, and a descriptive analysis was used. Results We included 4 HTAs, 11 SRs/meta-analyses, 2 RCTs, 5 guidelines, and 10 economic studies for assessment. The results showed that the disease detection rate of CE was higher than that of many other traditional technologies and that the main adverse event for CE was retention (0.7% to 3.0%). These results were consistent with those of the guidelines. Comprehensive results of economic studies showed the superiority of CE compared with other technologies. As the first choice, CE can decrease potential costs, especially when used in outpatients. Conclusions (i) CE has advantages in diagnostic yield, safety, and cost in the diagnosis of SBD, but some limitations exist. It still needs more high-quality evidence on CE diagnosis accuracy. (ii) When the government approves the introduction of CE in a hospital, many factors must be considered, such as the local disease burden, clinical demand, ability to pay, and staff. At the same time, it is necessary to standardize training for operating physicians, to reduce economic losses caused by poor technical ability of the medical staff.

Intestinal ischaemia/reperfusion (I/R) severely disrupts gut barriers and leads to high mortality in the critical care setting. Transforming growth factor (TGF)‐β1 plays a pivotal role in intestinal cellular and immune regulation. However, the effects of TGF‐β1 on intestinal I/R injury remain unclear. Thus, we aimed to investigate the effects of TGF‐β1 on gut barriers after intestinal I/R and the molecular mechanisms. Intestinal I/R model was produced in mice by clamping the superior mesenteric artery for 1 hr followed by reperfusion. Recombinant TGF‐β1 was intravenously infused at 15 min. before ischaemia. The results showed that within 2 hrs after reperfusion, intestinal I/R disturbed intestinal immunoglobulin A class switch recombination (IgA CSR), the key process of mucosal IgA synthesis, and resulted in IgA dysfunction, as evidenced by decreased production and bacteria‐binding capacity of IgA. Meanwhile, the disruptions of intestinal microflora and mucosal structure were exhibited. Transforming growth factor‐β1 activated IgA CSR as evidenced by the increased activation molecules and IgA precursors. Strikingly, TGF‐β1 improved intestinal mucosal IgA dysfunction, dysbiosis and epithelial damage at the early stage after reperfusion. In addition, SB‐431542, a specific inhibitor of activating mothers against decapentaplegic homologue (SMAD) 2/3, totally blocked the inductive effect of TGF‐β1 on IgA CSR and almost abrogated the above protective effects on intestinal barriers. Taken together, our study demonstrates that TGF‐β1 protects intestinal mucosal IgA immunity, microbiota and epithelial integrity against I/R injury mainly through TGF‐β receptor 1/SMAD 2/3 pathway. Induction of IgA CSR may be involved in the protection conferred by TGF‐β1.

Background Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury induced by intestinal I/R. Methods We used both an in vivo rat model of intestinal I/R injury and a cell culture model using IEC-6 cells (the rat intestinal epithelial cell line) subjected to oxygen and glucose deprivation (OGD). Remifentanil was administered before ischemia or OGD, and 3 specific opioid receptors antagonists, naltrindole (a δ-OR selective antagonist), nor-binaltorphimine (nor-BNI, a κ-OR selective antagonist), and CTOP (a μ-OR selective antagonist), were administered before preconditioning to determine the role of opioid receptors in the intestinal protection mediated by remifentanil. Results In the in vivo rat model, intestinal I/R induced obvious intestinal injury as evidenced by increases in the Chiu score, serum diamine oxidase activity, the apoptosis index, and the level of cleaved caspase-3 protein expression, whereas remifentanil preconditioning significantly improved these changes in vivo. In the in vitro cell culture exposed to OGD, cell viability (MTT, ie, (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometric analysis showed that remifentanil preconditioning enhanced IEC-6 cell viability and decreased apoptosis. In both in vitro and in vivo models, the aforementioned protective effects of remifentanil preconditioning were abolished completely by previous administration of the δ- or μ-opioid markedly attentuated but not the κ-opioid receptor antagonist. Conclusion Remifentanil preconditioning appears to act via δ- and μ-opioid receptors to protect the small intestine from intestinal I/R injury by attenuating apoptosis of the intestinal mucosal epithelial cells.

Intestinal ischemia/reperfusion (I/R) disrupts intestinal mucosal integrity and immunoglobulin A (IgA) generation. It has recently been shown that the programmed cell death-1 receptor (PD-1) plays a crucial role in regulating intestinal secreted IgA (sIgA).To evaluate changes in PD-1 and PD-ligand 1 (PD-L1) expression on Peyer's patches (PP) CD4(+) T cells and to investigate the correlation between PD-1/PD-L1 and intestinal IgA production/mucosal integrity in mice following intestinal I/R.I/R injury was induced by clamping the superior mesenteric artery for 1 h followed by 2-h reperfusion. PD-1/PD-L1 expression on PP CD4(+) T cells was measured in I/R and sham-operated mice. Additionally, transforming growth factor-β1 (TGF-β1) and interleukin-21 (IL-21) mRNA in CD4(+) T cells and IgA(+) and IgM(+) in PP B cells, as well as intestinal mucosal injury and sIgA levels, were assessed.PD-1/PD-L1, TGF-β1, and IL-21 expression was down-regulated after intestinal I/R. Furthermore, IgA(+) B cells decreased and IgM(+) B cells increased in mice with intestinal I/R. Importantly, decreased PD-1/PD-L1 expression was correlated with increased mucosal injury and decreased IgA levels, as well as with decreased TGF-β1 and IL-21 expression.Intestinal I/R inhibits PD-1/PD-L1 expression on PP CD4(+) T cells, which was associated with an impaired intestinal immune system and mechanical barriers. Our study indicates that PD-1/PD-L1 expression on CD4(+) T cells may be involved in the pathogenesis of intestinal I/R injury.

Intestinal ischemia/reperfusion (I/R) injury remains a major clinical event and contributes to high morbidity and mortality rates, but the underlying mechanisms remain elusive. Recent studies have demonstrated that microRNAs (miRNAs) have important roles in organ I/R injury, but the changes and potential roles of miRNAs in intestinal I/R-induced intestinal injury are unclear. This study was designed to analyze the miRNA expression profiles in intestinal mucosa after I/R injury and to explore the role of target miRNA during this process. Using miRNA microarray analysis, we found changes of 19 miRNAs from the expression profile of miRNAs in a mouse model of intestinal I/R and further verified them by RT-qPCR. Here, we report that miR-378 is one of the markedly decreased miRNAs and found the putative target mRNA that is linked to cell death after applying the TargetScan, miRanda, CLIP-Seq and miRDB prediction algorithms. Our results show that the overexpression of miR-378 significantly ameliorated intestinal tissue damage in wild-type and transgenic mice and oxygen glucose deprivation/reperfusion-challenged IEC-6 cell injury. Moreover, miR-378 overexpression reduced intestinal epithelial cell apoptosis in both in vivo and in vitro ischemic models and attenuated cleaved caspase-3 expression. Collectively, our results revealed that the suppression of caspase-3 activation by miRNA-378 overexpression may be involved in the protective effects of intestinal ischemic damage. MiRNA-378 may serve as a key regulator and therapeutic target in intestinal I/R injury.

15-F2t-isoprostane is not only a specific marker of lipid peroxidation but also demonstrated to have potent bioactivities and can exert deleterious effects via activating thromboxane A2 receptor (TxA2r). We already demonstrated that lipid peroxidation represents a mechanism of intestinal ischemia/reperfusion (I/R) injury. But no studies have focused on 15-F2t-isoprostane production and its biological actions on postischemic intestine during intestinal I/R. This study was carried to investigate whether the mechanism of endogenous 15-F2t-isoprostane action is involved in the pathogenesis of intestinal I/R and administration of synthetic 15-F2t-isoprostane could exacerbate intestinal insult after intestinal I/R in vivo and in vitro. In comparison with that of the sham control, we reported that endogenous 15-F2t-isoprostane was liberated following intestinal I/R injury in rats, and using the TxA2r antagonist SQ29548 resulted in significant intestinal protection, evidenced by reduced lipid peroxidation, inflammation, and alleviated intestinal mucosal microvascular vasoconstriction. Further research found that in vivo administration of synthetic 15-F2t-isoprostane exacerbated intestinal I/R injury by disturbing microvascular perfusion and accumulating anaerobic metabolism. Meanwhile, 15-F2t-isoprostane did not change Hypoxia/Reoxygenation-induced IEC-6 cell viability but aggravated HUVECs cell death in vitro. Collectively, our results showed that locally produced 15-F2t-isoprostane was in proportion to the severity of oxidative stress-induced intestinal injury and its detrimental effects can be attenuated through TxA2r inactivation. Exogenous 15-F2t-isoprostane exacerbated intestinal I/R injury, which may be contributable to its biological actions on endothelium, rather than intestinal epithelium.

Capsule endoscopy (CE) has been widely used in the diagnosis of small bowel disease (SBD) in the world. To bring CE into the national health insurance directory, and intensify its popularization in primary hospital, the government needs high-quality HTA evidence for decision makers. We were appointed by the National Health and Family Planning Commission of China to evaluate the effectiveness, safety, economy, and applicability of CE in the diagnosis of SBD, to provide the best currently available evidence for decision making.We searched the Cochrane Library (Issue 8, 2013), PubMed, EMbase, INAHTA, VIP, CBM, CNKI and WanFang Data. All confirmed or suspected SBD patients with diagnosis by CE versus other alternative therapies were considered. Health technology assessments (HTAs), systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), guidelines and economic studies were included. Two investigators selected studies, assessed the quality and extracted data independently, and a descriptive analysis was used.We included 4 HTAs, 11 SRs/meta-analyses, 2 RCTs, 5 guidelines, and 10 economic studies for assessment. The results showed that the disease detection rate of CE was higher than that of many other traditional technologies and that the main adverse event for CE was retention (0.7% to 3.0%). These results were consistent with those of the guidelines. Comprehensive results of economic studies showed the superiority of CE compared with other technologies. As the first choice, CE can decrease potential costs, especially when used in outpatients.(i) CE has advantages in diagnostic yield, safety, and cost in the diagnosis of SBD, but some limitations exist. It still needs more high-quality evidence on CE diagnosis accuracy. (ii) When the government approves the introduction of CE in a hospital, many factors must be considered, such as the local disease burden, clinical demand, ability to pay, and staff. At the same time, it is necessary to standardize training for operating physicians, to reduce economic losses caused by poor technical ability of the medical staff.

Helical tomotherapy (HT) can be applied to treat complex malignant cancer with high-precise radiotherapy, and it can reduce the damage to normal tissues and improve treatment effects. But the procurement of HT must be approved by relevant departments of administration affairs. This study, appointed by the National Health and Family Planning Commission of China and undertook by the National Health Development Research Center and the Chinese Evidence-Based Medicine Centre, was aimed to rapidly assess the effectiveness, safety, costs, and applicability of HT, so as to provide currently available best evidence for decision-makers of health policies.We electronically searched databases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, and other professional websites. Two reviewer independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed quality, and then performed descriptive analysis.(i) We finally included 150 studies, encompassing 5 HTAs, 18 CCTs, and 127 observational studies. (ii) The included HTAs were published during 2006-2009, providing fairly less evidence of low quality and the results of 145 primary studies showed that: HT had been used mainly in the treatments of 14 kinds of cancer, with low total toxicity and high survival rates. Although the quality of the included studies was poor, there was much evidence about prostate cancer, head and neck cancer, nasopharynx cancer, cervical cancer, lung cancer and liver cancer, with enough sample and fairly reliable results in HT efficacy and safety. And (iii) a total of 56 clinical trials were registered in Clinicaltrials.gov, most of which were registered by the occident. Among them, 9 were completed but the results had not been published yet.The evidence of this study showed that, HT is safe and effective in clinic. But the abovementioned conclusion needs to be verified by conducting more high-quality studies with long-term follow-up. The costs of HT in procurement, maintenance, and application are high; and the skills, training, and qualification of operators are required. We suggest that the procurement of HT should be reduced; it should be allocated rationally and effectively used after comprehensive assessment in China's cancer epidemiology characteristics, health resource allocation, disease burden, medical service level, etc.; and also high-quality studies with long-term follow-up should be financially supported on the basis of establishing projects, so as to provide local evidence and consistently guide and improve scientific decision-making.