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| 1 | Clinical value of rapid urine trypsinogen-2 test strip, urinary trypsinogen activation peptide, and serum and urinary activation peptide of carboxypeptidase B in acute pancreatitis显示文摘AIM: To assess the usefulness of urinary trypsinogen-2 test strip, urinary trypsinogen activation peptide (TAP),and serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) in the diagnosisof acute pancreatitis.METHODS: Patients with acute abdominal pain and hospitalized within 24 h after the onset of symptoms were prospectively studied. Urinary trypsinogen-2 was considered positive when a clear blue line was observed (detection limit 50 μg/L). Urinary TAP was measured using a quantitative solid-phase ELISA, and serum and urinary CAPAP by a radioimmunoassay method.RESULTS: Acute abdominal pain was due to acute pancreatitis in 50 patients and turned out to be extrapancreatic in origin in 22 patients. Patients with acute pancreatitis showed significantly higher median levels of serum and urinary CAPAP levels, as well as amylase and lipase than extrapancreatic controls. Median TAP levels were similar in both groups. The urinary trypsinogen-2 test strip was positive in 68% of patients with acute pancreatitis and 13.6% in extrapancreatic controls (P<0.01). Urinary CAPAP was the most reliable test for the diagnosis of acute pancreatitis (sensitivity 66.7%, specificity 95.5%, positive and negative predictive values 96.6% and 56.7%, respectively), with a 14.6 positive likelihood ratio for a cut-off value of 2.32 nmol/L.CONCLUSION: In patients with acute abdominal pain,hospitalized within 24 h of symptom onset, CAPAP in serum and urine was a reliable diagnostic marker of acute pancreatitis. Urinary trypsinogen-2 test strip showed a clinical value similar to amylase and lipase.Urinary TAP was not a useful screening test for the diagnosis of acute pancreatitis. | Jesús Sáez Juan Martínez Celia Trigo José Sánchez-Payá Luis Compay Raquel Laveda Pilar Grió Cristina García Miguel Pérez-Mateo | 2005 | World Journal of Gastroenterology2005，11，46： | 21 |
| 2 | Influence of gut microbiota on neuropsychiatric disorders显示文摘The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain(gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome(microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future. | María Carmen Cenit Yolanda Sanz Pilar Codoner-Franch | 2017 | World Journal of Gastroenterology2017，23，30： | 21 |
| 3 | The Immune System and the Role of Inflammation in Perinatal Depression显示文摘Major depression during pregnancy is a common psychiatric disorder that arises from a complex and multifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic–pituitary–adrenal axis hyperactivity. Dysregulation of this intricate neuroimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neuropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during pregnancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Th1/Th2 bias towards a predominant Th1/Th17 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy. | Philippe Leff-Gelman Ismael Mancilla-Herrera Monica Flores-Ramos Carlos Cruz-Fuentes Juan Pablo Reyes-Grajeda maría del pilar garcía-cuétara Marielle Danitza Bugnot-Perez David Ellioth Pulido-Ascencio | 2016 | Neuroscience Bulletin2016，32，4： | 17 |
| 4 | Endosonography-guided cholangiopancreatography as a salvage drainage procedure for obstructed biliary and pancreatic ducts显示文摘Endoscopic ultrasound allows transmural access to the bile or pancreatic ducts and subsequent contrast injection to provide ductal drainage under fluoroscopy using endoscopic retrograde cholangiopancreatography (ERCP)-based techniques.Differing patient specifics and operator techniques result in six possible variant approaches to this procedure,known as endosonography-guided cholangiopancreatography(ESCP). ESCP has been in clinical use for a decade now,with over 300 cases reported.It has become established as a salvage procedure after failed ERCP in the palliation of malignant biliary obstruction.Its role in the management of clinically severe chronic/relapsing pancreatitis remains under scrutiny.This review aims to clarify the concepts underlying the use of ESCP and to provide technical tips and a detailed step-by-step procedural description. | Manuel Perez-Miranda Carlos de la Serna Pilar Diez-Redondo Juan J Vila | 2010 | World Journal of Gastrointestinal Endoscopy2010，2，6： | 15 |
| 5 | Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk显示文摘AIM: To examine the relationships between pre-diagnostic biomarkers and colorectal cancer risk and assess their relevance in predictive models.METHODS: A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplémentation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007. Cases (n = 50) were matched with two randomly selected controls (n = 100). Conditional logistic regression models were used to investigate the associations between pre-diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory potential of the models. RESULTS: Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend = 0.03). Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend = 0.02). No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement = 0.01, RIDI = 26.5%). CONCLUSION: These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies. | Mathilde Touvier Léopold Fezeu Namanjeet Ahluwalia Chantal Julia Nathalie Charnaux Angela Sutton Caroline Méjean Paule Latino-Martel Serge Hercberg Pilar Galan Sébastien Czernichow | 2012 | World Journal of Gastroenterology2012，18，22： | 15 |
| 6 | Therapy with stem cells in inflammatory bowel disease显示文摘Inflammatory bowel disease(IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a significant percentage of patients are refractory to therapy. In recent years there have been great advances in our knowledge of stem cells and their therapeutic applications. In this context, autologous hematopoietic stem cell transplantation(HSCT) has been used in application to severe refractory Crohn's disease(CD), with encouraging results. Allogenic HSCT would correct the genetic defects of the immune system, but is currently not accepted for the treatment of IBD because of its considerable risks. Mesenchymal stem cells(MSCs) have immune regulatory and regenerative properties, and low immunogenicity(both autologous and allogenic MSCs). Based on these properties, MSCs have been used via the systemic route in IBD with promising results, though it is still too soon to draw firm conclusions. Their local administration in perianal CD is the field where most progress has been made in recent years, with encouraging results. The next few years will be decisive for defining the role of such therapy in the management of IBD. | María del Pilar Martínez-Montiel Gonzalo Jesús Gómez-Gómez Ana Isabel Flores | 2014 | World Journal of Gastroenterology2014，20，5： | 13 |
| 7 | Hepatitis B and inflammatory bowel disease: Role of antiviral prophylaxis显示文摘Hepatitis B virus (HBV) is a very common infection worldwide. Its reactivation in patients receiving immunosuppression has been widely described as being associated with significant morbidity and mortality unless anti-viral prophylaxis is administered. Treatment in inflammatory bowel disease (IBD) patients has changed in recent years and immunosuppression and biological therapies are now used more frequently than before. Although current studies have reported an incidence of hepatitis B in inflammatory bowel disease patients similar to that in the general population, associated liver damage remains an important concern in this setting. Liver dysfunction may manifest in several ways, from a subtle change in serum aminotransferase levels to fulminant liver failure and death. Patients undergoing double immunosuppression are at a higher risk, and reactivation usually occurs after more than one year of treatment. As preventive measures, all IBD patients should be screened for HBV markers at diagnosis and those who are positive for the hepatitis B surface antigen should receive antiviral prophylaxis before undergoing immunosuppression in order to avoid HBV reactivation. Tenofovir/entecavir are preferred to lamivudine as nucleos(t)ide analogues due to their better resistance profile. In patients with occult or resolved HBV, viral reactivation does not appear to be a relevant issue and regular DNA determination is recommended during immunosuppression therapy. Consensus guidelines on this topic have been published in recent years. The prevention and management of HBV infection in IBD patients is addressed in this review in order to address practical | Pilar López-Serrano Jose Lázaro Pérez-Calle Maria Dolores Sánchez-Tembleque | 2013 | World Journal of Gastroenterology2013，19，9： | 12 |
| 8 | Effect of initial material bulk density and easily-degraded organic matter content on temperature changes during composting of cucumber stalk显示文摘To inactivate the potentially pathogenic microorganisms and safely utilize vegetable waste compost, ultra-high temperatures(> 70°C) should be maintained during the composting without having an inhibitory effect on maturity. This study investigated the influence of bulk density(part 1) and easily-degraded organic matter content(EDOMC, part 2) on temperature evolution during vegetable waste composting: Part 1: corn straw with different particle sizes was used to achieve different bulk densities in the composting material(BD1–BD3); Part 2: partial or total substitution of the corn straw by corn starch was carried out to obtain different EDOMC(ED1–ED4). The composting experiments were conducted in a labscale reactor(1.75 kg material) and lasted for 30 d. Temperature and CO2 emission were recorded daily, and the organic matter, lignocellulose, microbial activity, germination index(GI) and C/N of the samples were measured at different stages. The highest temperature(65.7°C) in part 1 occurred in the treatment with the bulk density of 0.35 g/cm3, which also had the longest thermophilic phase. Bulk density was found to seriously influence the utilization efficiency of O2 and heat transfer through materials, rather than heat production from organic matter degradation. In experiment part 2, the highest temperature was obtained with EDOMC of 45%(71.4°C). Therefore, adjusting the bulk density to 0.35 g/cm3 and the easily-degraded organic matter content of the initial material to 45% was the best combination for reaching temperatures above 70°C during composting, with no inhibitory effect on the maturity of the compost product. | Ruixue Chang Qiuyue Guo Qing Chen Maria Pilar Bernal Qian Wang Yanming Li | 2019 | Journal of Environmental Sciences2019，31，6： | 11 |
| 9 | Inflammatory status in human hepatic cirrhosis显示文摘This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus(HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcoholinduced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis(HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared withHCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gutmesenteric lymph nodes-peritoneal-systemic axis. | María Martínez-Esparza María Tristán-Manzano Antonio J Ruiz-Alcaraz Pilar García-Penarrubia | 2015 | World Journal of Gastroenterology2015，21，41： | 10 |
| 10 | Are proton pump inhibitors a new antidiabetic drug? A cross sectional study显示文摘AIM: To investigate the effect of proton pump inhibitors (PPIs) on glycemic control (HbA1c) in type 2 diabetic patients. METHODS: A crosssectional study of consecutive in-patients admitted to hospital in any department during the fi rst semester of the year 2010 who had a recent HbA1c measurement. The study excluded those with a diagnosis of hyperglycemic decompensation, diabetic onset or pregnancy. It compared HbA1c levels of those taking PPIs and those not. RESULTS: A total of 97 patients were recruited. The average HbA1C level was 7.0% ± 1.2%. Overall PPI consumption was 55.7%. HbA1c was signif icantly lower in individuals who took PPIs: -0.6%, 95% CI: -0.12 to-0.83. People who used PPIs with some type of insulin therapy had a HbA1c reduction by -0.8%, 95% CI: -0.12 to -1.48. For the rest of subgroup analysis based on the antidiabetic drug used, PPI consumption always exhibited lower HbA1c levels. CONCLUSION: PPIs seems to be consistently associated with better glycemic control in type 2 diabetes. HbA1c reduction observed is similar to incretin-based therapies. | Diana Boj-Carceller Pilar Bocos-Terraz Miguel Moreno-Vernis Alejandro Sanz-Paris Pablo Trincado-Aznar Ramón Albero-Gamboa | 2011 | World Journal of Diabetes2011，2，12： | 7 |
| 11 | Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?显示文摘Inflammatory bowel diseases are inflammatory, chronic and progressive diseases of the intestinal tract for which no curative treatment is available. Research in other fields with stem cells of different sources and with immunoregulatory cells(regulatory T-lymphocytes and dendritic T-cells) opens up new expectations for their use in these diseases. The goal for stem cell-based therapy is to provide a permanent cure. To achieve this, it will be necessary to obtain a cellular product, original or genetically modified, that has a high migration capacity and homes into the intestine, has high survival after transplantation, regulates the immune reaction while not being visible to the patient's immune system, and repairs the injured tissue. | Ana I Flores Gonzalo J Gómez-Gómez ángeles Masedo-González M Pilar Martínez-Montiel | 2015 | World Journal of Stem Cells2015，7，2： | 7 |
| 12 | Circadian rhythms in the pathogenesis of gastrointestinal diseases显示文摘The etiology of digestive pathologies such as irritable bowel syndrome(IBS), inflammatory bowel diseases(IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms(chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets. | Pilar Codonr-Franch Marie Gombert | 2018 | World Journal of Gastroenterology2018，24，38： | 7 |
| 13 | Gene expression changes in spleens of the wildlife reservoir species,Eurasian wild boar(Sus scrofa),naturally infected with Brucella suis biovar 2显示文摘Brucella suis is responsible for swine brucellosis worldwide.Of the five different B.suis biovars(bv.),bv.2 appears restricted to Europe where it is frequently isolated from wild boar and hares,can infect pigs and can cause human brucellosis.In this study,the differential gene expression profile was characterized in spleens of Eurasian wild boar naturally infected with B.suis bv.2.Of the 20,201 genes analyzed in the microarray,633 and 1,373 were significantly(fold change > 1.8;P < 0.01) upregulated and downregulated,respectively,in infected wild boar.The analysis was focused on genes that were over represented after conditional test for biological process gene ontology.Upregulated genes suggested that B.suis bv.2 infection induced cell maturation,migration and/or proliferation in infected animals.The genes downregulated in infected wild boar impaired the activity of several important cellular metabolic pathways such as metabolism,cytoskeleton organization and biogenesis,immune response and lysosomal function and vesicle-mediated transport.In addition,the response to stress,sperm fertility,muscle development and apoptosis seemed to be also impaired in infected animals.These results suggested that B.suis bv.2 may use strategies similar to other smooth brucellae to facilitate intracellular multiplication and the development of chronic infections.To our knowledge,this is the first report of the analysis of gene expression profile in hosts infected with B.suis bv.2,which is important to understand the molecular mechanisms at the host-pathogen interface in the main reservoir species with possible implications in the zoonotic cycle of the pathogen. | Ruth C.Galindo Pilar M.Muoz María J.de Miguel Clara M.Marin Javier Labairu Miguel Revilla José M.Blasco Christian Gortazar José de la Fuente | 2010 | Journal of Genetics and Genomics2010，37，11： | 6 |
| 14 | A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C显示文摘 | Bruno Sangro Carlos Gomez-Martin Manuel de la Mata Mercedes I?arrairaegui Elena Garralda Pilar Barrera Jose Ignacio Riezu-Boj Esther Larrea Carlos Alfaro Pablo Sarobe Juan José Lasarte Jose L. Pérez-Gracia Ignacio Melero Jesús Prieto | 2013 | Journal of Hepatology2013，，： | 6 |
| 15 | Management of Crohn’s disease in smokers:Is an alternative approach necessary?显示文摘Inflammatory bowel disease(IBD) is a chronic condition with a pathogenic background that involves both genetic and environmental factors.Although important progress has been made regarding the former in the last decade,scarce knowledge is available for the latter.In this sense,smoking remains the most important environmental factor in IBD.Active smoking increases the risk of developing Crohn's disease(CD).Moreover,CD patients who start or continue smoking after disease diagnosis are at risk for poorer outcomes such as higher therapeutic requirements and disease-related complications,as compared to those patients who quit smoking or who never smoked.However,the harmful effect of active smoking is not uniform in all patients or in all clinical scenarios.Interventions designed to facilitate smoking cessation may impact the course of the disease.In this article,the available evidence of the deleterious effects of smoking on CD is reviewed in detail,and alternative therapeutic approaches to CD in smokers are proposed. | Pilar Nos Eugeni Domènech | 2011 | World Journal of Gastroenterology2011，17，31： | 6 |
| 16 | Current stage in inflammatory bowel disease: What is next?显示文摘In recent years,the incidence of inflammatory bowel disease(IBD) has been on the rise,extending to countries where it was infrequent in the past. As a result,the gap between high and low incidence countries is decreasing. The disease,therefore,has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently,new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. | Gonzalo Jesús Gómez-Gómez ángeles Masedo Carmen Yela Maria del Pilar Martínez-Montiel Begona Casís | 2015 | World Journal of Gastroenterology2015，21，40： | 6 |
| 17 | Regulatory T cells in patients with inflammatory bowel diseases treated with adacolumn granulocytapheresis显示文摘AIM: To investigate if the clinical efficacy of granulocytes and monocytes by adsorption (GMA) is associated with an increased frequency of peripheral regulatory T cells (Tregs), as these cells have proven to be successful in suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report four cases of corticosteroid- dependent ulcerative colitis (UC) and two Crohn’s disease (CD) cases with severe cutaneous lesions who received GMA therapy. The frequency of CD4+ CD25high (Tregs) in peripheral blood was analyzed by flow cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was determined by real time PCR prior to and one month after the last apheresis session, and at the time of endoscopic and clinical assessing. RESULTS: Increased expression of Fox P3 mRNA was found in all five patients who responded to cytapheresis with remission of clinical symptoms, mucosal inflammation and cutaneous lesions, and an increased frequency of circulating Tregs was found in four patients. These changes were not observed in the patient with UC who did no respond to GMA. Variations in TGF-β (mRNA) did not parallel that of FoxP3 mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra intestinal manifestations was associated with an expansion of circulating CD4+ CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with IBD and other chronic relapsing-remitting inflammatory conditions during treatment with GMA. | Emilio Cuadrado Marta Alonso Maria Dolores de Juan Pilar Echaniz Juan Ignacio Arenas | 2008 | World Journal of Gastroenterology2008，14，10： | 6 |
| 18 | 新型分子靶向药物联合放疗在肺癌中的应用显示文摘非小细胞肺癌(non-small cell lung cancer,NSCLC)约占肺癌总病例数的80%-85%,对于Ⅲ期患者来说,NSCLC约占肺癌总病例数的40%。不可切除Ⅲ期NSCLC的治疗为以铂类为基础的化疗联合胸部放疗。本文将综述正在研发中且有可能用于联合治疗的新型靶向制剂。其中最具前景的策略之一为表皮生长因子受体(epidermal growth factor receptor,EGFR)通路的抑制。放疗可激活EGFR信号,通过诱导细胞增殖并增强DNA修复而导致放疗抵抗。几项临床前模型研究表明西妥昔单抗与放疗联合具有协同效应。几项Ⅱ期试验评估了西妥昔单抗与放疗同步使用的安全性与疗效,结果喜人。吉非替尼对多种细胞系具有放疗增敏作用,其与放疗的联合已被试验用于不可切除Ⅲ期NSCLC的治疗。然而,放化疗后使用吉非替尼作为维持治疗的结果不容乐观。一项Ⅰ期试验评估了厄洛替尼与放化疗联合的疗效。放疗可通过损伤细胞膜、DNA以及微血管内皮细胞而诱导肿瘤死亡,而这反过来可增加促血管生成生长因子的产生。抗血管生长制剂可降低血管密度,但可改善肿瘤的含氧量。应用血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)抑制剂可通过阻断亚致死量辐射损伤的修复而增强放疗对人NSCLC的疗效。厄洛替尼、贝伐珠单抗与胸部放疗联合试验正在进行中。该三种药物联合治疗的新策略尚需制订。由于放疗可增强HSP90分子伴侣的功能从而引起肺癌细胞的放疗抵抗,此通路的阻断剂可通过抑制HIF-1a和VEGF的表达进而抑制肺癌细胞的生存和血管生成,因而可能用于减少放疗抵抗。在NSCLC和间皮瘤的临床前模型中,Aurora激酶抑制剂似乎对放疗具有增效作用。 | Mariano PROVENCIO Antonio SANCHEZ Pilar GARRIDO Francisco VALCARCEL 丁燕 李军 | 2010 | 中国肺癌杂志2010，，8： | 6 |
| 19 | Sports-related sudden cardiac death due to myocardial diseases on a population from 1-35 years: a multicentre forensic study in Spain显示文摘This is a multicentre forensic study that identifies all sports-related sudden deaths (SRSDs) in young people,due to myocardial diseases (MDs) that occurred in a large area of Spain.The aim of the study is to assess the epidemiology,causes of death,and sport activities associated with these fatalities.This is a retrospective study based on forensic autopsies performed in the provinces of Biscay,Seville,Valencia and in the jurisdiction covered by the National Institute of Toxicology and Forensic Sciences in Madrid (Spain).The retrospective study encompasses from 2010 to 2017.All sudden cardiac deaths (SCDs) in persons 1-35years old were selected.The total number of SCDs were divided into death occurred during exercise (SRSD) and death during rest,sleep or normal activities (non-SRSD).Each of these two groups was subdivided according to the cause of death into MD (primary cardiomyopathies and myocarditis) and non-MD.Clinic-pathological,toxicological and genetic characteristics of SRSD due to MD were analysed.Over the 8-year study period,we identified 645 cases of SCD in the young: 75 SRSD (11.6%) and 570 non-SRSD (88.4%).MD was diagnosed in 33 (44.0%) of the SRSD and in 112 (19.6%) of the non-SRSD cases.All cases of SRSD due to MD were males (mean age (24.0±7.6) years) practicing recreational sports (85%).SRSDs were more frequent in arrhythmogenic cardiomyopathy (ACM) (37%) and hypertrophic cardiomyopathy (HCM) (24%),followed by myocarditis (15%) and idiopathic left ventricular hypertrophy (ILVH) (9%).Only in five cases of SRSD the MD responsible of death (HCM) had been diagnosed in life.Cardiovascular symptoms related to the disease were present in other seven patients (six of them with ACM).Postmortem genetic studies were performed in 15/28 (54%) primary cardiomyopathies with positive results in 12 (80%) cases.The most frequent sports disciplines were football (49%) followed by gymnastics (15%) and running (12%).In Spain,SRSD in young people due to MDs occurs in males who perform a recreational activity.Compared with control group we observed a strong association between MDs and exertion.One in three SRSDs are due to cardiomyopathy,especially ACM,which reinforces the need for preparticipation screening to detect these pathologies in recreational sport athletes.Further studies are warranted to understand the causes and circumstances of sudden death to facilitate the development of preventive strategies. | Benito Morentin M.Paz Suárez-Mier Ana Monzó Pilar Molina Joaquín S.Lucena | 2019 | Forensic Sciences Research2019，4，3： | 6 |
| 20 | The strigolactone receptor D14 targets SMAX1 for degradation in response to GR24 treatment and osmotic stress显示文摘The effects of the phytohormone strigolactone(SL)and smoke-derived karrikins(KARs)on plants are generally distinct,despite the fact that they are perceived through very similar mechanisms.The homologous receptors DWARF14(D14)and KARRIKIN-INSENSITIVE2(KAI2),together with the F-box protein MORE AXILLARY GROWTH2(MAX2),mediate SL and KAR responses,respectively,by targeting different SMAX1-LIKE(SMXL)family proteins for degradation.These mechanisms are putatively well-insulated,with D14-MAX2 targeting SMXL6,SMXL7,and SMXL8 and KAI2-MAX2 targeting SMAX1 and SMXL2 in Arabidopsis thaliana.Recent evidence challenges this model.We investigated whether D14 can target SMAX1 and whether this occurs naturally.Genetic analysis indicates that the SL analog GR24 promotes D14-SMAX1 crosstalk.Although D14 shows weaker interactions with SMAX1 than with SMXL2 or SMXL7,D14 mediates GR24-induced degradation of SMAX1 in plants.Osmotic stress triggers SMAX1 degradation,which is protective,through SL biosynthesis and signaling genes.Thus,D14-SMAX1 crosstalk may be beneficial and not simply a vestige of the evolution of the SL pathway. | Qingtian Li Elena Sánchez Martín-Fontecha Aashima Khosla Alexandra R.F.White Sunhyun Chang Pilar Cubas David C.Nelson | 2022 | Plant Communications2022，3，2： | 5 |
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