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1miR-182参与调节胶质母细胞瘤的凋亡、生长和分化(英文)显示文摘Glioblastoma multiforme(GBM)is a lethal,therapy-resistant brain cancer consisting of numerous tumor cell subpopulations,including stem-like glioma-initiating cells(GICs),which contribute to tumor recurrence following initial response to therapy.Here,we identified miR-182 as a regulator of apoptosis,growth,and differentiation programs whose expression level is correlated with GBM patient survival.Repression of Bcl2-like12(Bcl2L12),c-Met,and hypoxia-inducible factor 2α(HIF2A)is of central importance to miR-182 anti-tumor activity,as it results in enhanced therapy susceptibility,decreased GIC sphere size,expansion,and stemness in vitro.To evaluate the tumor-suppressive function of miR-182 in vivo,we synthesized miR-182-based spherical nucleic acids(182-SNAs);i.e.,gold nanoparticles covalently functionalized with mature miR-182 duplexes.Intravenously administered 182-SNAs penetrated the bloodbrain/blood-tumor barriers(BBB/BTB)in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma,causing reduced tumor burden and increased animal survival.Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM.Kouri FM Hurley LA Daniel WL Day ES Hua Y Hao L Peng CY Merkel TJ Queisser MA Ritner C Zhang H James CD Sznajder JI Chin L Giljohann DA Kessler JA Peter ME Mirkin CA Stegh AH 2015中华神经外科疾病研究杂志2015,14,2:14
2Pathogenesis of occult chronic hepatitis B virus infection显示文摘Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this'occult'HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.Rocio Aller de la Fuente María L Gutiérrez Javier Garcia-Samaniego Conrado Fernández-Rodriguez Jose Luis Lledó Gregorio Castellano 2011World Journal of Gastroenterology2011,17,12:12
3Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation显示文摘Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.Maria J Citores Jose L Lucena Sara de la Fuente Valentin Cuervas-Mons 2019World Journal of Hepatology2019,11,1:12
4Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery显示文摘AIM: To evaluate the surface expression of triggering receptor on myeloid cell 1 (TREM-1), class Ⅱ major histocompatibility complex molecules (HLA-DR), andthe expression of the splicing variant (svTREM-1) ofTREM-1 in septic patients and those subjected to major abdominal surgery.METHODS: Using flow cytometry, we examined the surface expression of TREM-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers. svTREM-1 levels were analyzed by RT-PCR. RESULTS: Basal expression of TREM-1 and HLA-DR in healthy volunteers was 35.91±14.75 MFI and75.8±18.3%, respectively. In septic patients, TREM-1 expression was 59.9±23.9 MFI and HLA-DR expression was 44.39±20.25%, with a significant differencebetween healthy and septic groups (P<0.05) for bothmolecules. In the surgical patients, TREM-1 and HLA-DR expressions were 56.8±20.85 MFI and 71±13.8% before surgery and 72.65±29.92 MlFI and 72.82±22.55% after surgery. TREM-1 expression was significantly different(P = 0.0087) between the samples before and aftersurgery and svTREM-1 expression was 0.8590±0.1451 MF1, 0.8820±0.1460 MF1, and 2.210±0.7873MF1 in the healthy, surgical (after surgery) and septic groups, respectively. There was a significant difference (P = 0.048) in svTREM-1 expression between the healthy and surgical groups and the septic group.CONCLUSION: TREM-1 expression is increased during systemic inflammatory conditions such as sepsis and the postoperative phase. Simultaneous low expression of HLA-DR molecules correlates with the severity of illness and increases susceptibility to infection. Additionally, TREM-1 expression is distinctly different in surgical patients at different stages of the inflammatory response before and after surgery. Thus, surface TREM-1 appears to be an endogenous signal during the course of the inflammatory response. svTREM-1 expression is significantly increased during sepsis, appearing to be an indicator of severity of illness. Together, these data indicate that TREM-1 may play an important role in establishing and amplifying the systemic inflammatory response. TREM-1, HLA-DR, and svTREM-1 expression analysis can provide useful diagnostic and prognostic indicators during SIRS, CARS, and sepsis.Nestor González-Roldán Eduardo Ferat-Osorio Rosalía Aduna-Vicente Isabel Wong-Baeza Noemí Esquivel-Callejas Horacio Astudillo-de la Vega Patricio Sánchez-Fernández Lourdes Arriaga-Pizano Miguel Angel Villasís-Keever Constantino López-Macías Armando Isibasi 2005World Journal of Gastroenterology2005,11,47:9
5Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis显示文摘AIM:To evaluate the impact of metadoxine(MTD) on the 3- and 6-mo survival of patients with severe alcoholic hepatitis(AH).METHODS:This study was an open-label clinical trial,performed at the'Hospital General de México,Dr.Eduardo Liceaga'.We randomized 135 patients who met the criteria for severe AH into the following groups:35 patients received prednisone(PDN)40 mg/d,35patients received PDN+MTD 500 mg three times daily,33 patients received pentoxifylline(PTX)400 mg three times daily,and 32 patients received PTX+MTD 500 mg three times daily.The duration of the treatment for all of the groups was 30 d.RESULTS:In the groups treated with the MTD,thesurvival rate was higher at 3 mo(PTX+MTD 59.4%vs PTX 33.3%,P=0.04;PDN+MTD 68.6%vs PDN20%,P=0.0001)and at 6 mo(PTX+MTD 50%vs PTX18.2%,P=0.01;PDN+MTD 48.6%vs PDN 20%,P=0.003)than in the groups not treated with MTD.A relapse in alcohol intake was the primary independent factor predicting mortality at 6 mo.The patients receiving MTD maintained greater abstinence than those who did not receive it(74.5%vs 59.4%,P=0.02).CONCLUSION:MTD improves the 3-and 6-mo survival rates in patients with severe AH.Alcohol abstinence is a key factor for survival in these patients.The patients who received the combination therapy with MTD were more likely to maintain abstinence than those who received monotherapy with either PDN or PTX.Fátima Higuera-de la Tijera Alfredo I Servín-Caamano Aurora E Serralde-Zúniga Javier Cruz-Herrera Eduardo Pérez-Torres Juan M Abdo-Francis Francisco Salas-Gordillo JoséL Pérez-Hernández 2015World Journal of Gastroenterology2015,21,16:8
6Intravitreal dexamethasone implants for diabetic macular edema显示文摘AIM: To evaluate the safety and efficacy of a dexamethasone(DEX) intravitreal implant for diabetic macular edema(DME).METHODS: Totally 113 eyes of 84 patients were divided in three subgroups: naive patients(n=11), pseudophakic patients(n=72) and phakic patients(n=30). Inclusive criterion comprised adult diabetic patients with central fovea thickening and impaired visual acuity resulting from DME for whom previous standard treatments showed no improvement in both central macular thickness(CMT) and best corrected visual acuity(BCVA) after at least 3 mo of treatment. Outcome data were obtained from patient visits at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant injection. At each of these visits, patients underwent measurement of BCVA, a complete eye examination and measurement of CMT and macular volume(MV) carried out with optical coherence tomography(OCT) images. RESULTS: Seventy-three eyes(64.5%) received a single implant, 30(26.5%) received two implants and 10(9%) received three implants. At baseline, average in BCVA, CMT and MV were 43.5±20.8, 462.8±145 and 12.6±2.5 respectively. These values improved significantly at 1 mo(BCVA: 47.2±19.5, CMT: 339.6±120, MV: 11.11±1.4) and 3 mo(BCVA: 53.2±18.1, CMT: 353.8±141, MV: 11.3±1.3)(P≤0.05). At 5 mo(BCVA: 50.9±19.8, CMT: 425±150, MV: 12.27±2.3), 9 mo(BCVA: 48.4±17.6, CMT: 445.5±170, MV: 12.5±2.3) and 12 mo(BCVA: 47.7±18.8, CMT: 413.2±149, MV: 12.03±2.5), improvements in the three parameters were no longer statistically significant and decreased progressively but did not reach baseline values. There were no clinical differences between subgroups. Ocular complications were minimal.CONCLUSION: Patients with DEX implants show maximum efficacy at 3 mo which then declined progressively, but is still better than baseline values at the end of follow-up.Alicia Pareja-Ríos Paloma Ruiz-de la Fuente-Rodríguez Sergio Bonaque-González Maribel López-Gálvez Virginia Lozano-López Pedro Romero-Aroca 2018International Journal of Ophthalmology(English edition)2018,11,1:8
7Leukemia:研究鉴定出与34种AML白血病亚群相关联的基因突变显示文摘针对成年急性髓细胞白血病(acute myeloid leukemia,AML)患者的一项新的大型研究将80种癌症相关基因突变与5种AML亚型相关联。这5种AML亚型可通过特异性的染色体异常加以确定。在未来,这些发现可能有助指导基因突变测试和治疗决策。A-K Eisfeld K Mrózek J Kohlschmidt D Nicolet S Orwick C J Walker K W Kroll J S Blachly A J Carroll J E Kolitz B L Powell E S Wang R M Stone A de la Chapelle J C Byrd C D Bloomfield 2017现代生物医学进展2017,17,15:7
8Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy显示文摘AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.Carlos A Castaneda Elizabeth Mittendorf Sandro Casavilca Yun Wu Miluska Castillo Patricia Arboleda Teresa Nunez Henry Guerra Carlos Barrionuevo Ketty Dolores-Cerna Carolina Belmar-Lopez Julio Abugattas Gabriela Calderon Miguel De La Cruz Manuel Cotrina Jorge Dunstan Henry L Gomez Tatiana Vidaurre 2016World Journal of Clinical Oncology2016,7,5:6
9Cardiometabolic health among gastric bypass surgery patients with polycystic ovarian syndrome显示文摘AIM:To examine the effect of gastric bypass surgery on cardiometabolic health among women with polycystic ovarian syndrome(PCOS).METHODS:Retrospective medical chart review identified women(n = 389) with PCOS who underwent Roux-en-Y gastric bypass surgery from 2001-2009 in one surgical practice.Separate repeated measures linear mixed models were fit using the MIXED procedureto assess mean change in cardiometabolic disease risk factors from before to 1-year after surgery and were evaluated by ethnicity [Hispanic,non-Hispanic black(NHB) and white(NHW)].RESULTS:The majority of the sample was Hispanic(66%,25% NHB,9% NHW).Mean body mass index significantly improved 1 year post-surgery for all ethnic groups(45.5 to 35.5 kg/m2 for Hispanics,46.8 to 37.7 kg/m2 for NHB and 45.7 to 36.7 kg/m2 for NHW,P < 0.001).Among Hispanic women mean total cholesterol(198.1 to 160.2 mg/dL),low-density lipoproteins(LDL) cholesterol(120.9 to 91.0 mg/dL),triglycerides(148.6 to 104.8 mg/dL),hemoglobin A1c(6.2% to 5.6%),alanine aminotransferase(28.1 to 23.0 U/L) and aspartate aminotransferase(23.5 to 21.6 U/L) decreased significantly(P < 0.001).Among NHB,mean total cholesterol(184.5 to 154.7 mg/dL),LDL cholesterol(111.7 to 88.9 mg/dL) and triglycerides(99.7 to 70.0 mg/dL) decreased significantly(P < 0.05).Among NHW,mean total cholesterol(200.9 to 172.8 mg/dL) and LDL cholesterol(124.2 to 96.6 mg/dL),decreased significantly(P < 0.05).Pairwise ethnic group comparisons of all cardiometabolic outcomes adjusted for age and type of surgery before and 1 year after surgery showed no statistical difference between the three groups for any outcome.CONCLUSION:Cardiometabolic disease risk improvements vary by ethnicity and obesity may impact glucose tolerance and liver function changes more in Hispanic women with PCOS vs non-Hispanic women.Carley A Gomez-Meade Adriana Carrillo Gabriela Lopez-Mitnik Sarah E Messiah Kristopher L Arheart Nestor de la Cruz-Muoz 2013World Journal of Diabetes2013,4,3:6
10Embolization of splenorenal shunt associated to portal vein thrombosis and hepatic encephalopathy显示文摘Hepatic encephalopathy(HE)is a cognitive disturbance characterized by neuropsychiatric alterations.It occurs in acute and chronic hepatic disease and also in patients with portosystemic shunts.The presence of these portosystemic shunts allows the passage of nitrogenous substances from the intestines through systemic veins without liver depuration.Therefore,the embolization of these shunts has been performed tocontrol HE manifestations,but the presence of portal vein thrombosis is considered a contraindication.In this presentation we show a cirrhotic patient with severe HE and portal vein thrombosis who was submitted to embolization of a large portosystemic shunt.Case report:a 57 years-old cirrhotic patient who had been hospitalized many times for persistent HE and hepatic coma,even without precipitant factors.She had a wide portosystemic shunt and also portal vein thrombosis.The abdominal angiography confirmed the splenorenal shunt and showed other shunts.The larger shunt was embolized through placement of microcoils,and the patient had no recurrence of overt HE.There was a little increase of esophageal and gastric varices,but no endoscopic treatment was needed.Since portosystemic shunts are frequent causes of recurrent HE in cirrhotic patients,portal vein thrombosis should be considered a relative contraindication to perform a shunt embolization.However,in particular cases with many shunts and severe HE,we found that one of these shunts can be safely embolized and this procedure can be sufficient to obtain a good HE recovery.In conclusion,we reported a case of persistent HE due to a wide portosystemic shunt associated with portal vein thrombosis.As the patient had other shunts,she was successfully treated by embolization of the larger shunt.Letícia de Campos Franzoni Fábio Cardoso de Carvalho Rafael Gomes de Almeida Garzon Fábio da Silva Yamashiro Laís Augusti Lívia Alves Amaral Santos Mariana de Souza Dorna Júlio Pinheiro Baima Talles Bazeia Lima Carlos Antonio Caramori Giovanni Faria Silva Fernando Gomes Romeiro 2014World Journal of Gastroenterology2014,20,42:6
11High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn's disease显示文摘AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.Juan L Mendoza Amparo San-Pedro Esther Culebras Raquel Cíes Carlos Taxonera Raquel Lana Elena Urcelay Fernando de la Torre Juan J Picazo Manuel Díaz-Rubio 2010World Journal of Gastroenterology2010,16,36:5
12Validation of a new scoring system: Rapid assessment faecal incontinence score显示文摘AIM: To implement a quick and simple test- rapid assessment faecal incontinence score(RAFIS) and show its reliability and validity.METHODS: From March 2008 through March 2010, we evaluated a total of 261 consecutive patients, including 53 patients with faecal incontinence. Demographic and comorbidity information was collected. In a single visit, patients were administered the RAFIS. The results obtained with the new score were compared with those of both Wexner score and faecal incontinence quality of life scale(FIQL) questionnaire. The patient withoutinfluence of the surgeon completed the test. The role of surgeon was explaining the meaning of each section and how he had to fill. Reliability of the RAFIS score was measured using intra-observer agreement and Cronbach's alpha(internal consistency) coefficient. Multivariate analysis of the main components within the different scores was performed in order to determine whether all the scores measured the same factor and to conclude whether the information could be encompassed in a single factor. A sample size of 50 patients with faecal incontinence was estimated to be enough to detect a correlation of 0.55 or better at 5% level of significance with 80% power.RESULTS: We analysed the results obtained by 53 consecutive patients with faecal incontinence(median age 61.55 ± 12.49 years) in the three scoring systems. A total of 208 healthy volunteers(median age 58.41 ± 18.41 years) without faecal incontinence were included in the study as negative controls. Pearson's correlation coefficient between 'state' and 'leaks' was excellent(r = 0.92, P < 0.005). Internal consistency in the comparison of 'state' and 'leaks' yielded also excellent correlation(Cronbach's α = 0.93). Results in each score were compared using regression analysis and a correlation value of r = 0.98 was obtained with Wexner score. As regards FIQL questionnaire, the values of 'r ' for the different subscales of the questionnaire were: 'lifestyle' r =-0.87, 'coping/behaviour' r =-0.91, 'depression' r =-0.36 and 'embarrassment' r =-0.90,(P < 0.01). A multivariate analysis showed that all the scoring systems measured the same factor. A single factor may explain 80.84% of the variability of FI, so all the scoring systems measure the same factor. Patient's continence improves when RAFIS and Jorge-Wexner scores show low values and when the values obtained in the FIQL questionnaire are high.CONCLUSION: RAFIS is a valid and reliable tool to assess Faecal Incontinence.Fernando de la Portilla Arantxa Calero-Lillo Rosa M Jiménez-Rodríguez Maria L Reyes Manuela Segovia-González María Victoria Maestre Ana M García-Cabrera 2015World Journal of Gastrointestinal Surgery2015,7,9:5
13Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy显示文摘AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.Marco Galvez Carlos A Castaneda Joselyn Sanchez Miluska Castillo Lia Pamela Rebaza Gabriela Calderon Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Jorge Dunstan Henry Guerra Omar Mejia Henry L Gomez 2018World Journal of Clinical Oncology2018,9,2:4
14Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal 2017World Journal of Gastroenterology2017,23,48:4
15Aplastic anemia and severe pancytopenia during treatment with peg-interferon,ribavirin and telaprevir for chronic hepatitis C显示文摘Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin.Pancytopenia due to myelotoxicity caused by these drugs may occur,but severe hematological abnormalities or aplastic anemia(AA) have not been described.We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011.Among 142 cirrhotic patients receiving treatment,7 cases of severe pancytopenia(5%) were identified and three were consistent with the diagnosis of AA.Mean age was 59 years,five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation.Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy.Three patients had pre-treatment hematological abnormalities related to splenomegaly.In six patients,antiviral treatment was interrupted at the onset of hematological abnormalities.Two patients died due to septic complications and one patient due to acute alveolar hemorrhage.The remaining patients recovered.Severe pancytopenia and especially AA,are not rare during triple therapy with telaprevir in patients with advanced liver disease.Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications.Sabela Lens Jose L Calleja Ana Campillo Jose A Carrion Teresa Broquetas Christie Perello Juan de la Revilla Zoe Marino Maria-Carlota Londono Jose M Sanchez-Tapias Alvaro Urbano-Ispizua Xavier Forns 2015World Journal of Gastroenterology2015,21,17:4
16Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?显示文摘AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.Emilia Sugai María L Moreno Hui J Hwang Ana Cabanne Adriana Crivelli Fabio Nach-man Horacio Vázquez Sonia Niveloni Julio Argonz Roberto Mazure Graciela La Motta María E Caniggia Edgardo Smecuol Néstor Chopita Juan C Gómez Eduardo Maurińo Julio C Bai 2010World Journal of Gastroenterology2010,16,25:4
17Inheritance patterns of secondary symbionts during sexual reproduction of pea aphid biotypes显示文摘食草的昆虫经常怀有影响他们的生态学和进化的细菌的共生者。蚜虫招待应尽的 endosymbiont Buchnera,它为复制被要求,和其频率越过蚜虫人口变化的容许的共生者。这些似母亲播送了第二等的共生者特别地在豌豆蚜虫被学习了, Acyrthosiphon pisum,哪个港口穿上环境地依赖的效果的至少 8 不同细菌的种类(不数的 Buchnera ) 主人健康。特别地,这些共生者种类与豌豆蚜虫人口在特定的植物上喂被联系。尽管他们是继承的似母亲,这些细菌偶尔越过昆虫系被转移。如此的 nonmaternal 转移的一机制在性复制期间是到子孙的父亲的传播。迄今为止,第二等的共生者的传播在仅仅蚜虫系和 3 共生者种类的一把在蚜虫的性复制期间被调查了。更好描绘这个过程,我们通过包含属于 9 专业化主人的遗传因子型,和 117 个十字的 49 克隆的一个交叉实验在豌豆蚜虫的性复制期间调查了 7 共生者种类的继承模式。在子孙的共生者种类在从鸡蛋并且在以后的单性生殖的代孵化的 fundatrix 阶段与诊断质的 PCR 被检测。我们没发现共生者的父亲的传播的证实的案例到子孙,并且我们观察到特别共生者种(Serratia symbiotica ) 的母亲的传播是相当低效的。我们在尊重讨论这些观察到豌豆蚜虫的生态学。Jean Peccoud Joêl Bonhomme Frédérique Mahéo Manon de la Huerta Olivier Cosson Jean-Christophe Simon 2014Insect Science2014,21,3:4
18Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy显示文摘Currently immunosuppressive and biological agentsare used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus(HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to preemptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.Pilar López-Serrano Elsa de la Fuente Briongos Elisa Carrera Alonso Jose Lázaro Pérez-Calle Conrado Fernández 2015World Journal of Hepatology2015,7,3:4
19Proteomic analysis for developing new biomarkers of hepatocellular carcinoma显示文摘AIM: To identify new markers of hepatocellular carcinoma (HCC) using a proteomic analysis. METHODS: Patients with liver cirrhosis of the three most frequent etiologies: hepatitis C virus, hepatitis B virus and alcoholic liver disease, were included in the study. The samples were analysed by 2D-electrophoresis in order to determine the differential protein expression. The proteins were separated according to the charge in immobilized pH 3-10 gradient strips and then by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins of interest were excised, digested with trypsin and the resulting peptides were separated and identified. RESULTS: Three differentially expressed apolipoproteins (Apo) were identified based on the protein profile using proteomic techniques: Apo-A1, Apo-A4 and Apo-E. Apo-A4 levels were significantly lower in HCC than in non-HCC patients regardless of etiology (P < 0.01). Multivariate logistic regression showed that Apo-A4 and Apo-A1 were the only independent factors related to HCC diagnosis (P < 0.05). The receiver operating characteristic (ROC) curve including both Apo-A4 and Apo-A1 showed an area under the ROC of 0.944 (P < 0.001), a sensitivity of 0.89 and a specificity of 0.81 for diagnosis of HCC. CONCLUSION: Apo-A4 and Apo-A1 may be used clinically as biomarkers of HCC with a high sensibility and specificity. These findings may provide additional insights into the mechanism of HCC development and progression.Maria Pleguezuelo Laura M Lopez-Sanchez Antonio Rodriguez-Ariza Jose L Montero Javier Briceno Ruben Ciria Jordi Muntane Manuel de la Mata 2010World Journal of Hepatology2010,2,3:3
20中国基本药物改革:为实现最佳健康产出的选择显示文摘2009年4月,中国政府发布了《关于深化医药卫生体制改革的意见》,提出到2020年实现全民享有基本医疗卫生服务的目标。改革的重点任务之一是建立基本药物制度。在全球范围内,基本药物这一概念自1975年首次被世界卫生大会提出以来,一直具有非常重要的意义。这一概念最初强调药物的可及性和基本药物目录。但随时间推移,这一概念的内涵逐渐演变。现在各国引入基本药物概念,主要是为了确保药物可及性与可支付性、合理用药以及药物的质量和安全性。瑞典、挪威以及经合组织国家的经验表明,基本药物的概念可灵活适用于多种情形。在中国,基本药物制度的改革已取得良好成果,在非常短的时间内使公众更多获益,继续贯彻基本药物制度将有利于在中国实现最佳健康产出。Saral L Barber 黄宝斌 Budiono Santoso Richard Laing 2012中国卫生政策研究2012,5,7:3
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