简介：AbstractPhenuiviridae, a member of the Bunyavirales order, can lead to significant human morbidity and mortality. Various phenuiviruses target specific cellular proteins and have strategies to counteract the effects of type I interferon (IFN). Previous studies have shown that phenuiviruses infection inhibits the synthesis of type I IFNs, and viral nonstructural proteins (NSs) had been further identified as an IFN antagonist. This study found that the NSs proteins of Dabie bandavirus (DBV), Sandfly fever Sicilian virus (SFSV), and Uukuniemi virus (UUKV) can inhibit Sendai virus-induced activation of IFN-β promoter and phosphorylation of IFN regulatory factor 3 (IRF3). Moreover, detailed analysis revealed that the phenuivirus NSs protein could directly interact with retinoic acid inducible gene-I (RIG-I) and degrade it via a proteasome-dependent pathway. In short, this study demonstrate a novel mechanism of phenuiviruses to resist host antiviral immunity, which may help understand these pathogens and suggest novel therapeutic approaches.

简介：AbstractObjective:To identify risk factors for anastomotic leakage after gastrectomy in patients with Siewert type II/III adenocarcinoma (AEG) of the esophagogastric junction.Methods:This was a retrospective case-control study of 903 patients with Siewert type II/III AEG treated from January 2012 to January 2015 at the Shanxi Cancer Hospital in China. All patients underwent gastrectomy, and their clinical characteristics were analyzed to identify associations with anastomotic leakage. Independent risk factors were identified by binary logistic regression. The 2-year disease-free survival was calculated and compared between patients with anastomotic leakage and control patients. The study was approved by the Institutional Review Board of Shanxi Medical University (approval No. 2014-09-39) on September 19, 2014.Results:Out of the 903 patients were included in the study, 80 (8.86%, 80/903) experienced anastomotic leakage. The mortality rate attributed to anastomotic leakage was 8.75% (7/80). Logistic regression analysis revealed that preoperative hypoalbuminemia (odds ratio (OR)=3.249, 95% confidence interval (CI): 1.569-6.725, P=0.002), type of reconstruction (OR=1.795, 95% CI: 1.026-3.142, P=0.040), and combined organ resection (OR=1.807, 95% CI: 1.069-3.055, P=0.027) were independent risk factors for anastomotic leakage.Conclusion:Preoperative hypoalbuminemia, type of reconstruction, and combined organ resection were identified as risk factors for anastomotic leakage in patients undergoing gastrectomy for Siewert type II/III AEG.

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简介：Objective:ToinvestigatetheexpressionofHPV16mRNAinnormalhumankeratinocytestransfectedwithpSV2-neo/16.Firsthumankeratinocyteswereculturedintheserum-freemediumM154.Second,theplasmidpSV2-neo/16wastransfectedintothehumankeratinocytesusingatransfectingreagent.Third,RT-PCRandSouthernBlottingwereusedtodetecttheexpressionofHPV16mRNAandDNAinthetransfectedkeratinocytes,respectively.Results:TheexpressionofHPV16mRNAwassuccessfullyamplifiedandan110bpwasditectedbyRT-PCR.A7.9kbfragmentwasconfirmedinthetransfectedkeratinocytesbySouthernBlotanalysis.Conclusion:HPV16mRNAandDNAweresuccessfullydetectedinthehumankeratinocytes.

简介：AbstractBackground:Allogeneic natural killer (NK) cell immunotherapy is recognized as a promising anti-tumor strategy, but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1 (HIV-1) infected patients is unknown. This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders (INRs) receiving antiretroviral therapy (ART).Methods:From February to April 2018, a prospective, randomized, controlled, open-label clinical trial, which enrolled 20 HIV-1 INRs following specific inclusion criteria, was conducted at Nankai University Second People’s Hospital. Participants were randomly allocated (simple randomization 1:1) to either the combined treatment (NK + ART) group (n = 10) or the control (ART) group (n = 10). The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor (KIR)/human leukocyte antigen (HLA)-Cw mismatched healthy donor were prepared (108 cells in each injection) and intravenously infused to each recruited patient of NK+ART group in three courses. Key immune parameters (CD4 count, CD8 count, CD4/CD8 ratio), laboratory tests (count of blood cells, biochemistry panel) and symptoms at baseline and at month 1, 3, 6, 9, 12, and 24 were measured/collected to analyze the safety and efficacy of the therapy. Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance (ANOVA) test. Generalized estimating equations (GEE) model was performed to evaluate the overall effect of the NK+ART group vs. the ART group.Results:From baseline to 24 months, we noted a mean CD4 count augmentation (139 to 243 cells/μL) in the NK + ART group and (144 to 176 cells/μL) in the ART group (difference, 67; 95% CI, 10 to 124; P = 0.024). Our estimations revealed that NK+ART group could improve CD4 level (β = 54.59, P= 0.006) and CD8 level (β = 322.47, P= 0.010) on average among the six measurements compared with the ART group. Only two (2/10, 20%) participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs, allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio. The practical effects, however, need long-term follow-up observations. Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912 (No. ChiCTR1900020634).

简介：AbstractBackground:The preferred treatment for uncomplicated type B dissection (thoracic endovascular aortic repair [TEVAR] or medical) is still under debate. Since 2001, our center has performed TEVAR for uncomplicated type B dissection. Based on our data, 5- and 10-year survival rates among patients with uncomplicated type B dissection after TEVAR were 96.5% and 83.0%, respectively. We, therefore, believe that TEVAR is preferable for uncomplicated type B dissections. This study analyzed the impact of a pre-operative smoking history on long-term survival after TEVAR in patients with uncomplicated type B dissections.Methods:From May 2001 to December 2013, data from 751 patients with type B dissections were collected and analyzed. Patients were divided into two groups (337 smoking patients and 414 non-smoking patients). The Kaplan-Meier method and log-rank test were used to compare survival curves of the two groups. Multivariable analyses using the Cox proportional hazards model were used to estimate the effects of smoking on survival rates.Results:The 5- and 10-year survival rates of non-smokers were 97.6% (95% confidence interval [CI], 96.0%-99.2%) and 87.0% (95% CI, 81.6%-92.7%), respectively, and 94.9% (95% CI, 92.2%-97.7%) and 73.8% (95% CI, 62.3%-87.5%) for smokers, respectively (Log-rank test, P = 0.006). Multivariable analyses showed that smoking increased the risk of death during follow-up, 2.1-fold when compared to non-smokers (P = 0.039).Conclusion:A pre-operative smoking history increases long-term mortality rates after TEVAR in patients with uncomplicated type B dissections.

简介：BackgroundTheearlyendothelialdysfunctionofcarotidarteryinpatientswithtype2diabetesmellitus(T2DM)hasbeenrecognized.However,thefeasibilityandsignificanceofcarotidarteryendothelialdysfunctiondetectedbyultrasoundradio-frequencytechnologyhasbeenseldomstudied.MethodsThe2Dultrasoundimagesofthebilateralcommoncarotidarteriesfrom112casesofT2DMpatientsand50casesofnormalsubjectsinourhospitalwerecollectedtomeasureintima-mediathicknessmeans(IMTm),end-systolicinnerdiameter(Ds),end-diastolicinnerdiameter(Dd),resistanceindex(RI),pulseindex(PI),andthesystole/diastoleratio(S/D).Wealsoobservedthevariationoftheintima-mediathickness(IMT)aswellastheelasticityindexesofthecommoncarotidartery,suchasthecompliancecoefficient(CC),elasticitycoefficient(β),pulsewavevelocity(PWV)andaugmentationindex(AIx)throughinstrumentswithbuilt-inultrasoundradio-frequencytechniques,includingquantitativeintima-mediathickness(QIMT)andquantitativeanalysisofarterialstiffness(QAS).Thedifferencesoftheabove-mentionedparametersbetweenthetwogroupswereanalyzed.ResultsTherewerenostatisticallysignificantdifferencesinIMTm,Ds,Dd,RI,PIandS/DraitoofthecommoncarotidarteriesbetweengroupT2DMandthenormalgroup(P>0.01).Theβ,PWVandAIxingroupT2DMwereremarkablyhigherthanthoseinthecontrolgroup,withCCvaluebeingsignificantlylowerthanthelater(P<0.01or0.05).ConclusionUltrasoundradio-frequencytechniqueoffersearlierandmoreeffectiveevaluationofcarotidarteryendothelialdysfunctioninT2DMpatientswhencomparedwithconventional2Dultrasound,establishingimagingfoundationfortheearlypreventionandtreatmentofcardio-cerebrovascularcomplicationsinT2DMpatients.

简介：AbstractBackground:Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases.Methods:All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients’ selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student’s t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test.Results:A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%).Conclusions:Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people’s understanding. Meanwhile, the curing and transferring efficiency should also be improved.

简介：AbstractBackground:Gastric cancer (GC) is one of the most common malignancies, and intestinal-type GC is the main histopathologic type of GC in China. We previously reported that casein kinase 2 interacting protein 1 (CKIP-1) acts as a candidate tumor suppressor in intestinal-type GC. CKIP-1 participates in the regulation of multiple signaling pathways, including the Wnt/β-catenin pathway, of which caudal-related homeobox 1 (CDX1) may be a downstream target gene. The purpose of this study was to investigate the relationship between CKIP-1 and CDX1 in intestinal-type GC.Methods:Sixty-seven gastroscopy biopsy specimens and surgically resected gastric specimens were divided into four groups: gastric mucosa group, intestinal metaplasia (IM) group, dysplasia group, and intestinal-type GC group. The expression levels of CKIP-1 and CDX1 were detected in these groups and GC cell lines, and the correlations between these expression levels were analyzed. SGC7901 and BGC823 cells were divided into CKIP-1 shRNA groups and CKIP-1 over-expression groups, and CDX1 expression was detected. β-Catenin expression was detected in intestinal-type GC tissue samples and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 cells, and its correlation with CKIP-1 expression in intestinal-type GC tissue was analyzed. The Wnt/β-catenin pathway inhibitor DKK-1 and activator LiCl were incubated with SGC7901 cells, BGC823 cells, and CKIP-1 shRNA and CKIP-1 over-expression SGC7901 and BGC823 cells, following which CDX1 and Ki-67 expression were detected.Results:The expression levels of CKIP-1 and CDX1 were lower in patients with intestinal-type GC than in patients with IM and dysplasia (both P < 0.05). CKIP-1 and CDX1 expression levels were positively correlated in IM, dysplasia, and intestinal-type GC tissue and cell lines (r = 0.771, P < 0.01; r = 0.597, P < 0.01; r = 0.654, P < 0.01; r = 0.811, P < 0.01, respectively). CDX1 expression was decreased in the CKIP-1 shRNA groups and increased in the CKIP-1 over-expression groups of SGC7901 and BGC823 cells compared to that in the corresponding control groups (both P < 0.05). CKIP-1 expression was negatively correlated with β-catenin expression in intestinal-type GC patients (r = -0.458, P < 0.01). Compared to the control group, β-catenin expression was increased in the CKIP-1 shRNA SGC7901 cell group and decreased in the CKIP-1 over-expression SGC7901 cell group (P < 0.05). CDX1 expression was increased in SGC7901 and BGC823 cells treated with DKK-1, DKK-1 increased CDX1 expression and decreased Ki-67 expression in the CKIP-1 shRNA group; the opposite result was observed in SGC7901 and BGC823 cells treated with LiCl, and LiCl decreased CDX1 expression and increased Ki-67 expression in the CKIP-1 over-expression group (both P < 0.05).Conclusions:Through the Wnt/β-catenin signaling pathway, CKIP-1 may positively regulate CDX1 in intestinal-type GC.

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简介：尖锐吗啡管理被知道改变疱疹的功课单一的病毒感染。在这研究，潜伏的疱疹的复活上的尖锐吗啡管理的效果在一个老鼠模型被调查。因为cytolyticT淋巴细胞(CTL)的重要角色在疱疹的抑制的活动单一的病毒类型1(HSV-1)复活，CTL回答上的尖锐吗啡管理的效果也被评估。而且，淋巴细胞增长和IFN-生产在CTL反应的正式就职为他们的角色被评估。调查结果证明尖锐吗啡管理显著地减少了CTL回答，淋巴细胞增长，和IFN-生产。而且，尖锐吗啡管理被显示了重新激活潜伏的HSV-1。以前的研究证明了细胞的有免疫力的回答在HSV复活的抑制有重要角色。这些调查结果建议在尖锐吗啡管理以后的细胞的有免疫力的反应的部分的抑制可以组成导致HSV复活的机制的一部分。

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简介：AbstractBackground:Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control.Methods:Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models.Results:The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively).Conclusions:More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

简介：Objective:Panitumumabadministeredasmonotherapyincolorectalcancer(CRC)hasshownresponseanddiseasestabilizationratesofapproximately30%.Thecurrentstudyaimedtoevaluatetheprogression-freesurvival(PFS)andoverallsurvival(OS)ofpatientswithmetastaticcolorectalcancer(mCRC)treatedwithpanitumumabevery3weeksasasecondlinetreatment.Methods:Thisstudyisaretrospectiveanalysisof18patients,agedmorethan18years,withwild-typeKRASexon2mCRCtreatedwithpanitumumabasasecond-linesingleagentafterprogressiononfirst-linechemotherapy.Results:Themediannumberofcoursesreceivedwas10(range,4-29),andthemediandurationoftreatmentwas30weeks(range,12-96weeks).Afteramedianfollow-upperiodof13months,themedianPFSwas6months(range,4.3-7.7months)andthemedianOSwas11months(range,7.4-14.5months).ThemedianPFSwas4monthsforpatientswith

简介：树枝状的房间(DC)有力量通过有免疫力的回答的调整调整autoimmunity的结果。抗原的正式就职特定的忍耐为allograft拒绝的预防和处理是批评的。在现在的学习，我们transfectedIL-10基因进DC并且在老鼠在小岛allograft上在有免疫力的忍耐的vitro和正式就职在淋巴细胞活动的抑制上调查了他们的效果。一个IDDMC57BL/6老鼠模特儿被streptozotocin劝诱。从BALB/c老鼠孤立的小岛房间被移植进老鼠由IL-10的注射跟随了的模型的肾capules修改DC(mDCs)。结果证明mDCs能显著地禁止T淋巴细胞增长由同种抗免疫球蛋白房间调停了并且导致它的apoptosis，而，未修改的DC(umDCs)能显著地支持鼠科的淋巴细胞增长。mDCs的注射能延长同种抗免疫球蛋白小岛的幸存移植IDDM老鼠。在mDCs的平均血浆葡萄糖(PG)水平对待在3天以内还给正常并且持续了大约2个星期的老鼠。在控制老鼠的拒绝反应在移植以后发生了5天。当IL-4在mDCs是更高的时，IFN-的水平更低在umDCs比那对待老鼠对待老鼠，它显示Th1/Th2偏差发生了。我们的研究建议那IL-10基因修改了DC能导致有免疫力的忍耐到小岛接枝并且由在同种抗免疫球蛋白老鼠禁止T房间增长延长接受者的幸存。

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