A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept

BackgroundViral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs.ObjectivesTo investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein.MethodImmunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection.ResultThe results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4⁺CD25⁺ lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study.ConclusionThis study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies.     

Safety evaluation of metal exposure from commonly used moisturizing and skin-lightening creams in Nigeria

The concentrations of ten metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were measured in some commonly used moisturizing and skin-lightening creams in Nigeria with a view to providing information on the risk of exposure to metals from the use of these products. The metal concentrations in these products were measured by atomic absorption spectrometry after acid digestion of the samples. The measured concentrations of metals in the skin moisturizing creams ranged from <0.15 to 6.3 μg/g Cd, <0.02 to 17.5 μg/g Cu, 2.25 to 6.25 μg/g Cr, <0.25 to 124.3 μg/g Al, 0.2 to 7.3 μg/g Pb, <0.03 to 10.7 μg/g Ni, 17.3 to 372.0 μg/g Zn, <0.02 to 1.0 μg/g Co, 17.75 to 28.8 μg/g Mn, <0.1 to 89.8 μg/g Fe while the concentrations of metals in the skin-lightening products ranged from <0.15 to 16.5 μg/g Cd, <0.02 to 10.0 μg/g Cu, 4.25 to 8.0 μg/g Cr, <0.25 to 128.0 μg/g Al, 0.5 to 4.5 μg/g Pb, <0.03 to 1.65 μg/g Ni, 24.7 to 267.5 μg/g Zn, <0.02 to 2.5 μg/g for Co, 19.3 to 31.8 μg/g Mn, 9.5 to 211.63 μg/g Fe. In a significant number (>93%) of the samples investigated the concentrations of Pb, Cd, Ni and Co were below the specified limit, or the maximal limit for impurities in colour additives in cosmetics for external use. However, Cr was found at concentrations above the allergenic limit of 1 μg/g. The results also showed that skin-lightening creams contained higher concentrations of the studied metals than the moisturizing creams, except for Ni, which indicates that persons who uses skin-lightening creams in preference to moisturizing ones, are exposed to higher concentrations of metals.     

Impact of serum uric acid on subclinical myocardial injury in general population

Background and aimsHyperuricemia is widely thought as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the relation of serum uric acid (sUA) and subclinical myocardial injury (SCeMI) remains unclear. We hypothesize that sUA is associated with subclinical myocardial injury.Methods and resultsA total of 5880 adult individuals (57.9 ± 13.0 years, 54.23% women) without known cardiovascular disease from National Health and Nutrition Examination Survey (NHANES) III were included. Determined by Cardiac Infarction Injury Score (CIIS) from 12-lead electrocardiogram, SCeMI was defined by CIIS ≥10 units. The relationship between sUA and SCeMI was analyzed by using logistic regression models and the smooth curve fitting. Subgroup analyses were conducted. After adjusting for potential confounding variables, the smooth curve fitting revealed a non-linear relationship between sUA level and SCeMI. When sUA was above the inflection point 266.5 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 15%. In women group, when sUA>340.3 μmol/L, each 100 unit increase in sUA increase the risk of SCeMI by 71%, but no significant correlation was observed in men group.ConclusionsOur findings confirm that sUA is an independent risk factor for subclinical myocardial injury after adjusting for potential confounding variables, and existence of such an association in women only, which require more random control trials to confirm the strategy of cardiovascular disease prevention based on sUA reduction in female.     

Associations of peroxisome proliferator-activated receptor-γ Pro12Ala polymorphism with non-alcoholic fatty liver disease: A meta-analysis

BackgroundPolymorphisms in peroxisome proliferator-activated receptor-γ pro12Ala (PPAR-γ Pro12Ala) have been associated with Non-alcoholic Fatty Liver Disease (NAFLD) in several studies. However, the results of these studies are not entirely consistent. Thus, we performed a meta-analysis to investigate the association between the PPAR-γ Pro12Ala polymorphisms and NAFLD.MethodsStudies were identified by searching PubMed database and manual assessment of the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95 % confidence intervals (CIs) were estimated using a random-effect model. Study quality was assessed using the Newcastle–Ottawa scale.ResultsRelevant medical researches show that 11 studies have been conducted on the analysis of NAFLD for meta-analysis, with a total of 2404 cases and 3959 participating controls. Meta-analysis results show that PPAR-γ Pro12Ala polymorphism and NALAD Ala alleles[no association between dominance model (OR = 0.968, 95%CI: 0.734–1.276, P = 0.815); Pro/Ala vs. Pro/Pro (OR = 0.930, 95 % CI: 0.701–1.233, P = 0.612); Ala/Ala vs. Pro/Pro (OR = 1.220, 95 % CI: 0.668–2.230, P = 0.518); recessive model (OR = 0.907, 95 % CI: 0.516–1.596, P = 0.736)]. Moreover, stratification by ethnicity also revealed that no matter it is in Caucasian populations or in Asian populations, NAFLD has no association with the PPAR-γ Pro12Ala polymorphism.ConclusionsAccording to the meta-analysis, both in Asians and Caucasian populations, the PPAR-γ Pro12Ala polymorphism can't be demonstrated to have any link with susceptibility to NAFLD.     

Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram

BackgroundEarly recurrence results in poor prognosis of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). This study aimed to explore the value of computed tomography (CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT.MethodsA cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled. A total of 1218 features were extracted from enhanced CT images. The least absolute shrinkage and selection operator algorithm (LASSO) logistic regression was used for dimension reduction and radiomics signature building. The clinical model was constructed after the analysis of clinical factors, and the nomogram was constructed by introducing the radiomics signature into the clinical model. The predictive performance and clinical usefulness of the three models were evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration curves were plotted to assess the calibration of the nomogram.ResultsThere were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort (P < 0.001) and validation cohort (P < 0.001). The nomogram showed the best predictive performance, with the largest area under the ROC curve in the training (0.882) and validation (0.917) cohorts. Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training (P = 0.138) and validation (P = 0.396) cohorts. DCA showed if the threshold probability is within 0.06-1, the nomogram had better clinical usefulness than the clinical model.ConclusionsOur CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.     

Aging is only significant factor causing CPR-induced injuries and serious injuries

BackgroundCardiopulmonary resuscitation (CPR) sometime cause severe injuries and can affect quality of life, lead to long-term disabilities or death of the patient. The aim of this study is to identify the risk factors causing CPR-induced injuries and those of serious injuries.MethodsThis was a retrospective forensic autopsy study in a single institution. Among 885 forensic autopsies undertaken between 2011 and 2018, those in which the victim had undergone CPR immediately after cardiac arrest were recorded. ‘Serious injuries’ were defined as an Abbreviated Injury Scale (AIS) score ≥ 3. CPR-induced injuries were evaluated by three experienced forensic pathologists. With the background and history of the patient, the circumstances of cardiac arrest and risks of causing CPR-induced injuries were determined by multivariate analyses.ResultsSeventy-five victims comprised the study cohort. CPR-induced injuries were found in 52 victims (69.3%). Rib fracture was the most common (60.0%), followed by sternal fracture (37.3%), heart injury (21.3%) and liver injury (8.0%). Multivariate analysis revealed higher age to be an independent factor causing CPR-induced injuries (odds ratio [OR], 1.07, P < 0.001). Thirty-six victims had 39 serious injuries in the chest or abdomen: fracture of ≥ 3 ribs (35 cases), aortic dissection (two), lung contusion (one) and rupture of the heart (one). Multivariate analysis revealed higher age to be an independent factor causing CPR-induced serious injuries (OR, 1.09; P < 0.001).ConclusionAging was the significant factor causing CPR-induced injuries and serious injuries.     

高尿酸血症大鼠模型的实验研究

以含腺嘌呤的饲料在SD大鼠建立高尿酸血症动物模型 ,以别嘌呤醇治疗能降低高尿酸血症大鼠血尿酸值     

CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

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内源性大麻素及其代谢酶与孤独症谱系障碍严重程度的相关性

目的探讨内源性大麻素(endocannabinoid,eCB)及其代谢酶与孤独症谱系障碍(autism spectrum disorder,ASD)的关联,为ASD的病因及发病机制研究提供理论依据。方法采用病例对照的研究方法,收集2017年6月至2018年12月在哈尔滨医科大学儿童发育行为研究中心就诊和在省孤独症定点康复机构接受康复训练的58名ASD儿童作为ASD组。按照性别、年龄1∶1匹配的原则,在黑龙江省抽取58名正常发育儿童作为对照组。采集两组儿童空腹静脉血,采用液相色谱-质谱联用技术(LC-MS/MS)和实时荧光定量PCR(RT-qPCR)检测其外周血中内源性大麻素花生四烯酸乙醇胺(AEA)、花生四烯酸甘油(2-AG)、十六酰胺乙醇(PEA)、油酰乙醇胺(OEA)及其代谢酶花生四烯酸磷脂酰乙醇胺特异性磷脂酶D(NAPE-PLD)、酰胺水解酶(FAAH)、单酰基甘油脂酶(MAGL)和二酰基甘油脂酶(DAGL)的mRNA表达水平,采用Pearson相关分析eCB与ASD儿童症状严重程度之间的相关性。结果ASD儿童的AEA、OEA和PEA的水平[(10.10±2.60)nmol/L,(24.30±5.60)nmol/L,(15.92±2.28)nmol/L]均低于对照组儿童[(13.46±3.04)nmol/L,(27.85±6.89)nmol/L,(17.87±2.67)nmol/L,t=-6.612,-3.089,-4.579,均P<0.01];ASD儿童FAAH和DAGL mRNA的表达水平显著高于对照组,且差异有统计学意义(t=2.423,3.840,P<0.05),而NAPE-PLD和MAGL mRNA水平在两组间差异无统计学意义(t=0.024,0.885,均P>0.05);ASD组PEA水平与儿童孤独症行为量表(ABC)总分呈负相关(r=-0.288,P<0.05)。结论ASD儿童体内的eCB及其代谢酶可能存在代谢异常,且eCB水平与ASD的严重程度存在关联性。     

Genetic analysis of the IL8 gene polymorphism (rs4073) in generalized aggressive periodontitis

ObjectivesInterleukin (IL)-8 is an important chemokine for regulation of the inflammatory response. A single nucleotide polymorphism (SNP) reference sequence (rs) 4073 in the IL8 gene has been shown to regulate IL-8 levels after stimulation with lipopolysaccharide. This study investigates the transmission pattern of the IL8 rs4073 risk allele A and its association with susceptibility to aggressive periodontitis (AgP) in families and in a case–control cohort of unrelated individuals from a Brazilian population.DesignGenotyping was performed by standard polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) in 13 nuclear families and 184 unrelated subjects. Statistical analysis was performed using the transmission disequilibrium test (TDT) for the family dataset and Chi-square test and multivariate logistic regression modelling for the case–control dataset.ResultsTDT analyses did not detect evidence of over transmission of IL8 rs4073 alleles in affected and unaffected family members (allele T: 52%; allele A: 48%; p = 0.2252). How expected, analyses of cases and unrelated controls showed a significant and inverse association of age with AgP; however, a lack of association between genotypes, ethnic groups and generalized AgP was observed.ConclusionsThe SNP (rs4073) was not associated with AgP in unrelated individuals and there is no evidence of over transmission of the alleles in families with AgP, from Brazilian individuals.