Identification of serum biomarkers for evaluating seizure outcome after resective epilepsy surgery

Although patients with drug-resistant temporal lobe epilepsy (TLE) achieve good seizure control with resective surgery combined with anti-epileptic drugs (AEDs) treatment, it is still not clear when to withdraw AEDs after the surgery due to a lack of objective strategy for assessing the surgery outcome. Our aim is to identify objective and efficient biomarkers for assessment of surgery outcome to guide postoperative pharmacotherapy. Here, we detected 469 proteins differentially expressed between pre- and post-operative sera of TLE patients with postoperative seizure freedom, and identified six candidate proteins (HBA1, HBB, PRDX2, CA1, CAT and BLVRB) for validation. These six proteins were significantly reduced within three months after surgery, indicating these proteins may be potential biomarkers to assess the surgery outcome for TLE patients in the early stage. Interestingly,we found HBA1 to HBB ratio was superior to individual proteins to evaluate the postoperative surgery outcome with 90.0% sensitivity, 90% specificity and area under the curve of 0.960. We also suppose these proteins were derived from epilepsy foci due to the rat experiment results that HBA1, HBB, PRDX2, CA1 and CAT were highly expressed in cerebrospinal fluid of epilepsy rat models. Additionally, HBA1, HBB, PRDX2, CA1 and BLVRB proteins were highly expressed in the sera of TLE patients with postoperative seizure freedom when compared to TLE patients with postoperative seizure and patients with other types of epilepsy, suggesting surgery outcome or the original sites of seizure might be assessed before the operation through monitoring these protein levels in the sera. Our study provides experimental data for establishing objective indicators for assessing seizure freedom after resective surgery and also proposed potential markers for specific diagnoses of TLE and prediction of TLE surgery outcome.     

降黄散熏蒸联合捏脊、推拿治疗湿热蕴蒸型新生儿病理性黄疸临床研究

目的:观察降黄散熏蒸联合捏脊、推拿治疗湿热蕴蒸型新生儿病理性黄疸的临床疗效。方法:将92例湿热蕴蒸型病理性黄疸患儿按随机数字表法分为观察组和对照组各46例。对照组给予蓝光照射治疗,观察组在对照组基础上加降黄散熏蒸联合捏脊、推拿治疗,2组均治疗5 d。对比2组临床疗效和治疗前后的血清总胆红素水平、免疫球蛋白(Ig)及T细胞亚群的变化,记录黄疸消退时间。结果:观察组临床疗效优于对照组,差异有统计学意义(P<0.05)。治疗后,2组血清总胆红素水平均较治疗前下降(P<0.05),观察组血清总胆红素水平比对照组下降更明显(P<0.05);观察组黄疸消退时间短于对照组(P<0.05)。治疗后,2组血清IgA、IgG、IgM水平均较治疗前升高(P<0.05),观察组IgA、IgG、IgM水平均比对照组升高更明显(P<0.05)。治疗后,2组CD3^+、CD4^+、CD4^+/CD8^+值均较治疗前升高(P<0.05),观察组CD3^+、CD4^+、CD4^+/CD8^+值均比对照组升高更明显(P<0.05)。结论:降黄散熏蒸联合捏脊、推拿治疗湿热蕴蒸型新生儿病理性黄疸,可以有效降低患儿的血清总胆红素水平,缩短退黄时间,提高机体免疫功能。     

Serum 25-hydroxyvitamin-D and nonalcoholic fatty liver disease: Does race/ethnicity matter? Findings from the MESA cohort

Background and aimsLow serum 25-hydroxyvitamin D (25(OH)D) is associated with higher nonalcoholic fatty liver disease (NAFLD) risk in studies of mainly white participants. Significant racial/ethnic differences exist in serum 25(OH)D and NAFLD prevalence questioning extending this association to other racial/ethnic groups. We tested whether the association between serum 25(OH)D and NAFLD vary by race/ethnicity.Methods and resultsThis was a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) that included 3484 participants (44% male; 38.4% Whites, 27.8% African-Americans, 23.5% Hispanics, and 10.3% Chinese-Americans) who had serum 25(OH)D and upper abdominal CT images available at baseline. Serum 25(OH)D was measured by high-performance liquid chromatography–tandem mass spectrometry. NAFLD was identified if liver-to-spleen Hounsfield-Unit ratio was <1. Whites had the highest 25(OH)D level and African-Americans had the lowest level (mean ± SD: 29.5 ± 10.4 vs.19.9 ± 9.1, respectively). Six hundred and eleven (17.5%) participants had NAFLD; Hispanics had the highest prevalence (26.2%) followed by Chinese-Americans (19.8%), Whites (15.8%) and African-Americans (11.7%), P < 0.0001. In adjusted model, the association of 25(OH)D with NAFLD differed by race/ethnicity (P < 0.0001). Negative association was only evident in Causations (OR (95% CI):1.23 (1.03, 1.47) per 1 SD lower serum 25(OH)D). For other racial/ethnic groups, BMI, triglycerides, diabetic status and/or smoking, but not serum 25(OH)D, were common independent risk factors for NAFLD.ConclusionsThe negative association between serum 25(OH)D and NAFLD in Whites may not be broadly generalizable to other racial/ethnic groups. Modifiable risk factors including BMI, triglycerides, diabetic status and/or smoking associate with NAFLD risk in non-white racial/ethnic groups beyond 25(OH)D.     

血清补体C1q/肿瘤坏死因子相关蛋白3与2型糖尿病患者血尿酸水平的关联

目的探讨血清补体C1q/肿瘤坏死因子相关蛋白3(complement C1q/tumor necrosis factor-related protein-3,CTRP3)与新诊断2型糖尿病(type 2 diabetes mellitus,T2DM)患者血尿酸水平的相关性。方法选取中国人民解放军中部战区总医院新诊断T2DM患者152例,根据内脏脂肪面积(visceral fat area,VFA)分为非腹型肥胖组[AO(-)组]79例和腹型肥胖组[AO(+)组]73例。采用Spearman相关分析对CTRP3与血尿酸之间的相关性进行研究,采用多元逐步回归分析模型分析CTRP3对血尿酸的独立影响作用。结果与AO(-)组比较,AO(+)组的血尿酸更高(P=0.029),CTRP3水平更低(P<0.001)。Spearman相关分析显示:整体人群及AO(+)组中,CTRP3与血尿酸呈负相关(r=-0.180,r=-0.518,均有P<0.05);然而,AO(-)组CTRP3与血尿酸等参数均无相关性(均有P>0.05)。多元逐步回归分析显示,AO(+)组中,CTRP3水平独立影响血尿酸水平(β=-0.290,P=0.005),但AO(-)组未观察到这种关联。结论血清CTRP3与新诊断T2DM患者血尿酸水平独立负相关,该相关性具有肥胖依赖性的特点。     

Elevated serum neurofilament light chain in children autism spectrum disorder: A case control study

ObjectiveWe aimed to assess serum neurofilament light chain (sNfL) levels in autism spectrum disorder (ASD) and to investigate whether they are related to the severity of disease.MethodsThe cohorts consisted of 166 children aged 3–8 (83 children diagnosed with ASD and 83 children with typically-developing). sNfL were analyzed using Single Molecule Array (Simoa) technology. ASD symptom severity was assessed according to the Chinese version of the Childhood Autism Rating Scale (CARS) score.ResultsThe mean age of those included ASD was 5.1 years (standard deviations [S.D.]: 1.7) and 78.3 % were boys. The mean (SD) sNfL concentrations were significantly (P < 0.001) higher in ASD than in TP children (10.2[5.0] pg/mL and 7.1[3.2]pg/mL). For each 1 pg/mL increase of sNfL, the risk of ASD would increase by 19 % (with the OR _unadjusted of 1.19 [95 % CI 1.10–1.29], P < 0.001) and 11 % (with the OR _adjusted of 1.11 [1.03–1.23], P < 0.001), respectively. sNfL concentrations in children with severe ASD were higher than in those children with mild-to-moderate ASD (12.4[5.1] pg/mL vs. 8.3[4.2]pg/mL; P < 0.001). Among ASD cases, each 1 pg/mL increase of sNfL is associated with 20 % higher unadjusted or 11 % higher adjusted odds, respectively, of severe (vs. mild-to-moderate) ASD.ConclusionsThe data showed that sNfL was elevated in ASD and related to symptom severity, suggesting that sNfL may play a role in ASD progression.     

Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds

Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.     

Serum bactericidal antibody assays – The role of complement in infection and immunity

Complement is an essential component of the immune system and human pathogenic organisms have developed various mechanisms for evading complement mediated serum killing. The “gold standard” for measuring the ability of vaccine-induced antibody to kill Neisseria meningitidis is the serum bactericidal antibody (SBA) assay which measures complement mediated killing via antibody. This assay requires active complement, either intrinsic from the serum being tested or the addition of exogenous complement, either from a human or from another species such as rabbit. For serogroup C, an SBA titre of ≥4 was established as the correlate of protection when using human complement and ≥8 as the threshold when using rabbit complement, based on comparative assay results. Licensure of meningococcal vaccines, including polysaccharide protein conjugate vaccines and serogroup B vaccines has been based on the immune responses measured with the SBA assay, thus on a surrogate of vaccine efficacy. This review examines the use of complement and the SBA assay to assess immunity to meningococcal infection, and provides examples of vaccine trials in different age groups where various assays have been used.     

Comparison on serum biomarkers for anovulatory and ovulatory dysfunctional uterine bleeding in Lizu females

Objective:To screen,identify,and compare the serum biomarkers between anovulatory dysfunctional uterine bleeding(ADUB)and ovulatory dysfunctional uterine bleeding(ODUB)in Lizu females.Methods:The subjects included 128 ADLB patients,63 ODUB patients,and 93controls.The serum and supernate of the subjects'mense were collected and stored at-80°C until use.Differential proteins in the sera of three groups were screened using surface-enhaneed laser desorption ionization time-of-flight mass spectrometry.The screened proteins were then identified by tricine-SDS-PAGE gel and spectrometry.Protein expression levels in the menses of ADUB,ODUB,and control subjects were determined using ELISA,RT-PCR,and Western blotting.SPSS 14.1 was used for statistical analysis and chart drawing(a=0.05),Results:Three differentia)protein peaks with peak values of 11.80,13.59,and 14.68 km/z were,screened and identified as serum amyploid protein A(SAA),vascular endothelial growth factor,and vitamin K epoxide reductase,respectively.The SAA was highly expressed in the menses of ADUB and ODUB patients but poorly expressed in the controls.The vascular endothelial growth factor was highly expressed in the menses of ODUB and controls but poorly expressed in ADUB patients.Meanwhile,the vitamin K epoxide reductase was highly expressed in the menses of ADUB and control subjects but poorly expressed in ODUB patients.Conclusions:The SAA is the common serum biomarker of ADUB and ODUB.ADUB may be related to angiogenesis impairment,whereas ODUB may be associated with blood coagulation disruption.