Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

Alpha稳定分布噪声条件下的广义S变换时频分析

在分析Alpha稳定分布噪声干扰下的非高斯信号时,基于传统二阶广义S变换时频算法效果显著退化。针对该问题,提出了基于分数低阶的广义S变换时频分析(FLO-GST)算法。该算法将分数低阶谱理论和常规广义S变换时频分布算法有机结合,同时优化窗口调节因子改善时频聚集性,得到较好的时频图谱。通过计算机仿真,并与其他时频算法进行对比,结果表明,该算法能有效抑制脉冲噪声干扰,更好的描述稳定分布噪声下非平稳信号的时频图谱,具有良好的韧性。

利用多水平模型计算及校正Cronbach alpha系数

目的探讨使用多水平模型计算Cronbach alpha系数及校正混杂因素后的Cronbach alpha系数的方法。方法介绍Cronbach alpha的来源与常用计算方法,推导多水平模型计算Cronbach alpha的方法,从而通过模型校正混杂因素。利用医务人员工作特征量表纸质版(2013年)调查四川省乡镇卫生院424名医务人员与电子版(2017年)调查四川省9个乡镇卫生院220名医务人员的实例数据进行分析,比较不同计算方法的结果,并比较校正人群特征因素前后两种不同调查方式的内部信度。结果实例数据使用多水平模型计算Cronbach alpha系数的结果与其他公认计算方法结果一致。校正前后电子版调查结果的Cronbach alpha系数均高于纸质版,但校正前后置信区间均有重叠,说明该量表电子版调查的内部信度与纸质版调查的内部信度差异无统计学意义。结论多水平模型可用于计算Cronbach alpha系数,如果在比较不同Cronbach alpha系数时存在其他混杂因素,可通过多水平模型校正混杂因素,提高Cronbach alpha系数的可比性。

基于16S rDNA测序探索食管鳞状细胞癌患者肠道菌群特征

背景食管癌是我国的高发肿瘤之一,其发病与死亡人数均为世界平均水平的2倍以上。在我国大多数食管癌发现时已是中晚期,预后较差,所以迫切需要早期诊断及干预治疗,目前肠道菌群在食管癌诊断及治疗中的作用备受关注。目的探索食管鳞状细胞癌患者肠道菌群基本特征。方法纳入2022年4—8月就诊于河北医科大学第四医院未经任何抗肿瘤治疗的食管鳞状细胞癌患者35例作为食管癌组,健康志愿者35例作为对照组。收集两组人群粪便标本,应用16S rDNA技术检测肠道菌群,根据检测结果物种注释情况分析两组人群肠道菌群的Alpha多样性、Beta多样性〔主坐标分析(PCoA)〕及菌群物种差异性〔线性判别分析及影响因子(LEfSe)分析〕。结果两组人群肠道菌群Alpha多样性香农(Shannon)、辛普森(Simpson)、Chao1、ACE及Goods_coverage指数比较均无明显差异(P>0.05);而PCoA图显示两组样本整体上相距较远,群落结构存在差异(t=10.837,P<0.001)。两组人群肠道菌群T-test检验结果在属水平共有16类菌属的丰度存在明显差异,相对丰度较高的前8位菌属中,食管癌组栖粪杆菌属(Faecalibacterium)、罗斯氏菌属(Roseburia)、柠檬酸杆菌属(Citrobacter)丰度低于对照组,乳杆菌属(Lactobacillus)、罗姆布茨菌属(Romboutsia)、瘤胃球菌属组(Ruminococcus_torques_group)、肠杆菌属(Intestinibacter)、土杆菌属(Turicibacter)丰度高于对照组(P<0.05)。LEfSe分析结果显示14种肠菌丰度存在差异,在属及种水平上与对照组相比,食管癌组Faeculibacterium及普拉梭菌(Faecalibacterium-prausnitzii)丰度降低,Romboutsia及Rombutsia-ilealis丰度升高(P<0.05)。结论食管鳞状细胞癌患者具有显著性差异肠菌,其中Faecalibacterium、Faecalibacterium-prausnitzii、Romboutsia及Rombutsia-ilealis可能是食管癌特异性改变物种,与食管癌发生密切相关。

由春晚“Alpha 1S集体舞”浅析国产智能机器人

今年春晚上最吸引眼球的节目非"Alpha 1S集体舞"莫属,看到国产智能机器人的惊艳表现,也让我这个机器人从业者兴奋不已!Alpha 1S是具有16自由度可自定义编程的双足仿人形机器人。

Alpha-synuclein自身抗体用作帕金森病抗体治疗的探索研究

目的:通过从外周血中分离B细胞并进行培养,对外周血中存在的alpha-synuclein(α-syn)自身抗体进行分析,以探索用α-syn自身抗体开发治疗帕金森病(PD)抗体药物的可行性。方法:采集健康捐赠人的外周血并分离外周血B细胞进行培养,对B细胞培养上清进行ELISA结合活性分析,并用硫黄素T(ThT)法检测B细胞培养上清中α-syn自身抗体的生物学活性。结果:细胞培养13 d后,镜检发现B细胞扩增孔数可以达到90%以上,表明B细胞在实验条件下生长良好并能维持抗体分泌能力。ELISA结果表明检测的10530个样品中有48个可以和α-syn单体结合(OD 450>0.5),其中36个可以同时结合α-syn单体和聚合体(OD 450>0.5),并且该36个样品和α-syn家族蛋白β-synuclein以及γ-synuclein无交叉反应,具有α-syn结合特异性。用硫黄素T(ThT)法对该组样品进行的抑制聚合活性检测,结果表明36个样品中有9个样品能够显著性地抑制α-syn单体聚合,并且其中两个样品25G07和55F02的抑制率可以达到50%。结论:可以通过分离培养外周血B细胞获得具有生物学活性的α-syn自身抗体,用作治疗帕金森病的抗体药物研发。

大鼠Gs alpha亚基的原核表达和纯化

用 PCR的方法 ,在大鼠 Gs alpha亚基的 C端引入了 6个外源组氨酸 (即 6×His- Tag)并以此为纯化标记 .构成的表达载体 p QE60 /rat Gsα( L)在大肠杆菌 BL2 1 ( DE3)中获得了稳定的表达 .经 DEAE- Sephacel离子交换柱和 Ni- NTA Agarose亲和层析获得纯化的具有较高 [35S]- GTPγS结合活力的重组大鼠 Gs

Relationship between Randomness and Coefficient Alpha: A Monte Carlo Simulation Study

Cronbach’s Alpha coefficient is the most popular method of examining reliability. It is typically used when the researcher has several Likert-type items that are summed or averaged to make a composite score. Distribution of alpha coefficient has been subjected of many studies. In this study relationship between randomness and Cronbach alpha coefficient were investigated and in this context, present study was examined the question“What is the distribution of the coefficient alpha when a Likert-type scale is answered randomly?” Data were generated in the form of five point Likert-type items and Monte Carlosimulation was run for 5000 times for different item numbers.

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn's disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 =4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desir- able for individuals with such affected genotypes.

Screening, Identification and Fermentation Property of a Yeast Strain R6 Accumulating Alpha-ketoglutaric Acid

A yeast strain R6 was obtained by the method of thiamine（VB1） auxotrophic negative selection from the edible oil-polluted soil in Zibo, China. Physiological and biochemical experiments revealed that strain R6 shared common feature with Rhodotorula mucilaginosa according to the API 20 C AUX yeast identification system which has been tested previously. Furthermore, the 18 S r DNA gene of strain R6 was amplified and sequenced. Phylogenetic analysis based on the 18 S r DNA sequence and the relatives indicated that R6 shared 99% homologies with the members of R. mucilaginosa, suggesting that strain R6 belonged to R. mucilaginosa.Investigation showed that strain R6 possessed the capacity of accumulating exocellular alpha-ketoglutaric acid（alpha-KG）. Finally, the fermentation conditions of R6 to accumulate alpha-KG was optimized by controlling each single fermenting variable and detected through high performance liquid chromatography（HPLC）. Results showed that both VB1 and Ca CO3 in fermentation medium were the key factors influencing the cumulant of alpha-KG. The discovery of natural auxotrophic strain R6 not only broadened the microbial resource which can achieve lots of alpha-KG production through fermentation, but also laid a foundation for further fermentation regulation to achieve excessive alpha-KG accumulation.

Higher production of tumor necrosis factor alpha in hemozoin-fed human adherent monocytes is dependent on lipidic component of malarial pigment:new evidences on cytokine regulation in Plasmodium falciparum malaria

Objective:To investigate whether the increase of tumor necrosis factor alpha is dependent on lipidic component of malarial pigment.Methods:Adherent human monocytes were fed for 3 hours with different meals(native hemozoin;lipid free hemozoin;and control latex particles),then tumor necrosis factor alpha was monitored in cell supernatants up to 48 hours through western blotting or specific enzyme-linked immunoadsorbent assay.In selected experiments,unfed monocytes were treated with different doses of 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid or 4-hydroxynonenal instead of phagocytosis.Results:Hemozoin-fed monocytes produced higher levels of tumor necrosis factor alpha than unstimulated and latex-fed cells, while lipid-free hemozoin did not reproduce these results.Additionally,hemozoin effects were mimicked dose-dependently by 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid,but not by 4-hydroxynonenal.Conclusions:Present data suggest an essential role for lipids in hemozoindependent enhanced release of tumor necrosis factor alpha from monocytes,and 15(S,R)hydroxy -6,8,11,13-eicosatetraenoic acid could be one possible specific mediator.

Hypoxia inducible factor-1 alpha stabilization for regenerative therapy in traumatic brain injury

Mild traumatic brain injury（TBI）, also called concussion, initiates sequelae leading to motor deficits, cognitive impairments and subtly compromised neurobehaviors. While the acute phase of TBI is associated with neuroinflammation and nitroxidative burst, the chronic phase shows a lack of stimulation of the neurorepair process and regeneration. The deficiency of nitric oxide（NO）, the consequent disturbed NO metabolome, and imbalanced mechanisms of S-nitrosylation are implicated in blocking the mechanisms of neurorepair processes and functional recovery in the both phases. Hypoxia inducible factor-1 alpha（HIF-1α）, a master regulator of hypoxia/ischemia, stimulates the process of neurorepair and thus aids in functional recovery after brain trauma. The activity of HIF-1α is regulated by NO via the mechanism of S-nitrosylation of HIF-1α. S-nitrosylation is dynamically regulated by NO metabolites such as S-nitrosoglutathione（GSNO） and peroxynitrite. GSNO stabilizes, and peroxynitrite destabilizes HIF-1α. Exogenously administered GSNO was found not only to stabilize HIF-1α and to induce HIF-1α-dependent genes but also to stimulate the regeneration process and to aid in functional recovery in TBI animals.

Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease

BACKGROUND Interleukin 10 receptor alpha subunit(IL10RA)dysfunction is the main cause of very early-onset inflammatory bowel disease(VEO-IBD)in East Asians.AIM To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations.METHODS From May 2016 to September 2020,four young patients with clinically diagnosed VEO-IBD were recruited.Before hospitalization,using targeted gene panel sequencing and trio-whole-exome sequencing(WES),three patients were found to harbor a IL10RA mutation(c.301C>T,p.R101W in one patient;c.537G>A,p.T179T in two patients),but WES results of the fourth patient were not conclusive.We performed whole-genome sequencing(WGS)on patients A and B and reanalyzed the data from patients C and D.Peripheral blood mononuclear cells(PBMCs)from patient D were isolated and stimulated with lipopolysaccharide(LPS),interleukin 10(IL-10),and LPS+IL-10.Serum IL-10 levels in four patients and tumor necrosis factor-α(TNF-α)in the cell supernatant were determined by enzyme-linked immunosorbent assay.Phosphorylation of signal transducer and activator of transcription 3(STAT3)at Tyr705 and Ser727 in PBMCs was determined by western blot analysis.RESULTS The four children in our study consisted of two males and two females.The age at disease onset ranged from 18 d to 9 mo.After hospitalization,a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data.Patient D was homozygous for the 333 bp deletion.All four patients had elevated serum IL-10 levels.In vitro,IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-αproduction induced by LPS.Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS+IL-10 in both healthy subjects and in patient D.CONCLUSION WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD,whereas the WES results were inconclusive.

通过Mplus计算几种常用的测验信度

Cronbach’s alpha系数作为信度估计指标存在诸多弊端。为了克服其不足,研究者提出了多种信度估计,而流行的统计软件尚未直接提供这些参数,以致在实践中并未被广泛采用。为了缩小理论和实践的差距,文章通过具体实例给出几种常用的信度估计(合成信度,单个指标信度和ωh)的Mplus程序。

论负克伦巴赫alpha系数和分半信度系数

克伦巴赫alpha及分半信度为负值时,表明克伦巴赫alpha系数和斯皮尔曼-布朗信度校正原型公式对于估计信度系数而言已经失效。讨论了出现这种现象的原因和出现这种现象时克伦巴赫alpha系数和斯皮尔曼-布朗信度校正公式的相应替换公式。

脂质在帕金森病发生中的作用及机制研究进展

帕金森病(PD)是一种蛋白质构象疾病。生理状态的α-突触核蛋白(ASN)为无序单体,病理状态的ASN为聚合状态。ASN沿神经轴的病理性传播与PD的临床表现密切相关。病理性ASN可引起氧化应激,而神经炎症和相邻细胞中的蛋白质改变可加剧ASN的神经毒性,导致神经变性和神经元死亡。ASN可吸引并结合带负电荷的脂质,是脂质代谢调节、多巴胺产生和炎症反应中的关键介质,参与PD的发生发展。脂肪酸、甘油酯、磷脂等脂质异常代谢与ASN聚集密切相关,因此,脂质异常代谢在PD发生发展中发挥重要作用。本文主要综述脂质在PD发生发展中的作用及机制研究进展,以期为PD防治措施研究提供参考。

多囊卵巢综合征患者血清AMH、TNF-α、T、DHEA-S的水平及临床意义

目的探讨多囊卵巢综合征(PCOS)患者血清抗苗勒管激素(AMH)、肿瘤坏死因子-α(TNF-α)、睾酮(T)、硫酸脱氢表雄酮(DHEA-S)水平及临床意义,为患者的临床诊疗提供指导。方法选择2017年8月至2019年9月在深圳市宝安区妇幼保健院治疗的220例PCOS患者为观察组,并选择我院同期体检健康人群180例作为对照组。检测两组受检者的血清AMH、TNF-α、T、DHEA-S表达水平,计算各指标诊断PCOS的曲线下面积(AUC)及95%置信区间(95%CI),分析其诊断价值。结果观察组患者的AMH、TNF-α、T及DHEA-S水平分别为(8.74±4.27) pg/mL、(271.56±130.86) pg/mL、(0.72±0.26) nmoI/L、(8.17±3.23)μg/dL、(3.25±1.54) pg/mL,明显高于对照组的(5.46±2.19) pg/mL、(212.64±99.25) pg/mL、(0.46±0.18) nmoI/L、(6.69±2.78)μg/dL、(1.42±0.63) pg/mL,差异均有统计学意义(P<0.05);血清AMH诊断PCOS的AUC为0.754,95%CI为0.705~0.802;血清TNF-α诊断PCOS的AUC为0.629,95%CI为0.575~0.683;血清T诊断PCOS的AUC为0.815,95%CI为0.774~0.856;血清DHEA-S诊断PCOS的AUC为0.654,95%CI为0.601~0.70;AMH+TNF-α+T+DHEA-S诊断PCOS的AUC为0.892,95%CI为0.861~0.924;AMH+TNF-α+T+DHEA-S联合检测诊断PCOS的AUC明显高于单独检测,差异有统计学意义(P<0.05);AMH+TNF-α+T+DHEA-S联合检测的特异度及准确度均明显高于单独检测,差异均有统计学意义(P<0.05)。结论 PCOS血清AMH、TNF-α、T、DHEA-S水平均明显升高,四项指标联合检测对PCOS有较高的诊断价值,且各指标的变化有助于指导临床诊疗。

S-M(M=Al,Co)复合掺杂LiMn_2O_4的结构稳定性

应用量子化学电荷自洽离散变分Xα(SCC-DV-Xα)方法,研究了S-Al、S-Co复合掺杂增强尖晶石结构锂锰氧化物稳定性的作用机制.计算结果表明,S-Al复合掺杂锂锰尖晶石和S-Co复合掺杂锂锰尖晶石中的共价键强度均比未掺杂尖晶石LiMn2O4中的强,且与MnO2中的共价键强度相近;S-Al,S-Co复合掺杂尖晶石中Mn的电荷也与MnO2模型Mn6O2628-中十分接近.Mn原子的电荷密度次序是MnO2≈掺硫铝后锰锂尖晶石≈掺硫钴后的锂锰尖晶石<锰锂尖晶石.即LixMn3Co3O20S6n-和LixMn3Al3O20S6n-中Mn的状态与MnO2中的Mn相似.上述结果揭示了S和非Jahn-Teller效应阳离子(Al3+,Co3+)复合掺杂尖晶石结构锂锰氧化物在电化学过程中不会发生Jahn-Teller畸变的内在原因.

HIF-1α、GLUT1、MRP1和GST-π在非小细胞肺癌组织中的表达及意义

目的:探讨低氧诱导因子-1(hypoxia-inducible factor-1α,HIF-1α)、葡萄糖转运蛋白-1(glucose transporter1,GLUT1)、多药耐药相关蛋白(multidrug resistance-associated proteins,MRP1)和谷胱甘肽-S-转移酶(glutathione-S-tranferase,GST-π)的mRNA在非小细胞肺癌(non-small cell lungcancer,NSCLC)组织中的表达水平以及与肺癌生物学特性的关系。方法:采用RT-PCR、凝胶电泳半定量方法检测36例肺癌组织和12例癌旁组织中HIF-1α、GLUT1、MRP1和GST-π的表达,并采用SAS8.0统计软件分析它们在TNM分期中的表达情况。结果:4个基因的mRNA在癌症组织中的表达明显高于癌旁组织(P<0.01),在有淋巴结转移组和有远端转移组中的表达均明显高于无淋巴结转移组和无远处转移组(P<0.01和P<0.05);HIF-1α和GLUT1在T3、T4期中的表达明显高于在T1、T2期中的表达(P<0.01或P<0.05),MRP1、GST-π在各TNM分期中的表达则差异无统计学意义。结论:NSCLC组织中存在HIF-1α、GLUT1、MRP1和GST-π的过度表达,并均与淋巴结转移和远端转移相关;其中HIF-1α、GLUT1的表达随TNM分期的增加而增高,MRP1、GST-π表达则与TNM分期无关。HIF-1α与GLUT1的表达呈线性正相关(P<0.01),HIF-1α与MRP1和GST-π的表达均呈线性正相关(P<0.05),GLUT1与MRP1和GST-π的表达无相关性(P>0.05),MRP1和GST-π的表达呈线性正相关(P<0.05)。以上4个基因表达的增高可能是NSCLC发生、发展以及恶化的基因标志。

基于蒙特卡罗方法的α粒子细胞S值计算

在放射性免疫治疗以及硼中子俘获治疗(BNCT)等放射性治疗过程中,α粒子通过与人体组织材料相互作用产生次级δ电子将能量传递给人体组织,放射性核素在细胞尺度分布的不均匀性将严重影响靶区剂量分布。为深入了解放射性核素在细胞中不同位置分布对靶区剂量影响,采用基于历史凝聚算法的Monte Carlo工具包Geant4编写了细胞S值计算程序。计算了2种细胞尺寸,12种α粒子能量,3种源分布方式的细胞S值,与医学内照射剂量(MIRD)委员会解析算法的计算结果进行对比,发现两者差异在1%以内。证明了Geant4在μm尺度下细胞剂量计算的可行性,并对BNCT治疗过程中产生的α粒子(1.47MeV与1.78MeV)的细胞S值进行计算。