Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome

AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Associations between Borg's rating of perceived exertion and changes in urinary organic acid metabolites after outdoor weightbearing hiking

BACKGROUND Developing methods to monitor exercise load and evaluate body fatigue and muscle injury over time in hiking training remains a key problem to be solved.A widely used psycho-physical tool to assess the subjective perception of effort during exercise is Borg’s rating of perceived exertion(BRPE)scale.Data on the relationships and validity of the BRPE compared to objectively assessed metabolic criteria are still lacking,especially urinary organic acid concentrations.AIM To verify whether the BRPE scale could be used in the prescription of outdoor hiking with weight-bearing and reveal the relationship between the BRPE scale and urinary physiological measures.METHODS Eighty-nine healthy men(average age:22 years)were enrolled in a 40 km(6 h)hiking training exercise with a 20 kg load.After training,the BRPE scale(6-20)was completed.All participants were divided into three groups according to the rating of the BRPE scale.Urine samples were collected before and after training.Urinary myoglobin levels were measured immediately using the fluorescent immunoassay method.The remaining urine was subpacked and frozen for the subsequent detection of urinary organic acids using gas chromatography and mass spectrometry.RESULTS The contents of organic acids and myoglobin in urine were significantly increased after participants hiked 40 km(6 h)with a 20 kg load.Only orthogonal partial least-squares discrimination analysis performed well in separating the group with a BRPE score of 6-12 from the group with a BRPE score of 13-20.Significant differences in the urine levels of several organic acids were observed between the two groups,and the heatmap also presented different metabolic profiles based on BRPE.According to the standard of a variable importance in the projection>1,fold change>1.5 and P<0.05,19 different metabolites of urinary organic acids were screened and enriched in pathways mainly including the citrate cycle(tricarboxylic acid cycle)and alanine,aspartate and glucose metabolism.CONCLUSION The BRPE scale identified significantly different urinary organic acid profiles between the higher and lower BRPE value groups,and,thus,could be used to monitor body fatigue in individuals participating in long-distance outdoor hiking with weight bearing.

Prediction model of in-hospital mortality in elderly patients with acute heart failure based on retrospective study

学习是开发在老病人的在里面医院死亡是预兆的一个临床的风险模型的这的 ObjectivesThe 目的与尖锐的心就医了失败(AHF ) 从医院里的心病学部门的特别护理单位 60 岁以上的 .Methods2486 病人被分析。为在里面医院死亡的独立风险因素被二进制逻辑回归获得然后过去常建立风险预言分数系统(RPSS ) 。在接收装置操作符特征和 C 统计数值测试的曲线(AUC ) 下面的区域被采用估计 RPSS 的性能并且与指南心失败(GWTG-HF ) 与以前的 get 作比较 .ResultsBy 二进制代码逻辑回归分析，心率(或：1.043， 95% CI：1.030-1.057， P < 0.001 ) ，左室的喷射部分(或：0.918， 95% CI：0.833-0.966， P < 0.001 ) ， pH 价值(或：0.001， 95% CI：0.000-0.002， P < 0.001 ) ，肾的机能障碍(或：0.120， 95% CI：0.066-0.220， P < 0.001 ) 并且 NT 职业人员 BNP (或：3.463， 95% CI：1.870-6.413， P < 0.001 ) 是为老 AHF 病人的在里面医院死亡的独立风险因素。另外， RPSS，它是所有创作了上述参数，比 GWTG-THF 提供了更好的风险预言(AUC：0.873 对 0.818， P = 0.016 ).ConclusionsOur 风险预言模型， RPSS，在老病人为在里面医院死亡向好预言提供了 AHF。

Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer

AIM: To investigate the relationship of serum levels of polyunsaturated fatty acid(PUFA) with kinds of cytokines in colorectal cancer(CRC).METHODS: Serum samples of 100 CRC patients were collected. The concentration of total n-3 PUFA which included C18:3 n-3, C20:5 n-3, C22:5 n-3, C22:6 n-3 and the total n-6 PUFA included C18:2 n-6, C18:3 n-6, C20:3 n-6, C20:4 n-6, and C22:5 n-6 were detected onGC-2010 Plus Gas Chromatograph with a Omegawax TM 250 column. Cytokines were detected by Mag Plex TM-C microspheres. P values for the trend were estimated by creating a continuous variable using the median value within quartiles.RESULTS: Interleukin-6(IL-6) showed significantly positive association with the C20:4 n-6(P for trend = 0.004). Interferon gamma(IFN-γ) showed significant positive association with the C22:5 n-3(P for trend = 0.035). IL-8 and matrix metalloproteinase-9(MMP-9) showed significant inverse association with the C22:6 n-3(P for trend = 0.049, and 0.021). MMP-2 showed significant inverse association with the C20:5 n-3(P for trend = 0.008). MMP-7 showed significantly positive association with the ratio of n-6 PUFA and n-3 PUFA(P for trend = 0.008). MMP-7 also showed significantly inverse association with the ratio of C20:4 n-6 and(n-6 PUFA + n-3 PUFA)(P for trend = 0.024). IL-10(P for trend = 0.023) and IL-6(P for trend = 0.036) showed significantly positive association with the ratio of C20:4 n-6 and C20:5 n-3.CONCLUSION: Our data suggested that serum levels of PUFA is related to the inflammation of CRC, and also play different role in regulation of immune response.

hTERT rs2736098 genetic variants and susceptibility of hepatocellular carcinoma in the Chinese population:a case-control study

BACKGROUND:The human telomerase reverse transcriptase(hTERT) gene encodes the catalytic subunit of telomerase,which mediates pleiotropic effects,including the regulation of senescence and proliferation and plays an important role in carcinogenesis.This study attempts to clarify the genetic predisposition to hepatocellular carcinoma(HCC),focusing on the hTERT gene rs2736098 polymorphism.METHOD:Four hundred patients with HCC and 400 noncancer controls were genotyped to elucidate the potential association between hTERT rs2736098 polymorphism and HCC risks.RESULTS:Compared with the controls,the patients with HCC had a lower frequency of G/G genotype(33.3% vs 44.3%,P=0.001) and a higher frequency of G/A(51.5% vs 39.5%,P=0.001).Allele genotypic frequencies in the patients differed from those of the controls(P=0.040).The data of this study rs2736098[A] allele contributed significantly to HCC risk in female patients(OR=1.78,95% CI,1.17-2.72,P=0.007),patients with HCV infection(OR=2.89,95% CI,1.08-7.70,P=0.031),non-drinker patients(OR=1.32,95% CI,1.06-1.65,P=0.015),and patients not affected by HBV(OR=1.77,95% CI,1.30-2.40,P【0.001).CONCLUSIONS:rs2736098[A] may be an independent hereditary parameter in HCC,but some risk factors would cover up the association by more powerful hepatocarcinogenesis.These results are important guidance for further studies in detecting HCC-associated single nucleotide polymorphisms.

表面增强拉曼散射光谱结合化学计量学方法对蜂蜜中双甲脒的高效检测（英文）

本文建立了一种灵敏、快速、环保的表面增强拉曼光谱(SERS)方法,以银纳米棒阵列为基底,测定了蜂蜜中微量的双甲脒.银纳米棒采用斜角沉积法制备,具有良好的SERS活性,增强因子为-10^7.利用密度泛函理论首先对双甲脒的特征峰进行了归属.进一步探测了该方法用于双甲脒检测的可行性,其对蜂蜜中双甲脒的最低检测浓度为0.08mg/kg.另一方面,采用偏最小二乘回归分析方法,对SERS全波谱进行分析并与双甲脒的浓度进行关联,建立了一种多元的双甲脒预测模型.结果表明,蜂蜜样本中双甲脒的预测浓度与实际浓度吻合较好.与传统的基于SERS单峰强度的单变量定量模型相比,本文提出的多元预测模型综合了双甲脒的所有特征峰,提高了检测精度和抗干扰能力.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip

BACKGROUND DNA methylation is a part of epigenetic modification,that is closely related to the growth and development of colorectal cancer(CRC).Specific methylated genes and methylated diagnostic models of tumors have become current research focuses.The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC.AIM To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip.METHODS The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients(n=5)and colorectal adenoma patients(n=5).Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma.RESULTS A total of 1865 methylated CpG sites with significant differences were detected,including 676 hypermethylated sites and 1189 hypomethylated sites.The distribution of these sites covered from the 1^(st) to 22^(nd) chromosomes and are mainly distributed on the gene body and gene promoter region.GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation,molecular binding,transcription factor activity and signal transduction pathway.CONCLUSION The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

Proton pump inhibitors(PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease(GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls(HCs) using 16 S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPIuser and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae,Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on shortterm PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.