Biomarkers of Alzheimer’s disease in body fluids

Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.     

Mitochondrial haplogroups associated with Japanese centenarians,Alzheimer＇s patients,Parkinson＇s patients,type 2 diabetic patients and healthy non-obese young males

The relationships between five classes of Japanese people （i.e., 96 centenarians, 96 Alzheimer＇s disease （AD） patients, 96 Parkinson＇s disease （PD） patients, 96 type 2 diabetic （T2D） patients, and 96 healthy non-obese young males） and their mitochondrial single nucleotide polymorphism （mtSNP） frequencies at individual mtDNA positions of the entire mitochondrial genome were examined using the radial basis function （RBF） network and the modified method. New findings of mitochondrial haplogroups were obtained for individual classes. The five classes of people were associated with the following haplogroups： Japanese centenarians-M7b2, D4b2a, and B5b; Japanese AD patients-G2a, B4cl, and N9b1; Japanese PD patients-M7b2, B4e, and B5b; Japanese T2D patients-B5b, M8al, G, D4, and F1; and Japanese healthy non-obese young males-D4g and D4b1b. From the points of common haplogroups among the five classes, the cente- narians have the common haplogroups M7b2 and B5b with the PD patients and common haplogroup B5b with the T2D patients. In addition, the 112 Japanese semi-supercentenarians （over 105 years old） recently reported were also examined by the method proposed. The results obtained were the haplogroups D4a, B4c1a, M7b2, F1, M1, and B5b. These results are different from the previously reported haplogroup classifications. As the proposed analysis method can predict a person＇s mtSNP constitution and the probabilities of becoming a centenarian, AD patient, PD patient, or T2D patient, it may be useful in initial diagnosis of various diseases.     

Biomarkers of neurodegenerative disorders： How good are they？

Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies,biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differentiable between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance,are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer‘s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson‘s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington‘s gene mutations in Huntington‘s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.     

Epigenetics of human melanoma： promises and challenges

Melanoma is the deadliest form of skin cancer with rising incidence and mortality rates. Although early-stage melanoma is highly curable, advanced-stage melanoma is refractory to treatment. This underscores the importance of prevention and early detection as well as the need to improve treatment and prognostication of human melanoma. Elucidating the underlying mechanisms of the initi- ation and progression of human melanoma can help identify potential targets of intervention for prevention, diagnosis, therapy, and prognosis of this disease. Aberrant DNA methylation and histone modifications are the best-established epigenetic mechanisms of carcinogenesis. The occurrence of epigenetic changes prior to clinical diagnosis of cancer and their reversibility through pharmaco-logic/genetic approaches offer a promising avenue for basic and translational research on human melanoma. Candidate gene（s） or genome-wide aberrant DNA methylation and histone modifications have been observed in human melanoma tumor tissues and cell lines, and correlated to cellular and functional characteristics and/or clinicopathologicai features of this malignancy. The present review summarizes the published researches on aberrant DNA methylation and histone modifications in connection with human melanoma. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in these epigenetic fields of research. Examples of epigenetic therapy applied for human melanoma in vitro, and the challenges of its in vivo application for clinical treatment of solid tumors are discussed.     

Two new species of Hartigia Schidte from China(Hymenoptera:Cephidae)

Two new species of Hartigia Schidte, 1838 from China are described: H. maculothoracica sp. nov. from Xinjiang and H. fuscicosta sp. nov. from Jilin. A diagnosis of Hartigia and a key to Hartigia maculothoracica and its relatives are provided.     

Computational Cardiology—A New Discipline of Translational Research

正Over the past two decades,improved diagnosis,pharmaceutical therapies,and interventional strategies have impressively improved the armamentarium of modern cardiologists in the?ght against the most incident and lethal diseases:heart failure,ischemic heart disease,and arrhythmia.The innovations     

Artificial intelligence in computer-aided diagnosis of abdomen diseases

<正>The abdomen contains many organs, along with a range of abdominal diseases that require accurate diagnosis. Clinical imaging plays a crucial role in abdominal disease diagnosis,prognosis, and treatment assessment. For decades, physicists have focused on innovation in terms of imaging techniques, assisting radiologists to improve abdominal diseases detection and diagnosis. Consequently, many new     

Development of HBsAg-binding aptamers that bind HepG2.2.15 cells via HBV surface antigen

Hepatitis B virus surface antigen(HBsAg),a specific antigen on the membrane of Hepatitis B virus (HBV)-infected cells,provides a perfect target for therapeutic drugs.The development of reagents with high affinity and specificity to the HBsAg is of great significance to the early-stage diagnosis and treatment of HBV infection.Herein,we report the selection of RNA aptamers that can specifically bind to HBsAg protein and HBsAg-positive hepatocytes.One high affinity aptamer,HBs-A22,was isolated from an initial 115 mer library of ~1.1×10 15 random-sequence RNA molecules using the SELEX procedure.The selected aptamer HBs-A22 bound specifically to hepatoma cell line HepG2.2.15 that expresses HBsAg but did not bind to HBsAg-devoid HepG2 cells.This is the first reported RNA aptamer which could bind to a HBV specific antigen.This newly isolated aptamer could be modified to deliver imaging,diagnostic,and therapeutic agents targeted at HBV-infected cells.     

Submerged culture of chromium-enriched Termitomyces albuminosus

A species of mushroom, Termitomyces albuminosus, was cultured in liquid medium for production of chromium-enriched mycelium. The influence of chromium （Ⅲ） on mycelial growth of T. albuminosus was investigated. An optimum medium composed of 5.6g/L yeast extract, 51.6g/L hydrolyzed rice, 2g/L KH2PO4, and 20mg/L chromium（Ⅲ） with initial pH of 4.5 was obtained by using method of central composite design （CCD）. After incubation of 84h, the maximal biomass of chromium-enriched mycelia reached 24.23g DMW（dried mycelial weight）/L with 272μg/g DMW chromium content in 500mL flasks containing 100mL medium with an inoculum of 8% on a shaker of 100r/min under an optimized cultivation condition at 28 ℃.     

A parameter uniform essentially firsorder convergent numerical method for a parabolic system of singularly perturbed differential equations of reaction—diffusion type with initial and Robin boundary conditions

In this paper,a class of linear parabolic systems of singularly perturbed second-order differential equations of reaction-diffusion type with initial and Robin boundary conditions is considered.The components of the solution u→ of this system are smooth,whereas the components of αu→/αx exhibit parabolic boundary layers.A numerical method composed of a classical finite difference scheme on a piecewise uniform Shishkin mesh is suggested.This method is proved to be first-order convergent in time and essentially first-order convergent in the space variable in the maximum norm uniformly in the perturbation parameters.     

Apathy in Parkinson disease

Apathy is one of the least investigated symptom of Parkinson disease （PD）. In the article there are data of frequency, diagnostic features, pathophysiology and treatment of apathy in PD. The aim of the investigation was to evaluate the frequency of apathy in PD without dementia, evaluate the relationship with other neuropsychiatric and motor disorders, influence on the life quality. 115 patients （age-63.84±0.6 years, stage 2.6±0.3） with PD without dementia were included in the investigation. There were used the following scales： scale of evaluation stages of PD by Hoehn-Yahr, UPDRS （part 〈〈activity of daily living〉〉, 〈〈motor functions 〉〉）; Beck Depression Inventory, Spielberger State Trait Anxiety Inventory, Parkinson Disease Sleep Scale- PDSS, Epworth Sleepiness Scale, Parkinson Fatigue Scale-PFS- 16, SCOPA-Cog, Lilli Apathy Rating Scale LARS and Apathy Scale AS. Apathy was found in 25% of patients. The frequency and severity of apathy does not depend on stage and duration of PD. It was found positive correlation of apathy and hypokinesia. In different stages of PD there was variability of relationships of apathy with depression, executive functions and sleep disorders. We suppose the heterogeneity of apathy in PD because of the variability of the association with other neuropsychiatric （affective, cognitive, sleep） disorders. It was found the negative influence of apathy on daily activity, emotional and social aspects of life quality.     

Identification of A Novel SBF2 Frameshift Mutation in Charcot–Marie–Tooth Disease Type 4B2 Using Whole-exome Sequencing

Abstract Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma （CMT4B2, OMIM 604563） is a genetically-heterogeneous childhood-onset neuromuscular disorder. Here, we report the case of a 15-year-old male adolescent with lower extremity weakness, gait abnormalities, foot deformities and early-onset glaucoma. Since clinical diagnosis alone was insufficient for providing pathogenetic evidence to indicate that the condition belonged to a consanguineous family, we applied whole-exome sequencing to samples from the patient, his parents and his younger brother, assuming that the patient＇s condition is transmitted in an autosomal recessive pattern. A frame-shift mutation, c.4571delG （P.Gly1524Glufs＊42）, was revealed in the CMT4B2-related gene SBF2 （also known as MTMR13, MIM 607697）, and this mutation was found to be homozygous in the proband and heterozygous in his parents and younger brother. Together with the results of clinical diagnosis, this case was diagnosed as CMT4B2. Our finding further demonstrates the use of whole-exome sequencing in the diagnosis and treatment of rare diseases.     

Effects of cisplatin on telomerase activity and telomere length in BEL—7404 human hepatoma cells

INTRODUCTIONPrimary hepatocellular carcinoma (PHCC), oneof the most common malignancies in the world, isan aggressive cancer. The mean survival time fromestablishment of diagnosi8 is only about 4 months(2 months if the diagnosis is made 1ate). It causesab…     

A DSRPCL-SVM approach to informative gene analysis

Microarray data based tumor diagnosis is a very interesting topic in bioinformatics. One of the key problems is the discovery and analysis of informative genes of a tumor. Although there are many elaborate approaches to this problem, it is still difficult to select a reasonable set of informative genes for tumor diagnosis only with microarray data. In this paper, we classify the genes expressed through microarray data into a number of clusters via the distance sensitive rival penalized competitive learning （DSRPCL） algorithm and then detect the informative gene cluster or set with the help of support vector machine （SVM）. Moreover, the critical or powerful informative genes can be found through further classifications and detections on the obtained informative gene clusters. It is well demonstrated by experiments on the colon, leukemia, and breast cancer datasets that our proposed DSRPCL-SVM approach leads to a reasonable selection of informative genes for tumor diagnosis.     

Hsa＿Circ＿0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

Many circular RNAs(circRNAs) are reported to be abnormally expressed during the progression of various tumors, and these circRNAs can be used as anti-tumor targets. Therefore, it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here, we report that hsa＿Circ＿0000826(Circ＿0000826), a circ RNA with significantly reduced expression level in CRC tissues, is associated with a poor prognosis in patients. The silencing of C...     

The Performance of Whole Genome Amplification Methods and Next-Generation Sequencing for Pre-Implantation Genetic Diagnosis of Chromosomal Abnormalities

Reliable and accurate pre-implantation genetic diagnosis(PGD) of patient’s embryos by next-generation sequencing(NGS) is dependent on efficient whole genome amplification(WGA) of a representative biopsy sample. However, the performance of the current state of the art WGA methods has not been evaluated for sequencing. Using low template DNA(15 pg) and single cells, we showed that the two PCR-based WGA systems Sure Plex and MALBAC are superior to the REPLI-g WGA multiple displacement amplification(MDA) system in terms of consistent and reproducible genome coverage and sequence bias across the 24 chromosomes, allowing better normalization of test to reference sequencing data. When copy number variation sequencing(CNV-Seq) was applied to single cell WGA products derived by either Sure Plex or MALBAC amplification, we showed that known disease CNVs in the range of 3e15 Mb could be reliably and accurately detected at the correct genomic positions. These findings indicate that our CNV-Seq pipeline incorporating either Sure Plex or MALBAC as the key initial WGA step is a powerful methodology for clinical PGD to identify euploid embryos in a patient’s cohort for uterine transplantation.     

植入前遗传学诊断的原理、方法及适应症

植入前遗传学诊断是一种非常早的产前诊断,指在胚胎着床之前即对配子或胚胎的遗传物质进行分析,检测配子或胚胎是否有遗传物质异常,选择正常胚胎进行移植。与传统的产前诊断相比,能避免选择性流产异常妊娠给妇女带来的心身痛苦。本文就该领域的发展及现状和其诊断原理、方法及适应症进行了总结和综述。 Abstract:Preimplatation genetic diagnosis (PGD) is a very early form of prenatal diagnosis.Gametes or embryos are biopsied and a genetic diagnosis is carried out on the biopsied cells to investigate if the gametes or embryos is free of genetic disease.And the normal embryos is transferred to the mother.Comparing to the traditional prenatal diagnosis,PGD is a method that can avoid aborting a abnormal pregnant and reduce pains of women.In this review,we introduce the history of development and statues in quo,principle,method and application of PGD.     

Characterization of glucose-6-phosphate dehydrogenase deficiency and identification of a novel haplotype 487G>A/IVS5-612(G>C) in the Achang population of southwestern China

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its gene mutations were studied in the Achang population from Lianghe County in Southwestern China. We found that 7.31% (19 of 260) males and 4.35% (10 of 230) females had G6PD deficiency. The molecular analysis of G6PD gene exons 2―13 was performed by a PCR-DHPLC-Sequencing or PCR-Sequencing. Sixteen inde-pendent subjects with G6PD Mahidol (487G>A) and the new polymorphism IVS5-612 (G>C), which combined into a novel haplotype, were identified accounting for 84.2% (16/19). And 100% Achang G6PD Mahidol were linked to the IVS5-612 C. The percentage of G6PD Mahidol in the Achang group is close to that in the Myanmar population (91.3% 73/80), which implies that there are some gene flows between Achang and Myanmar populations. Interestingly, G6PD Canton (1376G>T) and G6PD Kaiping (1388G>A), which were the most common G6PD variants from other ethnic groups in China, were not found in this Achang group, suggesting that there are different G6PD mutation profiles in the Achang group and other ethnic groups in China. Our findings appear to be the first documented report on the G6PD genetics of the AChang people, which will provide important clues to the Achang ethnic group origin and will help prevention and treatment of malaria in this area.