Research progress of Mycobacterium abscessus complex diseases / 中华临床感染病杂志

Mycobacterium abscessus complex (MABC), a rapidly growing nontuberculous mycobacterium, has received increasing attention worldwide due to its rising isolation rate. The similarity of symptoms between MABC pulmonary disease and tuberculosis, different treatment methods required by different subtypes, as well as high levels of innate, adaptive and acquired antibiotic resistance, make MABC treatment more difficult and lead to unfavorable clinical outcomes of patients. This article reviews the basic characteristics, common antibiotic resistance mechanisms, as well as diagnosis and treatment of MABC, to provide reference for future research and clinical treatment of MABC lung disease.

A New Approach to Network Pharmacological Analysis Based on Key Pathophysiological Processes / 中国实验方剂学杂志

In recent years， the field of network pharmacology （NP） has developed rapidly， but the flawed and routine workflow has seriously affected the scientificity and reliability of NP analysis results. For complex diseases caused by environmental and genetic factors， symptomatic treatment or drugs targeting a single pathophysiological process cannot prevent or delay the progression of the disease， so the drug development fails or withdraws from the market. Therefore， there is an urgent need to develop new ideas for NP analysis that combines multiple pathophysiological processes. The key pathophysiological process is an important and complete set of pathological changes in the process of the occurrence， development， and outcome of the disease， which represents the current comprehensive and profound understanding of the nature of the disease. In order to improve the quality of NP research and promote the healthy development of the NP field， this paper proposes a new idea of NP analysis based on key pathophysiological processes. Based on the long-term clinical practice of traditional Chinese medicine and the key pathophysiological process of the disease， the method comprehensively analyzes the pharmacological mechanism and active ingredients of traditional Chinese medicine compound from the perspective of key pathophysiological process， which increases the scientifically， reliability， and repeatability of the analysis results. This paper takes Alzheimer's disease （AD） as an example to illustrate the necessity， feasibility， main workflow， advantages， and disadvantages of this method， and it is expected to screen disease-modifying drugs that prevent or reverse the course of the disease and promote the clinical transformation of research results.

Integración de la Bioinformática en la caracterización Clínica y Genómica de Retinitis Pigmentosa, Síndrome de Noonan y Síndrome de Retraso Mental Martin-Probs, en un mismo individuo. Reporte de un Caso / Integration of Bioinformatics in the Clinical and Genomic Characterization of Retinitis Pigmentosa, Noonan Syndrome and Martin-Probs Mental Retardation Syndrome, in the Same Individual. Case report

Introducción: El avance en las técnicas bioinformáticas ha permitido realizar acercamientos y mejoras en los diagnósticos clínicos, correlacionando genotipo ­ fenotipo y permitiendo el acercamiento a una terapia personalizada. Objetivo: Realizar mediante técnicas bioinformáticas, la caracterización molecular y de expresión génica de una paciente con manifestaciones clínicas (dismorfias, retraso en el desarrollo) de una enfermedad compleja (poligénica). Materiales y métodos: Se realizó la secuenciación de exoma completo a partir de una muestra de sangre periférica. Se analizaron los datos obtenidos mediante análisis in-sílico, utilizando programas como SIFT, Mutation Tester, UMD y Provean, para determinar la significancia clínica de variantes encontradas; además se usó programa GeneMania para determinar las interacciones génicas. Resultados:Se encontraron 3 variantes en los genes SEMA4A, PTPN11 y RAB40A, asociados a Retinitis pigmentosa 35, Síndrome de Noonan y Sindrome de retraso mental Martin-Probs, respectivamente; encontrando según los softwares predictores, en el primer caso un significado clínico aparentemente benigno, y en los dos últimos genes un significado clínico patogénico. El análisis de redes génicas reveló alteraciones en funciones biológicas como la señalización mediada por fosfatidilinositol, respuesta al factor del crecimiento fibroblástico, vía de señalización de neutrofina y la morfogénesis de vasos sanguíneo que permitieron explicar gran parte de la sintomatología observada. Conclusión: El análisis personalizado de las patologías complejas mediante el uso de la clínica, herramientas genómicas y bioinformaticas han permitido un avance significativo en las técnicas para el procesamiento y análisis de datos, beneficiando los estudios científicos que permiten el acercamiento a un correcto diagnóstico y adecuada consejería genética.

Introduction: Advances in bioinformatics techniques have allowed approaches and improvements in clinical diagnoses, correlating genotype - phenotype and allowing the approach to personalized therapy. Objective: In order to perform the molecular characterization and gene expression in a patient with complex clinical manifestations through bioinformatics techniques, complete exome sequencing was performed by a peripheral blood sample to a woman with facial dysmorphisms and developmental disorders. Material and methods: We analyzed the data obtained by in-silico analysis, using programs such as SIFT, Mutation Tester, UMD and Provean, to determine the clinical significance of the found variants and GeneMania program was used to determine gene interactions. Results: 3 variants were found in the genes SEMA4A, PTPN11 and RAB40A, associated with Retinitis pigmentosa 35, Noonan Syndrome and Mental Retardation Syndrome Martin-Probs, respectively; according to the predictive softwares, in the first case an apparently benign clinical meaning, and in the last two genes a clinical pathogenic meaning. The analysis of gene networks revealed alterations in biological functions such as signaling mediated by phosphatidylinositol, response to the fibroblastic growth factor, neutrophin signaling pathway and blood vessel morphogenesis that allowed us to explain a large part of the observed symptomatology. Conclusion: The personalized analysis of complex pathologies through the use of clinical, genomic and bioinformatic tools has allowed a significant advance in techniques for processing and analyzing data, benefiting scientific studies that allow the approach to a correct diagnosis and adequate genetic counseling.

Application of polygenic risk scores in risk prediction and precision prevention of complex diseases: opportunities and challenges / 中华流行病学杂志

Along with the rapid progress in the field of human genomics, genome-wide association studies have successfully identified numerous risk loci for complex diseases. Polygenic risk scores can predict disease risk by integrating the effects of multiple susceptibility loci, and begin to show good performance for improving risk prediction, screening strategy and precision prevention. This paper briefly reviews the recent progress of polygenic risk scores in disease prevention, and summarizes the opportunities and challenges of its application.

Application of network biology on study of traditional Chinese medicine / 中国中药杂志

With the completion of the human genome project, people have gradually recognized that the functions of the biological system are fulfilled through network-type interaction between genes, proteins and small molecules, while complex diseases are caused by the imbalance of biological processes due to a number of gene expression disorders. These have contributed to the rise of the concept of the "multi-target" drug discovery. Treatment and diagnosis of traditional Chinese medicine are based on holism and syndrome differentiation. At the molecular level, traditional Chinese medicine is characterized by multi-component and multi-target prescriptions, which is expected to provide a reference for the development of multi-target drugs. This paper reviews the application of network biology in traditional Chinese medicine in six aspects, in expectation to provide a reference to the modernized study of traditional Chinese medicine.

Clinical and genetic aspects of generalized aggressive periodontitis in families of Tumkur district of Karnataka, India.

Background: Aggressive periodontitis (AP) is a complex disease whose phenotype is determined by genetic and environmental influences on the affected individuals. About 45% of the adult population in India has periodontitis. In Tumkur district of Karnataka, India, consanguineous first cousin and uncle-niece marriages are common, with a high incidence of AP. These discrepancies in the expression of periodontal disease directed us to find genetic etiology with respect to the Tumkur population. The clinical and genetic aspects of AP from this area have been presented in this paper. Materials and Methods: A total of nine families were ascertained at the Department of Periodontics, Sri Siddhartha Dental College and Hospital (Sri Siddhartha University), Tumkur. The clinical and radiographic data were gathered according to 1999 Consensus Classification of Periodontal Diseases. Peripheral blood samples were collected for total genomic DNA isolation using a Wizard TM Genomic Purification Kit (Promega, USA). The homozygosity mapping was carried out in a large consanguineous family to map a novel locus using autosomal markers from the CHLC/Weber Human Screening Set 10 (Research Genetics Inc., USA) at Indian Institute of Sciences, Bangalore. Results: The pedigree analysis suggested that the disorder is segregating as an autosomal trait. The homozygosity mapping failed to identify a locus for generalized AP in the family. Conclusion: The disorder may not be segregating as an autosomal recessive trait and we could have been misled by consanguinity in the family. It could be a multifactorial trait, or it could be still segregating as an autosomal recessive trait, but the region of homozygosity could be small and we failed to detect it using microsatellite markers. Therefore, SNP-marker-based analysis is warranted in future.

Concepts and necessity of preventive medical services for the 21st century

Not only disease patterns but also the contents and concepts of medical services are rapidly changing recent years. A quick look at the evolution of health care services shows that it has evolved in two major ways. First, medical interventions are gradually moving towards the prevention before diseases development. Second, the medical services have become individualized or tailored. The shift to preventive medical care is the most anticipated change in medical services in the 21st century. Theses phenomena are believed as a logical progression in the transition and evolution of medical services, and as a equivalence of the changing medical environment, such as progress in health care technology and changes in life value etc. Clinical practice based on evidence-based medicine is what distinguishes modern medicine from traditional medicine. Preventive medical services have also been established based on scientific evidence. The academic knowledge used as a basis for preventive medical services comes from the investigation of disease etiology, i.e. epidemiology. In the 21st century, the preventive medical service will be differentiated and enlarged to broad areas of medical practice and the target of the service may be focused to the a variety of complex diseases.

Estudios de asociación mediante rastreo genómico y su contribución en la genética del asma / Genome-wide association studies (gwas) and its contribution to the genetic of asthma

A pesar de todos los esfuerzos realizados por más de una década, las bases genéticas de muchas enfermedades comunes y complejas aún siguen siendo desconocidas, sin desmeritar los notables avances que se han logrado con los estudios de ligamiento en familias y de asociación con genes candidatos. Recientemente, el desarrollo de metodologías más robustas, como los estudios de asociación con rastreos genómicos (GWAs), ha permitido replicar asociaciones ya reportadas y a la vez descubrir nuevos genes posiblemente asociados. Los GWAs se basan en la utilización de un número considerable de marcadores genéticos tipo SNPs o STRs, los cuales son detectados con el propósito de encontrarlos asociados con la aparición y/o desarrollo de ciertas enfermedades. Teniendo en cuenta el gran impacto que actualmente tienen los GWAs como herramienta genética en la búsqueda de asociaciones, se hace una revisión teórica acerca del diseño e interpretación de los resultados de los mismos y su contribución en el asma y fenotipos relacionados.

Despite all the efforts of more than a decade, the genetic basis of many common and complex diseases are still unknown, without demerit the remarkable progress that has been made with the linkage studies in families and association studies of candidate genes. Recently, development of more robust methodologies, like genome-wide associations studies (GWAs), has allowed to replicate previously reported associations and at the same time discovers new possibly associated genes. The GWAs are based on the use of a considerable number of genetic markers like SNPs or STRs which are searched in order to of associate them with the appearance or development of certain diseases. Given the large current impact of the GWAs as genetic tool in the search of associations this is a theoretical review on the design and interpretation of results and contribution of GWAs in asthma and related phenotypes.

Identificación de genes causales y de susceptibilidad para enfermedades de herencia mendeliana y compleja / Identification of susceptibility and causing genes for mendelian and complex diseases

Los factores genéticos participan en la etiología de la mayoría de las enfermedades comunes en la población. Las enfermedades en las que participan factores genéticos pueden ser clasificadas en varias categorías y de acuerdo con las características que presenten, se pueden utilizar distintas estrategias metodológicas para identificar los genes participantes. En la mayoría de las enfermedades con un patrón de herencia mendeliana, se han podido identificar las mutaciones causales de la enfermedad. En las enfermedades complejas, esta búsqueda ha sido menos exitosa a pesar de ser las más frecuentes en la población. Encontrar genes de susceptibilidad es importante no solo para entender el mecanismo de acción de la enfermedad, sino que podría contribuir en el desarrollo de medicamentos más eficaces para el tratamiento, conocer los factores ambientales y desarrollar intervenciones preventivas y, en algunos casos, la aplicación de terapia génica.

Genetic factors are involved in the etiology of most common diseases and traits present in populations. Different methodological approaches can be utilized to determine genes involvedaccording to their genetic features in diseases. In the majority of conditions that follow a simple Mendelian pattern culprit genetic mutations have been identified. Conversely complex traits that are most common in the population are also the most difficult to identify. Finding these genes is crutial no just to clarify the pathophysiology of these common diseases but also to identifyenvironmental factors involved and to improve their treatment, including in some specific cases gene therapy.

Study on Classification of Complex Diseases in Uygur Medicine and Its Prethrombotic State / 中国中医药信息杂志

Objective To observe the pre-thrombosis markers in patients of different body fluids and discuss the relations between body fluids type and prethrombosis state. Methods The expression of CD41, CD62p on platelets, the level of plasma tissue plasminogen activator (t-PA) and its inhibiter (PAI-1), endothelin (ET-1), activated partial thromboplastin time (APTT), fibrinogen (FIB), prothrombin time (PT) and thrombin time (TT) were tested by using flow cytometer, ELASA, radioimmunoassay method and auto coagulometer. Results Patients with Abnormal Savda syndrome occupy 65.96% and non Abnormal Savda syndrome occupy 34.04% in complex diseases. Compared with normal control group, the average expression of CD62p, the level of plasma PAI-1, ET-1, FIB both in Abnormal Savda syndrome and non Abnormal Savda syndrome groups were significantly increased (P

Genome-wide Association Analysis Based on Copy Number Variations / 生物化学与生物物理进展

Copy number variations (CNVs) refer as a DNA segment that is 1 kb or larger and is presented at a variable copy number in comparison with a reference genome. Classes of CNVs include insertions, deletions, duplications and their complex combinations. Because they widely distributed in the genome with some important characteristics, such as heritable, relative stable and heterogeneity, CNVs are considered as novel genomic polymorphism markers. And the alteration of gene dosage which resulted from CNVs could change phenotype, so a novel CNV genome-wide association analysis (CNV-GWAS) strategy appeared recently and began to used for identifying susceptible genes of complex diseases. It was approved that it could complement the tranditional genome-wide association studies based on single nucleotide polymorphisms. Therefore, genomic structure variances are favorable for revealing the molecular mechanisms and genetic foundation of complex diseases.

A case of membranous nephropathy in a patient with Graves' disease / 대한내과학회지

Membranous nephropathy is one of the most common causes of the nephrotic syndrome in adults. Membranous nephropathy is known as a disease associated with many other disorders and the presumed etiology of the disease is a deposition of circulating immune complexes. But, it has rarely been reported in association with autoimmune thyroiditis. We report a case of membranous nephropathy associated with Graves' disease and review the literature regarding this disease entity.

Single nucleotide polymorphism in studying complex diseases susceptibility gene / 第二军医大学学报

Most diseases are complex genetic traits caused by multiple genetic and environmental components. It has been proposed that common genetic variations, mainly single nucleotide polymorphisms (SNPs), influence the susceptibility to complex diseases. We have conducted an extensive review on the characters of SNPs, the related website information, and the genotyping methods of SNPs such as direct sequencing, SnaPshot, Taqman, real time quantitative (kinetic) PCR with allele specific amplification, denaturing high performance liquid chromatography, and OLA/PCR.The strategies for studying the relation between SNPs and complex diseases susceptible genes were also reviewed.