Controversies in chronic kidney disease staging

In 2002, a new chronic kidney disease staging system was developed by the US National Kidney Foundation. The classification system represented a new conceptual framework for the diagnosis of chronic kidney disease (moving to a schema based on disease severity defined by the glomerular filtration rate). While the introduction of the staging system stimulated significant clinical and research interest in kidney disease, there has been vigorous debate on its merits. This mini-review aims to summarise the recent controversies that have been raised since the introduction of the new classification.     

An active intracellular device to prevent lethal disease outcomes in virus-infected bacterial cells

Synthetic biology includes an effort to logically control cellular behavior. One long-term goal is to implement medical interventions inside living cells, creating intracellular "disease fighters"; one may imagine a system that detects viral infection and responds to halt the spread of the virus. Here, we explore a system designed to display some of the qualitative features that such disease prevention systems should have, while not claiming that the system itself has any medical application. An intracellular disease prevention mechanism should: lie dormant in the absence of the disease state; detect the onset of a lethal disease pathway; respond to halt or mitigate the disease's effects; and be subject to external deactivation when required. We have created a device that displays these properties, in the highly simplified case of a bacterial viral disease. Our system detects the onset of the lytic phase of bacteriophage lambda in Escherichia coli, responds by preventing this lethal pathway from being followed, and is deactivated by a temperature shift. We have formulated a mathematical model of the engineered system, using parameters obtained from the literature and by local experimental measurement, and shown that the model captures the essential experimental behavior of the system in most parameter regimes.     

Aberrant and alternative splicing in skeletal system disease

The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy.     

The Evolutions of Medical Building Network Structure for Emerging Infectious Disease Protection and Control

Emerging infectious disease is one of the most minatory threats in modern society. A perfect medical building network system need to be established to protect and control emerging infectious disease. Although in China a preliminary medical building network is already set up with disease control center, the infectious disease hospital, infectious diseases department in general hospital and basic medical institutions, there are still many defects in this system, such as simple structural model, weak interoperability among subsystems, and poor capability of the medical building to adapt to outbreaks of infectious disease. Based on the characteristics of infectious diseases, the whole process of its prevention and control and the comprehensive influence factors, three-dimensional medical architecture network system is proposed as an inevitable trend. In this conception of medical architecture network structure, the evolutions are mentioned, such as from simple network system to multilayer space network system, from static network to dynamic network, and from mechanical network to sustainable network. Ultimately, a more adaptable and corresponsive medical building network system will be established and argued in this paper.     

A telemetric study of physiologic changes in mice with induced autoimmune encephalomyelitis

Dysfunction of the autonomic nervous system may be an important component of disease progression in multiple sclerosis (MS), a paralytic inflammatory autoimmune disease of the central nervous system. Using the experimental autoimmune encephalomyelitis mouse model of MS, the authors carried out a pilot study to investigate whether telemetric monitoring might be a feasible approach for detecting disturbances in the autonomic control of heart rate and blood pressure after disease induction. Telemetric monitoring devices that were implanted in mice provided useful information regarding the physiologic changes that accompanied disease induction and progression. Changes were observed in heart rate, blood pressure, heart rate variability and diurnal rhythm immediately before and after disease onset. The device implantation procedure did not seem to alter the course of disease. Further investigation may establish these methods as a system for studying the relationships between MS progression and autonomic regulation of physiological status.     

Role of the endocannabinoid system in Alzheimer's disease: new perspectives

The role of the endocannabinoid system in several diseases is currently under intense study. Among these, Alzheimer's disease may be a new promising area of research. We have recently reported the existence of profound changes in the location and density of several elements of this system in Alzheimer's disease tissue samples, indicating that a non-neuronal endocannabinoid system is up-regulated in activated glia. Additional data from other groups suggest that glial cells may be important elements in the regulation of endocannabinoid system activity, both in health as in disease. Some of these aspects are briefly discussed in the present review.     

基于ICD-10编码应用的疾病数据质量管理体系建立

目的 基于国际疾病分类编码应用，建立综合考虑疾病命名和疾病分类的数据质量管理体系，以规范疾病诊断书写、保证疾病数据质量、客观反映临床现状。方法 运用版本差异分析和对照补缺的方法，临床医生在编码员的协助下对本专业类目下的疾病诊断和编码按照一定原则加以扩充。结果 院内诊断库和手术操作库健全完善并信息化运用，构建了一种既满足编码规范又便于临床使用的可持续改进的编码模式和疾病质量数据管理体系。结论 该管理体系能够有效推进临床医学语言的统一、引导病案管理部门的转型、实现临床医生编码的有效培训，夯实医院基础质量，促进医院内涵建设。     

Cerebral microinfarct is emergency consequence of Alzheimer's disease: a new insight into development of neurodegenerative diseases

Imbalance of Aβ and tau protein production and clearance are the key factors among many causes of Alzheimer''s disease that leading to neurons degeneration and cognitive disorders. As a novel approach, glymphatic system quickly clear metabolic waste (especially Aβ and tau) from cerebral environment, and dysfunction of glymphatic system may relate to occurrence of Alzheimer''s disease. Microinfarct is a common histopathologic situation occurring in aging brain and leads to dramatic increase the generation of metabolic by-product after neuronal injury, hindering the operation of glymphatic system and suppress cerebral spinal fluid (CSF) and cerebral interstitial fluid (interstitial fluid, ISF) exchange. Microinfarcts destruct the integrity of microvascular and microstructural tissue, result in Aβ deposition and tau phosphorylation that form neurofibrillary tangles and associated with the cause of Alzheimer''s disease. Currently, it has been found that glymphatic system is involved in the pathological process of Alzheimer''s disease. Improving the function of glymphatic system after cerebral microinfarcts could be developed as a new approach for Alzheimer''s disease prevention and treatment. In this review, we will provide in-depth discussion on functional changes of glymphatic system after cerebral microinfarcts, further reveal pathogenesis of Alzheimer''s disease and provide a potentially more effective method for treatment of Alzheimer''s disease.     

Neurological effects of American trypanosomyiasis: clinical aspects

Trypanosoma cruzi, causative agent of Chagas disease, affects not only cardiac and intestinal structures but also neurological structures. A high prevalence of T. cruzi infection occurs in Colombia, prompting the present study. First, a qualitative metaanalysis was undertaken using the PubMed database, the electronic internet engine Altavista, Colombian journals indexed by Colciencias, and three relevant textbooks. The following key words were used: Trypanosoma, Chagas disease, nervous system, spinal cord, central nervous system, peripheral nervous system, neuromuscular junction, autonomic nervous system, muscle, muscle disorders, neuromuscular disease, neuromuscular disorders, synapticopathies and dysautonomia. The documents analyzed numbered 116 and included original papers, reviews, case reports, editorials, brief communications, conferences and book chapters. At minimum, each document included data involving ELISA testing, indirect immunofluorescense, or parasitemia levels in the clinical, serological or histopathological studies. Polymerase chain reaction (PCR) studies were not included because of the recent introduction of PCR as a confirmatory technique for Chagas disease in Colombia. Chagas disease affects the central, the peripheral and the autonomic nervous system in humans, although its effects on the antonomic system is most commonly investigated in Colombia. Neurological lesions must be evaluated carefully, because patients may be misdiagnosed and treated as carriers of 'idiopathic' diseases. Neurological pathologies poses a serious threat in Colombia due to the prevalence of Chagas disease.     

肝脏免疫系统在酒精性肝损伤中的作用启示

酒精性肝病的致病因素是单一,但其发病机制复杂,目前尚不完全清楚。肝脏免疫系统被认为是独特的免疫系统,其作用越来越引起重视。肝内既有参与外周循环的淋巴细胞,也有长期定居于此的免疫细胞;加上肝脏解剖结构和血液循环的特殊性决定了肝脏独特的免疫微环境。研究肝脏免疫系统在酒精性肝病发病机制的作用,将有助于进一步阐明酒精性肝病发病机制,为酒精性肝病的预防和治疗提供新的靶点。     

Lymphatic Tissue Engineering and Regeneration

The lymphatic system is a major circulatory system within the body, responsible for the transport of interstitial fluid, waste products, immune cells, and proteins. Compared to other physiological systems, the molecular mechanisms and underlying disease pathology largely remain to be understood which has hindered advancements in therapeutic options for lymphatic disorders. Dysfunction of the lymphatic system is associated with a wide range of disease phenotypes and has also been speculated as a route to rescue healthy phenotypes in areas including cardiovascular disease, metabolic syndrome, and neurological conditions. This review will discuss lymphatic system functions and structure, cell sources for regenerating lymphatic vessels, current approaches for engineering lymphatic vessels, and specific therapeutic areas that would benefit from advances in lymphatic tissue engineering and regeneration.     

Compartment Analysis of Disease Progression in Time. II. Restricted Disease Increase

Three-compartmenl analysis was performed to describe the disease motion through presporulating (latent), sporulating (infectious) and postsporulating (removal) stages in the general case, where total disease increase is density dependent. A second-order Runge-Kutta method for numerical integration of the system of difterential equations was used to solve the equations. Total and postsporulating disease progress curves are S-shaped while latent and infectious disease progress in the form of optimum curves. The curve of a composite variable defined as total (latent and infectious) inoculum reservoir of the host progresses also in the form of an optimum curve showing a maxi at the total disease level y_t/K = 1 ? 1/iR, where K is the total population of infection sites, i is the infectious period, R the intrinsic infection rate and iR ≥ 1/(1 ? V_o/K). The size of this maxi is a monotone increasing function of the product iR by given initial disease level V_o. Condition iR =1/(1?y_o/K) is a threshold condition for total inoculum to increase over y_o, or alternatively a threshold condition for a rapid disease increase at the start resulting, possibly, in a large epidemic. Condition iR = O is a threshold condition for total disease to increase over initial disease level. Total disease reaches an asymptotic value less than unity if and only if infectious period is linite (existence of removals). In the compartment system there is a consistency regarding the threshold conditions for total disease to increase over initial disease level in the cases with and without a density-dependent factor. Conversely, in the Vanderplankian system of differential-difference equation the threshold conditions are iR = 0 and iR = 1 respectively due to the assumption of an exponential increase of total disease early in the epidemic. The particular cases without latent period and without removals are treated separately. The implications derived from the compartment analysis are compared with those derived from the Vanderplankian system of epidemiological analysis.     

OPG/RANK/RANKL系统与骨质疏松研究最新进展

骨质疏松是严重威胁中老年人健康的骨科常见病,OPG/RANK/RANKL是参与调节骨重建的最重要的分子系统之一,与骨疾病相关的骨质疏松有密切联系,并已成为药物设计的新靶点.因此,对该系统的深入研究将为骨生理、病理机制阐明及骨疾病防治带来积极影响.     

Relation of nutrition to health in aging persons; a four-year follow-up of a study in San Mateo County

A follow-up study of 577 San Mateo County residents over 50 years of age who were originally studied in 1948 was carried out. Three hundred fifty still were available for reevaluation. Mortality studies showed a higher death rate in males than in females, in persons of the lower economic levels, and in those with systolic blood pressure of more than 180 mm. of mercury. Correlations between factors studied and morbidity were not conclusive, but suggested relationships between low economic status and digestive system disease; low hemoglobin and high incidence of respiratory disease; high caloric intake and digestive system disease; low thiamine intake and nervous system disease; low ascorbic acid intake and diseases of the circulatory and digestive systems.     

COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.     

新城疫疫苗研究进展

新城疫（Newcastle disease,ND）是禽类的病毒性疾病之一,能引发禽类神经系统、消化系统和呼吸系统损伤,死亡率高达30%,对家禽养殖形成了严重制约,因此,研究ND具有重要的经济意义。合理使用疫苗是防控新城疫疫情的主要方法。自1950年以来,新城疫减毒活疫苗和灭活疫苗已被广泛使用,之后载体疫苗也进入商业化应用阶段。此外,疫苗佐剂的选择以及递送途径的优化也进入研究人员的视野。基于此,分析了新城疫传统疫苗、载体疫苗、病毒样颗粒疫苗的研发现状及前景,介绍了纳米粒子和新型免疫佐剂在新城疫疫苗研发过程中的应用进展,并总结了目前国内外常见的新城疫商业化疫苗,旨在为研制更高效、廉价的新城疫疫苗提供参考,从而进一步控制当前新城疫疫情的蔓延。     

Revealing the role of predator-dependent disease transmission in the epidemiology of a wildlife infection: a model study

It is well known that predation/harvesting on a species subjected to an infectious disease can affect both the infection prevalence and the population dynamics. In this paper, I model predator?Cprey?Cpathogen interactions in the case where the presence of a predator indirectly affects the transmission rate of the infection in its prey. I call this phenomenon the predator-dependent disease transmission. Such a scenario can arise, for example, as a consequence of anti-predator defence behaviour, debilitating the immune system of the prey. Although being well documented, the predator-dependent disease transmission has rarely been taken into account in ecoepidemiological models. Mathematically, I consider a classical S-I-P ecoepidemiological model in which the infected and/or the healthy host can be consumed by a predator where the coefficient in the mass action transmission term is predator-dependent. Investigation of the model shows that including such a predator-dependent disease transmission can have important consequences for shaping predator?Cprey?Cpathogen interactions. In particular, this can enhance the survival of the predator, restricted in a system with a predator-independent disease transmission. I demonstrate the emergence of a disease-mediated strong Allee effect for the predator population. I also show that in the system with predator-dependent disease transmission, the predator can indirectly promote epidemics of highly virulent infectious diseases, which would die out in a predator-free system. Finally, I argue that taking into account predator-dependent disease transmission can have a destabilizing effect in a eutrophic environment, which can potentially cause the extinction of both species. I also show that including the predator-dependent disease transmission may increase the infection prevalence, and this fact will question the ??keeping herds healthy?? hypothesis concerning the management of wildlife infections by natural predators.     

Drosophila models of human neurodegenerative disease

Drosophila has provided a powerful genetic system in which to elucidate fundamental cellular pathways in the context of a developing and functioning nervous system. Recently, Drosophila has been applied toward elucidating mechanisms of human neurodegenerative disease, including Alzheimer's, Parkinson's and Huntington's diseases. Drosophila allows study of the normal function of disease proteins, as well as study of effects of familial mutations upon targeted expression of human mutant forms in the fly. These studies have revealed new insight into the normal functions of such disease proteins, as well as provided models in Drosophila that will allow genetic approaches to be applied toward elucidating ways to prevent or delay toxic effects of such disease proteins. These, and studies to come that follow from the recently completed sequence of the Drosophila genome, underscore the contributions that Drosophila as a model genetic system stands to contribute toward the understanding of human neurodegenerative disease.     

Diversity of Virulence Phenotypes among Type III Secretion Negative Pseudomonas aeruginosa Clinical Isolates

Pseudomonas aeruginosa is a frequent cause of acute infections. The primary virulence factor that has been linked to clinical disease is the type III secretion system, a molecular syringe that delivers effector proteins directly into host cells. Despite the importance of type III secretion in dictating clinical outcomes and promoting disease in animal models of infections, clinical isolates often do not express the type III secretion system in vitro. Here we screened 81 clinical P. aeruginosa isolates for secretion of type III secretion system substrates by western blot. Non-expressing strains were also subjected to a functional test assaying the ability to intoxicate epithelial cells in vitro, and to survive and cause disease in a murine model of corneal infection. 26 of 81 clinical isolates were found to be type III secretion negative by western blot. 17 of these 26 non-expressing strains were tested for their ability to cause epithelial cell rounding. Of these, three isolates caused epithelial cell rounding in a type III secretion system dependent manner, and one strain was cytotoxic in a T3SS-independent manner. Five T3SS-negative isolates were also tested for their ability to cause disease in a murine model of corneal infection. Of these isolates, two strains caused severe corneal disease in a T3SS-independent manner. Interestingly, one of these strains caused significant disease (inflammation) despite being cleared. Our data therefore show that P. aeruginosa clinical isolates can cause disease in a T3SS-independent manner, demonstrating the existence of novel modifiers of clinical disease.