世纪之交:现代中药药理学的回顾与展望

几千年来, 中医药学的发展基本是一种封闭式的。虽然,在发展过程中,也曾不断吸收一些外国医学的内容,但中医药学主要靠自身经验的积累和提高,形成自己独特的、系统的理论和实践,为我国人民的健康繁衍和国家昌盛,作出了重大的贡献。到19 世纪末,20 世纪初,先进的西方医学引进中国,中医药学面临两种前景：或者是被排斥消灭,或者是汲取西医长处继续发展向前进。我国老一辈的医学家,尤其是受现代医学教育的医学家,其中有很多人在20 世纪从事把中西医学融合一起的伟大的、艰巨的工作,并取得很大成就。在中西医结合工作中,中药的现…     

Considerations of Traditional Chinese Medicine as Adjunct Therapy in the Management of Ulcerative Colitis

Ulcerative colitis (UC) has been treated with traditional Chinese medicine (TCM) for literally thousands of years. This paper gives an overview of TCM in the management of UC, provides an account of the state of the evidence, identifies gaps in the research base, and makes recommendations for future research. TCM is based on patterns and this influences the selection of the type of herbal medication or manipulation technique used for treatment. The majority of clinical studies on the efficacy of Chinese herbal medicine and acupuncture in the treatment of UC have methodological shortcomings. The extent of heterogeneity in many of these clinical trials, poor design quality of past studies prevent meaningful systematic reviews (SRs) or meta-analysis, although there are positive signs that TCM may be useful in relieving abdominal pain and reducing inflammation. Many unknowns still exist, including the active ingredients within Chinese herbal medicine and the potential for interaction with other drugs or western medications. While there may be a potential role for utilizing TCM in the treatment of UC patients relying on both traditional concepts and modern developments, it should be recognized that there are no studies that irrefutably support the use of TCM in the treatment of UC. Further basic or translational research must be done to elucidate mechanisms of action of these agents, and well-designed and well-conducted clinical studies must also be done to determine efficacy and safety of these agents.     

Text mining for traditional Chinese medical knowledge discovery: A survey

Extracting meaningful information and knowledge from free text is the subject of considerable research interest in the machine learning and data mining fields. Text data mining (or text mining) has become one of the most active research sub-fields in data mining. Significant developments in the area of biomedical text mining during the past years have demonstrated its great promise for supporting scientists in developing novel hypotheses and new knowledge from the biomedical literature. Traditional Chinese medicine (TCM) provides a distinct methodology with which to view human life. It is one of the most complete and distinguished traditional medicines with a history of several thousand years of studying and practicing the diagnosis and treatment of human disease. It has been shown that the TCM knowledge obtained from clinical practice has become a significant complementary source of information for modern biomedical sciences. TCM literature obtained from the historical period and from modern clinical studies has recently been transformed into digital data in the form of relational databases or text documents, which provide an effective platform for information sharing and retrieval. This motivates and facilitates research and development into knowledge discovery approaches and to modernize TCM. In order to contribute to this still growing field, this paper presents (1) a comparative introduction to TCM and modern biomedicine, (2) a survey of the related information sources of TCM, (3) a review and discussion of the state of the art and the development of text mining techniques with applications to TCM, (4) a discussion of the research issues around TCM text mining and its future directions.     

Multilingual chief complaint classification for syndromic surveillance: an experiment with Chinese chief complaints

PURPOSE: Syndromic surveillance is aimed at early detection of disease outbreaks. An important data source for syndromic surveillance is free-text chief complaints (CCs), which may be recorded in different languages. For automated syndromic surveillance, CCs must be classified into predefined syndromic categories to facilitate subsequent data aggregation and analysis. Despite the fact that syndromic surveillance is largely an international effort, existing CC classification systems do not provide adequate support for processing CCs recorded in non-English languages. This paper reports a multilingual CC classification effort, focusing on CCs recorded in Chinese. METHODS: We propose a novel Chinese CC classification system leveraging a Chinese-English translation module and an existing English CC classification approach. A set of 470 Chinese key phrases was extracted from about one million Chinese CC records using statistical methods. Based on the extracted key phrases, the system translates Chinese text into English and classifies the translated CCs to syndromic categories using an existing English CC classification system. RESULTS: Compared to alternative approaches using a bilingual dictionary and a general-purpose machine translation system, our approach performs significantly better in terms of positive predictive value (PPV or precision), sensitivity (recall), specificity, and F measure (the harmonic mean of PPV and sensitivity), based on a computational experiment using real-world CC records. CONCLUSIONS: Our design provides satisfactory performance in classifying Chinese CCs into syndromic categories for public health surveillance. The overall design of our system also points out a potentially fruitful direction for multilingual CC systems that need to handle languages beyond English and Chinese.     

人工智能在中医药的研究现状及展望

中医药在世界范围内难以被广泛接受的主要问题是缺少足够客观定量的数据支撑和完备而自洽的理论体系。此外,传统中医术语的模糊性、理论知识的难以理解性、治疗思维的抽象性、中医医案的繁杂性也对中医现代化发展带来了极大的挑战。随着信息技术的日新月异,大数据和人工智能技术为规范中医诊疗数据、构建智能中医诊疗体系以及突破传统中医诊疗模式提供了新方法,进一步推动了中医药智能化的发展。经过半个多世纪的发展,中医与人工智能技术的融合逐步深入,取得了一定的应用成果,如中医药中医信息化数据库、中医四诊采集设备、中医辅助诊疗系统以及智慧中医健康管理等。但就目前而言,中医药智能化发展中仍存在数据标准欠缺、相关制度不够完善、交叉人才匮乏等问题,未来还需进一步建立规范的数据标准,完善数据共享、知识产权、伦理规范等法律法规,加速培养学科交叉复合型人才,创新思维革新医疗模式等,促进人工智能背景下的中医药创新发展。本文从知识发现与机器学习的角度,对人工智能在中医药的研究进展概括总结,以期为中医药智能化提供助力。     

Retinitis pigmentosa in Spain

Retinitis pigmentosa is a term commonly given to a group of inherited and progressive disorders which affect the photoreceptors of the retina. As part of an ongoing research programme throughout Spain, clinical, epide-miological, and genetic studies have been carried out on these diseases. Here, we report the relative frequencies of the different genetic types in 503 non-syndromic and 89 syndromic RP families of Spanish origin. The most frequent syndromic RP forms were Usher syndrome type 1 (20/ 89 families=30%) and Usher syndrome type 2 (44 families=49%). Among non-syndromic RP forms, 12% were autosomal dominant, 39% autosomal recessive and 4% X-linked. Forty-one percent were isolated or simplex cases and in 4% the genetic type could not be established.     

Integrative mining of traditional Chinese medicine literature and MEDLINE for functional gene networks

OBJECTIVE: The amount of biomedical data in different disciplines is growing at an exponential rate. Integrating these significant knowledge sources to generate novel hypotheses for systems biology research is difficult. Traditional Chinese medicine (TCM) is a completely different discipline, and is a complementary knowledge system to modern biomedical science. This paper uses a significant TCM bibliographic literature database in China, together with MEDLINE, to help discover novel gene functional knowledge. MATERIALS AND METHODS: We present an integrative mining approach to uncover the functional gene relationships from MEDLINE and TCM bibliographic literature. This paper introduces TCM literature (about 50,000 records) as one knowledge source for constructing literature-based gene networks. We use the TCM diagnosis, TCM syndrome, to automatically congregate the related genes. The syndrome-gene relationships are discovered based on the syndrome-disease relationships extracted from TCM literature and the disease-gene relationships in MEDLINE. Based on the bubble-bootstrapping and relation weight computing methods, we have developed a prototype system called MeDisco/3S, which has name entity and relation extraction, and online analytical processing (OLAP) capabilities, to perform the integrative mining process. RESULTS: We have got about 200,000 syndrome-gene relations, which could help generate syndrome-based gene networks, and help analyze the functional knowledge of genes from syndrome perspective. We take the gene network of Kidney-Yang Deficiency syndrome (KYD syndrome) and the functional analysis of some genes, such as CRH (corticotropin releasing hormone), PTH (parathyroid hormone), PRL (prolactin), BRCA1 (breast cancer 1, early onset) and BRCA2 (breast cancer 2, early onset), to demonstrate the preliminary results. The underlying hypothesis is that the related genes of the same syndrome will have some biological functional relationships, and will constitute a functional network. CONCLUSION: This paper presents an approach to integrate TCM literature and modern biomedical data to discover novel gene networks and functional knowledge of genes. The preliminary results show that the novel gene functional knowledge and gene networks, which are worthy of further investigation, could be generated by integrating the two complementary biomedical data sources. It will be a promising research field through integrative mining of TCM and modern life science literature.     

Which accelerator photon beams are "clinic-like" for reference dosimetry purposes?

Previous work has demonstrated that, for photon beam dosimetry, TPR10(20) is not an ideal beam quality specifier for all bremsstrahlung beams, especially for lightly filtered beams in some standards laboratories. This paper addresses the following questions: Is TPR10(20) an adequate beam quality specifier for all modern clinical therapy accelerators? When can nonclinical beams in standards laboratories be used to calibrate ion chambers or measure kQ factors as a function of TPR10(20)? Based on detailed Monte Carlo simulations of Varian, Siemens, Elekta, and GE (Saturn) accelerators one can conclude that TPR10(20) is an adequate beam quality specifier for all these machines in the sense that for a given value of TPR10(20), the value of stopping-power ratios is the same. It is shown that, for the heavily filtered beams used in standards laboratories, TPR10(20) is an adequate beam quality specifier. It is also demonstrated that, for a larger range of bremsstrahlung beams than previously, %dd(10)x is a good beam quality specifier for all clinical beams as well as the lightly and heavily filtered beams in some standards laboratories. A criterion, based on the measured values of TPR10(20) and %dd(10)x for the beam, is proposed for determining whether a nonclinical beam is well specified by TPR10(20). Agreement between calculations for specific accelerators and measured beam quality specifiers is shown to be good, but agreement with published data for a variety of clinical accelerators is not as good. Possible reasons for the discrepancy are discussed.     

Toxicological effects of cigarette smoke on Ana-1 macrophages in vitro

Cigarette smoke exposure is associated with increased risk of different disorders. Immunological dysfunction especially in macrophages is one of important reasons in the initiation, progression and exacerbation of smoke-related pulmonary illnesses. However, it is still obscure how cigarette smoke impacts the vitality and functions of macrophages. In the present study, we examined the effects of cigarette smoke extract (CSE) on mouse Ana-1 macrophages and tried to elucidate the involved mechanism. The results showed CSE induced cell apoptosis accompanied by increased releasing of lactate dehydrogenase (LDH), mitochondrial injury and oxidative stress. It also inhibited anti-apoptosis protein Bcl-2 expression and promoted pro-apoptosis protein Bax and Bad expressions. Moreover, low-dose CSE increased nuclear NF-κB levels of macrophages; on the contrary, high-dose CSE or long-time treatment decreased it. These observations were in correspondence with changes of intracellular ROS level and antioxidant enzymes’ activity. Furthermore, pretreatment with 10 μM of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) for 1 h significantly enhanced macrophage apoptosis. Taken together, these data implied that mitochondrial dysfunction and oxidative stress played important roles in the injury of Ana-1 cells caused by CSE, which was related to NF-κB pathway; an anti-apoptotic program played a dominant role at low doses/short-term exposure to CSE, whereas a pro-apoptotic program was initiated at high doses/long-term exposure.     

Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT

PurposeCongenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES.MethodsWe conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping.ResultsIn 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype–phenotype correlation.ConclusionWe conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.     

从IL—2水平探讨黄芪及黄芪多糖的免疫调节作用

本文报道了黄芪及其多糖对正常小鼠和大黄脾虚模型小鼠体内、体外白细胞介素2(IL—2)产生的影响。大黄脾虚模型小鼠IL—2活性比正常小鼠明显降低;25～200%黄芪水煎剂以及50～200mg/ml黄芪多糖均能使大黄脾虚模型小鼠低下的IL—2活性提高;但对正常小鼠则无影响。提示IL—2产生增加可能是黄芪“扶正”的重要机制之一,也是其调节免疫功能的分子免疫学基础之一;IL—2活性有可能是“脾气”的内涵之一。     

A framework and its empirical study of automatic diagnosis of traditional Chinese medicine utilizing raw free-text clinical records

Automatic diagnosis is one of the most important parts in the expert system of traditional Chinese medicine (TCM), and in recent years, it has been studied widely. Most of the previous researches are based on well-structured datasets which are manually collected, structured and normalized by TCM experts. However, the obtained results of the former work could not be directly and effectively applied to clinical practice, because the raw free-text clinical records differ a lot from the well-structured datasets. They are unstructured and are denoted by TCM doctors without the support of authoritative editorial board in their routine diagnostic work. Therefore, in this paper, a novel framework of automatic diagnosis of TCM utilizing raw free-text clinical records for clinical practice is proposed and investigated for the first time. A series of appropriate methods are attempted to tackle several challenges in the framework, and the Naïve Bayes classifier and the Support Vector Machine classifier are employed for TCM automatic diagnosis. The framework is analyzed carefully. Its feasibility is validated through evaluating the performance of each module of the framework and its effectiveness is demonstrated based on the precision, recall and F-Measure of automatic diagnosis results.     

The prognostic significance of nuclear CSE1L in urinary bladder urothelial carcinomas

Prognosis of urinary bladder urothelial carcinomas may be challenging; many tumors with similar histopathologic features show significantly different clinical outcomes. CSE1L, the chromosome segregation 1-like protein, is both a cytoplasmic and nuclear protein. We investigated the cytoplasmic/nuclear expression pattern of CSE1L to determine its potential prognostic significance. In immunohistochemical analysis, nonneoplastic urothelium showed faint CSE1L staining, whereas all tumors in the bladder cancer specimens had significant staining for CSE1L (100%, or 38/38). CSE1L cytoplasmic/nuclear staining was defined based on relative staining intensity. A total of 20 (52.6%) of 38 cancer specimens had strong nuclear CSE1L staining, and 44.7.3% (17/38) of the samples had strong cytoplasmic CSE1L staining. Bladder urothelial carcinomas with high CSE1L nuclear staining had a significantly lower overall survival rate (log-rank test, P = .011). CSE1L expression was not correlated with tumor stage, likely reflecting the faultiness of current urothelial carcinoma evaluation methods. Our results suggest that nuclear CSE1L may play an oncogenic role in bladder tumor progression and that immunohistochemical staining of nuclear CSE1L may be useful for the prognosis of bladder urothelial carcinomas.     

Survey of professional education in ethics in clinical psychology intership programs

Attempted to assess the extent to which clinical psychology internship programs offer professional education in ethical standards. While almost 80% of the programs offer such training, less than half of these provide a formal, systematic, and comprehensive learning experience. Many of the programs only provide a limited exposure to ethical standards that occurs on an informal basis as issues emerge in supervision. All but two of the programs that do not offer training in ethical standards reported that this was the primary responsibility of the clinical psychology graduate school program. The immediate implementation of formal training in ethical standards is needed urgently.     

超声心动图辅助诊断系统的研究开发

目的 研究开发超声心动图计算机辅助诊断系统,提高超声心动图工作者的工作效率,使超声心动图诊断结果 更科学、合理和规范.方法 应用Macromedia Flash Professional为开发工具,以权威性专业协会组织最新发布的诊断指南或建议为蓝本,设计出多功能和多用途的辅助诊断软件,并根据临床实践使用中的反馈信息对系统进行完善.结果 系统能够与超声心动图检查同步进行;简便快捷地完成对心脏构型超声测量值的标准化处理和分级判断;能够实现负荷和造影超声心动图、瓣膜病变以及室壁运动等各种定量评级和评分过程;出具规范化的文字报告并能以彩色示意图形式直观地显示评判结果 .系统内置的测量示意图和演示动画有助于超声心动图的临床教学.结论 超声心动图计算机辅助诊断系统能够使诊断结果 更科学、合理和规范;使诊断工作更省时、高效,可以用于临床、科研和教学,具有较高的推广应用价值.     

Analysis of queries sent to PubMed at the point of care: Observation of search behaviour in a medical teaching hospital

Background

A dengue fever outbreak occured in French Guiana in 2006. The objectives were to study the value of a syndromic surveillance system set up within the armed forces, compared to the traditional clinical surveillance system during this outbreak, to highlight issues involved in comparing military and civilian surveillance systems and to discuss the interest of syndromic surveillance for public health response.

Methods

Military syndromic surveillance allows the surveillance of suspected dengue fever cases among the 3,000 armed forces personnel. Within the same population, clinical surveillance uses several definition criteria for dengue fever cases, depending on the epidemiological situation. Civilian laboratory surveillance allows the surveillance of biologically confirmed cases, within the 200,000 inhabitants.

Results

It was shown that syndromic surveillance detected the dengue fever outbreak several weeks before clinical surveillance, allowing quick and effective enhancement of vector control within the armed forces. Syndromic surveillance was also found to have detected the outbreak before civilian laboratory surveillance.

Conclusion

Military syndromic surveillance allowed an early warning for this outbreak to be issued, enabling a quicker public health response by the armed forces. Civilian surveillance system has since introduced syndromic surveillance as part of its surveillance strategy. This should enable quicker public health responses in the future.     

内源性H2S对LPS所致大鼠急性肺损伤时肺动脉高压的影响及其与一氧化氮的相互作用

目的： 探讨硫化氢（H2S）对脂多糖（LPS）所致急性肺损伤时肺动脉高压（PAH）的影响及H2S/胱硫醚-γ-裂解酶（CSE）体系和一氧化氮（NO）/一氧化氮合酶（NOS）体系在其发生机制中的相互作用。 方法： 将72只大鼠随机分为生理盐水（NS）对照组、LPS组、LPS+L-NAME组、LPS+PPG组，检测给药后2、4、6、8 h的平均肺动脉压（mPAP），以及4、8 h血浆H2S、NO含量和iNOS、cNOS活性、肺组织NO含量和iNOS、cNOS、CSE活性，免疫组化法测定肺组织iNOS蛋白表达，并结合肺光镜形态等指标综合评价肺损伤程度。 结果： LPS组各时点的mPAP显著高于对照组，给药后4、8 h，NO含量、iNOS活性和蛋白表达升高，cNOS活性及H2S含量、CSE活性降低，肺组织损伤较重。预先给予L-NAME可减轻LPS所致上述指标的改变。而预先给予PPG可加重LPS所致肺损伤，但对cNOS活性无明显影响。 结论： LPS使内源性H2S减少导致mPAP升高； H2S/CSE体系与NO/NOS体系共同参与LPS所致急性肺损伤时PAH形成的调控机制，在其中呈相互的负性调节作用。     

Genes responsible for nonspecific mental retardation

Mental retardation (MR) is a group of heterogeneous clinical conditions. There are more than 900 genetic disorders associated with MR and it affects around 3% of the general population. MR can be subdivided into syndromic, if it is characterized by consistent and distinctive clinical findings, and nonspecific, if mental retardation is the only primary symptom among affected individuals. Many MR conditions described are syndromic, fragile X syndrome being the most common clinical entity among them. In the past years, knowledge of the molecular basis of mental retardation has increased remarkably. Eight genes involved in nonspecific X-linked MR have been identified so far, including FMR2, OPHN1, GDI1, PAK3, IL1RAPL, TM4SF2, VCX-A, and ARHGEF6. Two other genes also located on the X chromosome have been involved both in syndromic and in MRX forms (RSK2 and XNP/ATR-X). New insights into the pathogenesis of mental retardation are being provided by the discovery of these genes involved in different cellular signaling pathways in the central nervous system although many others remain to be identified.     

An open architecture for medical imaging systems

Integration of medical imaging is the goal of many standards. Interfile and Digital Imaging and Communications in Medicine (DICOM) standards have made great strides in this area. The impact of DICOM is greater owing to its wider acceptance. However, the lack of conformance testing makes interoperability difficult, often requiring expensive consulting teams in a mixed-vendor environment. DICOM is difficult to learn and deploy because it does not use modern software paradigms. Many hardware and software advances in computer architectures and communications could greatly enhance diagnostic imaging if they could be quickly incorporated into medical imaging standards. These problems led to consideration of a solution able to take advantage of state-of-the-art technology and to allow diverse implementations while ensuring the accurate interchange of information between health care providers. It is an object-oriented system information model, with the common object request broker architecture (CORBA) as the vehicle to ensure interoperability between different implementations of the model. This report presents the model.     

X-linked mental retardation: further lumping, splitting and emerging phenotypes

X-linked mental retardation (XLMR) is a very heterogeneous condition, subdivided in two categories mainly based on clinical features: syndromic XLMR (MRXS) and non-syndromic XLMR (MRX). Although it was thought that 20-25% of mental retardation (MR) in males was caused by monogenetic X-linked factors, recent estimations are lower: in the range of 10-12%. The number of identified genes involved in XLMR has been rapidly growing in the past years. Subsequently, an increasing number of patients and families have been reported in which mutations in XLMR genes have been identified. It was observed previously, that mutations in several of XLMR genes can result in syndromic and in non-syndromic phenotypes. This observation has been confirmed for the more recently identified genes. Therefore, in this review, focus has been given on the clinical data and on phenotype-genotype correlations for those genes implicated in both non-syndromic and syndromic XLMR.