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Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional

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《医学前沿（英文）》 2014年 第8卷 第3期   页码 337-346 doi: 10.1007/s11684-014-0349-8

摘要：

Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills.

关键词： personalized medicine     complex network     clinical phenotype network     traditional Chinese medicine    

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IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to

《医学前沿（英文）》 2022年 第16卷 第3期   页码 403-415 doi: 10.1007/s11684-021-0858-1

摘要： The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P <0.05) and IRF4 (P<0.001) and between white blood cell (WBC) count and IRF4 expression (P <0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P <0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%, 10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

关键词： myeloproliferative neoplasms     IRF4     IRF8     hydroxyurea     essential thrombocythemia    

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A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

《医学前沿（英文）》 2023年 第17卷 第2期   页码 330-338 doi: 10.1007/s11684-022-0933-2

摘要： Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’ hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

关键词： Clouston syndrome     whole exome sequencing     GJB6 gene     novel variant     unique phenotype    

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Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype

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《医学前沿（英文）》 2013年 第7卷 第4期   页码 425-432 doi: 10.1007/s11684-013-0295-x

摘要：

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow limitation. Given that multiple systems other than the lung can be impaired in COPD patients, the traditional FEV1/FVC ratio shows many limitations in COPD diagnosis and assessment. Certain heterogeneities are found in terms of clinical manifestations, physiology, imaging findings, and inflammatory reactions in COPD patients; thus, phenotyping can provide effective information for the prognosis and treatment. However, phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD, and the role of phenotypes in COPD prevention and early diagnosis remains unclear. This shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain genes. This review briefly describes the heterogeneity of COPD, with focus on recent advances in the correlations between genotypes and phenotypes. The potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated.

关键词： chronic obstructive pulmonary disease     heterogeneity     phenotype     genotype     prediction    

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Effects of iron oxide nanoparticles on phenotype and metabolite changes in hemp clones ( L.)

《环境科学与工程前沿（英文）》 2022年 第16卷 第10期 doi: 10.1007/s11783-022-1569-9

摘要：

● Fe3O4 NPs increased the biomass and chlorophyll content of hemp clones.

关键词： Fe3O4 nanoparticle     Hemp     Growth enhancement     THC     Metabolite    

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Multistage analysis method for detection of effective herb prescription from clinical data

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《医学前沿（英文）》 2018年 第12卷 第2期   页码 206-217 doi: 10.1007/s11684-017-0525-8

摘要：

Determining effective traditional Chinese medicine (TCM) treatments for specific disease conditions or particular patient groups is a difficult issue that necessitates investigation because of the complicated personalized manifestations in real-world patients and the individualized combination therapies prescribed in clinical settings. In this study, a multistage analysis method that integrates propensity case matching, complex network analysis, and herb set enrichment analysis was proposed to identify effective herb prescriptions for particular diseases (e.g., insomnia). First, propensity case matching was applied to match clinical cases. Then, core network extraction and herb set enrichment were combined to detect core effective herb prescriptions. Effectiveness-based mutual information was used to detect strong herb–symptom relationships. This method was applied on a TCM clinical data set with 955 patients collected from well-designed observational studies. Results revealed that groups of herb prescriptions with higher effectiveness rates (76.9% vs. 42.8% for matched samples; 94.2% vs. 84.9% for all samples) compared with the original prescriptions were found. Particular patient groups with symptom manifestations were also identified to help investigate the indications of the effective herb prescriptions.

关键词： effective prescription detection     herb set enrichment analysis     core network extraction     insomnia     personalized treatment    

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麻醉与意识的脑网络研究进展——框架与临床应用 Review

刘军, 董康立, 孙毅, Ioannis Kakkos, 黄帆, 王国正, 齐鹏, 陈星, 张德林, Anastasios Bezerianos, 孙煜

《工程（英文）》 2023年 第20卷 第1期   页码 77-95 doi: 10.1016/j.eng.2021.11.013

摘要：

尽管麻醉与意识之间的关系一直是研究者关注的重点，但目前学界对于麻醉与意识的神经机制理解仍处在初级阶段，极大地限制了麻醉监测和意识评估系统的进一步发展。此外，现有麻醉监测方法难以提供足够的有效信息，对精准麻醉监测的目标构成了障碍。近年来，使用脑网络分析揭示麻醉机制已成为研究热点，其目的是为临床应用提供新的研究思路。针对这一新的研究趋势，本文全面回顾了麻醉相关脑网络研究的最新进展，系统地比较了麻醉和意识的几种潜在的神经机制以及不同层面大脑神经活动的测量方法；从皮层碎片化理论出发，介绍了连通性和网络分析的一些重要的研究方法和相关成果；在总结归纳现有研究成果的基础上，论证了全脑多模态网络数据可以提供现有麻醉监测方法所无法提供的信息；更重要的是，进一步探讨简化脑网络分析方法的可行性，这一方法将会在优化现有的临床麻醉监测系统中发挥重要作用。

关键词： 麻醉     脑网络     连通性     图论分析     临床监测系统    

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Changes of phenotype and function of human CD4 CD25 T cells induced by transfection of Foxp3

WU Kui, BI Yutian, WANG Yaoli, WANG Changzheng

《医学前沿（英文）》 2008年 第2卷 第4期   页码 366-369 doi: 10.1007/s11684-008-0070-6

摘要： The aim of this paper is to explore the effects of transfection of Foxp3 gene on the phenotype and function of naive CD4 T cells. The pMSCV-Foxp3 retroviral vector encoding Foxp3 gene was transduced into the PT67 packaging cell line. Virus-containing supernatant was applied to differentiate CD4CD25 T cells. The resulting cells were sorted with flow cytometry. The expressions of CD25, CD127, CTLA-4 and the proliferation of transfected T cells were examined. The effect of transfected CD4 T cells on the proliferation and cytokine production of CD4CD25 T cells was examined. Foxp3-gene transfected CD4 T cells could express Foxp3 and transfection of Foxp3 gene up-regulated the expressions of CD25 and CTLA-4, but down-regulated CD127 expression. After transfection, the proliferation of CD4 T cells was eliminated. Transfected T cells inhibited the proliferation of CD4CD25 T cells. CD4CD25 T cells acquired a regulatory phenotype and function after it was transduced with the Foxp3 gene. This suggested a key role of Foxp3 in the generation of CD4CD25 regulatory T cells.
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Natural killer cells in liver diseases

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《医学前沿（英文）》 2018年 第12卷 第3期   页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell     phenotype     immune activation     immune tolerance     liver diseases    

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Genetics analysis of haptoglobin gene in Fujian Han nationality

ZOU Qilian, LIN Ying, LIN Xiangquan, CHEN Yuanzhong

《医学前沿（英文）》 2008年 第2卷 第1期   页码 105-107 doi: 10.1007/s11684-008-0019-9

摘要： To study the genetic features (characteristics) of haptoglobin gene, four different age groups of Fujian Han people were investigated. The phenotypes of the haptoglobin of four different groups were analyzed by using polyacrylamide gel electrophoresis. The frequency of in the population of Fujian Han nationality accounted for 0.340, among which children, youths, middle aged and elder groups were 0.307, 0.338, 0.363 and 0.383, respectively. The Hp phenotype frequency was 0.026 in which the four age groups accounted for 0.032, 0.046, 0.014 and 0.014, respectively. The frequency of gene is rising with increasing age. The frequency of Hp phenotype is highest in the middle aged group and then tends to drop with increasing age.

关键词： different     haptoglobin     phenotype frequency     electrophoresis     middle    

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Ontological reconstruction of the clinical terminology of traditional Chinese medicine

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《医学前沿（英文）》 2014年 第8卷 第3期   页码 358-361 doi: 10.1007/s11684-014-0348-9

摘要：

This study proposes the ontological reconstruction of the current clinical terminology of traditional Chinese medicine (TCM). It also provides an overview of preliminary work related to the said reconstruction, including the ontology-based analysis of TCM clinical terminology. We conclude that the ontological reconstruction of TCM clinical terminology provides a proper translation from the idealized organizational model to real-world implementation and to a formalized, shared, and knowledge-based framework.

关键词： ontology     traditional Chinese medicine     clinical terminology    

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The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

《医学前沿（英文）》 2023年 第17卷 第3期   页码 527-533 doi: 10.1007/s11684-022-0967-5

摘要： In this study, we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation (TR), taking into account its dynamic nature, after biatrial orthotopic heart transplant (OHT). All consecutive adult patients undergoing biatrial OHT (1984−2017) with an available follow-up echocardiogram were included. Mixed-models were used to model the evolution of TR. The mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with mortality. In total, 572 patients were included (median age: 50 years, males: 74.9%). Approximately 32% of patients had moderate-to-severe TR immediately after surgery. However, this declined to 11% on 5 years and 9% on 10 years after surgery, adjusted for survival bias. Pre-implant mechanical support was associated with less TR during follow-up, whereas concurrent LV dysfunction was significantly associated with more TR during follow-up. Survival at 1, 5, 10, 20 years was 97% ± 1%, 88% ± 1%, 66% ± 2% and 23% ± 2%, respectively. The presence of moderate-to-severe TR during follow-up was associated with higher mortality (HR: 1.07, 95% CI (1.02–1.12), p = 0.006). The course of TR was positively correlated with the course of creatinine (R = 0.45). TR during follow-up is significantly associated with higher mortality and worse renal function. Nevertheless, probability of TR is the highest immediately after OHT and decreases thereafter. Therefore, it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.

关键词： orthotopic heart transplant     tricuspid regurgitation     clinical impact     biatrial heart transplantation    

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Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 340-348 doi: 10.1007/s11684-017-0570-3

摘要：

In light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 (C3) nonspecifically deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria (<3.5 g/d) is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin–angiotensin–aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

关键词： obesity-related glomerulopathy     pathogenesis     pathologic     clinical characteristics    

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Coronavirus disease 2019 (COVID-19): a clinical update

Min Zhou, Xinxin Zhang, Jieming Qu

《医学前沿（英文）》 2020年 第14卷 第2期   页码 126-135 doi: 10.1007/s11684-020-0767-8

摘要： Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

关键词： coronavirus disease 2019     epidemiology     pathology     radiology     clinical characteristics     treatment    

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标题 作者 时间 类型 操作

Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional

null

期刊论文

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to

期刊论文

A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

期刊论文

Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype

null

期刊论文

Effects of iron oxide nanoparticles on phenotype and metabolite changes in hemp clones ( L.)

期刊论文

Multistage analysis method for detection of effective herb prescription from clinical data

null

期刊论文

麻醉与意识的脑网络研究进展——框架与临床应用

刘军, 董康立, 孙毅, Ioannis Kakkos, 黄帆, 王国正, 齐鹏, 陈星, 张德林, Anastasios Bezerianos, 孙煜

期刊论文

Changes of phenotype and function of human CD4 CD25 T cells induced by transfection of Foxp3

WU Kui, BI Yutian, WANG Yaoli, WANG Changzheng

期刊论文

Natural killer cells in liver diseases

null

期刊论文

高敬书：基于就医人群的中国多囊卵巢综合征女性的临床表型和治疗结局（2021年7月23日）

2021年10月23日

会议视频

Genetics analysis of haptoglobin gene in Fujian Han nationality

ZOU Qilian, LIN Ying, LIN Xiangquan, CHEN Yuanzhong

期刊论文

Ontological reconstruction of the clinical terminology of traditional Chinese medicine

null

期刊论文

The clinical impact of tricuspid regurgitation in patients with a biatrial orthotopic heart transplant

期刊论文

Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

null

期刊论文

Coronavirus disease 2019 (COVID-19): a clinical update

Min Zhou, Xinxin Zhang, Jieming Qu

期刊论文