Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMPI) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Our studies focused on the role of LMP1 in...Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMPI) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Our studies focused on the role of LMP1 in NPC, and showed that LMP1 triggers the NF-κB, AP-1 and STAT signaling pathways. Strikingly, LMP1 was found to mediate the formation of a new heterodimer between c-Jun and JunB. Also, we have identified JAK/STAT and PI-PLC-PKC activation triggered by LMP1 through upregulating the expression of JAK3 and enhancing the phosphorylation of STATo The constitutive activation of these signaling cascades explains LMP1's ability to induce such a diverse array of morphological and phenotypic effects in cells and provides insight into how LMP1 may induce cell transformation, in which multihit targeted genes in the downstream play an essential role. All signaling cascades triggered by LMP1 ultimately lead to the disruption of the cell cycle: the acceleration of G1/S phase and the arrest of G2/M phase. We also found that LMP1 induced the expression of hTERT and promoted cell immortalization. Importantly, by intervening physical intracellular signal transduction pathways and disturbing the progression of the cell cycle, LMP1, an important oncoprotein encoded by EBV, is thought to be a key modulator in the pathogenesis of NPC. Interfering LMP1 signaling could be a promising strategy to target the malignant phenotype of NPC. Cellular & Molecular Immunology.展开更多
Nasopharyngeal carcinoma(NPC) is closely associated with Epstein-Barr virus(EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains e...Nasopharyngeal carcinoma(NPC) is closely associated with Epstein-Barr virus(EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains enigmatic. In contrast to infection of B lymphocytes, EBV infection does not directly transform nasopharyngeal epithelial cells into proliferative clones with malignant potential. EBV infection of normal pharyngeal epithelial cells is predominantly lytic in nature. Genetic alterations in premalignant nasopharyngeal epithelium, in combination with inflammatory stimulation in the nasopharyngeal mucosa, presumably play essential roles in the establishment of a latent EBV infection in infected nasopharyngeal epithelial cells during the early development of NPC. Establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells and expression of latent viral genes, including the BART transcripts and BART-encoded micro RNAs, are crucial features of NPC. Expression of EBV genes may drive further malignant transformation of premalignant nasopharyngeal epithelial cells into cancer cells. The difficulties involved in the establishment of NPC cell lines and the progressive loss of EBV epsiomes in NPC cells propagated in culture strongly implicate the contribution of host stromal components to the growth of NPC cells in vivo and maintenance of EBV in infected NPC cells. Defining the growth advantages of EBV-infected NPC cells in vivo will lead to a better understanding of the contribution of EBV infection in NPC pathogenesis, and may lead to the identification of novel therapeutic targets for NPC treatment.展开更多
Based on the daily precipitation data taken from 17 stations over South China during the period of 1961 2003, a sudden change in summer extreme precipitation events over South China in the early 1990s along with the p...Based on the daily precipitation data taken from 17 stations over South China during the period of 1961 2003, a sudden change in summer extreme precipitation events over South China in the early 1990s along with the possible mechanism connected with the anomalies of the latent heat flux over the South China Sea and the sensible heat flux over the Indochina peninsula are examined. The results show that both the annual and summer extreme precipitation events have obvious interdecadal variations and have increased significantly since the early 1990s. Moreover, the latent heat flux over the South China Sea and the sensible heat flux over the Indochina peninsula also have obvious interdecadal variations consistent with that of the extreme precipitation, and influence different months' extreme precipitation, respectively. Their effects are achieved by the interdecadal increases of the strengthening convection over South China through the South China Sea Summer Monsoon.展开更多
Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma,...Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma, Hodgkin's lymphoma, post-transplant lymphoproliferative disorders, nasopharyngeal carcinoma and gastric cancer. Evidence shows that phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) plays a key role in EBV-induced malignancies. The main EBV oncoproteins latent membrane proteins(LMP) 1 and LMP2 A can activate the PI3K/Akt pathway, which, in turn, affects cell survival, apoptosis, proliferation and genomic instability via its downstream target proteins to cause cancer. It has also been demonstrated that the activation of the PI3K/Akt pathway can result in drug resistance to chemotherapy. Thus, the inhibition of this pathway can increase the therapeutic efficacy of EBV-associated cancers. For example, PI3 K inhibitor Ly294002 has been shown to increase the effect of 5-fluorouracil in an EBV-associated gastric cancer cell line. At present, dual inhibitors of PI3 K and its downstream target mammalian target of rapamycin have been used in clinical trials and may be included in treatment regimens for EBV-associated cancers.展开更多
Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis...Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-[~ in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.展开更多
Background Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignant diseases including nasopharyngeal carcinoma (NPC), which is a common cancer in Southeastern Asia. Previous studies sh...Background Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignant diseases including nasopharyngeal carcinoma (NPC), which is a common cancer in Southeastern Asia. Previous studies showed that plasma levels of EBV-DNA might be a sensitive and reliable biomarker for the diagnosis, staging and evaluating of therapy for NPC. There are a few analyses of the levels of EBV-latent membrane protein 2 (LMP2)-specific cytotoxic T-lymphocytes (CTLs) in patients with NPC. This study was conducted to investigate the levels of EBV-LMP2-specific CTLs, EBV-DNA load and the level of CD4^+CD25^+T cells in such patients. Methods From February 2006 to April 2006, 62 patients with NPC, 40 healthy virus carriers positive for EBV viral capsid antigen (EBV-IgA-VCA) and 40 controls were enrolled in the study. We used a highly sensitive ELISPOT assay, real-time polymerase chain reaction (PCR) and flow cytometry to measure the EBV-LMP2-specific CTL response, the EBV DNA load and the level of CD4^+CD25^+T cells, respectively. Results The EBV-LMP2-specific CTL responses of the samples from the control, healthy virus carriers and patients with NPC were significantly different from the LMP2 epitopes, with the control and healthy virus carrier samples displaying a stronger response in three cases. There were significant differences in EBV DNA load in serum between NPC and the healthy groups; patients with NPC at stages Ⅲ or Ⅳ had significantly higher viral loads compared with those at stages Ⅰ or Ⅱ. A significantly higher percentage of CD4^+CD25^+ T lymphocytes were detected in the patients, compared with healthy virus carriers and healthy controls. Moreover, patients with advanced stages of NPC (Ⅲ and Ⅳ) had significantly higher percentages than the patients with early stages (Ⅰ and Ⅱ). Conclusions Patients with NPC are frequently unable to establish or maintain sufficient immunosurveillance to control proliferating B cells harboring EBV and to destroy th展开更多
目的探讨orthogonal projection to latent structures(OPLS)方法的原理、特点及其在代谢组学高维数据分析中的应用。方法通过R语言编程实现OPLS方法,利用模拟试验探索OPLS的特性及适用条件,并通过实际数据进行验证。结果利用一个OPLS...目的探讨orthogonal projection to latent structures(OPLS)方法的原理、特点及其在代谢组学高维数据分析中的应用。方法通过R语言编程实现OPLS方法,利用模拟试验探索OPLS的特性及适用条件,并通过实际数据进行验证。结果利用一个OPLS预测主成分的模型拟合效果与利用偏最小二乘(PLS)多个主成分的模型拟合效果相同,同时具有较好的判别能力,其得分图的可视化效果优于PLS。结论 OPLS能够有效去除自变量矩阵X中与因变量Y无关的信息,使模型变得简单、易于解释,同时具有较好的可视化效果,可有效地用于代谢组学数据分析中。展开更多
The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven...The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.展开更多
Due to the slow processing speed of text topic clustering in stand-alone architecture under the background of big data,this paper takes news text as the research object and proposes LDA text topic clustering algorithm...Due to the slow processing speed of text topic clustering in stand-alone architecture under the background of big data,this paper takes news text as the research object and proposes LDA text topic clustering algorithm based on Spark big data platform.Since the TF-IDF(term frequency-inverse document frequency)algorithm under Spark is irreversible to word mapping,the mapped words indexes cannot be traced back to the original words.In this paper,an optimized method is proposed that TF-IDF under Spark to ensure the text words can be restored.Firstly,the text feature is extracted by the TF-IDF algorithm combined CountVectorizer proposed in this paper,and then the features are inputted to the LDA(Latent Dirichlet Allocation)topic model for training.Finally,the text topic clustering is obtained.Experimental results show that for large data samples,the processing speed of LDA topic model clustering has been improved based Spark.At the same time,compared with the LDA topic model based on word frequency input,the model proposed in this paper has a reduction of perplexity.展开更多
There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transfo...There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.展开更多
Student contacts of tuberculosis(TB)cases are susceptible to latent tuberculosis infection(LTBI),and chemo-prophylaxis can reduce the risk of active TB among them.This study aimed to assess the acceptance of chemo...Student contacts of tuberculosis(TB)cases are susceptible to latent tuberculosis infection(LTBI),and chemo-prophylaxis can reduce the risk of active TB among them.This study aimed to assess the acceptance of chemo-prophylaxis for LTBI among students, and their concerns regarding TB and its preventive treatment.展开更多
The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main upda...The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main updates include a replacement of the water-only lake module by the common land model lake module(Co LM-lake) with a more realistic snow–ice–water–soil framework, a parameterization scheme for rice paddies added in the vegetation module, renewed parameterizations of snow cover fraction and snow surface albedo to accommodate the varied snow aging effect during different stages of a snow season, a revised parameterization to calculate the threshold temperature to initiate freeze(thaw) of soil water(ice) rather than being fixed at 0°C in BCC_AVIM1.0, a prognostic phenology scheme for vegetation growth instead of empirically prescribed dates for leaf onset/fall, and a renewed scheme to depict solar radiation transfer through the vegetation canopy. The above updates have been implemented in BCC_AVIM2.0 to serve as the land component of the BCC Climate System Model(BCC_CSM). Preliminary results of BCC_AVIM in the ongoing Land Surface, Snow, and Soil Moisture Model Intercomparison Project(LS3 MIP) of the Coupled Model Intercomparison Project Phase 6(CMIP6) show that the overall performance of BCC_AVIM2.0 is better than that of BCC_AVIM1.0 in the simulation of surface energy budgets at the seasonal timescale. Comparing the simulations of annual global land average before and after the updates in BCC_AVIM2.0 reveals that the bias of net surface radiation is reduced from-12.0 to-11.7 W m-2 and the root mean square error(RMSE) is reduced from 20.6 to 19.0 W m-2;the bias and RMSE of latent heat flux are reduced from 2.3 to-0.1 W m-2 and from 15.4 to14.3 W m-2, respectively;the bias of sensible heat flux is increased from 2.5 to 5.1 W m-2 but the RMSE is reduced from 18.4 to 17.0 W m-2.展开更多
基金grants from State Key Basic Research and Development Plan (973) of the Ministry of Science and Technology of China (2004CB518703) National High Technology Research and Development Program (863) of China (N0.2006AA02Z481)+1 种基金 National Science Fund for Distinguished Young Scholars 0verseas (30428008) Hong Kong Cooperation Fund Project of National Natural Science Foundation of China (30418004).
文摘Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMPI) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC). Our studies focused on the role of LMP1 in NPC, and showed that LMP1 triggers the NF-κB, AP-1 and STAT signaling pathways. Strikingly, LMP1 was found to mediate the formation of a new heterodimer between c-Jun and JunB. Also, we have identified JAK/STAT and PI-PLC-PKC activation triggered by LMP1 through upregulating the expression of JAK3 and enhancing the phosphorylation of STATo The constitutive activation of these signaling cascades explains LMP1's ability to induce such a diverse array of morphological and phenotypic effects in cells and provides insight into how LMP1 may induce cell transformation, in which multihit targeted genes in the downstream play an essential role. All signaling cascades triggered by LMP1 ultimately lead to the disruption of the cell cycle: the acceleration of G1/S phase and the arrest of G2/M phase. We also found that LMP1 induced the expression of hTERT and promoted cell immortalization. Importantly, by intervening physical intracellular signal transduction pathways and disturbing the progression of the cell cycle, LMP1, an important oncoprotein encoded by EBV, is thought to be a key modulator in the pathogenesis of NPC. Interfering LMP1 signaling could be a promising strategy to target the malignant phenotype of NPC. Cellular & Molecular Immunology.
基金the generous funding sources for the above study:the Health and Medical Research Fund (Grant No HMRF: 12110942 and 13120872) to CMTGRF grants from the Hong Kong Research Grant Council (17120814,779713,779312,780911,779810)+1 种基金Ao E NPC (Grant No. Ao E/M-06/08)the Theme-Based Research Scheme (Grant No. T12401/13-R) to SWT
文摘Nasopharyngeal carcinoma(NPC) is closely associated with Epstein-Barr virus(EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains enigmatic. In contrast to infection of B lymphocytes, EBV infection does not directly transform nasopharyngeal epithelial cells into proliferative clones with malignant potential. EBV infection of normal pharyngeal epithelial cells is predominantly lytic in nature. Genetic alterations in premalignant nasopharyngeal epithelium, in combination with inflammatory stimulation in the nasopharyngeal mucosa, presumably play essential roles in the establishment of a latent EBV infection in infected nasopharyngeal epithelial cells during the early development of NPC. Establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells and expression of latent viral genes, including the BART transcripts and BART-encoded micro RNAs, are crucial features of NPC. Expression of EBV genes may drive further malignant transformation of premalignant nasopharyngeal epithelial cells into cancer cells. The difficulties involved in the establishment of NPC cell lines and the progressive loss of EBV epsiomes in NPC cells propagated in culture strongly implicate the contribution of host stromal components to the growth of NPC cells in vivo and maintenance of EBV in infected NPC cells. Defining the growth advantages of EBV-infected NPC cells in vivo will lead to a better understanding of the contribution of EBV infection in NPC pathogenesis, and may lead to the identification of novel therapeutic targets for NPC treatment.
基金supported by the "National Key Developing Program (973 Programs) for Basic Science" Project under Grant No. 2004CB418300:"Theory and Methods of Inspection and Forecast for the Extreme Precipitation in South China""National Natural Science Foundation of China Program" under Grant No. 40675042: "Studies on the Climatic Extreme Temperature and Precipitation Events in China and Their Relations with the Nonuniformity of the Global Warming"The National Centers for Environmental Prediction/National Center for Atmospheric Research kindly provided the sen-sible heat flux and latent heat flux data
文摘Based on the daily precipitation data taken from 17 stations over South China during the period of 1961 2003, a sudden change in summer extreme precipitation events over South China in the early 1990s along with the possible mechanism connected with the anomalies of the latent heat flux over the South China Sea and the sensible heat flux over the Indochina peninsula are examined. The results show that both the annual and summer extreme precipitation events have obvious interdecadal variations and have increased significantly since the early 1990s. Moreover, the latent heat flux over the South China Sea and the sensible heat flux over the Indochina peninsula also have obvious interdecadal variations consistent with that of the extreme precipitation, and influence different months' extreme precipitation, respectively. Their effects are achieved by the interdecadal increases of the strengthening convection over South China through the South China Sea Summer Monsoon.
文摘Viruses have been shown to be responsible for 10%-15% of cancer cases. Epstein-Barr virus(EBV) is the first virus to be associated with human malignancies. EBV can cause many cancers, including Burkett's lymphoma, Hodgkin's lymphoma, post-transplant lymphoproliferative disorders, nasopharyngeal carcinoma and gastric cancer. Evidence shows that phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) plays a key role in EBV-induced malignancies. The main EBV oncoproteins latent membrane proteins(LMP) 1 and LMP2 A can activate the PI3K/Akt pathway, which, in turn, affects cell survival, apoptosis, proliferation and genomic instability via its downstream target proteins to cause cancer. It has also been demonstrated that the activation of the PI3K/Akt pathway can result in drug resistance to chemotherapy. Thus, the inhibition of this pathway can increase the therapeutic efficacy of EBV-associated cancers. For example, PI3 K inhibitor Ly294002 has been shown to increase the effect of 5-fluorouracil in an EBV-associated gastric cancer cell line. At present, dual inhibitors of PI3 K and its downstream target mammalian target of rapamycin have been used in clinical trials and may be included in treatment regimens for EBV-associated cancers.
文摘Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-[~ in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.
基金The study was supported by grants from the Guangxi Science Foundation (No. 0640114) and the "863" program of China (No. 2006AA02A229).
文摘Background Epstein-Barr virus (EBV) is a herpesvirus commonly associated with several malignant diseases including nasopharyngeal carcinoma (NPC), which is a common cancer in Southeastern Asia. Previous studies showed that plasma levels of EBV-DNA might be a sensitive and reliable biomarker for the diagnosis, staging and evaluating of therapy for NPC. There are a few analyses of the levels of EBV-latent membrane protein 2 (LMP2)-specific cytotoxic T-lymphocytes (CTLs) in patients with NPC. This study was conducted to investigate the levels of EBV-LMP2-specific CTLs, EBV-DNA load and the level of CD4^+CD25^+T cells in such patients. Methods From February 2006 to April 2006, 62 patients with NPC, 40 healthy virus carriers positive for EBV viral capsid antigen (EBV-IgA-VCA) and 40 controls were enrolled in the study. We used a highly sensitive ELISPOT assay, real-time polymerase chain reaction (PCR) and flow cytometry to measure the EBV-LMP2-specific CTL response, the EBV DNA load and the level of CD4^+CD25^+T cells, respectively. Results The EBV-LMP2-specific CTL responses of the samples from the control, healthy virus carriers and patients with NPC were significantly different from the LMP2 epitopes, with the control and healthy virus carrier samples displaying a stronger response in three cases. There were significant differences in EBV DNA load in serum between NPC and the healthy groups; patients with NPC at stages Ⅲ or Ⅳ had significantly higher viral loads compared with those at stages Ⅰ or Ⅱ. A significantly higher percentage of CD4^+CD25^+ T lymphocytes were detected in the patients, compared with healthy virus carriers and healthy controls. Moreover, patients with advanced stages of NPC (Ⅲ and Ⅳ) had significantly higher percentages than the patients with early stages (Ⅰ and Ⅱ). Conclusions Patients with NPC are frequently unable to establish or maintain sufficient immunosurveillance to control proliferating B cells harboring EBV and to destroy th
基金supported by Hong Kong Research Grants Council under grants No.16202515 and16212516Guangzhou HKUST Fok Ying Tung Research Institute,China Ministry of Science and Technology TCM Special Research Projects Program under grants No.200807011,No.201007002 and No.201407001-8+2 种基金Beijing Science and Technology Program under grant No.Z111107056811040Beijing New Medical Discipline Development Program under grant No.XK100270569Beijing University of Chinese Medicine under grant No.2011-CXTD-23
文摘The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.
基金This work is supported by the Science Research Projects of Hunan Provincial Education Department(Nos.18A174,18C0262)the National Natural Science Foundation of China(No.61772561)+2 种基金the Key Research&Development Plan of Hunan Province(Nos.2018NK2012,2019SK2022)the Degree&Postgraduate Education Reform Project of Hunan Province(No.209)the Postgraduate Education and Teaching Reform Project of Central South Forestry University(No.2019JG013).
文摘Due to the slow processing speed of text topic clustering in stand-alone architecture under the background of big data,this paper takes news text as the research object and proposes LDA text topic clustering algorithm based on Spark big data platform.Since the TF-IDF(term frequency-inverse document frequency)algorithm under Spark is irreversible to word mapping,the mapped words indexes cannot be traced back to the original words.In this paper,an optimized method is proposed that TF-IDF under Spark to ensure the text words can be restored.Firstly,the text feature is extracted by the TF-IDF algorithm combined CountVectorizer proposed in this paper,and then the features are inputted to the LDA(Latent Dirichlet Allocation)topic model for training.Finally,the text topic clustering is obtained.Experimental results show that for large data samples,the processing speed of LDA topic model clustering has been improved based Spark.At the same time,compared with the LDA topic model based on word frequency input,the model proposed in this paper has a reduction of perplexity.
基金supported by 2016JQ0054 and NSFC grants 81470711 to L.Z.National Key Research and Development Program of China 2016YFC1102700 to X.Z.
文摘There is currently no effective medical treatment for temporomandibular joint osteoarthritis(TMJ-OA) due to a limited understanding of its pathogenesis. This study was undertaken to investigate the key role of transforming growth factor-β(TGF-β)signalling in the cartilage and subchondral bone of the TMJ using a temporomandibular joint disorder(TMD) rat model, an ageing mouse model and a Camurati–Engelmann disease(CED) mouse model. In the three animal models, the subchondral bone phenotypes in the mandibular condyles were evaluated by μCT, and changes in TMJ condyles were examined by TRAP staining and immunohistochemical analysis of Osterix and p-Smad2/3. Condyle degradation was confirmed by Safranin O staining, the Mankin and OARSI scoring systems and type X collagen(Col X), p-Smad2/3 a and Osterix immunohistochemical analyses. We found apparent histological phenotypes of TMJ-OA in the TMD, ageing and CED animal models, with abnormal activation of TGF-βsignalling in the condylar cartilage and subchondral bone. Moreover, inhibition of TGF-β receptor I attenuated TMJ-OA progression in the TMD models. Therefore, aberrant activation of TGF-β signalling could be a key player in TMJ-OA development.
基金supported by the National Key Science&Technology project against major infectious diseases[No.2017ZX10105012]the Fourth Round of Three-Year Public Health Action Plan of Shanghai,China[No.15GWZK0101]
文摘Student contacts of tuberculosis(TB)cases are susceptible to latent tuberculosis infection(LTBI),and chemo-prophylaxis can reduce the risk of active TB among them.This study aimed to assess the acceptance of chemo-prophylaxis for LTBI among students, and their concerns regarding TB and its preventive treatment.
基金Supported by the National Key Research and Development Program of China(2017YFA0604300,2016YFA0602100,and2016YFA0602602)National Natural Science Foundation of China(41275075 and 91437219)
文摘The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main updates include a replacement of the water-only lake module by the common land model lake module(Co LM-lake) with a more realistic snow–ice–water–soil framework, a parameterization scheme for rice paddies added in the vegetation module, renewed parameterizations of snow cover fraction and snow surface albedo to accommodate the varied snow aging effect during different stages of a snow season, a revised parameterization to calculate the threshold temperature to initiate freeze(thaw) of soil water(ice) rather than being fixed at 0°C in BCC_AVIM1.0, a prognostic phenology scheme for vegetation growth instead of empirically prescribed dates for leaf onset/fall, and a renewed scheme to depict solar radiation transfer through the vegetation canopy. The above updates have been implemented in BCC_AVIM2.0 to serve as the land component of the BCC Climate System Model(BCC_CSM). Preliminary results of BCC_AVIM in the ongoing Land Surface, Snow, and Soil Moisture Model Intercomparison Project(LS3 MIP) of the Coupled Model Intercomparison Project Phase 6(CMIP6) show that the overall performance of BCC_AVIM2.0 is better than that of BCC_AVIM1.0 in the simulation of surface energy budgets at the seasonal timescale. Comparing the simulations of annual global land average before and after the updates in BCC_AVIM2.0 reveals that the bias of net surface radiation is reduced from-12.0 to-11.7 W m-2 and the root mean square error(RMSE) is reduced from 20.6 to 19.0 W m-2;the bias and RMSE of latent heat flux are reduced from 2.3 to-0.1 W m-2 and from 15.4 to14.3 W m-2, respectively;the bias of sensible heat flux is increased from 2.5 to 5.1 W m-2 but the RMSE is reduced from 18.4 to 17.0 W m-2.