Advances in high-throughput sequencing(HTS)have fostered rapid developments in the field of microbiome research,and massive microbiome datasets are now being generated.However,the diversity of software tools and the c...Advances in high-throughput sequencing(HTS)have fostered rapid developments in the field of microbiome research,and massive microbiome datasets are now being generated.However,the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field.Here,we systematically summarize the advantages and limitations of microbiome methods.Then,we recommend specific pipelines for amplicon and metagenomic analyses,and describe commonly-used software and databases,to help researchers select the appropriate tools.Furthermore,we introduce statistical and visualization methods suitable for microbiome analysis,including alpha-and betadiversity,taxonomic composition,difference comparisons,correlation,networks,machine learning,evolution,source tracing,and common visualization styles to help researchers make informed choices.Finally,a stepby-step reproducible analysis guide is introduced.We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.展开更多
Background Systemic lupus erythematosis(SLE)is a complex and clinically heterogeneous autoimmune disease.A variety of immunological defects contribute to SLE,including dysregulated innate and adaptive immune response....Background Systemic lupus erythematosis(SLE)is a complex and clinically heterogeneous autoimmune disease.A variety of immunological defects contribute to SLE,including dysregulated innate and adaptive immune response.A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment.The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.Data sources Literature reviews and original research articles were collected from database,including PubMed and Wanfang.Relevant articles about SLE were included.Results Breakdown of self-tolerance is the main pathogenesis of SLE.The innate and adaptive immune networks are interlinked with each other through cytokines,complements,immune complexes and kinases of the intracellular machinery.Treatments targeted at possible targets of immunity have been assessed in clinical trials.Most of them did not show better safety and efficacy than traditional treatments.However,novel targeting treatments are still being explored.Conclusions Dysregulated immune response plays a critical role in SLE,including innate immunity and adaptive immunity.Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.展开更多
Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasin...Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasing in the developing countries that are undergoing economic growth.Several environmental risk factors,mainly changes in diet and life style,have been suggested to underlie the rise of CRC in these populations.Diet and lifestyle impinge on nuclear receptors,on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis.In this respect,the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations.The data from these studies may have important implications for the global prevention and treatment of CRC.展开更多
For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Thl/Th2 paradigm implied the existence of two different, mutu-...For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Thl/Th2 paradigm implied the existence of two different, mutu- ally regulated, CD4＋ T helper subsets： Thl cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particu- larly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4＋ T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Thl or Th2 cells. The Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Thl, Th2 and Th17 effector cells but there is also a di- chotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-β or TGF-β plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.展开更多
Microbial cells significantly outnumber human cells in the body,and the microbial flora at mucosal sites are shaped by environmental factors and,less intuitively,act on host immune responses,as demonstrated by experim...Microbial cells significantly outnumber human cells in the body,and the microbial flora at mucosal sites are shaped by environmental factors and,less intuitively,act on host immune responses,as demonstrated by experimental data in germ-free and gnotobiotic studies.Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown,as observed in rheumatic fever triggered by Streptococci via molecular mimicry,epitope spread and bystander effects.The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases,including rheumatoid arthritis,type 1 diabetes,multiple sclerosis and autoimmune liver disease.It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena.In fact,there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity,and microbial therapeutics is being investigated to prevent or halt autoimmune diseases.As a putative mechanism,it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens,giving rise to the differentiation of autoreactive Th17 cells and other T helper cells.This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity,with an emphasis on how dysbiosis may influence systemic autoimmunity.In particular,a gut–liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm,considering its anatomic and physiological connections.展开更多
Air pollution is a world public health problem. Particulate matter (PM), a mix of solid and liquid particles in the air, becomes an increasing concern in the social and economic development of China. For decades, epid...Air pollution is a world public health problem. Particulate matter (PM), a mix of solid and liquid particles in the air, becomes an increasing concern in the social and economic development of China. For decades, epidemiological studies have confirmed the association between fine particle pollutants and respiratory diseases. It has been reported in different populations that increased fine particulate matter (PM2.5) concentrations cause elevated susceptibility to respiratory diseases, including acute respiratory distress, asthma, chronic obstructive pulmonary disease, and lung cancer. This review will discuss the pathophysiology of PM2.5 in res-piratory diseases, which are helpful for the prevention of air pollution and treatment of respiratory tract inflammatory diseases.展开更多
Background A20,a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene(TNFAIP3),plays a vital role in the negative regulation of inflammation and immunity.Loss-of-function mutation in TNFAIP3 leads...Background A20,a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene(TNFAIP3),plays a vital role in the negative regulation of inflammation and immunity.Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20(HA20).Since HA20 was first described in 2016,a number of new cases have been described in this literature,however,the disease and its pathogenesis are poorly understood.This review seeks to improve clinical recognition of this disorder,and promote both earlier diagnosis and initiation of targeted therapies to improve patients’outcomes.Methods We reviewed 26 papers about A20 and HA20,and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20.Additionally,we discussed the pathogenesis and treatment of HA20.Results A total of 24 pathogenic variants of A20 had been reported.There was significant clinical heterogeneity,even among those with the same variants in TNFA1P3.Prior to receiving a molecular diagnosis of HA20,patients had been diagnosed with Behcet's disease,rheumatoid arthritis,rheumatic fever,juvenile idiopathic arthritis,systemic lupus erythematosus,and even adult-onset Stills'disease.The patients with HA20 that presented with inflammatory signatures in NF-kB signaling were mostly responsive to treatment.Conclusions HA20 is a monogenic autoinflammatory disease with highly variable clinical manifestations.This extensive heterogeneity makes it difficult to set a clinical diagnostic criteria,and genetic sequencing is necessary for a definitive diagnosis of HA20.展开更多
The Coronavirus Disease 2019(COVID-19)pandemic has become a global crisis and is more devastating than any other previous infectious disease.It has affected a significant proportion of the global population both physi...The Coronavirus Disease 2019(COVID-19)pandemic has become a global crisis and is more devastating than any other previous infectious disease.It has affected a significant proportion of the global population both physically and mentally,and destroyed businesses and societies.Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis,including lymphopenia,neutrophilia,dysregulation of monocytes and macrophages,reduced or delayed type I interferon(IFN-I)response,antibody-dependent enhancement,and especially,cytokine storm(CS).The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis.These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells,resulting in complicated medical symptoms including fever,capillary leak syndrome,disseminated intravascular coagulation,acute respiratory distress syndrome,and multiorgan failure,ultimately leading to death in the most severe cases.Therefore,it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19.Herein,we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved.We also discuss the induction,function,downstream signaling,and existing and potential interventions for targeting these cytokines or related signal pathways.We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.展开更多
Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemo...Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January 2014.The patients were divided into HCT and chemotherapy(CT)groups.The HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Al展开更多
Background Allergen micro-arrays are powerful tools for screening of serum IgE-reactivity. In this study allergen micro-arrays were used to identify dominating IgE-binding allergens and cross-reactivity patterns among...Background Allergen micro-arrays are powerful tools for screening of serum IgE-reactivity. In this study allergen micro-arrays were used to identify dominating IgE-binding allergens and cross-reactivity patterns among selected Chinese allergy patients. Methods The study was conducted using patient sera from the cities of Guangzhou, Nanjing, Chengdu and Shenyang. In total 100 sera with Dermatophagoides pteronyssinus （Der p） specific IgE-levels higher than 50 kU/L were selected for testing against 103 individual allergens. Results Among 100 selected patients, 95% showed IgE-reactivity towards house-dust mite allergens Dermatophagoides farinae （Der f） 1, Der f 2 and Der p 2 and 94% were IgE positive against Der p 1, and 60% of sera contained IgE reacting against allergen Euroglyphus maynei （Eur m） 2. IgE against cat allergen, Felisdomesticus （Fel d） 1, was seen in 20%. Only 2% showed specific IgE-reactivity to Der p 10, a panallergen belonging to the tropomyosin family. Serum IgE-reactivity towards other allergens was in general low. IgE-reactivity against pollen allergens showed geographic differences. Conclusions This study clearly confirms that group 1 and group 2 are major allergens of house dust mites. These selected house-dust mite allergy patients are close to being mono-sensitized. Der p 10 is not an important allergen for cross-reactivity. Specific IgE-sensitization towards pollen allergens is low in southern China compared to other regions. The prevalence of food and stinging insect allergens known to give rise to IgE-mediated cross-reactivity is 2% or less.展开更多
A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now consid...A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.展开更多
Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A ...Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an importa展开更多
Background： Drug reaction with eosinophilia and systemic symptoms （DRESS） is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubat...Background： Drug reaction with eosinophilia and systemic symptoms （DRESS） is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice. Methods： Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 （IBM, Armonk, NY, USA）, and a value ofP 〈 0.05 was considered statistically significant. Results： Among 104 patients, 38 were male and 66 female （aged 18-83 years）. The latent period was 13 （interquartile range [IQR]： 10-17） days. The most common allergy-inducing drugs were antibiotics （n = 37, 35.6%）, followed by antiepileptic drugs and traditional Chinese medicines （TCMs）. Eighty-two cases （78.8%） had rash with area 〉50% body surface area （BSA）. Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin （IVIG） group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature 〉38.5℃ were not significantly different between the two groups. However, the number of patients meeting the criteria of＂definite＂ and ＂probable＂ （X2 =5.852, P = 0.016）, with an eosinophilic granulocyte count of〉1.5 x10^9/L 0,2 7.129, P = 0.008）, and with rash area of〉50% BSA （X2 = 4.750, P = 0.029）, was significantly different. Conclusions： Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation perio展开更多
AIM:To investigate if echocardiographic and hemodynamic determinations obtained at the time of transjugular intrahepatic portosystemic shunt(TIPS)can provide prognostic information that will enhance risk stratificatio...AIM:To investigate if echocardiographic and hemodynamic determinations obtained at the time of transjugular intrahepatic portosystemic shunt(TIPS)can provide prognostic information that will enhance risk stratification of patients.METHODS:We reviewed medical records of 467 patients who underwent TIPS between July 2003 and December 2011 at our institution.We recorded information regarding patient demographics,underlying liver disease,indication for TIPS,baseline laboratory values,hemodynamic determinations at the time of TIPS,and echocardiographic measurements both before and after TIPS.We recorded patient comorbidities that may affect hemodynamic and echocardiographic determinations.We also calculated Model for Endstage Liver Disease(MELD)score and Child Turcotte Pugh(CTP)class.The following pre-and post-TIPS echocardiographic determinations were recorded:Left ventricular ejection fraction,right ventricular(RV)systolic pressure,subjective RV dilation,and subjective RV function.We recorded the following hemodynamic measurements:Right atrial(RA)pressure before and after TIPS,inferior vena cava pressure before and after TIPS,free hepatic vein pressure,portal vein pressure before and after TIPS,and hepatic venous pressure gradient(HVPG).RESULTS:We reviewed 418 patients with portal hypertension undergoing TIPS.RA pressure increased by a mean ± SD of 4.8 ± 3.9 mmH g(P < 0.001),HVPG decreased by 6.8 ± 3.5 mmH g(P < 0.001).In multivariate linear regression analysis,a higher MELD score,lower platelet count,splenectomy and a higher portal vein pressure were independent predictors of higher RA pressure(R = 0.55).Three variables predicted 3-mo mortality after TIPS in a multivariate analysis:Age,MELD score,and CTP grade C.Change in the RA pressure after TIPS predicted long-term mortality(per 1 mm Hg change,HR = 1.03,95%CI:1.01-1.06,P < 0.012).CONCLUSION:RA pressure increased immediately after TIPS particularly in patients with worse liver function,portal hypertension,emergent TIPS placement and history of splenectomy.The i展开更多
Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wn...Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1(CTNNB1)-dependent(also known as "canonical") and CTNNB1-independent(often referred to as "non-canonical") pathways. Specifically,the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes(the cell-surface receptor complex,the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported,two main non-canonical pathways,Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway,participate in the regulation of hepatocarcinogenesis. Interestingly,the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover,other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore,crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.展开更多
Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T cell...Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T cells.The etiology remains to be determined,yet data suggest that both a susceptible genetic background and unknown environmental factors determine disease onset.Multiple infectious and chemical candidates have been proposed to trigger the disease in a genetically susceptible host,mostly by molecular mimicry.Most recently,several murine models have been reported,including genetically determined models as well as models induced by immunization with xenobiotics and bacteria.展开更多
Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(...Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.展开更多
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor mi...Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments.Toll-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells.However,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these cells.In this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor microenvironment.In particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer therapy.An improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.展开更多
Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a ...Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.展开更多
Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalo...Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalovirus （CMV） is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients.This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.Methods： Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated.GraphPad Prism version 5.013 （San Diego, CA, USA） was used to conduct statistical analysis.The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test.Significance between qualitative data was analyzed using Pearson＆#39;s Chi-squared test.The cut-offthresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic （ROC） curve analysis.Results： One hundred and forty-two patients had positive CMV viral load tests.Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic.The symptomatic group received higher doses ofprednisolone （PSL） and more frequently immunosuppressants than the asymptomatic group （P 〈 0.01）.The symptomatic group had lower lymphocyte counts, especially CD4＋ T-cells, than the asymptomatic group （P 〈 0.01）.By ROC curve analysis, when CD4＋ T-cell count was 〈0.39 ＆#215; 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection.The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients （P 〈 0.01;t展开更多
基金This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(Precision Seed Design and Breeding,XDA24020104)the Key Research Program of Frontier Sciences of the Chinese Academy of Science(grant nos.QYZDB-SSW-SMC021)the National Natural Science Foundation of China(grant nos.31772400).
文摘Advances in high-throughput sequencing(HTS)have fostered rapid developments in the field of microbiome research,and massive microbiome datasets are now being generated.However,the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field.Here,we systematically summarize the advantages and limitations of microbiome methods.Then,we recommend specific pipelines for amplicon and metagenomic analyses,and describe commonly-used software and databases,to help researchers select the appropriate tools.Furthermore,we introduce statistical and visualization methods suitable for microbiome analysis,including alpha-and betadiversity,taxonomic composition,difference comparisons,correlation,networks,machine learning,evolution,source tracing,and common visualization styles to help researchers make informed choices.Finally,a stepby-step reproducible analysis guide is introduced.We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.
文摘Background Systemic lupus erythematosis(SLE)is a complex and clinically heterogeneous autoimmune disease.A variety of immunological defects contribute to SLE,including dysregulated innate and adaptive immune response.A clearer understanding of the mechanisms driving disease pathogenesis combined with recent advances in medical science is predicted to enable accelerated progress towards improved SLE-personalized approaches to treatment.The aim of this review was to clarify the immunological pathogenesis and treatment of SLE.Data sources Literature reviews and original research articles were collected from database,including PubMed and Wanfang.Relevant articles about SLE were included.Results Breakdown of self-tolerance is the main pathogenesis of SLE.The innate and adaptive immune networks are interlinked with each other through cytokines,complements,immune complexes and kinases of the intracellular machinery.Treatments targeted at possible targets of immunity have been assessed in clinical trials.Most of them did not show better safety and efficacy than traditional treatments.However,novel targeting treatments are still being explored.Conclusions Dysregulated immune response plays a critical role in SLE,including innate immunity and adaptive immunity.Biologic agents that aim to specifically target abnormal immune processes were assessing and may bring new hope to SLE patients.
基金Supported by Institutional NRSA,clinical oncology research training program,No.T32 CA079447(Bishehsari F)the Associazione Italiana per la Ricerca sul Cancro(AIRC),Milan to Mariani-Costantini R+3 种基金the Office for Internationalization,G.d’Annunzio University,Chietithe Carichieti Foundation,ChietiMinistero dell’Istruzione,dell’Universitàe della Ricerca(MIUR),Rome,Italythe Fondazione Umberto Veronesi,Milan,Italy and the MRC(5PT57)to Vacca M
文摘Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasing in the developing countries that are undergoing economic growth.Several environmental risk factors,mainly changes in diet and life style,have been suggested to underlie the rise of CRC in these populations.Diet and lifestyle impinge on nuclear receptors,on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis.In this respect,the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations.The data from these studies may have important implications for the global prevention and treatment of CRC.
文摘For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. The Thl/Th2 paradigm implied the existence of two different, mutu- ally regulated, CD4＋ T helper subsets： Thl cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particu- larly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4＋ T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Thl or Th2 cells. The Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Thl, Th2 and Th17 effector cells but there is also a di- chotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-β or TGF-β plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.
基金This work was supported by awards from the National Nature Science Foundation of China(#81771732 and 81620108002 to Xiong Ma,#81400608 to Ruqi Tang).
文摘Microbial cells significantly outnumber human cells in the body,and the microbial flora at mucosal sites are shaped by environmental factors and,less intuitively,act on host immune responses,as demonstrated by experimental data in germ-free and gnotobiotic studies.Our understanding of this link stems from the established connection between infectious bacteria and immune tolerance breakdown,as observed in rheumatic fever triggered by Streptococci via molecular mimicry,epitope spread and bystander effects.The availability of high-throughput techniques has significantly advanced our capacity to sequence the microbiome and demonstrated variable degrees of dysbiosis in numerous autoimmune diseases,including rheumatoid arthritis,type 1 diabetes,multiple sclerosis and autoimmune liver disease.It remains unknown whether the observed differences are related to the disease pathogenesis or follow the therapeutic and inflammatory changes and are thus mere epiphenomena.In fact,there are only limited data on the molecular mechanisms linking the microbiota to autoimmunity,and microbial therapeutics is being investigated to prevent or halt autoimmune diseases.As a putative mechanism,it is of particular interest that the apoptosis of intestinal epithelial cells in response to microbial stimuli enables the presentation of self-antigens,giving rise to the differentiation of autoreactive Th17 cells and other T helper cells.This comprehensive review will illustrate the data demonstrating the crosstalk between intestinal microbiome and host innate and adaptive immunity,with an emphasis on how dysbiosis may influence systemic autoimmunity.In particular,a gut–liver axis involving the intestinal microbiome and hepatic autoimmunity is elucidated as a paradigm,considering its anatomic and physiological connections.
基金grants from the National Key Research and Development Program of China(2018YFC1313600)Major International(Regional)Joint Research Project(81820108001)+4 种基金National Natural Science Foundation of China(81670029,81370133 and 81170018)Jiangsu Key Principal Investigator of Medi-cine ZDRCA2016018,Project 333 for Cultivation of High-Level Talents 2016 and 2011,Jiangsu Key Program of Social Development BE2015651,Preventive Medical Research Project of Jiangsu Health and Family Planning Committee Y2015026,Jiangsu Science and TechnoNational Institute of Environmental Health Sciences ES006096,Center for Environmental GeneticsNational Institute of Allergy and Infectious Diseases AI115358NIH P01HL107151.
文摘Air pollution is a world public health problem. Particulate matter (PM), a mix of solid and liquid particles in the air, becomes an increasing concern in the social and economic development of China. For decades, epidemiological studies have confirmed the association between fine particle pollutants and respiratory diseases. It has been reported in different populations that increased fine particulate matter (PM2.5) concentrations cause elevated susceptibility to respiratory diseases, including acute respiratory distress, asthma, chronic obstructive pulmonary disease, and lung cancer. This review will discuss the pathophysiology of PM2.5 in res-piratory diseases, which are helpful for the prevention of air pollution and treatment of respiratory tract inflammatory diseases.
基金This study was supported by Basic Public Welfare Research Project of Zhejiang Province(LGF19H100002).
文摘Background A20,a protein encoded by the tumor necrosis factor alpha-induced protein 3 gene(TNFAIP3),plays a vital role in the negative regulation of inflammation and immunity.Loss-of-function mutation in TNFAIP3 leads to a new described autoinflammatory disease-haploinsufficiency of A20(HA20).Since HA20 was first described in 2016,a number of new cases have been described in this literature,however,the disease and its pathogenesis are poorly understood.This review seeks to improve clinical recognition of this disorder,and promote both earlier diagnosis and initiation of targeted therapies to improve patients’outcomes.Methods We reviewed 26 papers about A20 and HA20,and we summarized genetic variants and clinical manifestations of a total of 61 reported patients from 26 families identified to have a genetic diagnosis of germline pathogenic variants in TNFAIP3/A20.Additionally,we discussed the pathogenesis and treatment of HA20.Results A total of 24 pathogenic variants of A20 had been reported.There was significant clinical heterogeneity,even among those with the same variants in TNFA1P3.Prior to receiving a molecular diagnosis of HA20,patients had been diagnosed with Behcet's disease,rheumatoid arthritis,rheumatic fever,juvenile idiopathic arthritis,systemic lupus erythematosus,and even adult-onset Stills'disease.The patients with HA20 that presented with inflammatory signatures in NF-kB signaling were mostly responsive to treatment.Conclusions HA20 is a monogenic autoinflammatory disease with highly variable clinical manifestations.This extensive heterogeneity makes it difficult to set a clinical diagnostic criteria,and genetic sequencing is necessary for a definitive diagnosis of HA20.
基金This work was supported by grants from the National Key R&D Program of China(2016YFC1305102 to Y.Z.)National Natural Science Foundation of China(81671561,81974248 to Y.Z.)+5 种基金the International Joint Laboratory Program of National Children’s Medical Center(EK1125180109 to Y.Z.)Program for Outstanding Medical Academic Leader(2019U19 to Y.Z.)Shanghai Municipal Planning Commission of Science and Research Fund(201740065 to Y.Z.)Shanghai Committee of Science and Technology(21140902400 to Y.Z.,21ZR1410000,19ZR1406400 to J.F.)Versus Arthritis UK(21327 to D.X.)Shenzhen Science and Technology Peacock Team Project(KQTD20170331145453160).
文摘The Coronavirus Disease 2019(COVID-19)pandemic has become a global crisis and is more devastating than any other previous infectious disease.It has affected a significant proportion of the global population both physically and mentally,and destroyed businesses and societies.Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis,including lymphopenia,neutrophilia,dysregulation of monocytes and macrophages,reduced or delayed type I interferon(IFN-I)response,antibody-dependent enhancement,and especially,cytokine storm(CS).The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis.These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells,resulting in complicated medical symptoms including fever,capillary leak syndrome,disseminated intravascular coagulation,acute respiratory distress syndrome,and multiorgan failure,ultimately leading to death in the most severe cases.Therefore,it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19.Herein,we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved.We also discuss the induction,function,downstream signaling,and existing and potential interventions for targeting these cytokines or related signal pathways.We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.
基金the Scientific Research Foundation of Shanxi Province Healthy Commission(No.2017068)Shanxi Province Science Foundation for Youths(No.201801D221259).
文摘Background:In the era of precision medicine,chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations.How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring.This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy(HCT)for advanced patients with non-small cell lung cancer(NSCLC),especially those with malignant pleural effusion.Methods:We retrospectively evaluated medical records of 93 patients with advanced NSCLC(stage IIIB-IV)from March 2011 to January 2014.The patients were divided into HCT and chemotherapy(CT)groups.The HCT group was treated with gemcitabine and cisplatin(GP)regimen combined with regional radiofrequency deep hyperthermia,while the CT group was treated with GP regimen only.Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not.Clinical treatment results and adverse reactions were compared and analyzed after treatment.SPSS 19.0 software(SPSS Inc.,USA)was used for statistical data processing.P values less than 0.05 were accepted to be statistically significant.Results:Among the 93 patients,HCT group included 48 patients(16 patients with malignant pleural effusion),CT group included 45 patients(10 patients with malignant pleural effusion).There was no significant difference between the two groups in patient characteristics.The overall response rate(ORR)of pleural effusions was much better in HCT group than that in CT group(81.2%vs.40.0%,P=0.046).The patients in HCT group had lower incidence rate of weakness(12.5%us.46.7%,χ^2=13.16,P<0.001)and gastrointestinal(25.0%vs.77.8%,χ^2=25.88,P<0.001)adverse reactions than that in CT group.The objective tumor response and survival showed no significant differences.Conclusions:Hyperthermia combined with chemotherapy might lead to the development of better therapeutic strategy for advanced NSCLC with malignant pleural effusion patients.Al
文摘Background Allergen micro-arrays are powerful tools for screening of serum IgE-reactivity. In this study allergen micro-arrays were used to identify dominating IgE-binding allergens and cross-reactivity patterns among selected Chinese allergy patients. Methods The study was conducted using patient sera from the cities of Guangzhou, Nanjing, Chengdu and Shenyang. In total 100 sera with Dermatophagoides pteronyssinus （Der p） specific IgE-levels higher than 50 kU/L were selected for testing against 103 individual allergens. Results Among 100 selected patients, 95% showed IgE-reactivity towards house-dust mite allergens Dermatophagoides farinae （Der f） 1, Der f 2 and Der p 2 and 94% were IgE positive against Der p 1, and 60% of sera contained IgE reacting against allergen Euroglyphus maynei （Eur m） 2. IgE against cat allergen, Felisdomesticus （Fel d） 1, was seen in 20%. Only 2% showed specific IgE-reactivity to Der p 10, a panallergen belonging to the tropomyosin family. Serum IgE-reactivity towards other allergens was in general low. IgE-reactivity against pollen allergens showed geographic differences. Conclusions This study clearly confirms that group 1 and group 2 are major allergens of house dust mites. These selected house-dust mite allergy patients are close to being mono-sensitized. Der p 10 is not an important allergen for cross-reactivity. Specific IgE-sensitization towards pollen allergens is low in southern China compared to other regions. The prevalence of food and stinging insect allergens known to give rise to IgE-mediated cross-reactivity is 2% or less.
基金supported,in part,by the NIH(R01AI121302,R21AI14889801,R01AI074745,and R01AI080769)Kenneth and Judy Betz Professorship at the Mary H.Weiser Food Allergy Center at the University of Michigan to C.H.K.
文摘A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.
基金This study is funded by Zhejiang Basic Public Welfare Research Project(LGF19H100002).
文摘Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an importa
文摘Background： Drug reaction with eosinophilia and systemic symptoms （DRESS） is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice. Methods： Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 （IBM, Armonk, NY, USA）, and a value ofP 〈 0.05 was considered statistically significant. Results： Among 104 patients, 38 were male and 66 female （aged 18-83 years）. The latent period was 13 （interquartile range [IQR]： 10-17） days. The most common allergy-inducing drugs were antibiotics （n = 37, 35.6%）, followed by antiepileptic drugs and traditional Chinese medicines （TCMs）. Eighty-two cases （78.8%） had rash with area 〉50% body surface area （BSA）. Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin （IVIG） group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature 〉38.5℃ were not significantly different between the two groups. However, the number of patients meeting the criteria of＂definite＂ and ＂probable＂ （X2 =5.852, P = 0.016）, with an eosinophilic granulocyte count of〉1.5 x10^9/L 0,2 7.129, P = 0.008）, and with rash area of〉50% BSA （X2 = 4.750, P = 0.029）, was significantly different. Conclusions： Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation perio
文摘AIM:To investigate if echocardiographic and hemodynamic determinations obtained at the time of transjugular intrahepatic portosystemic shunt(TIPS)can provide prognostic information that will enhance risk stratification of patients.METHODS:We reviewed medical records of 467 patients who underwent TIPS between July 2003 and December 2011 at our institution.We recorded information regarding patient demographics,underlying liver disease,indication for TIPS,baseline laboratory values,hemodynamic determinations at the time of TIPS,and echocardiographic measurements both before and after TIPS.We recorded patient comorbidities that may affect hemodynamic and echocardiographic determinations.We also calculated Model for Endstage Liver Disease(MELD)score and Child Turcotte Pugh(CTP)class.The following pre-and post-TIPS echocardiographic determinations were recorded:Left ventricular ejection fraction,right ventricular(RV)systolic pressure,subjective RV dilation,and subjective RV function.We recorded the following hemodynamic measurements:Right atrial(RA)pressure before and after TIPS,inferior vena cava pressure before and after TIPS,free hepatic vein pressure,portal vein pressure before and after TIPS,and hepatic venous pressure gradient(HVPG).RESULTS:We reviewed 418 patients with portal hypertension undergoing TIPS.RA pressure increased by a mean ± SD of 4.8 ± 3.9 mmH g(P < 0.001),HVPG decreased by 6.8 ± 3.5 mmH g(P < 0.001).In multivariate linear regression analysis,a higher MELD score,lower platelet count,splenectomy and a higher portal vein pressure were independent predictors of higher RA pressure(R = 0.55).Three variables predicted 3-mo mortality after TIPS in a multivariate analysis:Age,MELD score,and CTP grade C.Change in the RA pressure after TIPS predicted long-term mortality(per 1 mm Hg change,HR = 1.03,95%CI:1.01-1.06,P < 0.012).CONCLUSION:RA pressure increased immediately after TIPS particularly in patients with worse liver function,portal hypertension,emergent TIPS placement and history of splenectomy.The i
基金Supported by National Natural Science Foundation of China,No.31470264 and No.81502418the Key Program of Natural Science Foundation of Hubei Province of China,No.2014CFA078+7 种基金the Hubei Provincial Natural Science Foundation of China,No.2015CFB168 and No.2012FFB04304the Scientific research Innovation Team in Hubei,No.2015CFA009the General Financial Grant from the China Postdoctoral Science Foundation,No.2014M550411the Fundamental research Funds for the Central Universities,No.2042014kf0029the Tianqing Liver Disease research Fund of the China Foundation for Hepatitis Prevention and Control,No.TQGB20140250the Innovation Seed Fund of Wuhan University School of Medicinethe Science and Technology Department Supported Program of Jiangxi Province of China,No.2010BSA13500the Science and Technology Project of Education Department of Jiangxi Province of China,No.GJJ11570
文摘Hepatocellular carcinoma(HCC) is one of the most lethal malignancies in the world. Several signaling pathways,including the wingless/int-1(Wnt) signaling pathway,have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1(CTNNB1)-dependent(also known as "canonical") and CTNNB1-independent(often referred to as "non-canonical") pathways. Specifically,the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes(the cell-surface receptor complex,the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported,two main non-canonical pathways,Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway,participate in the regulation of hepatocarcinogenesis. Interestingly,the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover,other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore,crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.
文摘Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T cells.The etiology remains to be determined,yet data suggest that both a susceptible genetic background and unknown environmental factors determine disease onset.Multiple infectious and chemical candidates have been proposed to trigger the disease in a genetically susceptible host,mostly by molecular mimicry.Most recently,several murine models have been reported,including genetically determined models as well as models induced by immunization with xenobiotics and bacteria.
基金Supported by the Austrian EURASIA-PACIFIC UNINET Technology Scholarship,the Austrian Federal Ministry of Science and Research and the Austrian Federal Ministry of Health(GZ 402.000/0006-II/6b/2012)the National Basic Research Program of China(No.2014CB543203)
文摘Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.
基金supported by grants from the American Cancer Society(RSG-10-160-01-LIB,to GP)Melanoma Research Alliance(to GP)and the NIH(AI097852,AI094478 and CA184379 to GP).
文摘Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments.Toll-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells.However,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these cells.In this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor microenvironment.In particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer therapy.An improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.
基金This study was supported by grants from the National Natural Science Foundation of China,NSFC 31671438 and NSFC 31471295the Graduate Innovation Fund of Jilin University,Hyundai Hope On Wheels,the Ring Screw Textron Endowed Chair for Pediatric Cancer Research,Children’s Hospital of Michigan Foundation,Kids Without Cancer,Lafontaine Family/U Can-Cer Vive Foundation,the Decerchio/Guisewite Family,Justin’s Gift,Elana Fund,and the Ginopolis/Karmanos Endowment and supported by Jilin University,Changchun,China,Wayne State University School of Medicine,the China Scholarship Council,and the Barbara Ann Karmanos Cancer Institute.
文摘Acute myeloid leukemia(AML)is a serious disease.The 5-year survival rates remain frustratingly low(65%for children and 26%for adults).Resistance to frontline chemotherapy(usually cytarabine)often develops;therefore a new treatment modality is needed.Bcl-2 family proteins play an important role in balancing cell survival and apoptosis.The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML.ABT-199,a BH3 mimetic,was developed to target antiapoptotic protein Bcl-2.Although ABT-199 has demonstrated promising results,resistance occurs.Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2,but this is compensated by increased association of Bim with prosurvival protein Mcl-1,stabilizing Mcl-1,resulting in resistance to ABT-199.In this study,we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells.We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples.The synergistic induction of apoptosis was decreased upon Bak,Bax and Bim knockdown.While A-1210477 treatment alone also increased Mcl-1 protein levels,combination with ABT-199 reduced binding of Bim to Mcl-1.Our results demonstrate that sequestration of Bim by Mcl-1,a mechanism of ABT-199 resistance,can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.
文摘Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalovirus （CMV） is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients.This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.Methods： Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated.GraphPad Prism version 5.013 （San Diego, CA, USA） was used to conduct statistical analysis.The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test.Significance between qualitative data was analyzed using Pearson＆#39;s Chi-squared test.The cut-offthresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic （ROC） curve analysis.Results： One hundred and forty-two patients had positive CMV viral load tests.Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic.The symptomatic group received higher doses ofprednisolone （PSL） and more frequently immunosuppressants than the asymptomatic group （P 〈 0.01）.The symptomatic group had lower lymphocyte counts, especially CD4＋ T-cells, than the asymptomatic group （P 〈 0.01）.By ROC curve analysis, when CD4＋ T-cell count was 〈0.39 ＆#215; 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection.The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients （P 〈 0.01;t
