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
AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales.
Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complica...Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.展开更多
AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls.METHODS: Urine samples from ...AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls.METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dim展开更多
dOn the basis of the CTD data obtained by the two cruises before and after summer monsoon burst (25th May, 1998), several significant hydrographic characteristics, their variation and formation mechanism in the South ...dOn the basis of the CTD data obtained by the two cruises before and after summer monsoon burst (25th May, 1998), several significant hydrographic characteristics, their variation and formation mechanism in the South China Sea (SCS) are analyzed. The results show that the Kuroshio water intrudes into the SCS in the form of loop current, and its main part is limited to the east of 118degreesE near the Luzon Strait. Then it continuously extends westwards under the influence of the large-scale circulation, and has a distinct impact on the area north of 16degreesN. There are two high temperature and low salinity regions: west off Luzon and east off Vietnam respectively. One region west off Luzon strengthens obviously after summer monsoon burst, the other east off Vietnam shows a tendency of weakening in the north and strengthening in the south. The formation of these two high temperature and low salinity regions is related to the anti-cyclonic eddies existing in this area, besides, it is also related to the high temperature feature west of Luzon, the influx of Sulu Sea water and the influence of the large-scale air circulation. There is a cold region below the depth of 50 m in the south of Zhongsha Islands, and it strengthens after monsoon burst. The formation of cold water is related to the upwelling there.展开更多
<span><b><span style="font-family:"">Objective: </span></b></span><span><span><span style="font-family:"">The COVID-19 pandemic has p...<span><b><span style="font-family:"">Objective: </span></b></span><span><span><span style="font-family:"">The COVID-19 pandemic has presented extraordinary challenges that have tested the resolve of the world and transformed our daily lives. We sought to capture COVID-related attitudes and behaviors of older adults and <span>relate these to views of adolescents from a national study in the USA. <b>Methods: </b></span>This mixed-methods online survey accepted responses from adult volunteers, age 55+, from April to July 2020 (N = 223). We used a snowball approach to recruitment initiated in the state of Maine (USA). <b>Results:</b> Older respondents tended to report congruent attitudes concerning COVID-19 risks and associated preventative behaviors. Most reported taking Centers for Disease Control and Prevention guidance seriously. In contrast, adolescents surveyed in a prior study reported similar adherence, but less concern. Thematic review of open-ended responses highlights key intergenerational similarities and differences. <b>Discussion:</b> COVID-19 has changed day-to-day life in myriad ways. Attitudes vary within and between age groups. Further research could focus on intergenerational differences in motivations underlying behaviors as well as differing needs for public health education and support.展开更多
Colorectal adenocarcinoma （CRC） is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most a...Colorectal adenocarcinoma （CRC） is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A field of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specificities for early detection of several solid tumors. This emerging field uses mass spectrometry-based protein profiles/patterns of easy accessible body fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of： （i） proteins being abnormally produced or shed and added to the serum proteome, （2） proteins clipped or modified as a consequence of the disease process, or （3） proteins subtracted from the proteome owing to disease-related proteolytic degradation pathways. Therefore, protein pattern diagnostics would provide easy and reliable tools for detection of cancer. This paper focuses on the current status of clinical proteomics research in oncology and in colorectal cancer especially, and will reflect on pitfalls and fears in this relatively new area of clinical medicine, which are reproducibility issues and pre-analytical factors, statistical issues, and identification and nature of discriminating proteins/peptides.展开更多
Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,...Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic facto展开更多
BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a vari...BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication. DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation. RESULTS: The most frequent indications of liver retrans- plantation are primary non-function, hepatic artery throm- bosis, graft rejection and recurrent diseases. The results af- ter liver retransplantation remain inferior to those after first transplantation. CONCLUSION: Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.展开更多
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.
文摘AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales.
基金MMEC is supported by a Fellowship from the Sir Halley Stewart Trust (Cambridge, United Kingdom)SDT-R, MMEC, HKSF and RN have been participant workers in the PROLIFICA project in West Africafunded by the European Union Framework 7
文摘Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.
文摘AIM: To establish if a distinct urinary metabolic profile could be identified in Bangladeshi hepatitis-B hepatocellular carcinoma (HCC) patients compared to cirrhosis patients and controls.METHODS: Urine samples from 42 Bangladeshi patients with HCC (39 patients with hepatitis-B HCC), 47 with cirrhosis on a background of hepatitis B, 46 with chronic hepatitis B, and seven ethnically-matched healthy controls were analyzed using nuclear magnetic resonance (NMR) spectroscopy. A full dietary and medication history was recorded for each subject. The urinary NMR data were analyzed using principal component analysis (PCA) and orthogonal partial least squared discriminant analysis (OPLS-DA) techniques. Differences in relative signal levels of the most discriminatory metabolites identified by PCA and OPLS-DA were compared between subject groups using an independent samples Kruskal-Wallis one-way analysis of variance (ANOVA) test with all pairwise multiple comparisons. Within the patient subgroups, the Mann-Whitney U test was used to compare metabolite levels depending on hepatitis B e-antigen (HBeAg) status and treatment with anti-viral therapy. A Benjamini-Hochberg adjustment was applied to acquire the level of significance for multiple testing, with a declared level of statistical significance of P < 0.05.RESULTS: There were significant differences in age (P < 0.001), weight (P < 0.001), and body mass index (P < 0.001) across the four clinical subgroups. Serum alanine aminotransferase (ALT) was significantly higher in the HCC group compared to controls (P < 0.001); serum α-fetoprotein was generally markedly elevated in HCC compared to controls; and serum creatinine levels were significantly reduced in the HCC group compared to the cirrhosis group (P = 0.004). A three-factor PCA scores plot showed clustering of the urinary NMR spectra from the four subgroups. Metabolites that contributed to the discrimination between the subgroups included acetate, creatine, creatinine, dim
文摘dOn the basis of the CTD data obtained by the two cruises before and after summer monsoon burst (25th May, 1998), several significant hydrographic characteristics, their variation and formation mechanism in the South China Sea (SCS) are analyzed. The results show that the Kuroshio water intrudes into the SCS in the form of loop current, and its main part is limited to the east of 118degreesE near the Luzon Strait. Then it continuously extends westwards under the influence of the large-scale circulation, and has a distinct impact on the area north of 16degreesN. There are two high temperature and low salinity regions: west off Luzon and east off Vietnam respectively. One region west off Luzon strengthens obviously after summer monsoon burst, the other east off Vietnam shows a tendency of weakening in the north and strengthening in the south. The formation of these two high temperature and low salinity regions is related to the anti-cyclonic eddies existing in this area, besides, it is also related to the high temperature feature west of Luzon, the influx of Sulu Sea water and the influence of the large-scale air circulation. There is a cold region below the depth of 50 m in the south of Zhongsha Islands, and it strengthens after monsoon burst. The formation of cold water is related to the upwelling there.
文摘<span><b><span style="font-family:"">Objective: </span></b></span><span><span><span style="font-family:"">The COVID-19 pandemic has presented extraordinary challenges that have tested the resolve of the world and transformed our daily lives. We sought to capture COVID-related attitudes and behaviors of older adults and <span>relate these to views of adolescents from a national study in the USA. <b>Methods: </b></span>This mixed-methods online survey accepted responses from adult volunteers, age 55+, from April to July 2020 (N = 223). We used a snowball approach to recruitment initiated in the state of Maine (USA). <b>Results:</b> Older respondents tended to report congruent attitudes concerning COVID-19 risks and associated preventative behaviors. Most reported taking Centers for Disease Control and Prevention guidance seriously. In contrast, adolescents surveyed in a prior study reported similar adherence, but less concern. Thematic review of open-ended responses highlights key intergenerational similarities and differences. <b>Discussion:</b> COVID-19 has changed day-to-day life in myriad ways. Attitudes vary within and between age groups. Further research could focus on intergenerational differences in motivations underlying behaviors as well as differing needs for public health education and support.
文摘Colorectal adenocarcinoma （CRC） is the third most common type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A field of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specificities for early detection of several solid tumors. This emerging field uses mass spectrometry-based protein profiles/patterns of easy accessible body fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of： （i） proteins being abnormally produced or shed and added to the serum proteome, （2） proteins clipped or modified as a consequence of the disease process, or （3） proteins subtracted from the proteome owing to disease-related proteolytic degradation pathways. Therefore, protein pattern diagnostics would provide easy and reliable tools for detection of cancer. This paper focuses on the current status of clinical proteomics research in oncology and in colorectal cancer especially, and will reflect on pitfalls and fears in this relatively new area of clinical medicine, which are reproducibility issues and pre-analytical factors, statistical issues, and identification and nature of discriminating proteins/peptides.
文摘Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic facto
文摘BACKGROUND: Liver transplantation is a life-saving the- rapeutic modality for patients with end-stage liver diseases. After liver transplantation, however, more than 10% pa- tients may lose the grafts caused by a variety of reasons. This review covers the most frequent indications for liver retransplantation as well as the results and specific problems with each indication. DATA RESOURCES: Searching MEDLINE (1997-2003) for articles on liver retransplantation. RESULTS: The most frequent indications of liver retrans- plantation are primary non-function, hepatic artery throm- bosis, graft rejection and recurrent diseases. The results af- ter liver retransplantation remain inferior to those after first transplantation. CONCLUSION: Liver retransplantation, which is the only means of prolonging survival in those patients whose initial graft has failed, makes an important contribution to overall survival.
