The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are ...The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are am- plified in several cascades by a combination of reductases, oxygenases, and transferases to result in an organ and devel- opmentally specific pattern of metabolites, characteristic for each plant species. During the last decade, methodology driven targeted and non-targeted approaches in several plant species have enabled the identification of the participating enzymes of this complex biosynthetic machinery, and revealed numerous genes, enzymes, and metabolites essential for regulation and compartmentation. Considerable success in structural and computational biology, combined with the an- alytical sensitivity to detect even trace compounds and smallest changes in the metabolite, transcript, or enzyme pattern, has facilitated progress towards a comprehensive view of the plant response to its biotic and abiotic environment. Trans- genic approaches have been used to reveal insights into an apparently redundant gene and enzyme pattern required for functional integrity and plasticity of the various phenylpropanoid biosynthetic pathways. Nevertheless, the function and impact of all members of a gene family remain to be completely established. This review aims to give an update on the various facets of the general phenylpropanoid pathway, which is not only restricted to common lignin or flavonoid biosynthesis, but feeds into a variety of other aromatic metabolites like coumarins, phenolic volatiles, or hydrolyzable tannins.展开更多
Background Diabetes management could be improved by diabetes education, through influencing attitudes towards diabetes, knowledge and behaviors of patients. The purpose of this study was to characterize the impact of ...Background Diabetes management could be improved by diabetes education, through influencing attitudes towards diabetes, knowledge and behaviors of patients. The purpose of this study was to characterize the impact of diabetes education on glycemic control, and to assess the attitude, knowledge and self-care behavior in patients with type 2 diabetes in China. Methods This questionnaire-based survey was conducted in 50 medical centers across China from April to July of 2010. The patients with type 2 diabetes were eligible for the study. The information of glycemic control and diabetes education was collected. The diabetes attitude scale-3 formulae, a questionnaire of diabetes knowledge and Summary of Diabetes Self-care Activities scale were used to assess attitude, knowledge and the self-care of patients, respectively. Results Among the 5961 eligible respondents （3233 males; mean age （59.50＋12.48） years; mean hemoglobin Alc （HbAlc） （8.27＋2.23）%）, most patients （79.8%） considered themselves educated on diabetes. Compared with patients without diabetes education, their educated counterparts showed significant lower value of HbAlc, after controlling for age, gender, body mass index and duration of diabetes （P 〈0.01）. The patients who received diabetes education also performed significant higher scores on attitude, knowledge and self-care than their uneducated counterparts. Patients with lower income or education level tended to have higher glucose levels, and showed lower percentage of patients received diabetic education. Conclusions Chinese patients with diabetes education achieved better glycemic control than un-educated patients. Our study indicates effort is required to provide professional education to patients, with emphasis on lower income and lower education level populations.展开更多
Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live...Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.展开更多
AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men ...AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.展开更多
Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and invol...Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.展开更多
Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the ...Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LP展开更多
Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibito...Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.展开更多
Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Severa...Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Several lifestyle factors may increase,or reduce,an individual’s risk of developing AD.Much has been written over the ages about the benefits of exercise and physical activity.Among the risk factors associated with AD is a low level of physical activity.The relationship between physical and mental health was established several years ago.In this review,we discuss the role of exercise(aerobic and resistance)training as a therapeutic strategy for the treatment and prevention of AD.Older adults who exercise are more likely to maintain cognition.We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies.We will pay especial attention to the potential role of exercise in the modulation of amyloid b turnover,inflammation,synthesis and release of neurotrophins,and improvements in cerebral blood flow.Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide.Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.展开更多
Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resis-tance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increas...Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resis-tance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflamma-tion.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. In-terleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce in-flammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabe-tes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory mark-ers. Retinopathy drugs are used to target vascular en-dothelial growth factor, angiopoietin-2, various protein-ases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapa-mycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, per-oxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory thera-pies represent a potential approach for the therapy of diabetes and its complications.展开更多
Collateral circulation plays a vital role in sustaining blood flow to the ischaemic areas in acute,subacute or chronic phases after an ischaemic stroke or transient ischaemic attack.Good collateral circulation has sho...Collateral circulation plays a vital role in sustaining blood flow to the ischaemic areas in acute,subacute or chronic phases after an ischaemic stroke or transient ischaemic attack.Good collateral circulation has shown protective effects towards a favourable functional outcome and a lower risk of recurrence in stroke attributed to different aetiologies or undergoing medical or endovascular treatment.Over the past decade,the importance of collateral circulation has attracted more attention and is becoming a hot spot for research.However,the diversity in imaging methods and criteria to evaluate collateral circulation has hindered comparisons of findings from different cohorts and further studies in exploring the clinical relevance of collateral circulation and possible methods to enhance collateral flow.The statement is aimed to update currently available evidence and provide evidence-based recommendations regarding grading methods for collateral circulation,its significance in patients with stroke and methods under investigation to improve collateral flow.展开更多
The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune c...The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.展开更多
Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no eff...Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.展开更多
Background Vaspin is a newly-identified adipocytokine related to obesity and insulin sensitivity. However, its pathophysiologic role in humans remains largely unknown. The aim of our study was to investigate the relat...Background Vaspin is a newly-identified adipocytokine related to obesity and insulin sensitivity. However, its pathophysiologic role in humans remains largely unknown. The aim of our study was to investigate the relationship between serum vaspin level and glucose metabolism or obesity in Chinese adults. Methods A total of 123 subjects, including 84 subjects with normal glucose tolerance （NGT） and 39 subjects with diabetes, were enrolled in this study. Anthropometric parameters, abdominal fat areas, plasma glucose concentration, serum insulin, lipids, and vaspin level were measured in each participant. Results Serum vaspin concentration was significantly higher in diabetic patients than that in NGT subjects （592 （438-695） pg/ml vs 380 （294-517） pg/ml, P=0.020） in women. In all participants, age, fasting plasma glucose concentration （FPG）, 2-hour post-load plasma glucose （PG2h）, hemoglobin Alc （HbAlc） and high-density lipoprotein cholesterol （HDL-c） significantly increased from the lower tertile to the higher tertile of vaspin. Univariate linear regression analyses revealed that vaspin level was only positively correlated with age （β=0.340, P=0.002） in NGT subjects. And vaspin was positively associated with FPG （β=0.365, P=0.023）, PG2h （β=0.526, P=0.001）, HbAlc （β=0.388, P=0.016）, and HDL-c （β=0.353, P=0.027）, while negatively with homeostasis model assessment of beta cell function （HOMA-β） （β=-0.361, P=-0.024） in diabetic patients. In stepwise multivariate regression analyses, age was independently associated with circulating vaspin in NGT subjects, whereas PG2h was an independent predictor of vaspin in diabetic patients. In addition, there was no significant difference of serum vaspin level between men and women. And no significant correlations between vaspin and body fat indexes were detected. Conclusions Serum vaspin level is higher in diabetic patients than that in NGT subjects in women. Age predicts serum vaspin level in NGT subjects, while PG展开更多
The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however mos...The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.展开更多
Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gast...Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.展开更多
AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for ...AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose 展开更多
A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels ...A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.展开更多
Background Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We ...Background Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose （FPG） during the development of diabetes. Methods A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index （△I30/△G30）, the area under the curve of insulin （AUC-Ⅰ）, and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions. Results The △I30/△G30 decreased much more rapidly than the AUC-Ⅰ accompanying with the elevation of FPG. At the FPG of 110 mg/dl （a pre-diabetic stage）, the AI30/AG30 lost 50% of its maximum while the AUC-Ⅰ was still at a compensated normal level. The AUC-Ⅰ exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher （overt diabetes）, while the △I30/△G30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at 〉 180 mg/dl, both the AI30/AG30 and AUC-Ⅰ were totally lost. Conclusion The increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.展开更多
Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated...Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. Methods A total of 248 aged T2DM patients wore a continuous glucose monitoring system （CGMS） for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions （MAGE） and mean of daily difference （MODD）. All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination （MMSE）. The relationship between MAGE and MODD and performance on these cognitive tests was assessed. Results The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Conclusion Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.展开更多
文摘The general phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates of the shikimate pathway as the core unit. The resulting hydroxycinnamic acids and esters are am- plified in several cascades by a combination of reductases, oxygenases, and transferases to result in an organ and devel- opmentally specific pattern of metabolites, characteristic for each plant species. During the last decade, methodology driven targeted and non-targeted approaches in several plant species have enabled the identification of the participating enzymes of this complex biosynthetic machinery, and revealed numerous genes, enzymes, and metabolites essential for regulation and compartmentation. Considerable success in structural and computational biology, combined with the an- alytical sensitivity to detect even trace compounds and smallest changes in the metabolite, transcript, or enzyme pattern, has facilitated progress towards a comprehensive view of the plant response to its biotic and abiotic environment. Trans- genic approaches have been used to reveal insights into an apparently redundant gene and enzyme pattern required for functional integrity and plasticity of the various phenylpropanoid biosynthetic pathways. Nevertheless, the function and impact of all members of a gene family remain to be completely established. This review aims to give an update on the various facets of the general phenylpropanoid pathway, which is not only restricted to common lignin or flavonoid biosynthesis, but feeds into a variety of other aromatic metabolites like coumarins, phenolic volatiles, or hydrolyzable tannins.
文摘Background Diabetes management could be improved by diabetes education, through influencing attitudes towards diabetes, knowledge and behaviors of patients. The purpose of this study was to characterize the impact of diabetes education on glycemic control, and to assess the attitude, knowledge and self-care behavior in patients with type 2 diabetes in China. Methods This questionnaire-based survey was conducted in 50 medical centers across China from April to July of 2010. The patients with type 2 diabetes were eligible for the study. The information of glycemic control and diabetes education was collected. The diabetes attitude scale-3 formulae, a questionnaire of diabetes knowledge and Summary of Diabetes Self-care Activities scale were used to assess attitude, knowledge and the self-care of patients, respectively. Results Among the 5961 eligible respondents （3233 males; mean age （59.50＋12.48） years; mean hemoglobin Alc （HbAlc） （8.27＋2.23）%）, most patients （79.8%） considered themselves educated on diabetes. Compared with patients without diabetes education, their educated counterparts showed significant lower value of HbAlc, after controlling for age, gender, body mass index and duration of diabetes （P 〈0.01）. The patients who received diabetes education also performed significant higher scores on attitude, knowledge and self-care than their uneducated counterparts. Patients with lower income or education level tended to have higher glucose levels, and showed lower percentage of patients received diabetic education. Conclusions Chinese patients with diabetes education achieved better glycemic control than un-educated patients. Our study indicates effort is required to provide professional education to patients, with emphasis on lower income and lower education level populations.
基金Supported by(in part)the Southampton National Institute for Health Research Biomedical Research Centre(Byrne CD)grants from the School of Medicine of the Verona University(Targher GT)
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
基金Supported by a grant from the Gifu Medical Association
文摘AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.
文摘Cardiac autonomic neuropathy(CAN)is an often overlooked and common complication of diabetes mellitus.CAN is associated with increased cardiovascular morbidity and mortality.The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death.In addition,autoimmune and genetic factors are involved in the development of CAN.CAN might be subclinical for several years until the patient develops resting tachycardia,exercise intolerance,postural hypotension,cardiac dysfunction and diabetic cardiomyopathy.During its sub-clinical phase,heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic.Newer imaging techniques(such as scintigraphy)have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system.One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN;however,the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN,and also proposed screening for CAN in patients with diabetes mellitus.A major challenge,however,is the lack of specific treatment to slow the progression or prevent the development of CAN.Lifestyle changes,improved metabolic control might prevent or slow the progression of CAN.Reversal will require combination of these treatments with new targeted therapeutic approaches.The aim of this article is to review the latest evidence regarding the epidemiology,pathogenesis,manifestations,diagnosis and treatment for CAN.
基金This study was supported by grants from The National Natural Science Foundation of China(81772950)Tongji Hospital Clinical Research Flagship Program(2019CR203)to RQ.
文摘Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LP
基金supported by the National Natural Science Foundation of China(No.82070883)Scientific Research Foundation for high-level faculty,China Pharmaceutical University(Nanjing,China)。
文摘Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.
基金TagedPThis work was supported by the following grants:Instituto de Salud Carlos III and co-funded by FEDER(Grant number PIE15/00013)SAF2016-75508-R from the Spanish Ministry of Education and Science(MEC)+2 种基金CB16/10/00435(CIBERFES)PROMETEOII2014/056 from Conselleria,de Sanitat de la Generalitat Valenciana and EU Funded CM1001 and FRAILOMICHEALTH.2012.2.1.1-2ADVANTAGE-724099 Join Action(HP-JA)3rd EU Health Programme and DIALBFRAIL-LATAM(825546 H2020-SC1-BHC).
文摘Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Several lifestyle factors may increase,or reduce,an individual’s risk of developing AD.Much has been written over the ages about the benefits of exercise and physical activity.Among the risk factors associated with AD is a low level of physical activity.The relationship between physical and mental health was established several years ago.In this review,we discuss the role of exercise(aerobic and resistance)training as a therapeutic strategy for the treatment and prevention of AD.Older adults who exercise are more likely to maintain cognition.We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies.We will pay especial attention to the potential role of exercise in the modulation of amyloid b turnover,inflammation,synthesis and release of neurotrophins,and improvements in cerebral blood flow.Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide.Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.
文摘Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resis-tance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflamma-tion.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. In-terleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce in-flammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabe-tes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory mark-ers. Retinopathy drugs are used to target vascular en-dothelial growth factor, angiopoietin-2, various protein-ases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapa-mycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, per-oxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory thera-pies represent a potential approach for the therapy of diabetes and its complications.
文摘Collateral circulation plays a vital role in sustaining blood flow to the ischaemic areas in acute,subacute or chronic phases after an ischaemic stroke or transient ischaemic attack.Good collateral circulation has shown protective effects towards a favourable functional outcome and a lower risk of recurrence in stroke attributed to different aetiologies or undergoing medical or endovascular treatment.Over the past decade,the importance of collateral circulation has attracted more attention and is becoming a hot spot for research.However,the diversity in imaging methods and criteria to evaluate collateral circulation has hindered comparisons of findings from different cohorts and further studies in exploring the clinical relevance of collateral circulation and possible methods to enhance collateral flow.The statement is aimed to update currently available evidence and provide evidence-based recommendations regarding grading methods for collateral circulation,its significance in patients with stroke and methods under investigation to improve collateral flow.
基金supported in part by the National Natural Science Foundation of China(grants#81830016,81771732,and 81620108002 to X.M.,#81922010 and 81873561 to R.T.)supported in part by services provided by the NIH centers P30 DK120515 and P50 AA011999+1 种基金supported by the excellence initiative VASCage(Centre for Promoting Vascular Health in the Ageing Community)R8fD K-Centre(COMET program-Competence Centers for Excellent Technologies)funded by the Austrian Ministry for Transport,Innovation and Technology,the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol,Salzburg and Vienna.
文摘The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology.The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota.The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens.Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases.Of immense importance is the step from high-throughput sequencing(correlation)to mechanistic studies(causality)and therapeutic intervention.Here,we review the gut microbiota,liver immunology,and the interaction between the gut and liver.In addition,the impairment in the gut-liver axis found in various liver diseases is reviewed here,with an emphasis on alcohol-associated liver disease(ALD),nonalcoholic fatty liver disease(NAFLD),and autoimmune liver disease(AILD).On the basis of growing evidence from these preclinical studies,we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.
文摘Baicalein, wogonin, and their glycosides are major bioactive compounds found in the medicinal plant Scutellaria baicalensis Georgi. These flavones can induce apoptosis in a variety of cancer cell lines but have no effect on normal cells. Furthermore, they have many additional benefits for human health, such as antioxidant, antiviral, and liver-protective properties. Here, we report the isolation and characterization of two CYP450 enzymes, SbCYP82D1.1 and SbCYP82D2, which function as the flavone 6-hydroxylase （F6H） and flavone 8-hydroxylase （F8H）, respectively, in S. baicalensis. SbCYP82D1.1 has broad substrate speci- ficity for flavones such as chrysin and apigenin and is responsible for biosynthesis of baicalein and scutel- larein in roots and aerial parts of S. baicalensis, respectively. When the expression of SbCYP82D1.1 is knocked down, baicalin and baicalein levels are reduced significantly while chrysin glycosides accumulate in hairy roots. SbCYP82D2 is an F8H with high substrate specificity, accepting only chrysin as its substrate to produce norwogonin, although minor 6-hydroxylation activity can also be detected. Phylogenetic analysis suggested that SbCYP82D2 might have evolved from SbCYP82D1.1 via gene duplication followed by neofunctionalization, whereby the ancestral F6H activity is partially retained in the derived SbCYP82D2.
文摘Background Vaspin is a newly-identified adipocytokine related to obesity and insulin sensitivity. However, its pathophysiologic role in humans remains largely unknown. The aim of our study was to investigate the relationship between serum vaspin level and glucose metabolism or obesity in Chinese adults. Methods A total of 123 subjects, including 84 subjects with normal glucose tolerance （NGT） and 39 subjects with diabetes, were enrolled in this study. Anthropometric parameters, abdominal fat areas, plasma glucose concentration, serum insulin, lipids, and vaspin level were measured in each participant. Results Serum vaspin concentration was significantly higher in diabetic patients than that in NGT subjects （592 （438-695） pg/ml vs 380 （294-517） pg/ml, P=0.020） in women. In all participants, age, fasting plasma glucose concentration （FPG）, 2-hour post-load plasma glucose （PG2h）, hemoglobin Alc （HbAlc） and high-density lipoprotein cholesterol （HDL-c） significantly increased from the lower tertile to the higher tertile of vaspin. Univariate linear regression analyses revealed that vaspin level was only positively correlated with age （β=0.340, P=0.002） in NGT subjects. And vaspin was positively associated with FPG （β=0.365, P=0.023）, PG2h （β=0.526, P=0.001）, HbAlc （β=0.388, P=0.016）, and HDL-c （β=0.353, P=0.027）, while negatively with homeostasis model assessment of beta cell function （HOMA-β） （β=-0.361, P=-0.024） in diabetic patients. In stepwise multivariate regression analyses, age was independently associated with circulating vaspin in NGT subjects, whereas PG2h was an independent predictor of vaspin in diabetic patients. In addition, there was no significant difference of serum vaspin level between men and women. And no significant correlations between vaspin and body fat indexes were detected. Conclusions Serum vaspin level is higher in diabetic patients than that in NGT subjects in women. Age predicts serum vaspin level in NGT subjects, while PG
文摘The burden of diabetic foot disease(DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy(DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities.
基金Supported by Comisión Nacional de Investigación Científica y Tecnológica-Fondos de Financiamiento de Centros de Investigación en áreas Prioritarias,No.15130011(to Quest AF)Fondo Nacional de Desarrollo Científico y Tecnológico,No.1170925(to Quest AF)and No.1171615(to Valenzuela MA)Fondo para la Investigación en Odontología Universidad de Chile,No.17/020(to Bravo D)
文摘Helicobacter pylori(H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
基金Supported by National Science Foundation of China, No. 30973230 and No. 81070281
文摘AIM:To explore differences in biochemical indices between neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and that with other etiologies. METHODS:Patients under 6 mo of age who were referred for investigation of conjugated hyperbiliru-binaemia from June 2003 to December 2010 were eligible for this study. After excluding diseases affecting the extrahepatic biliary system, all patients were screened for the two most common SLC25A13 mutations; the coding exons of the entire SLC25A13 gene was sequenced and Western blotting of citrin protein performed in selected cases. Patients in whom homo-zygous or compound heterozygous SLC25A13 mutation and/or absence of normal citrin protein was detected were defined as having NICCD. Cases in which no specific etiological factor could be ascertained after a com-prehensive conjugated hyperbilirubinaemia work-up were defined as idiopathic neonatal cholestasis (INC). Thirty-two NICCD patients, 250 INC patients, and 39 infants with cholangiography-confirmed biliary atresia (BA) were enrolled. Laboratory values at their first visit were abstracted from medical files and compared. RESULTS:Compared with BA and INC patients, the NICCD patients had significantly higher levels of total bile acid (TBA) [all measures are expressed as median (inter-quartile range):178.0 (111.2-236.4) μmol/L in NICCD vs 112.0 (84.9-153.9) μmol/L in BA and 103.0 (70.9-135.3) μmol/L in INC, P = 0.0001]. The NICCD patients had significantly lower direct bilirubin [D-Bil 59.6 (43.1-90.9) μmol/L in NICCD vs 134.0 (115.9-151.2) μmol/L in BA and 87.3 (63.0-123.6) μmol/L in INC, P = 0.0001]; alanine aminotransferase [ALT 34.0 (23.0-55.0) U/L in NICCD vs 108.0 (62.0-199.0) U/L in BA and 84.5 (46.0-166.0) U/L in INC, P = 0.0001]; aspartate aminotransferase [AST 74.0 (53.5-150.0) U/L in NICCD vs 153.0 (115.0-239.0) U/L in BA and 130.5 (81.0-223.0) U/L in INC, P = 0.0006]; albumin [34.9 (30.7-38.2) g/L in NICCD vs 38.4 (36.3-42.2) g/L in BA and 39.9 (37.0-42.3) g/L in INC, P = 0.0001]; glucose
文摘A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.
文摘Background Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose （FPG） during the development of diabetes. Methods A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index （△I30/△G30）, the area under the curve of insulin （AUC-Ⅰ）, and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions. Results The △I30/△G30 decreased much more rapidly than the AUC-Ⅰ accompanying with the elevation of FPG. At the FPG of 110 mg/dl （a pre-diabetic stage）, the AI30/AG30 lost 50% of its maximum while the AUC-Ⅰ was still at a compensated normal level. The AUC-Ⅰ exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher （overt diabetes）, while the △I30/△G30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at 〉 180 mg/dl, both the AI30/AG30 and AUC-Ⅰ were totally lost. Conclusion The increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.
基金funded by the Medical College Natural Science Foundation of Shanghai Jiaotong University (09XJ21028)
文摘Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. Methods A total of 248 aged T2DM patients wore a continuous glucose monitoring system （CGMS） for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions （MAGE） and mean of daily difference （MODD）. All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination （MMSE）. The relationship between MAGE and MODD and performance on these cognitive tests was assessed. Results The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Conclusion Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.
