The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding ...The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.展开更多
Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and...Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.展开更多
To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis.METHODSA prospective cohort of 102 consecutive patient...To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis.METHODSA prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.RESULTSAt the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A.CONCLUSIONUndiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.展开更多
Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can l...Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.展开更多
AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Fort...AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.展开更多
AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seve...AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.展开更多
We surveyed all known wintering areas of the Black-necked Crane (Grus nigricollis) in Zhigatse Prefecture of the Tibet Autonomous Region during three winters.Our surveys confirm that Zhigatse Prefecture is the most im...We surveyed all known wintering areas of the Black-necked Crane (Grus nigricollis) in Zhigatse Prefecture of the Tibet Autonomous Region during three winters.Our surveys confirm that Zhigatse Prefecture is the most important wintering area for the species,accounting in some years for as much as 39% of the estimated world population.Counts ranged from a high of 4240 cranes in January 2007 to a low of 2636 in February 2009.Chick recruitment (chicks/100 cranes) ranged from 8.2 (January 2010) to 11.3 (January 2007).The highest concentration of cranes during all three surveys occurred on the 60 km stretch of the Yarlung Tsangpo (River) between Lhaze and Phuntsoling.To evaluate potential impacts of the Xietongmen Copper Mine,we monitored wintering crane numbers prior to mine installation in an intensive study area located between the Shab Chu Valley and the city of Zhigatse.Our surveys recorded on average 820 ± 83 cranes (SE; n =8) in this area.With the installation of the mine at a location ~50 km west of Zhigatse,increased traffic and development on the north side of the Yarlung River will likely result in a shift in crane distribution away from the north side,to nearby suitable habitats.Based on our survey results,we recommend three areas hosting high numbers of cranes in the vicinity of the mine be added to the Yarlung Tsangpo Middle Reaches Black- necked Crane Nature Reserve.These areas are Nierixiong and Jiaqingze Villages in Nierixiong Xiang and the Shab Chu Valley.展开更多
The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferroox...The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferrooxidans,Leptospirillum ferriphilum and Acidithiobacillus thiooxidans)was used to leach three kinds of chalcopyrites with different iron-sulfur ratios.After 36 d of leaching,the chalcopyrite with iron-sulfur ratio of about 1:1 achieved the highest copper extraction(69.62%).In the early stage,iron oxidizing bacteria predominated,and the expression of rus and rio was 8 times higher than that in the late stage.In the late stage,sulfur oxidizing bacteria predominated,and the expression of tetH and HdrAB was 4 times higher than that in the early stage.Furthermore,the three bioleaching systems above were added with elemental sulfur(3 g/L);the chalcopyrite with iron-sulfur ratio of about 2:1 achieved the highest copper extraction(80.63%).The results suggest that the energy metabolism structure of the microbial community could be changed by changing the iron-sulfur ratio during the leaching process for improving the leaching efficiency of chalcopyrite.展开更多
AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.METHODS Mono-infected patients with hepatitis C were treated with gu...AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.METHODS Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol(TCHOL), high density lipoprotein(HDL), low density lipoprotein(LDL), triglycerides(TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component(direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3.RESULTS Three hundred and seventy five patients enrolled with 321(85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1(GT1), 18.1% genotype 2(GT2), 9.7% genotype 3(GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3(ΔGT1, p and ΔGT3, p), with TCHOL increasing(+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing(+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing(+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing(-5.9, P = 0.044 and-9.80 P = 0.067). Among genotypes(ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL(+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL(+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2(P = 0.028 and P = 0.019).CONCLUSION Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.展开更多
The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
As an important part of traditional Chinese medicine (TCM) nursing technology, moxibustion plays a unique role in improving the symptoms of ankylosing spondylitis (AS). The research on the mechanism of moxibustion int...As an important part of traditional Chinese medicine (TCM) nursing technology, moxibustion plays a unique role in improving the symptoms of ankylosing spondylitis (AS). The research on the mechanism of moxibustion intervention in AS mainly focuses on anti-inflammatory effects, immune regulation, bone metabolism regulation, intestinal flora regulation, and so on. Molecular medicine is of great significance to further clarify the mechanism of moxibustion intervention in AS. However, there are still some problems in the research on the molecular mechanism of moxibustion intervention in AS: the existing biomedical research methods only explore from a specific field and lack the exploration of moxibustion-targeted molecules based on biomedical network. In the future, the molecular network effect of moxibustion on AS can be discussed comprehensively and systematically with the help of omics technology and the construction of biological information interaction network between omics. The effect of moxibustion on upstream osteogenic transcription factors and related signaling pathways such as WNT, β-catenin, and BMP/Smads is not yet clear. Future research can focus on the relevant signal targets of bone reconstruction and clarify the mechanism of moxibustion against the new bone formation. In addition, there is a lack of research on the molecular mechanism of moxibustion in the treatment of AS from the perspective of metabolites. It is necessary to further explore the mechanism of moxibustion in the treatment of AS with the help of metabonomics technology.展开更多
With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituen...With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases.This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight,the possible structural transformation of CMM components in vitro and in vivo,and their pharmacological contribution.When a decoction is prepared,significant chemical reactions are observed,including degradation and production of polymers and self-assembling supramolecules,leading to the construction of a component library with diverse decoction structures.After ingestion,compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota,microbial enzymes,and endogenous drug-metabolizing enzymes(mainly liver enzymes).At this stage,they are modified and assembled into novel and complex compounds,such as newly generated metabolites,conjugates,and self-assembling superamolecules.This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.展开更多
Characteristics of a microbial community are important as they indicate the status of aquatic ecosystems. In the present study, the metabolic and phylogenetic profile of the bacterioplankton community in Guishan coast...Characteristics of a microbial community are important as they indicate the status of aquatic ecosystems. In the present study, the metabolic and phylogenetic profile of the bacterioplankton community in Guishan coastal water(Pearl River Estuary), South China Sea, at 12 sites(S1–S12) were explored by community-level physiological profiling(CLPP) with BIOLOG Eco-plate and denaturing gradient gel electrophoresis(DGGE). Our results showed that the core mariculture area(S6, S7 and S8) and the sites associating with human activity and sewage discharge(S11 and S12) had higher microbial metabolic capability and bacterial community diversity than others(S1–5, S9–10). Especially, the diversity index of S11 and S12 calculated from both CLPP and DGGE data(H >3.2) was higher than that of others as sewage discharge may increase water nitrogen and phosphorus nutrient. The bacterial community structure of S6, S8, S11 and S12 was greatly influenced by total phosphorous, salinity and total nitrogen. Based on DGGE fingerprinting, proteobacteria, especially γ- and α-proteobacteria, were found dominant at all sites. In conclusion, the aquaculture area and wharf had high microbial metabolic capability. The structure and composition of bacterial community were closely related to the level of phosphorus, salinity and nitrogen.展开更多
基金The National Natural Science Foundation of China(No.11171065,81130068)the Natural Science Foundation of Jiangsu Province(No.BK2011058)the Fundamental Research Funds for the Central Universities(No.JKPZ2013015)
文摘The nonlinear mixed-effects model with stochastic differential equations (SDEs) is used to model the population pharmacokinetic (PPK) data that are extended from ordinary differential equations (ODEs) by adding a stochastic term to the state equation. Compared with the ODEs, the SDEs can model correlated residuals which are ubiquitous in actual pharmacokinetic problems. The Bayesian estimation is provided for nonlinear mixed-effects models based on stochastic differential equations. Combining the Gibbs and the Metropolis-Hastings algorithms, the population and individual parameter values are given through the parameter posterior predictive distributions. The analysis and simulation results show that the performance of the Bayesian estimation for mixed-effects SDEs model and analysis of population pharmacokinetic data is reliable. The results suggest that the proposed method is feasible for population pharmacokinetic data.
文摘Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
文摘To characterize natural history of cryptogenic cirrhosis (CC) and compare its clinical features and outcomes to those of hepatitis C virus (HCV)-related cirrhosis.METHODSA prospective cohort of 102 consecutive patients at their first diagnosis of CC were enrolled in this study. The clinical data and outcomes were compared to an age- and Child-Pugh class-matched cohort of 110 patients with HCV-related cirrhosis. Diagnosis of cirrhosis was based on compatible clinical and laboratory parameters, ultrasound/endoscopic parameters and, whenever possible, on histological grounds and transient elastography. All cases of cirrhosis without a definite etiology were enrolled in the CC group. The parameters assessed were: (1) severity of liver disease at the time of first diagnosis; (2) liver decompensation during follow-up; (3) hepatocellular carcinoma (HCC); (4) orthotopic liver transplantation; and (5) death. The independent associated factors were evaluated by multiple logistic regression analysis, and survival and its determinants by the Kaplan-Meier model, log-rank test and Cox regression.RESULTSAt the first observation, median age was 66 and 65 years and male gender was 36% and 58% for CC and HCV cirrhosis, respectively. CC showed Child-Pugh class A/B/C of 47%/31%/22%, respectively. Compared to HCV cirrhosis, CC exhibited a significantly higher prevalence of metabolic syndrome (12% vs 54%, respectively), overweight/obesity, high BMI, impaired glucose tolerance, high blood pressure, dyslipidemia, hyperuricemia, cardiovascular diseases, extrahepatic cancer, and gallstones. Over a median period of 42 mo of follow-up, liver decompensation, HCC development and death for CC and HCV-related cirrhosis were 60.8%, and 54.4%, 16.7% and 17.2%, 39.2% and 30%, respectively. The median survival was 60 mo for CC. Independent predictors of death were age and Child-Pugh class at diagnosis. CC showed an approximately twofold higher incidence of HCC in Child-Pugh class A.CONCLUSIONUndiagnosed nonalcoholic fatty liver disease has an etiologic role in CC that is associated with a poor prognosis, early HCC development, high risk of cardiovascular disease and extrahepatic cancer.
文摘Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.
基金Supported by Fondo per gli Investimenti della Ricerca di Base,No.RBAP10MY35_002Ente Cassa di Risparmio di FirenzeFior Gen ONLUS to Galli A
文摘AIM To determine the clinical effectiveness of nutritional counseling on reduction of non-alcoholic fatty liver disease(NAFLD) severity, weight loss, metabolic and anthropometric indexes and liver enzymes.METHODS Forty-six adults with NAFLD received a 6-mo clinical and a dietary intervention(based on Mediterranean diet) carried out respectively by a gastroenterologist and a nutritionist with counseling license. The counseling process consisted of monthly meeting(about 45 min each). The effect of the treatment was evaluated monitoring liver enzymes, metabolic parameters, cardiovascular risk indexes, NAFLD severity [assessed by ultrasound(US)] and related indexes. All parameters were assessed at baseline. Biochemistry was also assessed at mid-and end-interventions and US was repeated at end-intervention.RESULTS The percentage of patients with steatosis grade equal or higher than 2 was reduced from 93% to 48% and steatosis regressed in 9 patients(20%). At the end of the treatment the end-point concerning the weight(i.e., a 7% weight reduction or achievement/maintenance of normal weight) was accomplished by 25 out of 46 patients(i.e., 54.3%). As far as the liver enzymes is concerned, all three liver enzymes significantly decrease during the treatment the normalization was particularly evident for the ALT enzyme(altered values reduced from 67% down to 11%). Several parameters, i.e., BMI, waist circumference, waist-to-hip ratio, AST, ALT, GGT, HDL, serum glucose, Tot-Chol/HDL, LDL/HDL, TG/HDL, AIP, HOMA, FLI, Kotronen index, VAI, NAFLD liver fat score and LAP, showed a significant improvement(P < 0.01) between baseline and end-treatment.CONCLUSION Outcomes of this study further strengthen the hypothesis that Med Diet and more active lifestyle can be considered a safe therapeutic approach for reducing risk and severity of NAFLD and related disease states. The proposed approach may be proposed as a valid and recommended approach for improving the clinical profile of NAFLD patients.
基金the National Natural Science Foundation,No.81270521(to Wang B)
文摘AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.
文摘We surveyed all known wintering areas of the Black-necked Crane (Grus nigricollis) in Zhigatse Prefecture of the Tibet Autonomous Region during three winters.Our surveys confirm that Zhigatse Prefecture is the most important wintering area for the species,accounting in some years for as much as 39% of the estimated world population.Counts ranged from a high of 4240 cranes in January 2007 to a low of 2636 in February 2009.Chick recruitment (chicks/100 cranes) ranged from 8.2 (January 2010) to 11.3 (January 2007).The highest concentration of cranes during all three surveys occurred on the 60 km stretch of the Yarlung Tsangpo (River) between Lhaze and Phuntsoling.To evaluate potential impacts of the Xietongmen Copper Mine,we monitored wintering crane numbers prior to mine installation in an intensive study area located between the Shab Chu Valley and the city of Zhigatse.Our surveys recorded on average 820 ± 83 cranes (SE; n =8) in this area.With the installation of the mine at a location ~50 km west of Zhigatse,increased traffic and development on the north side of the Yarlung River will likely result in a shift in crane distribution away from the north side,to nearby suitable habitats.Based on our survey results,we recommend three areas hosting high numbers of cranes in the vicinity of the mine be added to the Yarlung Tsangpo Middle Reaches Black- necked Crane Nature Reserve.These areas are Nierixiong and Jiaqingze Villages in Nierixiong Xiang and the Shab Chu Valley.
基金Project(2017zzts382)supported by Central South University Postgraduate Independent Exploration and Innovation,ChinaProject(2014jpkc003)supported by Central South University Graduate Excellent Course,China+1 种基金Project(2015JJ2165)supported by Hunan Provincial Natural Science Foundation of ChinaProject(165611031)supported by Central South University Fundamental Research Funds Special Funding,China。
文摘The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferrooxidans,Leptospirillum ferriphilum and Acidithiobacillus thiooxidans)was used to leach three kinds of chalcopyrites with different iron-sulfur ratios.After 36 d of leaching,the chalcopyrite with iron-sulfur ratio of about 1:1 achieved the highest copper extraction(69.62%).In the early stage,iron oxidizing bacteria predominated,and the expression of rus and rio was 8 times higher than that in the late stage.In the late stage,sulfur oxidizing bacteria predominated,and the expression of tetH and HdrAB was 4 times higher than that in the early stage.Furthermore,the three bioleaching systems above were added with elemental sulfur(3 g/L);the chalcopyrite with iron-sulfur ratio of about 2:1 achieved the highest copper extraction(80.63%).The results suggest that the energy metabolism structure of the microbial community could be changed by changing the iron-sulfur ratio during the leaching process for improving the leaching efficiency of chalcopyrite.
文摘AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.METHODS Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol(TCHOL), high density lipoprotein(HDL), low density lipoprotein(LDL), triglycerides(TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component(direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene's test and student's t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3.RESULTS Three hundred and seventy five patients enrolled with 321(85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1(GT1), 18.1% genotype 2(GT2), 9.7% genotype 3(GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3(ΔGT1, p and ΔGT3, p), with TCHOL increasing(+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing(+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing(+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing(-5.9, P = 0.044 and-9.80 P = 0.067). Among genotypes(ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL(+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL(+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2(P = 0.028 and P = 0.019).CONCLUSION Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
基金supported by the National Natural Science Foundation of China(81904274).
文摘As an important part of traditional Chinese medicine (TCM) nursing technology, moxibustion plays a unique role in improving the symptoms of ankylosing spondylitis (AS). The research on the mechanism of moxibustion intervention in AS mainly focuses on anti-inflammatory effects, immune regulation, bone metabolism regulation, intestinal flora regulation, and so on. Molecular medicine is of great significance to further clarify the mechanism of moxibustion intervention in AS. However, there are still some problems in the research on the molecular mechanism of moxibustion intervention in AS: the existing biomedical research methods only explore from a specific field and lack the exploration of moxibustion-targeted molecules based on biomedical network. In the future, the molecular network effect of moxibustion on AS can be discussed comprehensively and systematically with the help of omics technology and the construction of biological information interaction network between omics. The effect of moxibustion on upstream osteogenic transcription factors and related signaling pathways such as WNT, β-catenin, and BMP/Smads is not yet clear. Future research can focus on the relevant signal targets of bone reconstruction and clarify the mechanism of moxibustion against the new bone formation. In addition, there is a lack of research on the molecular mechanism of moxibustion in the treatment of AS from the perspective of metabolites. It is necessary to further explore the mechanism of moxibustion in the treatment of AS with the help of metabonomics technology.
基金supported by the National Natural Science Foundation of China(81873192 and 81202877)Postgraduate Research and Innovation Project of Tianjin(2021YJSB288 and YJSKC-20211004)the Science and Technology Program of Tianjin(Grant No.20ZYJDJC00070)
文摘With its long-term empirical clinical practice and increasing number of health benefits reported,Chinese Materia Medica(CMM)is gaining increasing global acceptance.Importantly,the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases.This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight,the possible structural transformation of CMM components in vitro and in vivo,and their pharmacological contribution.When a decoction is prepared,significant chemical reactions are observed,including degradation and production of polymers and self-assembling supramolecules,leading to the construction of a component library with diverse decoction structures.After ingestion,compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota,microbial enzymes,and endogenous drug-metabolizing enzymes(mainly liver enzymes).At this stage,they are modified and assembled into novel and complex compounds,such as newly generated metabolites,conjugates,and self-assembling superamolecules.This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.
基金supported by the Support Project of Science and Technology of China (Grant No. 2012BAD18B01)Special Fund for Agro-scientific Research in the Public Interest (201403008)+1 种基金the Natural Science Foundation of China (Grant Nos. U1301235, 41173079)special scientific research funds for central non-profit institutes,South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences (2014TS04)
文摘Characteristics of a microbial community are important as they indicate the status of aquatic ecosystems. In the present study, the metabolic and phylogenetic profile of the bacterioplankton community in Guishan coastal water(Pearl River Estuary), South China Sea, at 12 sites(S1–S12) were explored by community-level physiological profiling(CLPP) with BIOLOG Eco-plate and denaturing gradient gel electrophoresis(DGGE). Our results showed that the core mariculture area(S6, S7 and S8) and the sites associating with human activity and sewage discharge(S11 and S12) had higher microbial metabolic capability and bacterial community diversity than others(S1–5, S9–10). Especially, the diversity index of S11 and S12 calculated from both CLPP and DGGE data(H >3.2) was higher than that of others as sewage discharge may increase water nitrogen and phosphorus nutrient. The bacterial community structure of S6, S8, S11 and S12 was greatly influenced by total phosphorous, salinity and total nitrogen. Based on DGGE fingerprinting, proteobacteria, especially γ- and α-proteobacteria, were found dominant at all sites. In conclusion, the aquaculture area and wharf had high microbial metabolic capability. The structure and composition of bacterial community were closely related to the level of phosphorus, salinity and nitrogen.