Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis...Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.展开更多
Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consu...Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.展开更多
AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to Octob...AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to October 2007） to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppresion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals （CI）.RESULTS： We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth rrelative risk （RR） = 1.01; 95% CI： 0.87-1.16], specific individual adverse events, with the exception of dark stools （RR = 5.06; 95% CI： 1.59-16.12）, or adverse events leading to withdrawal of therapy （RR = 0.86; 95% CI： 0.54-1.37）. CONCLUSION： Bismuth for the treatment of H py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.展开更多
There is a rapidly rising trend in the development and application of molecular marker assays for gene map- ping and discovery in field crops and trees. Thus far, more than 50 SNP arrays and 15 different types of geno...There is a rapidly rising trend in the development and application of molecular marker assays for gene map- ping and discovery in field crops and trees. Thus far, more than 50 SNP arrays and 15 different types of genotyping-by-sequencing （GBS） platforms have been developed in over 25 crop species and perennial trees. However, much less effort has been made on developing ultra-high-throughput and cost-effective genotyping platforms for applied breeding programs. In this review, we discuss the scientific bottlenecks in existing SNP arrays and GBS technologies and the strategies to develop targeted platforms for crop mo- lecular breeding. We propose that future practical breeding platforms should adopt automated genotyping technologies, either array or sequencing based, target functional polymorphisms underpinning economic traits, and provide desirable prediction accuracy for quantitative traits, with universal applications under wide genetic backgrounds in crops. The development of such platforms faces serious challenges at both the technological level due to cost ineffectiveness, and the knowledge level due to large genotype- phenotype gaps in crop plants. It is expected that such genotyping platforms will be achieved in the next ten years in major crops in consideration of （a） rapid development in gene discovery of important traits, （b） deepened understanding of quantitative traits through new analytical models and population designs, （c） integration of multi-layer -omics data leading to identification of genes and pathways responsible for important breeding traits, and （d） improvement in cost effectiveness of large-scale genotyping. Crop breeding chips and genotyping platforms will provide unprecedented opportunities to accelerate the development of cultivars with desired yield potential, quality, and enhanced adaptation to mitigate the effects of climate change.展开更多
AIM： To evaluate the antibacterial activity of Sapindus mukorossi （S. mukorossl） and Rheum emodi （R. emodl）. METHODS： Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzen...AIM： To evaluate the antibacterial activity of Sapindus mukorossi （S. mukorossl） and Rheum emodi （R. emodl）. METHODS： Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylon, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram ＋ve （S. aureus, B. subtilis） and two Gram -ve （E. coli, P. vugaris） organisms were screened for their susceptibility patterns against these extracts. RESULTS： In our screening, all 30 resistant isolates and the other four organisms （two Gram ＋ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris） were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited Hpylori at very low concentrations, In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations （10 μg/mL） for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi （2.5 mg/mL） and R. emodi （3.0 mg/mL） given orally for seven days. CONCLUSION： We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.展开更多
Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the dia...Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.展开更多
Humic acid （HA）, a fairly stable product of decomposed organic matter that consequently accumulates in ecological systems, enhances plant growth by chelating unavailable nutrients and buffering pH. We examined the e...Humic acid （HA）, a fairly stable product of decomposed organic matter that consequently accumulates in ecological systems, enhances plant growth by chelating unavailable nutrients and buffering pH. We examined the effect of HA derived from lignite on growth and macronutrient uptake of wheat （Triticum acstivum L.） grown in earthen pots under greenhouse conditions. The soils used in the pot experiment were a calcareous Haplustalf and a non-calcareous Haplustalf collected from Raisalpur and Guliana, respectively, in Punjab Province, Pakistan. The experiment consisted of four treatments with HA levels of 0 （control without HA）, 30, 60, and 90 mg kg^-1 soil designated as HA0, HA1, HA2, and HA3, respectively. In the treatment without HA （HA0）, nitrogen （N）, phosphorus （P）, and potassium （K） were applied at 200, 100, and 125 mg kg^-1 soil, respectively. Significant differences among HA levels were recorded for wheat growth （plant height and shoot weight） and N uptake. On an average of both soils, the largest increases in plant height and shoot fresh and dry weights were found with HA2 （60 mg kg^-1 soil）, being 10%, 25%, and 18%, respectively, as compared to the control without HA （HA0）. Both soils responded positively towards HA application. The wheat growth and N uptake in the non-calcareous soil were higher than those of the calcareous soil. The HA application significantly improved K concentration of the non-calcareous soil and P and NO3-N of the calcareous soil. The highest rate of HA （90 mg kg^-1 soil） had a negative effect on growth and nutrient uptake of wheat as well as nutrient accumulation in soil, whereas the medium dose of HA （60 mg kg^-1 soil） was more efficient in promoting wheat growth.展开更多
In recent years,natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal cancer has attracted widespread attention.The potential benefits of NOSES including reduction in postoperative pain and ...In recent years,natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal cancer has attracted widespread attention.The potential benefits of NOSES including reduction in postoperative pain and wound complications,less use of postoperative analgesic,faster recovery of bowel function,shorter length of hospital stay,better cosmetic and psychological effect have been described in colorectal surgery.Despite significant decrease in surgical trauma of NOSES have been observed,the potential pitfalls of this technique have been demonstrated.Particularly,several issues including bacteriological concerns,oncological outcomes and patient selection are raised with this new technique.Therefore,it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery.After three rounds of discussion by all members of the International Alliance of NOSES,the consensus is finally completed,which is also of great significance to the long-term progress of NOSES worldwide.展开更多
Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added t...Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic stra展开更多
This study focused on the changes of soil microbial diversity and potential inhibitory effects of heavy metals on soil enzymatic activities at different application rates of Cd and/or Pb. The soil used for experiments...This study focused on the changes of soil microbial diversity and potential inhibitory effects of heavy metals on soil enzymatic activities at different application rates of Cd and/or Pb. The soil used for experiments was collected from Beijing and classified as endoaquepts. Pots containing 500 g of the soil with different Cd and/or Pb application rates were incubated for a period of 0, 2, 9, 12 weeks in a glasshouse and the soil samples were analyzed for individual enzymes, including catalase, alkaline phosphatase and dehydrogenase, and the changes of microbial community structure. Results showed that heavy metals slightly inhibited the enzymatic activities in all the samples spiked with heavy metals. The extent of inhibition increased significantly with increasing level of heavy metals, and varied with the incubation periods. The soil bacterial community structure, as determined by polymerase chain reaction- denaturing gradient gel electrophoresis techniques, was different in the contaminated samples as compared to the control. The highest community change was observed in the samples amended with high level of Cd. Positive correlations were observed among the three enzymatic activities, but negative correlations were found between the amounts of the heavy metals and the enzymatic activities.展开更多
BACKGROUND： Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay ...BACKGROUND： Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES： The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS： The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species （ROS） and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly（I：C） induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis （HBV, HCV）, drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS： The mouse animal models of hepatitis provide a parallel approach for the study of human展开更多
A systematic geometric model has been presented for calibration of a newly designed 5-axis turbine blade grinding machine. This machine is designed to serve a specific purpose to attain high accuracy and high efficien...A systematic geometric model has been presented for calibration of a newly designed 5-axis turbine blade grinding machine. This machine is designed to serve a specific purpose to attain high accuracy and high efficiency grinding of turbine blades by eliminating the hand grinding process. Although its topology is RPPPR （P： prismatic; R： rotary）, its design is quite distinct from the competitive machine tools. As error quantification is the only way to investigate, maintain and improve its accuracy, calibra- tion is recommended for its performance assessment and acceptance testing. Systematic geometric error modeling technique is implemented and 52 position dependent and position independent errors are identified while considering the machine as five rigid bodies by eliminating the set-up errors of workpiece and cutting tool. 39 of them are found to have influential errors and are accommodated for finding the resultant effect between the cutting tool and the workpiece in workspace volume. Rigid body kinematics techniques and homogenous transformation matrices are used for error synthesis.展开更多
The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted...The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.展开更多
Nosocomial infections or healthcare associated infections occur in patients under medical care.These infections occur worldwide both in developed and developing countries.Nosocomial infections accounts for 7% in devel...Nosocomial infections or healthcare associated infections occur in patients under medical care.These infections occur worldwide both in developed and developing countries.Nosocomial infections accounts for 7% in developed and 10% in developing countries.As these infections occur during hospital stay,they cause prolonged stay,disability,and economic burden.Frequently prevalent infections include central line-associated bloodstream infections,catheter-associated urinary tract infections,surgical site infections and ventilator-associated pneumonia.Nosocomial pathogens include bacteria,viruses and fungal parasites.According to WHO estimates,approximately 15% of all hospitalized patients suffer from these infections.During hospitalization,patient is exposed to pathogens through different sources environment,healthcare staff,and other infected patients.Transmission of these infections should be restricted for prevention.Hospital waste serves as potential source of pathogens and about 20%–25% of hospital waste is termed as hazardous.Nosocomial infections can be controlled by practicing infection control programs,keep check on antimicrobial use and its resistance,adopting antibiotic control policy.Efficient surveillance system can play its part at national and international level.Efforts are required by all stakeholders to prevent and control nosocomial infections.展开更多
In this paper,we propose enhancements to Beetle Antennae search(BAS)algorithm,called BAS-ADAIVL to smoothen the convergence behavior and avoid trapping in localminima for a highly noin-convex objective function.We ach...In this paper,we propose enhancements to Beetle Antennae search(BAS)algorithm,called BAS-ADAIVL to smoothen the convergence behavior and avoid trapping in localminima for a highly noin-convex objective function.We achieve this by adaptively adjusting the step-size in each iteration using the adaptive moment estimation(ADAM)update rule.The proposed algorithm also increases the convergence rate in a narrow valley.A key feature of the ADAM update rule is the ability to adjust the step-size for each dimension separately instead of using the same step-size.Since ADAM is traditionally used with gradient-based optimization algorithms,therefore we first propose a gradient estimation model without the need to differentiate the objective function.Resultantly,it demonstrates excellent performance and fast convergence rate in searching for the optimum of noin-convex functions.The efficiency of the proposed algorithm was tested on three different benchmark problems,including the training of a high-dimensional neural network.The performance is compared with particle swarm optimizer(PSO)and the original BAS algorithm.展开更多
基金The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and support: AIG is funded by a scholarship from the Egyptian Government SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)+5 种基金 SDTR is funded by grants from the British Medical Research Council (MRC), London, United Kingdomthe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United Kingdomthe Alan Morement Memorial Fund AMMF, Essex, UK Broad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.
文摘Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
文摘AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to October 2007） to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppresion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals （CI）.RESULTS： We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth rrelative risk （RR） = 1.01; 95% CI： 0.87-1.16], specific individual adverse events, with the exception of dark stools （RR = 5.06; 95% CI： 1.59-16.12）, or adverse events leading to withdrawal of therapy （RR = 0.86; 95% CI： 0.54-1.37）. CONCLUSION： Bismuth for the treatment of H py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.
基金This study was supported by the National Key Research and Development Program of China （2016YFD0101802 and 2016YFE0108600） and National Natural Science Foundation of China （31550110212）.
文摘There is a rapidly rising trend in the development and application of molecular marker assays for gene map- ping and discovery in field crops and trees. Thus far, more than 50 SNP arrays and 15 different types of genotyping-by-sequencing （GBS） platforms have been developed in over 25 crop species and perennial trees. However, much less effort has been made on developing ultra-high-throughput and cost-effective genotyping platforms for applied breeding programs. In this review, we discuss the scientific bottlenecks in existing SNP arrays and GBS technologies and the strategies to develop targeted platforms for crop mo- lecular breeding. We propose that future practical breeding platforms should adopt automated genotyping technologies, either array or sequencing based, target functional polymorphisms underpinning economic traits, and provide desirable prediction accuracy for quantitative traits, with universal applications under wide genetic backgrounds in crops. The development of such platforms faces serious challenges at both the technological level due to cost ineffectiveness, and the knowledge level due to large genotype- phenotype gaps in crop plants. It is expected that such genotyping platforms will be achieved in the next ten years in major crops in consideration of （a） rapid development in gene discovery of important traits, （b） deepened understanding of quantitative traits through new analytical models and population designs, （c） integration of multi-layer -omics data leading to identification of genes and pathways responsible for important breeding traits, and （d） improvement in cost effectiveness of large-scale genotyping. Crop breeding chips and genotyping platforms will provide unprecedented opportunities to accelerate the development of cultivars with desired yield potential, quality, and enhanced adaptation to mitigate the effects of climate change.
文摘AIM： To evaluate the antibacterial activity of Sapindus mukorossi （S. mukorossl） and Rheum emodi （R. emodl）. METHODS： Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylon, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram ＋ve （S. aureus, B. subtilis） and two Gram -ve （E. coli, P. vugaris） organisms were screened for their susceptibility patterns against these extracts. RESULTS： In our screening, all 30 resistant isolates and the other four organisms （two Gram ＋ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris） were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited Hpylori at very low concentrations, In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations （10 μg/mL） for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi （2.5 mg/mL） and R. emodi （3.0 mg/mL） given orally for seven days. CONCLUSION： We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.
基金Supported by The NIHR Biomedical Research Centre funding scheme and the following for authors’ funding and supportAIG is funded by a scholarship from the Egyptian Government+5 种基金SAK is supported by a grant from the Higher Education Funding Council for England (HEFCE)SDTR is funded by grants from the British Medical Research Council (MRC), London, United KingdomThe British Engineering, Physics and Science Research Council (EPSRC), Swindon, United KingdomThe Alan Morement Memorial Fund AMMF, Essex, United KingdomBroad Foundation, Los Angeles, United StatesPfizer Global Research and Development Inc, Sandwich, United Kingdom and GlaxoSmithKline, Ware, United Kingdom
文摘Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, particularly in parts of the developing world, and is increasing in incidence. This article reviews the current modalities employed for the diagnosis of HCC, including serum markers, radiological techniques and histological evaluation, and summarises international guidelines for the diagnostic approach to HCC.
基金Supported by the University of Azad Jammu and Kashmir,Muzaffarabad,Pakistan
文摘Humic acid （HA）, a fairly stable product of decomposed organic matter that consequently accumulates in ecological systems, enhances plant growth by chelating unavailable nutrients and buffering pH. We examined the effect of HA derived from lignite on growth and macronutrient uptake of wheat （Triticum acstivum L.） grown in earthen pots under greenhouse conditions. The soils used in the pot experiment were a calcareous Haplustalf and a non-calcareous Haplustalf collected from Raisalpur and Guliana, respectively, in Punjab Province, Pakistan. The experiment consisted of four treatments with HA levels of 0 （control without HA）, 30, 60, and 90 mg kg^-1 soil designated as HA0, HA1, HA2, and HA3, respectively. In the treatment without HA （HA0）, nitrogen （N）, phosphorus （P）, and potassium （K） were applied at 200, 100, and 125 mg kg^-1 soil, respectively. Significant differences among HA levels were recorded for wheat growth （plant height and shoot weight） and N uptake. On an average of both soils, the largest increases in plant height and shoot fresh and dry weights were found with HA2 （60 mg kg^-1 soil）, being 10%, 25%, and 18%, respectively, as compared to the control without HA （HA0）. Both soils responded positively towards HA application. The wheat growth and N uptake in the non-calcareous soil were higher than those of the calcareous soil. The HA application significantly improved K concentration of the non-calcareous soil and P and NO3-N of the calcareous soil. The highest rate of HA （90 mg kg^-1 soil） had a negative effect on growth and nutrient uptake of wheat as well as nutrient accumulation in soil, whereas the medium dose of HA （60 mg kg^-1 soil） was more efficient in promoting wheat growth.
文摘In recent years,natural orifice specimen extraction surgery(NOSES)in the treatment of colorectal cancer has attracted widespread attention.The potential benefits of NOSES including reduction in postoperative pain and wound complications,less use of postoperative analgesic,faster recovery of bowel function,shorter length of hospital stay,better cosmetic and psychological effect have been described in colorectal surgery.Despite significant decrease in surgical trauma of NOSES have been observed,the potential pitfalls of this technique have been demonstrated.Particularly,several issues including bacteriological concerns,oncological outcomes and patient selection are raised with this new technique.Therefore,it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery.After three rounds of discussion by all members of the International Alliance of NOSES,the consensus is finally completed,which is also of great significance to the long-term progress of NOSES worldwide.
文摘Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic stra
基金Project supported by the Key Project of Chinese Academy of Sciences(No. KZCX3-SW-431, KZCX2-YW-408)the National Natural Sci-ence Foundation of China (No. 40321101, 40571082).
文摘This study focused on the changes of soil microbial diversity and potential inhibitory effects of heavy metals on soil enzymatic activities at different application rates of Cd and/or Pb. The soil used for experiments was collected from Beijing and classified as endoaquepts. Pots containing 500 g of the soil with different Cd and/or Pb application rates were incubated for a period of 0, 2, 9, 12 weeks in a glasshouse and the soil samples were analyzed for individual enzymes, including catalase, alkaline phosphatase and dehydrogenase, and the changes of microbial community structure. Results showed that heavy metals slightly inhibited the enzymatic activities in all the samples spiked with heavy metals. The extent of inhibition increased significantly with increasing level of heavy metals, and varied with the incubation periods. The soil bacterial community structure, as determined by polymerase chain reaction- denaturing gradient gel electrophoresis techniques, was different in the contaminated samples as compared to the control. The highest community change was observed in the samples amended with high level of Cd. Positive correlations were observed among the three enzymatic activities, but negative correlations were found between the amounts of the heavy metals and the enzymatic activities.
基金supported by a grant from Higher Education Commission(HEC)at University of Agriculture,Faisalabad,Pakistan(No.20-4613/NRPU/R&D/HEC/14/45)
文摘BACKGROUND： Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES： The data of mouse hepatic models and rele- vant human liver diseases presented in this review are system- atically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS： The hepatotoxic liver injury in mice induced by the metabolites of CC14, acetaminophen or alcohol represent ne- crotic cell death with activation of cytochrome pathway, for- mation of reactive oxygen species （ROS） and mitochondrial damage. The Fas or TNF-a induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrat- ed the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The a-GalCer-induced liver injury was mediated by TNF-a. The LPS-induced hepatitis involved TNF-a, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly（I：C） induced liver injury was mediated by natural killer cells and TNF-a signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune ceils and cell death mediators in viral hepatitis （HBV, HCV）, drug-induced liver injury, non-alcohol- ic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS： The mouse animal models of hepatitis provide a parallel approach for the study of human
文摘A systematic geometric model has been presented for calibration of a newly designed 5-axis turbine blade grinding machine. This machine is designed to serve a specific purpose to attain high accuracy and high efficiency grinding of turbine blades by eliminating the hand grinding process. Although its topology is RPPPR （P： prismatic; R： rotary）, its design is quite distinct from the competitive machine tools. As error quantification is the only way to investigate, maintain and improve its accuracy, calibra- tion is recommended for its performance assessment and acceptance testing. Systematic geometric error modeling technique is implemented and 52 position dependent and position independent errors are identified while considering the machine as five rigid bodies by eliminating the set-up errors of workpiece and cutting tool. 39 of them are found to have influential errors and are accommodated for finding the resultant effect between the cutting tool and the workpiece in workspace volume. Rigid body kinematics techniques and homogenous transformation matrices are used for error synthesis.
基金The Drug Development Unit of the Royal Marsden NHS Foundation TrustThe Institute of Cancer Research is supported in part by a program grant from Cancer Research U.K.+1 种基金Support was also provided by the Experimental Cancer Medicine Centre (to The Institute of Cancer Research)the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research)
文摘The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.
文摘Nosocomial infections or healthcare associated infections occur in patients under medical care.These infections occur worldwide both in developed and developing countries.Nosocomial infections accounts for 7% in developed and 10% in developing countries.As these infections occur during hospital stay,they cause prolonged stay,disability,and economic burden.Frequently prevalent infections include central line-associated bloodstream infections,catheter-associated urinary tract infections,surgical site infections and ventilator-associated pneumonia.Nosocomial pathogens include bacteria,viruses and fungal parasites.According to WHO estimates,approximately 15% of all hospitalized patients suffer from these infections.During hospitalization,patient is exposed to pathogens through different sources environment,healthcare staff,and other infected patients.Transmission of these infections should be restricted for prevention.Hospital waste serves as potential source of pathogens and about 20%–25% of hospital waste is termed as hazardous.Nosocomial infections can be controlled by practicing infection control programs,keep check on antimicrobial use and its resistance,adopting antibiotic control policy.Efficient surveillance system can play its part at national and international level.Efforts are required by all stakeholders to prevent and control nosocomial infections.
文摘In this paper,we propose enhancements to Beetle Antennae search(BAS)algorithm,called BAS-ADAIVL to smoothen the convergence behavior and avoid trapping in localminima for a highly noin-convex objective function.We achieve this by adaptively adjusting the step-size in each iteration using the adaptive moment estimation(ADAM)update rule.The proposed algorithm also increases the convergence rate in a narrow valley.A key feature of the ADAM update rule is the ability to adjust the step-size for each dimension separately instead of using the same step-size.Since ADAM is traditionally used with gradient-based optimization algorithms,therefore we first propose a gradient estimation model without the need to differentiate the objective function.Resultantly,it demonstrates excellent performance and fast convergence rate in searching for the optimum of noin-convex functions.The efficiency of the proposed algorithm was tested on three different benchmark problems,including the training of a high-dimensional neural network.The performance is compared with particle swarm optimizer(PSO)and the original BAS algorithm.
