Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich （80.9...Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.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
Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis...Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma(CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA(HLCCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliaryenteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.展开更多
Autoimmune chronic pancreatitis （AIP） is increasingly being recognized worldwidely, as knowledge of this entity builds up. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response ...Autoimmune chronic pancreatitis （AIP） is increasingly being recognized worldwidely, as knowledge of this entity builds up. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to the oral steroid therapy in contrast to ordinary chronic pancreatitis. Although many characteristic findings of AIP have been described, definite diagnostic criteria have not been fully established. In the year 2002, the Japan Pancreas Society published the diagnostic criteria of AIP and many clinicians around the world use these criteria for the diagnosis of AIP. The diagnostic criteria proposed by the Japan Pancreas Society, however, are not completely satisfactory and some groups use their own criteria in reporting AIP. This review discusses several potential limitations of current diagnostic criteria for this increasingly recognized condition. The manuscript is organized to emphasize the need for convening a consensus to develop improved diagnostic criteria.展开更多
Propelled partly by the Materials Genome Initiative,and partly by the algorithmic developments and the resounding successes of data-driven efforts in other domains,informatics strategies are beginning to take shape wi...Propelled partly by the Materials Genome Initiative,and partly by the algorithmic developments and the resounding successes of data-driven efforts in other domains,informatics strategies are beginning to take shape within materials science.These approaches lead to surrogate machine learning models that enable rapid predictions based purely on past data rather than by direct experimentation or by computations/simulations in which fundamental equations are explicitly solved.Data-centric informatics methods are becoming useful to determine material properties that are hard to measure or compute using traditional methods—due to the cost,time or effort involved—but for which reliable data either already exists or can be generated for at least a subset of the critical cases.Predictions are typically interpolative,involving fingerprinting a material numerically first,and then following a mapping(established via a learning algorithm)between the fingerprint and the property of interest.Fingerprints,also referred to as“descriptors”,may be of many types and scales,as dictated by the application domain and needs.Predictions may also be extrapolative—extending into new materials spaces—provided prediction uncertainties are properly taken into account.This article attempts to provide an overview of some of the recent successful data-driven“materials informatics”strategies undertaken in the last decade,with particular emphasis on the fingerprint or descriptor choices.The review also identifies some challenges the community is facing and those that should be overcome in the near future.展开更多
AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of ...AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.展开更多
AIM:To evaluate the efficacy of simple and extended cholecystectomy for mucosa(T1a) or muscularis(T1b) gallbladder(GB) cancer. METHODS:Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer w...AIM:To evaluate the efficacy of simple and extended cholecystectomy for mucosa(T1a) or muscularis(T1b) gallbladder(GB) cancer. METHODS:Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer were searched from MEDLINE(PubMed) ,Cochrane Library,EMBase,and CancerLit using the search terms of GB,cancer/carcinoma/tumor/neoplasm. RESULTS:Twenty-nine out of the 2312 potentially relevant publications met the eligibility criteria.Of the 1266 patients with GB cancer included in the publications,706(55.8%) and 560(44.2%) had T1a and T1b GB cancer,respectively.Simple cholecystectomy for T1a and T1b GB cancer was performed in 590(83.6%) and 375(67.0%) patients,respectively(P<0.01) .In most series,the treatment of choice was simple cholecystectomy for T1a GB cancer patients with a 5-year survival rate of 100%.Lymph node metastasis was detected in 10.9% of the T1b GB cancer patients and in 1.8%of the T1a GB cancer patients,respectively(P<0.01) .Eight patients(1.1%) with T1a GB cancer and 52 patients(9.3%) with T1b GB cancer died of recurrent GB cancer(P<0.01) . CONCLUSION:Simple cholecystectomy represents the adequate treatment of T1a GB cancer.There is no definite evidence that extended cholecystectomy is advantageous over simple cholecystectomy for T1b GB cancer.展开更多
AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the d...AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.展开更多
AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC sur...AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC surveillance were included in this study.Of the 168 patients,90(53.6%)had HCC including newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment.HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which were obtained during routine surveillance with a suspicion of HCC.AFP,AFP-L3 and PIVKA-Ⅱwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients,38(42.2%)patients had AFP<20 ng/mL,20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients,74(94.9%)patients had AFP<20 ng/mL.After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels(<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve(AUC)for HCC were 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-Ⅱand the combined markers,respectively.The combined AUC for three markers showed higher value than the AUCs of individual marker(P<0.05).AFP-L3 had higher AUC value than PIVKA-Ⅱfor HCC detection in entire patients(P =0.043).With combination of AFP-L3(cut-off>5%) and PIVKA-Ⅱ(cut-off>40 AU/L),the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patients with low AFP levels(<20 ng/mL),AUCs展开更多
AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesi...AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.展开更多
AIM: To evaluate the prevalence of preoperative and postoperative malnutrition and the relationships between objective and subjective nutritional assessment of gastric cancer patients. METHODS: From October 2005 to Ju...AIM: To evaluate the prevalence of preoperative and postoperative malnutrition and the relationships between objective and subjective nutritional assessment of gastric cancer patients. METHODS: From October 2005 to July 2006, we studied 80 patients with no evidence of recurrent disease and no loss to follow-up after curative surgery for gastric cancer. In this group, 9 patients underwent total gastrectomy and 71 patients subtotal gastrectomy. At admission, 6 and 12 mo after surgery, the patients were assessed on the subjective global assessment (SGA), nutritional risk screening (NRS-2002), nutritional risk index (NRI) and by anthropometric measurements and laboratory data. Differences between the independent groups were assessed with the Student's t test and oneway analysis of variance. Spearman's rank correlation coefficients were calculated to evaluate the association between the scores and variables. RESULTS: The prevalence of malnutrition at admissionwas 31% by SGA and 43% by NRS-2002. At admission, the anthropometric data were lower in the malnourished groups defined by the SGA and NRS-2002 assessments, but did not differ between the groups using the NRI assessment. Body weight (BW), body mass index (BMI), triceps skin fold and midarm circumference were significantly reduced, but the total lymphocyte count, albumin, protein, cholesterol and serum iron levels did not decrease during the postoperative period. Six months after surgery, there was a good correlation between the nutritional assessment tools (SGA and NRS-2002) and the other nutritional measurement tools (BW, BMI, and anthropometric measurements). However, 12 mo after surgery, most patients who were assessed as malnourished by SGA and NRS-2002 had returned to their preoperative status, although their BW, BMI, and anthropometric measurements still indicated a malnourished status. CONCLUSION: A combination of objective and subjective assessments is needed for the early detection of the nutritional status in case of gastric cancer patients after gastre展开更多
AIM: To evaluate the nature of the 'learning curve' for laparoscopy-assisted distal gastrectomy (LADG) with systemic lymphadenectomy for early gastric cancer. METHODS: The data of 90 consecutive patients with ...AIM: To evaluate the nature of the 'learning curve' for laparoscopy-assisted distal gastrectomy (LADG) with systemic lymphadenectomy for early gastric cancer. METHODS: The data of 90 consecutive patients with early gastric cancer who underwent LADG with systemic lymphadenectomy between April 2003 and November 2004 were reviewed. The 90 patients were divided into 9 sequential groups of 10 cases in each group and the average operative time of these 9 groups were determined. Other learning indicators, such as transfusion requirements, conversion rates to open surgery, postoperative complication, time to first flatus, and postoperative hospital stay, were evaluated. RESULTS: After the first 10 LADGs, the operative time reached its first plateau (230-240 min/operation) and then reached a second plateau (＜200 min/operation) for the final 30 cases. Although a significant improvement in the operative time was noted after the first 50 cases, there were no significant differences in transfusion requirements, conversion rates to open surgery, postoperative complications, time to first flatus, or postoperative hospital stay between the groups. CONCLUSION: Based on operative time analysis, this study show that experience of 50 cases of LADG with systemic lymphadenectomy for early gastric cancer is required to achieve optimum proficiency.展开更多
AIM:To investigate the clinical implications of lipid deposition in the pancreas(fatty pancreas). METHODS:The subjects of this study were 293 patients who had undergone abdominal computed tomography(CT)and sonography....AIM:To investigate the clinical implications of lipid deposition in the pancreas(fatty pancreas). METHODS:The subjects of this study were 293 patients who had undergone abdominal computed tomography(CT)and sonography.Fatty pancreas was diagnosed by sonographic findings and subdivided into mild,moderate,and severe fatty pancreas groups comparing to the retroperitoneal fat echogenicity. RESULTS:Fatty pancreas was associated with higher levels for visceral fat,waist circumference,aspartate aminotransferase(AST),alanine aminotransferase (ALT),total cholesterol,triglyceride,high density lipoprotein,free fatty acid,γ-GTP,insulin,and the homeostasis model assessment of insulin resistance (HOMA-IR)than the control group(P<0.05).HOMAIR,visceral fat,triglyceride,and ALT also tended to increase with the degree of fat deposition in the pancreas on sonography.In a multivariate logistic regression analysis,HOMA-IR,visceral fat,and ALT level were independently related to fatty pancreas after adjustment for age,body mass index,and lipid profile.The incidence of metabolic syndrome in the fatty pancreas group was significantly higher than in the control group,and the numbers of metabolic syndrome parameters were significantly higher in the fatty pancreas group(P<0.05).CONCLUSION:Sonographic fatty pancrease showed higher insulin resistance,visceral fat area,triglyceride, and ALT levels than normal pancreases.Fatty pancreas also showed a strong correlation with metabolic syndrome.展开更多
Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is...Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.展开更多
Sessile plants have developed a very delicate system to sense diverse kinds of endogenous developmental cues and exogenous environmental stimuli by using a simple Ca^2＋ ion. Calmodulin （CAM） is the predominant Ca^2...Sessile plants have developed a very delicate system to sense diverse kinds of endogenous developmental cues and exogenous environmental stimuli by using a simple Ca^2＋ ion. Calmodulin （CAM） is the predominant Ca^2＋ sensor and plays a crucial role in decoding the Ca^2＋ signatures into proper cellular responses in various cellular compartments in eukaryotes. A growing body of evidence points to the importance of Ca^2＋ and CaM in the regulation of the transcriptional process during plant responses to endogenous and exogenous stimuli. Here, we review recent progress in the identification of transcriptional regulators modulated by Ca^2＋ and CaM and in the assessment of their functional significance during plant signal transduction in response to biotic and abiotic stresses and developmental cues.展开更多
基金This work was supported by the project of Yunnan Innovation Team Project, the Hundreds Oversea Talents Program of Yunnan Province, the Top Talents Program of Yunnan Province （Grant 20080A009）, the Key Project of the Natural Science Foundation of Yunnan Province （201401 PC00397）, National Science Foundation of China （U0936603）, Key Project of Natural Science Foundation of Yunnan Province （2008CC016）, Frontier Grant of Kunming Institute of Botany, CAS （672705232515）, Top Talents Program of Yunnan Province （20080A009）, and Hundreds Talents Program of Chinese Academy of Sciences （CAS） （to L.G.）.
文摘Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
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Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma(CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA(HLCCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliaryenteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.
文摘Autoimmune chronic pancreatitis （AIP） is increasingly being recognized worldwidely, as knowledge of this entity builds up. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to the oral steroid therapy in contrast to ordinary chronic pancreatitis. Although many characteristic findings of AIP have been described, definite diagnostic criteria have not been fully established. In the year 2002, the Japan Pancreas Society published the diagnostic criteria of AIP and many clinicians around the world use these criteria for the diagnosis of AIP. The diagnostic criteria proposed by the Japan Pancreas Society, however, are not completely satisfactory and some groups use their own criteria in reporting AIP. This review discusses several potential limitations of current diagnostic criteria for this increasingly recognized condition. The manuscript is organized to emphasize the need for convening a consensus to develop improved diagnostic criteria.
基金financial support from several grants from the Office of Naval Research that allowed them to explore many applications of machine learning within materials science,including N00014-14-1-0098,N00014-16-1-2580,and N00014-10-1-0944.
文摘Propelled partly by the Materials Genome Initiative,and partly by the algorithmic developments and the resounding successes of data-driven efforts in other domains,informatics strategies are beginning to take shape within materials science.These approaches lead to surrogate machine learning models that enable rapid predictions based purely on past data rather than by direct experimentation or by computations/simulations in which fundamental equations are explicitly solved.Data-centric informatics methods are becoming useful to determine material properties that are hard to measure or compute using traditional methods—due to the cost,time or effort involved—but for which reliable data either already exists or can be generated for at least a subset of the critical cases.Predictions are typically interpolative,involving fingerprinting a material numerically first,and then following a mapping(established via a learning algorithm)between the fingerprint and the property of interest.Fingerprints,also referred to as“descriptors”,may be of many types and scales,as dictated by the application domain and needs.Predictions may also be extrapolative—extending into new materials spaces—provided prediction uncertainties are properly taken into account.This article attempts to provide an overview of some of the recent successful data-driven“materials informatics”strategies undertaken in the last decade,with particular emphasis on the fingerprint or descriptor choices.The review also identifies some challenges the community is facing and those that should be overcome in the near future.
文摘AIM:The prognosis of early gastric carcinoma (EGC) is generally excellent after surgery. The presence or absence of lymph node metastasis in EGC is an important prognostic factor. The survival and recurrence rates of node-negative EGC are much better than those of node-positive EGC. This study examined the factors related to lymph node metastasis in EGC to determine the appropriate treatment for EGC.METHODS: We investigated 748 patients with EGC who underwent surgery between January 1985 and December 1999 at the Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Hospital. Several clinicopathologic factors were investigated to analyze their relationship to lymph node metastasis: age, sex, tumor location, tumor size, gross type, histologic type, depth of invasion, extent of lymph node dissection, type of operation,and DNA ploidy.RESULTS:Lymph node metastases were found in 75 patients (10.0%). Univariate analysis showed that male sex, tumor size larger than 2.0cm, submucosal invasion of tumor, histologic differentiation, and DNA ploidy pattern were risk factors for regional lymph node metastasis in EGC patients. However, a multivariate analysis showed that three risk factors were associated with lymph node metastasis:large tumor size, undifferentiated histologic type and submucosal invasion. No statistical relationship was found for age, sex, tumor location, gross type, or DNA ploidy in multivariate analysis. The 5-year survival rate was 94.2% for those without lymph node metastasis and 87.3% for those with lymph node metastasis, and the difference was significant (P<0.05).CONCLUSION: In patients with EGC, the survival rate of patients with positive lymph nodes is significantly worse than that of patients with no lymph node metastasis. Therefore,a standard D2 lymphadenectomy should be performed in patients at high risk of lymph node metastasis: large tumor size, undifferentiated histologic type and submucosal invasion.
文摘AIM:To evaluate the efficacy of simple and extended cholecystectomy for mucosa(T1a) or muscularis(T1b) gallbladder(GB) cancer. METHODS:Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer were searched from MEDLINE(PubMed) ,Cochrane Library,EMBase,and CancerLit using the search terms of GB,cancer/carcinoma/tumor/neoplasm. RESULTS:Twenty-nine out of the 2312 potentially relevant publications met the eligibility criteria.Of the 1266 patients with GB cancer included in the publications,706(55.8%) and 560(44.2%) had T1a and T1b GB cancer,respectively.Simple cholecystectomy for T1a and T1b GB cancer was performed in 590(83.6%) and 375(67.0%) patients,respectively(P<0.01) .In most series,the treatment of choice was simple cholecystectomy for T1a GB cancer patients with a 5-year survival rate of 100%.Lymph node metastasis was detected in 10.9% of the T1b GB cancer patients and in 1.8%of the T1a GB cancer patients,respectively(P<0.01) .Eight patients(1.1%) with T1a GB cancer and 52 patients(9.3%) with T1b GB cancer died of recurrent GB cancer(P<0.01) . CONCLUSION:Simple cholecystectomy represents the adequate treatment of T1a GB cancer.There is no definite evidence that extended cholecystectomy is advantageous over simple cholecystectomy for T1b GB cancer.
基金Supported by the fund from the Korea Science and Engineering Foundation (Grant No. R01-2001-00098). Seung Oe Lim was supported by BK21 Research Fellowship from the Ministry of Education and Human Resources Development
文摘AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
基金Supported by The Industrial Core Technology Development Program funded by the Ministry of Knowledge Economy,No.10033183
文摘AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC surveillance were included in this study.Of the 168 patients,90(53.6%)had HCC including newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment.HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which were obtained during routine surveillance with a suspicion of HCC.AFP,AFP-L3 and PIVKA-Ⅱwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients,38(42.2%)patients had AFP<20 ng/mL,20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients,74(94.9%)patients had AFP<20 ng/mL.After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels(<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve(AUC)for HCC were 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-Ⅱand the combined markers,respectively.The combined AUC for three markers showed higher value than the AUCs of individual marker(P<0.05).AFP-L3 had higher AUC value than PIVKA-Ⅱfor HCC detection in entire patients(P =0.043).With combination of AFP-L3(cut-off>5%) and PIVKA-Ⅱ(cut-off>40 AU/L),the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patients with low AFP levels(<20 ng/mL),AUCs
基金the Research Institute of Veterinary Science,College of Veterinary Medieine,Seoul National University
文摘AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.
基金Supported by The Bisa Research Grant of Keimyung University in 2006
文摘AIM: To evaluate the prevalence of preoperative and postoperative malnutrition and the relationships between objective and subjective nutritional assessment of gastric cancer patients. METHODS: From October 2005 to July 2006, we studied 80 patients with no evidence of recurrent disease and no loss to follow-up after curative surgery for gastric cancer. In this group, 9 patients underwent total gastrectomy and 71 patients subtotal gastrectomy. At admission, 6 and 12 mo after surgery, the patients were assessed on the subjective global assessment (SGA), nutritional risk screening (NRS-2002), nutritional risk index (NRI) and by anthropometric measurements and laboratory data. Differences between the independent groups were assessed with the Student's t test and oneway analysis of variance. Spearman's rank correlation coefficients were calculated to evaluate the association between the scores and variables. RESULTS: The prevalence of malnutrition at admissionwas 31% by SGA and 43% by NRS-2002. At admission, the anthropometric data were lower in the malnourished groups defined by the SGA and NRS-2002 assessments, but did not differ between the groups using the NRI assessment. Body weight (BW), body mass index (BMI), triceps skin fold and midarm circumference were significantly reduced, but the total lymphocyte count, albumin, protein, cholesterol and serum iron levels did not decrease during the postoperative period. Six months after surgery, there was a good correlation between the nutritional assessment tools (SGA and NRS-2002) and the other nutritional measurement tools (BW, BMI, and anthropometric measurements). However, 12 mo after surgery, most patients who were assessed as malnourished by SGA and NRS-2002 had returned to their preoperative status, although their BW, BMI, and anthropometric measurements still indicated a malnourished status. CONCLUSION: A combination of objective and subjective assessments is needed for the early detection of the nutritional status in case of gastric cancer patients after gastre
文摘AIM: To evaluate the nature of the 'learning curve' for laparoscopy-assisted distal gastrectomy (LADG) with systemic lymphadenectomy for early gastric cancer. METHODS: The data of 90 consecutive patients with early gastric cancer who underwent LADG with systemic lymphadenectomy between April 2003 and November 2004 were reviewed. The 90 patients were divided into 9 sequential groups of 10 cases in each group and the average operative time of these 9 groups were determined. Other learning indicators, such as transfusion requirements, conversion rates to open surgery, postoperative complication, time to first flatus, and postoperative hospital stay, were evaluated. RESULTS: After the first 10 LADGs, the operative time reached its first plateau (230-240 min/operation) and then reached a second plateau (＜200 min/operation) for the final 30 cases. Although a significant improvement in the operative time was noted after the first 50 cases, there were no significant differences in transfusion requirements, conversion rates to open surgery, postoperative complications, time to first flatus, or postoperative hospital stay between the groups. CONCLUSION: Based on operative time analysis, this study show that experience of 50 cases of LADG with systemic lymphadenectomy for early gastric cancer is required to achieve optimum proficiency.
文摘AIM:To investigate the clinical implications of lipid deposition in the pancreas(fatty pancreas). METHODS:The subjects of this study were 293 patients who had undergone abdominal computed tomography(CT)and sonography.Fatty pancreas was diagnosed by sonographic findings and subdivided into mild,moderate,and severe fatty pancreas groups comparing to the retroperitoneal fat echogenicity. RESULTS:Fatty pancreas was associated with higher levels for visceral fat,waist circumference,aspartate aminotransferase(AST),alanine aminotransferase (ALT),total cholesterol,triglyceride,high density lipoprotein,free fatty acid,γ-GTP,insulin,and the homeostasis model assessment of insulin resistance (HOMA-IR)than the control group(P<0.05).HOMAIR,visceral fat,triglyceride,and ALT also tended to increase with the degree of fat deposition in the pancreas on sonography.In a multivariate logistic regression analysis,HOMA-IR,visceral fat,and ALT level were independently related to fatty pancreas after adjustment for age,body mass index,and lipid profile.The incidence of metabolic syndrome in the fatty pancreas group was significantly higher than in the control group,and the numbers of metabolic syndrome parameters were significantly higher in the fatty pancreas group(P<0.05).CONCLUSION:Sonographic fatty pancrease showed higher insulin resistance,visceral fat area,triglyceride, and ALT levels than normal pancreases.Fatty pancreas also showed a strong correlation with metabolic syndrome.
文摘Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.
文摘Sessile plants have developed a very delicate system to sense diverse kinds of endogenous developmental cues and exogenous environmental stimuli by using a simple Ca^2＋ ion. Calmodulin （CAM） is the predominant Ca^2＋ sensor and plays a crucial role in decoding the Ca^2＋ signatures into proper cellular responses in various cellular compartments in eukaryotes. A growing body of evidence points to the importance of Ca^2＋ and CaM in the regulation of the transcriptional process during plant responses to endogenous and exogenous stimuli. Here, we review recent progress in the identification of transcriptional regulators modulated by Ca^2＋ and CaM and in the assessment of their functional significance during plant signal transduction in response to biotic and abiotic stresses and developmental cues.
