Hypertension is a major determinant of health and is likely to have an effect on medical economics.The economic burden due to hypertension may be attributable not only to antihypertensive medication but also to the ve...Hypertension is a major determinant of health and is likely to have an effect on medical economics.The economic burden due to hypertension may be attributable not only to antihypertensive medication but also to the very expensive procedures required for cases of cardiovascular disease that occur more frequently in hypertensive compared with normotensive individuals.The objective of this article was to review articles published on prospective cohort studies that measured medical expenditure attributable to hypertension in community-dwelling populations in Japan.Many medical services in these populations are provided under the medical insurance system that requires the enrolment of all Japanese residents.Personal medical expenditure attributable to hypertension increases with worsening severity of the condition.Medical expenditure was increased further in cases of hypertensive patients who have another concomitant cardiovascular risk factor.In particular,hypertension,especially moderate-to-severe untreated hypertension,increases the risk of long-term hospitalization resulting in considerably higher medical expenditure,compared with non-hospitalized cases.Therefore,assuming that the use of antihypertensive medication is essential for hypertensive patients to prevent serious vascular diseases,a cost-effective highrisk strategy needs to be considered to reduce both ill-health and the economic burden due to hypertension.However,from a population perspective,medical expenditure attributable to hypertension comes mainly from pre-to-mild hypertension.Therefore,there is also a need to consider a population strategy that aims to shift the entire population to lower levels of blood pressure.展开更多
The gravest prognostic factor in early gastric cancer is lymph-node metastasis,with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treat...The gravest prognostic factor in early gastric cancer is lymph-node metastasis,with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treatment based on clinicpathological data. Thus, the tumor can be resected by endoscopic submucosal dissection. In the remaining third, surgical resection is necessary because of the possibility of nodal metastasis. Nevertheless, almost all patients can be cured by gastrectomy with D1+ lymph-node dissection. Laparoscopic or robotic gastrectomy has become widespread in East Asia because perioperative and oncological safety are similar to open surgery. However, after D1+ gastrectomy,functional symptoms may still result. Physicians must strive to minimize postgastrectomy symptoms and optimize long-term quality of life after this operation.Depending on the location and size of the primary lesion, preservation of the pylorus or cardia should be considered. In addition, the extent of lymph-node dissection can be individualized, and significant gastric-volume preservation can be achieved if sentinel node biopsy is used to distinguish node-negative patients.Though the surgical treatment for early gastric cancer may be less radical than in the past, the operative method itself seems to be still in transition.展开更多
Liver cirrhosis(LC)patients often have protein-energy malnutrition(PEM)and decreased physical activity.These conditions often lead to sarcopenia,which is the loss of skeletal muscle volume and increased muscle weaknes...Liver cirrhosis(LC)patients often have protein-energy malnutrition(PEM)and decreased physical activity.These conditions often lead to sarcopenia,which is the loss of skeletal muscle volume and increased muscle weakness.Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients.Nutrition and exercise management can improve PEM and sarcopenia in those patients.Nutrition management includes sufficient dietary intake and improved nutrient metabolism.With the current high prevalence of obesity,the number of obese LC patients has increased,and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients.Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients.Exercise management can increase skeletal muscle volume and strength and improve insulin resistance;however,nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients.The establishment of optimal exercise regimens for LC patients is currently required.In this review,we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.展开更多
Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and ...Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.展开更多
Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in para...Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.展开更多
Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatiti...Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.展开更多
Liver cirrhosis(LC)is a critical stage of chronic liver disease,including that caused by hepatitis C virus(HCV).In the absence of antiviral therapy,67%-91%of patients with HCV-related LC patients die of liver-related ...Liver cirrhosis(LC)is a critical stage of chronic liver disease,including that caused by hepatitis C virus(HCV).In the absence of antiviral therapy,67%-91%of patients with HCV-related LC patients die of liver-related causes,including hepatocellular carcinoma(HCC)and liver failure.Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin,which induces a sustained virological response(SVR)in 25%of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3.SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation,HCC,and mortality.More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy,with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50%of patients with HCV genotype 1 LC.Branched-chain amino acid supplementation,improvement of insulin resistance,and the use ofβ-blockers for portal hypertension may also reduce liverrelated complications.Here,we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.展开更多
AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endo...AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.展开更多
BACKGROUND The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography(MDCT)is still unclear.AIM To examine the diagnostic ability of MDCT more precisely by ...BACKGROUND The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography(MDCT)is still unclear.AIM To examine the diagnostic ability of MDCT more precisely by using data on intranodal pathological metastatic patterns.METHODS A total of 108 patients with advanced gastric cancer who underwent MDCT and curative gastrectomy at Kanazawa Medical University Hospital were enrolled in this study.The nodal sizes measured on computed tomography(CT)images were compared with the pathology results.A receiver-operating characteristic curve was constructed,from which the critical value(CV)was calculated by using the data of the first 69 patients retrospectively.By using the CV,sensitivity and specificity were calculated with prospectively collected data from 39 consecutive patients.This enabled a more precise one-to-one correspondence of lymph nodes between CT and pathological examination by using the size data of lymph node mapping.The intranodal pathological metastatic patterns were classified into the following four types:Small nodular,peripheral,large nodular,and diffuse.RESULTS Although all the cases were clinically suspected as having metastasis,81 had lymph node metastasis and 27 had no metastasis.The number of dissected,detected on CT,and metastatic nodes were,4241,897,and 801,respectively.The CV obtained from the receiver-operating characteristic was 7.6 mm for the long axis.The sensitivity was 91.4%and the specificity was 47.3%in the prospective phase.The large nodular and diffuse metastases were easy to diagnose becausemetastatic nodes with a large axis often exhibit these forms.CONCLUSION The ability of MDCT to contribute to a nodal diagnosis of advanced gastric cancer was examined prospectively with precise size data from node mapping,using a CV of 7.6 mm for the long axis that was calculated from the retrospectively collected data.The sensitivity was as high as 91%,and would be improved when referring to the enhanced patterns.However,its specificity was as low as 47%,because most of metastatic nodes in gastric cancer being small in size.The small nodular or peripheral type metastatic nodes were often small and considered difficult to diagnose.展开更多
BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back ta...BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back table(ex vivo).Even with lymphatic basin dissection,blood flow to the residual stomach can be preserved,and functionpreserving curative gastrectomy can be performed.The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated.We hypothesized that the oncological safety of sentinel node navigation surgery(SNNS)is not inferior to that of the guidelines.AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery.METHODS This was a retrospective cohort study.Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016.Patients from April 1999 to August 2008 were from the Department of Surgery II,Kanazawa University Hospital,and patients from August 2009 to March 2016 were from the Department of Surgical Oncology,Kanazawa Medical University Hospital.Patients who were diagnosed with gastric cancer,which was preoperatively diagnosed as superficial type(type 0),5 cm or less in length,clinical T1-2 and node negative,and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected.The overall survival(OS)and relapsefree survival(RFS)of these patients(SNNS group)were investigated.Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group.RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included.Pathological nodal metastasis was observed in 10.5%and 10.4%of the SNNS and control groups,respectively.The diagnostic abilities of sentinel node biopsy were 84%and 98.6%for sensitivity and accuracy,respectively.In the SNNS group,81.6%of patients underwent modified gastrectomy or functionpreserving curative gastrectomy with lymphatic basin dissection,in which the extent of nodal dissection was further reduced compared to the guidelines.The OS rate in the SNNS group was 96.8%at 5 years and was significantly better than 91.3%in the control group(P=0.0014).The RFS rates were equal in both groups.After propensity score matching,there were 231 patients in both groups,and the cumulative recurrence rate was 0.43%at 5 years in the SNNS group and 1.30%in the control group,which was not statistically different.CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.展开更多
INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the lat...INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the latter undergoes furtherdegradation and enters in TCA cycle,as shown inFigure 1.α-ketoadipic aciduria (Mckusick 245130)is a rare inborn error in the metabolism of α-KA展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD),in which abnormal lipid metabolism plays an important role in disease progression,has become a pandemic.Abnormal lipid metabolism,for example an increased fat intake...BACKGROUND Non-alcoholic fatty liver disease(NAFLD),in which abnormal lipid metabolism plays an important role in disease progression,has become a pandemic.Abnormal lipid metabolism,for example an increased fat intake,has been thought to be an initial factor leading to NAFLD.The small intestine is the main site of dietary lipid absorption.A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism,which is closely associated with the progression of NAFLD.We therefore hypothesized that,acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of lipid.AIM To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse model.METHODS 8-wk-old male C57BL/6J mice were fed a methionine-and choline-deficient diet for 3 wk.Then,all mice were separated randomly into acupoints group(AG)or non-acupoints group(NG)with high fat diet feeding.Needling treatment was performed at Zu san li,Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG mice.Finally,mice were anesthetized with an injection of ketamine-medetomidine and euthanized by exsanguination.RESULTS An apparent improvement of obesity was found in AG mice after acupuncture treatment.In AG mice,the body weight was much lower(22.6±1.2 g vs 28.1±1.0 g,P<0.005)in comparison to NG mice.The length of small intestine in AG mice was significantly shorter(26.7±2.3 cm vs 32.7±2.7 cm,P<0.005).A large amount of chyme was observed in the lumen of the AG small intestine.The expression of microsomal triglyceride transfer protein,apolipoprotein B and apolipoprotein C2 was downregulated.Triacylglycerols(TGs),total cholesterol and nonesterified fatty acid(NEFA)levels of the small intestinal tissue were significantly higher in AG mice,but the serum TGs and NEFA levels were reduced in AG mice.CONCLUSION These results indicate that acupuncture at Zu san li,Guan yuan and Yong quan suppressed lipid absorption by downregulating the expression of apolipoproteins in the small intestine.展开更多
Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-rela...Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti- inflammatory cytokine.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirr...Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.展开更多
Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also be...Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.展开更多
AIM:To clarify the association between a polymorphism-449 C>G(rs72696119) in 5'-UTR of NFKB1 with ulcerative colitis(UC).METHODS:The studied population comprised 639 subjects,including patients with UC(UC cases...AIM:To clarify the association between a polymorphism-449 C>G(rs72696119) in 5'-UTR of NFKB1 with ulcerative colitis(UC).METHODS:The studied population comprised 639 subjects,including patients with UC(UC cases,n = 174) and subjects without UC(controls,n = 465).We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS:The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%,respectively(P = 0.10).Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls(P = 0.017),and the GG homozygote was significantly associated with susceptibility to UC [odds ratio(OR),1.88;95%CI,1.13-3.14].In male subjects,the GG homozygote was associated with an increased risk for UC(OR,3.10;95%CI,1.47-6.54;P = 0.0053),whereas this association was not found in female subjects.In addition,the GG homozygote was significantly associated with the risk of non-continuous disease(OR,2.06;95%CI,1.12-3.79;P = 0.029),not having total colitis(OR,2.40;95%CI,1.09-3.80,P = 0.040),disease which developed before 20 years of age(OR,2.80;95%CI,1.07-7.32,P = 0.041),no hospitalization(OR,2.28;95%CI,1.29-4.05;P = 0.0090) and with a maximum of 8 or less on the UCDAI score(OR,2.45;95%CI,1.23-4.93;P = 0.022).CONCLUSION:Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC.This polymorphism influences the susceptibility to and pathophysiological features of UC.展开更多
BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT o...BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.展开更多
We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 s...We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type.展开更多
文摘Hypertension is a major determinant of health and is likely to have an effect on medical economics.The economic burden due to hypertension may be attributable not only to antihypertensive medication but also to the very expensive procedures required for cases of cardiovascular disease that occur more frequently in hypertensive compared with normotensive individuals.The objective of this article was to review articles published on prospective cohort studies that measured medical expenditure attributable to hypertension in community-dwelling populations in Japan.Many medical services in these populations are provided under the medical insurance system that requires the enrolment of all Japanese residents.Personal medical expenditure attributable to hypertension increases with worsening severity of the condition.Medical expenditure was increased further in cases of hypertensive patients who have another concomitant cardiovascular risk factor.In particular,hypertension,especially moderate-to-severe untreated hypertension,increases the risk of long-term hospitalization resulting in considerably higher medical expenditure,compared with non-hospitalized cases.Therefore,assuming that the use of antihypertensive medication is essential for hypertensive patients to prevent serious vascular diseases,a cost-effective highrisk strategy needs to be considered to reduce both ill-health and the economic burden due to hypertension.However,from a population perspective,medical expenditure attributable to hypertension comes mainly from pre-to-mild hypertension.Therefore,there is also a need to consider a population strategy that aims to shift the entire population to lower levels of blood pressure.
文摘The gravest prognostic factor in early gastric cancer is lymph-node metastasis,with an incidence of about 10% overall. About two-thirds of early gastric cancer patients can be diagnosed as node-negative prior to treatment based on clinicpathological data. Thus, the tumor can be resected by endoscopic submucosal dissection. In the remaining third, surgical resection is necessary because of the possibility of nodal metastasis. Nevertheless, almost all patients can be cured by gastrectomy with D1+ lymph-node dissection. Laparoscopic or robotic gastrectomy has become widespread in East Asia because perioperative and oncological safety are similar to open surgery. However, after D1+ gastrectomy,functional symptoms may still result. Physicians must strive to minimize postgastrectomy symptoms and optimize long-term quality of life after this operation.Depending on the location and size of the primary lesion, preservation of the pylorus or cardia should be considered. In addition, the extent of lymph-node dissection can be individualized, and significant gastric-volume preservation can be achieved if sentinel node biopsy is used to distinguish node-negative patients.Though the surgical treatment for early gastric cancer may be less radical than in the past, the operative method itself seems to be still in transition.
文摘Liver cirrhosis(LC)patients often have protein-energy malnutrition(PEM)and decreased physical activity.These conditions often lead to sarcopenia,which is the loss of skeletal muscle volume and increased muscle weakness.Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients.Nutrition and exercise management can improve PEM and sarcopenia in those patients.Nutrition management includes sufficient dietary intake and improved nutrient metabolism.With the current high prevalence of obesity,the number of obese LC patients has increased,and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients.Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients.Exercise management can increase skeletal muscle volume and strength and improve insulin resistance;however,nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients.The establishment of optimal exercise regimens for LC patients is currently required.In this review,we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients.
文摘Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.
基金Supported by A Grant from Novo Nordisk Pharma,to Kitada MA Grant-in-Aid for Scientific Research(C)to Kitada M,No.24591218+4 种基金A Grant for Promoted Research from Kanazawa Medical University to Kitada M,No.S2012-4A Grant-in-Aid for Scientific Research(B)to Koya D,No.25282028A Grant-in-Aid for Challenging Exploratory Research to Koya D,No.25670414A grant for Specially Promoted Research from Kanazawa Medical University to Koya D,No.SR2012-06the 4th Annual Research Award Grant of the Japanese Society of Anti-Aging Medicine,to Koya D
文摘Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c < 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression.
文摘Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.
文摘Liver cirrhosis(LC)is a critical stage of chronic liver disease,including that caused by hepatitis C virus(HCV).In the absence of antiviral therapy,67%-91%of patients with HCV-related LC patients die of liver-related causes,including hepatocellular carcinoma(HCC)and liver failure.Among the therapeutic strategies used to prevent liver-related complications in these patients is standard therapy with pegylated interferon and ribavirin,which induces a sustained virological response(SVR)in 25%of HCV genotype 1-infected patients and in 69% of patients infected with genotypes 2 and 3.SVR in patients with HCV-related LC has been associated with reduced rates of hepatic decompensation,HCC,and mortality.More recently developed direct-acting antiviral agents have shown excellent antiviral efficacy,with preliminary data demonstrating that an interferon-free regimen that includes these direct-acting antiviral agents achieved SVR in more than 50%of patients with HCV genotype 1 LC.Branched-chain amino acid supplementation,improvement of insulin resistance,and the use ofβ-blockers for portal hypertension may also reduce liverrelated complications.Here,we review advances in antiviral and adjunctive therapies for improved outcomes in patients with HCV-associated LC.
基金Supported by Grants from the Japan Society for the Promotion of Science,Grant-in-Aid for Scientific Research(B),No.22300264
文摘AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.
文摘BACKGROUND The reliability of preoperative nodal diagnosis of advanced gastric cancer by multi-detector spiral computed tomography(MDCT)is still unclear.AIM To examine the diagnostic ability of MDCT more precisely by using data on intranodal pathological metastatic patterns.METHODS A total of 108 patients with advanced gastric cancer who underwent MDCT and curative gastrectomy at Kanazawa Medical University Hospital were enrolled in this study.The nodal sizes measured on computed tomography(CT)images were compared with the pathology results.A receiver-operating characteristic curve was constructed,from which the critical value(CV)was calculated by using the data of the first 69 patients retrospectively.By using the CV,sensitivity and specificity were calculated with prospectively collected data from 39 consecutive patients.This enabled a more precise one-to-one correspondence of lymph nodes between CT and pathological examination by using the size data of lymph node mapping.The intranodal pathological metastatic patterns were classified into the following four types:Small nodular,peripheral,large nodular,and diffuse.RESULTS Although all the cases were clinically suspected as having metastasis,81 had lymph node metastasis and 27 had no metastasis.The number of dissected,detected on CT,and metastatic nodes were,4241,897,and 801,respectively.The CV obtained from the receiver-operating characteristic was 7.6 mm for the long axis.The sensitivity was 91.4%and the specificity was 47.3%in the prospective phase.The large nodular and diffuse metastases were easy to diagnose becausemetastatic nodes with a large axis often exhibit these forms.CONCLUSION The ability of MDCT to contribute to a nodal diagnosis of advanced gastric cancer was examined prospectively with precise size data from node mapping,using a CV of 7.6 mm for the long axis that was calculated from the retrospectively collected data.The sensitivity was as high as 91%,and would be improved when referring to the enhanced patterns.However,its specificity was as low as 47%,because most of metastatic nodes in gastric cancer being small in size.The small nodular or peripheral type metastatic nodes were often small and considered difficult to diagnose.
基金This study was approved by the ethics committee of Kanazawa University Hospital and Kanazawa Medical University(Trial Number R093,M288)ICG mapping was approved by the ethics committee of Kanazawa Medical University(Trial NumberM404).
文摘BACKGROUND Lymphatic basin dissection is a sentinel node biopsy method that is specific for gastric cancer.In this method,the dyed lymphatic system is dissected en bloc,and sentinel nodes are identified at the back table(ex vivo).Even with lymphatic basin dissection,blood flow to the residual stomach can be preserved,and functionpreserving curative gastrectomy can be performed.The oncological safety of function-preserving curative gastrectomy combined with lymphatic basin dissection has not yet been fully investigated.We hypothesized that the oncological safety of sentinel node navigation surgery(SNNS)is not inferior to that of the guidelines.AIM To investigate the life prognosis of SNNS for gastric cancer in comparison with guidelines surgery.METHODS This was a retrospective cohort study.Patients were selected from gastric cancer patients who underwent sentinel node biopsy from April 1999 to March 2016.Patients from April 1999 to August 2008 were from the Department of Surgery II,Kanazawa University Hospital,and patients from August 2009 to March 2016 were from the Department of Surgical Oncology,Kanazawa Medical University Hospital.Patients who were diagnosed with gastric cancer,which was preoperatively diagnosed as superficial type(type 0),5 cm or less in length,clinical T1-2 and node negative,and underwent various gastrectomies guided by sentinel node navigation were retrospectively collected.The overall survival(OS)and relapsefree survival(RFS)of these patients(SNNS group)were investigated.Patients with gastric cancer of the same stage and who underwent guidelines gastrectomy with standard nodal dissection were also selected as the control group.RESULTS A total of 239 patients in the SNNS group and 423 patients in the control group were included.Pathological nodal metastasis was observed in 10.5%and 10.4%of the SNNS and control groups,respectively.The diagnostic abilities of sentinel node biopsy were 84%and 98.6%for sensitivity and accuracy,respectively.In the SNNS group,81.6%of patients underwent modified gastrectomy or functionpreserving curative gastrectomy with lymphatic basin dissection,in which the extent of nodal dissection was further reduced compared to the guidelines.The OS rate in the SNNS group was 96.8%at 5 years and was significantly better than 91.3%in the control group(P=0.0014).The RFS rates were equal in both groups.After propensity score matching,there were 231 patients in both groups,and the cumulative recurrence rate was 0.43%at 5 years in the SNNS group and 1.30%in the control group,which was not statistically different.CONCLUSION The oncological safety of patients who undergo gastrectomy guided by sentinel node navigation is not inferior to that of the guidelines surgery.
基金the grant from the J.A.M.W.Ogyaa Donation Foundation (JODF)National Science Foundation for High-Technology Research Center of Kanazawa Medical University (H98-3).
文摘INTRODUCTIONα-ketoadipate(α-KA),an intermediate in thecatabolism of L-lysine,hydroxylysine,and L-tryptophan,undergoes oxidative deearboxylation toform glutaryl-CoA and then dehydrogenates to formcrotonyl-CoA,the latter undergoes furtherdegradation and enters in TCA cycle,as shown inFigure 1.α-ketoadipic aciduria (Mckusick 245130)is a rare inborn error in the metabolism of α-KA
基金the Grants-in-Aid for Scientific Research,No.19K16783the Ministry of Education,Culture,Sports,Science and Technology,Tokyo,Japan,No.20K07454 and No.20K17363Grant for Promoted Research from Kanazawa Medical University,No.S2018-6.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD),in which abnormal lipid metabolism plays an important role in disease progression,has become a pandemic.Abnormal lipid metabolism,for example an increased fat intake,has been thought to be an initial factor leading to NAFLD.The small intestine is the main site of dietary lipid absorption.A number of clinical trials have shown that acupuncture has positive effects in the regulation of lipid metabolism,which is closely associated with the progression of NAFLD.We therefore hypothesized that,acupuncture can improve the conditions of NAFLD by regulating intestinal absorption of lipid.AIM To study the role of acupuncture treatment in the improvement of metabolic syndrome secondary to NAFLD by mouse model.METHODS 8-wk-old male C57BL/6J mice were fed a methionine-and choline-deficient diet for 3 wk.Then,all mice were separated randomly into acupoints group(AG)or non-acupoints group(NG)with high fat diet feeding.Needling treatment was performed at Zu san li,Guan yuan and Yong quan acupoints as acupuncture treatment to AG mice while non-acupoints place to NG mice.Finally,mice were anesthetized with an injection of ketamine-medetomidine and euthanized by exsanguination.RESULTS An apparent improvement of obesity was found in AG mice after acupuncture treatment.In AG mice,the body weight was much lower(22.6±1.2 g vs 28.1±1.0 g,P<0.005)in comparison to NG mice.The length of small intestine in AG mice was significantly shorter(26.7±2.3 cm vs 32.7±2.7 cm,P<0.005).A large amount of chyme was observed in the lumen of the AG small intestine.The expression of microsomal triglyceride transfer protein,apolipoprotein B and apolipoprotein C2 was downregulated.Triacylglycerols(TGs),total cholesterol and nonesterified fatty acid(NEFA)levels of the small intestinal tissue were significantly higher in AG mice,but the serum TGs and NEFA levels were reduced in AG mice.CONCLUSION These results indicate that acupuncture at Zu san li,Guan yuan and Yong quan suppressed lipid absorption by downregulating the expression of apolipoproteins in the small intestine.
文摘Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti- inflammatory cytokine.
基金Supported by The Japan Society for the Promotion of Science(JSPS)KAKENHI Grant,No.19300254,22300264 and 25282029(Takeuchi M)Kanazawa Medical University,No.SR2012-04(Tsutsumi M)the Ministry of Education,Culture,Sports,Science,and Technology(MEXT),Regional Innovation Strategy Support Program(Takeuchi M)
文摘Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)synthesis.In our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.
基金Supported by The Japan Society for the Promotion of Science(JSPS)KAKENHI,Grant No.22300264 and No.25282029(to Takeuchi M)the Ministry of Education,Culture,Sports,Science+1 种基金Technology(MEXT),Regional Innovation Strategy Support Program(to Takeuchi M)Kanazawa Medical University,No.SR2012-04
文摘Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.
基金Supported by Grant for Specially Promoted Research from Kanazawa Medical University(SR2012-01)
文摘AIM:To clarify the association between a polymorphism-449 C>G(rs72696119) in 5'-UTR of NFKB1 with ulcerative colitis(UC).METHODS:The studied population comprised 639 subjects,including patients with UC(UC cases,n = 174) and subjects without UC(controls,n = 465).We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS:The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%,respectively(P = 0.10).Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls(P = 0.017),and the GG homozygote was significantly associated with susceptibility to UC [odds ratio(OR),1.88;95%CI,1.13-3.14].In male subjects,the GG homozygote was associated with an increased risk for UC(OR,3.10;95%CI,1.47-6.54;P = 0.0053),whereas this association was not found in female subjects.In addition,the GG homozygote was significantly associated with the risk of non-continuous disease(OR,2.06;95%CI,1.12-3.79;P = 0.029),not having total colitis(OR,2.40;95%CI,1.09-3.80,P = 0.040),disease which developed before 20 years of age(OR,2.80;95%CI,1.07-7.32,P = 0.041),no hospitalization(OR,2.28;95%CI,1.29-4.05;P = 0.0090) and with a maximum of 8 or less on the UCDAI score(OR,2.45;95%CI,1.23-4.93;P = 0.022).CONCLUSION:Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC.This polymorphism influences the susceptibility to and pathophysiological features of UC.
文摘BACKGROUND Solitary fibrous tumor(SFT)is a rare fibroblastic mesenchymal neoplasm that affects spindle cell soft tissues with broad-spectrum biological behavior;it is predominantly benign,and rarely metastasizes.SFT occurs mainly in the tissue structure of the serosa in the pleura and the thorax,and can be found throughout the body,though extra-thoracic localization,including the cephalic region,is uncommon.We reported the first case of intracranial malignant SFT metastasized to the chest wall.CASE SUMMARY An 81-year-old Japanese man was referred to our hospital due to progressive gait disturbance and appetite loss.His medical history included partial resection due to brain tumor,four times,and 50-Gray radiation therapy at another hospital,starting when he was 74 years old.An unenhanced head computed tomography(CT)scan revealed an 8 cm×5.1 cm×6.5 cm mixed-density mass at the left frontal lobe,accompanying a midline shift,and an unenhanced chest-abdomen CT scan revealed a 6 cm×4.1 cm×6.5 cm low-density mass in the left chest wall.A CT-guided percutaneous lung biopsy was performed,and the pathological findings were SFT corresponding to brain tumor.Finally,the correct diagnosis of his brain tumor in history of past illness revealed to be SFT,and the unremovable tumor,namely present brain lesions enlarged and metastasized to the chest wall.We established a definitive diagnosis of intracranial malignant SFT metastasized to the chest wall.We notified him and his family of the disease,and offered palliative care.He passed away on the 29 th hospital day.CONCLUSION This case suggests the need for careful,detailed examination,and careful followup when encountering patients presenting with a mass.
文摘We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type.