AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men ...AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.展开更多
Endoscopic submucosal dissection (ESD) is efficient for en bloc resection of large colorectal tumors. However, it has several technical difficulties, because the wall of the colon is thin and due to the winding nature...Endoscopic submucosal dissection (ESD) is efficient for en bloc resection of large colorectal tumors. However, it has several technical difficulties, because the wall of the colon is thin and due to the winding nature of the colon. The main complications of ESD comprise postoperative perforation and hemorrhage, similar to endoscopic mucosal resection (EMR). In particular, the rate of perforation in ESD is higher than that in EMR. Perforation of the colon can cause fatal peritonitis. Endoscopic clipping is reported to be an efficient therapy for perforation. Most cases with perforation are treated conservatively without urgent surgical intervention. However, the rate of postoperative hemorrhage in ESD is similar to that in EMR. Endoscopic therapy including endoscopic clipping is performed and most of the cases are treated conservatively without blood transfusion. In blood examination, some degree of inflammation is detected after ESD. For the standardization of ESD, it is most important to decrease the rate of perforation. Adopting a safe strategy for ESD and a suitable choice of knife are both important waysof preventing perforation. Moreover, appropriate training and increasing experience can improve the endoscopic technique and can decrease the rate of perforation. In this review, we describe safe procedures in ESD to prevent complications, the complications of ESD and their management.展开更多
Hepatocellular carcinoma （HCC） has a decisive influence on the prognosis of cirrhotic patients. Although α-fetoprotein （AFP） is a known and specific tumor maker for HCC, it is not suitable for the screening and s...Hepatocellular carcinoma （HCC） has a decisive influence on the prognosis of cirrhotic patients. Although α-fetoprotein （AFP） is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound （US） plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near realtime 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound （HIFU） was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.展开更多
Novel technologies have been necessary for improving fruit quality and productivity of citrus,labor-saving and orchard conservation on steep slope lands since aging of growers and decrease in the number of successors ...Novel technologies have been necessary for improving fruit quality and productivity of citrus,labor-saving and orchard conservation on steep slope lands since aging of growers and decrease in the number of successors is remarkable in mountain areas of southwestern Japan.The purpose of this paper is to introduce new technologies for improving citrus production that have been developed in recent years.A new fruit quality control system using drip irrigation and liquid fertilization technique combined with year-round plastic mulching was developed,and it enables high quality and stable citrus fruit production.Water and/or nutrient solution is automatically supplied through drip tubes that are laid under the mulching sheets to give adequate water stress,so as to improve sugar and acid content of fruit.A new transportation system for steep sloping citrus orchards,which is a combination of the monorail system and contour narrow paths,was suggested.A small walking cultivator was developed to explain the procedure of narrow path excavation.After introducing the narrow path,working hours for fertilizer and chemical herbicide application were reduced.Disaster prevention mapping of citrus orchards on slope lands was developed based on computer-aided seepage estimation and topographic data.The mapping can show zones of both ascending flow and descending flow of underground water during heavy rains in citrus orchards.The mapping is considered to be effective for the management of orchards and prevention of erosion on slope lands.展开更多
Acute obstructive suppurative cholangitis(AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography(ERCP) with s...Acute obstructive suppurative cholangitis(AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography(ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy(EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis.展开更多
AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) we...AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells.展开更多
AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patient...AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy （CRT）. METHODS： Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma （ESCC） who were undergoing preoperative CRT. RESULTS： Fourteen out of 40 ESCC patients showed a pathological complete response （CR） after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression （P 〈 0.05）. There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement （P = 0.0277 and P = 0.0095, respectively）. COX-2 expression and VEGF expression had significant prognostic value for disease-free survival （log-rank test; P = 0.0073 and P = 0.0341, respectively）, but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.展开更多
AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed e...AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.展开更多
Photosynthetic rate at the present atmospheric condition is limited by the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)because of its extremely low catalytic rate(kcat)and poor affinity f...Photosynthetic rate at the present atmospheric condition is limited by the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)because of its extremely low catalytic rate(kcat)and poor affinity for C02(Kc)and specificity for CO2(Sc/O).Rubisco in C4 plants generally shows higher k cat than that in C3 plants.Rubisco consists of eight large subunits and eight small subunits(RbcS).Previously,the chimeric incorporation of sorghum C4-type RbcS significantly increased the k cat of Rubisco in a C3 plant,rice.In this study,we knocked out rice RbcS multigene family using the CRISPR-Cas9 technology and completely replaced rice RbcS with sorghum RbcS in rice Rubisco.Obtained hybrid Rubisco showed almost C4 plant-like catalytic properties,i.e.,higher kcai,higher Kc,and lower Sc/O.Transgenic lines expressing the hybrid Rubisco accumulated reduced levels of Rubisco,whereas they showed slightly but significantly higher photosynthetic capacity and similar biomass production under high C 02 condition compared with wild-type rice.High-resolution crystal structural analysis of the wild-type Rubisco and hybrid Rubisco revealed the structural differences around the central pore of Rubisco and the pC-pD hairpin in RbcS.We propose that such differences,particularly in the pC-pD hairpin,may impact the flexibility of Rubisco catalytic site and change its catalytic properties.展开更多
AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric ar...AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.展开更多
With the aim of developing a new silicon refining process for production of solar grade silicon, a low-temperature refining technique referred to as ＂solidification refining of silicon with a Si-Al solvent at low tem...With the aim of developing a new silicon refining process for production of solar grade silicon, a low-temperature refining technique referred to as ＂solidification refining of silicon with a Si-Al solvent at low temperature＂ was studied. The refinability of silicon by the partial solidification from a Si-Al solvent was discussed with thermodynamic evaluation for the impurity segregation between solid silicon and a Si-Al solvent. Impurity segregation ratios were measured by using temperature gradient zone melting method for phosphorus and boron and were estimated by the thermodynamic calculation for metallic impurities. The excellent refinability was clarified from the extremely small segregation ratios of impurities at lower temperature and was also confirmed by the test refining with the partial solidification under the induction heating. Furthermore, silicon crystal growth was studied by directional solidification experiments of a Si-Al alloy, and was estimated to be diffusion controlled.展开更多
Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobu...Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.展开更多
AIM： To investigate the ability of a genetically altered embryonic stem （ES） cell line to generate insulin-producing cells in vitro following transfer of the Nkx2.2 gene.METHODS： Hamster Nkx2.2 genes were transfer...AIM： To investigate the ability of a genetically altered embryonic stem （ES） cell line to generate insulin-producing cells in vitro following transfer of the Nkx2.2 gene.METHODS： Hamster Nkx2.2 genes were transferred into mouse ES cells. Parental and Nkx2.2-transfected ES cells were initiated toward differentiation in embryoid body （EB） culture for 5 d and the resulting EBs were transferred to an attached culture system. Dithizone （DTZ）, a zincchelating agent known to selectively stain pancreatic beta cells, was used to detect insulin-producing cells.The outgrowths were incubated in DTZ solution （final concentration, 100μg/mL） for 15 rain before being examined microscopically. Gene expression of the endocrine pancreatic markers was also analyzed by RT-PCR. In addition, insulin production was determined immunohistochemically and its secretion was examined using an ELISA.RESULTS： DTZ-stained cellular clusters appeared after approximately 14 d in the culture of Nkx2.2-transfected ES cells （Nkx-ES cells）, which was as much as 2 wk earlier, than those in the culture of parental ES cells （wt-ES）. The frequency of DTZ-positive cells among total cultured cells on day 28 accounted for approximately 1.0% and 0.1% of the Nkx-ES- and wt-ES-derived EB outgrowths, respectively. The DTZ-positive cellular clusters were found to be immunoreactive to insulin, while the gene expressions of pancreatic-duodenal homeobox 1 （PDX1）, proinsulin 1 and proinsulin 2 were observed in the cultures that contained DTZ-positive cellular clusters.Insulin secretion was also confirmed by ELISA, whereas glucose-dependent secretion was not demonstrated.CONCLUSION： Nkx2.2-transfected ES cells showed an ability to differentiate into insulin-producing cells.展开更多
In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nu...In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nursing domain of basic nursing education. The purpose of this research is to examine the current status of bioethics education in the pediatric nursing domain of basic nursing education and explore the challenges perceived by the pediatric nursing faculty regarding bioethics education. The research method was a questionnaire survey on 100 randomly selected pediatric nursing faculty members from nursing universities across Japan. The results revealed that although bioethics issues were considered important, the emphasis remained primarily on addressing bioethics as part of nursing that respects children’s rights. Furthermore, respondents expressed difficulties regarding teaching methods and content related to bioethics.展开更多
Pancreatic cancer remains difficult to treat and has a high mortality rate.It is difficult to diagnose early mainly due to the lack of screening imaging modalities and specific biomarkers.Consequently,it is important ...Pancreatic cancer remains difficult to treat and has a high mortality rate.It is difficult to diagnose early mainly due to the lack of screening imaging modalities and specific biomarkers.Consequently,it is important to develop biomarkers that enable the detection of early stage tumors.Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses.These circulating RNAs are upregulated in the serum and plasma of cancer patients,including those with pancreatic cancer,compared with healthy controls.The majority of RNA biomarker studies have assessed circulating microRNAs(miRs),which are often tissue-specific.There are few reports of the tumorspecific upregulation of other types of small noncoding RNAs(ncRNAs),such as small nucleolar RNAs and Piwi-interacting RNAs.Long ncRNAs(IncRNAs),such as HOTAIR and MALAT1,in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers.Among tissuederived RNAs,some miRs show increased expression even in pre-cancerous tissues,and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma.Additionally,some miRs and IncRNAs have been reported with significant alterations in expression according to disease progression,and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established.Furthermore,recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers.Although much work is required to clarify the release mechanism,origin of tumor-specific circulating RNAs,and selectivity of carrier complexes,and technical advances must also be achieved,such as creating a consensus normalizat展开更多
Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone metabolism.Smad ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting ...Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone metabolism.Smad ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling.Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling,its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated.In the present study,we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism.Absorbable collagen sponges containing 3μg of recombinant human BMP2(rhBMP2)were implanted in the dorsal muscle pouches of wild type(WT)and Smurf2−/−mice.The rhBMP2-induced ectopic bone in Smurf2−/−mice showed greater bone mass,higher mineral apposition and bone formation rates,and greater osteoblast numbers than the ectopic bone in WT mice.In WT mice,the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone.In contrast,in Smurf2−/−mice,the induced bone consisted of a thick,continuous outer cortical shell and abundant inner trabecular bone.Additionally,rhBMP2-stimulated bone marrow stromal cells(BMSCs)from Smurf2−/−mice showed increased osteogenic differentiation.Smurf2 induced the ubiquitination of Smad1/5.BMP/Smad signaling was enhanced in Smurf2−/−BMSCs stimulated with rhBMP2,and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs.These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling,thereby identifying a new regulatory mechanism in bone metabolism.展开更多
Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been ...Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies.展开更多
Double-balloon enteroscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is an effective endoscopic approach for pancreatobiliary disorders in patients with altered gastrointestinal anatomy. End...Double-balloon enteroscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is an effective endoscopic approach for pancreatobiliary disorders in patients with altered gastrointestinal anatomy. Endoscopic interventions via DBE in these postoperative settings remain difficult because of the lack of an elevator and the use of extra-long ERCP accessories. Here, we report the usefulness of direct cholangioscopy with an ultra-slim gastroscope during DBE-assisted ERCP. Three patients with choledocholithiasis in postoperative settings (two patients after Billroth Ⅱ gastrojejunostomy and one patient after Roux-en-Y gastrojejunostomy) were treated. DBE was used to gain access to the papilla under carbon dioxide insufflation, and endoscopic sphincterotomy was performed with a conventional sphincterotome. For direct cholangioscopy, the enteroscope was exchanged for an ultra-slim gastroscope through an incision in the overtube, which was inserted directly into the bile duct. Direct cholangioscopy was used to extract retained bile duct stones in two cases and to confirm the complete clearance of stones in one case. Bile duct stones were eliminated with a 5-Fr basket catheter under direct visual control. No adverse events were noted in any of the three cases. Direct cholangioscopy with an ultra-slim gastroscope facilitates subsequent treatment within the bile duct. This procedure represents another potential option during DBE-assisted ERCP.展开更多
基金Supported by a grant from the Gifu Medical Association
文摘AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.
文摘Endoscopic submucosal dissection (ESD) is efficient for en bloc resection of large colorectal tumors. However, it has several technical difficulties, because the wall of the colon is thin and due to the winding nature of the colon. The main complications of ESD comprise postoperative perforation and hemorrhage, similar to endoscopic mucosal resection (EMR). In particular, the rate of perforation in ESD is higher than that in EMR. Perforation of the colon can cause fatal peritonitis. Endoscopic clipping is reported to be an efficient therapy for perforation. Most cases with perforation are treated conservatively without urgent surgical intervention. However, the rate of postoperative hemorrhage in ESD is similar to that in EMR. Endoscopic therapy including endoscopic clipping is performed and most of the cases are treated conservatively without blood transfusion. In blood examination, some degree of inflammation is detected after ESD. For the standardization of ESD, it is most important to decrease the rate of perforation. Adopting a safe strategy for ESD and a suitable choice of knife are both important waysof preventing perforation. Moreover, appropriate training and increasing experience can improve the endoscopic technique and can decrease the rate of perforation. In this review, we describe safe procedures in ESD to prevent complications, the complications of ESD and their management.
文摘Hepatocellular carcinoma （HCC） has a decisive influence on the prognosis of cirrhotic patients. Although α-fetoprotein （AFP） is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound （US） plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near realtime 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound （HIFU） was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.
文摘Novel technologies have been necessary for improving fruit quality and productivity of citrus,labor-saving and orchard conservation on steep slope lands since aging of growers and decrease in the number of successors is remarkable in mountain areas of southwestern Japan.The purpose of this paper is to introduce new technologies for improving citrus production that have been developed in recent years.A new fruit quality control system using drip irrigation and liquid fertilization technique combined with year-round plastic mulching was developed,and it enables high quality and stable citrus fruit production.Water and/or nutrient solution is automatically supplied through drip tubes that are laid under the mulching sheets to give adequate water stress,so as to improve sugar and acid content of fruit.A new transportation system for steep sloping citrus orchards,which is a combination of the monorail system and contour narrow paths,was suggested.A small walking cultivator was developed to explain the procedure of narrow path excavation.After introducing the narrow path,working hours for fertilizer and chemical herbicide application were reduced.Disaster prevention mapping of citrus orchards on slope lands was developed based on computer-aided seepage estimation and topographic data.The mapping can show zones of both ascending flow and descending flow of underground water during heavy rains in citrus orchards.The mapping is considered to be effective for the management of orchards and prevention of erosion on slope lands.
基金Supported by The Japan Society for the Promotion of Science and the Japanese Foundation for the Research and Promotion of Endoscopy,No.22590764 and 25461035
文摘Acute obstructive suppurative cholangitis(AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography(ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy(EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis.
文摘AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells.
文摘AIM： To investigate the relationship between cycloo- xygenase-2 （COX-2）, and vascular endothelial growth factor （VEGF）, and to determine the clinical significance of this relationship in esophageal cancer patients undergoing chemoradiotherapy （CRT）. METHODS： Immunohistochemical staining was used to evaluate COX-2 and VEGF expression in 40 patients with histologically-confirmed esophageal squamous carcinoma （ESCC） who were undergoing preoperative CRT. RESULTS： Fourteen out of 40 ESCC patients showed a pathological complete response （CR） after CRT. COX-2 and VEGF protein expressions were observed in the cytoplasm of 17 and 13 tumors, respectively, with null expression in 9 and 13 tumors, respectively. COX-2 expression was strongly correlated with VEGF expression （P 〈 0.05）. There were also significant associations between COX-2 expression, tumor recurrence, and lymph-node involvement （P = 0.0277 and P = 0.0095, respectively）. COX-2 expression and VEGF expression had significant prognostic value for disease-free survival （log-rank test; P = 0.0073 and P = 0.0341, respectively）, but not for overall survival, as assessed by univariate analysis. expression correlates with VEGF expression and might be a useful prognostic factor for more frequent tumor recurrence in ESCC patients undergoing neoadjuvant CRT. These findings support the use of anti-angiogenic COX-2 inhibitors in the treatment of ESCC.
基金Supported by grants from the Medical Research Fund of Hyogo Medical Association
文摘AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence ofCXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.
基金Grants-in-Aid for Scientific Research(17H05732,18K06094,19H04735,and 19K07582 to H.M.,24580021 and 15H04443 to H.F.)the Program for the Third-Phase R-GIRO。
文摘Photosynthetic rate at the present atmospheric condition is limited by the CO2-fixing enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)because of its extremely low catalytic rate(kcat)and poor affinity for C02(Kc)and specificity for CO2(Sc/O).Rubisco in C4 plants generally shows higher k cat than that in C3 plants.Rubisco consists of eight large subunits and eight small subunits(RbcS).Previously,the chimeric incorporation of sorghum C4-type RbcS significantly increased the k cat of Rubisco in a C3 plant,rice.In this study,we knocked out rice RbcS multigene family using the CRISPR-Cas9 technology and completely replaced rice RbcS with sorghum RbcS in rice Rubisco.Obtained hybrid Rubisco showed almost C4 plant-like catalytic properties,i.e.,higher kcai,higher Kc,and lower Sc/O.Transgenic lines expressing the hybrid Rubisco accumulated reduced levels of Rubisco,whereas they showed slightly but significantly higher photosynthetic capacity and similar biomass production under high C 02 condition compared with wild-type rice.High-resolution crystal structural analysis of the wild-type Rubisco and hybrid Rubisco revealed the structural differences around the central pore of Rubisco and the pC-pD hairpin in RbcS.We propose that such differences,particularly in the pC-pD hairpin,may impact the flexibility of Rubisco catalytic site and change its catalytic properties.
文摘AIM: To investigate the protective effect of lansoprazoleon ischemia and reperfusion (I/R)-induced rat intestinalmucosal injury in vivo.METHODS: Intestinal damage was induced by clampingboth the superior mesenteric artery and the celiac trunkfor 30 rain followed by reperfusion in male Sprague-Dawleyrats. lansoprazole was given to rats intraperitoneally 1 hbefore vascular clamping.RESULTS: Both the intraluminal hemoglobin and proteinlevels, as indices of mucosal damage, significantlyincreased in I/R-groups comparion with those of sham-operation groups. These increases in intraluminal hemoglobinand protein levels were significantly inhibited by the treatmentwith lansoprazole at a dose of 1 mg/kg. Small intestineexposed to I/R resulted in mucosal inflammation that wascharacterized by significant increases in thiobarbituric acid-reactive substances (TBARS), tissue-associatedmyeloperoxidase activity (MPO), and mucosal content of ratcytokine-induced neutrophil chemoattractant-1 (CINC-1).These increases in TBARS, MPO activities and CINC-1 contentin the intestinal mucosa after I/R were all inhibited bypretreatment with lansoprazole at a dose of 1 mg/kg.Furthermore, the CINC-1 mRNA expression was increasedduring intestinal I/R, and this increase in mRNA expressionwas inhibited by treatment with lansoprazole.CONCLUSION: Lansoprazole inhibits lipid peroxidation andreduces development of intestinal mucosal inflammationinduced by I/R in rats, suggesting that lansoprazole mayhave a therapeutic potential for I/R injury.
文摘With the aim of developing a new silicon refining process for production of solar grade silicon, a low-temperature refining technique referred to as ＂solidification refining of silicon with a Si-Al solvent at low temperature＂ was studied. The refinability of silicon by the partial solidification from a Si-Al solvent was discussed with thermodynamic evaluation for the impurity segregation between solid silicon and a Si-Al solvent. Impurity segregation ratios were measured by using temperature gradient zone melting method for phosphorus and boron and were estimated by the thermodynamic calculation for metallic impurities. The excellent refinability was clarified from the extremely small segregation ratios of impurities at lower temperature and was also confirmed by the test refining with the partial solidification under the induction heating. Furthermore, silicon crystal growth was studied by directional solidification experiments of a Si-Al alloy, and was estimated to be diffusion controlled.
文摘Solitary organ autoimmune disorders,formerly known as autoimmune pancreatitis(AIP),autoimmune sialadenitis,and autoimmune sclerosing cholangitis,are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease(IgG4-RD).AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody(Ab),accumulation of IgG4-expressing plasmacytes in the affected organs,and involvement of multiple organs.It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity.However,a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype.In addition,disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone.Therefore,it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD.Recently,we found that activation of plasmacytoid dendritic cells producing both interferon-α(IFN-α)and interleukin-33(IL-33)mediate murine AIP and human IgG4-RD.More importantly,we provided evidence that serum concentrations of IFN-αand IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders.In this Frontier article,we have summarized and discussed biomarkers of AIP and IgG4-RD,including Igs,autoAbs,and cytokines to provide useful information not only for clinicians but also for researchers.
文摘AIM： To investigate the ability of a genetically altered embryonic stem （ES） cell line to generate insulin-producing cells in vitro following transfer of the Nkx2.2 gene.METHODS： Hamster Nkx2.2 genes were transferred into mouse ES cells. Parental and Nkx2.2-transfected ES cells were initiated toward differentiation in embryoid body （EB） culture for 5 d and the resulting EBs were transferred to an attached culture system. Dithizone （DTZ）, a zincchelating agent known to selectively stain pancreatic beta cells, was used to detect insulin-producing cells.The outgrowths were incubated in DTZ solution （final concentration, 100μg/mL） for 15 rain before being examined microscopically. Gene expression of the endocrine pancreatic markers was also analyzed by RT-PCR. In addition, insulin production was determined immunohistochemically and its secretion was examined using an ELISA.RESULTS： DTZ-stained cellular clusters appeared after approximately 14 d in the culture of Nkx2.2-transfected ES cells （Nkx-ES cells）, which was as much as 2 wk earlier, than those in the culture of parental ES cells （wt-ES）. The frequency of DTZ-positive cells among total cultured cells on day 28 accounted for approximately 1.0% and 0.1% of the Nkx-ES- and wt-ES-derived EB outgrowths, respectively. The DTZ-positive cellular clusters were found to be immunoreactive to insulin, while the gene expressions of pancreatic-duodenal homeobox 1 （PDX1）, proinsulin 1 and proinsulin 2 were observed in the cultures that contained DTZ-positive cellular clusters.Insulin secretion was also confirmed by ELISA, whereas glucose-dependent secretion was not demonstrated.CONCLUSION： Nkx2.2-transfected ES cells showed an ability to differentiate into insulin-producing cells.
文摘In the field of pediatric nursing, in the perinatal period, numerous ethical issues arise alongside the advancement of medical technology. However, sufficient education on bioethics is not provided in the pediatric nursing domain of basic nursing education. The purpose of this research is to examine the current status of bioethics education in the pediatric nursing domain of basic nursing education and explore the challenges perceived by the pediatric nursing faculty regarding bioethics education. The research method was a questionnaire survey on 100 randomly selected pediatric nursing faculty members from nursing universities across Japan. The results revealed that although bioethics issues were considered important, the emphasis remained primarily on addressing bioethics as part of nursing that respects children’s rights. Furthermore, respondents expressed difficulties regarding teaching methods and content related to bioethics.
基金Supported by(in part)Grants-in-Aid from the Ministry of Education,Culture,Sports,Science and Technology,Japan,No.25293076,No.26860492,No.25860520 and No.24390183(to Otsuka M,Kishikawa T,Yoshikawa T and Koike K)Health Sciences Research Grants of The Ministry of Health,Labour and Welfare of Japan(to Koike K)+2 种基金Japanese Society of Gastroenterology,Okinaka Memorial Institute for Medical Research,and Honjo International Scholarship Foundation(to Otsuka M)Mishima Kaiun Memorial Foundation(to Ohno M)The Japan Prize Foundation and Tokyo Biomarker Innovation Research Association(to Kishikawa T)
文摘Pancreatic cancer remains difficult to treat and has a high mortality rate.It is difficult to diagnose early mainly due to the lack of screening imaging modalities and specific biomarkers.Consequently,it is important to develop biomarkers that enable the detection of early stage tumors.Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses.These circulating RNAs are upregulated in the serum and plasma of cancer patients,including those with pancreatic cancer,compared with healthy controls.The majority of RNA biomarker studies have assessed circulating microRNAs(miRs),which are often tissue-specific.There are few reports of the tumorspecific upregulation of other types of small noncoding RNAs(ncRNAs),such as small nucleolar RNAs and Piwi-interacting RNAs.Long ncRNAs(IncRNAs),such as HOTAIR and MALAT1,in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers.Among tissuederived RNAs,some miRs show increased expression even in pre-cancerous tissues,and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma.Additionally,some miRs and IncRNAs have been reported with significant alterations in expression according to disease progression,and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established.Furthermore,recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers.Although much work is required to clarify the release mechanism,origin of tumor-specific circulating RNAs,and selectivity of carrier complexes,and technical advances must also be achieved,such as creating a consensus normalizat
基金the JSPS Grant-in-Aid(C)grant number 17K11005the JSPS bilateral Joint Research Project grant number 1007397 to T.K.,MEXT/JSPS grant number JP19K12218 to T.S.,MEXT/JSPS grant number JP15H05952(“Resonance Bio”)to T.S.and T.I.,and MEXT/JSPS KAKENHI grant number JP16H06280(“Advanced Bioimaging Support”)。
文摘Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone metabolism.Smad ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling.Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling,its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated.In the present study,we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism.Absorbable collagen sponges containing 3μg of recombinant human BMP2(rhBMP2)were implanted in the dorsal muscle pouches of wild type(WT)and Smurf2−/−mice.The rhBMP2-induced ectopic bone in Smurf2−/−mice showed greater bone mass,higher mineral apposition and bone formation rates,and greater osteoblast numbers than the ectopic bone in WT mice.In WT mice,the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone.In contrast,in Smurf2−/−mice,the induced bone consisted of a thick,continuous outer cortical shell and abundant inner trabecular bone.Additionally,rhBMP2-stimulated bone marrow stromal cells(BMSCs)from Smurf2−/−mice showed increased osteogenic differentiation.Smurf2 induced the ubiquitination of Smad1/5.BMP/Smad signaling was enhanced in Smurf2−/−BMSCs stimulated with rhBMP2,and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs.These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling,thereby identifying a new regulatory mechanism in bone metabolism.
基金Supported by Grants-in-Aid from the Ministry of Education,Culture,Sports,Science and Technology,Japan,Nos.#25293076,#26860492,#25860520,and#24390183(to Otsuka M,Kishikawa T,Yoshikawa T and Koike K)by Health Sciences Research Grants of The Ministry of Health,Labour and Welfare of Japan(to Koike K)+1 种基金by grants from the Japanese Society of Gastroenterology,Okinaka Memorial Institute for Medical Research,and Honjo International Scholarship Foundation(to Otsuka M)by a grant from the Mishima Kaiun Memorial Foundation(to Ohno M)
文摘Micro RNAs(mi RNAs) are small,noncoding RNA molecules that regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncoding RNAs(lnc RNAs),another class of noncoding RNAs,have been determined to be also involved in transcription regulation and translation of target genes. Since deregulated expression levels or functions of miR NAs and lncR NAs in hepatocellular carcinoma(HCC) are frequently observed,clinical use of noncoding RNAs for novel diagnostic and therapeutic applications in the management of HCCs is highly and emergently e xpe c t e d. H e r e,we s ummar iz e r e c e nt f indings regarding deregulated mi RNAs and lnc RNAs for their potential clinical use as diagnostic and prognostic biomarkers of HCC. Specifically,we emphasize the deregulated expression levels of such noncoding RNAs in patients' sera as noninvasive biomarkers,a field that requires urgent improvement in the clinical surveillance of HCC. Since nucleotide-based strategies are being applied to clinical therapeutics,we further summarize clinical and preclinical trials using oligonucleotides involving the use of miR NAs and small interfering RNAs against HCC as novel therapeutics. Finally,we discuss current open questions,which must be clarified in the near future for realistic clinical applications of these new strategies.
文摘Double-balloon enteroscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is an effective endoscopic approach for pancreatobiliary disorders in patients with altered gastrointestinal anatomy. Endoscopic interventions via DBE in these postoperative settings remain difficult because of the lack of an elevator and the use of extra-long ERCP accessories. Here, we report the usefulness of direct cholangioscopy with an ultra-slim gastroscope during DBE-assisted ERCP. Three patients with choledocholithiasis in postoperative settings (two patients after Billroth Ⅱ gastrojejunostomy and one patient after Roux-en-Y gastrojejunostomy) were treated. DBE was used to gain access to the papilla under carbon dioxide insufflation, and endoscopic sphincterotomy was performed with a conventional sphincterotome. For direct cholangioscopy, the enteroscope was exchanged for an ultra-slim gastroscope through an incision in the overtube, which was inserted directly into the bile duct. Direct cholangioscopy was used to extract retained bile duct stones in two cases and to confirm the complete clearance of stones in one case. Bile duct stones were eliminated with a 5-Fr basket catheter under direct visual control. No adverse events were noted in any of the three cases. Direct cholangioscopy with an ultra-slim gastroscope facilitates subsequent treatment within the bile duct. This procedure represents another potential option during DBE-assisted ERCP.
