AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mi...AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR展开更多
AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prosp...AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both展开更多
Osteoporosis is a common bone disease characterized by reduced bone and increased risk of fracture. In postmenopausal women, osteoporosis results from bone loss attributable to estrogen deficiency. Osteoclast differen...Osteoporosis is a common bone disease characterized by reduced bone and increased risk of fracture. In postmenopausal women, osteoporosis results from bone loss attributable to estrogen deficiency. Osteoclast differentiation and activation is mediated by receptor activator of nuclear factor-κB ligand(RANKL), its receptor receptor activator of nuclear factor-κB(RANK), and a decoy receptor for RANKL, osteoprotegerin(OPG). The OPG/RANKL/RANK system plays a pivotal role in osteoclast biology. Currently, a fully human antiRANKL monoclonal antibody named denosumab is being clinically used for the treatment of osteoporosis and cancer-related bone disorders. This review describes recent advances in RANKL-related research, a story from bench to bedside. First, the discovery of the key factors, OPG/RANKL/RANK, revealed the molecular mechanism of osteoclastogenesis. Second, we established three animal models:(1) a novel and rapid bone loss model by administration of glutathione-S transferase-RANKL fusion protein to mice;(2) a novel mouse model of hypercalcemia with anorexia by overexpression of soluble RANKL using an adenovirus vector; and(3) a novel mouse model of osteopetrosis by administration of a denosumab-like anti-mouse RANKL neutralizing monoclonal antibody. Lastly, anti-human RANKL monoclonal antibody has been successfully applied to the treatment of osteoporosis and cancer-related bone disorders in many countries. This is a real example of applying basic science to clinical practice.展开更多
AIM：To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C （CHC）.METHODS： Two hundred and thirty-seven patients wit...AIM：To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C （CHC）.METHODS： Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group （stage 0）. Twentyfive patients with sustained virological response （SVR） to interferon （IFN） therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness （LS） was performed by elastography.RESISTS： Medians （50% levels） of LS were 4.1 （3.5-4.9）, 6.3 （4.8-8.5）, 8.8 （6.8-12.0）, 14.6 （10.5-18.6）, and 22.2 （15.4-28.0）, respectively, in the fibrosis stages 0-4 （P 〈 0.001）. LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 （3.5-5.6）, 5.2 （4.4-6.8）, 6.8 （6.1-7.6）, and 6.1 （3.6-7.9）, respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide.CONCLUSION： LS correlated well with the histological stage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.展开更多
Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding compl...Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.展开更多
Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations...Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.展开更多
Currently, air pollution in Beijing has become a complex problem with two types of source pollutants： coal smoke and photochemical smog. Furthermore the maximum hourly mean concentration of O3 increases continuously,...Currently, air pollution in Beijing has become a complex problem with two types of source pollutants： coal smoke and photochemical smog. Furthermore the maximum hourly mean concentration of O3 increases continuously, especially in the summer. In order to simulate the photochemical reaction, develop an air quality simulation model and further improve the air quality of Beijing, a precisely temperature-controlled, indoor, smog chamber facility was designed and constructed at Tsinghua University. Characterization experiments have been carried out to acquire the basic parameters of the smog chamber, such as the wall loss rates of NO2, NO, O3, C3H6 and particulate matter （PM）, the intensity of ultraviolet （UV） light in the chamber, the reactivity of the purified air and the reproducibility of the experimental results. The results indicate that the facility performs up to specifications, and can meet the demands required for simulating the photochemical reaction. The effect of high primary contaminated PM on the formation of ozone and secondary organic aerosol （SOA） is under investigation.展开更多
AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serr...AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of muc展开更多
AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients ...AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients were classified into groups A （high GCIR, n = 101） and B （low GCIR, n = 90）. Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin （IL）-1β and IL-10 by PCRRFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS： Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach （mixed strain infection） were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR （P = 0.026 and 0.041, respectively）. IL- 1β＋3954_T/C （OR 2.1, 1.0-4.3）, IL-1RN^＊2/L （OR 3.5, 1.7-7.3） and IL-10-592_C/A （OR 3.2, 1.5-6.8） were individually associated with GC, and a combination of these cytokine polymorphisms with Hpylori vacA slb and ml further increased the risk （OR 7.2, 1.4-36.4）. CONCLUSION： Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of Hpylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.展开更多
Chronic kidney disease(CKD) patients receiving hemodialysis(HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of p...Chronic kidney disease(CKD) patients receiving hemodialysis(HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting(PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori(H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mildto-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.展开更多
BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancre...BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis.AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan.METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography(CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria.RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis(sensitivity,73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis(specificity, 62.5%). The area under the curve(AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade.CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.展开更多
In response to the ratio of available carbon （C） and nitrogen （N） nutrients, plants regulate their metabolism, growth, and development, a process called the C/N-nutrient response. However, the molecular basis of C...In response to the ratio of available carbon （C） and nitrogen （N） nutrients, plants regulate their metabolism, growth, and development, a process called the C/N-nutrient response. However, the molecular basis of C/N-nutrient signaling remains largely unclear. In this study, we identified three CALCINEURIN B-LIKE （CBL）-INTERACTING PROTEIN KINASES （CIPKs）, CIPK7, CIPK12, and CIPK14, as key regulators of the C/N-nutrient response during the post-germination growth in Arabidopsis. Single-knockout mutants of ClPK7, CIPK12, and CIPK14 showed hypersensitivity to high C/low N conditions, which was enhanced in their triple-knockout mutant, indicating that they play a negative role and at least partly function redun- dantly in the C/N-nutrient response. Moreover, these CIPKs were found to regulate the function of ATL31, a ubiquitin ligase involved in the C/N-nutrient response via the phosphorylation-dependent ubiquitination and proteasomal degradation of 14-3-3 proteins. CIPK7, CIPK12, and CIPK14 physically interacted with ATL31, and CIPK14, acting with CBL8, directly phosphorylated ATL31 in a Ca2＋-dependent manner. Further analyses showed that these CIPKs are required for ATL31 phosphorylation and stabilization, which medi- ates the degradation of 14-3-3 proteins in response to C/N-nutrient conditions. These findings provide new insights into C/N-nutrient signaling mediated by protein phosphorylationo展开更多
He and Ar isotopic compositions of megacrystal minerals from mantle xenoliths were measured by the technique of vacuum crushing extraction. The used samples were clinopyroxene, garnet and ilmenite in Cenozoic alkaline...He and Ar isotopic compositions of megacrystal minerals from mantle xenoliths were measured by the technique of vacuum crushing extraction. The used samples were clinopyroxene, garnet and ilmenite in Cenozoic alkaline basalts, which were from Nushan in Anhui Province and Yingfengling in Guangdong Province, respectively, and represented materials from the upper mantle in the continental margin of SE China. The results show 3He/4He ratios of 7.99 Ra to 8.58 Ra, consistent with the characteristic ratios of the MORB-type mantle. 40Ar/39Ar ratios vary from 313 to 909, suggesting a binary mixing between the MORB-type mantle and air argons. This may reflect the incorporation of the air argon absorbed in oceanic sediments into the mantle beneath the continental margin by subduction of oceanic plate. This study presents the first report that ilmenite megacrysts contain abundant fluid inclusions and noble gases in the mantle xenoliths.展开更多
This paper explores the conversion of raw seawater into drinking water from a religious water literacy (RWL) perspective. RWL is here defined as a socially just water literacy that is based on the respect for the dign...This paper explores the conversion of raw seawater into drinking water from a religious water literacy (RWL) perspective. RWL is here defined as a socially just water literacy that is based on the respect for the dignity of life of all living beings on the Earth. It discusses the importance of sustainable water sources and proposes purification methods. That is, the study aims to show a brief outline of the drinking water source (inland waters;mainly river water) and their purification technologies in recent times and today and propose the purification method (Freezing-Thawing-UV method) in case of taking the seawater as the source. And, it emphasizes the need for dialogue and cooperation between countries in order to proceed. The paper also discusses the relationship among religion, culture, and civilization, and highlights the similarities between Marx’s historical materialism and Umesao’s ecological view. It further discusses the importance of water purification technology, separation methods, and the potential for seawater as an energy source. The paper concludes by discussing the importance of dialogue, communication and understanding environmental decision-making. In order to carry them forward, it is convinced that citizens in the world are nothing but people with self-awareness of “Bodhisattvas of the Earth” as identities. As a result, the new findings that suggest the possibility of raw seawater into drinking water from a religious water literacy perspective through the lens of Kawakatsu’s maritime view have been obtained.展开更多
Carbazole-triazine dendrimers with a bulky terminal substituent were synthesized,and the thermally activated delayed fluorescence(TADF)property was investigated.Compared to unsubstituted carbazole dendrimers,dendrimer...Carbazole-triazine dendrimers with a bulky terminal substituent were synthesized,and the thermally activated delayed fluorescence(TADF)property was investigated.Compared to unsubstituted carbazole dendrimers,dendrimers with bulky terminal substituents showed comparable to better photoluminescence quantum yields(PLQY)in neat films.Phenylfluorene(PF)-substituted dendrimers showed the highest PLQY of 81%,a smallΔEst of 0.06 eV,and the fastest reverse intersystem crossing(RISC)rate of∼1×10^(5 )s^(−1) compared to other dendrimers.Phosphorescence measurements of dendrimers and dendrons(fragments)indicate that the close proximity of the triplet energy of phenylfluorene-substituted carbazole dendrons(^(3)LE)to that of phenylfluorene-substituted dendrimers(^(1)CT,^(3)CT)contributes to RISC promotion and improves TADF efficiency.Terminal modification fine-tunes the energy level and suppresses intermolecular interactions,and this study provides a guideline for designing efficient solution-processable and non-doped TADF materials.展开更多
This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underw...This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Rouxen-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers.展开更多
Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We ...Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We considered the pubic bone as a useful anatomical landmark to insert ureteral stents under fluoroscopic guidance. Thus, we categorized patients into three groups (proximal, middle, and distal groups) according to the position of the radiopaque tip of the push catheter when inserting the ureteral stent. Success was defined as a completely curled ureteral stent tail. We compared stent insertion success rates among the three groups. A multivariate analysis was performed to identify the factors affecting stent insertion success.Results: In men, 36 (63.2%) cases were deemed successful in the proximal group compared with 40 (80.0%) cases in the middle group and 12 (20.7%) cases in the distal group (p<0.001). In women, 26 (45.6%) cases were deemed successful in the proximal group compared with 54 (98.2%) cases in the middle group and 38 (76.0%) cases in the distal group (p<0.001). With the multivariate analysis, the stent pusher position was the most significant factor influencing successful stent insertion (men: odds ratio 6.00, 95% confidence interval 2.66-13.51, p<0.001;women: odds ratio 37.80, 95% confidence interval 4.94-289.22, p<0.001).Conclusion: The position of the stent pusher affects stent insertion success. The middle of the pubic symphysis is the optimal position for the radiopaque tip of the pusher when inserting ureteral stents under fluoroscopic guidance.展开更多
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan and from the Ministry of Health, Labor and Welfare of Japan
文摘AIM： To examine the effects of anti-high mobility group box 1 （HIGB1） neutralizing antibody in experimental severe acute pancreatitis （SAP）. METHODS： SAP was induced by creating closed duodenal loop inC3H/HeN mice. SAP was induced immediately after intrapedtoneal injection of anti-HMGB1 neutralizing antibody （200 pg）. Sevedty of pancreatitis, organ injury （liver, kidney and lung）, and bacterial translocation to pancreas was examined 12 h after induction of SAP. RESULTS： Anti-HHGB1 neutralizing antibody significantly improved the elevation of the serum amylase level and the histological alterations of pancreas and lung in SAR Anti-HHGB1 antibody also significantly ameliorated the elevations of serum alanine aminotransferase and creatinine in SAR However, anti-HHGB1 antibody worsened the bacterial translocation to pancreas. CONCLUSION： Blockade of HHGB1 attenuated the development of SAP and associated organ dysfunction, suggesting that HHGB1 may act as a key mediator for inflammatory response and organ injury in SAR
文摘AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both
文摘Osteoporosis is a common bone disease characterized by reduced bone and increased risk of fracture. In postmenopausal women, osteoporosis results from bone loss attributable to estrogen deficiency. Osteoclast differentiation and activation is mediated by receptor activator of nuclear factor-κB ligand(RANKL), its receptor receptor activator of nuclear factor-κB(RANK), and a decoy receptor for RANKL, osteoprotegerin(OPG). The OPG/RANKL/RANK system plays a pivotal role in osteoclast biology. Currently, a fully human antiRANKL monoclonal antibody named denosumab is being clinically used for the treatment of osteoporosis and cancer-related bone disorders. This review describes recent advances in RANKL-related research, a story from bench to bedside. First, the discovery of the key factors, OPG/RANKL/RANK, revealed the molecular mechanism of osteoclastogenesis. Second, we established three animal models:(1) a novel and rapid bone loss model by administration of glutathione-S transferase-RANKL fusion protein to mice;(2) a novel mouse model of hypercalcemia with anorexia by overexpression of soluble RANKL using an adenovirus vector; and(3) a novel mouse model of osteopetrosis by administration of a denosumab-like anti-mouse RANKL neutralizing monoclonal antibody. Lastly, anti-human RANKL monoclonal antibody has been successfully applied to the treatment of osteoporosis and cancer-related bone disorders in many countries. This is a real example of applying basic science to clinical practice.
文摘AIM：To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C （CHC）.METHODS： Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group （stage 0）. Twentyfive patients with sustained virological response （SVR） to interferon （IFN） therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness （LS） was performed by elastography.RESISTS： Medians （50% levels） of LS were 4.1 （3.5-4.9）, 6.3 （4.8-8.5）, 8.8 （6.8-12.0）, 14.6 （10.5-18.6）, and 22.2 （15.4-28.0）, respectively, in the fibrosis stages 0-4 （P 〈 0.001）. LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 （3.5-5.6）, 5.2 （4.4-6.8）, 6.8 （6.1-7.6）, and 6.1 （3.6-7.9）, respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type Ⅳ collagen, type Ⅳ collagen 7S, and type Ⅲ procollagen N peptide.CONCLUSION： LS correlated well with the histological stage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.
文摘Antiplatelet therapy is the standard of care for the secondary prevention of acute coronary syndrome and ischemic stroke, especially after coronary intervention. However, this therapy is associated with bleeding complications such as gastrointestinal bleeding, which is one of the most common life-threatening complications. Early endoscopy is recommended for most patients with acute upper gastrointestinal bleeding. After successful endoscopic hemostasis, immediate resumption of antiplatelet therapy with proton-pump inhibitors(PPIs) is recommended to prevent further ischemic events. PPI prophylaxis during antiplatelet therapy reduces the risk of upper gastrointestinal bleeding. The potential negative metabolic interaction between PPIs and clopidogrel is still unclear.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan
文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
文摘Currently, air pollution in Beijing has become a complex problem with two types of source pollutants： coal smoke and photochemical smog. Furthermore the maximum hourly mean concentration of O3 increases continuously, especially in the summer. In order to simulate the photochemical reaction, develop an air quality simulation model and further improve the air quality of Beijing, a precisely temperature-controlled, indoor, smog chamber facility was designed and constructed at Tsinghua University. Characterization experiments have been carried out to acquire the basic parameters of the smog chamber, such as the wall loss rates of NO2, NO, O3, C3H6 and particulate matter （PM）, the intensity of ultraviolet （UV） light in the chamber, the reactivity of the purified air and the reproducibility of the experimental results. The results indicate that the facility performs up to specifications, and can meet the demands required for simulating the photochemical reaction. The effect of high primary contaminated PM on the formation of ozone and secondary organic aerosol （SOA） is under investigation.
基金Supported by The Japanese Foundation for Research and Promotion of Endoscopy (JFE),in partThe Japanese Society of Gastroenterology (JSGE),to Watanabe Y+1 种基金The Princess Takamatsu Cancer Research FundA Generous Gift from both the JFE and the JSGE
文摘AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of muc
文摘AIM： To evaluate several risk factors for gastric cancer （GC） in Costa Rican regions with contrasting GC incidence rate （GCIR）. METHODS： According to GCIR, 191 Helicobacter pylori （H pylori）-positive patients were classified into groups A （high GCIR, n = 101） and B （low GCIR, n = 90）. Human DNA obtained from biopsy specimens was used in the determination of polymorphisms of the genes coding for interleukin （IL）-1β and IL-10 by PCRRFLP, and IL-1RN by PCR. H pylori DNA extractions obtained from clinical isolates of 83 patients were used for PCR-based genotyping of H pylori cagA, vacA and babA2. Human DNA from gastric biopsies of 52 GC patients was utilized for comparative purposes. RESULTS： Cytokine polymorphisms showed no association with GCIR variability. However, gastric atrophy, intestinal metaplasia and strains with different vacA genotypes in the same stomach （mixed strain infection） were more frequently found in group A than in group B, and cagA and vacA s1b were significantly associated with high GCIR （P = 0.026 and 0.041, respectively）. IL- 1β＋3954_T/C （OR 2.1, 1.0-4.3）, IL-1RN^＊2/L （OR 3.5, 1.7-7.3） and IL-10-592_C/A （OR 3.2, 1.5-6.8） were individually associated with GC, and a combination of these cytokine polymorphisms with Hpylori vacA slb and ml further increased the risk （OR 7.2, 1.4-36.4）. CONCLUSION： Although a proinflammatory cytokine genetic profile showed an increased risk for developing GC, the characteristics of Hpylori infection, in particular the status of cagA and vacA genotype distribution seemed to play a major role in GCIR variability in Costa Rica.
文摘Chronic kidney disease(CKD) patients receiving hemodialysis(HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting(PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori(H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mildto-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.
文摘BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide(TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis.AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan.METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography(CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria.RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis(sensitivity,73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis(specificity, 62.5%). The area under the curve(AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade.CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.
文摘In response to the ratio of available carbon （C） and nitrogen （N） nutrients, plants regulate their metabolism, growth, and development, a process called the C/N-nutrient response. However, the molecular basis of C/N-nutrient signaling remains largely unclear. In this study, we identified three CALCINEURIN B-LIKE （CBL）-INTERACTING PROTEIN KINASES （CIPKs）, CIPK7, CIPK12, and CIPK14, as key regulators of the C/N-nutrient response during the post-germination growth in Arabidopsis. Single-knockout mutants of ClPK7, CIPK12, and CIPK14 showed hypersensitivity to high C/low N conditions, which was enhanced in their triple-knockout mutant, indicating that they play a negative role and at least partly function redun- dantly in the C/N-nutrient response. Moreover, these CIPKs were found to regulate the function of ATL31, a ubiquitin ligase involved in the C/N-nutrient response via the phosphorylation-dependent ubiquitination and proteasomal degradation of 14-3-3 proteins. CIPK7, CIPK12, and CIPK14 physically interacted with ATL31, and CIPK14, acting with CBL8, directly phosphorylated ATL31 in a Ca2＋-dependent manner. Further analyses showed that these CIPKs are required for ATL31 phosphorylation and stabilization, which medi- ates the degradation of 14-3-3 proteins in response to C/N-nutrient conditions. These findings provide new insights into C/N-nutrient signaling mediated by protein phosphorylationo
基金supported by The National Natural Science Foundation of China(Grant Nos.49473175,49972062 and 40110104104).
文摘He and Ar isotopic compositions of megacrystal minerals from mantle xenoliths were measured by the technique of vacuum crushing extraction. The used samples were clinopyroxene, garnet and ilmenite in Cenozoic alkaline basalts, which were from Nushan in Anhui Province and Yingfengling in Guangdong Province, respectively, and represented materials from the upper mantle in the continental margin of SE China. The results show 3He/4He ratios of 7.99 Ra to 8.58 Ra, consistent with the characteristic ratios of the MORB-type mantle. 40Ar/39Ar ratios vary from 313 to 909, suggesting a binary mixing between the MORB-type mantle and air argons. This may reflect the incorporation of the air argon absorbed in oceanic sediments into the mantle beneath the continental margin by subduction of oceanic plate. This study presents the first report that ilmenite megacrysts contain abundant fluid inclusions and noble gases in the mantle xenoliths.
文摘This paper explores the conversion of raw seawater into drinking water from a religious water literacy (RWL) perspective. RWL is here defined as a socially just water literacy that is based on the respect for the dignity of life of all living beings on the Earth. It discusses the importance of sustainable water sources and proposes purification methods. That is, the study aims to show a brief outline of the drinking water source (inland waters;mainly river water) and their purification technologies in recent times and today and propose the purification method (Freezing-Thawing-UV method) in case of taking the seawater as the source. And, it emphasizes the need for dialogue and cooperation between countries in order to proceed. The paper also discusses the relationship among religion, culture, and civilization, and highlights the similarities between Marx’s historical materialism and Umesao’s ecological view. It further discusses the importance of water purification technology, separation methods, and the potential for seawater as an energy source. The paper concludes by discussing the importance of dialogue, communication and understanding environmental decision-making. In order to carry them forward, it is convinced that citizens in the world are nothing but people with self-awareness of “Bodhisattvas of the Earth” as identities. As a result, the new findings that suggest the possibility of raw seawater into drinking water from a religious water literacy perspective through the lens of Kawakatsu’s maritime view have been obtained.
基金Ministry of Education,Culture,Sports,Science and Technology,Grant/Award Number:ARIM/JPMXP1222JI0040Japan Society for the Promotion of Science,Grant/Award Numbers:KAKENHI/JP20KK0316,KAKENHI/JP21H05405,KAKENHI/JP22H02055,KAKENHI/JP23H02026,KAKENHI/JP23H03966,KAKENHI/JP20H02801。
文摘Carbazole-triazine dendrimers with a bulky terminal substituent were synthesized,and the thermally activated delayed fluorescence(TADF)property was investigated.Compared to unsubstituted carbazole dendrimers,dendrimers with bulky terminal substituents showed comparable to better photoluminescence quantum yields(PLQY)in neat films.Phenylfluorene(PF)-substituted dendrimers showed the highest PLQY of 81%,a smallΔEst of 0.06 eV,and the fastest reverse intersystem crossing(RISC)rate of∼1×10^(5 )s^(−1) compared to other dendrimers.Phosphorescence measurements of dendrimers and dendrons(fragments)indicate that the close proximity of the triplet energy of phenylfluorene-substituted carbazole dendrons(^(3)LE)to that of phenylfluorene-substituted dendrimers(^(1)CT,^(3)CT)contributes to RISC promotion and improves TADF efficiency.Terminal modification fine-tunes the energy level and suppresses intermolecular interactions,and this study provides a guideline for designing efficient solution-processable and non-doped TADF materials.
文摘This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Rouxen-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers.
文摘Objective: To examine factors to predict the optimal stent pusher position when inserting ureteral stents under fluoroscopy.Methods: We retrospectively reviewed 327 patients who underwent ureteral stent insertion. We considered the pubic bone as a useful anatomical landmark to insert ureteral stents under fluoroscopic guidance. Thus, we categorized patients into three groups (proximal, middle, and distal groups) according to the position of the radiopaque tip of the push catheter when inserting the ureteral stent. Success was defined as a completely curled ureteral stent tail. We compared stent insertion success rates among the three groups. A multivariate analysis was performed to identify the factors affecting stent insertion success.Results: In men, 36 (63.2%) cases were deemed successful in the proximal group compared with 40 (80.0%) cases in the middle group and 12 (20.7%) cases in the distal group (p<0.001). In women, 26 (45.6%) cases were deemed successful in the proximal group compared with 54 (98.2%) cases in the middle group and 38 (76.0%) cases in the distal group (p<0.001). With the multivariate analysis, the stent pusher position was the most significant factor influencing successful stent insertion (men: odds ratio 6.00, 95% confidence interval 2.66-13.51, p<0.001;women: odds ratio 37.80, 95% confidence interval 4.94-289.22, p<0.001).Conclusion: The position of the stent pusher affects stent insertion success. The middle of the pubic symphysis is the optimal position for the radiopaque tip of the pusher when inserting ureteral stents under fluoroscopic guidance.
