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Lenvatinib is a molecular-targeted agent with proven efficacy against hepatocellular carcinoma (HCC). We herein report a case of lenvatinib-associated Fournier gangrene. A 66-year-old man with advanced HCC presented with a high fever 4 weeks after switching to lenvatinib. He had severe erythema in the inguinal region, and abdominal computed tomography revealed extensive emphysema and scrotal abscesses. He was diagnosed with Fournier's gangrene, and his symptoms were successfully treated with local debridement and antimicrobial therapy. Although reports of lenvatinib-associated Fournier's gangrene are rare, they should be kept in mind, as the condition could progress rapidly and have poor outcomes.

This case report describes a patient who received hormone replacement therapy for secondary panhypopituitarism and subsequently developed diabetes. His physician decided to discontinue growth hormone (GH) replacement, which was previously deemed contraindicated. Following the diagnosis of fatty liver, the patient began to exhibit liver damage that progressed over the ensuing years, ultimately leading to cirrhosis. Common factors linked to cirrhosis were excluded, leading to the belief that GH deficiency over several years was the primary contributor to cirrhosis. Therefore, when treating patients with GH insufficiency and diabetes, clinicians should carefully consider the potential implications of GH replacement therapy.

Background/Aims: Numerous patients with ulcerative colitis (UC) become mentally unstable after experiencing a long-standing, physically painful life, and their long-term prognosis is poorer than that of those who are mentally stable. The current study aimed to evaluate serum biomarkers for predicting mental instability, which is challenging to objectively quantify. Methods: In total, 29 refractory UC patients newly treated with filgotinib underwent measurements of blood parameters associated with depression and a quantitative assessment of quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ) before and after treatment initiation with a 12-week interval. The data collected were examined in relation to each other. Results: The induction of remission treatment with filgotinib resulted in a clinical response rate of 89.7% and a clinical remission rate of 86.2%, with all eight extraintestinal manifestations resolved. No adverse events were observed. The serum zinc, high-density lipoprotein cholesterol, mature brain-derived neurotrophic factor (BDNF) concentrations, and the IBDQ psychiatric subscores increased significantly after treatment ( p < 0.05). Among these parameters, the mature-BDNF concentration and the IBDQ psychiatric subscore had the strongest positive correlation (R = 0.29, p = 0.08). Based on the logistic regression analysis, the mature-BDNF concentration (cutoff value: 20.5 ng/mL) had a sensitivity of 68.2%, specificity of 64.7%, and area under the curve of 0.67 for predicting psychiatric remission (subscore > 42.5) ( p = 0.04). Conclusions: While it is not easy to objectively predict the degree of psychiatric instability in patients with refractory UC, serum mature-BDNF levels can be a useful biomarker.

Background : Esophago-tracheobronchial fistula is a severe and often fatal complication in patients with advanced esophageal cancer, requiring prompt attention. The standard treatment involves the placement of a covered stent, which is relatively simple to perform and effectively seals the fistula. However, stent migration remains a common issue, highlighting the need for improved methods to prevent it. Case Presentation : We developed an innovative double stenting method approach utilizing two types of metal stents for cases where conventional stenting led to early stent dislodgement. This technique combines the benefits of uncovered and fully covered stents while minimizing their limitations. Furthermore, it is straightforward and adaptable. In two cases treated at our facility, this method successfully maintained complete fistula coverage until the patients' deaths, allowing them to consume food orally. Conclusions : Here, we describe the procedure in detail and discuss its significance, as our findings demonstrate the effectiveness of the double stenting technique.

The driving force of charge separation in the initial photovoltaic conversion process is theoretically investigated using ITIC, a nonfullerene acceptor material for organic photovoltaic devices. The density functional theory calculations show that the pseudo-Jahn-Teller (PJT) distortion of the S 1 excimer state induces spontaneous symmetry-breaking charge separation between the identical ITIC molecules even without the asymmetry of the surrounding environment. The strong PJT effect arises from the vibronic coupling between the pseudodegenerate S 1 and S 2 excited states with different irreducible representations (irreps), i.e., A u for S 1 and A g for S 2 , via the asymmetric vibrational mode with the A u irrep. The vibrational mode responsible for the spontaneous polarization, which is opposite in one ITIC monomer and the other, is the intramolecular C-C stretching vibration between the core IT and terminal IC units. These results suggest that controlling the PJT effect can improve the charge separation efficiency of the initial photovoltaic conversion process.

Background/aims: Although the World Health Organization declared the end of the public health emergency of international concern focusing on COVID-19 in May 2023, this bothersome virus continues to mutate, and the possibility of the emergence of mutant strains with high infectivity and severe disease rates has not disappeared. Thus, medical evidence must be accumulated, which is indispensable for protecting both patients under immunosuppressive treatments and the healthy population. This study examined SARS-CoV-2 vaccination responses in Japanese patients with autoimmune hepatitis (AIH) compared with healthy controls., Methods: This observational study registered 22 patients with histologically diagnosed AIH and 809 healthy controls in our hospital. Their Elecsys anti-SARS-CoV-2 spike antibody concentrations before and after vaccination were evaluated., Results: In this study, 72.7% and 18.2% of patients with AIH received steroids and azathioprine, respectively. Significant negative correlations were found between age and anti-SARS-CoV-2 spike antibody concentration in both groups; however, no sex differences were found. Although anti-SARS-CoV-2 spike antibody concentration was drastically augmented after the second vaccination ( p < 0.05) in the AIH group, these levels were significantly lower than those in the controls ( p < 0.05). In the age- and sex-matched analysis, the population ratio with a minimum response (≤100 binding antibody units (BAU/mL) was higher among patients with AIH than among controls 26 weeks after the second vaccination (44% vs. 7%, p < 0.05)., Conclusions: The anti-SARS-CoV-2 spike antibody concentration in AIH patients was significantly lower than that in controls after the second vaccination. Continued and widespread vaccination, particularly for patients requiring medical immunomodulation, is recommended.

Background/Aims: The search for noninvasive biomarkers that can efficiently estimate the extent of liver fibrosis progression is ongoing. Although Fibrosis-4 (FIB-4), the aspartate transaminase-to-platelet ratio index (APRI), and the Forns index have been reported as useful biomarkers, their investigation in autoimmune hepatitis (AIH) is limited. This study aimed to examine the usefulness of these serological indices and a newly developed index in predicting liver fibrosis progression in AIH. Methods: The study analyzed data from 190 patients diagnosed with AIH at our institution between 1990 and 2015. Their histological liver fibrosis progression and clinical long-term prognosis were evaluated retrospectively (cohort 1). In 90 patients, receiver operating characteristic (ROC) curves were compared to choose severe fibrosis cases with respect to existing indices (FIB-4, APRI, and Forns index) and the ferritin-zinc ratio (cohort 2). Results: In cohort 1, liver-related death and hepatocellular carcinoma rates were significantly higher in the severe (n = 27) than in the mild (n = 63) fibrosis group ( p = 0.0001 and 0.0191, respectively). In cohort 2, liver-related death in the severe fibrosis group was significantly frequent ( p = 0.0071), and their ferritin-zinc ratio was higher (median 2.41 vs. 0.62, p = 0.0011). ROC analyses were performed to compare the ability of the ferritin-zinc ratio, FIB-4, APRI, and the Forns index to predict severe and mild fibrosis. Accordingly, areas under the ROC were 0.732, 0.740, 0.721, and 0.729, respectively. Conclusions: The serum ferritin-zinc ratio can noninvasively predict liver fibrosis progression in AIH and be applied to predict long-term prognosis.

The use of organic radicals as building blocks is an effective approach to the production of open-shell coordination polymers (CPs). Two-dimensional (2D) CPs with honeycomb spin-lattices have attracted attention because of the unique electronic structures and physical properties afforded by their structural topology. However, radical-based CPs with honeycomb spin-lattices tend to have low chemical stability or poor crystallinity, and thus novel systems with high crystallinity and persistence are in strong demand. In this study, a novel triangular organic radical possessing three pyridyl groups, tris(3,5-dichloro-4-pyridyl)methyl radical (trisPyM) was prepared. It exhibits luminescence, high photostability, and a coordination ability, allowing formation of defined and persistent 2D CPs. Optical measurements confirmed the luminescence of trisPyM both in solution and in the solid state, with emission wavelengths, λ em , of 665 and 700 nm, respectively. trisPyM exhibits better chemical stability under photoirradiation than other luminescent radicals: the half-life of trisPyM in CH 2 Cl 2 was 10 000 times that of the tris(2,4,6-trichlorophenyl)methyl radical (TTM), a conventional luminescent radical. Complexation between trisPyM and Zn II (hfac) 2 yielded a single crystal of a 2D CP trisZn , possessing a honeycomb lattice with graphene-like spin topology. The coordination structure of trisZn is stable under evacuation at 60 °C. Moreover, trisZn exhibits luminescence at 79 K, with λ em = 695 nm, and is a rare example of a luminescent material among 2D radical-based CPs. Our results indicate that trisPyM may be a promising building block in the construction of a new class of 2D honeycomb CPs with novel properties, including luminescence.

Background: Chronic active Epstein-Barr virus infection (CAEBV) is defined as Epstein-Barr virus (EBV)-positive T/NK cell-related neoplasia, and its major clinical symptom is systemic inflammation presenting as infectious mononucleocytosis, whereas enteritis and diarrhea are minor clinical symptoms. The complex mixture of tumorigenic processes of EBV-positive cells and physical symptoms of systemic inflammatory disease constitutes the varied phenotypes of CAEBV. Herein, we describe a case of CAEBV that was initially diagnosed as Crohn's disease (CD) based on ileal ulcers and clinical symptoms of enteritis., Case Presentation: A 19-year-old woman complained of abdominal pain and fever. Blood examination showed normal blood cell counts without atypical lymphocyte but detected modest inflammation, hypoalbuminemia, slight liver dysfunction, and evidence of past EBV infection. The esophagogastroduodenoscopic findings were normal. However, colonoscopy revealed a few small ulcers in the terminal ileum. The jejunum and ileum also exhibited various forms of ulcers, exhibiting a cobblestone appearance, on capsule endoscopy. Based on these clinical findings, she was strongly suspected with CD. In the course of treatment by steroid and biologics for refractory enteritis, skin ulcers appeared about 50 months after her initial hospital visit. Immunohistology of her skin biopsy revealed proliferation of EBV-encoded small RNA (EBER)-positive atypical lymphocytes. We retrospectively assessed her previous ileal ulcer biopsy before treatment and found many EBER-positive lymphocytes. Blood EBV DNA was also positive. Therefore, she was diagnosed with extranodal NK/T-cell lymphoma with CAEBV-related enteritis rather than CD. She was treated with cyclosporine and prednisolone combination therapy for CAEBV-related systemic inflammation and chemotherapy for malignant lymphoma. Unfortunately, her disease continued to progress, leading to multiple organ failure and death at the age of 23 years., Conclusion: Clinicians need to remember the possibility of CAEBV as a differential diagnosis of refractory enteritis. Enteritis with intestinal ulcer is a rare symptom of CAEBV, and it is impossible to acquire a definitive diagnosis by ulcer morphology only. In cases where the possibility of CAEBV remains, tissue EBVR expression should be checked by in situ hybridization and blood EBV DNA.

We introduce a new augmented adaptation of the recently developed full coupled-cluster reduction (FCCR) with a second-order perturbative correction, abbreviated as FCCR(2). FCCR is a selected coupled-cluster expansion aimed at optimally reducing the excitation manifold and commutator expansions for high-rank excitations for obtaining accurate solutions of the electronic Schödinger equation in a size-extensive manner. The present FCCR(2) enables estimating the residual correlation of FCCR by the second-order perturbative correction E (2) from the complementary space of the FCCR projection manifold. The linear relationship between E (2) and the energy of FCCR(2) allows accurate estimates of near-exact energies for a wide variety of molecules with strong electron correlation. The potential of the method is demonstrated using challenging cases, the ground-state electronic energy of the benzene molecule in equilibrium and stretched geometries, and the isomerization energy of the transition metal complex [Cu(NH 3 )] 2 O 2 2+ .

We report on a quadratically convergent self-consistent field (QC-SCF) algorithm for the spin-projected unrestricted Hartree-Fock (SUHF) to mitigate the slow convergence of SUHF due to the presence of small eigenvalues in the orbital Hessian matrix. The new QC-SCF is robust and stable, allowing us to obtain the SUHF solutions very quickly. To demonstrate the applicability of the method, we present results for test systems with abundant non-dynamic correlation in comparison with the Roothaan repeated diagonalization, Pople extrapolation, and direct inversion of iterative subspace.

We implement Epstein-Nesbet perturbative corrections in the third-order for the initiator approximation of the configuration space quantum Monte Carlo. An improved sampling algorithm is proposed to address the stochastic noise of the corrections. The stochastic error for the perturbative corrections is considerably larger than that for the reference energy, and it fails to provide reasonable results unless a very long imaginary time integration is performed. The new sampling algorithm accumulates rejected walkers from multiple independent steps to cover a larger portion of the secondary space. The performance of the perturbative corrections is demonstrated for small molecules.

We herein report a 52-year-old man with multiple hypoechoic lesions in the body and tail of the pancreas detected during a screening ultrasound. Computed tomography (CT) showed no lesions other than those in the pancreas and peripheral lymph nodes. Contrast-enhanced CT identified hypovascular tumors in the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) demonstrated partial fibrosis and noncaseating granulomas with Langhans giant cells. To our knowledge, this is the first report of isolated pancreatic sarcoidosis diagnosed by EUS-FNA. Although pancreatic sarcoidosis is very rare, clinicians should be aware of this possibility in patients presenting with multiple hypovascular pancreatic tumors.

Aim: A novel jelly lactulose preparation (SK-1202) has been developed to improve compliance and reduce the elevation of blood glucose levels in diabetic patients. To compare the equivalence in the efficacy and safety of SK-1202 and an approved commercially available syrup preparation, we undertook a randomized multicenter cross-over study in hyperammonemia patients with liver cirrhosis who were taking lactulose., Methods: Forty-four patients were enrolled and took each preparation for 2 weeks. Efficacy was evaluated using the Number Connection Test, blood ammonia concentration, coma grade, and the flapping tremor grade. Safety was evaluated by the number of adverse events observed, vital signs, and laboratory tests. We also examined the acceptability of each preparation using questionnaires evaluating sweetness, aftertaste, ease of use, and preference of the preparations., Results: There were no differences in efficacy or safety between SK-1202 and the approved syrup preparation. With regard to the acceptability evaluation, given over 80% of the participants chose the SK-1202 preparation, it appears to be preferred by patients., Conclusions: It is expected that SK-1202 could represent a useful agent for patients with hepatic encephalopathy., (© 2018 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

A full coupled-cluster expansion suitable for sparse algebraic operations is developed by expanding the commutators of the Baker-Campbell-Hausdorff series explicitly for cluster operators in binary representations. A full coupled-cluster reduction that is capable of providing very accurate solutions of the many-body Schrödinger equation is then initiated employing screenings to the projection manifold and commutator operations. The projection manifold is iteratively updated through the single commutators ⟨κ|[H[over ^],T[over ^]]|0⟩ comprised of the primary clusters T[over ^]&#95;{λ} with a substantial contribution to the connectivity. The operation of the commutators is further reduced by introducing a correction, taking into account the so-called exclusion-principle-violating terms that provides a fast and near-variational convergence in many cases.

A 59-year-old man had been admitted to our hospital because of general malaise and abdominal fullness caused by massive ascites. He was diagnosed with alcoholic liver cirrhosis. Following the removal of ascites, he was referred to our department because of hematochezia. Emergent colonoscopy revealed the rupture of ascending colonic varices. Endoscopic variceal sclerotherapy using topical skin adhesive (75% Histoacryl) was performed to treat the colonic varices, which proved to be an effective treatment. Enhanced computerized tomography performed 5 days after the treatment of ascending colonic varices showed complete obstruction of the ileocolic varices without complication. It is important to consider the possibility of ectopic varices when a patient with liver cirrhosis reports bloody stool.

Hepatocellular carcinoma (HCC) is prone to recurrence following curative treatment. The purpose of the present study was to identify the predisposing factors of HCC recurrence following complete remission achieved by transarterial chemoembolization (TACE). A retrospective cohort study of 70 consecutive patients with HCC who underwent TACE as the initial treatment was conducted. The patients were divided into two groups according to their 1-year disease-free survival (DFS) status; the early recurrence group (ER group; n=32), with HCC recurring within 1 year of initial TACE; and the non-early recurrence group (NER group; n=38), who did not experience recurrence within 1 year. The parameters identified as significantly associated with DFS time on univariate analysis were aspartate aminotransferase (AST), alanine aminotransferase and α-fetoprotein levels, as well as the tumor number (P=0.003, P=0.027, P=0.002 and P=0.005, respectively). Multivariate analysis revealed that AST levels and tumor number were significantly associated with a shorter DFS period (P=0.009 and P=0.038, respectively). The Mantel-Haenszel test revealed a significant trend of decreasing DFS with increasing tumor number. Among the patients with HCC in the ER group, locoregional recurrence occurred more frequently in those who received TACE alone compared with those treated with TACE combined with radiofrequency ablation treatment. In summary, multinodularity of HCC is the most potent predictive factor for the recurrence of HCC within 1 year of initial TACE.

Aims: The efficacy of the vasopressin V2 receptor antagonist tolvaptan for difficult-to-treat cirrhotic ascites has recently been reported. However, its effect is variable among patients. This study aimed to clarify the predictive factors for obtaining a good response to tolvaptan in patients with difficult-to-treat ascites., Methods: Data were collected from 50 patients with liver cirrhosis having ascites (hepatitis B, n = 1; hepatitis C, n = 22; alcoholism, n = 11; and others, n = 16) after treatment with tolvaptan (3.75-7.5 mg/day) in addition to conventional diuretics. A follow-up assessment was carried out after 7-day tolvaptan treatment for all patients., Results: After an uneventful 7-day tolvaptan treatment, 18 patients (36.0%) lost more than 2 kg of their body weight (responders). Twenty-six patients (52.0%) showed an increase in urine volume (>300 mL) on day 2. Tolvaptan was also effective for patients with pleural effusion, portal vein thrombosis, and hepatocellular carcinoma. Basal blood urea nitrogen (BUN) levels, plasma renin activity, and aldosterone levels were significantly higher in the poor responders (<2 kg weight loss), who were considered to be in the relative vascular underfilling state, than in the responders. Basal BUN was extracted as a predictive factor of responsiveness by multivariate logistic regression analysis., Conclusions: Tolvaptan is useful and safe for the treatment of cirrhotic ascites. This report showed that BUN will predict the response of tolvaptan even when measured before tolvaptan treatment., (© 2016 The Japan Society of Hepatology.)

Excessive alcohol consumption is the most common cause of liver disease in the world. Chronic alcohol abuse leads to liver damage, liver inflammation, fibrosis and hepatocellular carcinoma. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, induce liver injury, which leads to the develo-pment of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as interleukin (IL)-6 and IL-10, are also associated with ALD. IL-6 improves ALD via the activation of STAT3 and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. Alcohol consumption promotes liver inflammation by incre-asing the translocation of gut-derived endotoxins to the portal circulation and by activating Kupffer cells through the lipopolysaccharide/Toll-like receptor 4 pathways. Oxidative stress and microflora products are also associated with ALD. Hepatic stellate cells play an important role in angiogenesis and liver fibrosis. Anti-angiogenic therapy has been found to be effective in the prevention of fibrosis. This suggests that blocking angiogenesis could be a promising therapeutic option for patients with advanced fibrosis. This review discusses the main pathways associated with liver inflammation and liver fibrosis as well as new therapeutic strategies.

We develop a geometrical optimization technique for the projection-after-variation (PAV) scheme of the recently refined projected Hartree-Fock (PHF) as a fast alternative to the variation-after-projection (VAP) approach for optimizing the structures of molecules/clusters in symmetry-adapted electronic states at the mean-field computational cost. PHF handles the nondynamic correlation effects by restoring the symmetry of a broken-symmetry single reference wavefunction and moreover enables a black-box treatment of orbital selections. Using HF orbitals instead of PHF orbitals, our approach saves the computational cost for the orbital optimization, avoiding the convergence problem that sometimes emerges in the VAP scheme. We show that PAV-PHF provides geometries comparable to those of the complete active space self-consistent field and VAP-PHF for the tested systems, namely, CH 2 , O 3 , and the [Cu 2 O 2 ] 2+ core, where nondynamic correlation is abundant. The proposed approach is useful for large systems mainly dominated by nondynamic correlation to find stable structures in many symmetry-adapted states.

Background: Inadequate response to ursodeoxycholic acid (UDCA) is associated with unfavorable outcomes in patients with primary biliary cholangitis (PBC). We aimed to identify surrogate markers for predicting long-term prognosis and biochemical response to UDCA in patients with PBC., Patients and Methods: In this single-center, retrospective study, 99 patients with PBC were classified into responders (n=53) and nonresponders (n=46) based on reductions in the γ-glutamyl transpeptidase levels at 1 year after initiating UDCA therapy (Nara criteria). We assessed whether the criteria for patentability by different countries are useful in predicting the prognosis of PBC. The accuracy of Scheuer and Nakanuma staging systems in predicting prognosis and treatment response was compared., Results: Nara definition had comparable utility to the Paris-II definition for selecting patients in whom UDCA monotherapy can be safely continued. Patients at Scheuer stage 1 had a significantly better prognosis than those at Scheuer stages 3 or 4 (P<0.05 and 0.0001, respectively). Patients at Nakanuma stage 4 had decreased survival compared with those at stage 1 (P<0.05). The proportion of responders to nonresponders was significantly higher in stages 1-3 PBC than in stage 4 PBC, according to both staging systems (P<0.05 for both). All patients with Scheuer stage 4 PBC were nonresponders, whereas only 28.6% (2/7) of those with Nakanuma stage 4 PBC were responders., Conclusion: The Scheuer staging system had greater utility in predicting long-term prognosis and UDCA response than the Nakanuma staging system.

Heyde syndrome describes the triad of aortic stenosis, acquired coagulopathy, and anemia due to bleeding from intestinal angiodysplasia. An 87-year-old man with iron deficiency anemia due to melena was admitted to our hospital. On examination, a systolic murmur was heard and echocardiography confirmed the presence of aortic stenosis. Esophagogastroduodenoscopy and colonoscopy were unremarkable. Capsule endoscopy and double balloon endoscopy revealed angiodysplasia throughout the small intestine. Laboratory investigations were significant for reduced plasma levels of high molecular weight von Willebrand factor multimers. On the basis of these findings, the patient was diagnosed with Heyde syndrome. The patient required frequent blood transfusions because of the intestinal bleeding, and underwent bioprosthetic aortic valve replacement. Twenty months after the operation, the gastrointestinal bleeding resolved and the patient no longer required blood transfusions. This is the first case report to describe an improvement in bleeding from angiodysplasia, one year after aortic valve replacement. It demonstrates the effective treatment of Heyde syndrome with aortic valve replacement, and highlights the importance of considering this differential diagnosis when evaluating patients presenting with repeated episodes of gastrointestinal bleeding and a concurrent systolic murmur.

Aim: To clarify whether Agtr1a methylation is involved in the development of nonalcoholic steatohepatitis (NASH)-related liver fibrosis in adult rats., Methods: A choline-deficient amino acid (CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis. Agtr1a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid (CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR. Hepatic stellate cells (HSCs) were isolated by collagenase digestion of the liver, followed by centrifugation of the crude cell suspension through a density gradient. Agtr1a methylation and its gene expression were also analyzed during the activation of HSCs., Results: The mean levels of Agtr1a methylation in the livers of CDAA-fed rats (11.5% and 18.6% at 8 and 12 wk, respectively) tended to be higher ( P = 0.06 and 0.09, respectively) than those in the livers of CSAA-fed rats (2.1% and 5.3% at 8 and 12 wk, respectively). Agtr1a was not methylated at all in quiescent HSCs, but was clearly methylated in activated HSCs (13.8%, P < 0.01). Interestingly, although Agtr1a was hypermethylated, the Agtr1a mRNA level increased up to 2.2-fold ( P < 0.05) in activated HSCs compared with that in quiescent HSCs, suggesting that Agtr1a methylation did not silence its expression but instead had the potential to upregulate its expression. These findings indicate that Agtr1a methylation and its upregulation of gene expression are associated with the development of NASH-related liver fibrosis., Conclusion: This is the first study to show that DNA methylation is potentially involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Gastric adenocarcinoma of fundic gland type [chief cell predominant type; (GA-FD-CCP)] is a rare gastric cancer variant arising from non-atrophic mucosa without Helicobacter pylori infection in the upper third portion of the stomach. GA-FD-CCP originates deep in the mucosal layer; hence, endoscopic lesion detection is often difficult at an early stage because of a minimal change in the mucosal surface. Here we present a 66-year-old man with an early stage of GA-FD-CCP showing characteristic endoscopic features. Esophagogastroduodenoscopy demonstrated a flat, slightly reddish area with black pigment dispersion and irregular micro-surface structure at the gastric fornix. The tumor was resected by endoscopic submucosal dissection and was pathologically diagnosed as GA-FD-CCP. Prussian blue staining revealed that the black pigment was a hemosiderin deposition. We reported a rare case of successfully treated GA-FD-CCP with black pigmentation that aided in early lesion detection., (© Acta Gastro-Enterologica Belgica.)

Photoluminescent diamino-substituted dinaphthopentalenes were synthesized successfully by the treatment of in situ prepared dinaphthocyclooctadiyne with lithium amide. This reaction involves a series of transformations including the nucleophilic addition of the lithium amide to a triple bond of the cyclooctadiyne moiety, transannulation, protonation of the resulting pentalene anion, and the nucleophilic substitution of the pentalene core with the lithium amide. In this procedure, a novel double amination step plays a key role. When the diamino-substituted dinaphthopentalenes were irradiated with UV light in toluene, fluorescence was observed at around 580 nm (ΦF < 0.03).

A theoretical design principle for enhancement of the quantum yield of light-emitting molecules is desired. For the establishment of the principle, we focused on the S1 states of blue-emitting anthracene derivatives: 2-methyl-9,10-di(2'-naphthyl)anthracene (MADN), 4,9,10-bis(3',5'-diphenylphenyl)anthracene (MAM), 9-(3',5'-diphenylphenyl)-10-(3'',5''-diphenylbiphenyl-4''-yl) anthracene (MAT), and 9,10-bis(3''',5'''-diphenylbiphenyl-4'-yl) anthracene (TAT) [Kim et al., J. Mater. Chem., 2008, 18, 3376]. The vibronic coupling constants and transition dipole moments were calculated and analyzed by using the concepts of vibronic coupling density (VCD) and transition dipole moment density (TDMD), respectively. It is found that the driving force of the internal conversions and vibrational relaxations originate mainly from the anthracenylene group. On the other hand, fluorescence enhancement results from the large torsional distortion of the side groups in the S1 state. The torsional distortion is caused by the diagonal vibronic coupling for the lowest-frequency mode in the Franck-Condon (FC) S1 state, which originates from a small portion of the electron density difference on the side groups. These findings lead to the following design principles for anthracene derivatives with a high quantum yield: (1) reduction in the electron density difference and overlap density between the S0 and S1 states in the anthracenylene group to suppress vibrational relaxation and radiationless transitions, respectively; (2) increase in the overlap density in the side group to enhance the fluorescence.

To provide data required for assessing the environmental health and safety risks of nanocomposites, abrasion-induced particle release from single-wall carbon nanotube (SWCNT)/polymer composites with or without thermal aging were evaluated by a shot blast system. First, overall composite weight loss (i.e., overall particle release) as a result of shot blasting was measured. Incorporating 5 wt% SWCNTs in polystyrene (PS) matrix was observed to reduce overall particle release by approximately 30% compared with pure PS. Heat treatment of the 5 wt% SWCNT/PS composites at 100°C for 10 days induced very slight change in overall particle release due to shot blasting. However, heat treatment at 350°C for 1 hr greatly deteriorated the abrasion resistance of the composites, enhancing overall particle release. Second, to verify the existence and form of SWCNTs released from the composites, released particles were observed by electron microscopy. Micron-sized particles with protruding SWCNTs and submicron-sized SWCNT clusters were observed in the particles released from the composites. Heat treatment of the composites at 350°C for 1 hr enhanced SWCNT release, which mainly formed clusters or rope-like bundles.

The vibronic coupling constants and reorganization energies of oligofluorenes OF(n) (n = 1-6) are calculated for their cationic states (hole transport). Those of oligothiophenes OT(2n) (n = 1-6) are also calculated for comparison. The vibronic coupling constants of OF(n) are smaller than those of OT(2n), and decrease with increasing n. For the elucidation of the small vibronic couplings of the oligofluorenes, the calculated vibronic coupling constants are analyzed on the basis of the concept of vibronic coupling density. The vibronic coupling density of OF(n) becomes small in the middle of the chain with increasing n because of the reduction in the electron-density difference between the neutral and cationic states. It is found that orbital relaxation plays a crucial role in the distribution of the electron-density difference. From the fragment molecular orbital analyses, the large orbital relaxation in OF(n) is found to originate from the small transfer integral between the fragment molecular orbitals. These findings led to a design principle for a carrier-transporting oligomer/polymer with small vibronic couplings, or small reorganization energy, as follows: the orbital interaction between the monomers should be small from the view of vibronic couplings.

A 77-year-old man with jaundice and a pancreatic head tumor was referred to our hospital in August 2006. The initial laboratory tests, computed tomography (CT) scan, magnetic resonance imaging (MRI), and endoscopic retrograde cholangiopancreatography suggested IgG4-related cholangitis and autoimmune pancreatitis. Oral prednisolone (PSL) was then administered. This treatment reduced the size of the pancreatic parenchyma, and the lower common bile duct (CBD) returned to its normal size. Thus, the oral PSL was gradually tapered to a maintenance dose. In February 2010, a CT scan and MRI showed segmental wall thickening and stenosis of the middle CBD, the progression of which led to extrahepatic obstructive jaundice. We suspected the emergence of a cholangiocarcinoma rather than the exacerbation of the IgG4-related sclerosing cholangitis because the stricture of the CBD was short and localized. Then, a percutaneous transhepatic biliary drainage was performed. The biopsy specimens obtained via the percutaneous transhepatic tract indicated an abnormal glandular formation, suggesting the presence of a moderate, well-differencated adenocarcinoma. The gross examination, microscopic examination and immunohistochemical analysis of the pancreaticoduodenectomy specimen suggested that a cholangiocarcinoma developed from the IgG4-related sclerosing cholangitis.

Branched-chain amino acids (BCAAs) reportedly inhibit the incidence of hepatocellular carcinoma (HCC) in patients with liver cirrhosis and obesity that is frequently associated with insulin resistance (IR). We previously reported that BCAAs exert a chemopreventive effect against HCC under IR conditions in rats. The aim of the present study was to examine the effect of BCAAs on the cumulative recurrence of HCC under IR conditions in the clinical practice. BCAA granules (Livact®, 12 g/day) were administered for 60 months following the local curative therapy for HCC, and several indices were determined. Treatment with BCAAs markedly inhibited the cumulative recurrence of HCC in patients with a high IR index [homeostasis model assessment (HOMA)-IR >2.5], but not in patients with HOMA-IR of ≤2.5. BCAA also improved the HOMA-IR, and the inhibitory effect was observed regardless of the serum albumin (Alb) levels. Similarly, BCAA treatment revealed a marked suppressive effect in patients with high fasting insulin [immune reactive insulin (IRI)>15 U/ml], but not with IRI of ≤15. BCAA treatment did not result in differences in HCC recurrence in patients with high and low glucose levels [fasting blood sugar (FBS)>110 and ≤110, respectively]. Furthermore, serum levels of the soluble form of vascular endothelial growth factor receptor 2 (sVEGFR2) were significantly inhibited along with these clinical effects. Our findings indicate that the inhibitory effect of BCAAs was achieved, at least partly, by coordinated effects of anti-angiogenesis and IR improvement. Since BCAAs are widely and safely used in clinical practice to treat patients with chronic liver diseases, BCAAs may represent a new strategy for secondary chemoprevention for HCC patients with IR. Moreover, our findings suggest that sVEGFR2 may be a useful clinical predictive marker for BCAA treatment under IR conditions.