Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis.

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.

Association between equol and non-alcoholic fatty liver disease in Japanese women in their 50s and 60s.

BACKGROUND AND AIM: Equol is a metabolite of soy isoflavone and has estrogenic activity. The incidence of non-alcoholic fatty liver disease (NAFLD) increases after menopause in women, which is thought to result in a decrease in estrogen. This study aimed to evaluate the association between equol and NAFLD. METHODS: We evaluated 1185 women aged 50-69 years who underwent health check-ups at four health centers in Fukushima, Japan. Equol producers were defined by a urinary equol concentration of 1.0 µM or more. In addition to comparison between equol producers and non-producers, the association between equol and NAFLD was estimated using logistic regression analysis adjusting for fast walking and eating habits. RESULTS: Of the 1185 participants, 345 (29.1%) women were equol producers. The proportions of women who had NAFLD (34.8% vs 45.2%) were significantly lower in the equol-producing group than in the non-producing group. Multivariable logistic regression analysis showed that equol production was significantly associated with NAFLD (odds ratio = 0.66, 95% confidence interval: 0.51-0.86). CONCLUSIONS: Equol production was significantly associated with NAFLD in women in their 50s and 60s.

Long-term outcomes in patients with primary biliary cholangitis complicated with CREST syndrome.

Primary biliary cholangitis (PBC) is frequently associated with autoimmune disease. Although PBC complicated with CREST syndrome (PBC-CREST) has been reported, the long-term outcomes of the affected patients have not been fully investigated. Herein, the long-term outcomes of PBC-CREST were evaluated. Next, the GLOBE and UK-PBC scores were validated and compared between the PBC alone and PBC-CREST groups. A total of 302 patients who were diagnosed with PBC between December 1990 and August 2021 at Fukushima Medical University Hospital were included. The liver transplantation (LT)-free survival rates were compared between patients with PBC alone (n = 245) and those with PBC-CREST (n = 57). Moreover, 173 patients, excluding those with liver-related death/LT within 1 year after ursodeoxycholic acid administration, were divided into two subgroups (PBC alone (n = 147) and PBC-CREST (n = 26)), and the GLOBE and UK-PBC scores were compared between the subgroups. The survival rates without LT (3/5/10 years) were 92/87/80% for the PBC-alone group and 98/96/96% for the PBC-CREST group, with a significantly better prognosis in the PBC-CREST group (log-rank P = 0.0172). Multivariate analysis revealed that the presence of CREST syndrome is an independent protective factor for the presence of cirrhosis. The predicted 5/10/15-year risks of liver-related death or LT based on the UK-PBC score were significantly lower in the PBC-CREST group (2.4/7.6/13.2%) than in the PBC-alone group (4.8/11.8/18.8%) (P < 0.05). The predicted 3/5-year LT-free survival rates based on the GLOBE score were significantly higher in the PBC-CREST group (93/88%) than in the PBC-alone group (88/81%) (P < 0.05). Patients with PBC-CREST may have better long-term outcomes than those with PBC alone.

Association between sleep duration and a new onset of nonalcoholic fatty liver disease.

Objective A short sleep duration is associated with non-alcoholic fatty liver disease (NAFLD). However, the causal relationship between a short sleep duration and the onset of NAFLD remains unknown because of the lack of any longitudinal studies. Therefore, we evaluated the association between sleep duration and the onset of NAFLD. Methods We evaluated health checkup data for 1,862 NAFLD-free Japanese adults aged 33-86 years at baseline and followed those individuals for a median of 41 months. Hepatic steatosis was examined using ultrasonography (US). The Cox proportional hazards model was used to evaluate the association between sleep duration and NAFLD onset. Results Among the 1,862 participants, 483 (25.9%) developed NAFLD. The proportion of women who developed NAFLD was the highest in the group with a sleep duration of <6 hours and lowest in the group with a sleep duration of 7 to <8 hours. The multivariable-adjusted hazard ratio (95% confidence interval) for the onset of NAFLD in women with a sleep duration <6 hours compared with those with a sleep duration of 7 to <8 hours was 1.55 (1.09-2.20; p=0.02). Conclusions In women, a short sleep duration was independently associated with the onset of NAFLD, thus suggesting that an adequate sleep duration can be a promising preventive factor for the onset of NAFLD in women.

Lifestyle factors affecting new-onset nonalcoholic fatty liver disease.

Evidence for the influence of lifestyle factors on nonalcoholic fatty liver disease (NAFLD) onset is limited because the association between lifestyle factors and NAFLD has been reported mostly in cross-sectional studies. Our purpose was to elucidate which lifestyle factors are associated with NAFLD onset by performing a longitudinal study. This was a longitudinal study of 1,713 Japanese participants who underwent multiple health checkups from June 2013 to the end of March 2018 and were not diagnosed with NAFLD at the first health checkup at Watari Hospital in Fukushima, Japan. Baseline characteristics, including lifestyle factors, were compared among participants with and without NAFLD. Cox proportional hazards models were used to identify the association between lifestyle factors and NAFLD onset. Among the 1,713 participants, 420 (24.5 %) developed NAFLD during the observation period (median 47 months). There were significant differences in body mass index and hepatobiliary enzyme levels between participants with and without NAFLD. In Cox proportional hazards models, eating between meals (hazard ratio (HR): 2.08, 95 % confidence interval (CI): 1.25-3.45, p < 0.01) and eating fast (HR: 1.59, 95 % CI: 1.26-2.00, p < 0.01) were risk factors for NAFLD onset in men and women, respectively. Moreover, fast walking was a protective factor against NAFLD onset in women (HR: 0.76, 95 % CI: 0.60-0.96, p = 0.02). These findings could help to identify patients at risk and prevent future NAFLD onset.

Mixed high-grade serous and large cell neuroendocrine carcinoma arising from rectal endometriosis 11 years after hysterectomy.

The malignant gastrointestinal endometriosis transformation is represented by endometriosis-associated intestinal tumors. Endometrioid adenocarcinoma and clear cell adenocarcinoma are most common among the endometrial cancers of all organs. Only four cases of mixed serous carcinoma and large cell neuroendocrine carcinoma have been reported, and all these cases originated from the uterus. A 59-year-old woman with a month's history of bloody stools was admitted. She was stable until the hematochezia occurred but is 11 years post-hysterectomy. A circumferential type-3 advanced upper rectum tumor was seen on colonoscopy. Adenocarcinoma was revealed from the forceps biopsies of the type-3 tumor component. Computed tomography showed narrowed lumen with a thickened rectum wall, a continuing mass, and a component on the anorectal side. Swollen lymph nodes were observed around the rectum, but no distant metastatic lymph nodes or organs were found. To treat the lesion, rectal surgical resection with D3 lymph node dissection was performed. Histological examination revealed combined high-grade serous and large cell neuroendocrine carcinomas. Tumor was contiguous to the endometrium in the sub-serosa. Endometriosis was determined to be the origin of both carcinomas. Therefore, endometriosis-associated intestinal tumors should be included in the differential diagnosis when rectal tumors with cystic structures are found post-hysterectomy.

Retroperitoneal liposarcoma with pancreatic metastasis and gastric cancer: a case report.

On computed tomography scanning, a 63-year-old man with vomiting and anorexia was discovered to have a mass in the pancreatic body and a retroperitoneal mass extending to the right lobe of the liver. An esophagogastroduodenoscopy revealed an advanced gastric carcinoma in the middle gastric body, and a biopsy specimen revealed a poorly differentiated adenocarcinoma. The pancreatic and retroperitoneal masses were considered metastatic lesions of gastric cancer, and a biopsy was taken from the pancreatic lesion using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The histology of the EUS-FNA pancreatic specimen revealed atypical spindle-shaped cells and increased stromal collagen fibrosis, and liposarcoma was considered. Conversely, a percutaneous ultrasound-guided biopsy was taken for the retroperitoneal lesion, and the histology revealed that it was a dedifferentiated liposarcoma. On the basis of histopathological and imaging findings, the retroperitoneal liposarcoma was identified as the primary lesion, the pancreatic lesion as a metastasis of the primary liposarcoma, and the gastric carcinoma as an independent tumor. As far as we know, there have only been three reports of metastatic pancreatic liposarcoma diagnosed via EUS-FNA. In this case, the patient also had gastric cancer, and EUS-FNA was helpful in differentiating metastatic pancreatic tumors from gastric cancer.

Purification, crystallization and preliminary X-ray analysis of two hydrogen sulfide-producing enzymes from Fusobacterium nucleatum.

Hydrogen sulfide produced by oral bacteria is responsible for oral malodour. Two homologous hydrogen sulfide-producing enzymes, Fn1220 and Cdl, from Fusobacterium nucleatum (which actively produces hydrogen sulfide) were overproduced, purified and crystallized. X-ray diffraction data were collected from the crystals using a synchrotron-radiation source. The Fn1220 crystal belonged to tetragonal space group P4(1)2(1)2 or P4(3)2(1)2 (unit-cell parameters a=b=116.8, c=99.2 Å) and the Cdl crystal belonged to monoclinic space group P2(1) (unit-cell parameters a=84.9, b=70.9, c=87.6 Å, ß=90.3°).

Transjejunal endoscopic ultrasound-guided pancreatic drainage for pancreatic jejunostomy stricture using a forward-viewing echoendoscope in a patient with altered anatomy.

Pancreatic jejunostomy stricture (PJS) is one of the major late complications after pancreaticoduodenectomy. Endoscopic ultrasound-guided pancreatic drainage (EUS-PD) is considered a salvage treatment for symptomatic PJS after endoscopic retrograde pancreatography failure; however, the technical success rate of the endoscopic treatment of PJS remains unsatisfactory, mainly due to surgically altered anatomy. Herein, we describe a case of PJS successfully treated with transjejunal EUS-PD using a forward-viewing echoendoscope. A 62-year-old man who suffered from repetitive severe back pain due to PJS was referred to our hospital. Since transgastric EUS-PD was difficult, we attempted transjejunal EUS-PD using a forward-viewing echoendoscope. To facilitate scope insertion, we first straightened the afferent jejunal loop and placed a stiff guidewire. With this scheme, we successfully performed transjejunal EUS-PD and placed a 5-Fr plastic stent. In conclusion, this technique is useful for treating patients with PJS when transgastric EUS-PD is difficult.

Machine-learning prediction of self-care activity by grip strengths of both hands in poststroke hemiplegia.

To investigate the relationships between grip strengths and self-care activities in stroke patients using a non-linear support vector machine (SVM).Overall, 177 inpatients with poststroke hemiparesis were enrolled. Their grip strengths were measured using the Jamar dynamometer on the first day of rehabilitation training. Self-care activities were assessed by therapists using Functional Independence Measure (FIM), including items for eating, grooming, dressing the upper body, dressing the lower body, and bathing at the time of discharge. When each FIM item score was ≥6 points, the subject was considered independent. One thousand bootstrap grip strength datasets for each independence and dependence in self-care activities were generated from the actual grip strength. Thereafter, we randomly assigned the total bootstrap datasets to 90% training and 10% testing datasets and inputted the bootstrap training data into a non-linear SVM. After training, we used the SVM algorithm to predict a testing dataset for cross-validation. This validation procedure was repeated 10 times.The SVM with grip strengths more accurately predicted independence or dependence in self-care activities than the chance level (mean ±â€Šstandard deviation of accuracy rate: eating, 0.71 ±â€Š0.04, P < .0001; grooming, 0.77 ±â€Š0.03, P < .0001; upper-body dressing, 0.75 ±â€Š0.03, P < .0001; lower-body dressing, 0.72 ±â€Š0.05, P < .0001; bathing, 0.68 ±â€Š0.03, P < .0001).Non-linear SVM based on grip strengths can prospectively predict self-care activities.

Characterization of Interfacial Charge-Transfer Photoexcitation of Polychromium-Oxo-Electrodeposited TiO2 as an Earth-Abundant Photoanode for Water Oxidation Driven by Visible Light.

Polychromium-oxo-deposited TiO2 (CrIII x Oy /TiO2 ) electrodes were fabricated by a simple electrochemical technique by using different TiO2 basal electrodes (anatase, rutile, and mixed polymorphic phases P25) as earth-abundant photoanodes for visible-light-driven water oxidation. The high-resolution transmission electron microscopy (HR-TEM) observation illustrated that an CrIII x Oy layer with approximately 2-3 nm thickness was formed on the surface of the crystalline TiO2 particles. Upon visible-light irradiation of the electrodes, the photoanodic current based on water oxidation was generated at the CrIII x Oy /TiO2 electrodes. However, the wavelength (below 620 nm) for photocurrent generation at CrIII x Oy /TiO2 -rutile was longer than that (below 560 nm) at CrIII x Oy /TiO2 -P25 by 60 nm, which is in agreement with the difference (0.2 eV) in the conduction band (CB) edge energy between rutile and anatase TiO2 . This gives a quantitative account for the photocurrent generation based on interfacial charge transfer (IFCT) from Cr 3d of the deposited CrIII x Oy layer to the TiO2 CB. The photocurrent generated for CrIII x Oy /TiO2 -rutile was higher than that for CrIII x Oy /TiO2 -anatase, which is ascribed to 1) more effective CrIII x Oy deposition on the rutile particles, 2) a larger electrolyte/CrIII x Oy interface for water oxidation as a result of smaller rutile particles (ca. 30-40 nm) compared with larger P25 particles (ca. 40-80 nm), and 3) more effective use of visible light owing to the low energy IFCT transition of rutile.

Open pore architecture of an ordered mesoporous IrO2 thin film for highly efficient electrocatalytic water oxidation.

We report the first accessible channel-like open pore architecture of ordered 2D hexagonal mesoporous IrO2 films and its utilization as an efficient anode for electrocatalytic water oxidation. A well-ordered mesostructure of circa 7 nm pores were obtained by a facile one-pot soft-templating strategy, employing a [Ir(OH)6](2-) precursor stabilized by a triblock copolymer "Pluronic F127" as a pore-directing template. A mesoporous IrO2 film calcined at 400 °C (∼70 nm thick) affords a high surface area of 512 m(2) cm(-3) and 2 times higher O2 evolution during the electrocatalytic water oxidation relative to an untemplated IrO2 coating film.

Visible-light-driven water oxidation at a polychromium-oxo-electrodeposited TiO2 electrode as a new type of earth-abundant photoanode.

A polychromium-oxo-deposited TiO2 electrode was fabricated as an earth-abundant photoanode for visible-light-driven water oxidation by a simple electrochemical technique. The photoelectrocatalytic water oxidation could occur based on a specific interfacial charge transfer (IFCT) from a Cr(III) to the TiO2 conduction band.