BACKGROUND: Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD). METHODS: We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation. RESULTS: Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells. CONCLUSIONS Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals ; DNA, Mitochondrial/genetics* ; Humans ; Male ; DNA Copy Number Variations ; Female ; Fatty Liver/blood* ; Rats ; Middle Aged ; Longitudinal Studies ; Rats, Sprague-Dawley ; Adult ; Japan/epidemiology* ; Aged ; Biomarkers/blood* ; Hep G2 Cells ; Diet, High-Fat/adverse effects*

Objective: To investigate the effect on early mobilization in patients undergoing extra-corporeal membrane oxygenation (ECMO) and acute blood purification therapy in the intensive care unit (ICU). Methods: We conducted this multicenter retrospective cohort study by collecting data from six ICUs in Japan. Consecutive patients who were admitted to the ICU, aged ≥18 years, and received mechanical ventilation for >48 hours were eligible. The analyzed were divided into two groups: ECMO/blood purification or control group. Clinical outcomes; time to first mobilization, number of total ICU rehabilitations, mean and highest ICU mobility scale (IMS); and daily barrier changes were also investigated. Results: A total of 204 patients were included in the analysis, 43 in the ECMO/blood purification group and 161 in the control group. In comparison of clinical outcome, the ECMO/blood purification group had a significantly longer time to first mobilization: ECMO/blood purification group 6 vs. control group 4 (p=0.003), higher number of total ICU rehabilitations: 6 vs. 5 (p=0.042), lower mean: 0 vs. 1 (p=0.043) and highest IMS: 2 vs. 3 (p=0.039) during ICU stay. Circulatory factor were most frequently described as barriers to early mobilization on days 1 (51%), 2 (47%), and 3 (26%). On days 4 to 7, the most frequently described barrier was consciousness factors (21%, 16%, 19%, and 21%, respectively) Conclusion The results of this study comparing the ECMO/blood purification group and the untreated group in the ICU showed that the ECMO/blood purification group had significantly longer days to mobilization and significantly lower mean and highest IMS.

Background/Aims: Endoscopic ultrasound gallbladder drainage (EUS-GBD) is gaining attention as a treatment method for cholecystitis. However, only a few studies have assessed the outcomes of permanent stenting with EUS-GBD. Therefore, we evaluated the clinical outcomes of permanent stenting using EUS-GBD. Methods: This was a retrospective, single-center cohort study. The criteria for EUS-GBD at our institution are a high risk for surgery, inability to perform surgery owing to poor performance status, and inability to obtain consent for emergency surgery. EUS-GBD was performed using a 7-Fr double-pigtail plastic stent with a dilating device. The primary outcomes were the recurrence-free rate of cholecystitis and the late-stage complication-avoidance rate. Secondary outcomes were technical success, clinical success, and procedural adverse events. Results: A total of 41 patients were included in the analysis. The median follow-up period was 168 (range, 10–1,238) days. The recurrence-free and late-stage complication-avoidance rates during the follow-up period were 95% (38 cases) and 90% (36 cases), respectively. There were only two cases of cholecystitis recurrence during the study period. Conclusions EUS-GBD using double-pigtail plastic stent was safe and effective with few complications, even in the long term, in patients with acute cholecystitis.

Background: Remimazolam is a novel ultrashort-acting benzodiazepine that has recently become available for general anesthesia. However, the incidence of postoperative nausea and vomiting (PONV) associated with remimazolam remains unknown. In this propensity score-matched, retrospective, observational study, we compared the rates of PONV between remimazolam and propofol. Methods: In this retrospective observational study, propensity score-matching was performed to minimize selection bias. Patients who received total intravenous anesthesia with remimazolam or propofol at the Hamamatsu University Hospital between August 2020 and July 2021 were enrolled in the study. Data on patient demographics, anesthetic agents, and PONV within the first 24 h were collected and analyzed. Results: Of the 1,239 patients who met the study selection criteria, 585 received remimazolam and 684 received propofol. After propensity score matching, 333 matched pairs were further analyzed. Patient demographics and the anesthetic agents used were comparable between the matched cohorts. The incidence of PONV was significantly higher in the remimazolam group than in the propofol group (35% vs. 21%, P < 0.001). Conclusions The incidence of PONV is higher with remimazolam anesthesia than with propofol anesthesia. The findings of this study require confirmation in larger prospective randomized controlled trials.

We report a case of surgery for an infectious left subclavian artery aneurysm in a patient with metal allergy. The patient was a 41-year-old man allergic to iron, silver, manganese, and chromium. He had received a Nitinol stent in the left subclavian artery at a previous hospital. One stent had fallen out during implantation, and was put away in the terminal aorta. Ten days after the left subclavian implantation, the patient developed left shoulder pain and fever, which continued for 2 weeks. Contrastenhanced CT scan revealed a pseudoaneurysm of the left subclavian artery and abdominal aortitis. The patient underwent left subclavian artery aneurysmectomy, aorto-left subclavian artery bypass using the great saphenous vein, and removal of the stents in the left subclavian artery and abdominal aorta. The surgery was performed through a median sternotomy with cardiopulmonary support. A contrast-enhanced CT scan taken on the 12th postoperative day revealed a pseudoaneurysm of the abdominal aorta, and the patient underwent abdominal aortic artery replacement surgery on the 14th postoperative day. The patient was discharged from the hospital on the 27th day after the first surgery. The treatment of an aneurysm should be selected according to the patient’s background as well as anatomical factors.

A 72-year-old female received surgical aortic valve replacement for severe aortic stenosis in our hospital. During surgery, black pigmentation was observed in the aortic valve, aorta intima and mitral valve anterior leaflet collocated with calcification. We suspected Alkaptonuria (AKU) as a possible diagnosis for those surgical findings, past medical history and physical findings. A urine test for organic acids showed homogentisic, confirming the diagnosis of AKU. AKU is very rare genetic metabolic abnormality that occurs in about 1 in 25,000 to 100,000 people. AKU involves deficiency in the gene coding for HGA-1,2-dioxygenase, which metabolizes homogentisic acid to maleylacetoacetic acid in the tyrosine metabolic pathway. HGA accumulates in the body, causing black pigmentation in places including the aorta intima and mitral valve.

Methods: Sixty patients with PCSA who underwent surgical treatment of the cervical spine were enrolled. The radiological findings on plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) were evaluated. The cervical lordotic angles, C2–C7 sagittal vertical axis (SVA), and T1 slope were assessed on a lateral radiograph in the neutral position. CT was used to assess the width of the intervertebral foramen and the anterior protrusion of the superior articular process on the axial view. MRI was used to determine the number of levels of compression (NLC) and the presence of a high-intensity area in the spinal cord in the T2- weighted midsagittal view. The preoperative and postoperative strengths of the most atrophic muscles were evaluated using manual muscle testing. Improvements in strength were classified as excellent (five grades recovered), good (more than one grade recovered), fair (no improvement), or poor (worsened). Results: The prevalence of C5 palsy was 17% (10/60). Patients with poor outcomes had higher NLC and Δ C2–C7 SVA than patients with excellent, good, and fair outcomes (p =0.015; odds ratio [OR], 5.758; 95% confidence interval [CI], 1.397−23.726 for a change of 10% and p =0.048; OR, 1.068; 95% CI, 0.992−1.141 for a change of 10%, respectively). Conclusions ΔC2–C7 SVA and NLC may be used as prognostic factors for achieving a poor outcome following surgery in patients with PCSA. More focus is needed on preventing the increase in ΔC2–C7 SVA.

Objective: A study was conducted to clarify the anti-influenza virus effect of agricultural, forest and fishery products in Ishikawa Prefecture. Method: The samples were prepared by both hot-water and ethanol extraction. The Madin-Darby canine kidney (MDCK) cells infected with PR8 strain were cultured in Dulbecco's Modified Eagle Medium（DMEM） containing extract for 24 hours and measured virus titer of supernatants by focus-forming reduction assay. Time-of-addition assay was performed to determine the inhibition stage in virus proliferation by the extract. The active ingredients were purified using a solid-phase extraction column (silica gel base C18). Results: We revealed that many products have anti-influenza virus activity. Especially, four products ( Matteuccia struthiopteris, Colocasia esculenta, Sagittaria trifolia, and Eleucine coracana) show strong activity and inhibit several stages in virus proliferation. Conclusion: We performed screening to 46 agricultural, forest and fishery products and found the four products ( Matteuccia struthiopteris, Colocasia esculenta, Sagittaria trifolia, and Eleusine coracana) inhibit virus proliferation strongly. In addition, the isolation and identification of the active ingredients contained in these remain as a future study.

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

We conducted a clinical trial in 26 healthy adult women to evaluate the effect of foods containing placental extract ingested for 12 consecutive weeks on 9 constitutional types in Traditional Chinese Medicine.The body constitution analysis set consisted of 23 subjects (excluding 3 dropouts). Twelve-week ingestion of placental extract-containing foods improved individual scores for “Gentleness” type, a healthy constitution, and “Qi-deficiency,” “Yang-deficiency,” “Yin-deficiency,” “Wet-heat” and “Qi-depression” types, which are all mibyou constitution.The safety analysis set consisted of 25 subjects (excluding 1 dropout). Only one subject experienced an adverse event (exacerbation of urticaria, an underlying disease). No other safety concerns arose.