The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 261, Issue 4
December
Displaying 1-9 of 9 articles from this issue
Regular Contribution
  • Jialuo Cai, Yilin Zhu, Xiaoping Li, Guiming Deng, Yuanshan Han, Feiyun ...
    2023 Volume 261 Issue 4 Pages 257-265
    Published: 2023
    Released on J-STAGE: December 16, 2023
    Advance online publication: June 22, 2023
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    Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was −4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-β1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-β1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.

Case
  • Yuki Ishikawa, Ryusuke Saito, Keigo Murakami, Atsushi Fujio, Koji Miya ...
    2023 Volume 261 Issue 4 Pages 267-272
    Published: 2023
    Released on J-STAGE: December 16, 2023
    Advance online publication: September 28, 2023
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    Biliary atresia is an obliterative cholangiopathy of unknown etiology. Hepatic portoenterostomy, in which obliterated extrahepatic bile ducts are resected and bile flow is restored, known as Kasai operation, is performed within 3 months after birth. While this operation enhances long-term survival of patients, the occurrence of primary malignant hepatic tumors has been increasing. We report a case of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation. A 49-year-old man, who underwent Kasai operation for biliary atresia when he was 2 months old, experienced rapidly progressive jaundice and liver dysfunction. Deceased-donor liver transplantation was performed for liver failure. Macroscopically, there was a white-yellow tumor located at the anastomotic site of hepatic portoenterostomy of the resected liver. Pathological examination revealed a well-differentiated adenocarcinoma with some Paneth cells in the neoplastic lesion. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) but positive for cytokeratin 20 (CK20) and a homeobox domain-containing transcription factor (CDX2). Mucin expression in tumor cells was negative for mucin 1 (MUC1) and mucin 6 (MUC6) and positive for mucin 2 (MUC2) and mucin 5AC (MUC5AC). The pathological diagnosis was small intestinal adenocarcinoma originating from the jejunum. The patient was discharged 48 days after the operation. The patient had not experienced recurrence at 10 months after the operation. This is the first report of small intestinal adenocarcinoma arising at the anastomotic site after Kasai operation for biliary atresia. Special care should be taken for the patients after Kasai operation with acute progressive jaundice and liver dysfunction because there is a possibility of malignancy in their native liver.

Regular Contribution
  • Hiroyuki Teraura, Kazuhiko Kotani, Eiji Sato, Soichi Koike
    2023 Volume 261 Issue 4 Pages 273-281
    Published: 2023
    Released on J-STAGE: December 16, 2023
    Advance online publication: September 21, 2023
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    In Japan, there are rural clinics designated for areas without physicians to ensure the availability of medical care for rural area residents. The purpose of this study was to clarify the attributes of physicians working in the rural clinics. Using the 2018 Ministry of Health, Labour and Welfare data in Japan, we compared the attributes and board certifications of physicians in rural clinics with those of physicians in other clinics. The age group with the highest percentage of physicians was the over 70 group (16%) and the early 30s group (15%) at rural clinics; however, the highest percentage of physicians at other clinics was the 70 over group (20%) and the early 60s group (16%). The number of physicians working in the internal medicine field at rural clinics was 550 (89%). There were 147 (27%) board-certified physicians in that field. Among them, the number of board certifications in internal medicine, surgery, and other than internal medicine or surgery were 79 (54%), 17 (12%), and 51 (35%), respectively. The proportion of board-certified surgery physicians within the internal medicine field in rural clinics was significantly higher than in other clinics (5%). In rural clinics, the age distribution of physicians was different from that in other clinics, and many of the physicians worked in the internal medicine field, but some of them seemed to have a mismatch between their board-certifications and their fields of practice. Further studies are necessary to clarify what the mismatches mean in rural practice.

  • Lifen Chen, Shuyi Shen, Songyu Wang
    2023 Volume 261 Issue 4 Pages 283-289
    Published: 2023
    Released on J-STAGE: December 23, 2023
    Advance online publication: September 14, 2023
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    Diabetic foot ulcers are caused by nerve abnormalities and vascular lesions in the distal lower limbs of diabetic patients. However, the causes of diabetic foot ulcers are diverse and the treatment process is complex. Therefore, understanding the pathogenesis of diabetic foot ulcers through lncRNA and formulating effective means are the key to the cure of patients. Tissues were collected from 76 diabetic foot ulcer patients and 50 non-diabetic patients undergoing traumatic amputation. Human dermal fibroblasts (HDFs) were induced by high glucose to obtain diabetic foot ulcer cell model. The lncRNA SNHG16 (SNHG16) and miR-31-5p expression in tissues and cells was detected by real-time quantitative reverse transcription PCR (RT-qPCR). Cell Counting Kit-8 (CCK-8) and Transwell assays were used to evaluate the biological behavior of the cells, and the association between SNHG16 and miR-31-5p was explored by luciferase reporting assay. SNHG16 was distinctly expressed in diabetic foot ulcer tissue samples, while miR-31-5p was decreased. In vitro cell function assays confirmed that the proliferation level was inhibited in the constructed diabetic foot ulcer cell model (HG group), as was the migration and invasion ability. After transfection with silencing SNHG16, the biological behavior of the cells was promoted. Mechanistically, SNHG16 sponge miR-31-5p regulated disease progression. Recovery experiments revealed that miR-31-5p inhibitor counteracted the effect of silencing SNHG16 on cell viability. SNHG16 knockdown may regulate the biological function of cells by targeting miR-31-5p to promote wound healing and ameliorate the condition of diabetic foot ulcer patients.

  • Rina Takeshita, Keiji Muramatsu, Shinya Matsuda
    2023 Volume 261 Issue 4 Pages 291-297
    Published: 2023
    Released on J-STAGE: December 23, 2023
    Advance online publication: October 05, 2023
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    Japan has a high suicide mortality rate compared to other developed countries. To reduce suicide mortality in Japan, it is important to systematically analyze factors related to death of patients with suicide attempt. This study aimed to analyze the characteristics of patients with suicide attempt, and the factors related to their death using the Diagnosis Procedure Combination (DPC) data— a nationally representative inpatient database. We collected 81,407 cases of suicide attempt from 2016 to 2018 from DPC data and performed a multilevel logistic analysis of factors associated with death discharges. The analysis results showed that patients who received psychiatric liaison care had a lower mortality rate, but only 0.6% of surviving patients received psychiatric liaison care after admission. The odds ratio (OR) of death was high for hanging (28.86; p < 0.001) and jumping (16.28; p < 0.001), compared to wrist cutting. Patients without a psychiatric diagnosis were more likely to choose means such as hanging (14.1%) than those with a psychiatric disorder. The weekend cases had a higher OR of death than weekday (Wednesday as reference) cases (Friday 1.14, p = 0.011; Saturday 1.60, p < 0.001; Sunday 1.67, p < 0.001). Based on these findings, we suggest that improving the availability and quality of psychiatric care in acute care hospitals and primary care settings, as well as enhancing the emergency department system on weekends, could help reduce the mortality of suicide attempts.

  • Junqing Zong, Lingbo Yang, Lei Wei, Dong Wang, Xuening Wang, Zhongjie ...
    2023 Volume 261 Issue 4 Pages 299-307
    Published: 2023
    Released on J-STAGE: December 23, 2023
    Advance online publication: September 14, 2023
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    Mucosa-associated lymphoid tissue 1 (MALT1) regulates inflammation and T helper (Th) cell differentiation, which may participate in the progression of Stanford type A aortic dissection (TAAD). This study intended to assess the association of MALT1 expression with prognosis in TAAD patients. In this prospective study, MALT1 expression was measured by reverse transcription-quantitative polymerase chain reaction assay from peripheral blood samples in 100 TAAD patients and 100 non-AD controls (non-AD patients with chest pain) before treatment. Besides, Th1, Th2, and Th17 cells of TAAD patients before treatment were measured by flow cytometry assay, and their 30-day mortality was recorded. MALT1 expression was ascended in TAAD patients vs. non-AD controls (P < 0.001). In TAAD patients, elevated MALT1 expression was linked with hypertension complication (P = 0.009), increased systolic blood pressure (r = 0.291, P = 0.003), C-reactive protein (CRP) (r = 0.286, P = 0.004), and D-dimer (r = 0.359, P < 0.001). Additionally, MALT1 expression was positively correlated with Th1 cells (r = 0.312, P = 0.002) and Th17 cells (r = 0.397, P < 0.001), but not linked with Th2 cells (r = −0.166, P = 0.098). Notably, the 30-day mortality of TAAD patients was 28.0%. MALT1 expression [odds ratio (OR) = 1.936, P = 0.004], CRP (OR = 1.108, P = 0.002), D-dimer (OR = 1.094, P = 0.003), and surgery timing (emergency vs. selective) (OR = 8.721, P = 0.024) independently predicted increased risk of death within 30 days in TAAD patients. Furthermore, the combination of the above-mentioned independent factors had an excellent ability in predicting 30-day mortality with the area under curve of 0.949 (95% confidence interval: 0.909-0.989). MALT1 expression relates to increased Th1 cells, Th17 cells, and 30-day mortality risk in TAAD patients.

  • Shunji Kasaoka, Hisaki Naito, Yuri Uchigashima
    2023 Volume 261 Issue 4 Pages 309-315
    Published: 2023
    Released on J-STAGE: December 23, 2023
    Advance online publication: October 26, 2023
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    When disasters occur, affected people in evacuation shelters may experience health problems, such as exacerbation of chronic diseases or development of new diseases. This study examined the factors contributing to sudden illness in evacuation shelters used for the 2016 Kumamoto Earthquake. The subjects were evacuees of the Kumamoto Earthquake who were transported to hospitals from evacuation shelters by ambulance. Data on patients transported from evacuation shelters were obtained from emergency transport records at the Kumamoto City Fire Department and from medical institutions. The assessment of the living conditions in the shelter was obtained from the Emergency Medical Information System. A total of 576 patients were transported by ambulance from evacuation shelters in Kumamoto City. Of these, 300 patients for whom detailed information was obtained from medical institutions were included in the analysis. The median age was 71 years, and 213 patients (71%) were over 60 years old. There were 235 patients (78%) with pre-existing medical conditions. The most common reasons for emergency transport were falls and dyspnea, followed by fever, disturbance of consciousness, and abdominal pain. The most common final diagnosis at the medical institutions was trauma due to falls, followed by cardiovascular disease, infectious disease, and cerebral neurological disease. A survey of living conditions in the shelters identified problems with scarcity of space and provision of medical care and food. In order to prevent adverse health outcomes in evacuation shelters, the provision of appropriate living conditions and medical care is important from the acute phase of a disaster.

  • Yoichi Sato, Keiko Kabasawa, Yumi Ito, Shoichiro Tsugane, Kazutoshi Na ...
    2023 Volume 261 Issue 4 Pages 317-323
    Published: 2023
    Released on J-STAGE: December 26, 2023
    Advance online publication: October 19, 2023
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    Supplementary material

    Physical activity is crucial to prevent sarcopenia, but there is scant data on the link between sarcopenia and physical activity in rural communities. Therefore, this study investigated associations of farming activity and snow removal with sarcopenia in a middle-aged and older population in rural Japan. This cross-sectional study enrolled 3,056 residents aged ≥ 40 years (49.2% men; mean age, 64.2 years) in Yuzawa, Japan. Information on farming activity and snow removal were collected via questionnaire from May through November and from December through April, respectively. Sarcopenia was assessed by the SARC-F (strength, ambulation, rising from a chair, stair climbing, and history of falling) score. Associations of farming activity and snow removal with sarcopenia were assessed using multivariable logistic regression analysis with adjustment for potential confounders. Participants who engaged in farming activity, snow removal, and both accounted for 3.8%, 40.5%, and 29.4% of the total, respectively. In the multivariable logistic regression analysis, adjusted odds ratios [95% confidence intervals (CI)] of sarcopenia for farming activity and snow removal were 0.80 (0.63-1.03) and 0.68 (0.53-0.87), respectively. Compared with participants who did not engage in farming activity or snow removal, participants who engaged in both had a significantly lower adjusted odds ratio of sarcopenia [0.63 (95% CI 0.47-0.86)]. Participants who engaged in snow removal and those who engaged in both farming activity and snow removal showed inverse associations with sarcopenia. Our findings further support the importance of physical activity in preventing or mitigating sarcopenia in rural communities.

  • Susumu Tsunoo, Yumi Sugawara, Ichiro Tsuji
    2023 Volume 261 Issue 4 Pages 325-333
    Published: 2023
    Released on J-STAGE: December 26, 2023
    Advance online publication: October 12, 2023
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    Supplementary material

    Social isolation is frequently observed among survivors of disaster. However, there is limited evidence regarding the association between social isolation and adverse health outcomes among survivors of disaster. The purpose of this study was to investigate the association between social isolation and the risk of incident functional disability (IFD) among survivors of the 2011 Great East Japan Earthquake (GEJE). We conducted a prospective cohort study of 1,039 residents aged ≥ 65 years who lived in four areas affected by the GEJE. Information regarding social isolation and other lifestyle factors was collected between June and November 2011 via a self-reported questionnaire. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6). Data regarding the incidence of functional disability were retrieved from the Long-term Care Insurance database. The Cox model was used to calculate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for IFD. During 7,030 person-years of follow-up, 300 cases of IFD were certified (42.7disability events per 1,000 person-years). Social isolation was associated with increased risk of IFD in disaster survivors (HR = 1.32, 95% CI = 0.98-1.76). In addition, this association tended to be more remarkable among men and those whose houses were completely/seriously damaged. The present results suggest us that it would be possible to identify those who are more likely to be affected by social isolation after disaster. This finding would be useful in screening and supporting high risk group right after the occurrence of disaster.

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