The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 262, Issue 4
April
Displaying 1-7 of 7 articles from this issue
Regular Contribution
  • Kou Kitabayashi, Suguru Yamamoto, Ichiei Narita
    2024 Volume 262 Issue 4 Pages 221-228
    Published: 2024
    Released on J-STAGE: April 24, 2024
    Advance online publication: January 12, 2024
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    Supplementary material

    The Geriatric Nutritional Risk Index (GNRI) is a popular nutritional screening tool. However, the calculation of ideal body weight (IBW) differs among studies. We aimed to compare GNRI calculated using the Lorentz formula (LF) with a body mass index (BMI) and to investigate the cutoffs based on original or quartile criteria for the association with mortality in elderly patients in Japan. This retrospective study enrolled patients aged 65 and older in a long-term care hospital. The GNRI was calculated using two different IBW methods: the LF and a BMI of 22 kg/m2. We categorized GNRI results based on the original criteria or quartile criteria. Mortality outcomes were analyzed using the GNRI based on IBW (LF or BMI) and its classification (original criteria or quartile) through Cox proportional hazard regression. There were 262 participants, including 160 women, with a median age of 86. There was a notable difference between GNRI-BMI and GNRI-LF. The GNRI-LF original and quartile criteria did not show an association with mortality. A significant association with mortality was found between Q1 and Q4 in the GNRI-BMI quartile criteria (hazard ratio: 2.60; 95% confidence interval: 1.66-4.07, p < 0.01), but not the GNRI-BMI original criteria. The GNRI calculated using BMI with quartile criteria proved to be a reliable predictor of mortality for Japanese elderly inpatients. The calculation method of GNRI and the appropriate cutoff point should be considered based on the patient’s background.

  • Libo Guo, Chunna Lin, Jinrong Qu
    2024 Volume 262 Issue 4 Pages 229-238
    Published: 2024
    Released on J-STAGE: April 27, 2024
    Advance online publication: January 12, 2024
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    Specific, measurable, achievable, relevant, timed (SMART) principle improves the nursing utility by setting individual goals for participants and helping them to achieve these goals. Our study intended to investigate the impact of a SMART nursing project on reducing mental stress and post-traumatic stress disorder (PTSD) in parents of childhood or adolescent osteosarcoma patients. In this randomized, controlled study, 66 childhood or adolescent osteosarcoma patients and 126 corresponding parents were enrolled and divided into SMART or normal care (NC) groups at a 1:1 ratio. All parents received a 3-month corresponding intervention and a 6-month interview. Our study revealed that the self-rating anxiety scale score at the 3rd month (M3) (P < 0.05) and the 6th month (M6) (P < 0.01), and anxiety rate at M3 (P < 0.05) and M6 (P < 0.05) were lower in parents in SMART group vs. NC group. The self-rating depression scale score at M3 and M6, and depression rate at M3 and M6 were lower in parents in SMART group vs. NC group (all P < 0.05). Impact of events scale-revised score at the 1st month (M1) (P < 0.05), M3 (P < 0.05), and M6 (P < 0.01) were lower in parents in SMART group vs. NC group. By subgroup analyses, the SMART nursing project showed better impacts on decreasing anxiety, depression, and PTSD in parents with an undergraduate education or above than in those with a high school education or less. Conclusively, SMART nursing project reduces anxiety, depression, and PTSD in parents of childhood or adolescent osteosarcoma patients, which is more effective in those with higher education.

Case
  • Toshiki Inotani, Akira Horaguchi, Yuko Morishita, Ayuko Yoshida, Misak ...
    2024 Volume 262 Issue 4 Pages 239-244
    Published: 2024
    Released on J-STAGE: April 24, 2024
    Advance online publication: January 25, 2024
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    Selective dorsal rhizotomy (SDR) has been used to treat children with spastic cerebral palsy (CP), and its beneficial effect on quality of life and ambulation has been confirmed in long-term follow-up studies. However, the role of SDR in the treatment of spasticity in patients with hereditary spastic paraplegia (HSP) and related disorders is not well-established. Here, we report the first patient with the ZC4H2 variant who underwent SDR to treat spastic paraplegia. Abnormal gait was discovered during a regular checkup at the age of 3 years and 9 months, and she was diagnosed with spastic paraplegia. She was heterozygous for the ZC4H2 variant and underwent SDR at the age of 5 years and 11 months, which alleviated the spasticity. The patient underwent inpatient postoperative rehabilitation for 4 months and continued outpatient physiotherapy after discharge. The Gross Motor Function Measure-88 score and maximum walking speed decreased transiently 1 month postoperatively, but gradually recovered, and continuously improved 6 months postoperatively. SDR and postoperative intensive rehabilitation were effective in improving motor and walking functions up to 6 months after surgery, although long-term follow-up is needed to draw conclusions.

Regular Contribution
  • Hye Rim Suh, Hwi-young Cho
    2024 Volume 262 Issue 4 Pages 245-252
    Published: 2024
    Released on J-STAGE: April 25, 2024
    Advance online publication: January 25, 2024
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    Transcutaneous electrical nerve stimulation (TENS) has been used to reduce pain or improve motor function in musculoskeletal and neurological disorders in the clinic. Although some studies have suggested electrotherapy as an intervention for edema, the effects and mechanisms of TENS on inflammation-induced edema remain unclear. Thus, we aimed to investigate the effects of TENS on arthritic pain with edema. 1% carrageenan was injected into the right tibiofemoral joint of 69 male Sprague–Dawley rats (200-250 g). After the development of arthritic pain, low-frequency (4-Hz, Low-TENS, n = 25) and high-frequency (100-Hz, High-TENS, n = 25) TENS with sub-motor threshold or placebo-TENS (n = 19) was applied for 20-min to medio-lateral part of the ipsilateral side. Weight bearing and knee-bend tests were used to assess pain-like behaviors. Also, we examined the size of edema and measured tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the synovium by western blot. Eight rats in each of the two TENS groups were injected with Naloxone. Edema was reduced in the low- and high-frequency TENS groups at 6-h. TENS-treated rats showed reduced pain in the knee-bend test at 6-h. We observed decreased weight load shifts on the ipsilateral side in TENS groups. Naloxone reduced these effects. TNF-α and IL-1β expression decreased in the synovial membrane at 6-h. These results suggest that low- and high-frequency TENS have acutely positive effects on inflammatory edema, with the management of arthritic pain and reduction in pro-inflammatory mediators. Therefore, Low-TENS and High-TENS may be useful in treating acute inflammatory pain and edema.

  • Ling Zhang, Shenglan Zhang, Zhao Han, Zhao Liu, Yanyan Xu, Xiaojing Li ...
    2024 Volume 262 Issue 4 Pages 253-261
    Published: 2024
    Released on J-STAGE: April 26, 2024
    Advance online publication: November 09, 2023
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    Supplementary material

    Polo-like kinase 4 (PLK4) involves in tumor progression via regulating centriole duplication. This study aimed to investigate correlations of PLK4 with tumor characteristics and survival in cutaneous melanoma patients undergoing surgical resection. Tumor specimens of 43 patients were retrieved for PLK4 determination by immunohistochemistry (IHC). The IHC score was a multiplication of staining intensity and percentage of staining-positive cells. This study found the median and mean tumor PLK4 IHC score was 0.0 (interquartile range: 0.0-6.0) and 3.5 ± 3.2 (mean ± SD), respectively. Elevated tumor PLK4 IHC score correlated with lymph node metastasis (P = 0.028), higher tumor node metastasis (TNM) stage (P = 0.004), and adjuvant therapy (P =0.029). Tumor PLK4 IHC score > 0 did not relate to disease-free survival (DFS) or overall survival (OS) (both P > 0.050). Tumor PLK4 IHC score > 3 associated with decreased DFS (P = 0.027), but not OS (P = 0.098). Five-year DFS rate of patients with tumor PLK4 IHC score = 0 and > 0 was 75.0% and 53.9%, correspondingly; while the rate of patients with the score ≤ 3 and > 3 was 81.0% and 37.5%, respectively. Five-year OS rate of patients with the score = 0 and > 0 was 100.0% and 66.3%, accordingly; whereas the rate of patients with the score ≤ 3 and > 3 was 85.7% and 61.5%, correspondingly. According to forward-step multivariate analysis, neither the score > 0 nor > 3 independently related to worse DFS and OS (all P > 0.050). Further validation via THE HUMAN PROTEIN ATLAS database showed high PLK4 RNA expression associated with shortened OS in melanoma patients (P = 0.001). PLK4 correlates with lymph node metastasis, increased TNM stage, and poor DFS in cutaneous melanoma patients undergoing surgical resection.

Case
  • Junpei Yamamoto, Hiroshi Onodera, Yuki Kaminaga, Yoko Kayaba, Masahiro ...
    2024 Volume 262 Issue 4 Pages 263-268
    Published: 2024
    Released on J-STAGE: May 01, 2024
    Advance online publication: February 08, 2024
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    Anamorelin (ANAM) is a novel ghrelin receptor agonist for the treatment of cancer cachexia. In clinical trials of ANAM, glucose metabolism disorders as adverse effects were relatively frequent, however, when and how they occur remains unclear. Moreover, the safety in patients with pancreatic cancer and/or diabetes has not been clarified because most previous studies focused on patients with non-small cell lung cancer and had excluded patients with poorly controlled diabetes. Herein, a 66-year-old man with advanced pancreatic cancer and diabetes was administered ANAM, and acute hyperglycemia was developed and could be monitored by the self-monitoring of blood glucose (SMBG). Increasing the insulin dose failed to control hyperglycemia adequately, but the hyperglycemia ameliorated quickly after ANAM discontinuation. The continuous glucose monitoring (CGM) revealed that the sensor glucose levels had remained in the high range throughout the day during ANAM administration despite using 1.5 times more insulin. Our report is one of the few that describe the details of ANAM-induced hyperglycemia and provides important information for the safe and effective use of ANAM.

Regular Contribution
  • Haoyue Yu, Zhiguo Wang, Yan Dong, Li Li, Xianming Fan, Nan Zheng, ji J ...
    2024 Volume 262 Issue 4 Pages 269-276
    Published: 2024
    Released on J-STAGE: May 01, 2024
    Advance online publication: January 18, 2024
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    Supplementary material

    Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs). The PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to identify the key genes for clinical prognosis and gene correlation respectively. Protein expression was determined by western blot analysis. Cell viability assay and Ki67 staining were used to evaluate the effect of osimertinib on tumor cells. Finally, we screened out two hub genes, myelocytomatosis oncogene (Myc) and axis inhibition protein 1 (Axin1), upregulated in three osimertinib-resistant cell lines through RNA sequencing and bioinformatics analysis. Next, cell experiment confirmed that expression of C-MYC and AXIN1 were elevated in different EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, compared with their corresponding parental cell lines. Furthermore, we demonstrated that AXIN1 upregulated the expression of C-MYC and mediated the acquired resistance of EGFR mutant NSCLC cells to osimertinib in vitro. In conclusion, AXIN1 affected the sensitivity of EGFR mutant NSCLC to osimertinib via regulating C-MYC expression in vitro. Targeting AXIN1/MYC signaling may be a potential new strategy for overcoming acquired resistance to osimertinib.

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