JOURNAL OF MEDICAL INVESTIGATION最新文献

Background: The number of elderly patients with frailty who require hepatectomy is increasing. This study aimed to investigate the effect of Ninjin'yoeito (NYT) on the post-hepatectomy state in naturally aged frailty model mice.

Methods: Seventy-two-week-old mice were subjected to 70% partial hepatectomy and then divided into an NYT-treated group and a control group. Mice were sacrificed immediately (0 hours) or 24 or 48 hours after hepatectomy. Body weight, grip strength, endurance, and survival duration were investigated. Furthermore, liver function was assessed, and mRNA expression was measured using reverse-transcription PCR.

Results: The body weight tended to be higher in the NYT group than in the control group 24 hours after hepatectomy (p=0.09). The grip strength was significantly stronger in the NYT group before and 48 hours after hepatectomy (p<0.05). Although survival time was slightly prolonged in the NYT group, there was no significant difference between the two groups. HMGB1 mRNA expression in the liver was significantly suppressed in the NYT group compared with that in the control group at 24 and 48 hours after hepatectomy (p<0.05).

Conclusions: NYT may affect the postoperative state, including body weight and motor function, in aged model mice. Suppression of HMGB1 might affect postoperative survival. J. Med. Invest. 72 : 245-251, August, 2025.

Background: Tumor-infiltrating CD8+ T cells express many immune checkpoint proteins and are currently the focus of therapeutic targeting, although dramatic results have not yet been achieved in hepatocellular carcinoma (HCC). In this study, we performed a statistical analysis of immune checkpoint proteins and prognosis in HCC to evaluate its utility as a biomarker for predicting prognosis.

Methods: We analyzed 474 HCC patients with two comprehensive miRNA profiling datasets (GSE76427:n=115 and TCGA:n=359) with clinical and transcriptomic data to examine associations between mRNA levels of CD8, TIM3, and PD-1/PD-L1. Each gene was divided into low- and high-expression groups using the tertiles of RNA expression.

Results: CD8 and TIM3 expression were associated with overall survival (OS) (P=0.021 and P=0.025, respectively), while PD-1/PD-L1 levels were not associated with OS (P=0.306 and P=0.318, respectively) in TCGA dataset. Among patients with high CD8 expression, low TIM3 expression was associated with better OS (TCGA:P=0.009, Whole patient cohort (TCGA+GSE dataset):P=0.008).

Conclusions: The combination of CD8 and TIM3 expression which indicates T cell exhaustion was useful biomarker for predicting HCC prognosis than PD-1/PD-L1, suggesting that TIM3 may be a future target for immune checkpoint inhibition. J. Med. Invest. 72 : 354-360, August, 2025.

Neurological immune-related adverse events can manifest as paraneoplastic neurological syndrome (PNS), especially in patients with small-cell lung cancer (SCLC). We herein report a 73-year-old man with SCLC treated with an immune checkpoint inhibitor (ICI) combined with chemotherapy. Although the chemo-immunotherapy induced a favorable response to SCLC, he later developed acute cerebellar ataxia. He was diagnosed with paraneoplastic cerebellar degeneration associated with anti-Sry-like high mobility group box 1 (SOX1) autoantibody. The antibody was also identified in serum collected at the diagnosis of SCLC and before ICI administration, which retrospectively suggested that the patient was at risk of ICI-induced PNS. J. Med. Invest. 72 : 172-176, February, 2025.

The high rate of chronic hepatitis, including hepatitis B, C and D, in Mongolia creates a large health burden of advanced liver disease. This includes liver failure and the highest incidence rate of hepatocellular carcinoma (HCC) worldwide. In the present study, we histopathologically examined 69 recent cases of HCC from the Mongolian National Center for Pathology, which collects specimens from across the country. The background liver histology of HCC exhibited a bimodal distribution, with one peak corresponding to advanced liver fibrosis and another to mild liver fibrosis. The fibrosis severity negatively correlated with age. Additionally, the frequency of poorly differentiated tumors was significantly higher in the HCC with early stage of fibrosis. A comparison of the pathological characteristics of HCC in urban and rural areas showed that poorly differentiated tumors were highly prevalent in urban areas. The characteristics of HCC in Mongolia are different from those in other countries, suggesting that the causes of liver disease are not only related to viruses but also other factors that depend on the region. This study will provide insight into what research is needed next for liver cancer control in Mongolia. J. Med. Invest. 72 : 47-53, February, 2025.

Objective: There have been no studies on the effectiveness of raloxifene as an antiresorptive agentfollowing discontinuation of romosozumab. The aim of this study was to investigate the potential effectiveness of raloxifene following a romosozumab therapy.

Methods: This study had an observational pre-post design and included 23 patients. Romosozumab 210 mg was administered subcutaneously once every 4 weeks for 12 months, after which all patients received raloxifene 60 mg/day for 24 months. We investigated the incidence of new fractures, safety, and bone mineral density (BMD).

Results: We found no new fractures or adverse events. After the treatment with romosozumab, percent changes from baseline in BMD at the spine and total hip in treatment-naïve patients with primary osteoporosis (the Naïve-P group) were 12.3% and 4.6%, respectively. After subsequent administration of raloxifene, spinal and total hip BMD in the Naïve-P group decreased to baseline levels at 36 months and 30 months, respectively. Six months after switching to raloxifene, the respective percent changes from baseline in spinal and total hip BMD were 12.0% and 5.8%.

Conclusion: Romosozumab followed by raloxifene is acceptable for use for only 6 months in the Naïve-P group. However, more aggressive use of this agent is not recommended. J. Med. Invest. 72 : 124-133, February, 2025.

Obesity-induced excess adipokine production is associated with malignancy and mortality in prostate cancer. We previously showed that fatty acid binding protein 4 (FABP4), a major adipokine of mature adipocytes, promotes the progression of prostate cancer cell growth and invasion. In this report, we present lipolysis-stimulated lipoprotein receptor (LSR) as a newly identified binding partner for FABP4. Their binding induced Akt phosphorylation, whereas LSR knockdown (KD) failed to phosphorylate Akt. Intraosseous injection of LSR-KD prostate cancer cells showed smaller areas of intraosseous tumor, lower Ki-67 labeling indices, and lower numbers of phospho-Akt-positive cancer cells compared with control prostate cancer cells. Moreover, the contact coculture of prostate cancer cells with bone marrow stromal cells (BMSCs) promoted FABP4 secretion by BMSCs. Our findings indicated that FABP4-mediated prostate cancer cell progression was regulated by cellular signaling via FABP4-LSR binding in the bone microenvironment. J. Med. Invest. 72 : 34-41, February, 2025.

Background: Women account for 23.6% of physicians in Japan yet account for only 5% of orthopedic surgeons and <1% of board-certified spine surgeons. We identified points along the training pathway where women perceive barriers to pursuing spine surgery.

Methods: In this sequential explanatory mixed-methods study, we surveyed all 5th- and 6th-year medical students at our institution and postgraduate year-1-2 residents and received responses from 62 trainees (29 women, 33 men). Counts, percentages, and χ2 or Fisher exact tests were used to compare the groups. We thematically analyzed the semi-structured e-mail interviews conducted with 10 female orthopedic trainees (4 residents, 1 non-spine surgeon, and 5 spine fellows).

Results: Interest in orthopedics was reported by 45% of women and 64% of men (p=0.22);within that subgroup interest in spine surgery was similar (31% vs. 33%;p=1.00). From the interviews, four categories of barriers to choosing spine surgery as a subspecialty emerged:(1) physical limitations, (2) radiation exposure, (3) demanding working hours/on‑call, and (4) a gender‑imbalanced environment.

Conclusions: Many early-career women already express interest in orthopedics. However, translating that interest into careers as spine surgeons will require sustained mentorship plus the adoption of assistive technologies, ergonomic instruments, and team-based shift schedules-interventions that could benefit the entire surgical workforce. J. Med. Invest. 72 : 425-429, August, 2025.

We investigated mid-term outcomes after aortic valve replacement (AVR) with INSPIRIS RESILIA (IR) aortic bioprosthesis for severe aortic stenosis (AS). A total of 60 patients with a mean age of 73.2±6.2 years underwent AVR with IR bioprosthesis for severe AS. We prospectively followed up on 59 survivors and collected transthoracic echocardiographic data at 3-6 months, and annually thereafter. The mean follow-up period was 3.0±1.5 years, with a 100% follow-up rate. The preoperative mean pressure gradient (PG) and the effective orifice area were 52.5±18.2 mmHg, and 0.73±0.23 cm2, respectively, which improved to 10.3±3.5 mmHg (P<0.001), and 1.85±0.48 cm2 (P<0.001) at discharge. The mean PG at 5 years was 10.2±2.7 mmHg, which was similar to one at discharge (P=0.307). Left ventricular mass index decreased from 119.6±33.1 g/m2 before AVR to 104.0±32.5 g/m2 (P<0.001) at discharge, and further decreased to 78.5±22.2 g/m2 at 5 years compared with postoperative one (P=0.011). Survival rate at 5 years was 97.4±2.6%. Freedom from valve-related events at 5 years was 91.4±5.5%. Incidental cerebral infarction (n=2) and heart failure (n=1) were noted. IR bioprosthesis demonstrated a stable hemodynamic performance and few valve-related events. J. Med. Invest. 72 : 390-395, August, 2025.

This review discusses the introduction of healthcare robots, such as those that provide transfer, toileting, bathing, and communication assistance, in Japanese facilities for older adults and considers these issues from the perspective of nursing ethics. Although healthcare robots can support older adults and their caregivers, they may cause ethical dilemmas when introduced in assisted living facilities. Nurses should make ethical decisions by considering different types of information to determine the best care for older adults ; they can resolve ethical dilemmas by referring to the 6 principles of nursing ethics. As healthcare robots are increasingly used in the care of older adults, nurses should protect patients' rights and ensure patient safety. Further, engineers and medical professionals must discuss and share issues related to the use of healthcare robots to build improved robotic technology for older adults. J. Med. Invest. 72 : 8-13, February, 2025.