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淡明腎細胞癌における偽被膜の形成および破綻の分子学的機序
The process and molecular mechanisms underlying the formation and destruction of a pseudo-capsule (PC) in clear cell renal cell carcinoma (ccRCC) are poorly understood. In the present study, the PCs of surgical specimens from primary tumors and metastatic lesions in 169 patients with ccRCC, and carcinogen-induced ccRCC rat models were semi-quantified using the invasion of PC (i-Cap) score system. This was based on the relationship among the tumor, PC and adjacent normal tissue (NT) as follows: i-Cap 0, tumor has no PC and does not invade NT; i-Cap 1, tumor has a complete PC and does not invade into the PC; i-Cap 2, tumor with focal absences in the PC, which partially invades the PC but not completely through the PC; i-Cap 3, tumor crosses the PC and invades the NT; i-Cap 4, tumor directly invades the NT without a PC. The study suggested that PC formation was not observed without physical compression, and also revealed that tumor invasion into the PC was a prognostic factor for postoperative oncological outcomes. Higher i-Cap, Fuhrman grade and tumor size were independent poor prognostic factors for postoperative disease-free survival. mRNA expression arrays generated from carcinogen-induced ccRCC rat models were used to explore genes potentially associated with the formation and destruction of a PC. Subsequently, human ccRCC specimens were validated for four genes identified via expression array; the results revealed that collagen type 4A2, matrix metalloproteinase-7 and l-selectin were upregulated alongside the progression of i-Cap score. Conversely, endoglin was downregulated. In conclusion, the present study provides insights into the formation and destruction of a PC, and the results may aid the treatment and management of patients with ccRCC.権利情報:© 2024 Shimizu et al. This is an open access article distributed under the terms of Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/)
がん微小環境におけるEGFRシグナルを介したメディエーターとしての肝発がんに対するエピレグリンの役割
Lipopolysaccharides (LPSs) have been reported to be important factors in promoting the progression of hepatocellular carcinoma (HCC), but the corresponding molecular mechanisms remain to be elucidated. We hypothesize that epiregulin (EREG), an epidermal growth factor (EGF) family member derived from hepatic stellate cells (HSCs) and activated by LPS stimulation, is a crucial mediator of HCC progression with epidermal growth factor receptor (EGFR) expression in the tumor microenvironment. We used a mouse xenograft model of Huh7 cells mixed with half the number of LX-2 cells, with/without intraperitoneal LPS injection, to elucidate the role of EREG in LPS-induced HCC. In the mouse model, LPS administration significantly enlarged the size of xenografted tumors and elevated the expression of EREG in tumor tissues compared with those in negative controls. Moreover, CD34 immunostaining and the gene expressions of angiogenic markers by a reverse transcription polymerase chain reaction revealed higher vascularization, with increased interleukin-8 (IL-8) expression in the tumors of the mice group treated with LPS compared to those without LPS. Our data collectively suggested that EREG plays an important role in the cancer microenvironment under the influence of LPS to increase not only the tumor cell growth and migration/invasion of EGFR-positive HCC cells but also tumor neovascularization via IL-8 signaling.権利情報:© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
A pediatric case of Evans syndrome with high titers of cold agglutinin
Evans syndrome (ES) is a disorder in which autoimmune hemolytic anemia (AIHA) and immune
thrombocytopenia (ITP) occur simultaneously or serially. Most AIHA in ES is warm-AIHA
in which anti-RBC IgG antibodies are the main body causing hemolysis. In this report,
we describe a case of ES diagnosed as warm-AIHA but with a markedly high level of cold
agglutinin (CA), where cold-AIHA was ruled out. A 9-year-old girl presented to the clinic with
headache and was pale. There was no past history or family history of autoimmune disease. On
admission, she was markedly anemic and thrombocytopenic with a positive direct Coombs test.
A bone marrow examination revealed increased erythroid cells and megakaryocytes. The CA
titer was very high of 2,048-fold, but cold-AIHA was considered negative because of the absence
of IgM elevation, improvement of anemia with steroid therapy, and absence of symptoms due
to cold exposure. She was diagnosed as ES with warm-AIHA and ITP. To our best knowledge,
this is the first case of ES with high titers of CA. Long-term follow-up into adulthood is important
in children with ES because of the high incidence of subsequent autoimmune disease after
remission, while the association of CA was unknown
【総説】Review of Issues in Community Mental Health for Forensic Patients and Support for Nurses
This study aimed to clarify the issues present in forensic community mental health, the difficulties faced by nurses, and the state of support for nurses using the relevant literature. To that end, we discussed the research topics that will be needed in the future.
There is a personnel shortage in forensic community mental health, and the nurses face various difficulties, such as preventing recidivism and supporting social reintegration. Regarding support for nurses, many studies have been conducted on assessing the risk of violence by forensic patients. In Japan, the nursing practice items necessary for community support based on the Medical Treatment and Supervision Act, which covers the treatment of forensic patients, have been clarified. However, few studies have been conducted on support for forensic community mental health nurses in Japan, so research that seeks evidence to facilitate effective nursing practice is needed. Additionally, nurse education related to forensic community mental health is not well developed, so research is needed to develop an educational system
MRI 正常海馬における術中棘波,高周波振動および位相振幅結合に対するセボフルラン麻酔の影響
Introduction: The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFO), and phase-amplitude coupling using a modulation index (MI) in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography (ioECOG) in identifying the epileptogenic hippocampus during sevoflurane administration. Methods: Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography (eoECoG) evaluation. Patients were assigned to the Ictal (+) or Ictal (−) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. IoECoG was performed under 0.5 and 1.5 minimum alveolar concentration. The rates of spikes, ripples, fast ripples (FR), ripples on spikes (RonS), fast ripples on spikes (FRonS), and MI HFO (3-4 Hz) were evaluated. Results: During the ioECoG procedure, sevoflurane administration was found to significantly increase the rate of spikes RonS, FRonS and MI HFO (3-4 Hz) in the Ictal (+) group (P < 0.01). In contrast, the Ictal (−) group exhibited a paradoxical increase in the rate of ripples and FR (P < 0.05). Conclusions: Our findings indicate that the administration of sevoflurane during ioECOG in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, RonS, FRonS, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and FR in the non-epileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the non-epileptogenic hippocampus.権利情報:@ 2023 by the American Clinical Neurophysiology Society. This is a non-final version of an article published in final form in [J Clin Neurophysiol. 2023 Oct 30. doi: 10.1097/WNP.0000000000001031]
特定健診受診者を対象とした血尿に関連した腎機能低下に対する蛋白尿の相乗的な影響についての検証
Background: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. Methods: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. Results: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: - 0.95 [- 0.98 to - 0.92] vs - 0.86 [- 0.87 to - 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. Conclusions: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small.権利情報:© The Author(s), under exclusive licence to Japanese Society of Nephrology 2023. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s10157-023-02390-
経カテーテル的大動脈弁置換術を受ける患者における麻酔導入時のレミマゾラムとプロポフォールの全静脈麻酔の血行動態の比較:無作為化比較試験
Purpose: This study aimed to compare the hemodynamic effects of remimazolam- and propofol-based total intravenous anesthesia in patients who underwent transcatheter aortic valve replacement. Methods: This was a single-center, single-blind, randomized controlled trial set at Nara Medical University, Kashihara, Japan. We included 36 patients aged ≥ 20 years scheduled to undergo elective transfemoral transcatheter aortic valve replacement (TAVR) under general anesthesia. The participants were randomly assigned to the remimazolam and propofol groups (n=18 each). Remimazolam- or propofol-based total intravenous anesthesia was initiated at 12 mg/kg/min or 2.5 mcg/mL via target-controlled infusion, respectively, along with remifentanil. After confirming the loss of consciousness, the administration rate was adjusted using electroencephalographic monitoring. The primary outcome was the rate of arterial hypotension, defined as a mean arterial pressure <60 mmHg, from anesthesia induction until the beginning of the surgical incision. The total doses of ephedrine and phenylephrine were also assessed. Results: During anesthesia induction, the arterial hypotension rates were 11.9% and 21.6% in the remimazolam and propofol groups, respectively (P=0.01). The total dose of ephedrine was higher in the propofol group (14.4 mg) than in the remimazolam group (1.6 mg) (P<0.001); however, the total dose of phenylephrine was not significantly different between the two groups (propofol: 0.31 mg vs. remimazolam: 0.17 mg, P=0.10). Conclusions: Remimazolam-based total intravenous anesthesia resulted in a lower hypotension rate than propofol-based total intravenous anesthesia during induction in patients undergoing TAVR. Remimazolam-based total intravenous anesthesia can be used safely during anesthetic induction in patients with severe aortic stenosis.権利情報:© The Author(s) under exclusive licence to Japanese Society of Anesthesiologists 2024. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00540-024-03311-