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Diagnostic performance of advanced tomosynthesis in patients with metal devices in the affected knee: a case report. 先进断层扫描对患膝关节金属装置患者的诊断效果:病例报告。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-101
Yasushi Oshima, Tokifumi Majima

Simple radiography is the most frequently and widely available technology to examine bone pathologies. Computed tomography (CT) can evaluate pathologies more accurately in multiple planes and three dimensions; however, radiation exposure is much higher than with simple radiography. In addition, diagnostic ability is decreased for both technologies when metal devices are present. Tomosynthesis is a radiographic technology used to evaluate tissues quasi-three-dimensionally with less radiation exposure. Tomosynthesis technology was recently upgraded to reduce the effects of metal artifacts. This case report compares examination time, medical expense, image resolution, and radiation exposure for upgraded tomosynthesis, simple radiography, CT, and standard tomosynthesis in three patients with metal devices in the affected knees. Examination times were similar for the imaging technologies. Diagnostic performance was better for upgraded tomosynthesis than for simple radiography and standard tomosynthesis, and similar to that for CT. Moreover, radiation exposure and expense were higher for tomosynthesis than for simple radiography but lower than for CT. These findings suggest that upgraded tomosynthesis is the best method for evaluating bone pathology when metal devices are present and radiation exposure must be limited.

简单的射线照相术是检查骨骼病变最常用、最广泛的技术。计算机断层扫描(CT)可在多个平面和三个维度上更准确地评估病变,但辐射量远高于简单的射线照相术。此外,如果存在金属装置,这两种技术的诊断能力都会下降。Tomosynthesis 是一种放射摄影技术,用于对组织进行准三维评估,辐射量较少。Tomosynthesis 技术最近进行了升级,以减少金属伪影的影响。本病例报告比较了升级版断层合成术、简单放射摄影、CT 和标准断层合成术对三名患膝有金属装置的患者的检查时间、医疗费用、图像分辨率和辐射暴露。各种成像技术的检查时间相似。升级断层扫描的诊断效果优于简单放射摄影和标准断层扫描,与 CT 相似。此外,断层合成术的辐射量和费用高于简单放射摄影,但低于 CT。这些研究结果表明,当存在金属装置且必须限制辐射照射时,升级断层合成术是评估骨病理学的最佳方法。
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引用次数: 0
Delayed Diagnosis of Painless Thyroiditis in an Adolescent Presenting with Aggression and Disruptive Behavior Initially Attributed to Worsening of a Psychiatric Disorder. 最初因精神障碍恶化而出现攻击和破坏行为的青少年被延迟诊断为无痛性甲状腺炎》(Delayed Diagnosis of Painless Thyroiditis in an Adolescent Presenting with Aggression and Disruptive Behavior Initially Attributed to Worseening of a Psychiatric Disorder)。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-302
Yutaka Furuta, Takahiro Masuoka, Ryuichiro Narishige, Amane Tateno

Painless thyroiditis, which is rare in children, exhibits the characteristic sequence of hyperthyroidism, including aggressive and disruptive behaviors. Unlike subacute thyroiditis or Graves' disease, painless thyroiditis is challenging to diagnose because of its mild symptoms and minimal or absent physical findings. Moreover, aggressive and disruptive behaviors in children with psychiatric disorders may be misconstrued as exacerbation of underlying symptoms. The present patient was a 16-year-old male with adjustment disorder who presented to a pediatric psychiatric clinic for assessment of irritability. After 4 months, he developed aggressive and disruptive behaviors that prompted initiation of risperidone but without improvement. After 1 month, he reported palpitations and dyspnea. His neck was supple and non-tender without thyroid enlargement. Thyroid studies revealed elevated free T4 and T3 levels and suppressed thyroid-stimulating hormone level, suggesting hyperthyroidism. A radioactive iodine uptake test revealed a barely visible thyroid gland, consistent with thyroiditis. Painless thyroiditis, without thyroid tenderness, was diagnosed. We describe a case of painless thyroiditis in an adolescent patient with aggressive and disruptive behaviors that were initially attributed to worsening of an underlying adjustment disorder. Even when minimal or no signs of hyperthyroidism are present, painless thyroiditis should be considered in the differential diagnosis of children with aggressive and disruptive behaviors. Awareness of potential anchoring bias is also recommended to prevent its delayed diagnosis of such behaviors.

无痛性甲状腺炎在儿童中很少见,它具有甲状腺功能亢进症的特征性表现,包括攻击性和破坏性行为。与亚急性甲状腺炎或巴塞杜氏病不同的是,无痛性甲状腺炎症状轻微,体征极少或无体征,因此诊断难度很大。此外,患有精神疾病的儿童的攻击性和破坏性行为可能会被误认为是潜在症状的加重。本例患者是一名 16 岁的男性,患有适应障碍,因易激惹到儿科精神病诊所就诊。4 个月后,他出现了攻击性和破坏性行为,因此开始服用利培酮,但未见改善。1 个月后,他出现心悸和呼吸困难。他的颈部柔软无触痛,无甲状腺肿大。甲状腺检查显示游离 T4 和 T3 水平升高,促甲状腺激素水平降低,提示甲状腺功能亢进。放射性碘摄取试验显示甲状腺几乎不可见,与甲状腺炎一致。诊断结果为无痛性甲状腺炎,无甲状腺压痛。我们描述了一例青少年患者的无痛性甲状腺炎病例,该患者具有攻击性和破坏性行为,最初被认为是潜在的适应障碍恶化所致。即使甲状腺功能亢进的症状很轻微或没有出现,在对有攻击性和破坏性行为的儿童进行鉴别诊断时,也应考虑无痛性甲状腺炎。此外,还建议注意潜在的锚定偏差,以防止此类行为被延误诊断。
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引用次数: 0
New-onset schizophrenia in an adolescent after COVID-19. 一名青少年在服用 COVID-19 后新发精神分裂症。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-301
Masatsugu Ishii, Kakusho C Nakajima-Ohyama, Hayato Saito, Tomoyuki Ohya, Shotaro Uchiyama, Mizuho Takahashi, Masanori Sakamaki, Akihiro Watanabe, Jun-Ichi Inoue, Tetsuro Sekine, Amane Tateno, Yasuhiro Kishi

Schizophrenia develops during adolescence. Maternal infections during the fetal period increase the incidence of schizophrenia in children, which suggests that the pathogenesis involves neuroinflammation. Here, we report a case of new-onset schizophrenia in a 16-year-old boy after COVID-19. After developing COVID-19, he entered a catatonic state 4 days later and was hospitalized. Benzodiazepines alleviated his catatonia, but hallucinations and delusions persisted. Encephalitis and epilepsy were excluded by magnetic resonance imaging (MRI), encephalography, and cerebrospinal fluid examination. Psychosis persisted after the virus titer declined and the inflammatory response subsided. Moreover, the patient exhibited delusions of control-a Schneider's first-rank symptom. Schizophrenia was diagnosed, and olanzapine improved his symptoms. He had a brief history of insomnia before COVID-19 but his symptoms did not satisfy the ultra-high-risk criteria. However, COVID-19 may have facilitated development of schizophrenia through neuroinflammation and volume reduction in the gray matter of the right medial temporal lobe. This case demonstrates that infectious diseases in adolescents should be carefully managed, to prevent schizophrenia.

精神分裂症在青春期发病。胎儿期母体感染会增加儿童精神分裂症的发病率,这表明发病机制涉及神经炎症。在此,我们报告了一例因 COVID-19 而新发精神分裂症的 16 岁男孩。患 COVID-19 后,他在 4 天后进入紧张性精神分裂症状态并住院治疗。苯二氮卓类药物缓解了他的紧张症,但幻觉和妄想仍然存在。通过磁共振成像(MRI)、脑电图和脑脊液检查,排除了脑炎和癫痫的可能性。病毒滴度下降、炎症反应消退后,精神错乱仍然存在。此外,患者还表现出控制妄想--施耐德的一级症状。诊断结果为精神分裂症,奥氮平改善了他的症状。在 COVID-19 之前,他曾有过短暂的失眠病史,但其症状并不符合超高风险标准。然而,COVID-19 可能通过神经炎症和右侧内侧颞叶灰质体积缩小促进了精神分裂症的发展。本病例表明,应谨慎处理青少年感染的传染性疾病,以预防精神分裂症的发生。
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引用次数: 0
Isolated prosopagnosia caused by damage to the right inferior longitudinal fasciculus: a case report. 右下纵筋膜受损导致的孤立性嗜眠症:病例报告。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-202
Harumi Morioka, Masaru Yanagihashi, Mikito Toda, Takanori Ikeda, Masafumi Mizuno, Masaaki Hori, Kouhei Kamiya, Osamu Kano

Prosopagnosia is a cognitive disorder in which facial recognition is severely impaired despite normal vision and intelligence. Prosopagnosia was first reported in the 1800s, but its cause remains unclear. Although other neurological symptoms are often present, some patients have pure prosopagnosia. The bilateral occipital lobes are believed to be associated with symptoms. Recent brain imaging techniques have identified the right fusiform gyrus (rFG), located at the junction of the right occipital temporal lobe, as the affected region. In this report, we present a case of associative prosopagnosia with no concomitant symptoms in a 76-year-old man. Brain magnetic resonance imaging detected a subcortical hemorrhage in the right temporal lobe. Using tractography based on diffusion tensor imaging, we visualized atrophy of the right inferior longitudinal fasciculus (ILF). This is the first time tractography has been used to show a clear association between associative prosopagnosia and ILF damage projecting from the rFG.

面容失认症是一种认知障碍疾病,患者虽然视力和智力正常,但面部识别能力却严重受损。障眼症在 19 世纪首次被报道,但其病因至今仍不清楚。虽然经常出现其他神经系统症状,但有些患者是纯粹的前额失认症。双侧枕叶被认为与症状有关。最近的脑成像技术发现,位于右枕颞叶交界处的右侧纺锤形回(rFG)是受影响的区域。在本报告中,我们介绍了一例无伴随症状的联想性前视障碍病例,患者是一名 76 岁的男性。脑磁共振成像检测到右侧颞叶皮质下出血。利用基于弥散张量成像的束成像技术,我们观察到右侧下纵筋束(ILF)萎缩。这是首次使用束成像技术来显示联想性嗜睡症与从rFG投射的ILF损伤之间存在明确的关联。
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引用次数: 0
Cerebrospinal fluid leakage due to dural thinning after endoscopic pituitary tumor resection. 内窥镜垂体瘤切除术后硬脑膜变薄导致脑脊液漏。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-102
Shinichiro Teramoto

Sellar reconstruction is important for preventing cerebrospinal fluid (CSF) leakage after transsphenoidal pituitary surgery. This report describes how, despite standard sellar reconstruction, CSF exudation resulted from dural thinning at the anterior skull base, outside the intrasellar area manipulated during pituitary tumor resection. A 76-year-old man underwent endoscopic transsphenoidal surgery for a pituitary tumor extending toward the anterior skull base. After opening the sellar floor, intractable bleeding from the anterior intercavernous sinus occurred during bone removal at the anterior skull base. Pseudocapsule-based extracapsular resection was completed after stopping the bleeding. On the 10th postoperative day, the patient developed CSF rhinorrhea complicated by marked pneumocephalus, and emergency endoscopic repair of the CSF leak was performed. CSF leakage originated from the thinned dura at the anterior skull base located outside the intrasellar area manipulated during tumor resection. The thinned dural area at the anterior skull base coincided with the site of intractable bleeding of the anterior intercavernous sinus during bone removal in tumor resection. The thinned anterior skull base dura was covered with fascia, overlaid with fat, and closed with the nasoseptal flap. Endoscopic CSF leak repair was successful. Severe damage to the anterior intercavernous sinus can cause extensive exposure of the single-layered inner meningeal dura, where thinning might result in CSF exudation. Therefore, use of autologous tissues to cover and reinforce the severely damaged area of the anterior intercavernous sinus might help prevent postoperative CSF exudation.

蝶窦重建对于经蝶垂体手术后防止脑脊液(CSF)渗漏非常重要。本报告描述了尽管进行了标准的蝶窦重建,但由于前颅底硬脑膜变薄,在垂体瘤切除术中操作的蝶窦内区域外导致了 CSF 渗漏。一名 76 岁的男性因垂体瘤向前方颅底延伸而接受了内窥镜经蝶窦手术。打开蝶窦底后,在前颅底进行骨切除时,前腔间窦发生了难治性出血。在止血后,完成了基于假囊的囊外切除术。术后第 10 天,患者出现 CSF 鼻溢液,并伴有明显的气胸,于是紧急进行了内镜下 CSF 渗漏修补术。CSF 渗漏源于前颅底的硬脑膜变薄,位于肿瘤切除术中操作的椎管内区域之外。前颅底硬脑膜变薄的部位与肿瘤切除术中切除骨时前腔窦难治性出血的部位相吻合。用筋膜覆盖变薄的前颅底硬脑膜,再覆盖脂肪,最后用鼻隔皮瓣缝合。内窥镜 CSF 漏修补术获得成功。前腔窦的严重损伤会导致单层内脑膜硬脑膜广泛暴露,变薄的硬脑膜可能会导致 CSF 渗出。因此,使用自体组织覆盖和加固前腔窦的严重受损部位可能有助于防止术后 CSF 渗出。
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引用次数: 0
Migraine-like headache with aura induced by a small infarct in the parieto-occipital cortex: A case report. 顶枕叶皮层小梗塞诱发的偏头痛样先兆头痛:病例报告。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-103
Hiroyuki Hokama, Yuki Sakamoto, Serika Yamamoto, Mizuho Takahashi, Hiroto Kodera, Akihito Kutsuna, Yosuke Fujisawa, Chikako Nito, Kazumi Kimura

A 56-year-old right-handed man was referred to our hospital for evaluation of sudden-onset transient quadrantanopia, which was followed by throbbing headache consistent with migraine with aura (MA). Magnetic resonance imaging (MRI) of the right parieto-occipital cortex on admission showed a hyperintense region on diffusion-weighted imaging, which disappeared 7 days later. A small cortical infarct in the parieto-occipital cortex can cause MA-like headache, and the present infarct lesion was only detectable on MRI during the acute phase. Performing MRI for patients with suspected acute MA might help identify the cause of MA-like headache and ensure appropriate management of patients.

一名 56 岁的右撇子男子因突发性一过性象限视力障碍转诊至我院,随后出现与先兆偏头痛(MA)一致的搏动性头痛。入院时右侧顶枕皮层的磁共振成像(MRI)显示,弥散加权成像上有一个高强度区域,7 天后该区域消失。顶枕叶皮质的小皮质梗死可导致 MA 样头痛,而目前的梗死病灶只有在急性期才能在核磁共振成像中发现。对疑似急性MA患者进行磁共振成像检查有助于确定MA样头痛的病因,确保对患者进行适当的治疗。
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引用次数: 0
Use of tocilizumab to treat arthritis associated with mixed connective tissue disease complicated by ovarian teratoma: a case report. 使用托西珠单抗治疗卵巢畸胎瘤并发混合结缔组织病相关关节炎:病例报告。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-06-18 DOI: 10.1272/jnms.JNMS.2025_92-303
Haruka Ota, Toru Igarashi, Ryosuke Matsui, Hikaru Takeshita, Koji Hashimoto, Masaki Miyao, Norio Motoda, Tsubasa Takahashi, Jun Hayakawa, Makoto Migita, Yasuhiko Itoh

Mixed connective tissue disease (MCTD) is characterized by mixed features of systemic lupus erythematosus, systemic sclerosis, and polymyositis/dermatomyositis and is rare in children. Here, we report a case of MCTD in a 10-year-old girl who presented at our hospital with arthralgia, Raynaud's phenomenon, and fatigue. Blood tests were positive for anti-U1-ribonucleoprotein (RNP) antibodies and for rheumatoid factors (RFs) IgG-RF and anti-galactose-deficient IgG. Levels of myogenic enzymes and hypergammaglobulinemia were elevated. Macrophages were prominent in bone marrow, with scattered phagocytic macrophages. MCTD was diagnosed based on the patient's symptoms and laboratory findings. Methylprednisolone pulse therapy combined with oral tacrolimus was administered, which led to resolution of symptoms. Three months after pulse therapy, arthralgia worsened and methotrexate was administered. Arthralgia improved but did not resolve. Magnetic resonance imaging performed to investigate the hip pain revealed a mature ovarian teratoma, which was surgically removed. Because the pain persisted and interfered with her daily life, she was treated with tocilizumab for joint pain relief, which decreased the pain level. Tocilizumab is a candidate for additional treatment of juvenile idiopathic arthritis-like arthritis associated with childhood-onset MCTD.

混合性结缔组织病(MCTD)的特征是系统性红斑狼疮、系统性硬化症和多发性肌炎/皮肌炎的混合症状,在儿童中非常罕见。在此,我们报告了一例 10 岁女孩的 MCTD 病例,她因关节痛、雷诺现象和乏力到我院就诊。血检结果显示抗 U1 核糖核蛋白(RNP)抗体、类风湿因子(RFs)IgG-RF 和抗半乳糖缺乏 IgG 阳性。肌酶和高丙种球蛋白血症水平升高。骨髓中巨噬细胞突出,并伴有散在的吞噬性巨噬细胞。根据患者的症状和实验室检查结果,确诊为 MCTD。患者接受了甲基强的松龙脉冲疗法,同时口服他克莫司,症状有所缓解。脉冲疗法三个月后,关节痛加重,于是使用了甲氨蝶呤。关节痛有所改善,但没有缓解。为检查髋部疼痛而进行的磁共振成像检查发现了一个成熟的卵巢畸胎瘤,并进行了手术切除。由于疼痛持续存在,影响了她的日常生活,她接受了托珠单抗治疗以缓解关节疼痛,疼痛程度有所减轻。托西珠单抗是治疗与儿童期发病的 MCTD 相关的幼年特发性关节炎样关节炎的一种候选药物。
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引用次数: 0
Difficulties Nurses Report in Caring for Patients with Bone Metastases and Their Expectations after Participating in a Bone Metastasis Cancer Board: A Questionnaire Study. 护士在护理骨转移患者时遇到的困难及其参加骨转移癌症委员会后的期望:一项问卷调查研究。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-21 Epub Date: 2024-03-02 DOI: 10.1272/jnms.JNMS.2024_91-210
Tsunemi Kitagawa, Yasuyuki Kitagawa, Yoichiro Aoyagi, Tokifumi Majima

Background: Patients with bone metastases often face physical, mental, and social challenges that require multidisciplinary management. To improve treatment and practice, we conducted a questionnaire survey to assess nurses' opinions of problems related to caring for patients with bone metastases. In addition, we investigated nurses' perceptions of bone metastases after participating in a Bone Metastasis Cancer Board (BMCB).

Methods: An anonymous questionnaire survey on problems in bone metastasis treatment and the BMCB was conducted. The respondents were nurses with more than 1 year of clinical experience working in wards where patients with bone metastases were admitted.

Results: The number of valid responses was 224. Almost all the nurses felt anxiety about the risk of pathological fracture and paralysis while caring for patients with bone metastases. To reduce this anxiety, about 90% of the nurses supported the suggestion that "patients should be referred to an orthopedic surgeon in advance to obtain opinions on load restrictions". Nurses who had participated in the BMCB had higher expectations regarding treatment, multidisciplinary collaboration, and sharing and accumulating knowledge and experience.

Conclusion: To improve treatment and nursing care for patients with bone metastases, it is important to make regular BMCB meetings more functional and to actively consult with specialists.

背景:骨转移患者通常面临身体、精神和社会方面的挑战,需要多学科的管理。为了改善治疗和实践,我们进行了一项问卷调查,以评估护士对护理骨转移患者相关问题的看法。此外,我们还调查了护士参加骨转移癌委员会(BMCB)后对骨转移的看法:方法:我们就骨转移治疗和骨转移癌委员会中存在的问题进行了匿名问卷调查。调查对象为在收治骨转移患者的病房工作一年以上、具有临床经验的护士:有效回答数为 224 个。几乎所有护士都对护理骨转移患者时发生病理性骨折和瘫痪的风险感到焦虑。为减轻这种焦虑,约 90% 的护士支持 "应提前将患者转诊至骨科医生处,以获得有关负荷限制的意见 "的建议。参加过 BMCB 的护士对治疗、多学科合作以及分享和积累知识和经验有更高的期望:结论:为改善骨转移患者的治疗和护理,必须使 BMCB 定期会议发挥更大作用,并积极向专家咨询。
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引用次数: 0
Oxidative Stress and Antioxidant Capacity in Patients with Endometrioma. 子宫内膜瘤患者的氧化应激和抗氧化能力。
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-21 Epub Date: 2024-03-02 DOI: 10.1272/jnms.JNMS.2024_91-204
Go Ichikawa, Yasuyuki Negishi, Ryo Tsuchiya, Lilika Higuchi, Tatsunori Shiraishi, Mariko Ikeda, Hanako Kaseki, Rimpei Morita, Shunji Suzuki

Background: Endometriosis has several clinical features, including dysmenorrhea, infertility, and endometrioma (EMO). Although oxidative stress status is closely related to endometriosis, it is unclear how the balance between oxidative stress capacity and antioxidant capacity correlates with treatment of or factors that worsen endometriosis. In this study, we used peritoneal fluid from patients with EMO to investigate the role of oxidative stress capacity and antioxidant capacity.

Materials and methods: Participants with EMO (n = 30) and without EMO (uterine myoma, n = 13) were enrolled. All peritoneal fluid samples were collected at the beginning of surgery. We evaluated oxidative stress capacity and antioxidant capacity in peritoneal fluid samples by using the diacron-reactive oxygen metabolites (d-ROM) and biological antioxidant potential (BAP) tests, respectively. The d-ROM and BAP values and the d-ROM/BAP ratio were measured, and their correlations with the CA125 level, revised American Society for Reproductive Medicine (r-ASRM) score, and tumor size were analyzed.

Results: The d-ROM/BAP ratio was significantly higher in patients with EMO than in those without EMO. In addition, the d-ROM/BAP ratio was positively correlated with CA125 level and r-ASRM scores in patients with EMO.

Conclusions: Oxidative stress is correlated with factors that worsen EMO. The d-ROM/BAP test may be useful for assessing disease status in patients with EMO.

背景子宫内膜异位症有多种临床特征,包括痛经、不孕和子宫内膜瘤(EMO)。虽然氧化应激状态与子宫内膜异位症密切相关,但氧化应激能力和抗氧化能力之间的平衡与子宫内膜异位症的治疗或恶化因素之间的关系尚不清楚。在这项研究中,我们使用 EMO 患者的腹腔液来研究氧化应激能力和抗氧化能力的作用。所有腹腔液样本均在手术开始时采集。我们分别使用二电子反应氧代谢物(d-ROM)和生物抗氧化潜能(BAP)测试评估了腹腔液样本的氧化应激能力和抗氧化能力。结果EMO患者的d-ROM/BAP比值明显高于非EMO患者。此外,EMO 患者的 d-ROM/BAP 比值与 CA125 水平和 r-ASRM 评分呈正相关。d-ROM/BAP测试可用于评估EMO患者的疾病状态。
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引用次数: 0
Methylation of PLK-1 Potentially Drives Bendamustine Resistance in Leukemia Cells. PLK-1的甲基化可能导致白血病细胞对本达莫司汀产生抗药性
IF 1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-05-21 Epub Date: 2023-12-08 DOI: 10.1272/jnms.JNMS.2024_91-206
Toshikazu Itabashi, Takahiro Ueda, Ryohei Fukunaga, Takeshi Asano, Yasuhiko Itoh

Background: Drug resistance remains a significant impediment in leukemia treatment. While Bendamustine hydrochloride (BH) stands out as a promising therapeutic agent for non-Hodgkin's lymphoma and mantle cell lymphoma, the mechanisms of resistance to BH are not yet fully understood. Our study focuses on elucidating the mechanisms behind bendamustine resistance in leukemia cells, with a specific emphasis on epigenetics.

Methods: Bendamustine-resistant cells were cultivated from human B cell lymphoblastic leukemia cell lines through systematic and sustained exposure to bendamustine, using the limiting dilution method. Gene expression was assessed via real-time polymerase chain reaction, while the expression of the multidrug resistance protein 1 (MDR1) was evaluated using flow cytometry.

Results: Bendamustine-resistant leukemia cells exhibited a decreased RNA expression level for Polo-like kinase-1 (PLK-1). Notably, after treatment with the demethylating agent 5-aza-2'-deoxycytidine, PLK-1 gene expression surged significantly, enhancing bendamustine's cytotoxicity in the resistant leukemia cells. However, MDR1 expression, as determined by flow cytometry, remained consistent between parental and bendamustine-resistant leukemia cells.

Conclusions: Our findings indicate that the methylation of the PLK-1 gene plays a pivotal role in modulating PLK-1 expression and is central to the development of bendamustine resistance in leukemia cells.

背景:耐药性仍然是白血病治疗的一大障碍。虽然盐酸苯达莫司汀(BH)是治疗非霍奇金淋巴瘤和套细胞淋巴瘤的一种很有前景的药物,但对 BH 产生耐药性的机制尚未完全清楚。我们的研究重点是阐明白血病细胞对苯达莫司汀产生耐药性的机制,特别强调表观遗传学:方法:使用极限稀释法,从人类 B 细胞淋巴母细胞白血病细胞系中培养出苯达莫司汀耐药细胞,这些细胞系通过系统、持续地接触苯达莫司汀而产生耐药。基因表达通过实时聚合酶链反应进行评估,多药耐药蛋白1(MDR1)的表达则通过流式细胞术进行评估:结果:对苯达莫司汀耐药的白血病细胞表现出Polo-like kinase-1(PLK-1)的RNA表达水平下降。值得注意的是,在使用去甲基化药物 5-aza-2'-deoxycytidine 处理后,PLK-1 基因表达明显增加,从而增强了苯达莫司汀对耐药白血病细胞的细胞毒性。然而,通过流式细胞术测定的MDR1表达在亲代白血病细胞和苯达莫司汀耐药白血病细胞中保持一致:我们的研究结果表明,PLK-1基因的甲基化在调节PLK-1表达方面起着关键作用,是白血病细胞产生苯达莫司汀耐药性的核心。
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引用次数: 0
期刊
Journal of Nippon Medical School
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