IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100581

Qie Liu , Lu Zhang , Xin Xu

Objective

The authors explored differentially expressed circRNAs in Acute Ischemic Stroke (AIS) and revealed the role and potential downstream molecular mechanisms of circLOC375190.

Methods

circLOC375190 expression was modulated by lentiviral injection in the brain of transient Middle Cerebral Artery Occlusion (tMCAO) mice. Neurological dysfunction was assessed, as well as infarction size, histopathological changes, and neuronal apoptosis in tMCAO mice. An in vitro Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) PC-12 cell model was established. PC-12 cells were transfected and evaluated for viability, cytotoxicity, apoptosis, and autophagy. Inflammatory factors in mouse brain tissues and PC-12 cells were examined via enzyme-linked immunosorbent assay, and related genes were measured via real-time reverse transcriptase-polymerase chain reaction and Western blot. The ring structure of circLOC375190 was assessed by actinomycin-D and RNase-R assays. circRNA targeting to downstream factors was assessed by Fluorescence in situ hybridization assay, dual luciferase reporter assay, and RNA immunoprecipitation assay.

Results

circLOC375190 level was increased in tMCAO mice. Knocking down circLOC375190 reduced infarct size, attenuated cerebral pathological injury and neuronal apoptosis, and inhibited inflammatory damage and autophagy in tMCAO mice. circLOC375190 knockdown enhanced neuronal viability and reduced cytotoxicity, apoptosis, and autophagy in OGD/R-treated PC12 cells. Mechanistically, circLOC375190 acted as a sponge for miR-93-5p to upregulate MAP kinase interacting serine/threonine kinase 2 expression and activate the mechanistic target of rapamycin complex 1/transcription factor EB pathway.

Conclusion

circLOC375190 exacerbates tMCAO-mediated neurological injury by regulating neuronal autophagy.

目的：探讨急性缺血性卒中（AIS）中差异表达的circRNAs，揭示cirloc375190的作用及其潜在的下游分子机制。方法：用慢病毒注射调节短暂性大脑中动脉闭塞（tMCAO）小鼠脑内circLOC375190的表达。评估tMCAO小鼠的神经功能障碍、梗死大小、组织病理学改变和神经元凋亡。建立体外氧葡萄糖剥夺/再氧化（OGD/R） PC-12细胞模型。转染PC-12细胞并评估其活力、细胞毒性、凋亡和自噬。采用酶联免疫吸附法检测小鼠脑组织和PC-12细胞中的炎症因子，采用实时逆转录-聚合酶链反应和Western blot检测相关基因。通过放线菌素- d和RNase-R测定circLOC375190的环结构。通过荧光原位杂交法、双荧光素酶报告基因法和RNA免疫沉淀法评估circRNA对下游因子的靶向性。结果：tMCAO小鼠体内circLOC375190水平升高。敲除circLOC375190可减少tMCAO小鼠的梗死面积，减轻脑病理损伤和神经元凋亡，抑制炎症损伤和自噬。在OGD/ r处理的PC12细胞中，敲低circLOC375190可增强神经元活力，降低细胞毒性、凋亡和自噬。机制上，circLOC375190作为miR-93-5p的海绵，上调MAP激酶相互作用的丝氨酸/苏氨酸激酶2的表达，激活雷帕霉素复合物1/转录因子EB通路的机制靶点。结论：circLOC375190通过调节神经元自噬加重tmcao介导的神经损伤。

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引用次数: 0

A study on the intervention of eight-section brocade exercises in combination with comprehensive measures on the physical function status of patients with chronic obstructive pulmonary disease 八段锦操配合综合措施对慢性阻塞性肺疾病患者身体功能状况的干预研究

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2024.100536

Jiezhen Li , Yan Lei , Meini Li

Background

Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease with a long course and recurrent symptoms, seriously affecting patients' quality of life.

Objectives

This study aimed to explore the interventional value of eight-section brocade exercises in combination with comprehensive measures of the physical function status of patients with COPD.

Method

This is a retrospective study. A total of 94 COPD patients admitted to the studied hospital were divided into two groups according to different intervention methods. The control group was treated with comprehensive intervention, and the research group received eight-section brocade exercises combined with comprehensive intervention.

Results

After an intervention, the research group exhibited longer exercise endurance time (p < 0.05); the modified Medical Research Council (mMRC) scores and quality of life scores in the research group were lower than those in the control group (p < 0.05); sleep quality scores of the research group being lower than those of the control group (p < 0.05); both groups experienced a decrease in adverse emotion scores, with the research group scoring lower than the control group (p < 0.05); the research group achieving better physical function status than the control group (p < 0.05); the nursing efficiency rate and satisfaction rate in the research group was higher than those in the control group (p < 0.05).

Conclusions

Eight-section brocade exercises can enhance the exercise endurance of and improve the lung function of COPD patients, which is of great significance for the recovery of patients’ physical function.

背景：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease， COPD）是一种常见的慢性呼吸系统疾病，病程长，症状反复发作，严重影响患者的生活质量。目的：探讨八段锦操结合COPD患者身体功能状态综合测量的干预价值。方法：回顾性研究。将94例COPD住院患者根据干预方式的不同分为两组。对照组采用综合干预治疗，研究组采用八段锦操结合综合干预治疗。结果：实验组干预后运动耐力时间延长（p < 0.05）；研究组改良医学研究理事会（mMRC）评分和生活质量评分低于对照组（p < 0.05）；研究组睡眠质量评分低于对照组（p < 0.05）；两组患者不良情绪评分均降低，且研究组低于对照组（p < 0.05）；研究组身体功能状态优于对照组（p < 0.05）；研究组护理有效率、满意率均高于对照组（p < 0.05）。结论：八段锦操可增强COPD患者的运动耐力，改善肺功能，对患者身体功能的恢复具有重要意义。

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引用次数: 0

Role of centchroman in regression of fibroadenoma: A 2-arm randomized control trial centchroman在纤维腺瘤消退中的作用：一项两组随机对照试验。

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2024.100567

Priyanka Rai , Soniya Nityanand , Amarjot Singh , Sunil Kumar Singh , Neha Singh , Arvind Kumar Singh , Dhananjay Singh

Background

Fibroadenomas are common benign breast lumps that can cause anxiety due to malignancy concerns, and Centchroman, a selective estrogen receptor modulator, has shown promise in reducing their size. This study aimed to evaluate the efficacy of Centchroman in reducing fibroadenoma size, mastalgia, anxiety, and depression in affected patients.

Methodology

A parallel-arm randomized controlled trial was conducted at a tertiary care Breast Clinic with 104 patients aged 18‒45 years having fibroadenomas ≤ 3 cm. Group A received Centchroman (30 mg on alternate days) and Group B received a placebo for 12 weeks. The primary outcome was fibroadenoma volume reduction measured by ultrasound, while secondary outcomes included reductions in mastalgia and improvements in anxiety and depression (HADS scores).

Results

Both groups showed fibroadenoma volume reduction over 12-weeks, with a greater reduction in the intervention group (3.67 ± 1.65 cm³ to 2.29 ± 1.04 cm³) than the control group (3.12 ± 1.16 cm³ to 2.73 ± 0.78 cm³), though the difference was not statistically significant (p = 0.342 and p = 0.781). However, 28.8 % of the intervention group experienced over 50 % volume reduction compared to 13.5 % in the control group (p = 0.007). Mastalgia significantly improved in the intervention group (VAS: 5.76 ± 2.13 to 2.24 ± 0.93, p = 0.023), with minimal improvement in controls. Anxiety and depression scores significantly decreased in the intervention group, with anxiety dropping from 9 to 5 and depression from 6 to 4 (p = 0.001).

Conclusion

Centchroman effectively reduces fibroadenoma size especially those with multiple fibroadenoma, mastalgia, and psychological distress in patients with fibroadenoma.

背景：纤维腺瘤是一种常见的良性乳腺肿块，可引起因恶性肿瘤引起的焦虑，而选择性雌激素受体调节剂Centchroman已显示出缩小其大小的希望。本研究旨在评估Centchroman在减少纤维腺瘤大小、乳房痛、焦虑和抑郁方面的疗效。方法：在一家三级乳腺诊所进行了一项平行组随机对照试验，纳入了104例年龄在18-45岁、纤维腺瘤≤3 cm的患者。A组服用Centchroman （30 mg，隔天服用），B组服用安慰剂，疗程12周。主要结果是超声测量纤维腺瘤体积缩小，次要结果包括乳房痛的减少和焦虑和抑郁的改善（HADS评分）。结果：两组患者12周内纤维腺瘤体积均缩小，干预组缩小幅度（3.67±1.65 cm3至2.29±1.04 cm3）大于对照组（3.12±1.16 cm3至2.73±0.78 cm3），但差异无统计学意义（p = 0.342和p = 0.781）。然而，28.8%的干预组经历了超过50%的体积缩小，而对照组为13.5% （p = 0.007）。干预组乳痛明显改善（VAS: 5.76±2.13 ~ 2.24±0.93,p = 0.023），对照组改善最小。干预组焦虑和抑郁得分显著下降，焦虑从9分降至5分，抑郁从6分降至4分（p = 0.001）。结论：Centchroman能有效地减少纤维腺瘤的大小，特别是对多发纤维腺瘤、乳房疼痛和纤维腺瘤患者的心理困扰。

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引用次数: 0

Descriptive study of claims in primary care during the year 2022 in a health area of Spain 对西班牙某卫生地区2022年初级保健索赔的描述性研究。

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2024.100546

María F. Velázquez-López , María García-Pérez , Montserrat Souto-Pereira , Juan M. Vazquez-Lago

Background

Primary Health Care (PHC) plays a pivotal role in the healthcare system as the initial point of contact for users and patients. In the healthcare area, claims are presented and managed through a web app. It also enables systematic analysis of emerging information to drive continuous improvement. The present objective was to describe the complaints filed at PHC in 2022.

Methods

A cross-sectional study was conducted, examining complaints filed by patients in 2022. For inclusion of the complaints, it was established that it had to do with the treatment received by healthcare personnel and that was presented through the web app. Complaint texts signaling dissatisfaction with the information received were subjected to qualitative coding.

Results

The study involved 326 users who submitted a total of 358 complaints specifically related to treatment and information. The average age of the participants was 33.5 ± 16.2 years, and the majority were women (72.4 %, n = 236). In 2022, the Cumulative Incidence (CCI) was 55.2 complaints per 100,000 healthcare act and the Complaint Incidence Rate (CIR), defined as the number of complaints/1000 users/year, was 6.5. The prevalence of complaints related to information was 12.4 %. The main reasons for complaints about information were issues related to communication with the patient (79 %), followed by the patient's disagreement with the techniques applied by healthcare staff (17 %).

Conclusions

Results show us the fundamental characteristics of complaints in primary care with respect to the information received by health professionals, not allowing us to know where the authors can influence through interventions or training actions to try to improve.

背景：初级卫生保健（PHC）作为用户和患者的初始接触点，在卫生保健系统中起着关键作用。在医疗保健领域，索赔是通过网络应用程序呈现和管理的。它还可以对新出现的信息进行系统分析，以推动持续改进。目前的目标是描述2022年在PHC提出的投诉。方法：采用横断面研究，对2022年患者提出的投诉进行调查。为了纳入投诉，确定投诉与卫生保健人员接受的治疗有关，并通过网络应用程序呈现。对收到的信息表示不满的投诉文本进行了定性编码。结果：该研究涉及326名用户，他们总共提交了358起与治疗和信息相关的投诉。参与者的平均年龄为33.5±16.2岁，以女性为主（72.4%,n = 236）。2022年，累计发病率（CCI）为每10万次医疗保健法案55.2次投诉，投诉发生率（CIR）为6.5次投诉，定义为每1000名用户/年的投诉数量。与信息相关的投诉占12.4%。投诉信息的主要原因是与患者沟通有关的问题（79%），其次是患者不同意医护人员使用的技术（17%）。结论：结果向我们展示了初级保健投诉的基本特征，以及卫生专业人员收到的信息，但不允许我们知道作者可以通过干预或培训行动影响哪些方面，以试图改善。

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引用次数: 0

Infiltration of micro-fragmented adipose tissue under local anesthesia for knee osteoarthritis treatment is a safe procedure: A case series 局部麻醉下微碎片脂肪组织浸润治疗膝骨关节炎是一种安全的方法：一个病例系列。

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2024.100527

Bruno Butturi Varone, Daniel Peixoto Leal, Daniel Duarte Perini, Vitor Penteado Figueiredo Pagotto, Riccardo Gomes Gobbi, Marco Kawwamura Demange

Introduction

Knee osteoarthritis is a debilitating disease that has been increasing in prevalence, especially due to the aging population and rising incidence of obesity. Biological therapies (orthobiologics) have emerged, demonstrating efficacy in improving functional scores, including the injection of microfragmented Adipose Tissue (mFAT). The purpose of this study is to evaluate the safety of adipose tissue harvesting and mFAT injection under local anesthesia.

Materials/methods

A case series involving 34 patients who underwent adipose tissue collection from the abdomen under local anesthesia, without sedation, in a sterile environment, and who received the infiltration of microfragmented adipose tissue after single-time preparation, using a fat washing and microfragmentation kit.

Results

Evaluation was performed at the time of the procedure and after 7 days of follow-up. Only ecchymosis (76.5 %) and mild discomfort at the harvested site (70.6 %), as well as mild discomfort at the infiltrated knee (61.8 %), were identified. No major adverse events were identified.

Conclusion

The harvesting and injection of mFAT under local anesthesia is safe, with no major adverse events identified during this procedure.

导读：膝关节骨性关节炎是一种使人衰弱的疾病，其发病率一直在上升，特别是由于人口老龄化和肥胖发病率的上升。生物疗法（orthobiologics）已经出现，显示出改善功能评分的有效性，包括注射微碎片脂肪组织（microfragmentation Adipose Tissue, mFAT）。本研究的目的是评估局麻下脂肪组织采集和mFAT注射的安全性。材料/方法：34例患者在局部麻醉下，不使用镇静，无菌环境下从腹部收集脂肪组织，使用脂肪洗涤和微碎片化试剂盒，一次性制备后进行微碎片化脂肪组织浸润。结果：在手术时和随访7天后进行评估。仅发现瘀斑（76.5%）和收获部位轻度不适（70.6%），以及浸润膝关节轻度不适（61.8%）。未发现重大不良事件。结论：局麻下mFAT的采集和注射是安全的，在此过程中未发现重大不良事件。

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引用次数: 0

mtDNA deletion m.8753_16566 with < 10 % heteroplasmy in muscle and isolated complex-V dysfunction misinterpreted as chronic fatigue syndrome over 21-years mtDNA缺失m.8753_16566，肌肉异质性< 10%，孤立的复合体- v功能障碍，21年来被误解为慢性疲劳综合征

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100604

Josef Finsterer , Ana C. Fiorini , Fulvio A. Scorza , Carla A. Scorza

引用次数: 0

Magnetic resonance-guided focused ultrasound for uterine fibroids 磁共振引导聚焦超声治疗子宫肌瘤

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100603

Pedro Felipe Magalhães Peregrino, Marcos de Lorenzo Messina, José Maria Soares Júnior, Edmund Chada Baracat

Introduction

The uterine leiomyoma is a pelvic solid tumor more frequent in women. The Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) is a technique aimed at diminishing hypermenorrhagia and dysmenorrhea in symptomatic women.

Objective

To show the effects subsequent to MRgFUS application on symptoms, quality of life, and myoma volume in symptomatic women.

Methods

Fifty-two patients with symptomatic uterine myomas underwent MRgFUS followed by clinical evaluation, pelvis MRI, and administration of the UFS-QoL questionnaire at 6 months and 12 months to detect symptom improvements and decrease in myoma volume.

Results

The mean myoma volume decreased 24 % after 6 months and 42 % after 12 months. The mean score on the UFS-QoL questionnaire increased 54 % after 6 months and 81 % after 12 months. There were no serious complications. Four patients had first-degree burns. No infection cases were reported. Two patients progressed to a myomectomy by surgical hysteroscopy and one of them underwent total hysterectomy 11 months after the MRgFUS treatment.

Conclusion

This case series suggests that MRgFUS therapy is viable and effective in reducing symptoms and improving the life quality of symptomatic patients.

子宫平滑肌瘤是一种多发于女性的盆腔实体瘤。磁共振引导聚焦超声（MRgFUS）是一种旨在减少月经过多和痛经症状妇女的技术。目的探讨MRgFUS应用后对有症状女性肌瘤患者的症状、生活质量和肌瘤体积的影响。方法52例有症状的子宫肌瘤患者分别于6个月和12个月行MRgFUS、骨盆MRI和UFS-QoL问卷调查，观察症状改善和肌瘤体积减少情况。结果术后6个月肌瘤体积平均减少24%，术后12个月肌瘤体积平均减少42%。6个月后UFS-QoL问卷的平均得分增加了54%，12个月后增加了81%。没有严重的并发症。4名患者有一级烧伤。无感染病例报告。2例患者通过手术宫腔镜进行子宫肌瘤切除术，其中1例在MRgFUS治疗11个月后进行了全子宫切除术。结论本病例系列提示MRgFUS治疗在减轻症状和改善有症状患者生活质量方面是可行和有效的。

{"title":"Magnetic resonance-guided focused ultrasound for uterine fibroids","authors":"Pedro Felipe Magalhães Peregrino, Marcos de Lorenzo Messina, José Maria Soares Júnior, Edmund Chada Baracat","doi":"10.1016/j.clinsp.2025.100603","DOIUrl":"10.1016/j.clinsp.2025.100603","url":null,"abstract":"<div><h3>Introduction</h3><div>The uterine leiomyoma is a pelvic solid tumor more frequent in women. The Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) is a technique aimed at diminishing hypermenorrhagia and dysmenorrhea in symptomatic women.</div></div><div><h3>Objective</h3><div>To show the effects subsequent to MRgFUS application on symptoms, quality of life, and myoma volume in symptomatic women.</div></div><div><h3>Methods</h3><div>Fifty-two patients with symptomatic uterine myomas underwent MRgFUS followed by clinical evaluation, pelvis MRI, and administration of the UFS-QoL questionnaire at 6 months and 12 months to detect symptom improvements and decrease in myoma volume.</div></div><div><h3>Results</h3><div>The mean myoma volume decreased 24 % after 6 months and 42 % after 12 months. The mean score on the UFS-QoL questionnaire increased 54 % after 6 months and 81 % after 12 months. There were no serious complications. Four patients had first-degree burns. No infection cases were reported. Two patients progressed to a myomectomy by surgical hysteroscopy and one of them underwent total hysterectomy 11 months after the MRgFUS treatment.</div></div><div><h3>Conclusion</h3><div>This case series suggests that MRgFUS therapy is viable and effective in reducing symptoms and improving the life quality of symptomatic patients.</div></div>","PeriodicalId":10472,"journal":{"name":"Clinics","volume":"80 ","pages":"Article 100603"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel variants of the ATRX gene identified in MYCN non-amplified Neuroblastoma in Brazilian patients 在巴西患者的MYCN非扩增神经母细胞瘤中发现了新的ATRX基因变异

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100652

Thamiris Magalhães Gimenez , Vanessa Pretes Peralta , Ricardo Rodrigues Giorgi , Karina Morikawa , Carolina Camargo Vince , Nathalia Halley , Sheila Aparecida Siqueira , Israel Bendit , Lilian Maria Cristofani , Vicente Odone Filho , Estela Maria Novak

Background

Neuroblastoma is one of the most common extracranial solid tumors in children and it frequently displays high heterogeneity throughout the course of the disease. It has previously been described those changes in the ATRX gene (Alpha Thalassemia/Mental Retardation, X-linked) are the most common recurring events in the indolent clinical subtype (∼30 %) of MYCN amplified neuroblastoma. There is no effective treatment for this type of neuroblastoma, which is associated with overall poor survival. On the other hand, few studies have detected an association between high-risk (stage IV) non-amplified MYCN neuroblastoma patients and mutant ATRX.

Methods

In this study, 37 tumor samples from Brazilian patients with stages I to IV MYCN non-amplified neuroblastoma, according to the International Neuroblastoma Staging System (INSS), were analyzed using the panel Oncomine™ Childhood Cancer Research Assay.

Results

The authors found two older children (NB1 and NB2) with advanced MYCN non-amplified neuroblastoma carried each one of the two following novel nonsense ATRX variants (p.Gln1670* or p.Glu1984*). These variants created a stop codon in the helicase domain of the ATRX gene, leading to ATRX loss-of-function. These mutations were confirmed by Sanger sequencing and the protein loss-of-function was confirmed by immunohistochemistry. The finding of these heterozygous mutations in two patients with MYCN non-amplified neuroblastoma deserves further investigation. Thus, the authors analyzed each of these cases to better understand how these mutations may be related to disease severity and prognosis.

Conclusion

ATRX loss-of-function from p.Gln1670* or p.Glu1984* mutations turn MYCN non-amplified neuroblastoma more aggressive and similar to what is seen in MYCN amplified neuroblastoma. This information may help clinical decision-making and facilitate establishing an accurate prognosis for patients with MYCN non-amplified neuroblastoma.

神经母细胞瘤是儿童最常见的颅外实体瘤之一，在整个病程中表现出高度的异质性。先前有报道称，在MYCN扩增型神经母细胞瘤的惰性临床亚型（约30%）中，ATRX基因（α地中海贫血/智力低下，x连锁）的变化是最常见的复发事件。这种类型的神经母细胞瘤没有有效的治疗方法，它与总体生存率低有关。另一方面，很少有研究发现高风险（IV期）非扩增型MYCN神经母细胞瘤患者与突变型ATRX之间存在关联。方法在本研究中，根据国际神经母细胞瘤分期系统（INSS），使用Oncomine™儿童癌症研究检测，分析了来自巴西I至IV期MYCN非扩增神经母细胞瘤患者的37例肿瘤样本。结果作者发现两名患有晚期MYCN非扩增神经母细胞瘤的年龄较大的儿童（NB1和NB2）携带了以下两种新的无意义ATRX变体（p.Gln1670*或p.g l1984 *）。这些变异在ATRX基因的解旋酶结构域产生了一个停止密码子，导致ATRX功能丧失。Sanger测序证实了这些突变，免疫组织化学证实了蛋白质功能丧失。在两例MYCN非扩增神经母细胞瘤患者中发现这些杂合突变值得进一步研究。因此，作者分析了这些病例，以更好地了解这些突变如何与疾病严重程度和预后相关。结论p.Gln1670*或p.Glu1984*突变引起的atrx功能丧失使MYCN非扩增型神经母细胞瘤更具侵袭性，且与MYCN扩增型神经母细胞瘤相似。这些信息可能有助于临床决策，并有助于MYCN非扩增型神经母细胞瘤患者建立准确的预后。

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引用次数: 0

RBBP4 downregulation increases the sensitivity of A549 and HeLa cells to cisplatin by inhibiting cyclin D1 expression RBBP4下调通过抑制cyclin D1表达增加A549和HeLa细胞对顺铂的敏感性

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100637

Zhiyu Zeng , Meiqing Mai , Dandan Wang , Jie Ouyang , Zhiru Chen , Jingjing Zhong , Jinjun Rao

Introduction

Retinoblastoma-Binding Protein 4 (RBBP4), belonging to the WD-40 family, is an important member of the Polycomb Repressor Complex 2 (PRC2), the Nucleosome Remodeling and Deacetylation complex (NuRD), and is involved in chromatin remodeling, histone deacetylation, and H3K27 methylation.

Methods

The effects of cisplatin treatment on cell viability were evaluated using the MTT assay. Western blotting was employed to analyze protein expression, and RNA interference-mediated knockdown of RBBP4 and cyclin D1 was conducted using Lipofectamine 2000. The formation of colonies was evaluated following a 14-day cisplatin treatment period. Cisplatin uptake was quantified by atomic absorption spectrophotometry. RNA sequencing was conducted on total RNA extracted from cells, and lentiviral vectors were employed for gene overexpression, followed by puromycin selection. Immunohistochemistry was performed on tissue microarrays of lung and cervical adenocarcinoma in order to evaluate RBBP4 expression.

Results

In this study, cisplatin was found to induce RBBP4 expression in human lung cancer A549 cells, and RBBP4 expression in cisplatin-resistant A549/DDP cells was significantly higher than in A549 cells. Downregulating RBBP4 expression by small interfering RNA significantly increased the sensitivity of A549 and A549/DDP cells to cisplatin. Conversely, lentiviral-mediated RBBP4 overexpression reduced sensitivity to cisplatin. Mechanistic studies showed that downregulated RBBP4 increased cell sensitivity to cisplatin mainly by inhibiting cyclinD1 expression, and lentiviral-mediated cyclinD1 caused the opposite effects. These same results were verified in human HeLa cells and in cisplatin-resistant HeLa/DDP cells.

Discussion

This study showed that RBBP4 regulates the sensitivity of tumor cells to cisplatin and is a potential target for reversing cisplatin resistance in tumor cells.

视网膜母细胞瘤结合蛋白4 （RBBP4）属于WD-40家族，是多梳抑制因子复合体2 （PRC2）、核小体重塑和去乙酰化复合体（NuRD）的重要成员，参与染色质重塑、组蛋白去乙酰化和H3K27甲基化。方法采用MTT法评价顺铂治疗对细胞活力的影响。Western blotting分析蛋白表达，Lipofectamine 2000检测RNA干扰介导的RBBP4和cyclin D1的下调。在14天顺铂治疗期后评估菌落的形成。原子吸收分光光度法测定顺铂的吸收量。对提取的细胞总RNA进行RNA测序，利用慢病毒载体进行基因过表达，选择嘌呤霉素。对肺和宫颈腺癌组织微阵列进行免疫组化，以评估RBBP4的表达。结果本研究发现顺铂可诱导人肺癌A549细胞中RBBP4的表达，且RBBP4在顺铂耐药的A549/DDP细胞中的表达明显高于A549细胞。通过小干扰RNA下调RBBP4表达可显著提高A549和A549/DDP细胞对顺铂的敏感性。相反，慢病毒介导的RBBP4过表达降低了对顺铂的敏感性。机制研究表明，RBBP4下调主要通过抑制cyclinD1表达来提高细胞对顺铂的敏感性，而慢病毒介导的cyclinD1则起到相反的作用。在人HeLa细胞和顺铂耐药HeLa/DDP细胞中证实了相同的结果。本研究表明，RBBP4调节肿瘤细胞对顺铂的敏感性，是逆转肿瘤细胞顺铂耐药的潜在靶点。

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引用次数: 0

Thrombin generation indices and Wells score predict pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease 凝血酶生成指数和Wells评分可预测慢性阻塞性肺疾病急性加重期患者的肺栓塞

IF 2.2 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics

Pub Date : 2025-01-01 DOI: 10.1016/j.clinsp.2025.100582

Linjie Luo , Dan Zheng , Li Da, Jian Cheng, Yirui Cao, Na Wang

Objective

This study investigated the predictive value of thrombin generation indices and Wells score in the development of Pulmonary Embolism (PE) in patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD).

Methods

160 patients who were admitted for AECOPD and underwent CT Pulmonary Arteriography (CTPA) were collected. Among them, a total of 62 cases were diagnosed with PE as the AECOPD with PE group, and the other 98 cases were not diagnosed with PE as the AECOPD group. The general data, past history and combined basic diseases, laboratory tests and other related clinical data of the two groups were compared, and the data collected were statistically analyzed to explore the diagnostic indexes that can predict PE in AECOPD.

Results

History of venous thromboembolism, d-Dimer as well as Endogenous Thrombin Potential (ETP), Activated Partial Thromboplastin Time (APTT) coagulation indices, and Wells score was significantly higher in the AECOPD with PE group than in the AECOPD group, and Time to Peak (ttpeak), Albumin (ALB) and total protein were lower than those in the AECOPD group. The Wells score had a positive correlation with ETP and APTT and a negative correlation with ttpeak, which were all independent risk factors for PE in AECOPD. The Wells score had the best efficacy in predicting the occurrence of PE in patients with AECOPD with a cutoff value of 4.62.

Conclusion

Significant correlations were found between the thrombin generation indices (ETP, APTT and ttpeak) and the Wells score, which can also be used for early diagnosis of PE in patients with AECOPD.

目的探讨凝血酶生成指数和Wells评分对慢性阻塞性肺疾病急性加重期（AECOPD）患者肺栓塞（PE）发生的预测价值。方法收集我院收治的AECOPD行CT肺动脉造影（CTPA）的患者160例。其中诊断为PE的共62例为有PE组，未诊断为PE的共98例为AECOPD组。比较两组患者的一般资料、既往病史及合并基础疾病、实验室检查等相关临床资料，并对收集到的资料进行统计分析，探讨预测AECOPD患者PE的诊断指标。结果AECOPD合并PE组静脉血栓栓塞史、d-二聚体、内源性凝血酶电位（ETP）、活化部分凝血酶时间（APTT）凝血指标、Wells评分均显著高于AECOPD组，峰值时间（ttpeak）、白蛋白（ALB）、总蛋白均显著低于AECOPD组。Wells评分与ETP、APTT呈正相关，与ttpeak呈负相关，均为AECOPD中PE的独立危险因素。Wells评分预测AECOPD患者PE发生的效果最好，临界值为4.62。结论凝血酶生成指数（ETP、APTT、ttpeak）与Wells评分有显著相关性，也可用于AECOPD患者PE的早期诊断。

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