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Association of heart rate variability with cardiorespiratory fitness and muscle strength in patients after hospitalization for COVID-19: An analytical cross-sectional study. 心率变异性与 COVID-19 住院患者心肺功能和肌肉力量的关系:横断面分析研究
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-19 DOI: 10.1016/j.clinsp.2024.100534
Daniele Ferreira Rodrigues, Victor Ribeiro Neves, Ulisses Ramos Montarroyos, Washington José Dos Santos, Isabelle Carolline Verissimo de Farias, Dário Celestino Sobral Filho

Introduction: Patients with a moderate to severe clinical condition of COVID-19 who need hospitalization may have dysfunction in Cardiac Autonomic Control (CAC) and functional capacity.

Objective: To assess the association of HRV with cardiorespiratory fitness and respiratory and peripheral muscle strength in patients after hospitalization for COVID-19.

Method: Cross-sectional study with individuals > 18-years old, post-hospitalization for COVID-19, with a positive RT-PCR test. Data on clinical condition and hospital admission were collected, and parameters of respiratory and peripheral muscle strength and functional capacity were evaluated with the 6-Minute Walk Test (6MWT). CAC was assessed by analyzing (Heart Rate Variability) HRV in the time (SDNN, RMSSD) and frequency domains (HF, LF, HF/LF ratio). Pearson correlation was performed between HRV measures and functional parameters.

Results: The results showed low HRV in study participants, with positive correlations between 6MWT and RMSSD and between SDNN and HF power and negative correlations between Heart Rate and the LF/HF ratio. On the other hand, respiratory and peripheral muscle strength correlated positively with parameters that represent sympathetic nervous system expression (LF nu and LF power) and negatively with the LF/HF ratio. However, changes in HRV parameters were not associated with disease severity.

Conclusion: The dysautonomia of COVID-19 patients was correlated with functional sequelae, though not associated with disease severity parameters. There was low HRV, with low vagal expression, and imbalance in sympathetic/parasympathetic modulation in the study group.

导言:需要住院治疗的COVID-19中重度患者可能会出现心脏自主神经控制(CAC)和功能障碍:评估心率变异与 COVID-19 患者住院后心肺功能、呼吸肌和外周肌力的关系:方法:对因 COVID-19 住院后 RT-PCR 检测呈阳性、年龄大于 18 岁的患者进行横断面研究。收集临床状况和入院数据,并通过 6 分钟步行测试(6MWT)评估呼吸肌、外周肌力和功能能力参数。通过分析时域(SDNN、RMSSD)和频域(HF、LF、HF/LF 比值)的心率变异(HRV)来评估 CAC。心率变异测量值与功能参数之间存在皮尔逊相关性:结果显示,研究参与者的心率变异较低,6MWT 与 RMSSD 之间、SDNN 与高频功率之间呈正相关,而心率与低频/高频比值之间呈负相关。另一方面,呼吸和外周肌力与代表交感神经系统表现的参数(低频 nu 和低频功率)呈正相关,而与低频/高频比值呈负相关。然而,心率变异参数的变化与疾病的严重程度无关:结论:COVID-19 患者的自主神经功能障碍与功能性后遗症相关,但与疾病严重程度参数无关。研究组的心率变异较低,迷走神经表达较低,交感/副交感神经调节失衡。
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引用次数: 0
Expression of NGF, proNGF, p75NTR in lung injury induced by cerebral ischemia-reperfusion in young and elderly rats. NGF、proNGF和p75NTR在青年和老年大鼠脑缺血再灌注所致肺损伤中的表达
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100532
Hong Chen, Qiang Du, Jie Chen, Qiang Tian, Lei Xu, Ying Wang, Xiaoyan Gu

Objective: This study aims to investigate the expression levels of Nerve Growth Factor (NGF), the precursor form of NGF (proNGF), and p75 neurotrophin receptor (p75NTR) in lung injury induced by cerebral Ischemia-Reperfusion (I/R) in both young and elderly rats.

Methods: Male Sprague-Dawley rats, categorized as young (3-months-old) and elderly (16-months-old), were divided into four experimental groups: Young Sham, Young I/R, Elderly Sham, and Elderly I/R. Each group underwent either sham surgery or ischemia-reperfusion treatment. Following 24 h post-procedure, the severity of cerebral ischemia was assessed using the Zea Longa 5-point scoring system, and lung tissue pathological changes were examined using Hematoxylin and Eosin (HE) staining. Western blot analysis was utilized to measure the expression levels of NGF, proNGF, and p75NTR proteins in lung tissue.

Results: Both young and elderly I/R groups exhibited lung tissue congestion and edema compared to their respective sham groups, with a significant increase in pathological scores (p < 0.05). Furthermore, the elderly I/R group demonstrated a significantly higher pathological score compared to the young I/R group (p < 0.05). Western blot analysis revealed that compared to the young sham group, the expression of NGF in the lung tissue of elderly sham rats decreased (p < 0.05), while proNGF and p75NTR increased (p < 0.05). Additionally, compared to the sham group, the levels of NGF, proNGF, and p75NTR in lung tissue were elevated in both young and elderly I/R groups of rats (p < 0.05). Moreover, the expression of proNGF and p75NTR in lung tissue was higher in the elderly I/R group than in the young I/R group (p < 0.05).

Conclusion: Cerebral ischemia-reperfusion-induced lung injury was associated with increased expression of proNGF and p75NTR, as well as decreased NGF expression in lung tissue. These alterations in NGF, proNGF, and p75NTR may contribute to the susceptibility to age-related lung injury.

研究目的本研究旨在探讨神经生长因子(NGF)、NGF的前体形式(proNGF)和p75神经营养素受体(p75NTR)在幼年和老年大鼠脑缺血再灌注(I/R)诱导的肺损伤中的表达水平:雄性 Sprague-Dawley 大鼠分为幼年组(3 个月大)和老年组(16 个月大):年轻假手术组、年轻 I/R 组、老年假手术组和老年 I/R 组。每组均接受假手术或缺血再灌注治疗。术后 24 小时后,使用 Zea Longa 5 点评分法评估脑缺血的严重程度,并使用苏木精和伊红(HE)染色法检查肺组织的病理变化。用 Western 印迹分析法检测肺组织中 NGF、proNGF 和 p75NTR 蛋白的表达水平:结果:与假组相比,年轻组和老年 I/R 组均表现出肺组织充血和水肿,病理评分显著增加(P < 0.05)。此外,老年 I/R 组的病理评分明显高于青年 I/R 组(P < 0.05)。Western 印迹分析显示,与年轻假大鼠组相比,老年假大鼠肺组织中 NGF 的表达量减少(p < 0.05),而 proNGF 和 p75NTR 的表达量增加(p < 0.05)。此外,与假组相比较,年轻组和老年 I/R 组大鼠肺组织中 NGF、proNGF 和 p75NTR 的水平均升高(p < 0.05)。此外,老年 I/R 组大鼠肺组织中 proNGF 和 p75NTR 的表达高于年轻 I/R 组(P < 0.05):结论:脑缺血再灌注诱导的肺损伤与肺组织中proNGF和p75NTR的表达增加以及NGF的表达减少有关。NGF、proNGF和p75NTR的这些变化可能会导致老年性肺损伤的易感性。
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引用次数: 0
Protocol for the collection, packaging, and transportation of preterm newborn stool samples. 早产新生儿粪便样本的采集、包装和运输规程。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-13 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100531
Jessica Santos Passos Costa, Heli Vieira Brandão, Mara Viana Cardoso Amaral, Gabriela Cintra Dos Santos, Camilla da Cruz Martins, Michelle de Santana Xavier Ramos, Tatiana de Oliveira Vieira, Raquel Guimarães Benevides, Graciete Oliveira Vieira

Background: The newborn's intestinal microbiota can vary with gestational age. Reliable analyses of stool samples require establishing the steps of collection, packaging, transportation, and storage.

Objective: To describe the development of a protocol and test an algorithm for the sequence of actions and procedures for the collection, packaging, transportation, and storage of stool samples from Preterm Newborn (PTNB) admitted to a Neonatal Intensive Care Unit (NICU).

Materials and methods: This is a descriptive, observational study linked to a non-randomized controlled clinical trial conducted in the NICU of two public hospitals covenanted to the Unified Health System of a large city in inland northeastern Brazil. The methodology adopted in its development followed the Brazilian Ministry of Health Preparation Guide recommendations.

Results: The flow of actions and procedures was consistent with scientific evidence. The sequence of work process steps to implement the proposed protocol was tested and resulted in a graphical representation of an algorithm compatible with the reality of Brazilian public hospitals.

Conclusion: Following the protocol steps with the description of the rules of conduct and recommendations regarding the collection, packaging, transportation, and storage of stool samples from PTNBs ensured the preservation and integrity of the bacterial DNA in the stools sample. The details of the recommendations will allow their reproducibility and improvement by professionals and researchers with similar study objects.

Trial registration: World Health Organization (WHO) under Universal Trial Number (UTN) code U1111-1266-2295, under register RBR-3mm7cs in the Brazilian Registry of Clinical Trials (REBEC).

背景:新生儿的肠道微生物群会随着胎龄的变化而变化。对粪便样本进行可靠的分析需要确定收集、包装、运输和储存的步骤:描述早产新生儿(PTNB)在新生儿重症监护病房(NICU)的粪便样本收集、包装、运输和储存的操作顺序和程序的协议制定和算法测试:这是一项与非随机对照临床试验相关的描述性观察研究,在巴西东北部内陆一个大城市的两家隶属于统一卫生系统的公立医院的新生儿重症监护室进行。研究方法遵循了巴西卫生部《准备指南》的建议:结果:行动和程序的流程符合科学依据。对实施建议规程的工作流程步骤顺序进行了测试,得出了符合巴西公立医院实际情况的图解算法:结论:按照规程中关于 PTNB 粪便样本的收集、包装、运输和储存的行为规则和建议所描述的步骤进行操作,可确保粪便样本中细菌 DNA 的保存和完整性。这些建议的细节将使专业人员和研究人员在进行类似研究时具有可重复性和改进性:世界卫生组织(WHO)通用试验编号(UTN)U1111-1266-2295,巴西临床试验登记处(REBEC)登记号RBR-3mm7cs。
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引用次数: 0
LRP1B associated with immune cell infiltration influenced the efficacy of immunotherapy in colorectal cancer patients. 与免疫细胞浸润相关的 LRP1B 会影响结直肠癌患者免疫疗法的疗效。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-11 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100516
Weiming Weng, Shengquan He, Guoxiong Zhang, Xindong Zhou, Kang Li, Jiajun Lai

Objective: Colorectal cancer is one of the most common malignant tumors in the world, which seriously threatens human health. It is essential for the search for new oncogene targets in colorectal cancer.

Methods: Samples from 57 colorectal cancer patients were collected in this study. Next-Generation Sequencing (NGS) was performed to detect gene mutation, assess Microsatellite Instability (MSI), and evaluate Tumor Mutational Burden (TMB). RNA data from 528 CRC patients from the TCGA database were analyzed.

Results: A total of 57 colon cancer patients were included in this study, including 30 males and 27 females, with a mean age of 56 years. In this study, the most common mutations were APC (79 %), TP53 (61 %), TTN (48 %), KRAS (42 %), SYNE1 (28 %), MUC16 (25 %), PIK3CA (25 %), FAT4 (22 %), RYR2 (19 %), OBSCN (18 %), and ZFHX4 (18 %). Subsequently, the authors analyzed gene mutations in colorectal cancer patients according to gender, age, and TMB status. Significant differences in immune cell infiltration were found between colorectal cancer tissues and normal tissues by CIBERSORT analysis. LRP1B may serve as a potential colorectal cancer therapeutic target, and its absence leads to changes in immune cell infiltration.

Conclusion: The authors described the molecular characteristics of CRC. Loss of LRP1B leads to changes in immune cell infiltration and can be used as a therapeutic target for colorectal cancer.

目的:大肠癌是世界上最常见的恶性肿瘤之一,严重威胁人类健康:大肠癌是世界上最常见的恶性肿瘤之一,严重威胁人类健康。寻找结直肠癌新的癌基因靶点至关重要:方法:本研究收集了 57 名结直肠癌患者的样本。方法:本研究收集了 57 名结直肠癌患者的样本,并进行了下一代测序(NGS),以检测基因突变、评估微卫星不稳定性(MSI)和肿瘤突变负荷(TMB)。对 TCGA 数据库中 528 例 CRC 患者的 RNA 数据进行了分析:本研究共纳入了 57 例结肠癌患者,其中男性 30 例,女性 27 例,平均年龄 56 岁。在这项研究中,最常见的突变是 APC(79%)、TP53(61%)、TTN(48%)、KRAS(42%)、SYNE1(28%)、MUC16(25%)、PIK3CA(25%)、FAT4(22%)、RYR2(19%)、OBSCN(18%)和 ZFHX4(18%)。随后,作者根据性别、年龄和 TMB 状态分析了结直肠癌患者的基因突变情况。通过 CIBERSORT 分析发现,结直肠癌组织与正常组织的免疫细胞浸润存在显著差异。LRP1B可能是结直肠癌的潜在治疗靶点,它的缺失会导致免疫细胞浸润的变化:作者描述了 CRC 的分子特征。结论:作者描述了 CRC 的分子特征,LRP1B 的缺失会导致免疫细胞浸润的变化,可作为结直肠癌的治疗靶点。
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引用次数: 0
Assessing the impact of implementing the clinical protocol and therapeutic guidelines in COPD in real-life. 评估在现实生活中实施慢性阻塞性肺病临床方案和治疗指南的影响。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100529
Daiana Abreu Lourenço Sales, Priscila Carla Moura Honório, Vanusa Barbosa Pinto, Frederico Leon Arrabal Fernandes, Regina Maria de Carvalho Pinto, Alberto Cukier
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引用次数: 0
Willingness and skills among students from non-health academic fields in providing efficient basic life support. 非卫生专业学生提供高效基本生命支持的意愿和技能。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-08 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100518
Perola Nakandakari Sugimoto, Gabriela Buno Gouvêa, Igor Caitano Salles, Heráclito Barbosa de Carvalho, Priscila Aikawa, Liana Maria Torres de Araújo Azi, Luiz Fernando Ferraz da Silva, Mariangela Macchione, Federico Semeraro, Andrew Lockey, Robert Greif, Maria José Carvalho Carmona, Bernd Walter Böttiger, Naomi Kondo Nakagawa

Education in basic life support is widely proposed to increase survival in out-of-hospital sudden cardiac arrest. The authors aimed to assess knowledge, skills, and attitudes, including willingness to help, regarding myocardial infarction and sudden cardiac arrest among university students of all fields of knowledge.

Methods: An Ethical Research Committee approved this cross-sectional study. An electronic survey "KIDS SAVE LIVES BRAZIL" was sent to 58,862 students of 82 disciplines in three universities, aged ≥ 18 years. The survey covered three categories: knowledge, skills, and attitude. Each category was graded between 0 and 10 points (the highest).

Results: Among students, 4,803 undergraduates (8.2 %) answered the survey, and were divided into three groups of disciplines: medicine (219, ∼21.7 years, 38 % male), other-healthcare (n = 1,058; ∼22.9 years; 36 % male), and non-health-care (n = 3,526; ∼22.9 years; 35 % male). All three groups showed significant differences between them (p < 0.001). The non-health-care compared with medicine and other healthcare groups showed, respectively, the lowest median scores (25 %‒75 %) in knowledge (4.0 [0.0‒9.3], 4.0 [4.0‒8.0], and 4.0 [4.0‒4.7]), skills (2.4 [1.2‒3.3], 6.4 [4.0‒8.3], 4.0 [2.4‒6.2]), and attitude (5.9 [5.9‒6.8], 7.3 [5.9‒7.3], and 7.3 [5.9‒7.3]).

Conclusion: University students who answered the e-survey have the willingness to help victims suffering from myocardial infarction or sustaining sudden cardiac arrest. However, non healthcare students markedly lack the knowledge and skills to perform cardiopulmonary resuscitation and automated external defibrillation. These findings reveal a stark difference in basic life support competencies between students in related healthcare fields and those in non-health fields, emphasizing the need for universal basic life support training.

基本生命支持教育被广泛认为可以提高院外心脏骤停患者的存活率。作者旨在评估各专业大学生对心肌梗死和心脏骤停的知识、技能和态度,包括救助意愿:伦理研究委员会批准了这项横断面研究。向三所大学 82 个专业的 58862 名年龄≥ 18 岁的学生发送了 "巴西儿童拯救生命 "电子调查问卷。调查涵盖三个类别:知识、技能和态度。每个类别的分值从 0 分到 10 分(最高分)不等:在学生中,有 4 803 名本科生(8.2%)回答了调查,他们被分为三个学科组:医学(219 人,21.7 岁,38% 为男性)、其他医疗保健学科(1 058 人,22.9 岁,36% 为男性)和非医疗保健学科(3 526 人,22.9 岁,35% 为男性)。三个组别之间均存在明显差异(P < 0.001)。非医疗保健组与医疗保健组和其他医疗保健组相比,在知识方面的中位数得分(25 %-75 %)分别最低(4.0 [0.0-9.3]、4.0 [4.0-8.0]和 4.0 [4.0-8.0])。0-8.0]、4.0[4.0-4.7])、技能(2.4[1.2-3.3]、6.4[4.0-8.3]、4.0[2.4-6.2])和态度(5.9[5.9-6.8]、7.3[5.9-7.3]、7.3[5.9-7.3]):结论:回答电子调查的大学生有帮助心肌梗塞或心脏骤停患者的意愿。然而,非医学生明显缺乏进行心肺复苏和自动体外除颤的知识和技能。这些发现揭示了相关医护专业学生与非医护专业学生在基本生命支持能力方面的明显差异,强调了普及基本生命支持培训的必要性。
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引用次数: 0
A critical evaluation of the status of HPV vaccination in São Paulo State, Brazil. 对巴西圣保罗州人乳头瘤病毒疫苗接种情况的重要评估。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-06 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100526
Toni Ricardo Martins, Steven S Witkin, Andressa da Silva Ferreira, Juliana Yukari K Viscondi, Maryana Stephany Ferreira Branquinho, Lise Cury, Lucy Santos Vilas Boas, Adhemar Longatto-Filho, Maria Cássia Mendes-Corrêa

Cervical cancer, whose well-recognized etiological agent is the Human Papillomavirus (HPV), is responsible for approximately 300,000 deaths worldwide, 80% of cases occurring in developing countries. In Brazil, 17,010 cases were expected, with 2,550 cases in São Paulo State, in 2023. The Papanicolaou test is the diagnostic method for the detection of precancerous lesions of the cervix, and HPV vaccination is now available for prevention.

Materials and methods: This is a descriptive and exploratory, retrospective investigation, carried out through analysis of data obtained from Brazilian Information Technology (DATASUS) of the Brazilian Federal Government: Cancer Information System (SISCAN), Brazilian National Immunization Program (PNI) and Mortality Information System (SIM). Electronic Library and data made available by the Government of the State of São Paulo.

Results: The number of women in São Paulo State who underwent cytological examinations and histological tests for cervical cancer decreased between the Years 2013 and 2022.

Conclusion: The continuous increase in cervical cancer over the study period was probably due to the lack of adherence to the primary and secondary prevention opportunities offered by the Public Health Authorities.

宫颈癌的病原体是人类乳头瘤病毒(HPV),已被公认为是导致全球约 30 万人死亡的罪魁祸首,其中 80% 的病例发生在发展中国家。预计到 2023 年,巴西将出现 17 010 例病例,其中圣保罗州将出现 2 550 例。巴氏涂片是检测宫颈癌前病变的诊断方法,目前可通过接种人乳头瘤病毒疫苗进行预防:这是一项描述性和探索性的回顾性调查,通过分析从巴西联邦政府的巴西信息技术(DATASUS)获得的数据进行:癌症信息系统(SISCAN)、巴西国家免疫计划(PNI)和死亡率信息系统(SIM)。圣保罗州政府提供的电子图书馆和数据:结果:2013年至2022年期间,圣保罗州接受宫颈癌细胞学检查和组织学检测的妇女人数有所下降:在研究期间,宫颈癌发病率持续上升,这可能是由于缺乏对公共卫生部门提供的一级和二级预防机会的坚持。
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引用次数: 0
Ventilation with hyperoxia promotes cochlear bleeding in rabbits with congenital diaphragmatic hernia. 高氧通气可促进患有先天性膈疝的兔子耳蜗出血。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100525
Eduardo Tanaka Massuda, Solange Natalia Seibert, Ana Maria Bicudo Diniz, Luiza Almeida Lima, Maria Rossato, Vanessa Maciel Bráulio da Fonseca, Marcos de Carvalho Borges, Jason Xia, Amaury Lelis Dal Fabbro, Lourenço Sbragia

Objective: The authors hypothesized that ventilation and hyperoxia may harm the cochlea vasculature in an experimental model of Congenital Diaphragmatic Hernia (CDH) performed in rabbits.

Methods: New Zealand rabbits underwent CDH creation at 25 days of gestation (term = 30 days). CDH was created in fetuses (n = 15) and compared with Controls (n = 15). Six groups were studied: Control, Control Ventilated 21% FiO2 (Control 21%), Control Ventilated 100% FiO2 (Control 100%), CDH, CDH Ventilated 21% FiO2 (CDH 21%) and CDH Ventilated 100% FiO2 (CDH 100%). Dynamic Compliance (CRS), dynamic Elastance (ERS), and dynamic Resistance (RRS) were measured. The cochleae were then removed, and the apical, middle, and basal slopes of the cochleae were evaluated. Samples were graded using a scoring system for the severity of bleeding: 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). Statistical analysis was performed by contingence and ANOVA.

Results: There was no difference in the severity of cochlear bleeding between Controls and CDH without ventilation. Control 21% and 100% had average scores of 2 and 1.2 respectively; CDH 21% and 100% had average scores of 0.4 and 3.8 respectively; RR [CDH 100% / Control 100%] (95% CI) = 3.16 (p < 0.005).

Conclusions: The severity of bleeding was 3.16 times worse with 100% oxygenation in CDH. This information may be helpful for future therapeutic strategies for decreasing SNHL in CDH patients.

目的:作者假设在兔子先天性膈疝(CDH)实验模型中,通气和高氧可能会损害耳蜗血管:方法:新西兰兔在妊娠 25 天(足月 = 30 天)时进行 CDH 创建。在胎儿(n = 15)中创建 CDH,并与对照组(n = 15)进行比较。研究共分六组对照组、对照组通气 21% FiO2 (对照组 21%)、对照组通气 100% FiO2 (对照组 100%) 、CDH 组、CDH 组通气 21% FiO2 (CDH 21%) 和 CDH 组通气 100% FiO2 (CDH 100%) 。测量动态顺应性(CRS)、动态弹性(ERS)和动态阻力(RRS)。然后取出耳蜗,评估耳蜗的顶端、中部和基底斜面。使用出血严重程度评分系统对样本进行分级:0(无)、1(轻度)、2(中度)和 3(重度)。统计分析采用或然法和方差分析:结果:对照组和不通气 CDH 患者的耳蜗出血严重程度没有差异。对照组 21% 和 100% 的平均得分分别为 2 分和 1.2 分;CDH 21% 和 100% 的平均得分分别为 0.4 分和 3.8 分;RR [CDH 100% / 对照组 100%] (95% CI) = 3.16 (p < 0.005):结论:CDH患者在100%吸氧的情况下,出血的严重程度要比对照组严重3.16倍。这一信息可能有助于未来减少 CDH 患者 SNHL 的治疗策略。
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引用次数: 0
Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients. SERPINA1基因的多态性与巴西ANCA相关性血管炎患者队列中较高的死亡率有关。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100524
Henrique Ayres Mayrink Giardini, Valeria de Falco Caparbo, Isac de Castro, Andréia Padilha Toledo, Carmen Silvia Valente Barbas, Samuel Katsuyuki Shinjo, Rosa Maria Rodrigues Pereira

Background: Alpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients.

Objective: The present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups.

Methods: In this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes.

Results: The authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years).

Conclusion: SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.

背景:α-1-抗胰蛋白酶(A1AT)是一种由 SERPINA1 基因编码的蛋白酶抑制剂。A1AT 是中性粒细胞中蛋白酶 3(PR3)的主要天然抑制剂。PR3 是抗中性粒细胞胞浆抗体(ANCA)的抗原靶标。尽管许多研究已证实 SERPINA1 基因中的单核苷酸多态性(SNPs)与 ANCA 相关性血管炎(AAV)之间存在联系,但深入研究这些多态性对这些患者预后影响的研究却很有限:本研究旨在调查携带 SERPINA1 SNPs(rs7151526、rs28929454)的巴西 AAV 患者与非携带者的死亡率差异。此外,作者还分析了这两组患者的人口统计学、临床和血清学数据:在这项单中心前瞻性队列研究中,作者招募了AAV患者,对他们进行了长达三年的监测。SNPs 的鉴定是通过 RT-PCR 进行的。随后进行了包括 Kaplan-Meier 生存曲线在内的生存分析和 Cox 比例回归分析,以评估结果:作者对115名患者进行了评估(65.2%患有肉芽肿伴多血管炎,17.4%患有嗜酸性肉芽肿伴多血管炎,17.4%患有显微镜下多血管炎)。所有患者的年龄均≥18岁,37.4%为女性,54.7%为白人。事实证明,SERPINA1 SNPs之间的关联是与队列中死亡率相关的最重要因素(HR = 6.2,95% CI 1.4-27.1,p = 0.015)。SERPINA1 SNP携带者的平均生存期[rs7151526:57.4 (42.7-72.2) 年,p < 0.007;rs28929454:54.9 (40.9-68.9) 年,p < 0.0001]低于非携带者(68.0 [67.2-69.0] 年):结论:SERPINA1 SNPs 与巴西 AAV 患者死亡率的增加有关。
{"title":"Polymorphisms of the SERPINA1 gene are associated with higher mortality in a Brazilian cohort of ANCA-associated vasculitis patients.","authors":"Henrique Ayres Mayrink Giardini, Valeria de Falco Caparbo, Isac de Castro, Andréia Padilha Toledo, Carmen Silvia Valente Barbas, Samuel Katsuyuki Shinjo, Rosa Maria Rodrigues Pereira","doi":"10.1016/j.clinsp.2024.100524","DOIUrl":"10.1016/j.clinsp.2024.100524","url":null,"abstract":"<p><strong>Background: </strong>Alpha-1-Antitrypsin (A1AT) is a protease inhibitor encoded by the SERPINA1 gene. A1AT serves as the primary natural inhibitor of Proteinase 3 (PR3), an enzyme found in neutrophils. PR3 is an antigenic target of Anti-Neutrophil Cytoplasmic Antibodies (ANCA). While numerous studies have established a connection between Single Nucleotide Polymorphisms (SNPs) in the SERPINA1 gene and ANCA-Associated Vasculitis (AAV), limited research has delved into the impact of these polymorphisms on the prognosis of these patients.</p><p><strong>Objective: </strong>The present study's objective is to investigate mortality disparities among Brazilian AAV patients carrying SERPINA1 SNPs (rs7151526, rs28929454) compared to non-carriers. Additionally, the authors analyzed demographic, clinical, and serologic data in these two groups.</p><p><strong>Methods: </strong>In this single-center prospective cohort study, the authors enrolled AAV patients who were monitored for a duration of up to three years. The identification of SNPs was conducted through RT-PCR. Survival analysis, including Kaplan-Meier survival curves, and Cox proportional regression analysis was subsequently performed to evaluate outcomes.</p><p><strong>Results: </strong>The authors assessed 115 patients (65.2% with granulomatosis with polyangiitis, 17.4% with eosinophilic granulomatosis with polyangiitis, and 17.4% with microscopic polyangiitis). All patients were aged ≥ 18 years, with 37.4% being female, and 54.7% identified as White. The association between SERPINA1 SNPs proved to be the most significant factor linked to mortality in the cohort (HR = 6.2, 95% CI 1.4‒27.1, p = 0.015). SERPINA1 SNP carriers exhibited a lower mean survival [rs7151526: 57.4 (42.7‒72.2) years, p < 0.007; rs28929454: 54.9 (40.9‒68.9) years, p < 0.0001] than non-carriers (68.0 [67.2‒69.0] years).</p><p><strong>Conclusion: </strong>SERPINA1 SNPs are associated with increased mortality in Brazilian AAV patients.</p>","PeriodicalId":10472,"journal":{"name":"Clinics","volume":"79 ","pages":"100524"},"PeriodicalIF":2.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544138","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
CEMIP induces TGF-β/Smad signaling to promote keloid development by binding to SPARC. CEMIP 通过与 SPARC 结合,诱导 TGF-β/Smad 信号,促进瘢痕发育。
IF 2.2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.1016/j.clinsp.2024.100523
Xinyi Li, Wei Zhang, Xiaojing Li

Background: Cell Migration Inducing Hyaluronidase 1 (CEMIP) is a protein that plays regulatory functions in a variety of cellular processes in many diseases. Nevertheless, its role and molecular mechanism in keloid hyperplasia are still elusive.

Methods: Expressions of CEMIP and Secreted Protein acidic and Rich in Cysteine (SPARC) were detected by qRT-PCR and western blot. CCK-8 assay, along with immunofluorescence staining, was applied for the assessment of cell proliferation. The capabilities of cells to migrate and invade were evaluated utilizing wound healing and Transwell, while Extracellular Matrix (ECM) deposition was measured by immunofluorescence and western blot. The interaction of CEMIP and SPARC was predicted by the Coexpedia and PPA-red databases and verified by co-IP. Western blot was adopted for the estimation of TGF-β/Smad pathway-related proteins.

Results: The data demonstrated that CEMIP expression was elevated in Keloid Fibroblasts (KF). CEMIP interference suppressed cell proliferative, migrative and invasive capabilities and ECM deposition in KF. Mechanistically, bioinformatics analysis revealed that CEMIP was co-expressed with SPARC and CEMIP protein could bind to SPARC. SPARC expression was reduced in CEMIP-silenced cells. SPARC overexpression counteracted the impacts of CEMIP silencing on cell proliferative, migrative and invasive capabilities and ECM deposition in KF. In addition, the expressions of TGF-β/Smad signaling-related proteins were decreased by CEMIP silencing via the inhibition of SPARC.

Conclusion: In summary, this study revealed that CEMIP modulated KF proliferation, migration, invasion and ECM deposition by TGF-β/Smad signaling through binding to SPARC.

背景:细胞迁移诱导透明质酸酶1(CEMIP)是一种蛋白质,在许多疾病的多种细胞过程中发挥调控功能。然而,它在瘢痕疙瘩增生症中的作用和分子机制仍难以捉摸:方法:通过 qRT-PCR 和 western 印迹检测 CEMIP 和富含半胱氨酸的分泌蛋白(SPARC)的表达。CCK-8测定和免疫荧光染色被用于评估细胞增殖。利用伤口愈合和 Transwell 评估了细胞迁移和侵袭的能力,并通过免疫荧光和 Western 印迹检测了细胞外基质(ECM)的沉积。CEMIP和SPARC的相互作用由Coexpedia和PPA-red数据库预测,并通过co-IP验证。结果表明,CEMIP和SPARC之间的相互作用通过Coexpedia和PPA-red数据库进行预测,并通过co-IP进行验证;Western印迹用于评估TGF-β/Smad通路相关蛋白:结果:数据表明,CEMIP在瘢痕疙瘩成纤维细胞(KF)中表达升高。干扰 CEMIP 可抑制 KF 的细胞增殖、迁移和侵袭能力以及 ECM 沉积。生物信息学分析表明,CEMIP与SPARC共表达,CEMIP蛋白可与SPARC结合。在 CEMIP 沉默的细胞中,SPARC 的表达量减少。SPARC 的过表达抵消了 CEMIP 沉默对 KF 细胞增殖、迁移和侵袭能力以及 ECM 沉积的影响。此外,通过抑制 SPARC,沉默 CEMIP 可减少 TGF-β/Smad 信号相关蛋白的表达:综上所述,本研究揭示了 CEMIP 通过与 SPARC 结合,通过 TGF-β/Smad 信号调节 KF 的增殖、迁移、侵袭和 ECM 沉积。
{"title":"CEMIP induces TGF-β/Smad signaling to promote keloid development by binding to SPARC.","authors":"Xinyi Li, Wei Zhang, Xiaojing Li","doi":"10.1016/j.clinsp.2024.100523","DOIUrl":"10.1016/j.clinsp.2024.100523","url":null,"abstract":"<p><strong>Background: </strong>Cell Migration Inducing Hyaluronidase 1 (CEMIP) is a protein that plays regulatory functions in a variety of cellular processes in many diseases. Nevertheless, its role and molecular mechanism in keloid hyperplasia are still elusive.</p><p><strong>Methods: </strong>Expressions of CEMIP and Secreted Protein acidic and Rich in Cysteine (SPARC) were detected by qRT-PCR and western blot. CCK-8 assay, along with immunofluorescence staining, was applied for the assessment of cell proliferation. The capabilities of cells to migrate and invade were evaluated utilizing wound healing and Transwell, while Extracellular Matrix (ECM) deposition was measured by immunofluorescence and western blot. The interaction of CEMIP and SPARC was predicted by the Coexpedia and PPA-red databases and verified by co-IP. Western blot was adopted for the estimation of TGF-β/Smad pathway-related proteins.</p><p><strong>Results: </strong>The data demonstrated that CEMIP expression was elevated in Keloid Fibroblasts (KF). CEMIP interference suppressed cell proliferative, migrative and invasive capabilities and ECM deposition in KF. Mechanistically, bioinformatics analysis revealed that CEMIP was co-expressed with SPARC and CEMIP protein could bind to SPARC. SPARC expression was reduced in CEMIP-silenced cells. SPARC overexpression counteracted the impacts of CEMIP silencing on cell proliferative, migrative and invasive capabilities and ECM deposition in KF. In addition, the expressions of TGF-β/Smad signaling-related proteins were decreased by CEMIP silencing via the inhibition of SPARC.</p><p><strong>Conclusion: </strong>In summary, this study revealed that CEMIP modulated KF proliferation, migration, invasion and ECM deposition by TGF-β/Smad signaling through binding to SPARC.</p>","PeriodicalId":10472,"journal":{"name":"Clinics","volume":"79 ","pages":"100523"},"PeriodicalIF":2.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557329","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
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