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Diagnostic Accuracy of Computerized Bowel Sound Analysis with Non-Invasive Devices for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis 计算机肠鸣音分析与非侵入性设备对肠易激综合征的诊断准确性:系统回顾与元分析》。
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004307

Objective

To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome (IBS) with a systematic review and meta-analysis.

Methods

We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and IEEE Xplore databases until September 2023. Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified. We estimated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio with a 95% confidence interval (CI), and plotted a summary receiver operating characteristic curve and evaluated the area under the curve.

Results

Four studies were included. The pooled diagnostic sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.94 (95% CI, 0.87–0.97), 0.89 (95% CI, 0.81–0.94), 8.43 (95% CI, 4.81–14.78), 0.07 (95% CI, 0.03–0.15), and 118.86 (95% CI, 44.18–319.75), respectively, with an area under the curve of 0.97 (95% CI, 0.95–0.98).

Conclusions

Computerized bowel sound analysis is a promising tool for IBS. However, limited high-quality data make the results' validity and applicability questionable. There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.

目的 通过系统综述和荟萃分析评估肠易激综合征(IBS)肠鸣音分析的诊断准确性。方法 我们检索了 MEDLINE、EMBASE、Cochrane Library、Web of Science 和 IEEE Xplore 数据库,直至 2023 年 9 月。确定了肠鸣音分析对肠易激综合征诊断准确性的横断面研究和病例对照研究。我们估算了汇总的灵敏度、特异性、阳性似然比、阴性似然比和诊断几率比(含 95% 置信区间 (CI)),绘制了接收者操作特征曲线并评估了曲线下面积。结果 共纳入四项研究。汇总的诊断灵敏度、特异性、阳性似然比、阴性似然比和诊断几率比分别为 0.94(95% CI,0.87-0.97)、0.89(95% CI,0.81-0.94)、8.43(95% CI,4.81-14.78)、0.07(95% CI,0.03-0.15)和 118.86(95% CI,44.18-319.75),曲线下面积为 0.97(95% CI,0.95-0.98)。结论 计算机肠鸣音分析是一种治疗肠易激综合征的有效工具。然而,由于高质量数据有限,其结果的有效性和适用性值得怀疑。需要进行更多的诊断测试准确性研究和更好的可穿戴设备来进行监测和分析。
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引用次数: 0
Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia: A Promising Supportive Therapy 生玉米淀粉对胰岛素瘤导致的低血糖症的疗效:一种前景看好的辅助疗法
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004329

Objective

To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia.

Methods

We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events.

Results

The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50–2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05 – 0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30–5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60–2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60–3.95) mmol/L vs. 2.15 (IQR: 1.83 – 2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50–3.65) mmol/L vs. 2.20 (IQR: 1.80–2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose.

Conclusion

The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

目的 探讨生玉米淀粉(RCS)在胰岛素瘤所致低血糖临床治疗中的疗效。方法 回顾性收集术前接受RCS辅助饮食的胰岛素瘤患者的临床资料,分析RCS干预对血糖控制、体重变化及其不良反应的治疗效果。补充 RCS 饮食前,所有患者均频繁发生低血糖(2.51 ± 3.88 次/周),同时伴有神经性糖耐量减低症(83.3% 的患者)和自主神经表现(75.0% 的患者),空腹血糖(FBG)中位数为 2.70 [四分位数间距(IQR):2.50-2.90] mmol/L。患者体重每月增加 0.38(IQR:0.05-0.65)千克,其中 8 例(33.3%)发展为超重,7 例(29.2%)发展为肥胖。所有患者在接受肿瘤切除术(23 例)和经动脉化疗栓塞治疗肝转移瘤(1 例)之前,一直保持补充 RCS 的饮食习惯。19 名全天接受 RCS 的患者在营养管理一周内的 FBG 中位数为 4.30(IQR:3.30-5.70)mmol/L,与营养前水平 [2.25 (IQR:1.60-2.90)mmol/L;P = 0.000]相比显著增加。其中,10 名患者全天接受 RCS 超过四周,与治疗前相比,FBG 有持续改善 [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L;P = 0.000]。五名仅在夜间接受 RCS 的患者的 FBG 也在营养管理一周内显著增加 [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L;P = 0.000],但只有一名持续接受 RCS 超过 4 周的患者的 FBG 没有显著改善。补充 RCS 后体重增加没有改善。出现轻度腹泻(2 例)和胀气(1 例),减少 RCS 剂量后症状缓解。
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引用次数: 0
Development of a Decision Aid for Family Surrogate Decision Makers of Critically Ill Patients Requiring Renal Replacement Therapy in ICU: A User-Centered Design for Rapid Prototyping 为需要接受肾脏替代治疗的重症监护室危重病人的家庭代理决策者开发决策辅助工具:以用户为中心的快速原型设计。
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004326

Objective

Renal replacement therapy (RRT) is increasingly adopted for critically ill patients diagnosed with acute kidney injury, but the optimal time for initiation remains unclear and prognosis is uncertain, leading to medical complexity, ethical conflicts, and decision dilemmas in intensive care unit (ICU) settings. This study aimed to develop a decision aid (DA) for the family surrogate of critically ill patients to support their engagement in shared decision-making process with clinicians.

Methods

Development of DA employed a systematic process with user-centered design (UCD) principle, which included: (i) competitive analysis: searched, screened, and assessed the existing DAs to gather insights for design strategies, developmental techniques, and functionalities; (ii) user needs assessment: interviewed family surrogates in our hospital to explore target user group's decision-making experience and identify their unmet needs; (iii) evidence syntheses: integrate latest clinical evidence and pertinent information to inform the content development of DA.

Results

The competitive analysis included 16 relevant DAs, from which we derived valuable insights using existing resources. User decision needs were explored among a cohort of 15 family surrogates, revealing four thematic issues in decision-making, including stuck into dilemmas, sense of uncertainty, limited capacity, and delayed decision confirmation. A total of 27 articles were included for evidence syntheses. Relevant decision-making knowledge on disease and treatment, as delineated in the literature sourced from decision support system or clinical guidelines, were formatted as the foundational knowledge base. Twenty-one items of evidence were extracted and integrated into the content panels of benefits and risks of RRT, possible outcomes, and reasons to choose. The DA was drafted into a web-based phototype using the elements of UCD. This platform could guide users in their preparation of decision-making through a sequential four-step process: identifying treatment options, weighing the benefits and risks, clarifying personal preferences and values, and formulating a schedule for formal shared decision-making with clinicians.

Conclusions

We developed a rapid prototype of DA tailored for family surrogate decision makers of critically ill patients in need of RRT in ICU setting. Future studies are needed to evaluate its usability, feasibility, and clinical effects of this intervention.

目的 肾脏替代疗法(RRT)越来越多地被确诊为急性肾损伤的重症患者所采用,但最佳的启动时间仍不明确,预后也不确定,导致重症监护病房(ICU)的医疗复杂性、伦理冲突和决策困境。本研究旨在为重症患者的代理家属开发一种决策辅助工具(DA),以支持他们参与与临床医生的共同决策过程。方法 DA 的开发采用了以用户为中心的设计(UCD)原则的系统流程,其中包括(i)竞争分析:搜索、筛选和评估现有的DA,以收集对设计策略、开发技术和功能的见解;(ii)用户需求评估:采访家庭代理,以探索目标用户群的决策经验,并确定他们未满足的需求;(iii)证据综合:整合最新的临床证据和相关信息,为DA的内容开发提供依据。我们对 15 位家庭代理的用户决策需求进行了调查,发现了决策中的四个主题问题,包括陷入两难境地、不确定感、能力有限和决策确认延迟。共有 27 篇文章被纳入证据综述。从决策支持系统或临床指南中获取的相关疾病和治疗决策知识被格式化为基础知识库。提取了 21 项证据,并将其整合到 RRT 的益处和风险、可能的结果以及选择的理由等内容板块中。利用统一设计元素,将数据采集草拟成基于网络的图片模型。该平台可指导用户通过以下四个步骤为决策做准备:确定治疗方案、权衡益处和风险、明确个人偏好和价值观、制定与临床医生正式共同决策的时间表。未来的研究需要评估这一干预措施的可用性、可行性和临床效果。
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引用次数: 0
A Chinese Multi-Specialty Delphi Consensus to Optimize RAASi Usage and Hyperkalaemia Management in Patients with Chronic Kidney Disease and Heart Failure 中国多专科德尔菲共识:优化慢性肾病和心衰患者 RAASi 的使用和高钾血症管理
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004327

Objective

Variations are present in common clinical practices regarding best practice in managing hyperkalaemia (HK), there is therefore a need to establish a multi-specialty approach to optimal rennin-angiotension-aldosterone system inhibitors (RAASi) usage and HK management in patients with chronic kidney disease (CKD) & heart failure (HF). This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF.

Methods

A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique. The group then created a list of 41 statements for a consensus questionnaire, which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China. Consensus was assessed using a modified Delphi technique, with agreement defined as “strong” (≥75% and <90%) and “very strong” (≥90%). The steering group, data collection, and analysis were aided by an independent facilitator.

Results

A total of 150 responses from 21 provinces across China were recruited in the survey. Respondents were comprised of an even split (n=75, 50%) between cardiologists and nephrologists. All 41 statements achieved the 75% consensus agreement threshold, of which 27 statements attained very strong consensus (≥90% agreement) and 14 attained strong consensus (agreement between 75% and 90%).

Conclusion

Based on the agreement levels from respondents, the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.

目的:在处理高钾血症(HK)的最佳实践方面,常见的临床实践存在差异,因此有必要建立一种多专业方法,以优化肾素-血管紧张素-醛固酮系统抑制剂(RAASi)的使用以及慢性肾脏病(CKD)和心力衰竭(HF)患者的HK管理:由来自中国各地的心脏病学和肾脏病学专家组成的专家指导小组召开会议,通过名义小组技术(NGT)讨论香港管理面临的挑战。然后,专家组编制了一份包含 41 项陈述的共识调查问卷,并将其分发给全国各地的心脏病学家和肾脏病学家组成的扩大小组,以进一步调查。采用改良的德尔菲技术对共识进行评估,将一致定义为 "强"(≥75%)和 "结果":调查共收到来自全国 21 个省份的 150 份回复。受访者中心脏病专家和肾病专家各占一半(75 人,50%)。所有 41 项陈述均达到了 75% 的共识一致阈值,其中 27 项陈述达到了非常强烈的共识(≥ 90% 的一致),14 项陈述达到了强烈的共识(75% 至 90% 的一致)。结论根据受访者的同意程度,指导小组达成了一系列建议,旨在改善中国使用 RAASi 治疗和香港管理的患者预后。
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引用次数: 0
Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces 对涉及脑机接口的临床研究进行伦理审查的挑战和建议。
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004377

Brain-computer interface (BCI) technology is rapidly advancing in medical research and application. As an emerging biomedical engineering technology, it has garnered significant attention in the clinical research of brain disease diagnosis and treatment, neurological rehabilitation, and mental health. However, BCI also raises several challenges and ethical concerns in clinical research. In this article, the authors investigate and discuss three aspects of BCI in medicine and healthcare: the state of international ethical governance, multidimensional ethical challenges pertaining to BCI in clinical research, and suggestive concerns for ethical review. Despite the great potential of frontier BCI research and development in the field of medical care, the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI. To ensure “responsible innovation” in BCI research in healthcare and medicine, the creation of an ethical global governance framework and system, along with special guidelines for cutting-edge BCI research in medicine, is suggested.

脑机接口(BCI)技术在医学研究和应用领域发展迅速。作为一种新兴的生物医学工程技术,它在脑疾病诊断和治疗、神经康复和心理健康的临床研究中备受关注。然而,BCI 也给临床研究带来了一些挑战和伦理问题。在本文中,作者从三个方面研究和讨论了医疗和保健领域的生物识别技术:伦理管理现状、临床研究中与生物识别技术相关的多维度伦理挑战以及伦理审查的建议性关注点。尽管前沿的生物识别(BCI)研究和开发在医疗保健领域具有巨大潜力,但其本身、临床研究和脑功能的复杂性所引发的伦理挑战为生物识别(BCI)伦理提出了新的特殊领域。为确保在医疗保健和医学领域开展 "负责任的创新 "BCI 研究,建议建立全球伦理治理框架和体系,并为医学领域的前沿 BCI 研究提供专门的指导方针。
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引用次数: 0
PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing PPP1R14A与头颈部鳞状细胞癌的免疫疗法耐受性有关--通过单细胞和大容量RNA测序发现
Q2 Medicine Pub Date : 2024-06-01 DOI: 10.24920/004354

Objective

To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma (HNSCC) using single-cell and bulk RNA-sequencing data.

Methods

The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes (DEGs) between nivolumab resistant and nivolumab sensitive patients using R software. The Least Absolute Shrinkage Selection Operator (LASSO) regression and Recursive Feature Elimination (RFE) algorithm were performed to identify key genes associated with nivolumab resistance. Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The relationships of key genes with immune cell infiltration, differentation trajectory, dynamic gene expression profiles, and ligand-receptor interaction were explored.

Results

We found 83 DEGs. They were mainly enriched in T-cell differentiation, PD-1 and PD-L1 checkpoint, and T-cell receptor pathways. Among six key genes identified using machine learning algorithms, only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy (P < 0.05). The high PPP1R14A gene expression group had lower immune score (P < 0.01), higher expression of immunosuppressive factors (such as PDCD1, CTLA4, and PDCD1LG2) (r > 0, P < 0.05), lower differentiation of infiltrated immune cells (P < 0.05), and a higher degree of interaction between HLA and CD4 (P < 0.05).

Conclusions

PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients. Therefore, PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

目的 利用单细胞和大容量RNA测序数据鉴定头颈部鳞状细胞癌(HNSCC)患者的尼夫单抗耐药相关基因。方法 使用R软件分析从基因表达总库(Gene Expression Omnibus)数据库下载的单细胞和大容量RNA测序数据,筛选出尼伐单抗耐药患者和尼伐单抗敏感患者之间的差异表达基因(DEGs)。通过最小绝对收缩选择操作符(LASSO)回归和递归特征消除(RFE)算法,找出了与尼夫单抗耐药相关的关键基因。利用基因本体论和京都基因组百科全书分析了DEGs的功能富集。探讨了关键基因与免疫细胞浸润、分化轨迹、动态基因表达谱和配体-受体相互作用的关系。结果 我们发现了 83 个 DEGs。它们主要富集在 T 细胞分化、PD-1 和 PD-L1 检查点通路以及 T 细胞受体通路中。在使用机器学习算法确定的六个关键基因中,只有 PPP1R14A 基因在免疫治疗前后在尼夫单抗耐药组和尼夫单抗敏感组之间有差异表达(P < 0.05)。PPP1R14A基因高表达组的免疫评分较低(P<0.01),免疫抑制因子(如PDCD1、CTLA4和PDCD1LG2)表达较高(r>0,P<0.05),浸润免疫细胞分化较低(P<0.05),HLA与CD4之间的相互作用程度较高(P<0.05)。结论 PPP1R14A 基因与 HNSCC 患者对尼伐单抗的耐药性密切相关。因此,PPP1R14A 可能是改善 HNSCC 患者尼伐单抗耐药性的靶点。
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引用次数: 0
A Dataset on Population Activity Patterns in Typical Regions of North China 华北典型地区人口活动模式数据集。
Q2 Medicine Pub Date : 2024-04-01 DOI: 10.24920/004324
Yi-Sen Yang , Sheng-Yu Liu , Ya-Yuan Mei , Quan Zhou , Mei-Duo Zhao , Qun Xu , Si-Zhu Wu

This data article describes the “Typical Regional Activity Patterns” (TRAP) dataset, which is based on the Tackling Key Problems in Air Pollution Control Program. In order to explore the interaction between air pollution and physical activity, we collected activity patterns of 9,221 residents with different occupations and lifestyles for three consecutive days in typical regions (Jinan and Baoding) where air pollutant concentrations were higher than those in neighboring areas. The TRAP dataset consists of two aspects of information: demographic indicators (personal information, occupation, personal habits, and living situation) and physical activity pattern data (activity location and intensity); additionally, the exposure measures of physical activity patterns are included, which data users can match to various endpoints for their specific purpose. This dataset provides evidence for exploring the attributes of activity patterns of residents in northern China and for interdisciplinary researchers to develop strategies and measures for health education and health promotion.

这篇文章介绍了 "典型区域活动模式"(TRAP)数据集,该数据集基于《大气污染防治重点攻关计划》。为了探讨空气污染与身体活动之间的相互作用,我们在空气污染物浓度高于周边地区的典型区域(济南和保定)收集了 9221 名不同职业和生活方式的居民连续三天的活动模式。TRAP 数据集包括两方面的信息:人口统计指标(个人信息、职业、个人习惯和生活状况)和身体活动模式数据(活动地点和强度);此外,还包括身体活动模式的暴露测量值,数据用户可根据具体目的将其与各种终点进行匹配。该数据集为探索中国北方居民的活动模式属性提供了证据,也为跨学科研究人员制定健康教育和健康促进的策略和措施提供了依据。
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引用次数: 0
Body Positions Alter Hemodynamics and Respiration in Healthy Adults: A Systematic Review and Meta-Analysis 体位改变健康成年人的血液动力学和呼吸:系统回顾与元分析》。
Q2 Medicine Pub Date : 2024-04-01 DOI: 10.24920/004281
Ruchada Sriamad, Sirinut Chaiduang, Thaniya Klinsophon, Premtip Thaveeratitham

Objective

Different body positions can exert both positive and negative physiological effects on hemodynamics and respiration. This study aims to conduct a literature review and examine hemodynamic and respiratory alterations to different body positions.

Methods

The study protocol was registered with the International Prospective Registry of Systematic Reviews (register no. CRD42021291464). Two independent reviewers evaluated the methodological quality of all included studies using the Down and Black checklist, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The overall effects of different body positions were reported from random effects meta-analysis.

Results

Three studies with low risk of bias and ten with high risk of bias met the eligibility criteria. The supine resulted in the highest cardiac output compared to the 70 deg head-up tilt, sitting, and standing positions (very low- to moderate-quality evidences) and the lowest systemic vascular resistance compared to the 70 deg head-up tilt and standing positions (moderate-quality evidence). Additionally, the supine was associated with the highest total respiratory resistance compared to the 70 deg head-up tilt, left lateral, and standing positions (very low-to moderate-quality evidence) and higher alveolar ventilation than the prone (low-quality evidence).

Conclusions

The supine position has the most positive association with hemodynamic variables, resulting in the highest cardiac output and the lowest systemic vascular resistance. The upright positions (70 deg head-up tilt and standing positions) has the most positive association with the respiratory variables, resulting in the lowest total respiratory resistance.

目的 不同体位会对血液动力学和呼吸产生积极和消极的生理影响。本研究旨在进行文献综述,探讨不同体位对血液动力学和呼吸系统的影响。方法 研究方案已在国际系统综述前瞻性注册中心注册(注册号:CRD42021291464)。两位独立审稿人采用 Down and Black 检查表对所有纳入研究的方法学质量进行了评估,并采用建议、评估、发展和评价分级法对证据质量进行了评估。随机效应荟萃分析报告了不同体位的总体效果。结果 有三项低偏倚风险研究和十项高偏倚风险研究符合资格标准。与 70 度抬头仰卧位、坐位和站立位相比,仰卧位的心输出量最高(极低至中等质量证据),与 70 度抬头仰卧位和站立位相比,仰卧位的全身血管阻力最低(中等质量证据)。此外,与 70 度抬头仰卧位、左侧卧位和站立位相比,仰卧位的总呼吸阻力最高(极低至中等质量证据),肺泡通气量比俯卧位高(低质量证据)。结论 仰卧位与血液动力学变量的关系最为密切,可产生最高的心输出量和最低的全身血管阻力。直立体位(70 度抬头仰卧位和站立位)与呼吸变量的正相关性最强,导致总呼吸阻力最低。
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引用次数: 0
Protective Effect of Dihydromyricetin Against ExerciseInduced Muscle Damage and Its Mechanism 二氢杨梅素对运动引起的肌肉损伤的保护作用及其机制
Q2 Medicine Pub Date : 2024-04-01 DOI: 10.24920/004272
Ying Wu , Da-Wei Wang , Jun Li , Xian-Jie Xu , Zhi-Dan Gao , Hong-Yan Li , Yong Zhang , Peng Liu

Objective

To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.

Methods

Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight •d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.

Results

Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.

Conclusion

DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

目的 研究二氢杨梅素(DHM)对小鼠运动诱发肌肉损伤(EIMD)的保护作用及其潜在机制。方法 将成年雄性 C57BL/6J 小鼠随机分为对照组(CG)、运动组(EG)和 DHM(100 毫克/千克体重-d)+运动组(DHM)。干预持续四周,在此期间,EG 组和 DHM 组的动物每天接受 1 小时的运动训练。训练结束后的第二天,EG 组和 DHM 组都进行了 90 分钟的跑步机运动(坡度:0,速度:18 米/分钟)。运动 24 小时后采集三组样本,然后测定血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性、总超氧化物歧化酶(T-SOD)活性、丙二醛含量以及骨骼肌线粒体酶复合物 I 和 II 活性。最后,观察骨骼肌的组织学变化,并通过 Western 印迹法检测线粒体功能相关通路的蛋白质表达。结果 与 EG 组相比,DHM 组的骨骼肌形态学变化和线粒体损伤有所减轻。DHM 干预后,EIMD 标志物 CK 和 LDH 的活性以及脂质过氧化水平显著降低,血清 T-SOD 活性提高。结论 DHM 可缓解小鼠的 EIMD,可能是通过激活 SIRT3 信号通路促进高强度运动后小鼠骨骼肌线粒体结构和功能的恢复。
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引用次数: 0
Influence of GPRC5A-Regulated ABCB1 Expression on Lung Adenocarcinoma Proliferation GPRC5A 调节的 ABCB1 表达对肺腺癌增殖的影响
Q2 Medicine Pub Date : 2024-04-01 DOI: 10.24920/004216
Yun Li , Wen-Wen Cui , Zhong-Fa Yang , Wen-Hao Liu , Mao-Wang Bian , Jiong Deng , Tong Wang

Objective

Aberrant expression of ATP binding cassette subfamily B member 1 (ABCB1) plays a key role in several cancers. However, influence of G protein coupled receptor family C group 5 type A (GPRCSA)-regulated ABCB1 expression on lung adenocarcinoma proliferation remains unclear. Therefore, this study investigated the effect of GPRC5A regulated ABCB1 expression on the proliferation of lung adenocarcinoma.

Methods

ABCBI expressions in lung adenocarcinoma cell lines, human lung adenocarcinoma tissues, and tracheal epithelial cells and lung tissues of GPRC5A knockout mice and wild-type mice were analyzed with RT-PCR, Western blot, or immunohistochemical analysis. Cell counting kit-8 assay was performed to analyze the sensitivity of tracheal epithelial cells from GPRC5A knockout mice to chemotherapeutic agents. Subcutaneous tumor formation assay was performed to confirm whether down-regulation of ABCBI could inhibit the proliferation of lung adenocarcinoma in vivo. To verify the potential regulatory relationship between GPRCS A and ABCB1, immunofluorescence and immunoprecipitation assays were performed.

Results

ABCB1 expression was up-regulated in lung adenocarcinoma cell lines and human lung adenocarcinoma tissues. ABCBI expression in the tracheal epithelial cells and lung tissues of GPRC5A deficient mice was higher than that in the wild type mice. Tracheal epithelial cells of GPRC5A knockout mice were much more sensitive to tariquidar and doxorubicin than those of GPRC5A wild type mice. Accordingly, 28 days after injection of the transplanted cells, the volume and weight of lung tumor in ABCBI knockout cell-transplanted GPRCS A-/C57BL/6 mice were significantly smaller than those in wild type cell-transplanted mice (P = 0.0043, P = 0.0060). Furthermore, immunofluorescence and immunoprecipitation assays showed that GPRC5A regulated ABCBI expression by direct binding.

Conclusion

GPRC5A reduces lung adenocarcinoma proliferation via inhibiting ABCBI expression. The pathway by which GPRC5A regulates ABCBI expression needs to be investigated.

目的 ATP 结合盒 B 亚家族成员 1(ABCB1)的异常表达在多种癌症中起着关键作用。然而,G蛋白偶联受体C家族5组A型(GPRC5A)调控的ABCB1表达对肺腺癌的影响仍不清楚。本研究采用 RT-PCR、Western 印迹或免疫组化等方法分析了 GPRC5A 基因敲除小鼠和野生型小鼠的肺腺癌细胞系、人肺腺癌组织、气管上皮细胞和肺组织中 ABCB1 的表达。细胞计数试剂盒-8测定分析了GPRC5A基因敲除小鼠气管上皮细胞对化疗药物的敏感性。进行皮下肿瘤形成试验,以确认下调 ABCB1 是否能抑制体内肺腺癌的增殖。为了验证 GPRC5A 和 ABCB1 之间的潜在调控关系,进行了免疫荧光和免疫沉淀试验。结果 ABCB1 在肺腺癌细胞系和人肺腺癌组织中表达上调。GPRC5A 基因缺陷小鼠气管上皮细胞和肺组织中 ABCB1 的表达高于野生型小鼠。GPRC5A基因敲除小鼠的气管上皮细胞对tariquidar和多柔比星的敏感性远高于GPRC5A野生型小鼠。因此,注射移植细胞 28 天后,ABCB1 基因敲除细胞移植 GPRC5A-/- C57BL/6 小鼠肺肿瘤的体积和重量明显小于野生型细胞移植小鼠(P = 0.0043,P = 0.0060)。此外,免疫荧光和免疫沉淀试验表明,GPRC5A 通过直接结合调控 ABCB1 的表达。结论 GPRC5A 通过抑制 ABCB1 的表达减少肺腺癌的增殖。GPRC5A 调节 ABCB1 表达的途径还有待研究。
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Chinese Medical Sciences Journal
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