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Prognostic role of C-reactive protein to albumin ratio in lung cancer: An updated systematic review and meta-analysis C反应蛋白与白蛋白比率在癌症预后中的作用:一项最新的系统综述和荟萃分析
Q1 Medicine Pub Date : 2023-08-11 DOI: 10.1002/cdt3.91
Zhendong Lu, Siyun Fu, Wei Li, Xiang Gao, Jinghui Wang

Background

C-reactive protein to albumin ratio (CRP/Alb ratio, CAR) has been suggested as a potential prognostic biomarker in lung cancer. This updated systematic review and meta-analysis aimed to assess the association between CAR and lung cancer prognosis in current literature.

Methods

A systematic search of databases was conducted to identify relevant studies published up to April 2023. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the association between CAR and overall survival (OS) and progression-free survival (PFS) and recurrence-free survival (RF) in lung cancer patients.

Results

This meta-analysis includes 16 studies with a total of 5337 patients, indicating a significant association between higher CAR and poorer OS, PFS, and RFS in lung cancer patients, with a pooled HR of 1.78 (95% CI = 1.60–1.99), 1.57 (95% CI = 1.36–1.80), and 1.97 (95% CI = 1.40–2.77), respectively.

Conclusions

This updated meta-analysis provides evidence for the potential prognostic role of CAR in lung cancer, suggesting its utility as an effective and noninvasive biomarker for identifying high-risk patients and informing treatment decisions in a cost-effective manner. However, further large-scale studies will be necessary to establish the optimal cut-off value for CAR in lung cancer and confirm the present findings.

C反应蛋白与白蛋白比值(CRP/Alb ratio, CAR)已被认为是肺癌的潜在预后生物标志物。本最新的系统综述和荟萃分析旨在评估当前文献中CAR与肺癌预后之间的关系。系统检索数据库,确定截至2023年4月发表的相关研究。计算合并风险比(hr)和95%置信区间(CIs),以评估肺癌患者CAR与总生存期(OS)、无进展生存期(PFS)和无复发生存期(RF)之间的关系。该荟萃分析包括16项研究,共5337例患者,表明肺癌患者较高的CAR与较差的OS、PFS和RFS之间存在显著关联,合并HR分别为1.78 (95% CI = 1.60-1.99)、1.57 (95% CI = 1.36-1.80)和1.97 (95% CI = 1.40-2.77)。这项最新的荟萃分析为CAR在肺癌中的潜在预后作用提供了证据,表明其作为一种有效且无创的生物标志物,可用于识别高风险患者,并以具有成本效益的方式为治疗决策提供信息。然而,需要进一步的大规模研究来确定CAR在肺癌中的最佳临界值,并证实目前的发现。
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引用次数: 0
The public–private partnerships in healthcare sector in China 中国医疗保健领域的公私伙伴关系
Q1 Medicine Pub Date : 2023-08-11 DOI: 10.1002/cdt3.88
Bo Liu, Leiyu Shi, Hanyi Min, Hailun Liang, Jiahong Dong

This manuscript is a narrative review on experience in the healthcare public–private partnerships (PPP) field project in China. The PPP model allows healthcare officials to share the risk of building new facilities with the private sector. The objective of this study is to evaluate and to review the PPP of healthcare sector in China, and to investigate the critical success factors and best practice of PPP. We adapted the PPP evaluation framework of the World Bank Independent Evaluation Group as our conceptual framework to summarize the literatures. The current study systematically reviewed the evolution and current status of public and private hospitals development in China, and to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China, and to develop best practice models of PPP among hospitals of China. We found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure—potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes.

本文是对中国医疗卫生领域公私合作(PPP)项目经验的叙述性回顾。PPP模式允许医疗官员与私营部门共同承担建设新设施的风险。本研究的目的是评估和回顾中国医疗保健行业的PPP,并探讨PPP成功的关键因素和最佳实践。本文采用世界银行独立评估小组的PPP评估框架作为概念框架对文献进行总结。本研究系统回顾了中国公立医院和民营医院发展的沿革和现状,探讨了PPP在中国医疗卫生领域成功和不成功的相关因素,并建立了中国医院PPP的最佳实践模式。我们发现,PPP组织提供财务和政治风险覆盖,从而使具体的PPP交易达到财务结清——潜在地设置示范效应。这样的公私伙伴关系可能有助于改善获得基础设施和社会服务的机会,从而推动经济增长和其他最优结果。
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引用次数: 0
IgA nephropathy with podocytic infolding glomerulopathy IgA肾病伴足细胞折叠肾小球病变
Q1 Medicine Pub Date : 2023-08-02 DOI: 10.1002/cdt3.86
Zhouyang Wang, Yujie Diao, Zhendong Wang, Xiangdong Yang, Junhui Zhen, Guangyi Liu

(A) Immunofluorescence staining showed moderate immunoglobulin A depositions in the mesangial areas (++) of glomeruli (Bars = 100 μm). (B) Segmentally mild mesangial proliferation and mesangial matrix expansion (arrowhead) with mild thickening of glomerular capillary walls (PAS, ×400).

(A) 免疫荧光染色显示肾小球系膜区(++)有中度免疫球蛋白A沉积(Bars = 100 μm)。(B) 节段性轻度系膜增殖和系膜基质扩张(箭头),肾小球毛细血管壁轻度增厚(PAS,×400)。
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引用次数: 0
Cardiovascular risk assessment: The key path toward precision prevention 心血管风险评估:精准预防的关键途径
Q1 Medicine Pub Date : 2023-08-01 DOI: 10.1002/cdt3.90
Jianxin Li, Xiangfeng Lu

Cardiovascular disease (CVD) is the most common noncommunicable disease and the leading cause of death globally.1 It has resulted in enormous economic and social burdens, while posing a great challenge for the prevention and control of CVD worldwide, especially in China. Assessment and management of cardiovascular risk is the foundation of CVD prevention, and is strongly recommended by guidelines.2-4 Additionally, it can help screen the target population who would benefit most from the lower-cost intervention, while informing them the cardiovascular risk, which will help in promoting self-management. It can also guide doctors in making logical management decisions, and implement precision prevention and treatment strategies to reduce the CVD burden.2, 4 Therefore, it is a key approach in achieving the goals of “Good Health and Well-being” in the United Nations and “Healthy China 2030” in China. Here, we briefly highlight several advances in cardiovascular risk assessments.

The Framingham Heart Study introduced the term “risk factor” in 1961, and identified a series of risk factors of CVD subsequently, such as cholesterol, blood pressure, glucose, and obesity.5 By integrating multiple conventional risk factors, a general cardiovascular risk instrument was further developed to assist in identifying and treating individuals at high risk.6 Since the concept of cardiovascular risk assessment and stratification was adopted by the third Adult Treatment Panel of the National Cholesterol Education Program in 2001, it has led to the development of effective treatment and preventive strategies in clinical practice.

A systematic approach to cardiovascular risk assessment includes the collection of information to calculate the cardiovascular risk, identification of the target high-risk population, and implementation of individual management according to the risk level. Therefore, risk-prediction models are major components of risk-based CVD prevention and control efforts. Several cardiovascular risk models have been developed using conventional risk factors to assist in clinical practice, such as the Reynolds Risk Score7, 8 and the Pooled Cohort Equations (PCE)9 in the United States, the QRISK in the United Kingdom,10 the ASSIGN Score in Scotland,11 the Systematic Coronary Risk Evaluation (SCORE) model in Europe,12 and the Prediction for Atherosclerotic CVD Risk in China (China-PAR) equations.13 In addition, World Health Organization has derived the risk prediction charts for 21 Global Burden of Disease regions to facilitate the risk-based CVD prevention in low- and middle-income countries.4 These models, taking account of balance between good performance and ac

小分子代谢物,如氨基酸、脂质和代谢副产物,可以反映宿主对外界暴露的多参数反应。它们可以解释心血管疾病与传统危险因素之间的个体差异,并为心血管风险评估提供潜在信息此外,其他组学生物标志物,如表观遗传学、转录组学和肠道微生物组,也可以帮助提供个体健康状况的纵向快照,并实现更精确的风险预测和治疗方法虽然多组学生物标志物很有前景,但未来的研究需要更好地评估它们在心血管疾病风险评估中的作用,并确定将这些生物标志物整合到心血管疾病一级预防中的成本效益和可用性。ML是人工智能的一个分支,可以提高心血管疾病风险预测的准确性,帮助将大数据转化为临床决策。ML已被用于评估心血管风险,并且优于传统的风险模型此外,机器学习驱动的组学数据整合在风险预测方面很有希望使用ML进行个性化风险预测可以为迫切需要优化护理的患者量身定制更好的治疗方案。然而,机器学习并不是解决医学科学中所有问题的万能钥匙。ML模型受到用于训练它们的数据的质量和数量的限制。在模型中加入变量会由于测量方法和误差而产生噪声。因此,更多的努力应该集中在验证已建立的机器学习模型上,而不是开发新的方法。心血管风险评估是心血管疾病预防工作的基础,也是实现精准预防的重要基石。至关重要的是要改善利用互联网或智能手机进行风险评估的可及性,通过将其纳入电子健康记录平台来促进精确预防,并制定有效的政策以广泛实施风险评估。风险评估的增量改进可以通过风险增强因素、遗传学、蛋白质组学、代谢组学和ml驱动的数据挖掘来实现。但是,它们的成本效益和可得性应在今后的研究中加以评价。李建新、卢祥峰起草并修改了本稿。所有作者都阅读并编辑了手稿。作者声明无利益冲突。卢祥峰教授为《慢性疾病与转化医学》编委会成员,未参与本文的同行评议和决策过程。
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引用次数: 0
Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis 不同双重抗血小板策略在经皮冠状动脉介入治疗患者中的疗效和安全性:一项系统综述和网络meta分析
Q1 Medicine Pub Date : 2023-07-27 DOI: 10.1002/cdt3.85
Yuttana Wongsalap, Kirati Kengkla, Preyanate Wilairat, Khemanat Ratworawong, Surasak Saokaew, Chaisiri Wanlapakorn

Background

Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI.

Methods

We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs).

Results

A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64–0.98), bleeding (RR = 0.63, 95% CI = 0.49–0.82), and NACEs (RR = 0.69, 95% CI = 0.60–0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46–0.86) compared with standard DAPT.

Conclusions

De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

背景:双重抗血小板治疗(DAPT)是预防经皮冠状动脉介入治疗(PCI)后缺血性事件的关键。实施各种DAPT修改,如缩短持续时间或P2Y12抑制剂(P2Y12i)降级,以降低出血风险。然而,这些策略缺乏直接的比较研究。本研究旨在评估此类DAPT策略(包括降级和短期DAPT)在PCI患者中的疗效和安全性。方法:我们在PubMed、Embase、Cochrane Central Register of Controlled Trials和ClinicalTrials.gov数据库中搜索相关的随机对照试验(RCT)。我们进行了一项网络荟萃分析(NMA)来估计风险比(RR)和95%置信区间(CI)。主要疗效终点为主要心脏不良事件(MACE),主要安全性终点为主要出血。次要终点包括MACE的个体成分和净不良临床事件(NACE)。结果:共纳入17项随机对照试验,包括53156名患者(中位年龄62.0岁,女性24.8%)。NMA表明,降级DAPT与MACE风险显著降低相关(风险比[RR] = 0.79,95%置信区间[CI] = 0.64-0.98),出血(RR = 0.63,95%CI = 0.49-0.82)和NACE(RR = 0.69,95%CI = 0.60-0.79)。P2Y12i单药治疗后短期DAPT显著降低了大出血的风险(RR = 0.63,95%CI = 0.46-0.86)。结论:在不增加出血事件的情况下,降级DAPT是预防MACE风险的最有效策略,而短DAPT联合P2Y12i单药治疗是降低PCI患者出血风险的最高效策略。
{"title":"Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis","authors":"Yuttana Wongsalap,&nbsp;Kirati Kengkla,&nbsp;Preyanate Wilairat,&nbsp;Khemanat Ratworawong,&nbsp;Surasak Saokaew,&nbsp;Chaisiri Wanlapakorn","doi":"10.1002/cdt3.85","DOIUrl":"10.1002/cdt3.85","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64–0.98), bleeding (RR = 0.63, 95% CI = 0.49–0.82), and NACEs (RR = 0.69, 95% CI = 0.60–0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46–0.86) compared with standard DAPT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"9 4","pages":"299-308"},"PeriodicalIF":0.0,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44126978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nut consumption and urogenital and genital, gastrointestinal and women-related cancers: Assessment and review 坚果消费与泌尿生殖和生殖、胃肠道和女性相关癌症:评估和回顾
Q1 Medicine Pub Date : 2023-07-19 DOI: 10.1002/cdt3.87
Maryam Mohamadi, Periklis Dousdampanis, Zahra Ahmadi, Soheila Pourmasumi, Monavare Naderi, Nahid Zainodini, Alireza Nazari

The prevalence of cancer, especially in industrial countries, is a major problem for health and treatment systems. Cancer can affect the quality of life of all family members and has many negative effects on the community. Despite many advances in cancer treatment, this disease is still a major worldwide problem. There is strong evidence that dietary habits are effective in protecting against cancer and even helping in the disease treatment progress. Nuts with various biologically-active compounds, such as vitamins, phytosterols, isoflavones, flavonoids, and polyphenols have been reported to possess anticarcinogenic properties. Accordingly, this review provides an insight into the association between nut consumption and the prevention of some cancers. We considered the cancers related to the urogenital and genital tract, gastrointestinal tract, as well as women-related cancers. Both cell culture examinations and experimental animal studies alongside observational epidemiological studies demonstrated that regular consumption of a nut-enriched diet is able to reduce the risk of these cancers.

癌症的流行,特别是在工业国家,是卫生和治疗系统的一个主要问题。癌症会影响所有家庭成员的生活质量,并对社区产生许多负面影响。尽管癌症治疗取得了许多进展,但这种疾病仍然是世界范围内的一个主要问题。有强有力的证据表明,饮食习惯可以有效地预防癌症,甚至有助于疾病治疗的进展。据报道,含有多种生物活性化合物的坚果具有抗癌特性,如维生素、植物甾醇、异黄酮、类黄酮和多酚。因此,这篇综述深入了解了坚果消费与预防某些癌症之间的关系。我们考虑了与泌尿生殖道、胃肠道相关的癌症,以及与女性相关的癌症。细胞培养检查和实验动物研究以及观察性流行病学研究都表明,经常食用富含坚果的饮食能够降低患这些癌症的风险。
{"title":"Nut consumption and urogenital and genital, gastrointestinal and women-related cancers: Assessment and review","authors":"Maryam Mohamadi,&nbsp;Periklis Dousdampanis,&nbsp;Zahra Ahmadi,&nbsp;Soheila Pourmasumi,&nbsp;Monavare Naderi,&nbsp;Nahid Zainodini,&nbsp;Alireza Nazari","doi":"10.1002/cdt3.87","DOIUrl":"10.1002/cdt3.87","url":null,"abstract":"<p>The prevalence of cancer, especially in industrial countries, is a major problem for health and treatment systems. Cancer can affect the quality of life of all family members and has many negative effects on the community. Despite many advances in cancer treatment, this disease is still a major worldwide problem. There is strong evidence that dietary habits are effective in protecting against cancer and even helping in the disease treatment progress. Nuts with various biologically-active compounds, such as vitamins, phytosterols, isoflavones, flavonoids, and polyphenols have been reported to possess anticarcinogenic properties. Accordingly, this review provides an insight into the association between nut consumption and the prevention of some cancers. We considered the cancers related to the urogenital and genital tract, gastrointestinal tract, as well as women-related cancers. Both cell culture examinations and experimental animal studies alongside observational epidemiological studies demonstrated that regular consumption of a nut-enriched diet is able to reduce the risk of these cancers.</p>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"9 4","pages":"277-287"},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47968479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pure red cell aplasia and minimal residual disease conversion associated with immune reconstitution in a patient with high-risk multiple myeloma 高危多发性骨髓瘤患者的纯红细胞再生障碍和与免疫重建相关的最小残留疾病转化
Q1 Medicine Pub Date : 2023-07-16 DOI: 10.1002/cdt3.81
Xianghong Jin, Xianyong Jiang, Wei Wang, Shuangjiao Liu, Bing Han, Jianhua Han, Junling Zhuang

A second bone marrow aspiration and biopsy showed pure red cell aplasia in this case.

第二次骨髓抽吸术和活检显示该病例为纯红细胞再生障碍。
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引用次数: 0
The lack of association between different LDL-C levels and oxidized LDL in patients with type 2 diabetes 2型糖尿病患者不同LDL - C水平与氧化LDL之间缺乏相关性
Q1 Medicine Pub Date : 2023-07-06 DOI: 10.1002/cdt3.84
Soghra Rabizadeh, Seyed Arsalan Seyedi, Seyed Ali Nabipoorashrafi, Maryamossadat  Omidvar Siahkalmahalleh, Amirhossein Yadegar, Fatemeh Mohammadi, Armin Rajab, Alireza Esteghamati, Manouchehr Nakhjavani

Background

High concentrations of low-density lipoprotein cholesterol (LDL-C) have been a known risk factor for cardiovascular diseases. Also, the role of oxidized LDL (ox-LDL) in forming atherosclerosis plaque has been proven. However, it has not yet been proven that atherogenic LDL-C by-products like ox-LDL will decrease by keeping the LDL levels at the desired level. This study aimed to examine the relationship between LDL-C and ox-LDL in different LDL-C values in patients with type 2 diabetes (T2D).

Methods

In this cross-sectional study, 347 patients with T2D who received statins were enrolled. LDL-C values were defined into four groups as LDL-C < 55 mg/dL, 55 mg/dL ≤ to <70 mg/dL, 70 mg/dL ≤ to <100 mg/dL and LDL-C ≥ 100 mg/dL. Total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and ox-LDL were studied in the four defined groups.

Results

Ox-LDL levels were not different among the four groups (p = 0.30). In addition, LDL-C and ox-LDL levels had no significant correlation (r = 0.480, p = 0.376). Additionally, based on this study analysis, ox-LDL levels were significantly correlated with TG levels (r = 0.119, p < 0.05) and TG/HDL ratio (r = 0.390, p < 0.01).

Conclusions

It is concluded that ox-LDL levels were not associated with different LDL-C level categories from <55 mg/dL to >100 mg/dL in patients with T2D. However, the revealed association of ox-LDL with TG level and TG/HDL ratio may be considered in the clinic.

背景:高浓度低密度脂蛋白胆固醇(LDL-C)是心血管疾病的一个已知危险因素。此外,氧化型低密度脂蛋白(ox-LDL)在动脉粥样硬化斑块形成中的作用也已得到证实。然而,尚未证明引起动脉粥样硬化的LDL-C副产物(如ox-LDL)会通过将LDL水平保持在所需水平而降低。本研究旨在探讨2型糖尿病(T2D)患者不同LDL-C值下LDL-C和ox-LDL之间的关系。方法:在这项横断面研究中,347名接受他汀类药物治疗的T2D患者被纳入研究。LDL-C值分为四组,分别为LDL-C 结果:四组间Ox-LDL水平差异无统计学意义(p = 此外,LDL-C和ox-LDL水平无显著相关性(r = 0.480,p = 0.376)。此外,根据本研究分析,ox-LDL水平与TG水平显著相关(r = 0.119,p r = 0.390,p 结论:ox-LDL水平与100 mg/dL。然而,ox-LDL与TG水平和TG/HDL比率的相关性可能在临床上被考虑。
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引用次数: 0
Mechanism of RBBP8-mediated homologous recombination repair in gastric cancer synthetic lethal rbbp8介导的同源重组修复在胃癌合成致死中的作用机制
Q1 Medicine Pub Date : 2023-06-22 DOI: 10.1002/cdt3.75
Yang Yu, Shuxia Wang, Yanhua Yin, Guangsheng Wang

Background

It is of great clinical significance to further explore new strategies and potential combined therapeutic targets for gastric cancer. This study aimed to investigate the synthetic lethal effect of RBBP8 molecular intervention combined with a poly ADP ribose polymerase (PARP) inhibitor in non-BRCA mutant gastric cancer and clarify the mechanism by which RBBP8 regulates homologous recombination repair.

Methods

The role of RBBP8 in DNA damage repair was observed using bioinformatic analysis, western blot analysis, and immunofluorescence. The synthetic lethal effect was verified using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS)and flow cytometry apoptosis experiments.

Results

Among the patients with gastric cancer treated with chemotherapy, the prognosis of patients with high RBBP8 expression levels was worse (homologous recombination [HR] = 1.54, p = 0.028). RBBP8 knockdown induced DNA damage and had a synergistic effect with PARP inhibitor treatment on cell viability inhibition and cell apoptosis in AGS (generic code for human gastric adenocarcinoma cells) (t = 11.154, p < 0.001) and N87 (t = 6.362, p < 0.001) cells. RBBP8 knockdown inhibited RAD51 activation and DNA terminal excision in homologous recombination repair.

Conclusion

RBBP8 is involved in homologous recombination repair, and molecular intervention into RBBP8 could achieve a synthetic lethal effect with PARP inhibitor treatment in gastric cancer cells.

背景进一步探索胃癌的新策略和潜在的联合治疗靶点具有重要的临床意义。本研究旨在探讨RBBP8分子干预联合聚ADP核糖聚合酶(PARP)抑制剂对非brca突变型胃癌的合成致死作用,阐明RBBP8调控同源重组修复的机制。方法采用生物信息学分析、western blot分析和免疫荧光法观察RBBP8在DNA损伤修复中的作用。采用3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺苯基)- 2h -四氮唑、内盐(MTS)和流式细胞术细胞凋亡实验验证了合成致死效应。结果在接受化疗的胃癌患者中,RBBP8高表达患者预后较差(同源重组[HR] = 1.54, p = 0.028)。RBBP8敲低诱导DNA损伤,并与PARP抑制剂处理在AGS(人胃腺癌细胞通用代码)(t = 11.154, p < 0.001)和N87细胞(t = 6.362, p < 0.001)细胞活力抑制和细胞凋亡方面具有协同作用。RBBP8敲低抑制同源重组修复中RAD51的激活和DNA末端切除。结论RBBP8参与同源重组修复,分子干预RBBP8与PARP抑制剂治疗胃癌细胞可达到合成致死作用。
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引用次数: 0
Chronic complications risk among type 2 diabetes patients with a family history of diabetes 有糖尿病家族史的2型糖尿病患者的慢性并发症风险
Q1 Medicine Pub Date : 2023-06-22 DOI: 10.1002/cdt3.80
Dicky L. Tahapary, Syahidatul Wafa, Christian Tricaesario, Felix F. Widjaja, Jimmy Tandradynata, Rudy Kurniawan, William Djauhari, Afif H. Maruf, Muhammad Yamin, Sidartawan Soegondo

Family history of diabetes (FH+) has been associated with early metabolic alteration including insulin resistance, lipid metabolism, and ectopic fat accumulation even in healthy individuals.1-3 Furthermore, normoglycemic first-degree relatives of type 2 diabetes mellitus (T2DM) have been documented having increased carotid intima-media thickness and pro-inflammatory cytokines.4, 5 Taken together, individuals with FH+, who were otherwise healthy, have shown to possess susceptibility for diabetes mellitus (DM) chronic complication. Hence, this study aimed to investigate whether FH+ increased the risk of chronic complications in patients with overt T2DM.

This was a cross-sectional study which included adult patients with T2DM visiting a private hospital integrated diabetes center in South Tangerang (urban area outskirt of Jakarta), Indonesia from December 2020 to November 2021. Those without any documented blood test results were excluded. FH+ was defined as having first- and/or second-degree relatives with T2DM. Chronic complications investigated were atherosclerotic cardiovascular diseases (ASCVD) including coronary artery disease (CAD), stroke, and peripheral artery disease; microvascular complications including diabetic retinopathy, diabetic peripheral neuropathy, and diabetic kidney disease (DKD); diastolic dysfunction and heart failure (HF). Data were taken from hospital electronic medical records and were explored from clinical signs and symptoms, history of previously known chronic complications, laboratory and radiological examinations, and diagnosis made by the physicians. Additionally, if any, other tests were used for diagnosis such as treadmill stress test and coronary arteries calcium scoring for CAD; ankle-to-brachial index of ≤0.9 and limb vessels stenosis of ≥50% on doppler ultrasound for peripheral artery disease; non-mydriatic funduscopy for retinopathy; 10 g monofilament test and 128 Hz tuning fork test for neuropathy; presence of micro-/macroalbuminuria or proteinuria and glomerular filtration rate ≤60 mL/min for DKD; echocardiography for diastolic dysfunction and HF.

Results were presented in n (%), and median (interquartile range, IQR) depends on data type. Chi-squared test was used to compare nominal data, while Mann–Whitney was used to compare numerical data. Logistic regression analysis was used to determine FH+ association with chronic complications adjusted for age, sex, DM duration, alcohol and smoking history, systolic and diastolic blood pressure, body mass index, HbA1c, low-density lipoprotein, triglyceride, and estimated glomerular filtration rate, with no family history of diabetes (FH−) as the reference.

A total of 1011 T2DM patients were included, 24.8% of whom had family history of T2DM (FH+) (Table 1). There were higher proportions of dyslipidemia, smoking and alcohol history found in FH+, whereas FH− had older age, higher systolic blood

糖尿病家族史(FH+)与早期代谢改变有关,包括胰岛素抵抗、脂质代谢和异位脂肪积累,即使在健康个体中也是如此。1-3此外,血糖正常的2型糖尿病(T2DM)一级亲属有颈动脉内膜-中膜厚度和促炎细胞因子增加的记录。4,5综上所述,在其他方面健康的FH+个体显示出对糖尿病(DM)慢性并发症的易感性。因此,本研究旨在探讨FH+是否会增加显性T2DM患者慢性并发症的风险。这是一项横断面研究,包括2020年12月至2021年11月在印度尼西亚南坦格朗(雅加达市区郊区)一家私立医院综合糖尿病中心就诊的2型糖尿病成年患者。没有任何血液测试结果的人被排除在外。FH+被定义为有一级和/或二级亲属患有T2DM。慢性并发症包括动脉粥样硬化性心血管疾病(ASCVD),包括冠状动脉疾病(CAD)、中风和外周动脉疾病;微血管并发症,包括糖尿病视网膜病变、糖尿病周围神经病变和糖尿病肾病(DKD);舒张功能障碍和心力衰竭(HF)。数据取自医院电子病历,并从临床体征和症状、以前已知的慢性并发症史、实验室和放射检查以及医生的诊断中进行了探索。此外,如果有,其他测试用于诊断,如跑步机压力测试和冠心病冠状动脉钙评分;外周动脉病变多普勒超声显示踝臂指数≤0.9,肢体血管狭窄≥50%;视网膜病变的非晶状体眼底镜检查;10 g单丝试验和128 Hz音叉试验;存在微量/大量蛋白尿或蛋白尿,肾小球滤过率≤60ml /min;超声心动图检查舒张功能不全和心衰。结果以n(%)表示,中位数(四分位数范围,IQR)取决于数据类型。标称资料比较采用卡方检验,数值资料比较采用Mann-Whitney检验。在没有糖尿病家族史(FH−)作为参考的情况下,通过年龄、性别、糖尿病病程、饮酒和吸烟史、收缩压和舒张压、体重指数、HbA1c、低密度脂蛋白、甘油三酯和肾小球滤过率等因素,采用Logistic回归分析确定FH+与慢性并发症的相关性。共纳入1011例T2DM患者,其中24.8%有T2DM (FH+)家族史(表1)。FH+患者有较高比例的血脂异常、吸烟和饮酒史,而FH−患者年龄较大、收缩压和甘油三酯水平较高、eGFR较低(表1)。总体而言,FH+患者并发症比例较高,但统计学意义主要在于微血管并发症,而非ASCVD(图1)。FH+与舒张功能障碍(校正比值比[aOR]: 4.16[2.58-6.69])、视网膜病变(aOR: 3.76[1.94-7.28])、周围神经病变(aOR: 3.20[2.02-5.05])、复合微血管并发症(aOR: 1.93[1.26-2.96])、复合大血管和微血管并发症(aOR: 1.83[1.09-3.08])仍有显著相关性(图2)。在本研究中,我们发现FH+组中血脂异常和有吸烟、饮酒史的比例高于FH -组。然而,有糖尿病家族史与发生慢性并发症的风险增加独立相关,特别是舒张功能障碍、视网膜病变和周围神经病变。尽管FH+和FH -受试者的基线特征有统计学上的差异,但没有临床意义。事实上,我们注意到,在我们的研究中,与FH -组相比,FH+患者倾向于饮酒和吸烟。这可能是FH+患者血脂异常患病率较高的原因,此外,已知有糖尿病家族史的患者血脂异常的风险也会增加。1,2fh +与微血管并发症(视网膜病变和神经病变)独立相关,但与任何ASCVD无关。与先前的研究一致,FH+与视网膜病变和神经病变相关,但与DKD7-10无关;冠心病或中风家族史比糖尿病家族史更能预测ASCVD。10-12FH+与低龄糖尿病相关,低龄糖尿病的特点是血糖控制不良和更多的进行性并发症。
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Chronic Diseases and Translational Medicine
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