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Effects of long-term blood pressure variability on renal function in community population 社区人群长期血压变化对肾功能的影响
Q1 Medicine Pub Date : 2024-05-23 DOI: 10.1002/cdt3.127
Zhao Feng, Zhiquan Jing, Zeya Li, Gang Wang, Shanshan Wu,  Dan Li, Jing Hao, Chunlei Yang, Jiashu Song, Xianzhong Gu, Rongchong Huang

High blood pressure is a significant contributor to premature mortality, resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years, hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability (BPV), categorized into very short-term, short-term, and long-term BPV based on the time period of occurrence.2, 3 Long-term BPV has emerged as clinically significant, with studies demonstrating its superiority in predicting long-term cardiovascular events, stroke, and mortality compared to short-term variability. Given its association with pre-renal function decline, reducing blood pressure fluctuations is imperative.

Chronic kidney disease (CKD) poses a global public health challenge, with its incidence rising alongside aging populations and increasing rates of conditions like diabetes and hypertension. Hypertension and kidney disease are closely intertwined, with hypertension exacerbating renal damage. At present, the management of hypertension mainly focuses on average blood pressure, but the average blood level does not accurately reflect the long-term control status of blood pressure. Notably, some patients with ostensibly controlled average blood pressure still experience renal function deterioration within 5–10 years, potentially due to blood pressure fluctuations. Emerging evidence suggests a link between cardiovascular events, renal injury, and BPV, independent of average blood pressure.4, 5 However, the precise relationship between BPV and renal function remains elusive. This study aimed to explore the association between fluctuating blood pressure and rapid renal function decline in a prospective community health checkup-based cohort.

A total of 7153 patients aged ≥18 years who received at least twice regular physical examinations at the Community Health Service Centre in Beijing, between 2015 and 2021, were recruited consecutively in this study. Exclusion criteria included CKD stage 4–5, acute stroke, myocardial infarction, and heart failure (<3 months). Finally, 7130 patients were enrolled in the analysis (Figure S1).

Sociodemographic information, comorbidities, and lifestyle habits were obtained through questionnaires. Blood pressure was measured twice during each visit, and BPV indices were calculated based on measurements across all visits. Additionally, blood samples were collected after an 8-h fast for biochemical analyses. We calculated several indicators as measures of BPV based on data from all visits, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average successive variability (ASV). The measures have been used in previous studies.6, 7

Baseline data for this study were derived from the results of the initial annual health checkup, while endpoint data we

在对年龄、性别、平均血压、体重指数、腰围、吸烟和饮酒等混杂因素进行调整后,多变量逻辑回归结果显示,SBP-ASV 与 eGFR 下降之间存在显著关联(几率比 [OR]:1.01,95% 置信区间 [CI]:1.00-1.02,P = 0.005)。同样,DBP-ASV 也与 eGFR 下降相关(OR:1.02,95% CI:1.01-1.03,p = 0.001)(表 1)。在 6991 名肾功能基线正常的患者中,共有 199 人在 5 年随访期间达到次要终点,中位随访时间为 48 个月。调整混杂因素后,Cox 比例危险模型分析显示,SBP 变异指数(SBP-SD、SBP-VIM 和 SBP-ASV)与新发 CKD 之间存在显著关联。同样,DBP 变异指数(DBP-SD、DBP-CV、DBP-VIM 和 DBP-ASV)也与新发 CKD 相关(表 2)。我们的研究表明,无论是 SBP 还是 DBP,BPV 在预测未来 eGFR 下降和 CKD 发病方面都具有预测价值。因此,必须优先监测升高的 BPV。2010 年,Rothwell 等人证实随访收缩压变异性(SBPV)可独立预测卒中风险,突出了 BPV 与平均血压对高血压患者预后的重要性。9, 10 此外,在美国进行的一项大型队列研究显示,随着人群中 SBPV 水平的升高,全因死亡率、冠心病、中风和终末期肾病的发病率明显上升。BPV 影响肾功能的机制可能涉及微血管阻力,从而导致肾小球基底膜增厚、肾动脉透明变性和单核细胞渗出等病理变化,最终导致肾脏损伤。我们的研究发现,血压升高与 eGFR 下降之间存在密切联系,这与日本的一项研究结果一致。9、12、13 对 ASPREE 试验、ONTARGET 试验和 TRANSCEND 试验进行的事后分析得出了否定的结果,部分原因是研究人群的构成。ASPREE 试验的研究对象平均年龄超过 70 岁,这表明高龄可能会减轻 BPV 的效果。此外,ONTARGET 和 TRANSCEND 试验排除了血压水平≥160/100 mmHg 的患者,导致 BPV 相对较低。我们的研究基于现实世界中的中老年人群,为了解就诊 SBP 变化对肾功能管理的影响提供了宝贵的见解,即使在血压正常的患者中也是如此14。首先,由于现有检查信息的局限性,没有对抗高血压药物的使用情况进行分析。此外,医疗服务中心的就诊人群偏向女性,这可能会影响研究中观察到的总体血压值。最后,本研究的随访时间为31.8个月,进一步的纵向随访可获得更多关于血压升高对肾脏损害的长期影响的信息。总之,长期血压升高与未来的肾脏损害有关,应进一步关注每次就诊时SBP的变化。黄荣冲、赵峰、景志权、李泽亚、王刚、吴姗姗、李丹、郝静、杨春雷、宋家树、顾献忠对数据采集做出了贡献。黄荣冲、赵峰、景志权、李泽亚和吴姗姗参与了数据分析。黄荣冲、赵峰、景志权和李泽亚参与了稿件的准备、编辑和审阅。作者声明无利益冲突。该研究方案已获得首都医科大学附属北京友谊医院伦理委员会批准(批准号:京卫医字[2007]第2号)。
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引用次数: 0
Association between plasma growth differentiation factor 15 levels and pre-eclampsia in China 血浆生长分化因子 15 水平与中国先兆子痫之间的关系
Q1 Medicine Pub Date : 2024-05-12 DOI: 10.1002/cdt3.126
Shuhong Xu, Yicheng Lu, Mengxin Yao, Zhuoqiao Yang, Yan Chen, Yaling Ding, Yue Xiao, Fei Liang, Jiani Qian, Jinchun Ma, Songliang Liu, Shilan Yan, Jieyun Yin, Qiuping Ma

Background

Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).

Method

The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).

Results

MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI = 2.23–10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity.

Conclusions

These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

生长分化因子-15(GDF-15)是一种应激反应蛋白,与心血管疾病(CVD)有关。这项研究旨在调查 GDF-15 与先兆子痫(PE)之间的关系。研究涉及 299 名孕妇,其中 236 人正常怀孕,63 人患有先兆子痫。研究使用酶联免疫吸附试剂盒测定了母体血清中的GDF-15水平,然后将其转化为中位数的倍数(MOM),以避免采血时孕周的影响。经年龄、孕前体重指数、孕酮和胎次调整后,PE 参与者的 GDF-15 MOM 高于对照组(1.588 vs. 1.000,p 1),PE 风险增加 4.74 倍(95% CI = 2.23-10.08,p < 0.001)。GDF-15可作为诊断PE的生物标志物。
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引用次数: 0
Stem cell secretome restore the adipo-osteo differentiation imbalance in diabetic dental pulp-derived mesenchymal stem cells 干细胞分泌物可恢复糖尿病牙髓间充质干细胞的脂肪-骨骼分化失衡
Q1 Medicine Pub Date : 2024-05-06 DOI: 10.1002/cdt3.125
Avinash Sanap, Kalpana Joshi, Supriya Kheur, Ramesh Bhonde

Background

Mesenchymal stem cells (MSCs) from type 2 diabetes mellitus (T2DM) individuals exhibit increased adipogenesis and decreased osteogenesis. We investigated the potential of adipose tissue-derived MSCs (ADMSCs) secretome obtained from healthy individuals in restoring the tumor necrosis factor-α (TNF-α) mediated imbalance in the adipo/osteogenic differentiation in the dental pulp-derived MSCs obtained from T2DM individuals (dDPMSCs).

Methods

dDPMSCs were differentiated into adipocytes and osteocytes using a standard cocktail in the presence of (a) induction cocktail, (b) induction cocktail + TNF-α, and (c) induction cocktail+ TNF-α + ADMSCs-secretome (50%) for 15 and 21 days resp. Differentiated adipocytes and osteocytes were stained by oil red O and alizarin red and analyzed by using ImageJ software. Molecular expression of the key genes involved was analyzed by using reverse-transcription polymerase chain reaction (RT-PCR).

Results

Treatment of TNF-α augmented the adipogenesis (9571 ± 765 vs. 19,815 ± 1585 pixel, p < 0.01) and decreased the osteogenesis (15,603 ± 1248 vs. 11,894 ± 951 pixel, p < 0.05) of dDPMSCs as evidenced by the oil red O and alizarin red staining respectively. Interestingly, dDPMSCs differentiated along with TNF-α and 50% ADMSCs secretome exhibited enhanced osteogenesis (11,894 ± 951 vs. 41,808 ± 3344 pixel, p < 0.01) and decreased adipogenesis (19,815 ± 1585 vs. 4480 ± 358 pixel, p < 0.01). Additionally, dDPMSCs differentiated along with ADMSCs secretome exhibited decreased expression of PPARg (p < 0.01), C/EBPa (p < 0.05), and FAS (p < 0.01) whereas mRNA expression of Runx2 (p < 0.05), Osterix (p < 0.01), and OCN (p < 0.05) was upregulated as revealed by the RT-PCR analysis.

Conclusion

ADMSCs secretome from healthy individuals restore the TNF-α influenced differentiation fate of dDPMSCs and therefore can be explored for T2DM clinical management in the future.

来自2型糖尿病(T2DM)患者的间充质干细胞(MSCs)表现出脂肪生成增加和骨生成减少。我们研究了从健康人体内获得的脂肪组织间充质干细胞(ADMSCs)分泌组在恢复T2DM患者牙髓间充质干细胞(dDPMSCs)中肿瘤坏死因子-α(TNF-α)介导的脂肪/成骨分化失衡方面的潜力。在(a)诱导鸡尾酒、(b)诱导鸡尾酒+TNF-α和(c)诱导鸡尾酒+TNF-α+ADMSCs-分泌物(50%)存在下,使用标准鸡尾酒将dDPMSCs分化成脂肪细胞和骨细胞,分别持续15天和21天。油红 O 和茜素红染色分别显示,TNF-α 可促进 dDPMSCs 的脂肪生成(9571 ± 765 vs. 19815 ± 1585 像素,p < 0.01)和骨生成(15603 ± 1248 vs. 11894 ± 951 像素,p < 0.05)。有趣的是,与 TNF-α 和 50% ADMSCs 分泌物一起分化的 dDPMSCs 表现出骨生成增强(11,894 ± 951 vs. 41,808 ± 3344 像素,p < 0.01)和脂肪生成减少(19,815 ± 1585 vs. 4480 ± 358 像素,p < 0.01)。此外,与 ADMSCs 分泌物一起分化的 dDPMSCs 表现出 PPARg(p < 0.01)、C/EBPa(p < 0.05)和 FAS(p < 0.01)的表达减少,而 Runx2(p < 0.05)、Osterix(p < 0.RT-PCR分析表明,健康人的ADMSCs分泌组恢复了TNF-α对dDPMSCs分化命运的影响,因此可在未来的T2DM临床治疗中进行探索。
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引用次数: 0
Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants 通过 GWAS 和 RNA 修饰相关变异的综合分析,揭示主动脉细胞中的血压相关基因
Q1 Medicine Pub Date : 2024-04-30 DOI: 10.1002/cdt3.124
Huan Zhang, Yuxi Chen, Peng Xu, Dan Liu, Naqiong Wu, Laiyuan Wang, Xingbo Mo

Background

Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).

Methods

Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.

Results

A total of 355 RNAm-SNPs related to m6A, m1A, m5C, m7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m6A-SNPs, highlighting the potential functional relevance of m6A in physiological processes influencing BP. Notably, m6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells.

Conclusion

The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

背景 全基因组关联研究(GWAS)发现了一千多个血压(BP)基因位点。这些位点中的功能基因具有细胞类型特异性。本研究旨在通过利用 RNA 修饰相关单核苷酸多态性(RNAm-SNPs),阐明与主动脉血压相关的潜在功能基因。 方法 我们利用英国生物库和国际血压联盟(International Consortium of Blood Pressure consortium)的 757,601 人的大规模基因数据,确定了 RNAm-SNPs 与血压之间的关联。我们还研究了 RNAm-SNPs、基因表达和血压之间的关联。 结果 共有355个与m6A、m1A、m5C、m7G和A-to-I修饰相关的RNAm-SNPs与血压有关。相关基因富集于胰腺分泌途径和肾素分泌途径。血压 GWAS 信号与 m6A-SNPs 显著富集,突出了 m6A 在影响血压的生理过程中的潜在功能相关性。值得注意的是,在 CYP11B1、PDE3B、HDAC7、ACE、SLC4A7、PDE1A、FRK、MTHFR、NPPA、CACNA1D 和 HDAC9 中发现了 m6A-SNPs。在 FTO 高表达和 METTL14 敲除的血管平滑肌细胞中,检测到了 BP 基因的差异甲基化和差异表达。RNAm-SNPs与升主动脉和降主动脉直径相关,主动脉夹层(AD)病例和对照组之间的基因甲基化存在差异。在 scRNA-seq 研究中,我们发现 ARID5A、HLA-DPB1、HLA-DRA、IRF1、LINC01091、MCL1、MLF1、MLXIPL、NAA16、NADK、RERG、SRM 和 USP53 是主动脉细胞中 AD 的差异表达基因。 结论 本研究发现了血压基因座中的 RNAm-SNPs,并阐明了 RNAm-SNPs、基因表达和血压之间的关联。在主动脉细胞中鉴定出的血压相关基因与 AD 相关。
{"title":"Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants","authors":"Huan Zhang,&nbsp;Yuxi Chen,&nbsp;Peng Xu,&nbsp;Dan Liu,&nbsp;Naqiong Wu,&nbsp;Laiyuan Wang,&nbsp;Xingbo Mo","doi":"10.1002/cdt3.124","DOIUrl":"https://doi.org/10.1002/cdt3.124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 355 RNAm-SNPs related to m<sup>6</sup>A, m<sup>1</sup>A, m<sup>5</sup>C, m<sup>7</sup>G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m<sup>6</sup>A-SNPs, highlighting the potential functional relevance of m<sup>6</sup>A in physiological processes influencing BP. Notably, m<sup>6</sup>A-SNPs in <i>CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D</i>, and <i>HDAC9</i> were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified <i>ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM</i>, and <i>USP53</i> as differential expression genes for AD in aortic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":32096,"journal":{"name":"Chronic Diseases and Translational Medicine","volume":"10 2","pages":"118-129"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cdt3.124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141308853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling 钙传感受体(CaSR)介导的信号传导的分子调控
Q1 Medicine Pub Date : 2024-04-29 DOI: 10.1002/cdt3.123
Li Tian, Corey Andrews, Qiuyun Yan, Jenny J. Yang

Calcium-sensing receptor (CaSR), a family C G-protein-coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca2+, Mg2+, amino acids (e.g., L-Trp and L-Phe), small peptides, anions (e.g., HCO3 and PO43−), and pH. CaSR-mediated intracellular Ca2+ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca2+-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

钙感受体(CaSR)是一种 C 族 G 蛋白偶联受体,通过感知细胞外 Ca2+、Mg2+、氨基酸(如 L-Trp 和 L-Phe)、小肽、阴离子(如 HCO3- 和 PO43-)和 pH 的微小浓度变化,在调节钙稳态方面发挥着至关重要的作用。CaSR 介导的细胞内 Ca2+ 信号调节多种细胞过程,包括基因转录、细胞增殖、分化、细胞凋亡、肌肉收缩和神经元传导。CaSR 基因突变导致的功能障碍可导致常染色体显性低钙血症、家族性低钙尿症和新生儿严重甲状旁腺功能亢进症等疾病。CaSR 还影响骨质疏松症等降钙性疾病以及癌症、阿尔茨海默病和肺动脉高压等非降钙性疾病。本研究首先回顾了在生化和结构测定 CaSR 框架及其与天然配体以及外源正异位调节剂和负异位调节剂相互作用位点方面的最新进展。首个 CaSR 蛋白-蛋白相互作用组网络的建立揭示了 94 个参与内质网蛋白加工、转运、细胞表面表达、内吞、降解和信号通路的新角色。这些蛋白在 Ca2+ 依赖性细胞生理过程和 CaSR 依赖性细胞信号传导中的作用,为人们深入了解 CaSR 基因突变导致的疾病和 CaSR 蛋白相互作用体导致的 CaSR 活性失调的分子基础提供了新的视角,并有助于设计针对 CaSR 和其他 C 家族 G 蛋白偶联受体的治疗药物。
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引用次数: 0
Predictive value of total cholesterol to high-density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China 西北地区成年男性和女性总胆固醇与高密度脂蛋白胆固醇比值对慢性肾脏病的预测价值
Q1 Medicine Pub Date : 2024-04-17 DOI: 10.1002/cdt3.122
Yanli Liu, Kang Lyu, Shaodong Liu, Jinlong You, Xue Wang, Minzhen Wang, Desheng Zhang, Yana Bai, Chun Yin, Min Jiang, Shan Zheng

Background

Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females.

Methods

Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve.

Results

During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05–1.31), 0.84 (0.71–0.99), and 1.15 (1.06–1.25) for males, 0.94 (0.78–1.13), 0.58 (0.35–0.95), and 1.19 (1.01–1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose–response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males.

Conclusions

The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.

研究发现,总胆固醇与高密度脂蛋白胆固醇(TC/HDL-C)的比率与慢性肾脏病(CKD)的发病有关。但是,很少有人讨论不同性别之间的关系。本研究旨在探讨这一关系,并评估其对男性和女性的预测能力。基于中国西北地区的前瞻性队列平台,研究人员收集了 32,351 名未患 CKD 的基线参与者,并对其进行了约 5 年的随访。通过Cox比例危险模型和限制性三次样条回归分析,研究了成年女性和男性TC、HDL-C、TC/HDL-C与CKD之间的关系。在平均 2.2 年的随访期间,484 名男性和 164 名女性出现了 CKD。经相关混杂因素调整后,TC、HDL-C 和 TC/HDL-C 每增加一个标准差,CKD 的危险比(HRs)和 95% 置信区间(95% CIs)分别为 1.男性分别为 1.17(1.05-1.31)、0.84(0.71-0.99)和 1.15(1.06-1.25),女性分别为 0.94(0.78-1.13)、0.58(0.35-0.95)和 1.19(1.01-1.40)。结果还显示,TC、HDL-C 和 TC/HDL-C 与 CKD 呈线性剂量反应关系。与 TC 和 HDL-C 相比,TC/HDL-C 的曲线下面积(AUC)最大,且女性的 AUC 大于男性。TC/HDL-C 与成年男性和女性的 CKD 显著相关,在预测 CKD 方面比 TC 和 HDL-C 具有更好的临床价值,尤其是在女性中。
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引用次数: 0
COX-2 in lung cancer: Mechanisms, development, and targeted therapies 肺癌中的 COX-2:机制、发展和靶向疗法
Q1 Medicine Pub Date : 2024-03-12 DOI: 10.1002/cdt3.120
Xueqi Liu, Junli Zhang, Wenwu Sun, Jianping Cao, Zhuang Ma

Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.

肺癌(LC)是全球癌症相关死亡的主要原因,其中非小细胞肺癌(NSCLC)占所有病例的 85%。COX-2 是一种在压力条件下显著诱导的酶,催化游离花生四烯酸转化为前列腺素。它在各种肿瘤中的表达量都很高,与肺癌的进展密切相关。COX-2 通过促进前列腺素 E2 的合成,促进肿瘤细胞的发生和发展,在癌症发病机制中起着关键的驱动作用。此外,COX-2 还可作为早期 NSCLC 的预测标志物,指导对 COX-2 早期过表达患者的靶向治疗。此外,将 COX-2 抑制剂与多种治疗方法结合使用可提高肿瘤疗效,减少对健康组织的不良影响,并提高患者治疗后的总体生存率。总之,以 COX-2 为靶点的联合疗法为 NSCLC 治疗提供了一种前景广阔的新策略,为改善预后和有效治疗肿瘤提供了途径。本综述为开发新的治疗策略以改善 NSCLC 的预后提供了新的见解和思路。
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引用次数: 0
Guide for Authors 作者指南
Q1 Medicine Pub Date : 2024-03-05 DOI: 10.1002/cdt3.121
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引用次数: 0
Cardiovascular disease mortality and air pollution in countries with different socioeconomic status 不同社会经济地位国家的心血管疾病死亡率与空气污染
Q1 Medicine Pub Date : 2024-02-07 DOI: 10.1002/cdt3.116
Nikolai Khaltaev, Svetlana Axelrod

Background

Cardiovascular diseases (CVDs) account for 17.9 million deaths annually. Behavioral risk factors increase the risk of dying from CVD. Air pollution is not included in this risk calculation since the appreciation of air pollution as a modifiable risk factor is still limited. The purpose of this study was to analyze CVD mortality attributed to air pollution in all World Health Organization WHO member states and demonstrate the association of CVD mortality with air pollution depending on countries' income level.

Methods

The CVD death rate was calculated by dividing the number of deaths by the total population. The proportion of the population with primary reliance on clean fuels and technologies for cooking was calculated as an indicator of household air pollution. The annual mean concentration of fine particulate matter ≤2.5 µg/m3 and ≤10.0 µg/m3 to which the population is exposed was used as an indicator of ambient air pollution.

Results

There is a gradual increase in CVD mortality attributed to air pollution from high-income countries (HICs) to low-income countries (LICs). Household air pollution is the major cause of CVD mortality in LICs. Ischemic heart disease mortality attributed to ambient air pollution in all countries is higher than stroke mortality attributed to ambient air pollution. In LIC, mortality from stroke is attributed to household air pollution of 39.27 ± 14.47, which is more than twice the stroke mortality attributed to ambient air pollution at 18.60 ± 5.64, t = 7.17, p < 0.01.

Conclusion

Air pollution control should be an essential component of the CVD preventive strategy, along with lifestyle modifications and effective disease management.

心血管疾病(CVD)每年造成 1790 万人死亡。行为风险因素会增加死于心血管疾病的风险。由于对空气污染作为可改变风险因素的认识仍然有限,因此空气污染未被纳入风险计算。本研究的目的是分析世界卫生组织所有成员国因空气污染导致的心血管疾病死亡率,并根据各国的收入水平证明心血管疾病死亡率与空气污染的关系。计算主要依靠清洁燃料和技术做饭的人口比例,作为家庭空气污染的指标。人口所接触的细颗粒物年均浓度≤2.5 µg/m3 和≤10.0 µg/m3 被用作环境空气污染指标。家庭空气污染是导致低收入国家心血管疾病死亡的主要原因。在所有国家,环境空气污染导致的缺血性心脏病死亡率高于环境空气污染导致的中风死亡率。在低收入国家,家庭空气污染导致的中风死亡率为 39.27 ± 14.47,是环境空气污染导致的中风死亡率(18.60 ± 5.64)的两倍多,t = 7.17,p < 0.01。
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引用次数: 0
Governance of noncommunicable diseases in Afghanistan 阿富汗非传染性疾病的治理
Q1 Medicine Pub Date : 2024-02-03 DOI: 10.1002/cdt3.118
Narges Neyazi, Ali M. Mosadeghrad, Maryam Tajvar, Najibullah Safi

Background

Noncommunicable diseases (NCDs) are the main reasons of mortality worldwide. One of every two person is dying due to NCDs in Afghanistan. International policy actors, mainly the World Health Organization (WHO), published several reports and declarations on controlling and preventing NCDs. This study aimed to provide a situation for governance of NCDs in Afghanistan and proper solutions for identified challenges.

Methods

We conducted qualitative research utilizing interpretive phenomenology. A self-developed questionnaire was developed to conduct the semi-structured interviews with 39 experts from Afghanistan. The results were analyzed using a deductive framework analysis. Six building block framework of health system developed by the WHO was used as predefined framework for this study.

Results

The governance building block of health system consists of five subthemes including policy making, planning, organizing, stewardship, and control. We identified main strengths, weaknesses, opportunities, and challenges for these subthemes. The experts also provided key recommendations to address the challenges.

Conclusions

Management of NCDs is a neglected part of the health system in Afghanistan. Strengthening evidence-based policy making with technical and indigenous planning, establishing responsive units with adequate financial and human resources within different ministries to address “health in all policies” concept, passing and implementing national laws and regulations to support national strategies for prevention and control of NCDs, and establishing decentralized monitoring systems to control the implementation of these strategies are the main recommendations of this study. Local government and international policy actors should invest and support the development of a multisectoral coordination system at national level for Afghanistan.

非传染性疾病(NCDs)是造成全球死亡的主要原因。在阿富汗,每两个人中就有一人死于非传染性疾病。国际政策参与者,主要是世界卫生组织(世卫组织),发表了几份关于控制和预防非传染性疾病的报告和宣言。本研究旨在为阿富汗的非传染性疾病治理提供一个局面,并为已确定的挑战提供适当的解决方案。我们利用解释现象学进行了定性研究。我们编制了一份自行开发的调查问卷,对来自阿富汗的 39 名专家进行了半结构化访谈。我们采用演绎框架分析法对结果进行了分析。世界卫生组织制定的卫生系统六大构件框架被用作本研究的预定义框架。卫生系统的治理构件由五个子主题组成,包括政策制定、规划、组织、管理和控制。我们确定了这些子主题的主要优势、劣势、机遇和挑战。非传染性疾病的管理是阿富汗卫生系统中被忽视的一部分。本研究的主要建议包括:通过技术和本土规划加强循证决策;在不同部委内建立拥有充足财力和人力资源的响应单位,以应对 "将健康纳入所有政策 "的概念;通过并实施国家法律法规,以支持预防和控制非传染性疾病的国家战略;以及建立分散的监测系统,以控制这些战略的实施。地方政府和国际政策参与者应投资并支持阿富汗在国家一级建立多部门协调系统。
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引用次数: 0
期刊
Chronic Diseases and Translational Medicine
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