关键词： 非奈利酮   糖尿病肾病   安全性   有效性   Meta分析  

摘要： 背景非甾体类盐皮质激素拮抗剂非奈利酮是用于保护糖尿病肾病患者肾脏的新药,与血管紧张素转换酶抑制剂和钠-葡萄糖共转运蛋白2抑制剂均为糖尿病肾病患者的肾脏保护药物。近期,两项针对慢性肾病患者型荟萃分析,关于非奈利酮对估算肾小球滤过率下降的影响,得出了截然相反的结论。鉴于此,本研究专门聚焦于2型糖尿病患者,旨在深入探究非奈利酮的有效性和安全性。目的系统评价非奈利酮在2型糖尿病肾病患者中的有效性和安全性。方法计算机检索Cochrane Library、Web of Science、Embase和PubMed数据库,检索时间为建库至2024年4月。按照纳入与排除标准筛选文献、提取数据,采用Revman 5.3进行Meta分析,对应用非奈利酮治疗的2型糖尿病患者的尿白蛋白/肌酐比率、估算肾小球滤过率等指标进行比较。结果最终纳入7篇文献,共包括15528例患者。结果显示,干预组(使用非奈利酮)患者尿白蛋白/肌酐比率(SMD=-0.46,95%CI=-0.48~-0.39,P<0.05)、估算肾小球滤过率(SMD=-0.15,95%CI=-0.19~-0.10,P<0.05)、肾脏复合终点(OR=0.83,95%CI=0.75~0.92,P<0.05)、全因死亡率(OR=0.88,95%CI=0.78~0.99,P<0.05)和终末期肾病(OR=0.80,95%CI=0.64~0.99,P<0.05)与对照组比较,差异均有统计学意义。与对照组相比,干预组组高钾血症的风险显著增加(OR=2.13,95%CI=1.89~2.39,P<0.05)。结论非奈利酮能显著改善2型糖尿病肾病患者肾脏复合终点事件,降低尿白蛋白/肌酐比率并减缓估算肾小球滤过率下降;治疗时需注意高钾血症的风险。

关键词： 糖尿病   自我护理   糖尿病自我护理指数量表   信度   效度   慢性病自我护理中层理论  

摘要： 背景糖尿病难以治愈且患病过程长,自我护理水平对糖尿病患者的疾病转归和健康结局至关重要,迫切需要理论指导下内容全面的糖尿病自我护理水平评估工具,以便及时掌握患者的自我护理情况,对应开展精准化护理。目的本研究旨在对糖尿病自我护理指数量表(SCODI)进行汉化,并检验中文版SCODI的信效度,为中国糖尿病患者提供自我护理的科学评估工具。方法采用Brislin翻译模式将原版SCODI翻译成中文,并进行文化调试。采用连续抽样法,选取2022年12月—2023年6月南京医科大学第一附属医院和附属逸夫医院诊治的261例糖尿病患者进行调查。使用研究者自行编制的一般资料调查表和汉化修订之后的中文版SCODI进行资料收集。采用探索性因子分析评估中文版SCODI的结构效度。采用Cronbach'sα系数、折半信度和组合信度描述量表的信度。本研究以生理指标糖化血红蛋白作为效标检验中文版SCODI的效标关联效度,采用Spearman秩相关分析探讨中文版SCODI得分与糖化血红蛋白水平的相关性。结果中文版SCODI包含4个分量表,共40个条目:自我护理维持得分为(75.94±13.15)分,自我护理监测得分为(70.65±18.71)分,自我护理管理得分为(69.16±18.24)分,自我护理信心得分为(85.41±13.63)分。自我护理维持分量表提取出4个因子(并发症筛查、运动锻炼、卫生保健、饮食服药),自我护理监测分量表提取出2个因子(身体监测、症状识别),自我护理管理分量表提取出2个因子(自主管理、咨询管理),自我护理自信分量表提取出2个因子(监测与管理信心、健康维持信心)。中文版SCODI总量表的Cronbach'sα系数为0.915,折半信度为0.836,组合信度为0.912,4个分量表的Cronbach'sα系数为0.709~0.908。以生理指标糖化血红蛋白作为效标,各量表得分与糖化血红蛋白水平呈负相关(r_(s)=-0.160、-0.300、-0.177、-0.192,P<0.001)。结论基于慢性病自我护理中层理论开发的中文版SCODI具有良好的信度和效度,可用于评估中国糖尿病患者的自我护理水平。

关键词： 糖尿病   慢性疾病   基层医疗   慢性病防控  

摘要： 随着我国人口老龄化进程加快,糖尿病、心血管疾病及慢性呼吸系统疾病等慢性病发生率逐年增高。因此,必须强化基层医疗机构对老年人慢性病的预防与治疗,引进专业的社会服务力量,建立完善、高效的基层慢性病防控体系,为老年人的健康提供有力保障,实现慢性病的早发现、早干预、早治疗。加强基层卫生服务体系建设提升基层医疗服务能力。加大对基层医疗卫生单位的资金投入,保证医疗设备的更新换代和药品的充足供应,使基层医疗设施的硬件水平得到提高,为慢性疾病的预防和治疗奠定良好基础。在此过程中,必须强化人力资源的培养。通过开展经常性的专业培训,引进高层次专业技术人才。

关键词： 针刺   神经干细胞   脊髓损伤   继发性损伤   神经再生   炎症反应   氧化应激   神经保护   基质细胞衍生因子1α(SDF-1α)/CXC趋化因子受体4(CXCR4)轴   协同机制  

摘要： 背景:脊髓损伤是由创伤性或非创伤性事件引起的一种神经系统疾病,常导致损伤节段以下严重功能障碍。近年来,神经干细胞移植被认为在调控脊髓损伤后的炎症反应、抑制胶质瘢痕的过度增生以及促进神经再生方面具有显著的治疗潜力。目的:综述并讨论针刺及神经干细胞移植疗法在抑制脊髓损伤诱导的继发性损伤中的潜在作用机制,深入探讨其治疗脊髓损伤的科学依据。方法:以“脊髓损伤,针刺,神经干细胞,SDF-1α/CXCR4轴”为中文检索词,以“Spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis”为英文检索词,分别检索PubMed、Elsevier、万方及中国知网数据库,最终纳入96篇文献,汇总分析了针刺联合神经干细胞治疗脊髓损伤的相关研究成果,总结了这一联合疗法在治疗脊髓损伤后继发性损伤中的相关机制。结果与结论:①基质细胞衍生因子1α(stromal-derived factor 1α,SDF-1α)/CXC趋化因子受体4(chemokine receptor 4,CXCR4)轴在神经干细胞移植治疗脊髓损伤中扮演着至关重要的角色,该信号传导机制不仅影响神经干细胞的迁移、增殖和分化,更是决定干细胞归巢至损伤部位效率的关键因素。因此,针对该轴线的调控,对于提升脊髓损伤的治疗效果具有重要意义。②针刺作为一种传统中医疗法,在脊髓损伤的继发性损伤调控中展现出独特的优势,它能够通过调节炎症反应、抑制细胞凋亡、改善微循环、减少神经胶质瘢痕形成以及对抗氧化应激等多种途径,有效减轻脊髓损伤后的继发性损伤。③针刺还能够影响SDF-1α/CXCR4轴的表达与功能,从而增强神经干细胞的归巢和存活能力,促进神经再生和功能恢复。④结合针刺与干细胞移植的疗法,是一种创新且较好的脊髓损伤治疗策略,适用于修复神经环路,它结合了传统中医的智慧与现代生物技术的优势,为脊髓损伤患者提供了新的治疗选择。然而,目前这种联合疗法仍处于研究和探索阶段,其长期疗效和安全性尚需进一步验证。⑤综合而言,针刺及神经干细胞移植治疗脊髓损伤具有巨大的临床应用潜力,但仍需深入研究和优化治疗方案。未来,期待通过更多的临床试验和机制研究,进一步揭示这一疗法的疗效机制和最佳适应证,为脊髓损伤患者带来更好的康复希望和更高效的治疗效果。

关键词： 糖尿病   抑郁   慢性病共病   睡眠   体力活动   社交活动   健康管理  

摘要： 背景糖尿病和抑郁症是全球性公共卫生问题。糖尿病与抑郁症显著相关,因此对中老年人糖尿病、抑郁及糖尿病和抑郁共病进行监测和干预至关重要。目的探究中老年人糖尿病、抑郁状态及其共病患病率,以及睡眠、运动和社交活动对其的影响。方法基于2018年中国健康与养老追踪调查项目,纳入≥45岁中老年人为研究对象。收集其一般资料和糖尿病、抑郁状态患病情况及睡眠时长、运动、社交活动情况。采用多因素Logistic回归分析模型研究睡眠、运动和社交活动与糖尿病和抑郁状态共病之间的关联,将午睡时长和夜间睡眠时长的乘积纳入回归模型中进行交互作用分析。结果共纳入11177名为研究对象,其中糖尿病患病率为13.95%(1559/11177),抑郁状态患病率为24.85%(2777/11177),糖尿病和抑郁状态共病患病率为14.64%(1636/11177)。多元无序Logistic回归结果显示,夜间睡眠时长7~9 h(OR=0.337,95%CI=0.296~0.384)、夜间睡眠时长>9 h(OR=0.509,95%CI=0.374~0.692)以及午睡时长≥90 min(OR=0.792,95%CI=0.666~0.941)均是糖尿病和抑郁状态共病的保护因素(P<0.05);高水平社交同样能降低患共病的风险(OR=0.778,95%CI=0.686~0.882,P<0.05)。交互作用分析结果显示,保持7~9 h夜间睡眠时长,无论午休时间长短,均能有效降低糖尿病和抑郁状态共病患病风险(P<0.001);若夜间睡眠时长<7 h,午睡时长为60~<90 min能降低共病患病风险(OR=0.740,95%CI=0.577~0.950,P<0.05);在夜间睡眠时长>9 h,不午睡(OR=0.270,95%CI=0.125~0.581)或者保持60~<90 min的午睡时长(OR=0.165,95%CI=0.040~0.674)同样能够降低共病患病风险(P<0.05)。结论我国中老年人糖尿病和抑郁状态共病患病率较高,夜间睡眠时长≥7 h、午睡时长≥90 min以及高水平社交能有效降低糖尿病和抑郁状态共病患病风险,中等水平体力活动可分别降低糖尿病和抑郁状态患病风险。午睡则作为一种补偿机制,有助于弥补夜间睡眠不足,若夜间睡眠时长<7 h,午睡时长控制在60~<90 min同样能够降低糖尿病和抑郁状态共病患病风险。

关键词： Bioactive equivalent combinatorial   components   Xiao-Xu-Ming decoction   Coronary artery spasm   Calmodulin   MLCK/MLC   Vascular smooth muscle cells  

摘要： Background: Coronary artery spasm (CAS) is a severe pathological disorder with limited treatment options. Inhibiting vascular smooth muscle cell (VSMC) proliferation has emerged as a promising therapeutic strategy for CAS. Purpose: This study aims to investigate the potential function of Xiao-Xu-Ming decoction (XXMD) in the attenuation of CAS in rats. Methods: The involvement of bioactive equivalent combinatorial components (BECCs) of XXMD in CAS was predicted using network pharmacological analysis. A CAS rat model was established using pituitrin (Pit), and an Ang II-induced cell model was developed to assess the effects of BECCs on VSMC contraction. The expression of contractile phenotype markers was analyzed using RT-qPCR and Western blotting. Additionally, MTT assay, flow cytometry, Annexin V/PI staining, and Transwell assay were performed to evaluate cell proliferation, cell cycle progression, apoptosis, and migration. A collagen gel contraction assay was conducted to assess VSMC contraction. Results: Network pharmacological analysis suggested that BECCs in XXMD may influence CAS development through the Calmodulin (CaM)-MLCK/MLC axis. The drug-containing XXMD serum significantly inhibited VSMC proliferation and migration by reducing the expression of MLCK, alpha-SMA, Calponin, and SMHHC. Furthermore, it suppressed VSMC proliferation by downregulating MLCK expression via CaM inhibition. Importantly, BECCs of XXMD promoted anti-inflammatory responses, vasorelaxation, and oxidative stress reduction in Pit-induced CAS rats. Conclusion: These findings suggest that BECCs in XXMD may counteract CAS by modulating the CaM-mediated MLCK/MLC pathway in VSMCs. This mechanism may offer a foundation for novel and effective therapeutic strategies to treat CAS and prevent associated cardiac events, such as myocardial infarction and sudden cardiac death. Novelty: This study identifies a novel mechanism by which the "active ingredient cluster" of XXMD alleviates CAS through modul

关键词： p53   MDM2   PP2A   IER5   Phosphorylation   Ubiquitination  

摘要： The tumor suppressor p53 activates transcription of the IER5 gene, which encodes an adapter protein of protein phosphatase PP2A. IER5 binds to both the B55 regulatory subunit of PP2A and PP2A's target proteins, facilitating PP2A/B55-catalyzed dephosphorylation of these proteins. Here, we show that IER5 functions as a positive regulator of p53 by inhibiting its ubiquitination, thereby increasing cellular p53 levels. Mechanistically, this effect of IER5 requires its nuclear localization and binding to both PP2A/B55 and the p53 ubiquitin E3 ligase MDM2. Importantly, IER5 fails to inhibit p53 ubiquitination in cells treated with the MDM2 inhibitor Nutlin-3. The IER5-PP2A/B55 complex dephosphorylates MDM2 at Ser166, leading to MDM2 ubiquitination and a reduction in nuclear MDM2. Altogether, our data provide evidence that IER5-PP2A/B55 regulates the nuclear balance between MDM2 and p53 via MDM2 dephosphorylation.

关键词： Hydrogen sulfide   Cadmium stress   Calcium signaling pathway   Calmodulin   Detoxification  

摘要： The blood clam Tegilarca granosa is an economically important shellfish in Asia. The complex living environment often exposes the clams to cadmium (Cd) and hydrogen sulfide (H2S). H2S is well-known for its toxic effects, however, it is still unclear whether it can participate in regulating the heavy metal adaptation in clams. Here, we subjected T. granosa to chronic Cd stress (50 mu g/L, 14 days) to explore their physiological and molecular response patterns under the addition of 0.2, 0.4, and 0.8 mM H2S. The results indicated that the Cd stress induced the immune-toxicity and neurotoxicity in the gills and viscera. H2S could alleviate the toxicity by inducing phagocytosis rate, maintaining AChE and Ca2 +- ATPase activities, reducing MDA and O2-contents, promoting the excretion or degradation of Cd, and inhibiting the Ca2+ signaling pathway (CaM, CaMK2, CaMKK2). However, high concentrations of H2S also inhibited the ATPase activities and the apoptotic signaling pathway. Altogether, our results indicated that H2S has a special regulatory mechanism for Cd toxicity in the clam T. granosa, and this regulation may depend on the Ca2+ signaling pathway. Our results would offer insights into the sulfide and Cd-tolerant molecular mechanisms in this species and provide a useful tool for assessing the integrated biological impacts of Cd and sulfide on shellfish.

关键词： Alzheimer's disease   Innovative peptide   Ca 2+homeostasis   Targeted therapy   Amyloid-beta  

摘要： Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairments. Despite extensive research into the pathogenesis of AD, there is still a lack of effective clinical treatments drugs. In this study, we identified calmodulin (CaM) as a key molecule in the pathological process of AD through bioinformatics analysis and innovatively designed a peptide, TI-16, based on the binding specificity between CaM and amyloid-beta (A beta). We evaluated the improvement effect of TI-16 on the activity and apoptosis of A beta 25-35-induced SHSY5Y cells damage by Cell Counting Kit 8 (CCK-8) and Flow cytometry. MOE molecular docking and GST pull-down experiments demonstrated that TI-16 possesses binding affinity for A beta, and Immunofluorescence staining and Ca2+ concentration determination experiments showed that TI-16 reduced the co-localization of A beta and CaM, and could inhibit intracellular calcium overload. Subsequently, Morris water maze tests were conducted to assess the impact of TI-16 on learning and memory abilities in AD model mice. Furthermore, HE staining, Th-S staining, and Western blot analysis were utilized to investigate the improvement effect of TI-16 on the pathological damage of AD. The results indicate that TI-16 can target A beta to increase the intracellular free concentration of CaM, and effectively regulate intracellular Ca2+ homeostasis. Notably, TI-16 significantly enhanced cognitive function in AD model mice, reduced A beta deposition, alleviated neuronal damage, inhibited neuronal apoptosis, and thereby improved AD progression. As a potentially effective peptide therapeutic drug for AD, TI-16 offers a novel target and introduces a fresh perspective for future clinical applications.

关键词： AKI   ferroptosis   hypoxia-inducible factor 1α   iASPP   ischaemia–reperfusion  

摘要： Acute kidney injury (AKI) is a complex disease caused by different causes, especially ischaemia–reperfusion (I/R) injury. Ferroptosis is the main form of I/R-induced organ injury, and blocking ferroptosis has demonstrated therapeutic potential in ameliorating organ injury. We investigated the roles of apoptosis-stimulating protein of p53 (iASPP) and hypoxia-inducible factor-1α (HIF-1α) in ferroptosis during renal I/R injury. HIF-1α gene was knocked out in a hypoxia/reoxygenation model of renal tubular epithelial cells, and iASPP overexpression and knockdown plasmids were transfected. In I/R mouse models, conditional knockout of HIF-1α mice and injection of overexpressed iASPP adeno-associated viruses were used to validate downstream ferroptosis-related changes. The results showed that the ferroptosis level of mice in the I/R group was increased, and the addition of Ferrostatin-1 (Fer-1) and FG-4592 could alleviate the ferroptosis. HIF-1α conditional knockout mice showed exacerbated ferroptosis. HIF-1α can directly interact with SLC7A11, a key ferroptosis regulator, modulating ferroptosis progression. Similar to HIF-1α, iASPP expression was significantly increased in the I/R group, and overexpression of iASPP upregulated HIF-1α and SLC7A11 expression, consequently mitigating ferroptosis-mediated damage. In summary, our study suggests that iASPP exerts renal protection during I/R injury by regulating the HIF-1α/SLC7A11 axis to suppress ferroptosis.