CN114966024A - Method for predicting aging-related cognitive impairment based on PPP1R3G - Google Patents
Method for predicting aging-related cognitive impairment based on PPP1R3GDownload PDFInfo
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Abstract
Translated fromChinese
Description
Translated fromChinese技术领域technical field
本发明涉及衰老相关技术领域，具体为基于PPP1R3G预测衰老相关认知障碍的方法。The invention relates to the technical field of aging, in particular to a method for predicting aging-related cognitive impairment based on PPP1R3G.
背景技术Background technique
人口老龄化是全球面临的重大公共卫生问题。联合国最新统计，全球范围内，65岁及以上人口占总人口比的9.6%。预计到2050年，除非洲外，其他地区的老龄人口比例都将接近或超过25%。伴随机体衰老的脑老化对于老年人的危害越来越严重，认知功能也随着年龄的增加而逐渐下降，有超过50%的老人伴有认知功能障碍，其中部分人发展为阿尔茨海默病(Alzheimer’sdisease，AD)。伴认知功能障碍的老人不仅自身生活质量严重下降，还给社会和家庭带来沉重负担。目前，衰老相关认知障碍(age-relatedcognitiveimpairment，ARCI)已成为21世纪威胁人类健康的公共卫生难题，但其相关机制仍不清楚，也缺乏针对性的防治措施，尽早地识别并改善ARCI显得尤为重要，可有效降低患病率，阻止或延缓认知状况的恶化。但由于其起病隐匿，不易察觉，早期诊断主要依靠神经心理学、神经影像学和脑脊液生物标志物检查。认知功能量表评价存在一定的主观性，评价结果会随着患者的状态存在波动，且需要提问和回答，耗时耗力；神经影像学检测需用到磁共振成像（MRI）等昂贵设备，无法大量普及；脑脊液检测具有侵袭性，取样难度大，配合度差。目前尚无种准确性高，特异性强的ARCI外周血生物标志物。Population aging is a major public health problem facing the world. According to the latest statistics from the United Nations, people aged 65 and over account for 9.6% of the total population globally. By 2050, the proportion of the elderly population in all regions except Africa is expected to approach or exceed 25%. Brain aging with the aging of the body is more and more harmful to the elderly, and cognitive function also gradually declines with age. More than 50% of the elderly have cognitive dysfunction, and some of them develop Alzheimer's disease. Alzheimer's disease (AD). Elderly people with cognitive impairment not only have a serious decline in their quality of life, but also bring a heavy burden to society and their families. At present, age-related cognitive impairment (ARCI) has become a public health problem that threatens human health in the 21st century, but its related mechanism is still unclear, and there is a lack of targeted prevention and control measures. It is particularly important to identify and improve ARCI as soon as possible. Important, can effectively reduce the prevalence, prevent or delay the deterioration of cognitive status. However, due to its insidious onset and difficult to detect, early diagnosis mainly relies on neuropsychology, neuroimaging and cerebrospinal fluid biomarkers. Cognitive function scale evaluation is subject to a certain degree of subjectivity. The evaluation results will fluctuate with the patient's state, and it requires questions and answers, which is time-consuming and labor-intensive. Neuroimaging testing requires expensive equipment such as magnetic resonance imaging (MRI). , cannot be widely popularized; cerebrospinal fluid detection is invasive, sampling is difficult, and the degree of cooperation is poor. At present, there is no high-accuracy and specific ARCI peripheral blood biomarker.
衰老过程中，除了渐进性记忆障碍、认知功能障碍等神经精神症状外还有代谢方面的改变，表现为神经元对葡萄糖的利用下降、血清胆固醇和脑脊液胆固醇水平明显增高、能量代谢受损等。ARCI与糖脂代谢异常有关，并且后者是前者的基础，脑的胰岛素抵抗、脑中高胆固醇均有可能是ARCI发病的危险因素，相关的横断面研究也为发现更多的ARCI的生物标志物提供了希望，并且这些结果证明导致代谢紊乱的因子可能预测认知障碍的发生，但具体哪种物质能明确检测出作为辨别是认知障碍，还不清楚。In the process of aging, in addition to neuropsychiatric symptoms such as progressive memory impairment and cognitive dysfunction, there are also metabolic changes, which are manifested as decreased glucose utilization by neurons, significantly increased serum cholesterol and cerebrospinal fluid cholesterol levels, and impaired energy metabolism. . ARCI is related to abnormal glucose and lipid metabolism, and the latter is the basis of the former. Insulin resistance in the brain and high cholesterol in the brain may be risk factors for the onset of ARCI. Related cross-sectional studies have also found more biomarkers for ARCI. There is hope, and these results demonstrate that factors that contribute to metabolic disturbances may predict the development of cognitive impairment, but it is unclear exactly which substances are definitively detected as discriminating cognitive impairment.
蛋白磷酸酶-1调节亚基3（Proteinphosphatase-1regulatorysubunit3，PPP1R3）可以把蛋白磷酸酶-1（PP1）靶向到糖原，促进糖原合成，共有A-G7个成员。既往大量研究集中于PPP1R3A-3F对不同组织中的糖原和葡萄糖代谢的调控，直到2011年才首次证实PPP1R3G在糖脂代谢中起到重要的调控作用。例如有研究表明，PPP1R3G敲除可减少餐后肝糖原的积累及餐后血糖的清除，减轻高脂饮食诱导的脂肪肝，降低脂肪组织中的糖原水平；肝脏过表达则引起空腹血糖水平、脂肪及肝脏甘油三酯水平降低，还减轻乙醇诱导的脂质堆积、肝损伤和脂肪肝的形成。此外，PPP1R3G还参与了肿瘤免疫细胞浸润、炎症及凋亡调控。新近发现，PPP1R3B是阿尔茨海默病（Alzheimer'sDisease，AD）的潜在候选基因，但对相关机制未进行研究。目前未见关于PPP1R3G在神经退行性疾病中分布以及血清PPP1R3G与ARCI之间关系的报道。Protein phosphatase-1 regulatory subunit 3 (PPP1R3) can target protein phosphatase-1 (PP1) to glycogen and promote glycogen synthesis, with a total of A-G7 members. A large number of previous studies have focused on the regulation of PPP1R3A-3F on glycogen and glucose metabolism in different tissues, and it was not until 2011 that it was first confirmed that PPP1R3G plays an important regulatory role in glucose and lipid metabolism. For example, studies have shown that PPP1R3G knockout can reduce the accumulation of postprandial hepatic glycogen and the clearance of postprandial blood glucose, alleviate fatty liver induced by high-fat diet, and reduce the level of glycogen in adipose tissue; liver overexpression can cause fasting blood glucose levels , fat, and hepatic triglyceride levels, and also attenuated ethanol-induced lipid accumulation, liver damage, and fatty liver formation. In addition, PPP1R3G is also involved in the regulation of tumor immune cell infiltration, inflammation and apoptosis. Recently, PPP1R3B was found to be a potential candidate gene for Alzheimer's disease (AD), but the related mechanism has not been studied. There are no reports on the distribution of PPP1R3G in neurodegenerative diseases and the relationship between serum PPP1R3G and ARCI.
发明内容SUMMARY OF THE INVENTION
针对现有技术的不足，本发明提供了基于PPP1R3G预测衰老相关认知障碍的方法，解决了上述背景技术中提出的问题。In view of the deficiencies of the prior art, the present invention provides a method for predicting aging-related cognitive impairment based on PPP1R3G, which solves the problems raised in the above background art.
为实现以上目的，本发明通过以下技术方案予以实现：基于PPP1R3G预测衰老相关认知障碍的方法，包括试剂盒盒体和制冷机构，所述试剂盒盒体上铰接有盒盖，所述试剂盒盒体上还设有辅助压紧机构，所述试剂盒盒体内设有置物框架，所述置物框架内嵌入有若干个密封泡沫圈，所述密封泡沫圈内穿设有样品试管，所述置物框架的两侧均连接有支撑顶杆，所述支撑顶杆的一端螺纹固定在置物框架上。In order to achieve the above objects, the present invention is achieved by the following technical solutions: a method for predicting aging-related cognitive impairment based on PPP1R3G, comprising a kit box body and a refrigeration mechanism, the kit box body is hinged with a box cover, and the kit box body is hinged. The box body is also provided with an auxiliary pressing mechanism, and the test kit box body is provided with a storage frame, a plurality of sealing foam rings are embedded in the storage frame, and the sample test tubes are passed through the sealing foam ring, and the storage Both sides of the frame are connected with support ejector rods, and one end of the support ejector rods is threadedly fixed on the storage frame.
可选的，所述辅助压紧机构包括固定槽板、丝杆套柱块、压板、调节丝杆和手柄，所述固定槽板通过螺栓固定在试剂盒盒体上，所述固定槽板内设有丝杆套柱块，所述丝杆套柱块内穿出的调节丝杆延伸出固定槽板的内部，所述调节丝杆的输入端连接有手柄。Optionally, the auxiliary pressing mechanism includes a fixed groove plate, a screw sleeve column block, a pressure plate, an adjustment screw and a handle, the fixed groove plate is fixed on the kit box body by bolts, and the fixed groove plate is inside. A screw rod sleeve block is provided, the adjusting screw rod passing through the screw rod sleeve block block extends out of the interior of the fixed groove plate, and the input end of the adjusting screw rod is connected with a handle.
可选的，所述制冷机构包括开设在试剂盒盒体内的空腔，所述空腔与置物框架之间设有固定铝片和固定横板，所述固定横板内设有若干个制冷片，所述固定铝片内开设有若干个气孔。Optionally, the refrigerating mechanism includes a cavity opened in the box body of the kit, a fixed aluminum sheet and a fixed horizontal plate are arranged between the cavity and the storage frame, and a plurality of cooling pieces are arranged in the fixed horizontal plate. , a number of air holes are opened in the fixed aluminum sheet.
可选的，所述空腔的两侧均连通气管，所述气管连通制冷罐，所述制冷罐连通活性炭空气滤罐，所述制冷罐和活性炭空气滤罐均通过螺栓固定在试剂盒盒体上。Optionally, both sides of the cavity are connected to an air pipe, the air pipe is connected to a refrigeration tank, the refrigeration tank is connected to an activated carbon air filter tank, and the refrigeration tank and the activated carbon air filter tank are both fixed to the kit box by bolts. superior.
基于PPP1R3G预测衰老相关认知障碍的方法，包括以下步骤：A method for predicting aging-related cognitive impairment based on PPP1R3G, including the following steps:
S1、试验对象，以及试验对象的选取标准；S1, the test object, and the selection criteria of the test object;
S2、排除标准；S2, exclusion criteria;
S3、样本试验方法；S3, sample test method;
S4、评估方法。S4. Evaluation method.
可选的，所述步骤S1包括以下步骤：Optionally, the step S1 includes the following steps:
S11、年龄≥65岁；S11. Age ≥ 65 years old;
S12、精神状态良好，能够在医师的指导下完成所有神经心理评估，听、说、读、理解无障碍；S12. Good mental state, able to complete all neuropsychological assessments under the guidance of physicians, without obstacles in listening, speaking, reading and comprehension;
S13、自愿参与本次认知评估和静脉血采集。S13. Voluntarily participate in this cognitive assessment and venous blood collection.
可选的，所述步骤S2包括以下步骤：Optionally, the step S2 includes the following steps:
S21、突然起病；S21. Sudden onset;
S22、有影响认知功能的神经系统疾病；S22. Nervous system diseases affecting cognitive function;
S23、有精神障碍病史；S23. History of mental disorder;
S24、有严重头外伤史伴有持续性神经功能缺损或已知的脑结构异常；S24. History of severe head trauma with persistent neurological deficit or known abnormal brain structure;
S25、近一年内神经影像学检查证实的脑血管意外；S25. Cerebrovascular accident confirmed by neuroimaging within the past year;
S26、急性心血管疾病、肿瘤、甲状腺疾病、贫血、严重感染等严重的内科疾病；S26, acute cardiovascular disease, tumor, thyroid disease, anemia, serious infection and other serious medical diseases;
S27、已知或可能影响认知功能的药物服用史；S27. History of taking drugs known or likely to affect cognitive function;
S28、近两月内酒精及药物依赖史。S28. History of alcohol and drug dependence within the past two months.
可选的，所述步骤S3包括以下步骤：Optionally, the step S3 includes the following steps:
S31、标本收集为患者入院次日清晨7:00-8:00抽取空腹静脉血，前一天晚22:00后禁食禁水，抽取正中静脉血4-5ml，室温静置2小时，在4℃下3000rpm离心15min，取上清分装至0.5mlEP管后立即储存在-80℃冰箱中用来进一步检测。S31. Specimens are collected by taking fasting venous blood from 7:00-8:00 in the morning the next day after admission, fasting after 22:00 the night before, taking 4-5ml of median venous blood, standing at room temperature for 2 hours, and at 4 Centrifuge at 3000 rpm for 15 min at °C, take the supernatant and aliquot into 0.5 ml EP tubes and immediately store in -80 °C refrigerator for further detection.
可选的，所述步骤S4包括以下步骤：Optionally, the step S4 includes the following steps:
S41、神经心理评估；S41. Neuropsychological assessment;
S411、对所有受试者的总体认知功能进行全面评估，所有的病人的评估都是在精神状态良好，配合佳的情况下完成；S411. Conduct a comprehensive assessment of the overall cognitive function of all subjects, and all patients' assessments are completed under the condition of good mental state and good cooperation;
S412、总体认知功能使用简易精神状态量表MMSE和蒙特利尔认知量表MoCA：MMSE最高30分，≥27为正常，21-27为轻度认知障碍，10-20为中度认知障碍，≤9分重度认知障碍；S412. Use the Mini-Mental State Scale MMSE and Montreal Cognitive Scale MoCA for overall cognitive function: MMSE is up to 30 points, ≥27 is normal, 21-27 is mild cognitive impairment, 10-20 is moderate cognitive impairment , ≤9 points severe cognitive impairment;
S413、MoCA满分30分，≥26正常，18-26为轻度认知障碍，10-17为中度认知障碍，＜10为重度；S413, MoCA out of 30 points, ≥26 is normal, 18-26 is mild cognitive impairment, 10-17 is moderate cognitive impairment, <10 is severe;
S414、受教育年限≤12，可加1分，对量表评估结果，后根据各项认知板块拆分统计，以方便对各种认知域评估，因单独使用MMSE或MoCA量表分别会增加受试者的假阴性率及假阳性率，且认知功能障碍评价结果的一致性较差，故在本研究中，将MMSE及MoCA量表结合使用，做出综合判断；S414. Years of education ≤ 12, 1 point can be added to evaluate the results of the scale, and then split the statistics according to each cognitive section to facilitate the evaluation of various cognitive domains. The false negative rate and false positive rate of the subjects were increased, and the consistency of the evaluation results of cognitive dysfunction was poor. Therefore, in this study, the MMSE and MoCA scales were combined to make a comprehensive judgment;
S42、统计分析：所有的统计分析均在SPSS22.0上进行，并应用GraphPadPrism8.0.2辅助分析；S42. Statistical analysis: All statistical analyses were performed on SPSS 22.0, and GraphPad Prism 8.0.2 was used for auxiliary analysis;
S421、根据受试者血清PPP1R3G水平、MMSE和MoCA量表得分结果进行K-means聚类分析，考虑到样本量的平衡，设定k=3的初始簇中心，以及对于连续变量进行正态性检验，满足正态性的数据表示为平均值±标准差，非正态的数据以中位数表示；S421. Perform K-means cluster analysis according to the subjects' serum PPP1R3G level, MMSE and MoCA scale score results, consider the balance of sample size, set the initial cluster center of k=3, and perform normality for continuous variables Test, the data that meet the normality are expressed as the mean ± standard deviation, and the non-normal data is expressed as the median;
S422、对于计量资料，采用卡方检验比较，在两组比较中，两独立样本t检验被用来检验满足参数条件的数据；Mann-Whitney U检验则用于非参数检验。多组比较中，单因素方差分析(one-wayANOVA)用于参数检验，根据方差齐性与否采用LSD法或Dunnett’sT3法进行两两比较；不满足参数检验条件的用Kruskal-Wallis检验，进一步两两比较需采用Bonferroni法校正，计数资料用卡方检验进行组间比较；S422. For the measurement data, the chi-square test is used for comparison. In the comparison between the two groups, the two independent sample t test is used to test the data satisfying the parametric conditions; the Mann-Whitney U test is used for the nonparametric test. In the multi-group comparison, one-way ANOVA was used for the parametric test, and the LSD method or Dunnett's T3 method was used for pairwise comparison according to whether the variance was homogenous or not; the Kruskal-Wallis test was used if the parametric test conditions were not met Further pairwise comparisons should be corrected by the Bonferroni method, and the count data should be compared between groups by the chi-square test;
S423、变量间的相关分析，依据变量正态分布情况，采用Pearson或者Spearman相关分析，显著性水平设定为P＜0.05。双变量相关分析，鉴于双变量非正态分布资料，采用spearman相关分析；考虑到两个变量关系受多个其他变量的相互作用影响，采用偏相关分析；S423. For the correlation analysis between variables, according to the normal distribution of the variables, Pearson or Spearman correlation analysis was used, and the significance level was set as P<0.05. Bivariate correlation analysis, in view of bivariate non-normal distribution data, adopt spearman correlation analysis; considering that the relationship between two variables is affected by the interaction of multiple other variables, adopt partial correlation analysis;
S424、对双变量为连续性资料，绘制散点图，并进行线性相关性估计，分别根据MoCA和MMSE的认知评估结果，对研究对象认知障碍程度进行分类，计算其患病状况对认知障碍的比数比及血清PPP1R3G高低对认知障碍程度的比数比，并且分别在不同的纳入回归变量因素模型下，校正OR值；S424. For the bivariate continuous data, draw a scatter plot, and perform linear correlation estimation. According to the cognitive assessment results of MoCA and MMSE, classify the cognitive impairment of the research object, and calculate the correlation between the disease status and the cognitive impairment. The odds ratio of cognitive impairment and the odds ratio of serum PPP1R3G level to the degree of cognitive impairment, and the OR values were adjusted under different regression variable factor models respectively;
S425、对PPP1R3G含量高低的指标、及合并其他协变量因素后的复合效应指标进行受试者回归曲线分析，按照双侧P＜0.05表示差异有统计学意义。S425. Perform subject regression curve analysis on the indicators of PPP1R3G content and the composite effect indicators combined with other covariate factors. According to the two-sided P<0.05, the difference is statistically significant.
可选的，所述标本收集中所有病例的实验室测量均包括PPP1R3G水平，采用酶联免疫吸附试剂盒严格按照试验说明来操作。Optionally, the laboratory measurements of all cases in the specimen collection include PPP1R3G levels, and the enzyme-linked immunosorbent assay kit is used to operate in strict accordance with the test instructions.
本发明提供了基于PPP1R3G预测衰老相关认知障碍的方法，具备以下有益效果：The present invention provides a method for predicting aging-related cognitive impairment based on PPP1R3G, which has the following beneficial effects:
该基于PPP1R3G预测衰老相关认知障碍的方法，经严格筛选，纳入90例精神状态良好的≥65岁老年人，Elisa法检测血清PPP1R3G水平，采用简易精神状态量表、蒙特利尔认知评估量表作为主体认知功能评估；通过对血清PPP1R3G的Elisa结果、MMSE和MoCA得分的三维K-means聚类分成High-PPP1R3G组（47例）、Medium-PPP1R3G组（29例）及Low-PPP1R3G组（14例），另选取33名健康非老年人作为对照组，分析PPP1R3G与认知功能评分之间的关系。This method based on PPP1R3G to predict aging-related cognitive impairment was strictly screened and included 90 elderly people aged ≥ 65 years with good mental status. Elisa method was used to detect serum PPP1R3G levels, and the Simple Mental State Scale and Montreal Cognitive Assessment Scale were used as Subject cognitive function evaluation; divided into High-PPP1R3G group (47 cases), Medium-PPP1R3G group (29 cases) and Low-PPP1R3G group (14 cases) by three-dimensional K-means clustering of serum PPP1R3G Elisa results, MMSE and MoCA scores Example), and 33 healthy non-elderly people were selected as the control group to analyze the relationship between PPP1R3G and cognitive function scores.
本发明可将置物框架置于试剂盒盒体的内部，并将盒盖盖合在试剂盒盒体上，并通过手柄带动调节丝杆转动，使得调节丝杆推动丝杆套柱块沿固定槽板的中轴线移动，而丝杆套柱块与压板固定连接，可将丝杆套柱块与压板同步移动，使得压板压紧盒盖，用于限制盒盖的位置；经制冷罐的作用，可将外部气体经活性炭空气滤罐过滤处理后进入制冷罐的内部制冷，再将冷却气体经气管导入空腔的内部，冷却气体经气孔导入置物框架的内部，用于对样品试管内的样品制冷处理，并通过制冷片对固定铝片制冷处理，可使得固定铝片提高降温效率。In the present invention, the storage frame can be placed inside the kit box body, the box cover is closed on the kit box body, and the adjusting screw rod is driven to rotate by the handle, so that the adjusting screw rod pushes the screw sleeve column block along the fixing groove The central axis of the plate moves, and the screw sleeve column block is fixedly connected with the pressure plate, which can move the screw sleeve column block and the pressure plate synchronously, so that the pressure plate presses the box cover to limit the position of the box cover; through the action of the refrigeration tank, The external air can be filtered and processed by the activated carbon air filter canister and then enter the cooling tank for cooling, and then the cooling gas is introduced into the cavity through the trachea, and the cooling gas is introduced into the interior of the storage frame through the air hole to cool the sample in the sample test tube. The fixed aluminum sheet can be refrigerated and processed by the cooling sheet, so that the fixed aluminum sheet can improve the cooling efficiency.
附图说明Description of drawings
图1为老年状态与认知障碍发生的风险关系表；Figure 1 is a table showing the risk relationship between old age and cognitive impairment;
图2为衰老人群K-means聚类分析图；Figure 2 is the K-means cluster analysis diagram of the aging population;
图3三组衰老人群的人口统计学资料、临床特征比较表；Figure 3. Comparison table of demographic data and clinical characteristics of three groups of aging population;
图4为三组衰老人群的总体认知功能量表评分表；Figure 4 is the overall cognitive function scale score table of the three groups of aging population;
图5为血清PPP1R3G与认知量表的相关关系图；Figure 5 is a correlation diagram of serum PPP1R3G and cognitive scale;
图6为衰老人群认知障碍的二元Logistic回归分析（向后LR法）表；Figure 6 is a binary logistic regression analysis (backward LR method) table of cognitive impairment in aging population;
图7为衰老人群MMSE评分和MoCA评分的逐步线性回归表；Figure 7 is a stepwise linear regression table of the MMSE score and MoCA score of the aging population;
图8为PPP1R3G及其复合指标预测ARCI的ROC曲线；Figure 8 is the ROC curve of PPP1R3G and its composite indicators to predict ARCI;
图9为本发明的试剂盒盒体外部结构示意图；9 is a schematic diagram of the external structure of the kit box of the present invention;
图10为本发明的内部结构示意图。Figure 10 is a schematic diagram of the internal structure of the present invention.
图中：试剂盒盒体1、盒盖2、辅助压紧机构3、固定槽板301、丝杆套柱块302、压板303、调节丝杆304、手柄305、置物框架4、置物板5、密封泡沫圈6、支撑顶杆7、样品试管8、固定铝片9、气孔10、固定横板11、制冷片12、空腔13、气管14、制冷罐15、活性炭空气滤罐16。In the figure:
具体实施方式Detailed ways
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, but not all of the embodiments.
请参阅图9和图10，本发明提供一种技术方案：基于PPP1R3G预测衰老相关认知障碍的方法，包括试剂盒盒体1和制冷机构，试剂盒盒体1上铰接有盒盖2，试剂盒盒体1上还设有辅助压紧机构3，试剂盒盒体1内设有置物框架4，置物框架4内嵌入有若干个密封泡沫圈6，密封泡沫圈6内穿设有样品试管8，置物框架4的两侧均连接有支撑顶杆7，支撑顶杆7的一端螺纹固定在置物框架4上，辅助压紧机构3包括固定槽板301、丝杆套柱块302、压板303、调节丝杆304和手柄305，固定槽板301通过螺栓固定在试剂盒盒体1上，固定槽板301内设有丝杆套柱块302，丝杆套柱块302内穿出的调节丝杆304延伸出固定槽板301的内部，调节丝杆304的输入端连接有手柄305，可将置物框架4置于试剂盒盒体1的内部，并将盒盖2盖合在试剂盒盒体1上，并通过手柄305带动调节丝杆304转动，使得调节丝杆304推动丝杆套柱块302沿固定槽板301的中轴线移动，而丝杆套柱块302与压板303固定连接，可将丝杆套柱块302与压板303同步移动，使得压板303压紧盒盖2，用于限制盒盖2的位置，制冷机构包括开设在试剂盒盒体1内的空腔13，空腔13与置物框架4之间设有固定铝片9和固定横板11，固定横板11内设有若干个制冷片12，固定铝片9内开设有若干个气孔10，空腔13的两侧均连通气管14，气管14连通制冷罐15，制冷罐15连通活性炭空气滤罐16，制冷罐15和活性炭空气滤罐16均通过螺栓固定在试剂盒盒体1上，经制冷罐15的作用，可将外部气体经活性炭空气滤罐16过滤处理后进入制冷罐15的内部制冷，再将冷却气体经气管14导入空腔13的内部，冷却气体经气孔10导入置物框架4的内部，用于对样品试管8内的样品制冷处理，并通过制冷片12对固定铝片9制冷处理，可使得固定铝片9提高降温效率。Please refer to FIG. 9 and FIG. 10 , the present invention provides a technical solution: a method for predicting aging-related cognitive impairment based on PPP1R3G, comprising a
实施案例二Implementation case two
基于PPP1R3G预测衰老相关认知障碍的方法，包括试验对象与材料及评估方法，试验对象与材料中试验对象包括受试者筛选与标本收集，所述受试者筛选为收集2021年03月-2022年01月间徐州医科大学附属医院老年病科就诊的年龄≥65岁的住院病例资料，在到院随访同时，由两位经验丰富的内科医师分别对患者进行详细的人口统计学、病史病程、治疗情况等资料的采集及评估，所有的认知量表均在患者精神状态良好、配合佳的情况下进行评估。A method for predicting aging-related cognitive impairment based on PPP1R3G, including test objects, materials and evaluation methods. The test objects and materials in the test objects include subject screening and specimen collection. The subject screening is collected from March 2021 to 2022. The data of inpatient cases aged ≥ 65 years who visited the Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University in January 2009. At the same time of visiting the hospital, two experienced internal medicine physicians conducted detailed demographic statistics, medical history and disease course of the patients. The collection and evaluation of data such as treatment conditions, all cognitive scales are evaluated under the condition that the patient is in good mental state and cooperates well.
基于PPP1R3G预测衰老相关认知障碍的方法，包括以下步骤：A method for predicting aging-related cognitive impairment based on PPP1R3G, including the following steps:
S1、试验对象，以及试验对象的选取标准；S1, the test object, and the selection criteria of the test object;
S2、排除标准；S2, exclusion criteria;
S3、样本试验方法；S3, sample test method;
S4、评估方法。S4. Evaluation method.
可选的，所述步骤S1包括以下步骤：Optionally, the step S1 includes the following steps:
S11、年龄≥65岁；S11. Age ≥ 65 years old;
S12、精神状态良好，能够在医师的指导下完成所有神经心理评估，听、说、读、理解无障碍；S12. Good mental state, able to complete all neuropsychological assessments under the guidance of physicians, without obstacles in listening, speaking, reading and comprehension;
S13、自愿参与本次认知评估和静脉血采集。S13. Voluntarily participate in this cognitive assessment and venous blood collection.
可选的，所述步骤S2包括以下步骤：Optionally, the step S2 includes the following steps:
S21、突然起病；S21. Sudden onset;
S22、有影响认知功能的神经系统疾病(如明确诊断的AD、VaD、帕金森病、卒中、癫痫、中枢神经系统感染等)；S22. Nervous system diseases affecting cognitive function (such as clearly diagnosed AD, VaD, Parkinson's disease, stroke, epilepsy, central nervous system infection, etc.);
S23、有精神障碍病史(如精神分裂症或抑郁症患者)；S23. A history of mental disorders (such as patients with schizophrenia or depression);
S24、有严重头外伤史伴有持续性神经功能缺损或已知的脑结构异常(脑外伤、癫痫、脑炎和脑积水等)；S24. History of severe head trauma with persistent neurological deficit or known abnormal brain structure (brain trauma, epilepsy, encephalitis and hydrocephalus, etc.);
S25、近一年内神经影像学检查证实的脑血管意外；S25. Cerebrovascular accident confirmed by neuroimaging within the past year;
S26、急性心血管疾病、肿瘤、甲状腺疾病、贫血、严重感染等严重的内科疾病；S26, acute cardiovascular disease, tumor, thyroid disease, anemia, serious infection and other serious medical diseases;
S27、已知或可能影响认知功能的药物服用史；S27. History of taking drugs known or likely to affect cognitive function;
S28、近两月内酒精及药物依赖史。S28. History of alcohol and drug dependence within the past two months.
可选的，所述步骤S3包括以下步骤：Optionally, the step S3 includes the following steps:
S31、标本收集为患者入院次日清晨7:00-8:00抽取空腹静脉血，前一天晚22:00后禁食禁水，抽取正中静脉血4-5ml，室温静置2小时，在4℃下3000rpm离心15min，取上清分装至0.5mlEP管后立即储存在-80℃冰箱中用来进一步检测。S31. Specimens are collected by taking fasting venous blood from 7:00-8:00 in the morning the next day after admission, fasting after 22:00 the night before, taking 4-5ml of median venous blood, standing at room temperature for 2 hours, and at 4 Centrifuge at 3000 rpm for 15 min at °C, take the supernatant and aliquot into 0.5 ml EP tubes and immediately store in -80 °C refrigerator for further detection.
可选的，所述步骤S4包括以下步骤：Optionally, the step S4 includes the following steps:
S41、神经心理评估；S41. Neuropsychological assessment;
S411、对所有受试者的总体认知功能进行全面评估，所有的病人的评估都是在精神状态良好，配合佳的情况下完成；S411. Conduct a comprehensive assessment of the overall cognitive function of all subjects, and all patients' assessments are completed under the condition of good mental state and good cooperation;
S412、总体认知功能使用简易精神状态量表MMSE和蒙特利尔认知量表MoCA：MMSE最高30分，≥27为正常，21-27为轻度认知障碍，10-20为中度认知障碍，≤9分重度认知障碍；S412. Use the Mini-Mental State Scale MMSE and Montreal Cognitive Scale MoCA for overall cognitive function: MMSE is up to 30 points, ≥27 is normal, 21-27 is mild cognitive impairment, 10-20 is moderate cognitive impairment , ≤9 points severe cognitive impairment;
S413、MoCA满分30分，≥26正常，18-26为轻度认知障碍，10-17为中度认知障碍，＜10为重度；S413, MoCA out of 30 points, ≥26 is normal, 18-26 is mild cognitive impairment, 10-17 is moderate cognitive impairment, <10 is severe;
S414、受教育年限≤12，可加1分，对量表评估结果，后根据各项认知板块拆分统计，以方便对各种认知域评估，因单独使用MMSE或MoCA量表分别会增加受试者的假阴性率及假阳性率，且认知功能障碍评价结果的一致性较差，故在本研究中，将MMSE及MoCA量表结合使用，做出综合判断；S414. Years of education ≤ 12, 1 point can be added to evaluate the results of the scale, and then split the statistics according to each cognitive section to facilitate the evaluation of various cognitive domains. The false negative rate and false positive rate of the subjects were increased, and the consistency of the evaluation results of cognitive dysfunction was poor. Therefore, in this study, the MMSE and MoCA scales were combined to make a comprehensive judgment;
S42、统计分析：所有的统计分析均在SPSS22.0上进行，并应用GraphPadPrism8.0.2辅助分析；S42. Statistical analysis: All statistical analyses were performed on SPSS 22.0, and GraphPad Prism 8.0.2 was used for auxiliary analysis;
S421、根据受试者血清PPP1R3G水平、MMSE和MoCA量表得分结果进行K-means聚类分析，考虑到样本量的平衡，设定k=3的初始簇中心，以及对于连续变量进行正态性检验，满足正态性的数据表示为平均值±标准差，非正态的数据以中位数表示；S421. Perform K-means cluster analysis according to the subjects' serum PPP1R3G level, MMSE and MoCA scale score results, consider the balance of sample size, set the initial cluster center of k=3, and perform normality for continuous variables Test, the data that meet the normality are expressed as the mean ± standard deviation, and the non-normal data is expressed as the median;
S422、对于计量资料，采用卡方检验比较，在两组比较中，两独立样本t检验被用来检验满足参数条件的数据；Mann-WhitneyU检验则用于非参数检验。多组比较中，单因素方差分析(one-wayANOVA)用于参数检验，根据方差齐性与否采用LSD法或Dunnett’sT3法进行两两比较；不满足参数检验条件的用Kruskal-Wallis检验，进一步两两比较需采用Bonferroni法校正，计数资料用卡方检验进行组间比较；S422. For the measurement data, the chi-square test is used for comparison. In the comparison between the two groups, the two independent sample t test is used to test the data meeting the parametric conditions; the Mann-Whitney U test is used for the nonparametric test. In the multi-group comparison, one-way ANOVA was used for the parametric test, and the LSD method or Dunnett's T3 method was used for pairwise comparison according to whether the variance was homogenous or not; the Kruskal-Wallis test was used if the parametric test conditions were not met Further pairwise comparisons should be corrected by the Bonferroni method, and the count data should be compared between groups by the chi-square test;
S423、变量间的相关分析，依据变量正态分布情况，采用Pearson或者Spearman相关分析，显著性水平设定为P＜0.05。双变量相关分析，鉴于双变量非正态分布资料，采用spearman相关分析；考虑到两个变量关系受多个其他变量的相互作用影响，采用偏相关分析；S423. For the correlation analysis between variables, according to the normal distribution of the variables, Pearson or Spearman correlation analysis was used, and the significance level was set as P<0.05. Bivariate correlation analysis, in view of bivariate non-normal distribution data, adopt spearman correlation analysis; considering that the relationship between two variables is affected by the interaction of multiple other variables, adopt partial correlation analysis;
S424、对双变量为连续性资料，绘制散点图，并进行线性相关性估计，分别根据MoCA和MMSE的认知评估结果，对研究对象认知障碍程度进行分类，计算其患病状况对认知障碍的比数比及血清PPP1R3G高低对认知障碍程度的比数比，并且分别在不同的纳入回归变量因素模型下，校正OR值；S424. For the bivariate continuous data, draw a scatter plot, and perform linear correlation estimation. According to the cognitive assessment results of MoCA and MMSE, classify the cognitive impairment of the research object, and calculate the correlation between the disease status and the cognitive impairment. The odds ratio of cognitive impairment and the odds ratio of serum PPP1R3G level to the degree of cognitive impairment, and the OR values were adjusted under different regression variable factor models respectively;
S425、对PPP1R3G含量高低的指标、及合并其他协变量因素后的复合效应指标进行受试者回归曲线分析，按照双侧P＜0.05表示差异有统计学意义。S425. Perform subject regression curve analysis on the indicators of PPP1R3G content and the composite effect indicators combined with other covariate factors. According to the two-sided P<0.05, the difference is statistically significant.
可选的，所述标本收集中所有病例的实验室测量均包括PPP1R3G水平，采用酶联免疫吸附试剂盒严格按照试验说明来操作。Optionally, the laboratory measurements of all cases in the specimen collection include PPP1R3G levels, and the enzyme-linked immunosorbent assay kit is used to operate in strict accordance with the test instructions.
参照图1，为了确定衰老是认知功能下降的风险因素，按照制定标准，共有90名衰老（Age≥65）及33名对照（Age＜65）被纳入研究。如图1所示，基于MMSE得分，对照组MMSE评分均在27分及以上，判断无认知障碍，衰老组48人存在轻度或中度认知障碍，42人无认知障碍，四格表计算比数比(Oddsratio，OR)为6.40（2.27，18.07）；基于MoCA得分，对照组2人判断为轻度认知障碍，31人无认知障碍；衰老组22人存在轻到重度认知障碍，68人无认知障碍，OR值为5.02（1.11，22.67）。图1中*exposurefactor。Referring to Figure 1, in order to determine that aging is a risk factor for cognitive decline, according to the established criteria, a total of 90 aging (Age ≥ 65) and 33 controls (Age < 65) were included in the study. As shown in Figure 1, based on the MMSE score, the MMSE scores of the control group were all 27 points and above, and no cognitive impairment was judged. 48 people in the aging group had mild or moderate cognitive impairment, and 42 people had no cognitive impairment. The odds ratio (OR) calculated by the table was 6.40 (2.27, 18.07); based on the MoCA score, 2 people in the control group were judged to have mild cognitive impairment, and 31 people had no cognitive impairment; 22 people in the aging group had mild to severe cognitive impairment. Cognitive impairment, 68 people without cognitive impairment, OR value was 5.02 (1.11, 22.67). *exposurefactor in Figure 1.
参照图2，通过对老年人血清PPP1R3G、MMSE和MoCA的三维K-means聚类后，分为High-PPP1R3G组（47例），Medium-PPP1R3G组（29例）以及Low-PPP1R3G三个组（14例）(图2A）。对血清PPP1R3G水平进行比较，发现三组之前存在统计学差异（F=247.869，P＜0.000），进一步两两比较发现，各组间均存在统计学差异(图2B，P＜0.05，P＜0.01，P＜0.001)，表明按血清PPP1R3G含量高低的分组可获得较好的聚类效果。图2中MMSE，简易智能状态量表；MoCA，蒙特利尔认知评估量表。三组数据均数的比较采用one-wayANOVA，根据方差齐性检验结果，方差不齐采用1：Dunnett’sT3法，方差齐采用2：LSD法，显著性水平设定为P＜0.05，*P＜0.05，**P＜0.01，***P＜0.001。Referring to Figure 2, after three-dimensional K-means clustering of serum PPP1R3G, MMSE and MoCA of the elderly, they were divided into High-PPP1R3G group (47 cases), Medium-PPP1R3G group (29 cases) and Low-PPP1R3G group (3 groups). 14 cases) (Fig. 2A). The comparison of serum PPP1R3G levels showed that there was a statistical difference between the three groups before (F=247.869,P < 0.000), and further pairwise comparison found that there was a statistical difference between the groups (Figure 2B,P < 0.05,P < 0.01). ,P < 0.001), indicating that grouping according to the level of serum PPP1R3G content can obtain better clustering effect. In Figure 2, MMSE, Mini-Mental State Scale; MoCA, Montreal Cognitive Assessment Scale. One-way ANOVA was used to compare the means of the three groups of data. According to the test results of homogeneity of variance, 1: Dunnett's T3 method was used for unequal variance, and 2: LSD method was used for homogeneity of variance. The significance level was set asP < 0.05, *P <0.05, **P < 0.01, ***P < 0.001.
参照图3，人口统计学信息、临床特征及疾病情况如图3所示。三组衰老人群在年龄、性别、患糖尿病比例、吸烟、饮酒史上无统计学差异(P＞0.05)。在教育程度（年）、高中及以上学历比例和患高血压比例在明显差异。进一步分析发现:High-PPP1R3G组、Medium-PPP1R3G组、Low-PPP1R3G组在受教育程度（年）均存在两两差异(P＜0.05)；图3中A：卡方检验；B：单因素方差分析（one-wayANOVA）；C：非参数检验:Kruskal-Wallis检验；教育程度（年）使用Bonferroni法校正P值对两组进行比较。Referring to FIG. 3 , demographic information, clinical characteristics, and disease conditions are shown in FIG. 3 . There were no significant differences in age, gender, proportion of diabetes, smoking and drinking history among the three groups of aging population (P > 0.05). Significant differences were found in the educational level (years), the proportion of high school education and above, and the proportion of hypertension. Further analysis found that there were pairwise differences in educational attainment (years) in the High-PPP1R3G group, Medium-PPP1R3G group, and Low-PPP1R3G group (P <0.05); in Figure 3, A: Chi-square test; B: One-way variance Analysis (one-way ANOVA); C: Nonparametric test: Kruskal-Wallis test; education level (years)P values were compared using Bonferroni's method.
参照图4和图5，在三组衰老人群总体认知功能测试的组间比较中，各组间MMSE评分有统计学差异（χ2＝66.57，P＜0.001），进一步两两比较结果显示，High-PPP1R3G与Medium-PPP1R3G组，High-PPP1R3G与Low-PPP1R3G组，Medium-PPP1R3G组与Low-PPP1R3G组间差异均有统计学意义，未调整P值分别为P＜0.017、P＜0.001、P＜0.001，过Bonferroni法调整后的P值分别为P＜0.05、P＜0.001、P＜0.001，Spearman相关分析显示血清PPP1R3G含量与MMSE评分显著正相关性（R2=0.318，P＜0.0001）；MoCA评分在三组间的比较与MMSE评分类似，组间差异同样具有统计学意义（χ2＝247.87，P＜0.001），Person相关分析显示血清PPP1R3G含量与MoCA评分显著正相关性（R2=0.214，P＜0.0001）；图4中MMSE，简易智能状态量表；MoCA，蒙特利尔认知评估量表。MoCA满足正态分布，采用单因素方差分析（one-wayANOVA）；MMSE量表评分不满足正态分布，使用非参数检验Kruskal-Wallis检验对三组进行比较，结果需Bonferroni经校正，显著性水平设定为P＜0.05。Referring to Figure 4 and Figure 5, in the comparison between the three groups of aging population overall cognitive function test, there was a statistically significant difference in the MMSE score between the groups (χ2=66.57,P < 0.001). Further pairwise comparisons showed that High -PPP1R3G and Medium-PPP1R3G groups, High-PPP1R3G and Low-PPP1R3G groups, and Medium-PPP1R3G and Low-PPP1R3G groups were all significantly different, and the unadjustedP values wereP ＜ 0.017,P ＜ 0.001,P ＜ 0.001, the P values adjusted by the Bonferroni method wereP ＜ 0.05,P ＜ 0.001, andP ＜ 0.001, respectively. Spearman correlation analysis showed that the serum PPP1R3G content was significantly positively correlated with the MMSE score (R2 =0.318,P ＜ 0.0001); MoCA The comparison of scores among the three groups was similar to the MMSE score, and the difference between the groups was also statistically significant (χ2=247.87 ,P < 0.001).P <0.0001); MMSE in Figure 4, Mini-Mental State Scale; MoCA, Montreal Cognitive Assessment Scale. MoCA satisfies the normal distribution, and one-way ANOVA is used; the MMSE scale score does not satisfy the normal distribution, the nonparametric test Kruskal-Wallis test is used to compare the three groups, and the results need to be corrected by Bonferroni, and the significance level Set toP < 0.05.
参照图6及图7，为了找寻老年认知功能障碍的危险因素，我们进行了回归分析，在衰老人群认知障碍的二元Logistic回归分析模型中纳入了性别、年龄、教育程度(年)、高中及以上学历比例、患高血压比例、患糖尿病比例、吸烟、饮酒史和PPP1R3G（ng/ml）等变量，用似然比检验（LRT）进行了分析。霍斯默-莱梅肖（H-L）检验P＞0.05提示回归模型可以很好地拟合实验数据，结果显示对认知有显著影响的变量是PPP1R3G（ng/ml）和教育程度(年)。逐步线性回归分析显示，对MMSE评分产生影响的变量为PPP1R3G（ng/ml）、教育程度(年)、糖尿病，调整后R2为0.406；对MoCA评分产生影响的变量为PPP1R3G（ng/ml）和教育程度(年)，调整后R2为0.521。其中，PPP1R3G（ng/ml）和教育程度(年)对MMSE和MoCA的得分均产生了显著影响，患糖尿病比例仅对MMSE量表评分产生了影响；图6中衰老人群的二元Logistic回归分析，似然比检验（LRT）被用来评估ARCI的影响因素，性别、年龄、教育程度(年)、高中及以上学历比例、患高血压比例、患糖尿病比例、吸烟、饮酒史和PPP1R3G（ng/ml）等因素被纳入了方程，结果显示PPP1R3G（ng/ml）、教育程度(年)对老年人的认知功能产生了显著的影响；图7中PPP1R3G：蛋白磷酸酶-1调节亚基3G。用逐步线性回归来评估衰老人群MMSE、MoCA得分的影响因素。性别、年龄、教育程度(年)、高中及以上学历比例、患高血压比例、患糖尿病比例、吸烟、饮酒史和PPP1R3G（ng/ml）等因素被纳入了方程。图7为老年人MMSE评分、MoCA评分评分影响因素的逐步线性回归分析，结果表明PPP1R3G（ng/ml）、教育程度(年)、患糖尿病比例对老年人的MMSE得分产生了显著影响；PPP1R3G（ng/ml）、教育程度(年)对老年人患者的MoCA产生了显著的影响。Referring to Figure 6 and Figure 7, in order to find the risk factors of cognitive impairment in the elderly, we conducted regression analysis, and included gender, age, education level (years), gender, age, education level (years), Variables such as the proportion of high school education or above, the proportion of hypertension, the proportion of diabetes, smoking, drinking history, and PPP1R3G (ng/ml) were analyzed using the likelihood ratio test (LRT). Hosmer-Lameshaw (HL) testP > 0.05 indicated that the regression model could fit the experimental data well, and the results showed that the variables that had a significant impact on cognition were PPP1R3G (ng/ml) and education level (years). Stepwise linear regression analysis showed that the variables affecting the MMSE score were PPP1R3G (ng/ml), education level (years), and diabetes, with an adjusted R2 of 0.406; the variable affecting the MoCA score was PPP1R3G (ng/ml) and educational attainment (years), the adjusted R2 was0.521 . Among them, PPP1R3G (ng/ml) and education level (years) had a significant impact on the scores of MMSE and MoCA, and the proportion of diabetes only had an impact on the scores of the MMSE scale; the binary logistic regression analysis of the aging population in Figure 6 , Likelihood Ratio Test (LRT) was used to evaluate the influencing factors of ARCI, gender, age, education level (years), proportion of high school education or above, proportion of hypertension, proportion of diabetes, smoking, drinking history and PPP1R3G (ng Factors such as /ml) were incorporated into the equation, and the results showed that PPP1R3G (ng/ml) and education level (years) had a significant impact on the cognitive function of the elderly; PPP1R3G: protein phosphatase-1 regulatory subunit in Figure 7 3G. Stepwise linear regression was used to evaluate the influencing factors of MMSE and MoCA scores in aging population. Factors such as gender, age, education level (years), proportion of high school education or above, proportion of hypertension, proportion of diabetes, smoking, drinking history, and PPP1R3G (ng/ml) were included in the equation. Figure 7 shows the stepwise linear regression analysis of the factors affecting the MMSE score and MoCA score of the elderly. The results show that PPP1R3G (ng/ml), education level (years), and the proportion of diabetes have a significant impact on the MMSE score of the elderly; PPP1R3G ( ng/ml), education level (years) had a significant effect on MoCA in elderly patients.
参照图8，通过建立ROC曲线对PPP1R3G及复合指标预测ARCI的效力进行了分析，以评价其诊断ARCI的临床价值。在对ARCI的预测诊断中包括两组患者，分别为无认知障碍组及ARCI组，其区分是根据MMSE、MoCA的综合评分作为评判。PPP1R3G血清水平预测ARCI的ROC曲线(AUC=0.765，P＜0.001，95%CI：0.664-0.866)。我们进一步探讨了PPP1R3G及复合指标是否对ARCI有更好的诊断价值，通过逐步线性回归分析进行评价，ROC分析进行比较，PPP1R3G联合教育程度预测ARCI的ROC曲线结果(AUC=0.865，P＜0.001，95%CI：0.785-0.945)，而PPP1R3G、教育程度、患糖尿病比例预测ARCI的ROC曲线结果(AUC=0.847，P＜0.001，95%CI：0.763-0.931)，表明PPP1R3G联合教育程度诊断效果最优。建立PPP1R3G预测ARCI的受试者工作特征曲线（ReceiverOperatingCharacteristicCurve，ROC），曲线下面积（AreaUnderCurve，AUC）为0.765，P＜0.001，所以血清PPP1R3G可作为ARCI的诊断标记物，血清PPP1R3G可以有效地预测ARCI；图9中Model1线表示PPP1R3G预测ARCI的ROC曲线，AUC＝0.765，95%CI：0.664-0.866；Model2线为复合指标预测ARCI的ROC曲线，复合物＝(PPP1R3G、教育程度)，AUC=0.865，P＜0.001，95%CI：0.785-0.945；Model3线为复合物预测ARCI的ROC曲线，复合指标＝(PPP1R3G、教育程度、患糖尿病比例)，AUC=0.847，P＜0.001，95%CI：0.763-0.931。Referring to Fig. 8, the efficacy of PPP1R3G and composite indexes in predicting ARCI was analyzed by establishing ROC curve to evaluate its clinical value in diagnosing ARCI. Two groups of patients were included in the prediction and diagnosis of ARCI, namely the non-cognitive impairment group and the ARCI group, which were distinguished according to the comprehensive scores of MMSE and MoCA. PPP1R3G serum levels predicted the ROC curve of ARCI (AUC=0.765,P <0.001, 95%CI: 0.664-0.866). We further explored whetherPPP1R3G and composite indicators have better diagnostic value for ARCI, and evaluated by stepwise linear regression analysis and compared with ROC analysis. 95%CI: 0.785-0.945), and PPP1R3G, education level, and the proportion of diabetes mellitus predicted the ROC curve results of ARCI (AUC=0.847,P <0.001, 95%CI: 0.763-0.931), indicating that PPP1R3G combined with education level has the best diagnostic effect excellent. The receiver operating characteristic curve (ROC) of PPP1R3G for predicting ARCI was established, and the area under the curve (AreaUnderCurve, AUC) was 0.765,P < 0.001, so serum PPP1R3G can be used as a diagnostic marker for ARCI, and serum PPP1R3G can effectively predict ARCI ; The Model1 line in Figure 9 represents the ROC curve of PPP1R3G to predict ARCI, AUC=0.765, 95%CI: 0.664-0.866; the Model2 line is the ROC curve of the composite index to predict ARCI, composite=(PPP1R3G, education level), AUC=0.865 ,P ＜ 0.001, 95%CI: 0.785-0.945; Model3 line is the ROC curve of the composite prediction ARCI, composite index=(PPP1R3G, education level, proportion of diabetes), AUC=0.847,P ＜0.001, 95%CI: 0.763-0.931.
以上，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，根据本发明的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明的保护范围之内。The above are only preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Equivalent replacements or changes to the inventive concept shall all fall within the protection scope of the present invention.
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