Background: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies. Methods: The methodology included colocalization analysis, crossphenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses. Results: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg=-0.0982, P=0.0007; rg=-0.101, P=0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits. Conclusion: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

BACKGROUND:Type 2 diabetes-associated cognitive dysfunction (DCD) is a chronic complication of diabetes that has gained international attention. The medicinal compound Banxia Xiexin Decoction (BXXXD) from traditional Chinese medicine (TCM) has shown potential in improving insulin resistance, regulating endoplasmic reticulum stress (ERS), and inhibiting cell apoptosis through various pathways. However, the specific mechanism of action and medical value of BXXXD remain unclear. METHODS:We utilized TCMSP databases to screen the chemical constituents of BXXXD and identified DCD disease targets through relevant databases. By using Stitch and String databases, we imported the data into Cytoscape 3.8.0 software to construct a protein-protein interaction (PPI) network and subsequently identified core targets through network topology analysis. The core targets were subjected to Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results were further validated through in vitro experiments. RESULTS:Network pharmacology analysis revealed the screening of 1490 DCD-related targets and 190 agents present in BXXXD. The topological analysis and enrichment analysis conducted using Cytoscape software identified 34 core targets. Additionally, GO and KEGG pathway analyses yielded 104 biological targets and 97 pathways, respectively. BXXXD exhibited its potential in treating DCD by controlling synaptic plasticity and conduction, suppressing apoptosis, reducing inflammation, and acting as an antioxidant. In a high glucose (HG) environment, the expression of JNK, Foxo3a, SIRT1, ATG7, Lamp2, and LC3 was downregulated. BXXXD intervention on HT22 cells potentially involved inhibiting excessive oxidative stress, promoting neuronal autophagy, and increasing the expression levels of JNK, SIRT1, Foxo3a, ATG7, Lamp2, and LC3. Furthermore, the neuroprotective effect of BXXXD was partially blocked by SP600125, while quercetin enhanced the favorable role of BXXXD in the HG environment. CONCLUSION:BXXXD exerts its effects on DCD through multiple components, targets, levels, and pathways. It modulates the JNK/SIRT1/Foxo3a signaling pathway to mitigate autophagy inhibition and apoptotic damage in HT22 cells induced by HG. These findings provide valuable perspectives and concepts for future clinical trials and fundamental research.

BACKGROUND:Diabetic cognitive dysfunction (DCD) is emerging as a chronic complication of diabetes that is gaining increasing international recognition. The traditional Chinese medicine (TCM) formulation, Tangzhiqing decoction (TZQ), has shown the capacity to modulate the memory function of mice with DCD by ameliorating insulin resistance. Nevertheless, the precise mechanism underlying the effects of TZQ remains elusive. METHODS:The chemical constituents of TZQ were screened using TCMSP databases, and DCDassociated disease targets were retrieved from various databases. Subsequently, core targets were identified through network topology analysis. The core targets underwent analysis using Gene Ontology (GO) functional annotations and enrichment in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Models were established through high-fat and high-glucose diet feeding along with intraperitoneal injection of streptozotocin (STZ). TZQ and metformin were administered at varying doses over 8 weeks. The Morris water maze was employed to evaluate the cognitive capabilities of each rat group, while indicators of oxidative stress and insulin were assessed in mice. Neuronal apoptosis in distinct groups of mice's hippocampi was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL), and western blot (WB) analysis was conducted to assess the expression of apoptosis- and autophagy-related proteins, including Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, LC3, p62, and Lamp2, within the hippocampus. RESULTS:TZQ exhibited the capacity to modulate neuronal autophagy, ameliorate endoplasmic reticulum stress, apoptosis, inflammation, and oxidative stress, as well as to regulate synaptic plasticity and conduction. TZQ mitigated cognitive dysfunction in mice, while also regulating hippocampal inflammation and apoptosis. Additionally, it influenced the protein expression of autophagy-related factors such as Bax, Bcl2, Caspase3, Caspase8, Beclin1, ATG7, and LC3. Notably, this modulation significantly reduced neuronal apoptosis in the hippocampus and curbed excessive autophagy. CONCLUSION:TZQ demonstrated a substantial reduction in neuronal apoptosis within the hippocampus and effectively suppressed excessive autophagy.

Background: While the link between hypothyroidism and disturbed sleep patterns has been recognized, the available data are inconsistent, making it difficult to establish causality. This study aimed to investigate the causal relationship between certain sleep traits and hypothyroidism. Methods: Using publicly available genomewide association study (GWAS) data, we applied linkage disequilibrium score regression (LDSC) to identify genetic associations between hypothyroidism and various sleep traits. Two-sample Mendelian randomization (MR) analysis was then conducted to assess the causal relationship between aberrant sleep features and the risk of hypothyroidism. The IVW, MR-Egger regression, weighted median, and weighted mode methods were used. To detect level polymorphism and outliers, MR-Egger regression and MR-PRESSO methods were employed. Results: A genetic association between hypothyroidism and nap during the day and getting up in morning (rg=-0.0982, p=0.0007; rg=-0.101, p=0.0001). In addition, a causal relationship between hypothyroidism and sleep duration (IVW, OR 1.5208, 95%CI: 0.1082-0.7304, P=0.0082) and getting up in morning (IVW, OR 1.8375, 95%CI: 0.3717-0.8452, P=4.73×10-7). Furthermore, the reverse MR analysis did not reveal any causal link between hypothyroidism and aberrant sleep traits. Conclusion: MR analysis demonstrated a causal link between hypothyroidism and certain aberrant sleep traits. Sleep duration should be considered as a potential factor in disease models for improving sleep quality and reducing the risk of hypothyroidism.

Objective: To estimate the survival and prognosis of patients with thyroid carcinoma (THCA) based on the Long non-coding RNA (lncRNA) traits linked to cuproptosis and to investigate the connection between the immunological spectrum of THCA and medication sensitivity. Methods: RNA-Seq data and clinical information for THCA were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We built a risk prognosis model by identifying and excluding lncRNAs associated with cuproptosis using Cox regression and LASSO methods. Both possible biological and immune infiltration functions were investigated using Principal Component Analysis (PCA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immunoassays. The sensitivity of the immune response to possible THCA medicines was assessed using ratings for tumor immune dysfunction and exclusion (TIDE) and tumor mutational burden (TMB). Results: Seven cuproptosis-related lncRNAs were used to construct our prognostic prediction model: AC108704.1, DIO3OS, AL157388.1, AL138767.3, STARD13-AS, AC008532.1, and PLBD1-AS1. Using data from TCGA’s training, testing, and all groups, Kaplan-Meier and ROC curves demonstrated this feature’s adequate predictive validity. Different clinical characteristics have varying effects on cuproptosis-related lncRNA risk models. Further analysis of immune cell infiltration and single sample Gene Set Enrichment Analysis (ssGSEA) supported the possibility that cuproptosis-associated lncRNAs and THCA tumor immunity were closely connected. Significantly, individuals with THCA showed a considerable decline in survival owing to the superposition effect of patients in the high-risk category and high TMB. Additionally, the low-risk group had a higher TIDE score compared with the high-risk group, indicating that these patients had suboptimal immune checkpoint blocking responses. To ensure the accuracy and reliability of our results, we further verified them using several GEO databases. Conclusion: The clinical and risk aspects of cuproptosis-related lncRNAs may aid in determining the prognosis of patients with THCA and improving therapeutic choices.

目的:基于生物信息学方法对糖尿病脑病(DE)的关键基因进行初步筛选,探索与其相关的潜在靶点、生物过程及通路,进而预测治疗DE的潜在中药.方法:运用GEO数据库筛选出基因芯片原始数据集GSE161355作为样本进行研究.基于R Studio软件的质量评估和差异分析筛选差异基因,应用DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析,利用Cytoscape软件进行关键靶点筛选及关键功能模块构建、可视化.通过将关键靶点与Coremine Medical数据库相互映射,筛选治疗DE的潜在中药.结果:通过对GSE161355基因原始数据集的预处理,从DE患者中筛选出326个显著性差异基因,差异基因主要参与学习、记忆、神经元突触传递、细胞分裂、蛋白质分泌、血管生成调节等生物过程,与神经活性配体-受体信号通路、细胞周期通路等存在关联.蛋白质-蛋白质相互作用(PPI)网络显示MCHR2、CXCR2、GNAI1、P2RY13、NPY1R、C3、LPAR4、OXTR、CHRM5、CDC7、ORC5、ORC4、CCNA1可作为治疗DE的潜在靶点,多方位、多维度、多层面参与炎症反应、细胞凋亡、内质网应激、血管生成等生物过程.通过中药预测筛选发现人参、熟地黄、西红花、银杏叶、黄连、郁金等可作为潜在来源.结论:通过对显著性差异基因和潜在核心靶点的分析促进了对DE发病机制的进一步理解和探索,为今后治疗和评估提供了新的方向和临床依据.

目的:探讨"糖脂清"对高糖诱导的HT22细胞损伤的保护作用机制.方法:将Wistar大鼠随机分成正常组和"糖脂清"、二甲双胍含药血清组,依据成人临床剂量进行灌胃,灌胃后取每组大鼠腹主动脉血并进行离心、灭活、过滤,由此制备不同剂量的"糖脂清"和二甲双胍大鼠含药血清.通过CCK-8法筛选干预HT22细胞最适造模高糖浓度和最佳干预时间,将生长稳定的HT22细胞分为空白组、模型组、二甲双胍含药血清组、低剂量含药血清组、中剂量含药血清组和高剂量含药血清组,造模组采用最适高糖浓度进行诱导,再对高糖环境下的HT22细胞给予"糖脂清"高、中、低剂量和二甲双胍含药血清进行干预,检测各组HT22细胞氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)和乳酸脱氢酶(LDH)含量;免疫荧光法和Hoechst 33342染色法检测神经元凋亡和Lamp2的表达;Western Blot法检测各组HT22细胞凋亡、自噬相关蛋白Bax、Bcl-2、Caspase-3、SIRT1和JNK表达水平.结果:"糖脂清"能够调节和改善小鼠海马HT22细胞在长期高糖环境下的生长和形态变化,升高SOD含量(P<0.01),降低MDA和LDH水平(P<0.01),对HT22细胞遭受的氧化损伤起到一定程度的保护作用;与模型组相比,"糖脂清"的干预可下调炎症凋亡、自噬相关因子Bax、Caspase-3、SIRT1、JNK蛋白的表达,上调Bcl-2、Lamp2蛋白表达水平(P<0.05).结论:"糖脂清"可显著缓解海马区域神经元凋亡和氧化应激异常状态,并在一定程度上抑制细胞自噬,调控自噬体与溶酶体的结合过程,这些结果为"糖脂清"成为改善2型糖尿病合并认知功能的有效药物提供了全新的思路和方向.

目的:探索中药方剂治疗糖尿病皮肤瘙痒症的用药规律,为临床组方用药提供参考.方法:运用中国知网、万方数据、维普期刊全文数据库检索中医药治疗糖尿病皮肤瘙痒症的文献,并对其进行筛选建立数据库,通过BM SPSS Modeler 18.0、SPSS Statistics 25.0进行数据挖掘,研究用药规律.通过检索中药系统药理学数据库与分析平台(TCMSP)、OMIM、Genecards、PharmGkb、Digsee数据库获得核心组方的有效成分及疾病靶点,利用Cytoscape 3.8.2软件构建"药物-有效成分-靶点-疾病"网络图,运用Stitch和String构建蛋白质-蛋白质相互作用网络,并对于网络拓扑分析获得核心靶点.筛选DAVID数据库对核心靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析.结果:共纳入文献159篇,涉及中药处方215剂,获得高频中药24味,当归-白芍-防风、当归-白芍-生地黄、当归-白芍-蒺藜、当归-川芎等核心药对14组,聚类分析得到8类,通过因子分析获得9个公因子,核心组方有效成分功共169个,药物潜在靶点263个,疾病潜在靶点519个,核心靶点7个,共获得83条GO生富集功能及25条KEGG信号通路.结论:中医药治疗糖尿病皮肤瘙痒症以养血疏风、活血化瘀、补脾益肾为原则,其核心药物治疗本病多涉及胰岛素抵抗、炎症反应、氧化应激等.

目的:系统评价温胆汤治疗糖尿病胃轻瘫的临床有效性、安全性及复发率等.方法:通过计算机及手工检索Pub Med、The Cochrane Library、Web of Science、中国知网、万方、维普及生物医学文献数据库,纳入2000年1月-2020年10月使用温胆汤治疗糖尿病胃轻瘫的随机对照试验(randomized controlled trial,RCT).采用Rev man 5.4软件进行Meta分析.结果:研究共纳入8篇文献,总计688例患者,Meta分析结果显示温胆汤治疗有效率(RR=1.32,95％CI[1.23,1.42],P＜0.00001)优于对照组,温胆汤治疗复发率(RR=0.31,95％CI[0.18,0.53],P＜0.0001)、不良反应发生率(RR=0.27,95％CI[0.11,0.67],P=0.005)低于对照组,空腹血糖(MD=-0.22,95％C1[-0.55,0.11],P=0.18＞0.05)差异无统计学意义.结论:温胆汤能提高糖尿病胃轻瘫临床有效率,且复发率跟不良反应发生率较低,安全性较高.但部分纳入文献质量偏低,临床病例相对有限,仍需大样本、高质量的随机对照试验验证.

目的:对运用血府逐瘀汤治疗糖尿病脑病的安全性和有效性进行评价.方法:计算机检索和手工检索Pub Med、Web of Science、The Cochrane Library、知网、万方、维普及生物医学文献数据库2000年1月～2020年4月期间有关血府逐瘀汤治疗糖尿病脑病的临床随机对照研究,选择符合标准的文献运用Rev Man 5.3软件分析.结果:研究共纳入11篇文献和838例患者,Meta分析显示血府逐瘀汤在有效率[OR=3.71,95％CI(2.42,5.70),P<0.00001]、患者神经功能缺损程度评分[MD=?4.52,95％CI(?5.10,?3.94),P<0.00001]、空腹血糖[MD=?1.05,95％CI(?1.51,?0.59),P<0.00001]、餐后2 h血糖[MD=?1.31,95％CI(?1.94,?0.69),P<0.00001]、糖化血红蛋白[MD=?0.94,95％CI(?1.15,?0.72),P<0.00001]、中医证候积分评分[MD=?2.44,95％CI(?3.82,?1.06),P=0.0005]、生活能力评分[MD=12.79,95％CI(8.79,16.79),P<0.00001]方面的改善效果明显优于西医常规治疗.结论:血府逐瘀汤能提高糖尿病脑病患者临床有效率,减轻患者脑部损害,降低血糖和糖化血红蛋白水平,具有良好的安全性.但部分纳入文献质量偏低,临床病例数较少,可能影响Meta分析结果的真实性,仍需高质量大样本的临床随机对照试验进一步验证.

本文旨在通过探讨中医药治疗糖尿病认知功能障碍的用药特点与规律,为临床用药提供新的参考.运用中国知网(CNKI)、万方数据(WF)、维普期刊全文数据库(VIP)、生物医学文献数据库(CBM)、及中国科学引文数据库(CSCD)检索自1999年1月至2020年10月收载的中医药治疗糖尿病认知功能障碍文献,经筛选后建立数据库,运用Microsoft Excel 2019、SPSS Modeler 18.0、SPSS Statistics 25.0软件进行数据挖掘,分析用药规律.通过检索TCM-SP、OMIM、TTD、Pharm Gkb和Drugbank数据库获得核心药物组合和疾病的有效活性成分,利用Cytoscape 3.8.0软件构建"化合物-靶点"作用网络图,运用Stitch和String构建蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape进行网络拓扑分析获得药物和疾病交互的核心靶点.筛选DAVID数据库对核心靶点进行GO和KEGG富集分析.结果 共纳入文献33篇,中药处方123首,获得高频中药20味,桃仁-红花、当归-桃仁-川芎、熟地黄-菟丝子-枸杞子等26对核心药物组合,通过因子分析提取8个公因子,聚类分析得到6类,得到核心组方的有效活性成分109个,药物潜在基因靶点1620个,疾病潜在基因靶点1490个,核心组方治疗疾病的核心靶点76个,涉及237条GO富集功能和96条KEGG通路.发现中医治疗糖尿病认知功能障碍以活血化瘀、化痰开窍、滋益固肾为原则,其核心药物治疗糖尿病认知功能障碍的作用机制可能与胰岛素抵抗、细胞凋亡、炎症反应、内质网应激等密切相关.

[目的]探究从肾论治2型糖尿病合并轻度认知障碍(mild cognitive impairment,MCI)的可行性,为2型糖尿病合并MCI的辨证及治疗思路提供参考.[方法]通过对古今消渴病相关文献资料的分析和归纳,根据脏腑功能及关系,分析肾在本病中的地位,总结归纳出治疗本病的辨证和治疗要点.[结果]以2型糖尿病的中医辨病辨证为基,总结出"肾本论""肾虚论",进一步得出2型糖尿病合并MCI的主病在肾,辨证应从肾入手,首辨肾阴虚、肾阳虚或肾阴阳两虚,再进行兼症辨治,治疗上应以补肾为主,辅以补气、化痰、逐瘀等.[结论]"肾虚"是2型糖尿病合并MCI发生发展的关键,从肾论治本病疗效可期,值得临床推广.

围绝经期综合征的发生会对女性身心健康造成影响,目前多采用激素替代治疗.中医药是治疗围绝经期综合征的有效方法.本文对近年来国内外有关中医药治疗围绝经期综合征文献报道进行归纳、整理和总结.通过中医药治疗可以改善围绝经期综合征临床症状,提升生活质量,为今后治疗提供思路.

近年来运用中医药治疗糖尿病认知功能障碍(diabetic?cognitive?dysfunction,DCD)取得一定的进展,主要包括辨证论治、专方论治、针刺治疗及中西医结合治疗等,为防治DCD提供了新的思路.目前中医治疗DCD虽取得良好的临床疗效,但仍存在一些问题.如何在中医理论指导下深度分析不同证型间存在的联系,结合相关基础和临床随机对照实验以寻找有效的干预方案,是未来研究的方向.