Chronic kidney disease (CKD) stage 5 is frequently accompanied by systemic inflammation, and peripheral blood mononuclear cells (PBMCs) play an important role. To define the epitranscriptomic features of PBMC small RNAs in CKD stage 5, we profiled N6-methyladenosine (m6A) using small RNA modification microarrays. A total of 158 miRNAs, 149 pre-miRNAs, and 197 tsRNAs showed differential m6A modification. Enrichment analysis implicated PI3K-Akt, p53 signalling, and leukocyte transendothelial migration. Integrating target prediction with GEO transcriptomic datasets identified IRF1 and RUNX2 as key targets. MeRIP confirmed reduced m6A in miR-205-3p and miR-93-5p, accompanied by upregulation of RUNX2 and downregulation of IRF1 by qPCR. These results define an altered m6A-modification profile of PBMC small RNAs in CKD stage 5 and highlight miRNA-target gene axes with potential biomarker utility.
IgA nephropathy (IgAN) is the most common primary glomerular disease, but the mechanisms of renal injury and the role of necroptosis in IgAN remain unclear. In this exploratory study, we performed nanoparticle-based enrichment proteomics to profile low-abundance serum proteins an in-house cohort, focusing on curated necroptosis-related proteins (NRPs). By integrating bulk transcriptomic and single-cell sequencing data (scRNA-Seq), we identified key co-expression modules using weighted gene co-expression network analysis (WGCNA), gene set variation analysis (GSVA), and Mfuzz clustering, and assessed their associations with clinical indices of renal injury. Transcriptomic analysis identified necroptosis as the most significantly dysregulated PCD pathway in IgAN, with GSVA scores positively correlated with urinary protein-to-creatinine ratio, suggesting that necroptosis activity is associated with early renal injury. Proteomic profiling identified 1,627 differentially expressed proteins (DEPs; FDR < 0.05, |fold change|> 1.5), of which 156 were NRPs. WGCNA identified the MEbrown module as strongly associated with IgAN and Oxford T-score (the strongest pathological predictor of kidney injury). Integration of proteomic, transcriptomic, and network data identified BTK, SYK, and PLEC as key upregulated necroptosis-related proteins. scRNA-seq analysis revealed that BTK and SYK were primarily expressed in immune cells. Their expression levels showed strong inverse correlations with eGFR, and receiver operating characteristic (ROC) analysis indicated high diagnostic performance. In summary, our study demonstrates marked dysregulation of the necroptosis pathway in IgAN, while acknowledging that the elevated BTK and SYK reflect both canonical immune activation and concurrent necroptosis-related renal injury. These molecules correlate with disease severity and renal function decline, supporting their potential as exploratory serum biomarkers and candidate therapeutic targets. Our findings provide mechanistic insights linking immune dysregulation and programmed cell death in IgAN, and support further development of non-invasive diagnostic and therapeutic strategies in larger, independent cohorts.
BACKGROUND:This study analyzed global, regional, and national trends in the burden of Type 1 diabetes mellitus (T1DM)-related chronic kidney disease (CKD) from 1990 to 2021, stratified by sociodemographic development level. METHODS:Data on T1DM-related CKD incidence, prevalence, disability-adjusted life years (DALYs), and mortality were obtained from the Global Burden of Disease, Injury, and Risk Factor Study (GBD) 2021 system. Joinpoint regression analysis, health inequalities, frontier analysis, decomposition analysis, age-period-cohort modeling, and Bayesian age-period-cohort (BAPC) modeling were applied to assess disease burden trends and their associations with the sociodemographic index (SDI). RESULTS:From 1990 to 2021, the incidence and prevalence of T1DM-related CKD increased, mortality changed little, and DALYs declined. The burden was consistently higher in men than in women. Age-standardized mortality rates (ASMR) and age-standardized DALYs rates (ASDR) were highest in middle SDI countries. Across SDI levels, absolute inequality increased whereas relative inequality decreased. Frontier analysis indicated widening effective disparities with sociodemographic development. Population aging was a major driver of the rising burden. BAPC projections suggested a future decline in both mortality and DALYs. CONCLUSION:The global burden of T1DM-related CKD increased between 1990 and 2021, with men disproportionately affected. Absolute inequality across regions rose, while relative inequality decreased. Disparities became more pronounced with higher sociodemographic development. Projections indicate that mortality and DALYs may decline by 2050.
BACKGROUND:To evaluate the accuracy of implant placement assisted by a dynamic navigation system, as well as its influencing factors and learning curve. METHODS:At Macao We Care Dental Center, 55 cases of implant placement using dynamic navigation were retrospectively evaluated. To evaluate their accuracy, the apex, tip, and angle deviations of preoperatively planned and postoperatively placed implants were measured. The effects of the upper and lower jaws, different sites or lateral locations of dental implants, and the length and diameter of the implants on accuracy were analyzed, as well as the variation in accuracy with the increase in the number of surgical procedures performed by dentists. RESULTS:The implant had an apex deviation of 1.60 ± 0.94 mm, a tip deviation of 1.83 ± 1.03 mm, and an angle deviation of 3.80 ± 2.09 mm. Statistical differences were observed in the tip deviation of implants at different positions based on three factors: jaw position, lateral location, and tooth position (P < 0.05). The tip deviation of the anterior teeth area was significantly greater than those of the premolar and molar areas. There were no statistically significant differences in apex deviation, tip deviation, or angle deviation between the implants of different diameters and lengths (P > 0.05). There were significant differences in the angle deviation between the final 27 implants and the first 28 implants. Learning curve analysis revealed that angle deviation was negatively correlated with the number of surgical procedures, whereas the regression of apex deviation and tip deviation did not differ statistically. CONCLUSIONS:The accuracy of dynamic navigation-assisted dental implants meets the clinical needs and is higher than that of traditional implants. Different jaw positions, lateral locations, and implant diameters and lengths had no effect on the accuracy of the dental implants guided by the dynamic navigation system. The anterior teeth area had a larger tip deviation than the posterior teeth area did. As the number of dynamic implantation procedures performed by the same implant doctor increased, the angle deviation gradually decreased.
The effect of trace solvent bisphenol A (BPA) in polyether sulfone hollow fiber membrane Enttex™-16LF (E60) (produced by 3 M) low-throughput dialyzer was tested in this study. Animal experiments were conducted to evaluate its genotoxicity, carcinogenicity, and teratogenicity upon chronic exposure. The dialyzer was operated at 200 mL/min and 400 mL/min and coupled with LC-20AT liquid chromatography to detect BPA, which showed that the BPA content was less than 5 μ g/kg/d at both flow rates. In animal experiments, the tolerable intake (T.I.) was calculated to be 0.5 μ g/kg/d. With hemodialysis three times per week, the average patient weight was calculated at 70 kg, and the average daily BPA exposure was 0.0306 μ g/kg/d. The risk of residual BPA was within the acceptable limit with polyether sulfone membrane Enttex™-16LF (E60) hollow fiber dialyzer from 3 M, without inducing risk for disability, teratogenicity, or genotoxicity.
Background:Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease with multiple and complex pathogenic mechanisms. Currently, renal biopsy is considered the gold standard for diagnosing membranous nephropathy. However, there were limitations to the renal puncture biopsy, such as the relatively high cost, longer time consuming, and the risk of invasive procedures. We investigated the profile of serum metabolites in IMN patients based on the UHPLC-QE-MS metabolomics technique for exploring the potential disease biomarkers and clinical implementation. Methods:In our research, we collected serum samples from healthy control (n = 15) and IMN patients (n = 25) to perform metabolomics analysis based on the UHPLC-QE-MS technique. Result:We identified 215 differentially expressed metabolites (DEMs) between the IMN and healthy control (HC) groups. Furthermore, these DEMs were significantly identified in histidine metabolism, arginine and proline metabolism, pyrimidine metabolism, purine metabolism, and steroid hormone biosynthesis. Several key DEMs were significantly correlated with the level of clinical parameters, such as serum albumin, IgG, UTP, and cholesterol. Among them, dehydroepiandrosterone sulfate (DHEAS) was considered the reliable diagnostic biomarker in the IMN group. There was an increased abundance of actinobacteria, phylum proteobacteria, and class gammaproteobacterial in IMN patients for host-microbiome origin analysis. Conclusion:Our study revealed the profiles of DEMs from the IMN and HC groups. The result demonstrated that there were disorders of amino acids, nucleotides, and steroids hormones metabolism in IMN patients. The down-regulation of DHEAS may be associated with the imbalance of the immune environment in IMN patients. In host-microbiome origin analysis, the gut microbiota and metabolite disturbances were present in IMN patients.
随着数字化技术的发展,牙种植动态导航系统在口腔领域展现出巨大潜力.其在术前可以帮助医生进行合理的种植方案设计,术中实时追踪钻针的三维位置,全程监控种植位点、角度和深度.相对于静态导板技术,动态导航以其术前扫描当日可完成种植计划和手术、术中实时可视化追踪等优点,在某些病例中,动态导航引导种植是较好的选择,弥补了静态导板的不足.本文就国内外动态导航系统的结构、在口腔的应用、精度研究以及与静态导板比较等方面作一综述,旨在为口腔临床和基础研究提供帮助.
Object. The diagnostic superiority of functional magnetic resonance imaging (fMRI) over temporomandibular joint disc (TMJ) changes was investigated by comparing the diagnostic results of magnetic resonance imaging (MRI) and DC/TM. Methods. DC/TMD clinical questionnaire diagnosis was conducted for 30 patients with temporomandibular disorder (TMD) and 11 asymptomatic volunteers who were admitted to the Department of Oral Medicine of the First Hospital affiliated with Jinan University from June 2020 to June 2021. At the same time, MRI scanned the opening and closed positions to obtain the image information of the articular disc and compared the diagnostic difference between MRI and DC/TMD to the position of the articular disc through statistical analysis. Results. The probability of DC/TMD’s diagnosis of reusable/nonreusable anterior disc displacement (ADD) was 80.1% and 62.7%, respectively. Conclusion. DC/TMD’s diagnosis of abnormal articular disc position is less accurate than MRI testing. Therefore, the diagnosis of these two diseases for DC/TMD examination is of little significance, and MRI examination is required at the same time. It can improve diagnosis specificity and sensitivity, reduce missed diagnosis and misdiagnosis rates to ensure that true positive patients can be detected in time, and establish a basis for clinical diagnosis and treatment.
某滨海核电厂不锈钢管道发生腐蚀,影响管道的稳定运行.本文从不锈钢管道的成分、金相、涂层老化等方面对不锈钢腐蚀原因进行了分析,得出不锈钢的腐蚀机理为点蚀,然后对不锈钢管道的点蚀影响因素进行了讨论,最后提出了解决措施.
Background Proficient mismatch repair (pMMR) colorectal adenocarcinoma (CRAC) metastasizes to a greater extent than MMR-deficient CRAC. Prognostic biomarkers are preferred in clinical practice. However, traditional biomarkers screened directly from sequencing are often not robust and thus cannot be confidently utilized. Methods To circumvent the drawbacks of blind screening, we established a new strategy to identify prognostic biomarkers in the conserved and specific oncogenic pathway and its regulatory RNA network. We performed RNA sequencing (RNA-seq) for messenger RNA (mRNA) and noncoding RNA in six pMMR CRAC patients and constructed a glycosylation-related RNA regulatory network. Biomarkers were selected based on the network and their correlation with the clinicopathologic information and were validated in multiple centers (n = 775). Results We constructed a competing endogenous RNA (ceRNA) regulatory network using RNA-seq. Genes associated with glycosylation pathways were embedded within this scale-free network. Moreover, we further developed and validated a seven-glycogene prognosis signature, GlycoSig (B3GNT6, GALNT3, GALNT8, ALG8, STT3B, SRD5A3, and ALG6) that prognosticate poor-prognostic subtype for pMMR CRAC patients. This biomarker set was validated in multicenter datasets, demonstrating its robustness and wide applicability. We constructed a simple-to-use nomogram that integrated the risk score of GlycoSig and clinicopathological features of pMMR CRAC patients. Conclusions The seven-glycogene signature served as a novel and robust prognostic biomarker set for pMMR CRAC, highlighting the role of a dysregulated glycosylation network in poor prognosis.
某核电项目,安装两台百万汽轮发电机组,汽轮发电机机组安装结束至正式运行间隔时间长,同时由于项目所处位置在沿海地区,空气湿度达,空气中盐分含量也比较高,如果汽轮发电机组保养不当,必然会加重设备腐蚀程度.以设备维修保养手册为基础,参考同类型机组,制定了详细的保养程序,减缓腐蚀,确保了机组在长期停运期间的良好状态.
通过对秦山二厂2号机组发生的自动准同期并网系统故障的分析,系统的总结了类似发电机不能并网故障的处理思路和处理方法,同时提出减少和防止类似事故再次出现的良好建议。
从理论上详细阐述了进相运行的特点,分析了同步发电机稳定安全进相运行需要解决的问题,指出同步发电机进相运行对电网无功调节、更灵活有效的网络接线方式安排以及解决因电压过高对有功负荷的束缚具有的实际意义,并提出在进相运行过程中应关注的内容。
本文介绍了秦山第二核电厂汽机调节油系统的功能、油动机的工作原理,并对油动机各组成部件的作用进行了说明;以及从工作原理角度详细阐述了汽机调节油系统的特点,分析了MOOG阀故障在机组运行时的现象及处理方法。
凝汽器作为二回路的一个重要设备,它对汽轮机的正常经济运行起着至关重要的作用。秦山二期的凝汽器有5800根钛管,在长期的运行中一旦其中某些钛管破损,就有可能使海水泄露入凝汽器,随之带入SG(蒸汽发生器)二次侧,使二次侧水质变差,钠、氯离子浓度高会导致蒸汽发生器传热管腐蚀,引起蒸汽发生器破管,后果十分严重。所以,控制好凝汽器钛管的运行,对机组的稳定运行和电厂经济效益显得非常重要。
本文介绍了600MW发电机组双流环密封油系统日常运行中常见问题,分析密封油系统日常运行注意事项和各种风险的应对措施,以提高密封油系统运行的可靠性,进而有利于机组的安全运行和事故工况下对重要设备的保护。
常规岛暖通系统设备种类和运行方式比较多,温度控制各异,随着季节改变需要切换通风系统运行模式,以保证相关设备正常运行和工作人员适宜工作的环境。本文简述了常规岛暖通系统的组成分布、运行、切换及目前存在的问题,同时提出部分常规岛通风运行方式改变的建议。