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31.
Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up.A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected.Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014–0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin–angiotensin system blockade were significantly associated with declines in renal function.In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function. 相似文献
32.
目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征,为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统(Hospital Information System,HIS)中,出院诊断为“乳腺癌”的患者用药信息,采用SAS9.3统计软件,对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者,平均年龄(50.93者,平均年龄)岁;多以门诊入院,入院病情以“一般”为主;合并疾病主要为高血压,骨肿瘤,联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主;中医辨证以痰瘀互结证,气阴两虚证,肝气淤滞证,脾气亏虚证型最为常见,临床清热解毒剂、益气扶正剂,活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗,联用药物广泛,临床治疗基本符合临床指南。 相似文献
33.
34.
Yaobin Ouyang Gongmeizi Liu Wenting Xu Zhen Yang Nianshuang Li Chuan Xie Chun Zhou Jiang Chen Yin Zhu Junbo Hong Nonghua Lu 《Oncology Letters》2021,21(2)
Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development. 相似文献
35.
Feng He Yuanjun Ma Shi Li Haozhe Ren Qian Liu Xiaohua Chen Hui Miao Tao Ye Qian Lu Zuge Yang Tianle Li Xin Tong Hongxu Yang Mian Zhang Helin Wang Yazhou Wang Shibin Yu 《Journal of bone and mineral research》2022,37(5):1044-1055
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
36.
Mengdie Jiang Bihan Wu Yongbing Sun Yanhuai Ding Yixi Xie 《Toxicology mechanisms and methods》2019,29(4):291-299
In a biological microenvironment, free fatty acids (FFA) as ubiquitous biological molecules might interact with nanoparticles (NPs) and consequently change the toxicological responses. However, whether the chemical structures of FFA could influence their interactions with NPs remain unknown. This study investigated the interactions between ZnO NPs and saturated or unsaturated FFA (complexed to BSA), namely stearic acid (SA, C18:0), oleic acid (OA, C18:1), and α-linolenic acid (ALA, C18:3). It was shown that BSA, SA, OA, and ALA increased the atomic force microscope (AFM) heights as well the polydispersity index (PDI) of ZnO NPs. BSA modestly protected THP-1 macrophages from ZnO NP exposure, whereas OA and ALA led to relatively less cyto-protective effects of BSA. Moreover, only co-exposure to ZnO NPs and SA significantly promoted the release of interleukin-8. BSA, SA, OA, and ALA equally changed intracellular ROS and Zn ions associated with ZnO exposure, but co-exposure to ZnO NPs and OA/ALA particularly activated the expression of endoplasmic reticulum stress-apoptosis genes. In combination, these results showed that FFA could influence the colloidal aspects and toxicological signaling pathway of ZnO NPs, which is dependent on the number of unsaturated bonds of FFA. 相似文献
37.
痘病毒是自然界普遍存在的DNA病毒,能够高效表达外源基因,诱导较强的细胞免疫和体液免疫,受到基因治疗学者的广泛关注。痘病毒发生同源重组的概率较低,所以有效地筛选和纯化痘病毒十分重要。目前常用的筛选重组痘病毒方法有基于CRISPR进行筛选;根据报告基因GFP、LacZ、GPT等进行筛选;利用TK-和Brdu结合荧光进行筛选;利用药物抗性基因与荧光或显色基因融合,即可在药物筛选的同时观察荧光或显色基因表达情况。本文旨在对目前常用的痘病毒的筛选纯化方法进行综述。 相似文献
38.
The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the Peff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the Peff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the Peff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The Peff of CHS‐IVa in the duodenum was 1.76 × 10?3 to 2.00 × 10?3 cm/min. The Peff of CHS‐IVa in the jejunum was 1.26 × 10?3 to 1.39 × 10?3 cm/min. The Peff of CHS‐IVa in the ileum was 1.25 × 10?3 to 1.31 × 10?3 cm/min. The Peff of CHS‐IVa in the colon was 1.02 × 10?3 to 1.08 × 10?3 cm/min. There was no statistical difference of the Peff in the four segments at different CHS‐IVa concentrations. The Peff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported Peff (3.00 × 10?3 cm/min) in the jejunum. The Peff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP. 相似文献
39.
40.
目的:对比解剖性肝脏体积(ALV)和功能性肝脏体积(FLV)与肝功能Child-Pugh分级的相关性。方法:选择温州医科大学附属第二医院育英儿童医院2014年1月至2019年4月同时行增强CT和Gd-EOB-DTPA增强MRI扫描的肝硬化患者25例。对所有患者进行肝功能Child-Pugh评分,检测所有入组患者每个肝段的Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号对比增强率(CER),以CT扫描的数据为基础利用MI-3DVS计算每个肝段的ALV和全肝的FLV。分析ALV和FLV与肝功能Child-Pugh分级的相关性。结果:肝功能Child-Pugh分级与ALV呈负相关(r=-0.792,P<0.001),曲线拟合的决定系数(R2)=0.63;肝功能Child-Pugh分级与FLV亦呈负相关(r=-0.911,P<0.001),曲线拟合的R2=0.80。FLV与肝功能Child-Pugh分级有更显著的负相关性。结论:结合Gd-EOB-DTPA增强MRI平扫期和肝胆特异期的信号CER和ALV计算所得的FLV较ALV能更好地反映肝脏的功能状态。 相似文献