熊果酸对脂多糖作用下肺上皮细胞炎症因子表达的影响及机制研究

目的:熊果酸(ursolic acid,UA)对脂多糖(lipopolysaccharide,LPS)作用下人肺上皮细胞来源的A549细胞的生物学活性影响及潜在机制.方法:CCK-8检测不同浓度(10、50、100、150、200 μg/mL)UA对A549细胞增殖的影响.此外,检测浓度为10 μg/mL的UA作用于A549细胞不同时间点对细胞的增殖影响.荧光定量PCR检测UA对LPS作用下A549细胞的白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的mRNA表达.ELISA检测ERK、p38、JNK抑制剂对UA对LPS作用下A549细胞的IL-1β表达的影响,结果采用单因素方差分析.结果:UA能够显著抑制A549细胞的活性且呈浓度依赖性.CCK-8检测结果显示,UA作用A549细胞24h后,10 μg/mL的UA能够明显抑制A549细胞的活性(P＜0.05).此外,UA能够明显抑制LPS诱导的TNF-α、IL-1β、IL-6的mRNA表达(P＜0.05).其中,对LPS诱导的IL-1β抑制作用最为明显.ELISA结果显示,ERK、JNK信号通路抑制剂作用下并不能影响UA抑制炎症的效果,但p38信号通路抑制剂能显著逆转UA对LPS诱导的IL-1β的抑制作用(P＜0.05).p38信号通路的激活剂却可以逆转这种抑制作用(P＜0.05).结论:UA能够抑制LPS诱导的IL-1β,且通过p38信号通路作用.     

不同滴定方式使用芬太尼透皮贴剂对中重度癌痛患者家居治疗的临床观察

为了评价芬太尼透皮贴剂对中重度癌痛患者家居治疗的疗效及安全性,以及不同滴定方式对治疗效果和不良反应的影响,将全部在家接受治疗的784例患者,分为口服盐酸吗啡片滴定后转换为多瑞吉组（A组）及多瑞吉直接滴定组（B组）进行观察。记录其治疗前后疼痛强度、疼痛缓解度及不良反应。结果：A组543例总缓解率为99．1％,B组241例中,3例因严重不良反应无法耐受停止治疗,其余238例总缓解率为98．3％。不良反应中,B组恶心呕吐及头晕发生率较A组高,便秘、嗜睡和排尿困难等不良反应发生率两组相似。无呼吸抑制及精神依赖发生。初步研究结果提示,芬太尼透皮贴剂对中重度癌痛患者家居治疗的治疗效果满意。吗啡滴定后再转为多瑞吉治疗能减少嗜睡及恶心、呕吐等不良反应,提高患者的治疗依从性。     

Investigation on the Fatigue Crack Propagation of Medium-Entropy Alloys with Heterogeneous Microstructures

The behavior and the mechanism of fatigue crack propagation in CrCoNi medium-entropy alloys (MEAs) with heterogeneous microstructures were investigated in this paper. After cold-rolling and recrystallization annealing at different temperatures and times, five sets of heterostructured specimens were acquired with different recrystallization levels. Then, the structure characterizations of these five sets of specimens were carried out by nanoindentation testing and electron back-scatter diffraction (EBSD) mapping. Finally, the fatigue crack propagation tests were conducted on single edge crack specimens of these different heterogeneous microstructures. The experimental results indicate that the crack propagation rates of specimens with partial recrystallization microstructures are higher than those with complete recrystallization microstructures, and the effect on fatigue crack thresholds of these specimens is the opposite. The fatigue cracks grow along the slip planes or twin boundaries in recrystallization grains (RGs), which induced crack deflections and the roughness-induced crack closure effect. For this reason, the area percentage of recrystallization and the grain size of RGs have a great effect on the value of the fatigue crack growth threshold.     

Unveiling the Effect of CaF2 on the Microstructure and Transport Properties of Phosphosilicate Systems

As an effective flux, CaF₂ is beneficial in improving the fluidity of slag in the steel-making process, which is crucial for dephosphorization. To reveal the existence form and functional mechanism of CaF₂ in phosphosilicate systems, the microstructures and transport properties of CaO-SiO₂-CaF₂-P₂O₅ quaternary slag systems are investigated by molecular dynamics simulations (MD) combined with experiments. The results demonstrate that the Si-O coordination number does not vary significantly with the increasing CaF₂ content, but the P-O coordination number dramatically decreases. CaF₂ has a minor effect on the single [SiO₄] but makes the structure of the silicate system simple. On the contrary, F⁻ ions could reduce the stability of P-O bonds and promoted the transformation of [PO₄] to [PO₃F], which is beneficial for making the P element-enriched phosphate network structure more aggregated. However, the introduction of CaF₂ does not alter the tetrahedral character of the original fundamental structural unit. In addition, the results of the investigation of the transport properties show that the self-diffusion coefficients of each ion are positively correlated with CaF₂ content and arranged in the order of F⁻ > Ca²⁺ > O²⁻ ≈ P⁵⁺ > Si⁴⁺. Due to CaF₂ reducing the degree of polymerization of the whole melts, the viscosity decreases from 0.39 to 0.13 Pa·s as the CaF₂ content increases from 0% to 20%. Moreover, the viscosity of the melt shows an excellent linear dependence on the structural parameters.     

Patients with breath test positive are necessary to be identified from irritable bowel syndrome: a clinical trial based on microbiomics and rifaximin sensitivity

Background:As a non-invasive and effective diagnostic method for small intestinal bacterial overgrowth (SIBO), wild-use of breath test (BT) has demonstrated a high comorbidity rate in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and SIBO. Patients overlapping with SIBO respond better to rifaximin therapy than those with IBS-D only. Gut microbiota plays a critical role in both of these two diseases. We aimed to determine the microbial difference between IBS-D overlapping with/without SIBO, and to study the underlying mechanism of its sensitivity to rifaximin.Methods:Patients with IBS-D were categorized as BT-negative (IBSN) and BT-positive (IBSP). Healthy volunteers (BT-negative) were enrolled as healthy control. The patients were clinically evaluated before and after rifaximin treatment (0.4 g bid, 4 weeks). Blood, intestine, and stool samples were collected for cytokine assessment and gut microbial analyses.Results:Clinical complaints and microbial abundance were significantly higher in IBSP than in IBSN. In contrast, severe systemic inflammation and more active bacterial invasion function that were associated with enrichment of opportunistic pathogens were seen in IBSN. The symptoms of IBSP patients were relieved in different degrees after therapy, but the symptoms of IBSN rarely changed. We also found that the presence of IBSN-enriched genera (Enterobacter and Enterococcus) are unaffected by rifaximin therapy.Conclusions:IBS-D patients overlapping with SIBO showed noticeably different fecal microbial composition and function compared with IBS-D only. The better response to rifaximin in those comorbid patients might associate with their different gut microbiota, which suggests that BT is necessary before IBS-D diagnosis and use of rifaximin.Registration:Chinese Clinical Trial Registry, ChiCTR1800017911.     

SLC18A3 promoted renal cancer development through acetylcholine/cAMP signaling

Renal cancer displays a high metastatic potential and a poor response to chemotherapy. However, the critical contributors to renal cancer development remain elusive. This study focused on acetylcholine (ACh) signaling. We identified the vesicular acetylcholine transporter (SLC18A3) that upregulates in patients with renal cancer. We further discovered that SLC18A3 enhanced the uptake of ACh, a classical neurotransmitter mediating synaptic transmission. The elevated ACh activated the protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, which contributed to renal cancer cell proliferation and invasive migration. Consistently, SLC18A3 overexpression caused sustained tumor growth and increased lung metastases in A489-bearing mice. In summary, our study demonstrated that SLC18A3 contributed to cancer spread in an ACh/PKA/CREB-dependent manner, which may drive the design of efficacious treatment strategies.     

肺肝样分化腺癌 18F-FDG PET/CT显像一例

笔者报道了1例肺肝样分化腺癌（HAL）患者的 18F-氟脱氧葡萄糖（FDG）PET/CT显像,分别从临床症状、实验室检查、术前增强CT显像、手术所见及 18F-FDG PET/CT显像等方面分析了该病的特点,并通过文献回顾总结了HAL的组织病理学及影像学特征。HAL在临床上较为罕见,多为个案报道,目...