氯胺酮对人肺癌A549细胞生长的影响及相关机制研究

目的:探讨麻醉类药物氯胺酮和吗啡对人肺癌A549细胞生长的影响及相关作用机制?方法:体外培养肺癌细胞系A549,细胞培养24 h后,随机分为3组:对照组(NC组,加0.9% NaCl处理)?氯胺酮组(K1?K2?K3组,分别加氯胺酮100?200?400 ?滋g/mL处理)和吗啡组(M1?M2?M3组,分别加吗啡25?50?100 ?滋g/mL处理)?持续作用24 h后,Transwell小室培养体系测定肿瘤细胞的迁移率;双荧光素酶报告基因法测定NF-κB转录活性;48 h后MTT法测定细胞增殖抑制率;Western blot技术测定NF-κB P65的蛋白表达;QPCR技术检测细胞内IL-1β和COX-2的mRNA表达?结果:①与NC组比较,M1?M2组表现为促进A549细胞迁移(P < 0.05),M3组作用不明显;K1?K2?K3组表现为抑制A549细胞迁移(P < 0.05);②与NC组比较,M1?M2组表现为促进A549细胞增殖(P < 0.05),M3组作用不明显;K2?K3组表现为抑制A549细胞增殖(P < 0.05),K1组不明显;③与NC组比较,M1?M2?M3组表现为促进IL-1β?COX-2的mRNA表达(P < 0.05);K2?K3组表现为抑制IL-1β?COX-2的mRNA表达(P < 0.05),K1组不明显;④与NC组比较,M1?M2?M3组表现为促进P65的转录和蛋白表达(P < 0.05),K1?K2?K3组表现为抑制P65的转录和蛋白表达(P < 0.05)?结论:与阿片类药物不同,氯胺酮通过NF-κB信号通路及其下游因子IL-1β和COX-2抑制人肺腺癌细胞A549的迁移和增殖,可能更适用于肺癌患者的术后镇痛?     

Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort

Background and study aimTherapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM.Patients and methodsThis was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured.ResultsA total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn’s disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM.ConclusionsPatients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.     

HMGB1 gene silencing inhibits neuroinflammation via down-regulation of NF-κB signaling in primary hippocampal neurons induced by Aβ25–35

High mobility group box 1 protein (HMGB1) is potentially triggered by Aβ oligomers and other sterile injuries, and is a non-histone DNA binding nuclear protein with roles in neural development and neurodegeneration, which contribute to memory impairment and chronic neuroinflammation in the brain. However, the exact molecular mechanisms of HMGB1 activation in Alzheimer's disease (AD) were previously unknown. The present study aimed to elucidate the effects of HMGB1 in Aβ_25–35-induced neuroinflammation in hippocampal neuron cultures. RNA interference (RNAi) HMGB1 treatment significantly reduced Aβ_25–35-induced HMGB1 expression by almost 70% in primary hippocampal neurons. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) demonstrated that short hairpin RNA (shRNA) for HMGB1 ameliorated Aβ_25–35-treated neuroinflammation, including activation of advanced glycosylation end product-specific receptor (RAGE), toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB)-p65, as well as induced the release of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, and HMGB1 in primary hippocampal neurons and the culture supernatant. In addition, pretreatment with HMGB1-shRNA dramatically reduced both the degree of nuclear-cytoplasmic HMGB1 translocation of HMGB1 and NF-κB DNA binding. Together, the data indicate that HMGB1 mediates the pathogenesis of AD by activating RAGE/TLR4 signaling and that shRNA targeting HMGB1 may be a promising therapeutic strategy for treating AD.     

全程营养管理对消化道肿瘤患者围放疗期营养状况的影响

目的 探讨给予全程营养管理干预后，对围放疗期间消化道肿瘤患者营养状况以及住院日的影响。方法 选取2020年1月至2021年12月南通大学附属肿瘤医院收治的有放射治疗指征的消化道肿瘤患者160例，均采用精确放疗[三维适形放疗（3D-CRT）、调强放疗（IMRT）或容积调强放射治疗（VMAT）]，分为常规营养组（n=79）、营养干预组（n=81）。在放疗开始时、放疗结束时及放疗结束后1个月分别测量营养相关血液学指标，包括血红蛋白（Hb）、血白蛋白（Alb）、前白蛋白（PAB）浓度及评分营养评估量表[营养风险筛查（NRS-2002）和患者主观整体营养评估量表（PGSGA）]，比较两组指标变化情况。结果 营养干预组的Hb、Alb、PAB高于常规营养组（P<0.05），体质量、BMI、NRS-2002、PG-SGA评分优于常规营养组（P<0.05），平均住院日短于常规营养组（P<0.05）。结论 全程营养管理可以改善消化道相关肿瘤放、化疗患者基础营养状况，提高患者放疗依从性，缩短患者平均住院日。     

延续性健康教育提高康复期乳腺癌患者的自我效能感

目的探讨实施延续性健康教育提高康复期乳腺癌患者自我效能感的效果。方法 2012年1-12月,采用便利抽样法选取在南通大学附属肿瘤医院行择期手术的术后康复期乳腺癌患者120例,采用随机数字表法分为观察组和对照组,对照组采取常规随访,观察组采取延续性健康教育形式的随访管理,比较两组患者健康教育前后的自我效能感。结果健康教育后,观察组患者自我效能评分优于对照组,差异有统计学意义(P0.01)。结论延续性健康教育可增强康复期乳腺癌患者的自我效能感,是提高患者自我管理能力、建立健康行为方式的有效方法。     

Computed tomography in predicting smear-negative pulmonary tuberculosis in AIDS patients

Background The correct diagnosis of sputum smear-negative pulmonary tuberculosis in AIDS patients is very important to their therapy.We aimed to assess the value of the computed tomography (CT) and cli...     

消化性溃疡复发的常见因素分析

目的探讨分析消化性溃疡复发常见的因素,总结防治措施。方法对该院2008年1月—2011年12月收治的326例消化性溃疡的病例患者愈后定期随访或复诊,依据胃镜检查及病理结果分为复发组和未复发组,对两组患者进行相关因素(性别、年龄、职业、文化程度、不良饮食习惯、精神因素、药物因素、吸烟、维持用药、经济收入)回顾分析。结果复发114例,占34.97%,未复发212例,占65.03%。消化性溃疡的复发与性别、年龄、文化程度、不良饮食习惯、精神因素、药物因素、吸烟、维持用药、经济收入、季节等因素有关。结论消化性溃疡的复发是多因素综合作用的结果,应对针对上述因素采取防治措施,比如:健康教育、指导饮食、心理疏导、指导用药等等。     

Expression of GRP78 predicts taxane-based therapeutic resistance and recurrence of human gastric cancer

Cancer cells adapt to chronic stress in the tumor microenvironment by inducing the expression of glucose-regulated protein 78 (GRP78), a major endoplasmic reticulum chaperone with Ca^2 +-binding and antiapoptotic properties. The effect in and potential role of its expression in progression of and prognosis for gastric cancer (GC) are unclear. In the present study, we investigated the clinical value of GRP78 expression in judgment of the severity of and prognosis for GC in a retrospective cohort study of 160 patients who underwent D2 radical gastrectomy and adjuvant chemotherapy. GRP78 expression was detected using immunohistochemistry. The relationships of GRP78 expression with age, sex, differentiation, invasion depth, disease stage, lymph node metastasis, and time to recurrence (TTR) were analyzed. The GRP78 expression was higher in tumors from patients with deep tumor infiltration, with poor differentiation, at late disease stages, and with lymph node metastasis than that in tumors from patients without. Also, GRP78 positivity was associated with short TTR (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.07–4.85; P = 0.041). Subgroup analysis revealed that the HR in the GRP78-high group increased significantly in patients who did not receive taxane-containing regimens (HR, 2.21; 95% CI, 1.23–7.36; P = 0.038). In contrast, in the patients who received taxane-based chemotherapy, the association between GRP78 positivity and increased risk of recurrence was not statistically significant (HR, 1.16; 95% CI, 0.81–2.98; P = 0.111). In the patients with GRP78 expression, those who underwent taxane-containing chemotherapy had longer median TTRs than did those who did not undergo this treatment (P = 0.017). Downregulation of GRP78 expression markedly inhibited proliferation of the GC cells at the G1 phase, whereas GRP78 overexpression promoted cell-cycle progression. These findings suggest that GRP78 overexpression promotes GC cells proliferation and is an independent indicator of poor prognosis for GC.