Combined spectroscopy methods and molecular simulations for the binding properties of trametinib to human serum albumin

Trametinib is a novel anticancer drug for treating metastatic cutaneous melanoma. The present study probed into the binding of trametinib to human serum albumin (HSA) through spectroscopy methods and molecular simulations. Trametinib could quench the fluorescence of HSA through static quenching which could be probed via fluorescence spectroscopy and time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrogen bonds and van der Waals forces play crucial roles in this binding process, which exerts almost no effect on the HSA conformation under synchronous fluorescence, three-dimensional fluorescence, circular dichroism spectra, and molecular dynamics simulations. Site marker displacement experiments and molecular docking reveal that trametinib primarily binds to Sudlow site I of HSA. In addition, the trametinib–HSA interaction was hardly influenced by varying amino acid (glutamine, alanine, glycine, and valine) concentrations. This study can provide useful information for the pharmacokinetic properties of trametinib.

Probing the binding properties of trametinib to human serum albumin.     

不同剂量的1，25（OH）2D3对大鼠Thy1肾炎系膜细胞凋亡的影响

目的：探讨不同剂量的1,25（OH）2D3对大鼠抗胸腺细胞抗体（Thy1）肾炎系膜细胞凋亡的影响。方法将SD大鼠120只分为空白对照组（A组）、肾炎模型组（B组）、低剂量1,25（OH）2D3组（C组）和高剂量1,25（OH）2D3组（D组）,每组30只。C、D两组造模成功后给药干预,4组分别于干预后第1、3、7、14、21天每组随机处死6只大鼠,取肾组织标本经HE及PAS染色后确定肾脏病理损害分级;免疫组化法检测肾组织中半胱氨酸天冬氨酸蛋白酶3（Caspase‐3）的表达;TUNEL试剂盒检测其肾小球内细胞凋亡。结果与A组比较,B组Caspase‐3表达增强（P＜0．05）;与B组比较,C、D组Caspase‐3表达增强,但差异无统计学意义（P＞0．05）;D组表达最高,但与C组比较差异无统计学意义（P＞0．05）。与A组比较,B组肾小球内凋亡细胞明显增多（P＜0．05）,且随时间推移逐渐增强;与B组比较,C、D两组凋亡明显增多（P＜0．05）,并在3d达高峰,7、14d逐渐下降,21d趋于正常（P＜0．05）;C、D两组比较,D组凋亡细胞增多明显,但差异无统计学意义（P＞0．05）。结论1,25（OH）2D3具有诱导大鼠肾小球系膜细胞凋亡的作用,其参与了对Caspase‐3的调节,诱导系膜细胞凋亡,促进肾炎的修复,可延缓肾脏疾病进展。     

山西省41家医院胃癌住院日影响因素分析

目的了解胃癌患者住院日的影响因素,为医院及卫生主管部门管理决策提供参考依据。方法收集山西省41所三级医院2014年一季度胃癌患者出院首页数据,利用多重线性回归统计学方法,回顾性分析胃癌患者住院日与患者性别、年龄、地区、付费方式、伴随诊断数量、手术、医院类型7因素的相关性。结果不同性别组、年龄组、付费方式组住院日比较无统计学意义(t=0.210,P=0.834;F=1.342,P=0.252;2χ=5.945,P=0.312),是否手术、医院类型、伴随诊断数量、不同地区(Mann-Whitney检验)组住院日比较有统计学意义(2χ=52.489,P<0.001;2χ=32.924,P<0.001;t=-21.026,P<0.001;Z=-8.149,P<0.001)。结论医院加强手术患者的管理、严格把握手术适应症、优化手术患者诊疗流程设计与管理、开展与基层医院双向转诊服务等对降低患者住院日水平有帮助;同时,卫生主管部门应引导患者理性选择就医地点,不盲目追求名医名院,避免出现少数医院患者过度集中现象,这不仅可有效缓解患者看病难看病贵,而且对缩短患者住院日也有实际意义。     

Large-scale synthesis and luminescence of GdPO4 hollow microspheres

GdPO₄ hollow microspheres were synthesized by using a novel multi-step transformation synthetic route for the first time with polystyrene (PS) spheres as the template, followed by the combination of a facile homogeneous precipitation method, an ion-exchange process, and a calcination process. The XRD results indicated that the GdPO₄ hollow microspheres have a pure hexagonal phase. The SEM and TEM images confirmed that the as-obtained GdPO₄ hollow spheres have a uniform morphology with an average diameter of 2.7 μm and shell thickness of about 150 nm. The up-conversion luminescence properties as well as the emission mechanisms of the GdPO₄:Yb³⁺, Ln³⁺ (Ln³⁺ = Tm³⁺, Er³⁺ and Ho³⁺) hollow microspheres were systematically investigated, which show blue (Tm³⁺, ¹G₄ → ³H₆), green (Er³⁺, ⁴S_3/2, ²H_11/2 → ⁴I_15/2), and red (Ho³⁺, ⁵F₅ → ⁵I₈) luminescence under 980 nm NIR excitation, providing potential applications in bioanalysis, optoelectronic and nanoscale devices, future color displays and light-emitting devices, and so on.

GdPO₄ hollow microspheres were synthesized by using a novel multi-step route for the first time with polystyrene (PS) spheres as the template, followed by the combination of a facile homogeneous precipitation method, an ion-exchange process, and a calcination process.     

Seminar合案例教学法在中医诊断教学中的应用效果分析

目的 探讨案例教学法在中医诊断学教学中的应用与效果.方法 在本校中医专业学生中,对2012级至2013级2个年级4个班的中医诊断学进行Seminar合案例教学法尝试.并设同年级同类型4个班用传统教学法作对照.结果 实验班学生认同率达98％;实验班与对照班比较,老师的评价及理论考试成绩实验班与对照班比较差异有统计学意义(P＜0.01或0.05),试验班明显为优.结论 案例教学法对提高中医诊断学的教学质量和锻炼老师教学水平有积极意义.     

基质金属蛋白酶/组织金属蛋白酶抑制物表达失衡在大鼠肾脏衰老过程中的意义

目的:探讨基质金属蛋白酶(MMPs)及其抑制物(TIMPs)在大鼠肾脏衰老过程中的作用。方法:选用3、12和24月龄大鼠，采用免疫组化技术分别检测基质金属蛋白酶—2、9(MMP—2、9)、组织金属蛋白酶抑制物—1、2(TIMP—1、2)、转化生长因子—β1(TGF—β1)等在不同月龄大鼠肾组织中的表达。结果TIMP—1、TIMP—2及TGF—β1主要表达在肾小球、肾小管、间质及血管，并随增龄表达增强(P＜O．01)；MMP—9、MMP—2主要表达在肾小管上皮细胞，随增龄表达无变化；TIMP—1与TGF—β1与肾小球硬化面积有相关性(r分别为O．751、O．771，P＜O．05)；TIMP—1与TIMP—2与小管间质纤维化面积有相关性(r分别为O．783、O．766，P＜O．O5)。结论:MMPs／TIMPs表达失衡在肾脏衰老过程中可能起重要作用。     

Abnormalities of intrinsic brain activity in essential tremor: A meta‐analysis of resting‐state functional imaging

Neuroimaging studies using a variety of techniques have demonstrated abnormal patterns of spontaneous brain activity in patients with essential tremor (ET). However, the findings are variable and inconsistent, hindering understanding of underlying neuropathology. We conducted a meta‐analysis of whole‐brain resting‐state functional neuroimaging studies in ET compared to healthy controls (HC), using anisotropic effect‐size seed‐based d mapping, to identify the most consistent brain activity alterations and their relation to clinical features. After systematic literature search, we included 13 studies reporting 14 comparisons, describing 286 ET patients and 254 HC. Subgroup analyses were conducted considering medication status, head tremor status, and methodological factors. Brain activity in ET is altered not only in the cerebellum and cerebral motor cortex, but also in nonmotor cortical regions including prefrontal cortex and insula. Most of the results remained unchanged in subgroup analyses of patients with head tremor, medication‐naive patients, studies with statistical threshold correction, and the large subgroup of studies using functional magnetic resonance imaging. These findings not only show consistent and robust abnormalities in specific brain regions but also provide new information on the biology of patient heterogeneity, and thus help to elucidate the pathophysiology of ET.     

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

Aims

To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance.

Methods and results

Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression‐free survival in the patients with CD117‐positive tumours was shorter than that in the patients with CD117‐negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases.

Conclusions

CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality.     

Clinicopathological characteristics and prognosis of alpha-fetoprotein positive gastric cancer in Chinese patients

Purpose: This study aimed to review the clinicopathological, histochemical, and prognostic features of Alpha-Fetoprotein (AFP) positive gastric cancer. Patients and methods: Six hundred and fifty one patients with gastric cancer who underwent gastrectomy between January 2009 and December 2012 at The First Hospital of Jilin University were enrolled in the study. Among them, 45 patients were identified as AFP positive gastric cancer. The clinicopathologic characteristics and prognosis of the AFP positive gastric cancer patients were analyzed. Results: Among the 45 AFP positive patients, serum levels of AFP were < 100 µg/L in nine patients. The histological classification of 45 patients was as follows: hepatoid type, 25 (55.6%) cases; fetal gastrointestinal type, 12 (26.7%) cases; yolk sac tumor type, 2 (4.4%) cases; and mixed type, 6 (13.3%) cases. Twenty nine (64.4%) cases were AFP positive by immunohistochemical analysis; we found no significant difference in AFP positivity and histologic type. However, the differences in the number of metastasis lymph nodes, the maximum tumor diameter, pathological stage, vascular invasion and liver metastasis between the AFP positive group and the negative group were significant. At the same T stage, the liver metastasis status of the AFP positive group was higher than that of the negative group. The AFP positive group had a much poorer prognosis than the negative group. Conclusion: AFP positive gastric cancer is associated with aggressive behavior and poorer prognosis compared to that of AFP negative gastric cancer.