Co-expression of guanine-nucleotide exchange factor DOCK180 and ELMO1 in ovarian cancer cells

目的 寻找卵巢癌细胞中鸟嘌呤核苷交换因子Dock 180与Elmo1呈相互协同作用的依据.方法 采用Westem blot检测人卵巢癌组织、良性肿瘤组织及正常卵巢组织中的Dock 180与Elmo1的表达水平；免疫组化检测卵巢癌组织中Dock 180与Elmol的分布；免疫荧光检测Dock180与Elmo1在卵巢癌细胞SKOV3中的定位分布；检测Dock180表达缺失的SKOV3细胞中内源性Elmo1的表达水平.结果 Dock 180与Elmo1在人卵巢癌组织中的表达水平呈明显正相关(r=0.829,P＜0.05),在卵巢癌组织中二者的表达水平显著高于卵巢良性肿瘤组织组和卵巢正常组织组(P＜0.05)[Dock180:(1.054±0.114)、(0.518 ±0.126)、(0.425±0.072); Elmo1:(0.864 ±0.114)、(0.374±0.076)、(0.300±0.105)].免疫组化及细胞化学染色均显示二者在人卵巢癌组织和细胞内的分布具有一致性.而且在Dock180表达缺失细胞中,Elmol的表达水平也同时降低.结论 Dock180与Elmo1在促进卵巢癌的癌变过程中可能具有相互协同作用.     

Assessment of fluid and nutritional status using bioelectrical impedance methods in acute kidney injury patients requiring continuous renal replacement therapy

Objective To investigate the predictive value of nutritional and fluid status measured by bioelectrical impedance methods for the prognosis of acute kidney injury (AKI) patients undergoing continuous renal replacement therapy (CRRT). Methods Patients with severe AKI received CRRT in the First Affiliated Hospital of Nanjing Medical University from September 2016 to September 2018 were enrolled, and divided into death group and survival group according to 28-day survival. Cox regression was used to analyze the association between 28-day survival and lean tissue index (LTI), fat tissue index (FTI), the ratio of extracellular water (ECW) and body cell mass (BCM) (ECW/BCM), and overhydration (OH), respectively. Results A total of 156 patients were included, including 101 males and 55 females. The age was (62.7±15.4) years, with sequential organ failure assessment (SOFA) score of 9.9±3.9. The 28-day mortality rate was 46.2%. The pre-CRRT OH values in the 28-day survival group and death group were 2.95(1.80, 5.50) L and 4.20(2.95, 5.70) L(P=0.016), and ECW/BCM values were 1.00(0.76, 1.18) and 1.07(0.88, 1.25) (P=0.033), respectively. Univariate Cox regression analysis showed that pre-CRRT high OH values (HR=1.08, 95%CI 1.00-1.17, P=0.040) and high ECW/BCM values (HR=3.02, 95%CI 1.46-6.22, P=0.003) were associated with 28-day death. The changes of OH values (HR=0.83, 95%CI 0.72-0.95, P=0.008) and ECW/BCM values (HR=6.79, 95%CI 1.72-26.82, P=0.006) between pre-CRRT and the 7th day after CRRT initiation were significantly associated with 28-day mortality in patients who survived 7 days after CRRT initiation. After adjusting for age, gender, and SOFA scores, multivariate Cox regression analysis showed that the high OH value (HR=1.16, 95%CI 1.06-1.27, P=0.002) and the high ECW/BCM value (HR=2.80, 95%CI 1.30-6.06, P=0.003) before CRRT, the change of OH value (HR=0.82, 95%CI 0.72-0.95, P=0.008) and ECW/BCM value (HR=2.79, 95%CI 1.30-5.98, P=0.009) between the 7th day after CRRT initiation and pre-CRRT, were independently associated with 28-day death, while LTI (HR=0.93, 95%CI 0.86-1.02, P=0.113) and FTI (HR=0.98, 95%CI 0.92-1.04, P=0.475) before CRRT were uncorrelated with 28-day death. Conclusions In bioelectrical impedance analysis, the high OH value and high ECW/BCM value before CRRT are associated with 28-day mortality in patients with AKI, while the nutritional indicators LTI and FTI before CRRT are not significantly related. The correction of fluid overload by CRRT within 7 days may reduce the risk of 28-day mortality.     

McCune-Albright综合征患儿超说明书用药并文献复习

探讨甲羟孕酮、来曲唑和唑来膦酸超说明书用药的合理性。方法：1例6岁8个月男性患儿，出生时发现左臀部咖啡样色斑，4岁颅面部畸形，5岁时出现第二性征发育，同时出现骨龄超前，诊断为"McCune-Albright综合征"。入院后，相继给予甲羟孕酮片（4 mg bid po）+来曲唑片（1.25 mg qd po）+唑来膦酸注射液（3 mg once iv gtt）+碳酸钙片（250 mg qd po）和维生素AD滴剂（胶囊型）（1粒qdpo）治疗。结果：经过23 d的对症治疗后，患者一般情况及症状稳定，要求出院。结论：临床药师参与患者的药物治疗过程，对唑来膦酸和甲羟孕酮、来曲唑的超说明书用药有了进一步的认识，提高了药物的治疗水平。临床药师通过参与临床实践，协助医师参与患者的用药监护，提高药物治疗的安全性。     

橄榄苦苷对破骨细胞增殖影响的实验研究

目的探讨橄榄苦苷不同药物浓度及不同作用时间对破骨细胞增殖的影响。方法破骨细胞的制备,采用sRANKL与M-CSF诱导小鼠单核细胞RAW264.7细胞获得破骨细胞。设置实验组:4组分别加入400μg/mL、200μg/mL、100μg/mL、50μg/mL橄榄苦苷,另设空白对照组。运用抗酒石酸酸性磷酸酶染液试剂盒进行破骨细胞TRAP染色鉴定,并采用Cell Counting Kit法(CCK法)检测应用不同浓度橄榄苦苷及不同作用时间抑制破骨细胞增殖的情况。结果与空白对照组比较,400μg/mL、200μg/mL、100μg/mL橄榄苦苷对破骨细胞的增殖均具有明显抑制作用。当药物作用时间为24 h及72 h时,400μg/mL橄榄苦苷对破骨细胞增殖的抑制作用最强,当药物作用时间为48 h时,200μg/mL橄榄苦苷对破骨细胞增殖的抑制作用最强,差异有统计学意义(P0.05);50μg/mL橄榄苦苷对破骨细胞的增殖无明显抑制作用,差异不具有统计学意义(P0.05)。结论橄榄苦苷可能通过破坏破骨细胞细胞膜的完整性抑制破骨细胞的增殖。     

Delayed acute kidney injury recognition is not associated with poor short?term outcomes: a propensity score matched study

Objective Acute kidney injury (AKI) is common but usually under?diagnosed in hospitalized patients, of the impact of which on patients is still unclear. The paper was aimed to investigate the impact of delayed recognition of AKI on short?time prognosis of patients through a propensity score matched study． Methods From Oct 2013 to Sep 2014，1401 adult hospitalized patients with AKI in the First Affiliated Hospital of Nanjing Medical University were divided into delayed recognition group and timely?diagnosed group according to propensity score matching (1∶1) without replacement method. Primary endpoint was 30?day all?cause mortality, and secondary endpoints included recovery of kidney at discharge, length of hospitalization, length of intensive care unit stay and hospital costs．Results There were significant differences in age, department distribution, complications, stage of AKI, Charlson index, APACHEⅡ score, SOFA score between the two groups before matching. After matching, there were no significant difference in demographic data, department distribution, complications, stage of AKI, Charlson index, APACHE II score, SOFA score between the two groups except in blood urea nitrogen (P=0.039) and use of diuretics (P=0.018). Delayed recognition of acute kidney injury was not associated with 30?day all?cause mortality in univariate (P=0.711) and multivariate Logistic regression analyses. The secondary endpoints did not differ in two groups. Conclusion Delayed acute kidney injury recognition did not associate with poor short?term outcomes in adult hospitalized patients．     

Correlation of macrophage migration inhibitory factor gene polymorphism with the risk of early-stage cervical cancer and lymphatic metastasis

Associations of functional single nucleotide polymorphisms in MIF-173G/C with early stage cervical cancer were investigated in a hospital-based case-control study on 250 patients with cervical cancer prior to surgery (including 49 cases with and 201 cases without lymphatic metastasis) and 147 healthy controls. The polymorphism was assessed using restriction fragment length polymorphism polymerase chain reaction, and the MIF serum concentration was examined using the enzyme-linked immunosorbent assay to analyze the correlation between the polymorphism and the MIF serum concentration. Carriers of the variant C allele in MIF-173 were at a significantly higher risk of cervical cancer compared to carriers of the wild-type allele (aOR=1.508; 95% CI, 1.128-2.016, p=0.05). The GC and CC genotypes may be the causative factors for cervical cancer (aOR=1.851; 95% CI, 1.132-3.027, p=0.013). Individuals with the GC+CC genotype and C allele at the MIF-173G/C site were at a significantly higher risk of cervical cancer and lymphatic metastasis. The risk of lymphatic metastasis in early stage cervical cancer was increased more than 1.6 times in patients with the CC and GC genotypes compared with those with the GG genotype. The genotype distribution and allele frequency of MIF-173G/C were statistically significant in the well-, moderately and poorly differentiated groups (P<0.05). Compared to the GG genotype and G allele, patients with GC and CC genotypes and C allele exhibited a lower degree of differentiation and a higher degree of malignancy. A significant difference was observed in MIF serum concentrations among the various subgroups (P<0.05). The early cervical cancer, lymphatic metastasis and poorly differentiated groups exhibited higher MIF levels in serum. Moreover, patients with the CC genotype exhibited higher MIF serum concentration, which could increase the risk of early stage cervical cancer and lymphatic metastasis. The results presented in this study provide the first evidence that the genetic polymorphism MIF-173 is associated with cervical cancer in humans. Detection of MIF serum concentration and genotyping may be used as biomarkers for early diagnosis and therapy for cervical cancer.     

MR淋巴造影显影兔VX2乳腺癌模型内乳前哨淋巴结

目的 探讨MR淋巴造影（MR-LG）显影兔VX2乳腺癌内乳前哨淋巴结（SLN）的可行性。方法 将75只新西兰大白兔分别建立兔VX2乳腺癌（肿瘤组）及炎性（炎症组）实验动物模型,并对其行MR-LG检查,检查后进行淋巴结清扫术。记录内乳SLN及淋巴管的显示情况,分析影响其显像的因素。结果 实验兔建模成功率为97.33%（73/75）;MR-LG对内乳SLN及淋巴管的显示率分别为15.94%（11/69）和75.36%（52/69）,其在肿瘤组与炎症组差异均无统计学意义（P均>0.05）。肿瘤组内乳SLN显示与未显示实验兔间体质量,肿瘤生长时间,肿瘤长径,腋窝SLN数目、大小及阳性数目,内乳淋巴管显影情况差异均无统计学意义（P均>0.05）;内乳淋巴管显示与未显示实验兔间肿瘤大小及腋窝SLN数目差异有统计学意义（P均<0.05）。MR-LG检出内乳SLN的准确率、敏感度、特异度、假阴性率及假阳性率分别为76.81%（53/69）、39.13%（9/23）、95.65%（44/46）、60.86%（14/23）和4.35%（2/46）。结论 MR-LG可有效显像兔VX2乳腺癌模型内乳SLN及淋巴管。     

星点设计-效应面法优化阿昔洛韦口腔贴片处方

摘 要 目的： 星点设计 效应面法优化阿昔洛韦口腔贴片处方。方法: 以羟丙甲纤维素(HPMC) K4M和卡波姆974P NF的用量为因素,以阿昔洛韦在1 h,5 h和12 h的释放度和黏附力为指标,用多元线性方程、双因素模型和二次多项式模型分别描述各指标与因素的关系,根据较优数学模型绘制效应面图;各指标效应面二维等高线图的重叠部分,即为最佳处方区域,选择最佳处方,并进行预测分析。结果: 二次多项式模型拟合的相关系数和可信度较高。最佳处方各指标的实测值在预期范围内。结论: 星点设计 效应面优化法可以较好地用于阿昔洛韦口腔贴片处方的优化。     

IL-17抑制大鼠肾脏成纤维细胞NRK-49F向肌成纤维细胞转化

目的:研究白细胞介素-17(IL-17)对大鼠肾脏成纤维细胞(NRK-49F)转化为肌成纤维细胞?表达细胞外基质的影响,并进一步探讨该调节作用可能涉及的分子机制?方法:以转化生长因子β(TGF-β)诱导培养NRK-49F细胞,采用Western blot检测IL-17对NRK-49F表达α-平滑肌肌动蛋白(α-SMA)和细胞外基质Ⅰ型胶原和纤连蛋白的影响;并运用real-time PCR分析NRK-49F 在诱导培养24?48?72 h后细胞外基质Ⅰ型胶原和纤连蛋白mRNA的表达水平及IL-17的调节作用?最后,运用Western blot检测细胞内Smad与非Smad通路中相关信号分子的表达及其磷酸化水平,以解释IL-17对NRK-49F 调节作用的分子机制?结果:IL-17抑制NRK-49F细胞表达α-SMA,并抑制其表达细胞外基质Ⅰ型胶原和纤连蛋白?当IL-17对NRK-49F发挥上述抑制作用时,并未影响经典Smad 信号分子的表达,而是通过抑制非Smad通路Akt-TSC2-p70S6K的活化来实现的?结论:IL-17通过抑制TGF-β的非Smad通路Akt-TSC2-p70S6K的活化,从而抑制NRK-49F转化为肌成纤维细胞,并抑制其表达细胞外基质?