Résumé
【Objective】 To explore the correlation of preoperative fibrinogen-to-albumin ratio （FAR） with the clinicopathological characteristics and prognosis of patients with rectal cancer so as to clarify the role of coagulation function and nutritional status in the occurrence and progression of tumors. 【Methods】 We retrospectively analyzed the clinicopathological data of 647 patients with rectal cancer who underwent radical resection in The First Affiliated Hospital of Xi’an Jiaotong University from January 1， 2013 to December 31， 2016. According to the optimal cut-off point value of FAR determined by receiver operating characteristic curve， 647 rectal cancer patients were divided into high FAR level group and low FAR level group. The correlation between different preoperative FAR levels and clinicopathological characteristics of rectal cancer patients was analyzed. Multivariate Cox regression analysis was used to analyze the independent risk factors for the prognosis of rectal cancer patients. R software was used to construct the nomogram， and C index and calibration chart were used to evaluate the prediction efficiency of the nomogram. 【Results】 Preoperative FAR levels had a good predictive value for the prognosis of rectal cancer patients. The area under ROC curve was 0.771， the optimal cut-off point was 0.092， and the Youden index was 0.446. There were statistically significant differences in age， T stage， N stage， TNM stage， preoperative CEA levels and preoperative CA19-9 levels between rectal cancer patients with different preoperative FAR levels （P<0.05）. The overrall survival and disease-free survival of rectal cancer patients with different preoperative FAR levels had statistically significant differences （P<0.05）. In the multivariate analysis， preoperative FAR levels （≥0.092， HR=3.298， 95% CI： 2.365―4.600， P<0.001）， age （≥60 years， HR=2.110， 95% CI： 1.479―3.012， P<0.001）， TNM stage （Ⅲ grade， HR=6.743， 95% CI： 2.771―16.771， P<0.001）， grade of differentiation （poor， HR=1.639， 95% CI： 1.104―2.432，P=0.014）， preoperative CA19-9 levels （≥37 U/mL， HR=2.205， 95% CI： 1.529―3.180， P<0.001） and not perform postoperative chemoradiotherapy（HR=1.792， 95% CI： 1.294―2.480，P<0.001） were independent risk factors of overall survival for patients with rectal cancer. OS and DFS nomograms of rectal cancer were established by the Rlanguage software， and the C-index was （0.781， 95% CI： 0.749―0.815； 0.754， 95% CI： 0.693―0.760）， respectively. The calibration curve of the nomogram showed high consistence between predictions and actual results for 1-year， 3-year， 5-year OS and DFS. 【Conclusion】 The preoperative high FAR level was an independent risk factor for the prognosis of patients with rectal cancer. It can be supplemented with pathological factors such as TNM stage as prognostic indicators for patients with rectal cancer， which may be helpful for clinicians to follow up or make beneficial treatment for rectal cancer patients.
Résumé
Background The penetration of bacterial agents into the vitreous cavity is difficult because of the existence of blood-retina barrier.So conventional drug therapy is not enough effective on endophthalmitis.Drug delivery systems can decrease drug dose and reduce the drug toxicity.To construct nano controlled-release system of anti-bacterial agents is very important for the treatment of intraocular infectious diseases.Objective This study was to investigate the toxicology and intraocular pharmacoklnetics of intravitreal PNIPAAm-PEO loaded norvancomycin nanoparticles (NV-PNIPAAm-PEO) in normal rabbit eyes.Methods NV-PNIPAAm-PEO was constructed with the drug-loading rate about 22％,and then the drug gelatin solution (20 g/L) was prepared using normal saline solution.Forty-one New Zealand albino rabbits were randomized divided into experimental group and control group.20 g/L drug gelatin solution 0.1 ml was monocularly injected into the vitreous cavity in the experimental group,and the equal volume of sterilized normal saline solution was used in the control group.In 1 day,2,3,7,14,21 and 28 days after injection,ocular anterior and posterior segments were examined by slit lamp microscope and Bsonography,and electroretinogram (ERG) was recorded and the histopathological examination was performed to evaluate the biotoxicity of the drug.Norvancomycin contents in the cornea homogenate,aqueous humor,vitreous,retinochoroid homogenate were detected by high performance liquid chromatography (HPLC) system.Results The anterior and posterior segments were normal by the slit lamp microscope and B-sonography 1-28 days after injection of NV-PNIPAAm-PEO.In 7,14,21 and 28 days after injection,there were no statistically significant difference in the a-wave latency and amplitude of max-ERG between the two groups,as well as the b-wave amplitude(P＞0.05).The histopathological examination showed that the retinal structure was normal in both groups.HPLC assay showed that the norvancomycin level was gradually declined in different eye tissues from 1 day through 28 days after injection.Norvancomycin was undetectable in the cornea during the observing duration.The maximal norvancomycin content in the blood plasma was (0.34 ± 0.11) mg/L in the second day,and norvancomycin content ranged (0.08 ± 0.04)-(2.16±0.07) mg/L in the aqueous humor,(0.11 ±0.22)-(2.54 ±0.38) μg/g in the chorioretina,respectively.The drug concentration was (5.65 ± 1.14)-(406.69 ± 21.05) mg/L in the vitreous,which was higher than the minimal inhibitory concentration (MIC) to the most gram-positive bacteria.Conclusions The intravitreal injection of 22％ NV-PNIPAAm-PEO maintains the therapeutic drug concentration till 21 days in vitreous without the toxic effect on eye tissues,suggesting a great treating potential for intraocular infecting diseases.