Objective:To develop an evidence-based nursing program for a patient with oral complications of dysphagia due to cerebral infarction.Methods:According to the principle of PICO, and the problem of patients' clinical manifestations, using the method of combining subject words and free words, the database of Uptodate, NICE, SIGN. RNAO, medical pulse guide network, BMJ, Cochranc library, PubMed, EMbase, CINAHL, China National Knowledge Infrastructure were searched and collected the clinical guidelines, systematic evaluation and randomized controlled trial of oral complications in patients with dysphagia of cerebral infarction.Results:Totally 1 clinical decision, 5 clinical guidelines, 4 expert consensus, 2 systematic evaluations, 1 Meta-analysis, 3 randomized controlled trial (RCT) were included. Based on the search results and the patient′s condition and wishes, nurses performed swallowing function tests every two days according to the Standard Swallowing function rating Scale (SSA), raised the head of the bed 40°~45° and holded it for 1 hour. Three times a day, the teeth were brushed with chlorhexidine oral care solution under negative pressure. Sputum scab was removed by mechanical scrubbing. The back of tongue was scrubbed by 6x tongue scraping technique every night. After the infection was controlled, the teeth were washed twice a day with 0.9% sodium chloride solution. Oral condition and swallowing function were evaluated daily. High flow humidification oxygen therapy and mask spray atomization inhalation were used. Swallowing training was performed on the third day after admission. Seven days after the evidence was applied to clinical practice, the oral mucosa was moist without peculiar smell and sputum scab, and the swallowing function was changed from grade IV to grade II.Conclusion:Nursing cerebral infarction patients with dysphagia, nurses should timely assess the patient's oral cavity and swallowing function, the application of chlorhexidine and 0.9% sodium chloride solution oral care solution mechanical scrubbing method and negative pressure washing brushing method can effectively remove sputum scab, use 6x tongue scraping technology to scrub the back of tongue, can reduce micro organisms, reduce halitosis; the application of nasal mask high flow humidification oxygen therapy and spray atomization inhalation humidification effect is obvious Therefore, early swallowing training can reduce the incidence of oral complications.

Objective To evaluate the synergistic effect of everolimus on cisplatin-mediated cytotoxicity against human cutaneous squamous cell carcinoma COLO-16 cells.Methods Cultured COLO-16 cells were divided into several groups to be treated with everolimus at different concentrations of 50,100 and 200 nmol/L or 25 μmol/L cisplatin for 12 and 24 hours.Acridine orange (AO)-labeled autophagic vesicles combined with lysomal enzyme inhibitors (E64d and pepstatin) were used to detect the levels of autophagy and autophagic flow.Western blot analysis was performed to track the conversion of the autophagosome marker microtubule-associated protein 1 light chain-3 (LC3)-Ⅰ to LC3-Ⅱ,as well as to detect cleavage levels of Caspase 3 and poly-ADP-ribose polymerase (PARP).Lactate dehydrogenase (LDH) assay was conducted to detect cell death,and Annexin V-EGFP staining to evaluate cell apoptosis.Results The LC3-Ⅱ / LC3-Ⅰ ratios (LC3-Ⅰ conversion to LC3-Ⅱ) after 12-and 24-hour treatment did not differ among the 50-,100-and 200-nmol/L everolimus groups (12 hours:3.52 ± 0.21 vs.4.03 ± 0.39 vs.5.05 ± 0.22,P ＞ 0.05;24 hours:3.38 ± 0.26 vs.3.29 ± 0.06 vs.6.57 ± 0.16,P ＞ 0.05),but were significantly higher in the three everolimus groups than in the control group receiving no treatment (12 hours:2.07 ± 0.05,P ＜ 0.05;24 hours:2.61 ± 0.16,P ＜ 0.05).After 12-hour treatment,no significant differences were observed in the ratio of LC3-Ⅱ to β-actin between the 50-nmol/L everolimus + E64d + pepstatin group (1.26 ± 0.40),100-nmol/L everolimus ± E64d + pepstatin group (1.16 ± 0.34),200-nmol/L everolimus + E64d + pepstatin group (1.21 ± 0.39) and E64d + pepstatin group (1.19 ± 0.27,P ＞ 0.05).Moreover,there was no significant difference in the percentages of autophagic vesicle-positive cells between the 100-nmol/L everolimus + E64d + pepstatin group and E64d + pepstatin group (2.06％ ± 0.61％ vs.1.68％ ± 0.62％,P ＞ 0.05).After 24-hour treatment,the everolimus + cisplatin group showed significantly increased rate of cell death compared with the cisplatin alone group (42.58％ ± 0.93％ vs.18.20％ ± 1.46％).However,no significant differences were observed in the cleavage levels of Caspase 3 and PARP,the number of annexin V-labelled cells and ratio of LC3-Ⅱ to β-actin between the everolimus + cisplatin group and the cisplatin-alone group (P ＞ 0.05).Conclusion Everolimus has a synergistic effect on the cisplatin-mediated COLO-16 cell death,and this effect does not depend on cell apoptosis or autophagy.

Objective To investigate molecular mechanisms underlying the synergistic damage to the human squamous cell carcinoma cell line COLO-16 by everolimus and cisplatin.Methods In the signaling pathway experiment,COLO-16 cells were divided into 4 groups:control group receiving no treatment,50,100 and 200 nmol/L everolimus groups treated with 50,100 and 200 nmol/L everolimus respectively.In the combined experiment,COLO-16 cells were divided into another 4 groups:control group,50 nmol/L everolimus group,25 mol/L cisplatin group,and 50 nmol/L everolimus + 25 mol/L cisplatin group.Western blot analysis was performed to analyze changes in mammalian target of rapamycin (mTOR) pathway,Akt pathway,DNA damage-related pathway and Csk homologous kinase (Chk) pathway.Results After the treatment with everolimus at different concentrations of 50,100 and 200 nmol/L for 12 and 24 hours,the phosphorylation levels of mTOR at ser2448 and ser2481 as well as Rictor at thr1 135 in COLO-16 cells were all decreased compared with the control group.However,there were no significant changes in the phosphorylation levels of downstream signals ULK1 at ser757,p70 S6 at thr389 and PKCα at thr638/64.The treatment with everolimus did not change the total protein level and phosphorylation of Akt.After the treatment with cisplatin for 12 and 24 hours,the phosphorylation levels of Rictor at thr1135 and Chk1 at ser345 were significantly increased,but the treatment with everolimus alone showed no such effects.After the combined treatment with everolimus and cisplatin for 12 and 24 hours,the upregulation of Chk1 and Rictor phosphorylation were significantly inhibited compared with the cisplatin alone group.Conclusions mTOR signaling is sensitive to everolimus in COLO-16 cells,but its targeted pathway is not regulated simultaneously to develop a cascade reaction.Everolimus may increase the cisplatin-induced death of COLO-16 cells by inhibiting the activation of Chk 1,but can not aggravate DNA damage induced by cisplatin.