Objective:To design and develop a formula of solid lipid nanoparticles containing the total saponins of Paris Polyphylla using a quality by design ( QbD) method. Methods:The target product profile of solid lipid nanoparticles was determined according to the properties of dosage form and administration. The risk assessment was carried out according to the theoretical knowledge and experi-ence to define the critical variables influencing the properties of solid lipid nanoparticles. Firstly, Plackett-Burman test was used to screen out the key variables significantly affecting the pharmacological properties of solid lipid nanoparticles, and then the Box-Behnken effect surface method was use to further optimize the selected variables. The physicochemical properties of solid lipid nanoparticles con-taining the total saponins of Paris Polyphylla were studied, such as the particle size distribution, polydispersity index ( PdI) , zeta po-tential, morphology and in vitro drug release behavior. Results: The optimum formula and preparation process were as follows: the concentration of glycerol monostearate was 5. 5％, the concentration of soybean phospholipid was 8. 0％, the number of homogenization was 6 times, the concentration of drug was 5. 0％, the surfactant was Tween 80, the mass pressure was 600 bar and the homogeneous temperature was 65℃. The mean particle size, PdI and zeta potential of the optimized solid lipid nanoparticles was (116. 5 ± 32. 1) nm, (0. 198 ± 0. 018) and ( -23. 6. 5 ± 0. 9) mV, respectively. Transmission electron microscopy showed that the solid lipid nanop-articles were spherical. The results of in vitro release showed a sustained release property, and the cumulative release was 63. 5％ in 24 h. Conclusion:It is feasible to design and develop solid lipid nanoparticles containing the total saponins of Paris Polyphylla by using the QbD method, which can ensure the product quality to meet the requirements.

Objective To investigate the clinical significance of precursor of gastrin‐releasing peptide(ProGRP) for the differen‐tial diagnosis between small cell lung cancer (SCLC) and non‐small cell lung cancer(NSCLC) and efficacy assessment .Methods The levels of ProGRP were detected by ELISA in 210 healthy adults ,200 patients with lung benign disease ,260 patients with NSCLC and 182 patients with SCLC before treatment and after chemotherapy .Results The level of ProGRP in the SCLC group was significantly higher than that in the NSCLC group ,healthy control group and lung benign disease group(P<0 .01) .The sensi‐tivity of ProGRP for detecting SCLC was 56 .3% and the specificity was 92 .6% .When combination detection of ProGRP and NSE was used ,the sensitivity increased to 82 .6% ;the level of ProGRP in the patients with SCLC after 2‐cycle chemotherapy was signifi‐cantly lower than before treatment (P<0 .01) .Conclusion The tumor marker ProGRP has very important guidance significance to assisted diagnosis ,differential diagnosis and efficacy assessment of chemotherapy in the patients with SCLC .

Objective: To prepare the total saponins from Paris Polyphylla self-microemulsifying drug delivery system (SMEDDSs) and its solid fied granule, and investigate the in vitro release.Methods: The solubility of the total saponins from Paris Polyphylla in different excipients was investigated.The pseudo-ternary phase diagram composed of different oil phase, emulsifier and co-emulsifier was used to define the self-emulsifying area.The optimal formula of the total saponins from Paris Polyphylla SMEDDSs was prepared into granule.The appearance, morphology, particle size distribution, PdI and zeta potential of the microemulsion and the granule were determined by a dilution method.The drug release profile of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule were compared.Results: The optimal formula of SMEDDSs was as follows: propylene glycol monocaprylate as the oil phase, Tween-80 as the emulsifier and propylene glycol as the co-emulsifier with the optimum ratio of 7.0∶1.5∶1.5.After diluted by water,the total saponins from Paris PolyphyllaSMEDDSs and the granule formed a clear and transparent microemulsion solution with small homogeneous spheres as seen under a transmission electron microscope.The average particle size of the total saponins from Paris Polyphylla SMEDDSs and the granule was (58.6±16.4) nm and (68.1±12.1) nm with PdI of (0.183±0.04) and (0.209±0.05), respectively, and the zeta potential was (-20.2±1.9) mV and (-18.9±1.5) mV, respectively.The results of transmission electron microscopy showed the microemulsion was round, regular and spherical distribution.The in vitro release profile indicated that the accumulated release of the total saponins from Paris Polyphylla SMEDDSs and SMEDDSs granule was more than 85% in 45 min.Conclusion: The self-microemulsifying granule can significantly improve the in vitro dissolution rate of the total saponins from Paris Polyphylla, and the preparation process is simple and feasible.

Objective To retrospectively analyze the relationship between progression free survival (PFS) and overall survival (OS) in patients with non small cell lung cancer (NSCLC), and to detect the influence of plasma fibrinogen and D-dimer levels before treatment in the prognosis of advanced stage (stageⅢB-Ⅳ) of NSCLC. Methods The study comprised 134 NSCLC patients with clear pathological diagnosis. All patients were grouped by plasma fibrinogen and D-dimer levels before treatment. We set the normal values of fibrinogen as≤4 g/L and D-dimer as≤500μg/L(FEU). Patients with normal levels of fibrinogen and D-dimer were grouped into low risk group, patients with elevated fibrinogen or D-dimer were grouped into median risk group, and patients with both elevated values were grouped into high risk group. Chi-square test and one way ANOVA analysis were used to analyze the clinicopathologic features of different groups. The OS and PFS in different groups were analyzed by Kaplan-Meier analysis. Univariate analysis of PFS and OS were conducted. Then multivariate analysis was conducted with the Cox regression model in three groups. Results The clinicopathologic features showed no differences between different groups. There were significant differences in OS and PFS between high risk group and other groups. In the survival curves, the high risk group showed poor prognosis. The result of multivariate analysis showed that clinical stage (OS:RR=1.846, 95%CI 1.150-2.964,P=0.011; PFS:RR=1.762, 95%CI 1.190-2.609, P=0.005) and grouped by fibrinogen and D-dimer (OS:RR=1.415,95%CI 1.050-1.908,P=0.023;PFS:RR=1.373,95%CI 1.070-1.761,P=0.013) were prognostic factors for patients with NSCLC. Conclusion The plasma fibrinogen and D-dimer levels before treatment are closely related with the prognosis of NSCLC patients. And a high plasma fibrinogen and D-dimer levels before treatment are associated with poor prognosis in advanced stage of NSCLC patients.

BACKGROUND AND OBJECTIVEIt ha been proven that serum vascular endothelial growth factor (VEGF) concentration was elevated significantly after surgery in patients of non-small cell lung cancer (NSCLC). Platelet may be the main resource of serum VEGF. The aim of this study is to investigate the correlation between postoperative dynamic changes of serum VEGF levels and platelet counts in patients of NSCLC who underwent surgery.

METHODSSerum VEGF levels were determined in 76 patients of NSCLC who were treated with surgery by ELISA (enzyme linked immunosorbent assay) method before operation and on postoperative day 1, 7. At the same day the concentrations of platelet were determined. RESULTS (1) Serum VEGF in patients of NSCLC on preoperative day, postoperative 1 day and 7 day were (842.06 +/- 527.24) pg/mL, (1 119.28 +/- 609.62) pg/mL, (1 574.09 +/- 873.38) pg/mL, respectively (P < 0.001); (2) Platelet counts in patients of NSCLC on preoperative day, postoperative 1 day and 7 day were (230.42 +/- 82.56 x 10(9)/L, (196.47 +/- 81.48) x 10(9)/L, (237.90 +/- 86.94) x 10(9)/L; the value on postoperative 1 day was the lowest (P < 0.001); (3) On postoperative 7 day, serum VEGF in the group of lower than the mean and higher than the mean were respectively (1 398.81 +/- 734.00) pg/mL and (1 842.86 +/- 1 006.63) pg/mL (P = 0.043).

CONCLUSIONSerum VEGF in patients of NSCLC after surgery were elevated. In the group of higher platelet counts, serum VEGF increased more significantly.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; surgery ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Lung Neoplasms ; blood ; surgery ; Male ; Middle Aged ; Platelet Count ; Postoperative Period ; Vascular Endothelial Growth Factors ; blood

Objective: To compare the anti-inflammatory effect of Fraxini Cortex pieces between integrated production process and traditional processing method. Methods: The model of rat paw swelling induced by carrageenan was used to study the anti-inflammatory and swelling reliving effects of water extracts of Cortex Fraxini with different methods. The main chemical components of the 2 kinds of Cortex Fraxini herbal pieces were determined by high performance liquid phase. Results: Compared with the blank group, the water extracts of the 2 kinds of Cortex Fraxini could reduce the swelling of the rats and improve the various indicators of inflammation. However, the anti-inflammatory and swelling reliving effects of the integrated processing of Cortex Fraxini were more significant. The contents of 4 main active ingredients of esculine, fraxin, aesculetin and fraxetin in the integrated processing of Cortex Fraxini were higher than that of the traditionally processed Cortex Fraxini. The total amount of 4 kinds of coumarins in the integrated Cortex Fraxini was about 1.5 times that of the traditionally processed water extract of Cortex Fraxini. Conclusion: The integrated processing and traditional processing of Cortex Fraxini have similar effects on anti-inflammatory effects, and have the superiority of reducing the loss of active ingredients, which is worthy of popularization and application.

Objective:To study the effect of spousal voice stimulation on the recovery period of patients undergoing thoracic/lumbar surgery under general anesthesia.Methods:A total of 67 patients undergoing thoracic/lumbar surgery under general anesthesia who met the inclusion exclusion criteria were divided into 34 patients in the control group and 33 patients in the experimental group according to the random number table method. Awakening in the recovery period patients were given general anesthesia care, on the basis of the control group recovery period voice wake up by paramedics. The recovery time, pain score, the incidence of restlessness and nausea and vital signs between the two groups were compared.Results:The extubation time, exhalation time, recovery time of choking cough, recovery time, and pain score in the recovery stage were (14.00±3.90) min, (11.67±3.83) min, (10.03±3.58) min, (21.24±4.28) min, (4.15±0.79) points in the experimental group, respectively. Those were (18.00±6.60) min, (15.59±5.86) min, (12.68±5.01) min, (29.50±8.25) min, (5.26±0.86) points in the control group, respectively. The differences between the two groups were statistically significant ( t values were 2.481-5.483, P<0.05 or 0.01). There was no significant difference in the incidence of restlessness and nausea and vital signs between the two groups( P>0.05). Conclusions:Spoused-voice stimulation can shorten the extubation time, exhalation time, recovery time and recovery time of choking cough in patients undergoing thoracolumbar surgery under general anesthesia, and reduce the pain in the recovery period.

Objective To investigate the timing of stereotactic radiosurgery(SRS)in lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation treated with tyrosine kinase inhibitor(TKI).Methods A total of 90 patients with EGFR-mutated lung adenocarcinoma patients with brain metastasis admitted to the Fifth Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were collected.All patients received TKI treatment and were divided into two treatment groups according to the timing of SRS treatment:those who received SRS immediately after the diagnosis of lung cancer brain metastasis were called early SRS group(n=52),and those who received TKI treatment and then SRS after the progression of brain metastasis were called deferred SRS group(n=38).Objective response rate(ORR),disease control rate(DCR),intracranial progression-free survival(iPFS)and overall survival(OS)were compared between the two groups.Multivariate COX regression model was used to analyze the prognosis.Results There was no significant difference in ORR(59.6％vs 50.0％,P=0.365)and DCR(76.9％vs 73.7％,P=0.724)between the two groups.The median OS and iPFS of the whole group were 31.5months and 12.5months,respectively.The OS of the early SRS group was signifi-cantly longer than that of the late SRS group(35.5months vs 27.0months,P=0.001).iPFS was also significantly better in the early SRS group than in the late SRS group(15.0months vs 11.5months,P=0.004).The median OS was longer in patients with no symptoms of brain metastases than in patients with symptoms of brain metastases(35.5months vs 27.Omonths,P=0.011).Multivariate COX regression analysis showed that early SRS treatment was a protective factor for OS and iPFS(HR＜1,P＜0.05),and Lung-mol GPA score of 3.5-4.0 was a protective factor for OS(HR＜1,P＜0.01).Conclusion For patients with advanced EGFR-mutated lung adenocarcinoma with brain metastases,early SRS treatment after diagnosis of brain metastases has better intracranial control effect and greater survival benefit.

Objective To investigatethe significance of serum carbohydrate antigen (CA) 125,car cinoembryonic antigen (CEA),cytokeratin 19 fragment (CYFRA21-1),neuron-specific enolase (NSE),and squamous cell carcinoma antigen (SCCA) in the diagnosis of bone metastasis from lung cancer.Methods A total of 222 patients,including 91 lung cancer patients with bone metastasis (49 males,42 females,average age (60.07± 10.60) years;group A),75 lung cancerpatientswithout bone metastasis (57 males,18 females,average age (62.20± 12.63) years;group B),56 patients with benign lung diseases (34 males,22 females,average age (61.45± 10.66) years;group C) were recruited from January 2015 to January 2016.The electrochemiluminescence was applied to detect serum levels of CA125,CEA,CYFRA21-1,NSE and SCCA.Kruskal-Wallis,Wilcoxon rank sum test,x2 test and receiver operating characteristic (ROC) curve analysis were used to analyze data.Results The levels of serum CA125,CEA,CYFRA21-1,NSE in group A were higher than those in group B and C (H values:13.45-44.96,all P＜0.05);while SCCA was not significantly different among the 3 groups (H=2.56,P＞0.05).The areas under ROC curves for CA125,CEA,CYFRA21-1,NSE,SCCA were 0.667,0.702,0.602,0.664,0.440,respectively.The positive rate of serum NSE in small cell lung cancer (SCLC) patients was higher than that in non-small-cell lung cancer (NSCLC) patients (17/18 vs 32.88％ (24/73);x2=22.11,P＜0.05);CEA was highly expressed in adenocarcinoma,and SCCA was highly expressed in squamous cell carcinoma.Patients with grade Ⅲ+ Ⅳ metas tasis (n =52) had higher levels of CA 125,CEA,NSE compared to patients with Ⅰ + Ⅱ metastasis (n =39;z values:from-2.54 to-0.32,all P＜0.05).The sensitivity of combined detection of 5 tumor markers was 97.80％ (89/91),which was significantly higher than that of single tumor marker (x2 values:35.46-138.23,all P＜0.05).Conclusion Serum levels of CA125,CEA,CYFRA21-1,NSE and SCCA play a role in the diagnosis of bone metastasis from lung cancer,and the combined detection of the 5 tumor markers contribute to the early detection of bone metastases.

Objective: To explore the humanistic caring ability, and to analyze the relationship between the positive psychological qualities, emotional intelligence and humanistic caring ability among the nursing interns, and provide theoretical basis to improve nursing students’ humanistic caring ability. Methods: A total of 132 nursing interns from a three Level of first-class hospital in Liaoning province, were investigated by using the general questionnaire, caring ability inventory, emotional intelligence scale and Positive Mental Characters Scale for China normal university. Results: The score of humanistic caring ability was (180.74±18.75). Among them, the average score of cognitive was the highest (73.71±10.93) and the average score of courage was the lowest (48.43±11.91). Emotional intelligence and positive psychological qualities were positively correlated with the humanistic caring ability, and positive psychological qualities was a intermediate variable between emotional intelligence and humanistic caring ability, and the mediating effect size is 18.71%. Conclusion The level of humanistic caring ability in nursing interns is lower, which needs to be further improved. The emotional intelligence and positive psychological qualities have a significant positive effect on the humanistic caring ability. Schools and internship hospitals can improve their sense of humanistic caring ability by developing the emotional intelligence and positive psychological qualities to stabilize the development of nursing career.