Objective To optimize the formulation and preparation process of lenvatinib mixed micelles.Methods Hybrid micelles of lenvatinib were prepared by film hydration method,with Pluronic P123 and F127 as carrier materials.Optimal formulation was selected through single-factor experiments and central composite design-response surface methodology,and preliminary characterization of its physical properties was conducted.Results The optimized formulation and process conditions were identified as follows:P123 mass percentage of 80%,carrier material amount of 90 mg,drug loading of 10 mg,hydration volume of 6 ml,hydration time of 45 min,and rotary evaporation temperature of 55℃.The resulting lenvatinib mixed micelles had an average particle size of(104.0±0.32)nm,a polydispersity index(PDI)of 0.22±1.19,and a Zeta potential of(-2.56±0.81)mV.The average encapsulation efficiency was 83.33%±0.30%and the average drug loading was 8.67%±0.07%.The micelles displayed a uniform spherical morphology with a certain sustained-release capability.Conclusion The preparation process developed in this study was simple and feasible and produced drug-loaded micelles with high drug loading and encapsulation rates,and stable release,which could provide valuable insights for further research and development of lenvatinib mixed micelles.

Objective:To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating left recurrent laryngeal nerve lymph node metastasis in thoracic esophageal squamous cell carcinoma.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 628 patients with thoracic esophageal squamous cell carcinoma who were admitted to 2 medical centers (236 cases in the Sun Yat-sen University Cancer Center and 392 cases in the Affiliated Cancer Hospital of Zhengzhou University) from October 2009 to December 2016 were collected. There were 462 males and 166 females, aged from 38 to 85 years, with a median age of 62 years. Observation indicators: (1) operation status, dissection and metastasis of left recurrent laryngeal nerve lymph node; (2) efficacy of CT examination of the left recurrent laryngeal nerve lymph node short diameter in evaluating postoperative lymph node metastasis; (3) determination of the optimal cut-off value; (4) examination results using different diagnostic criteria. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages. The area under curve (AUC) of receiver operating characteristic curve (ROC) was used to estimate the efficiency of detection methods. The maximum value of Youden index corresponded to the optimal cut-off point. Results:(1) Operation status, dissection and metastasis of left recurrent laryngeal nerve lymph node: among the 628 patients, there were 572 cases undergoing two-field lymph node dissection while 56 cases undergoing three-field lymph node dissection, there were 408 cases undergoing minimally invasive surgery while 220 cases undergoing open surgery. Sixty of 628 patients had left recurrent laryngeal nerve lymph node metastasis. A total of 1 666 left recurrent laryngeal nerve lymph nodes were dissected from the 628 patients, among which 75 were metastatic lymph nodes, with a metastasis rate of 4.502%(75/1 666). (2) Efficacy of CT examination of the left recurrent laryngeal nerve lymph node short diameter in evaluating postoperative lymph node metastasis: the AUC of CT examination of the left recurrent laryngeal nerve lymph node short diameter in predicting postoperative lymph node metastasis was 0.854 (95% confidence interval as 0.792 to 0.916, P<0.05). (3) Determination of the optimal cut-off value: the Youden indices were 0.556, 0.384, 0.258, 0.063 and 0.003 respectively when using 5 mm, 6 mm, 7 mm, 8 mm, 9 mm or 10 mm as the optimal cut-off value for CT examination of the left recurrent laryngeal nerve lymph node short diameter. The short diameter as 5 mm was the optimal cut-off value for CT examination of the left recurrent laryngeal nerve lymph node short diameter. (4) Examination results using different diagnostic criteria: the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, cases being missed diagnosis were respectively 66.3%, 92.3%, 89.5%, 46.3%, 96.0%, 20 and 5.0%, 99.8%, 90.7%, 75.0%, 90.9%, 57 when using short diameter ≥5 mm or ≥10 mm in CT examination of the left recurrent laryngeal nerve lymph node as the diagnostic criteria for left recurrent laryngeal nerve lymph node metastasis of thoracic esophageal squamous cell carcinoma. Conclusions:CT examination of lymph node short diameter can be used to evaluate left recurrent laryngeal nerve lymph node metastasis in thoracic esophageal squamous cell carcinoma. The sensitivity, specificity and accuracy is preferable when using short diameter ≥5 mm in CT examina-tion of the left recurrent laryngeal nerve lymph node as the diagnostic criteria for left recurrent laryngeal nerve lymph node metastasis of thoracic esophageal squamous cell carcinoma.

Objective To evaluate the feasibility of dual-source low-dose computed tomography (CT) of the paranasal sinus in children, with acquisition at an ultra-low tube voltage (70 kVp) combined with the Flash scan. Methods CT scans of the paranasal sinus were performed on 80 pediatric patients who were divided into two groups according to different protocols (70 kVp protocol with Flash scan mode and the iterative reconstruction, pitch 3, the experimental group (group A), n = 40; 80 kVp protocol with conventional spiral mode, pitch 1.5, control group (group B), n = 40). For each examination, the CT dose index (CTDIvol), dose-length product (DLP) and effective dose (ED) were estimated. The image noise, signal-to-noise ratio (SNR) and overall subjective diagnostic image quality were also evaluated. Results The images of these two groups were all satisfied for the clinical diagnosis. For radiation dose, the CTDIvol (mGy), DLP (mGycm) and ED (mSv) values of the 70 kVp protocol were significantly lower than those of the 80 kVp protocol [CTDIvol: 0.39 ± 0.004 vs1.57 ± 0.009 mGy, P < 0.001; DLP: 6.31 ± 0.52 vs 19.88 ± 2.01 mGycm, P < 0.001; ED: 0.024 ± 0.005 vs 0.079 ± 0.016 mSv, P < 0.001. Compared with those of the 80-kVp protocol, the image noise and the SNR_bone increased, the SNR_soft-tissue decreased. There was no statistical difference in the subjective scores of the two groups of image quality by the two physicians (P > 0.05). Conclusion When diagnosing the paranasal sinus in children, an ultralow tube voltage (70 kVp) combined with the Flash scan technique can reduce the radiation dose significantly while maintaining diagnostic image quality with clinically acceptable image noise.

Objective:To investigate the knowledge of the disease and demands of medical intervention in high-risk individuals of arteriosclerotic cardiovascular diseases (ASCVD).Methods:The 10-year ASCVD incidence risk prediction model was used to screen ASCVD high-risk individuals from Luohu district of Shenzhen city. From October 2018 to April 2019,a semi-structured in-depth interview was conducted among ASCVD high-risk individuals selected by stratified sampling method according to age, gender and educational level. The original data were analyzed with Colaizzi′s seven-step analysis method.Results:Total 37 interviewees were enrolled with an average age of (65.2±8.9) years and with an average ASCVD risk value of (14.2±3.2). Three themes were extracted from the interview, including: (1) Majority interviewees had better Knowledge about the hazards and risk factors of ASCVD; (2) Most of the interviewees had lower medical demands; (3) The interviewees were more likely to focus on symptomatic diseases or diseases disturbing them.Conclusions:The asymptomatic high-risk ASCVD individuals generally have better awareness of ASCVD and less demands for intervention. The result indicates that for health education, not only the knowledge, but also the attitude and behavior should be enhanced.

Liver cirrhosis is the end-stage of chronic liver disease and can affect the function of multiple organs. Gastrointestinal tract damage resulting from cirrhosis is more common in clinic, which may cause gastroparesis, affect the digestion and absorption of nutrients, and destroy the intestinal mucosal barrier function. In addition, it may be accompanied by a series of gastrointestinal complications that affect the patient’s prognosis. Clinically, more attention should be paid to early monitoring, early diagnosis and early treatment of cirrhosis-related gastrointestinal complications so to control the progression of liver cirrhosis condition, reduce advanced stage complications, and improve patient’s quality of life.

Objective To modify polyethyleneimine (PEI) by using Poloxamer 188 (P188) , and evaluate its related feature as carriers of genes in vitro. Methods PEI was modified through conjugating one hydroxyl group of P188 to the amino group of PEI by carbonate method. Structural analysis of synthesized polymer was performed by using 1H-NMR. The particle size and Zeta potential of synthesized polymer /DNA complexes were measured. The cytotoxicity of the complexes was evaluated using MTT method in MCF-7 cells, HeLa cells and HepG2 cells. The pGL3-lus was used as a reporter gene, and the transfection efficiency of complexesat HeLa cells was evalutated by measuring activity of luciferase. Results The result of 1H-NMR showed the purity of these synthesized polymers was high. The particle size of complexes were decreased with the increment of N /P ratios. The Zeta potential of complexes increased with the increment of N /P ratios. The cytotoxicity of the complexes increased with the increment of N /P ratios. The synthesized polymers showed lower cytotoxicity than unmodified PEI. The new synthesized polymers had maintained the high transfection efficiency at high N /P ratios. In particular, the optimal transfection efficiency of (P188) 1- PEI (N /P = 24) was significantly higher than that of PEI (N /P = 6) . Conclusion The P188 modifed PEI can serve as a effective non-viral gene carriers to transfect Hela cells.

BACKGROUND: Thymoma is frequently associated with myasthenia gravis (MG). However, whether MG is a factor for the outcome of patients with thymoma following complete thymectomy remains unknown. The aim of this study is to investigate the effect of thymoma with MG prognostic factors. METHODS: A retrospective analysis of The Chinese Alliance for Research in Thymomas (ChART) database within 1992-2012 complete cases 875 cases, 20 years follow-up data analysis thymic tumor tissue type credits and MG, Masaoka staging and prognosis, postoperative adjuvant therapy and relationship with the prognosis of surgical removal of the way. RESULTS: Thymic tumor tissue type credit has correlation with MG, difference was statistically significant (χ²=24.908, P<0.001). MG: incidence of B2 type (58/178, 32.58%) > B3 type (65/239, 27.20%) > B1 (27/132, 20.45%) > AB (43/267, 16.10%) > type A, 10.17% (6/59), Masaoka stage has no correlation with MG (χ²=0.365, P=1.365). Survival analysis showed that the WHO classification, Masaoka stage associated with prognosis (P<0.05), and whether the merger MG (χ²=0.113, P=0.736), postoperative adjuvant radiotherapy (χ²=0.380, P=0.538) has nothing to do with the prognosis, postoperative adjuvant chemotherapy is associated with poor prognosis (χ²=14.417, P<0.001). Whether has nothing to do with the prognosis of the thymus resection (χ²=1.548, P=1.548), whether the whole correlated with the curative effect of thymus excision with MG (χ²=24.695, P<0.001). CONCLUSIONS Thymoma patients with MG and extended thymectomy have no correlation with prognosis. Extended thymectomy can improve the effect of MG patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; complications ; diagnosis ; surgery ; Prognosis ; Retrospective Studies ; Survival Analysis ; Thymoma ; complications ; Young Adult

OBJECTIVE:To improve the synthesis technology of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2 (1H)-ketone. METHODS:Using 2-methyl-4(3H)-quinazolone as starting material,the synthesis technology of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2(1H)-ketone was improved by clorination, nucleophilic substitution, diarylamine alkylation and nitro reductive cyclization. The yield of it was investigated. RESULTS:The structure of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2(1H)-ketone had been verified by 1H-NMR and ESI-MS. The yield was 43.5%and improved by 23.3% compared to 20.2% before improvement. CONCLUSIONS:Improved technology is simpler and milder, which is suitable for the batch preparation of laboratory study.

Objective:To establish a paclitaxel (PTX)-resistance cell line of human cervical carcinoma Hela/PTX and investigate its biological features. Methods:Using Hela as the negative cells,drug-resistant cervical cancer Hela/PTX cells were applied as the target cells. The morphology changes were observed under an optical microscope;the drug resistance of Hela/PTX to different chemotherapeutic drugs was detected by CCK-8 method. The accumulation of drugs in the cells was determined by HPLC. The expression of P-glycoprotein (P-gp), Survivin protein and mRNA was detected by Western blot and RT-PCR. Results:Hela/PTX multidrug resistant cell line was successfully established. The resistance index to PTX was 58.40 and the resistance index of cross-resistance to docetaxel and 5-fluorouracil was 8.11 and 4.62,respectively. The mRNA expression level of P-gp and Survivin protein in Hela/PTX cells respectively was(9.93 +0.90) times(P < 0.05) and(3.02 +0.57) times(P <0.05) of that in Hela cells. The expression of P-gp and Survivin protein in drug-resistant cells was significantly higher than that in parental cells.Conclusion:Human cervical cancer resistant cell line Hela/PTX with the basic biological characteristics of multidrug resistance is successfully established, which can be used as an in vitro model for the studies on paclitaxel resistance mechanism and provide experimental basis for the studies of multidrug resistance mechanism of cervical cancer.

Objective:To explore the effect of oxycontin combined with gabapentin on the clinical cure and immunity for patients with neuropathic cancer pain.Methods:80 patients with neuropathic cancer pain were enrolled in our hospital from June to 2016 July,of which patients divided into two groups randomly,Group A(n=40) accepted oxycontin treatment,and Group B (n=40) adopted gabapentin based on the patients in Group A.The VAS score and curative effect of the patients were compared between two groups;The quality of life of all patients were evaluated post-treatment,and the change of immunity indexes were compared and analyzed.Results:The VAS score of all patients was decreased significantly compared with pre-treatment (P＜0.05),and the score of Group B was lower than those patients in Group A (P＜0.05);The total remission rate of Group B was significantly higher than those of Group A (P＜0.05);after treatment,the score of appetite,emotion,sleep,daily activities,social communications of all patients decreased significantly compared with pre-treatment (P＜0.05),and the change of Group B was decrease significantly higher than those patients in Group A (P＜0.05);the immune index of two groups was significantly increased (P＜0.05),and the level of the indexes including IgG,IgA,IgM,CD4+,CD4+/CD8+ and circulating immune complex (CIC) increased compared with pre-treatment remarkably (P＜0.05),and which change in Group B was significantly higher than Group A (P＜0.05).Conclusions:Oxycontin combined with gabapentin for patients with neuropathic cancer pain deserved popularization in clinical,and which not only possessed well clinical effect,but also increased the quality of life.