To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

Objective:To investigate the progression pattern of acquired resistance to osimertinib and the treatment method as well as the therapeutic effect of salvage therapy in advanced lung cancer patients with epidermal growth factor receptor (EGFR) sensitive mutation or T790M mutation after the treatment of tyrosine-kinase inhibitor (TKI).Methods:The data of 145 patients with advanced lung cancer treated with osimertinib in Jiangsu Cancer Hospital between April 2017 (the approval time of osimertinib in China) and May 2019 were collected. At the last follow-up (December 2019), a total of 87 (60.0%) patients had acquired resistance to osimertinib, 61 (70.1%) of whom received salvage treatment; for patients with dramatic progression after resistance, chemotherapy was mainly given in the salvage therapy; for patients with gradual or local progression after resistance, the continuing targeted drug therapy and the local therapy were given. Imaging evaluation and Kaplan-Meier method were used to analyze the progression pattern of acquired resistance to osimertinib and the survival status, and to compare the salvage treatment results among subgroups.Results:The median follow-up time of 61 patients receiving salvage therapy was 11 months (4-32 months), among which 58 (95.1%) patients again had resistance to osimertinib, and 24 (39.3%) patients died of lung cancer. The median progression-free survival (PFS) time and overall survival (OS) time for the whole cohort was 2.5 months (95% CI 2.1-3.0 months) and 19.0 months (95% CI 13.7-26.3 months), respectively. The 1-year and 2-year OS rate was 72.1% and 41.7%, respectively. Among 61 patients receiving salvage therapy, 8 (13.1%) , 30 (49.2%) and 23 (37.7%) cases had dramatic progression, gradual progression and local progression, respectively; when given timely and proper salvage treatment, there were no statistically differences in PFS and OS of the patients in the above three subgroups (all P>0.05). There were no statistically differences in PFS and OS between patients receiving local therapy (24 cases) and patients not receiving local therapy (37 cases) after the progression occurred (all P>0.05). Among 58 patients with resistance to osimertinib again after the salvage therapy, 6 patients with gradual or local progression had more than 6-mouth PFS after the salvage therapy. Conclusions:Dramatic, gradual and local progression are the main patterns in patients with acquired resistance to osimertinib. The therapeutic efficacy of salvage therapy still shows some disappointing results.

Objective: To analyze the feature of breast complex cystic masses and to classify it at ultrasonography (US), which applied to the Breast Imaging Reporting and Data System (BI-RADS) categories 4a to 4c with pathological results as the golden standards. Methods: The ultrasonographic data and clinical features of 78 patients with complex cystic masses confirmed by pathology in Cancer Hospital from July 2014 to June 2017 were retrospectively reviewed. The complex cystic breast masses were divided into four classes on the basis of their US features: type 1 [thick wall and (or) thick septa (> 0.5 mm)], type 2 (one or more intra-cystic masses), type 3 (mixed cystic and solid components with cystic components more than 50%) and type 4 (mixed cystic and solid components with solid components more than 50%). Positive values (PPVs) were calculated for each type. Multiple linear regression analysis was used to analyze the ultrasonographic features of the masses (lesion size, margins, blood flow resistance index, calcification, and axillary lymph nodes, etc.) with malignant correlation. Results: There were 81 lesions in 78 patients. Among the 81 masses based on US appearance, 14 (17.3%) were classified as type Ⅰ, 18 (22.2%) as type Ⅱ, 18 (22.2%) as type Ⅲ, and 31 (38.3%) as type Ⅳ. The positive predictive values of the malignant lesions of type Ⅰ, type Ⅱ, Ⅲ and Ⅳ were 7.1%, 16.7%, 61.1% and 48.3%, respectively (P=0.040). In all the 81 masses, 14 were BI-RADS categories 4a, 18 were BI-RADS categories 4b and 49 were BI-RADS categories 4c. Masses with maximum diameter equal to or larger than 2.0 cm, unclear margins, RI≥0.7 and presence of abnormal axillary nodes assessment had a high probability of malignancy (P=0.030, 0.038, <0.001 and 0.025, respectively). Conclusion Ultrasound typing is helpful for differentiating benign and malignant breast complex cysts and classifying BI-AIDS 4a to 4c, thus providing clearer treatment for clinical practice.

Objective To investigate the relationship between the incidence of radiation-induced brain stem injury after intensity-modulated radiotherapy (IMRT) and the radiation dose volume in patients with nasopharyngeal carcinoma.Methods A retrospective analysis was performed on the data of 258 patients newly diagnosed with nasopharyngeal carcinoma who received IMRT in our group from 2005 to 2013.The radiation dose per unit volume of brain stem was analyzed.The relationship between the incidence of brain stem injury induced by IMRT and the radiation dose volume was studied.The survival rate was calculated using the Kaplan-Meier method.The factors influencing the radiation-induced brain stem injury were analyzed using the Cox regression model.Results Two patients with stage T3 disease and three patients with T4 disease had radiation-induced brain stem injury.The 3-and 5-year injury incidence rates were 1.6％ and 2.4％,respectively.The latency ranged between 9 and 58 months,with a median latency of 19 months.The median D1％ and Dmax for the brain stem were 54.24 and 59.22 Gy in all patients,54.31 and 59.45 Gy in patients with stage T3 disease,and 61.29 and 66.37 Gy in patients with stage T4 disease,respectively.In the five patients with brain stem injury,the D1％ and Dmax were larger than 60 and 63 Gy,respectively.The univariate analysis showed that the incidence of radiation-induced brain stem injury was correlated with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 (all P=0.01).The incidence of radiation-induced brain stem injury was significantly lower in patients with D1％,Dmax,D0.1 cm3,D0.5 cm3,and D1.0 cm3 no larger than 60,63,60,58,and 56 Gy,respectively (all P =0.00).Conclusions The incidence of radiation-induced brain stem injury after IMRT is relatively low in patients with nasopharyngeal carcinoma.Strict control of the dose to the brain stem may help to reduce the incidence of brain stem injury and improve the long-term quality of life.