Objective:To analyze the efficacy and safety of standard chemotherapy and immune checkpoint inhibitors (CI) combined with radiotherapy (RT) in driver-gene negative (wild-type) oligometastatic non-small cell lung cancer (NSCLC) patients with central nervous system involvement.Methods:In this multicenter retrospective cohort study, oligometastatic NSCLC patients receiving first-line chemo-immunotherapy-based therapy were analyzed. Between January 2017 and January 2023, a total of 98 eligible patients were enrolled from the National Cancer Center/Cancer Hospital (Beijing/Shenzhen) and Shanxi Province Cancer Hospital. All participants were divided into chemo-immunotherapy (CI) group (28.6%, n=28) and chemo-immuno-radiotherapy (CIR) group (71.4%, n=70) according to whether receiving radiotherapy. Baseline characteristics were well-balanced between two groups, with no statistically significant differences (all P>0.05). The primary endpoint of the study was overall survival (OS), while progression-free survival (PFS) was designated as a key secondary endpoint. Qualitative data were compared by Chi-square test. Survival analysis was conducted using Kaplan-Meier method, and prognostic analysis was performed by multivariate Cox regression models. Results:The median PFS in the CIR and CI groups was 21.8 and 11.5 months, respectively, and the difference was not statistically significant ( P=0.211). The median OS in the CIR group was significantly better ( P=0.036) than 25.3 months in the CI group. The median OS in the CIR group was not reached. The 2-year local regional control rates for the whole brain radiotherapy patients, stereotactic radiotherapy / stereotactic radiosurgery patients and CI groups were 33.3% ,100% and 83.4%, respectively. Multivariate analysis showed that brain radiotherapy was an independent protective factor for OS in patients with oligometastatic brain metastases at baseline ( HR=0.47, 95% CI=0.22-0.99, P=0.047). Subgroup analysis revealed that patients with 1-3 metastatic lesions benefited from radiotherapy (PFS: HR=0.47, 95% CI=0.22-1.03, P=0.060; OS: HR=0.34, 95% CI=0.12-0.98, P=0.046). Conclusions:For central nervous system involved oligometastatic NSCLC patients, the integration of chemo-immunotherapy with radiotherapy is well tolerated and can improve the efficacy, particularly among those with a limited number of metastatic lesions.

AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

Objective:To analyze the efficacy and safety of standard chemotherapy and immune checkpoint inhibitors (CI) combined with radiotherapy (RT) in driver-gene negative (wild-type) oligometastatic non-small cell lung cancer (NSCLC) patients with central nervous system involvement.Methods:In this multicenter retrospective cohort study, oligometastatic NSCLC patients receiving first-line chemo-immunotherapy-based therapy were analyzed. Between January 2017 and January 2023, a total of 98 eligible patients were enrolled from the National Cancer Center/Cancer Hospital (Beijing/Shenzhen) and Shanxi Province Cancer Hospital. All participants were divided into chemo-immunotherapy (CI) group (28.6%, n=28) and chemo-immuno-radiotherapy (CIR) group (71.4%, n=70) according to whether receiving radiotherapy. Baseline characteristics were well-balanced between two groups, with no statistically significant differences (all P>0.05). The primary endpoint of the study was overall survival (OS), while progression-free survival (PFS) was designated as a key secondary endpoint. Qualitative data were compared by Chi-square test. Survival analysis was conducted using Kaplan-Meier method, and prognostic analysis was performed by multivariate Cox regression models. Results:The median PFS in the CIR and CI groups was 21.8 and 11.5 months, respectively, and the difference was not statistically significant ( P=0.211). The median OS in the CIR group was significantly better ( P=0.036) than 25.3 months in the CI group. The median OS in the CIR group was not reached. The 2-year local regional control rates for the whole brain radiotherapy patients, stereotactic radiotherapy / stereotactic radiosurgery patients and CI groups were 33.3% ,100% and 83.4%, respectively. Multivariate analysis showed that brain radiotherapy was an independent protective factor for OS in patients with oligometastatic brain metastases at baseline ( HR=0.47, 95% CI=0.22-0.99, P=0.047). Subgroup analysis revealed that patients with 1-3 metastatic lesions benefited from radiotherapy (PFS: HR=0.47, 95% CI=0.22-1.03, P=0.060; OS: HR=0.34, 95% CI=0.12-0.98, P=0.046). Conclusions:For central nervous system involved oligometastatic NSCLC patients, the integration of chemo-immunotherapy with radiotherapy is well tolerated and can improve the efficacy, particularly among those with a limited number of metastatic lesions.

Objective:To analyze the symmetry of different reference planes in the surgical simulation design of patients with protrusive jaw deformity with high and low eyes.Methods:Fifteen patients with partial jaw deformity were selected from January 2019 to June 2020, including 3 males and 12 females, aged 18-26 years, with average 23.78 years. Inclusion criteria were that the patients, aged more than 18 years, were diagnosed as protrusive jaw deformity with maxillary occlusal plane tilt and high and low eyes by clinical and imaging analysis. Three different 3D reference plane systems were established by different modeling methods. The distance between the landmarks of soft and hard tissues and the median sagittal plane was measured. The symmetry of skull was qualitatively analyzed by mirror image technique. The difference of three reference planes in surgical simulation symmetry of patients with protrusion jaw and high and low eyes was evaluated by one-way ANOVA.Results:Qualitative analysis showed that in the three measurement planes, the symmetry of the third reference plane was the best, and the symmetry of the second and the first was poor. Quantitative analysis showed that in measurement index of hard tissue, there was statistical difference between the distance of each landmark in the reference plane established by Method 3 and Method 1, Method 2 [(1.65±1.19) mm; (3.37±1.58) mm; (3.26±2.36) mm, P<0.05], but there was no statistical difference between Method 1 and Method 2 (P > 0.05). The measurement result of soft tissue was consistent with that of hard tissue, and the distance of each landmark in Method 3 from the median sagittal plane was very small, and the mean error was less than 0.5 mm, which was consistent with the clinical results. Conclusions:Digital model surgery technology can assist orthognathic surgeons in the design and prediction of surgical scheme, especially for patients with special partial jaw deformity.

OBJECTIVETo prepare paeonol-beta-cyclodextrin inclusion complex (Pae-beta-CYD) loaded colon-specific release tablets.

METHODThe core tablets were prepared with the mixture of Pae-beta-CYD inclusion complex, peotin and calcium acetate, and coated with ethanolic solution of Eudragit S100. The effects of coating weight, amount of plasticizer, curing time and temperature on the release of drug from tablets were investigated in vitro.

RESULTAbout 5-6 h retarded release of paeonol in the dissolution media of pectinase or rats colon contents were obtained by 12% coating weight gain and 20% Dibutyl phthalate (DBP) was used as plasticizer, and subsequently curing the tablets at 45 degrees C for 12 h.

CONCLUSIONPae-beta-CYD loaded colon-specific release tablets showed pH environment and enzyme dependant release properties.

Acetophenones ; pharmacokinetics ; therapeutic use ; Animals ; Colitis, Ulcerative ; drug therapy ; Colon ; drug effects ; Drug Delivery Systems ; methods ; Excipients ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Rats ; Rats, Sprague-Dawley ; Tablets, Enteric-Coated ; chemistry ; beta-Cyclodextrins ; chemistry

OBJECTIVETo study the stability and degradation kinetics of Ketoprofen-Paeonol conjugate (Ket-Pae).

METHODRP-HPLC method was used to determine the solubility and partition coefficient of Ket-Pae. Stability test was carried out to investigate the factors affecting Ket-Pae. The kinetic studies of Ket-Pae degradation were conducted in different pH buffer solutions and 80% rat plasma at 37 degrees C.

RESULTKet-Pae showed significant degradation phenomenon at high temperature. The solubility of Ket-Pae was decreased about 200 to 300 times compared with parent drugs in water while the lnP increased about 4 times. The degradation curve displayed a V-shape, and kept maximum stability at week acidic (pH 5.0, t(1/2) = 11.4 d). Ket-Pae degraded quickly with very short half life of 1.3 min in plasma, therefore easily released ketoprofen and paeonol.

CONCLUSIONThe lipophilicity of Ket-Pae is increased, its stability is affected by temperature and pH value.

Acetophenones ; chemistry ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; Hydrogen-Ion Concentration ; Ketoprofen ; chemistry ; Kinetics ; Solubility

OBJECTIVETo prepare the diammonium glycyrrhizinate-loaded chitosan nanoparticles (DG-CS NPs), and evaluate its pharmaceutical properties and pharmacodynamic effects on ulcerative colitis (UC).

METHODDG-CS NPs were prepared by spray drying method and optimized by orthogonal design. The morphology, size and in vitro release of DG-CS NPs were investigated. The therapeutic effects of DG-CS NPs on UC mice induced by dextran sulfate were evaluated preliminarily through disease active index method.

RESULTThe size of DG-CS NPs with loading capacity about (51.25 +/- 1.75)% was in the range of 300-600 nm. The release of DG-CS NPs was associated with environmental pH value and displayed significant therapeutic and preventive effects on UC.

CONCLUSIONDG-CS NPs prepared by spray drying method showed efficacy on UC mice.

Animals ; Chitosan ; chemistry ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Dextran Sulfate ; toxicity ; Disease Models, Animal ; Female ; Glycyrrhizic Acid ; chemistry ; therapeutic use ; Male ; Mice ; Nanoparticles ; chemistry

AIM: To establish the preparative method of dispersible tablet of total notoginseng saponin (DTTNS) by powder direct compression,and to evaluate it pharmaceutical characteristics. METHODS: The effect of factors on the disintegration of DT-TNS was investigated by single factor method,and the formulation was optimized through orthogonal design. RESULTS: The disintegration time of DT-TNS containing 40% total notoginseng saponin was within 1 min while the formulation mainly consisted of 49% MCC as filler,12% of PVPP mixed with 3% L-HPC as disintegrating agent. In addition,the dissolution of DT-TNS was almost finished in 10-15 min. CONCLUSION: The preparative method of DT-TNS by powder direct compression is simple,with short disintegration time and high dissolution rate.