Porpose To investigate the optimal concentration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on DNA synthesis and their synergism indensity arrested human retinal pigment epithelial (RPE) cells. Methods Growth factor effects in cultured human RPE of the 6th generation were assessed by [3 H]-thymidine incorporation and radioautography. Results EGF and bFGF were potent stimulators when used alone,and their optimal concentrations were 10ng/ml in DMEM and 1ng/ml in 2% serum DMEM.When used in combination (10ng/ml EGF and 10ng/ml bFGF),they caused a significant enhancement of [3 H]-thymidine incorporation about 2.96 times. Conclusion EGF and bFGF were potent stimulators in RPE cells,and demonstrated synergism in their action. (Chin J Ocul Fundus Dis,1998,14:98-100)
Synergistic effects of drug combinations are very important in improving drug efficacy or reducing drug toxicity. However, due to the complex mechanism of action between drugs, it is expensive to screen new drug combinations through trials. It is well known that virtual screening of computational models can effectively reduce the test cost. Recently, foreign scholars successfully predicted the synergistic value of new drug combinations on cancer cell lines by using deep learning model DeepSynergy. However, DeepSynergy is a two-stage method and uses only one kind of feature as input. In this study, we proposed a new end-to-end deep learning model, MulinputSynergy which predicted the synergistic value of drug combinations by integrating gene expression, gene mutation, gene copy number characteristics of cancer cells and anticancer drug chemistry characteristics. In order to solve the problem of high dimension of features, we used convolutional neural network to reduce the dimension of gene features. Experimental results showed that the proposed model was superior to DeepSynergy deep learning model, with the mean square error decreasing from 197 to 176, the mean absolute error decreasing from 9.48 to 8.77, and the decision coefficient increasing from 0.53 to 0.58. This model could learn the potential relationship between anticancer drugs and cell lines from a variety of characteristics and locate the effective drug combinations quickly and accurately.
The synergistic effect of drug combinations can solve the problem of acquired resistance to single drug therapy and has great potential for the treatment of complex diseases such as cancer. In this study, to explore the impact of interactions between different drug molecules on the effect of anticancer drugs, we proposed a Transformer-based deep learning prediction model—SMILESynergy. First, the drug text data—simplified molecular input line entry system (SMILES) were used to represent the drug molecules, and drug molecule isomers were generated through SMILES Enumeration for data augmentation. Then, the attention mechanism in the Transformer was used to encode and decode the drug molecules after data augmentation, and finally, a multi-layer perceptron (MLP) was connected to obtain the synergy value of the drugs. Experimental results showed that our model had a mean squared error of 51.34 in regression analysis, an accuracy of 0.97 in classification analysis, and better predictive performance than the DeepSynergy and MulinputSynergy models. SMILESynergy offers improved predictive performance to assist researchers in rapidly screening optimal drug combinations to improve cancer treatment outcomes.
ObjectiveTo investigate the effectiveness of comprehensive rhinoplasty with autogenous costal cartilage grafting and prosthesis augmentation rhinoplasty in the treatment of secondary nasal deformity with saddle nasal deformity after cleft lip surgery. MethodsThe clinical data of 96 patients with secondary nasal deformity with saddle nasal deformity after cleft lip surgery between September 2008 and January 2019 were retrospectively analyzed. There were 17 males and 79 females with an average age of 25.6 years (range, 17-38 years). Autogenous costal cartilage grafts were used to construct stable nasal tip framework and enhance the strength of alar cartilage. Nasal dorsum prostheses (39 cases of bulge, 45 cases of silicone prosthesis) or autogenous costal cartilage (12 cases) were used for comprehensive rhinoplasty. Visual analogue scale (VAS) score was used to evaluate the postoperative satisfaction subjectively, and nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle were calculated to evaluate objectively before and after operation. ResultsAll patients were followed up 6 months to 8 years, with an average of 13.4 months. Nasal septal hematoma occurred in 3 patients after operation, which was improved after local aspiration and nasal pressure packing. Two cases had mild deformation of the rib cartilage graft of the nasal dorsum, one of which had no obvious deviation of the nasal dorsum and was not given special treatment, and one case underwent the cartilage graft of the nasal dorsum removed and replaced with silicone prosthesis. The incisions of the other patients healed by first intention, and there was no complication such as postoperative infection and prosthesis displacement. The nasal alar height symmetry index, nasal alar width symmetry index, nasal dorsum central axis deviation angle, and nasal columella deviation angle significantly improved after operation when compared with preoperative ones (P<0.05). Postoperative subjective satisfaction evaluation reached the level of basic satisfaction or above, and most of them were very satisfied. Conclusion Comprehensive rhinoplasty using autologous rib cartilage grafting to construct a stable nasal tip support, combined with dorsal nasal prosthesis or autologous cartilage implantation, can achieve good effectiveness on secondary nasal deformity with saddle nasal deformity after cleft lip surgery.
Objective To investigate the changes and significance of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in intestinal mucosa in rats with obstructive jaundice. MethodsTwenty-four SD rats were randomly divided into sham operation (SO) group and bile duct ligation (BDL) group, and each group were randomly divided into the day 7 and day 14 subgroup. The expression of ICAM-1 was assayed by immunohistochemistry. The level of TNF-α was determined by ELISA. The activity of myeloperoxidase (MPO) and diamine oxidase (DAO) was determined as well.ResultsOn the day 7 and 14, in the bile duct ligation group, the ICAM-1 protein was mainly expressed in the intestinal epithelia and increased with the time on (P<0.05); the level of TNFα increased from (14.25±1.01) ng/g to (23.83±1.43) ng/g (P<0.01); the intestinal DAO activity decreased from (1.70±0.36) U/mg to (1.22±0.41) U/mg (P<0.01),and plasma DAO activity increased from (6.44±1.74)U/ml to (8.93±1.29) U/ml (P<0.01); the MPO activity increased from (2.85±1.22 ) U/mg to (4.93±1.37) U/mg (P<0.01). ConclusionThe ICAM-1 expression is significantly upregulated and the level of TNFα significantly increases after bile duct ligation, which may be involved in the PMNmediated injury to intestinal mucosa.
Objective To investigate a best method of obtaining the sural neurofasciocutaneous flap by observing the models of different pedicles based sural neurofasciocutaneous flaps in rabbits and the effect of different pedicles on the survival of the flaps. Methods Forty adult New Zealand rabbits (male or female, weighing 2.5-3.0 kg) were randomly divided into 4 groups (10 rabbits in each). The flaps of 7 cm × 1 cm were designed at the lateral hind legs, and the pedicle was 0.5 cmin length. In group A, the flaps were elevated based on a single perforator pedicle; in group B, the flaps were elevated based on fascia pedicle; in group C, the flaps were elevated based on perforator-plus fascia pedicle; and in group D, the flaps were elevated and sutured in situ. At 7 days after operation, the flap survival rate was recorded, and the blood flow in the center of the flap was monitored by laser doppler flowmetry. The perfusion unit (PU) was measured. Results After operation, the flaps had no obvious swell ing, and the flaps had good color at the proximal end, but pale at the distal end in groups A and B. Obvious swell ing was observed with pale color at the distal flaps in group C, but swell ing decreased gradually. However, the skin color became dark gradually in group D after operation. The flap survival rates were 74.0% ± 2.7%, 60.0% ± 2.5%, 75.0% ± 3.5%, and 0 in groups A, B, C, and D respectively after 7 days of operation. The PU values were 83.39 ± 4.25, 28.96 ± 13.49, 81.85 ± 5.93, and 8.10 ± 3.36 in groups A, B, C, and D respectively. There were significant differences in flap survival rates and PU values between groups A, B, C and group D (P lt; 0.05). Significant differences were found between groups A, C and group B (P lt; 0.05), but no significant difference between group A and group C (P gt; 0.05). Conclusion The sural neurofasciocutaneous flap based on a single perforator pedicle has a rel iable blood supply and enough venous drainage, which is one of the best methods to obtain the sural neurofasciocutaneous flap.