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.
Objective To explore the clinical efficacy and safety of percutaneous kyphoplasty (PKP) in the treatment of Kummell disease. Methods We retrospectively analyzed the clinical data of 11 patients with Kummell disease treated by PKP between January 2013 and January 2016. There were 8 males and 3 females with an average age of 72.3 years old ranging from 64 to 78. The injured vertebra was located at T11 in 2 patients, T12 in 3, and L1 in 6. All the patients suffered from lower back pain for 2.5-15.0 months averaging 7.6 months. Preoperative CT and MRI examinations showed that there were clear signs of intravertebral vacuum cleft and abnormal fluid signals. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and the height and kyphotic angle of the injured vertebral body were measured to evaluate the clinical outcomes before and after surgery. Results Follow-up was conducted for all 11 patients. Cement leakage occurred in 4 patients with no symptoms. The vertebral height, Cobb angel of the injured vertebra, VAS and ODI improved significantly after surgery and during the latest follow-up. Compared with those parameters after surgery, only VAS score was different during the latest follow-up. Conclusion PKP is safe and effective in the treatment of Kummell disease.
目的 探討使用生物型非骨水泥假體治療髖臼內陷癥的近期療效。 方法 2007年6月－2010年5月，對11例12髖髖臼內陷患者行生物型假體全髖關節置換術。男2例，女9例；年齡38～57歲，平均47.3歲。其中繼發于類風濕性關節炎7例，創傷4例；病程1～18年，平均8.9年；輕度髖臼內陷6髖，中度髖臼內陷6髖。采用Harris評分標準進行臨床療效評估，攝X線片進行影像學評估。 結果 術后第2天X線片示，人工股骨頭距Kohler’s線外移（1.42 ± 2.27）mm，較術前股骨頭內陷（?5.17 ± 2.04）mm明顯改善（P＜0.05）。術后1周，患者Harris評分為（85.75 ± 4.73）分，較術前（39.75 ± 5.24）分顯著提高（P＜0.05）。術后1年X線片示髖臼假體與髖臼內側壁無透亮線，已骨融合。術后患者獲隨訪2～5年。髖臼假體均無松動移位、脫位或移植骨的吸收。 結論 使用生物型非骨水泥假體結合自體骨移植治療髖臼內陷癥，能有效恢復髖臼運動中心的解剖位置，近期臨床療效滿意。
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.
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.
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.
目的 通過觀察卵巢早衰 POF 患者外周血CD4+CD25+調節性T細胞 Treg 及干擾素-γ（IFN-γ）、轉化生長因子-β(TGF-β)的變化，探討POF的免疫學發病機制。 方法 收集2011年12月－2012年9月就診的POF患者17例，卵巢儲備功能減退 DOR 患者11例，以及生殖中心健康育齡女性16例，流式細胞儀定量檢測外周血Treg數量，Elisa方法檢測血清IFN-γ、TGF-β的水平，并以FSH/LH評價卵巢儲備功能，進行相關性分析。 結果 與對照組相比，POF組和DOR組IFN-γ水平增高 P＜0.01 、TGF-β水平降低 P＜0.01 ，POF患者及DOR患者Treg比例降低 P＜0.01 ，IFN-γ的增高與卵巢儲備功能的下降呈顯著正相關 r=0.70，P＜0.01 。 結論 Treg 和IFN-γ、TGF-β水平與卵巢早衰密切相關，IFN-γ對評估卵巢儲備功能、預測卵巢早衰具有參考價值。
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.
Objective To discuss the elbow skin fold extension line in Kirschner wire internal fixation of extended supracondylar humeral fractures in children. Methods The clinical data of 58 children with extended supracondylar fractures of the humerus who met the selection criteria between August 2021 and July 2024 were retrospectively analyzed. In 28 cases, needle placement of medial epicondyle of humerus was performed with the assistance of the elbow skin fold extension line (study group), and 30 cases were assisted by routine touch of the medial epicondyle of the humerus (control group). There was no significant difference in baseline data such as gender, age, side, cause of injury, Gartland type, Kirschner wire configuration, and time from injury to operation between the two groups (P>0.05). The closed reduction rate, total operation time, time of medial humeral condyle pin placement, fluoroscopy times during medial pin placement, rate of one-time determination of medial entry point, ulnar nerve injury incidence, and fracture healing time were recorded and compared between the two groups. At the same time, the closed reduction rate of patients with the time from injury to operation ≤24 hours and >24 hours was compared. The elbow function was evaluated by Mayo elbow function score. Results The closed reduction rate of the study group was significantly higher than that of the control group (P<0.05). Among all patients, the closed reduction rate of patients with the time from injury to operation ≤24 hours [73.3% (22/30)] was significantly higher than that of patients >24 hours [42.9% (12/28)] (χ2=5.545, P=0.019). The total operation time, medial needle placement time, and fluoroscopy times in the study group were significantly less than those in the control group, and the one-time determination rate of medial needle entry point in the study group was significantly higher than that in the control group (P<0.05). There were 4 cases of ulnar nerve injury in the control group, and no ulnar nerve injury in the study group, but there was no significant difference in the incidence of ulnar nerve injury between the two groups (P>0.05). All patients were followed up 6-12 months (mean, 8 months). There was no bone nonunion in both groups, and the fracture healing time of the study group was significantly shorter than that of the control group (P<0.05). Volkmann ischemic contracture, heterotopic ossification, myositis ossificans, and premature epiphyseal closure were not observed after operation. No complications such as loosening or fracture of Kirschner wire occurred. At last follow-up, the Mayo elbow joint function score was used to evaluate function, and there was no significant difference between the two groups (P>0.05). Conclusion In the treatment of extended supracondylar fractures of the humerus in children, the elbow skin fold extension line can help to quickly locate the medial epicondyle of the humerus, quickly insert Kirschner wire, and reduce the operation time and trauma.
Objective To investigate the effect of nidus vespae on lymphocyte blastisation in mixed culture system of lymphocyte and pancreatic islet. Methods Solution of nidus vespae was extracted with ethanol from its herb. Rat lymphocyte and pig pancreatic islet were isolated and then were mixed together and cultured in incubators of 37 ℃ (concentration in volume: 5%CO2). Three different concentrations of extracted solution of nidus vespae （experimental group Ⅰ: 4.0 g/ml, group Ⅱ: 0.4 g/ml, group Ⅲ: 0.2 g/ml） were added to the mixed culture system of lymphocyte, respectively. Radioactive nuclide counts per minute were measured by 3H-thymdine test in order to examine the role of nidus vespae in inhibiting blatisation of lymphocyte, and the results were also compared with control group and CsA group, respectively. Results The counts were all reduced significantly (P＜0.001) in 3 experimental groups compared with control group (group Ⅰ 45.3%, group Ⅱ 29.6%and group Ⅲ 9.2%). It also showed that the inhibitory effect became ber in higher concentration but still weaker than that in CsA group (80.7%). Conclusion Nidus vespae could inhibit the blastisation of lymphocyte in mixed culture system of lymphocyte and pancreatic islet, and the effect increased as the the concentration increased, which may suggest that nidus vespae could suppress the rejection induced by T cells.