Randomness Regularization with Simple Consistency Training for Neural Networks.

Randomness is widely introduced in neural network training to simplify model optimization or avoid the over-fitting problem. Among them, dropout and its variations in different aspects (e.g., data, model structure) are prevalent in regularizing the training of deep neural networks. Though effective and performing well, the randomness introduced by these dropout-based methods causes nonnegligible inconsistency between training and inference. In this paper, we introduce a simple consistency training strategy to regularize such randomness, namely R-Drop, which forces two output distributions sampled by each type of randomness to be consistent. Specifically, R-Drop minimizes the bidirectional KL-divergence between two output distributions produced by dropout-based randomness for each training sample. Theoretical analysis reveals that R-Drop can reduce the above inconsistency by reducing the inconsistency among the sampled sub structures and bridging the gap between the loss calculated by the full model and sub structures. Experiments on 7 widely-used deep learning tasks ( 23 datasets in total) demonstrate that R-Drop is universally effective for different types of neural networks (i.e., feed-forward, recurrent, and graph neural networks) and different learning paradigms (supervised, parameter-efficient, and semi-supervised). In particular, it achieves state-of-the-art performances with the vanilla Transformer model on WMT14 English → German translation ( 30.91 BLEU) and WMT14 English → French translation ( 43.95 BLEU), even surpassing models trained with extra large-scale data and expert-designed advanced variants of Transformer models. Our code is available at GitHub https://github.com/dropreg/R-Drop.

Manipulation of crystallization nucleation and thermal degradation of PLA films by multi-morphologies CNC-ZnO nanoparticles.

Currently, the quest for more renewable and biodegradable materials is a scientific priority to address the problems of petroleum-based plastics are difficult to degrade. In this work, cellulose nanocrystals (CNC) have been used as a template and four morphologies of CNC-ZnO nanocomposites were prepared via a hydrothermal method, and CNC-ZnO/polylactic acid (PLA) composite films were obtained by solution casting. We find that CNC-ZnO nanocomposites as heterogeneous nucleating agents improved the crystallinity and the film with flower-like CNC-ZnO was improved by 2.4 %. Ea required for thermal degradation of the PLA films decreased to 66-81 % of that of neat PLA, calculated by the Kissinger method, the Friedman method, and the Flynn-Wall-Ozawa (FWO) method. The R2 model was the solid degradation mechanism of the PLA films, analyzed through the Coats-Redfern method and the Criado method. The H-bond content of the composite films was significantly reduced after thermal aging at 150 °C. We found that three-dimensional CNC-ZnO (ZnO-3) made more prominent contributions to the crystallization, thermal degradation, and thermal aging of PLA films than other dimensional. The thermal properties can be regulated by the dimension, size, and apparent morphology of CNC-ZnO nanoparticles.

R2-DDI: relation-aware feature refinement for drug-drug interaction prediction.

Precisely predicting the drug-drug interaction (DDI) is an important application and host research topic in drug discovery, especially for avoiding the adverse effect when using drug combination treatment for patients. Nowadays, machine learning and deep learning methods have achieved great success in DDI prediction. However, we notice that most of the works ignore the importance of the relation type when building the DDI prediction models. In this work, we propose a novel R$^2$-DDI framework, which introduces a relation-aware feature refinement module for drug representation learning. The relation feature is integrated into drug representation and refined in the framework. With the refinement features, we also incorporate the consistency training method to regularize the multi-branch predictions for better generalization. Through extensive experiments and studies, we demonstrate our R$^2$-DDI approach can significantly improve the DDI prediction performance over multiple real-world datasets and settings, and our method shows better generalization ability with the help of the feature refinement design.

Characterization of a novel detergent-resistant type I pullulanase from Bacillus megaterium Y103 and its application in laundry detergent.

This study aims to find a moderate pullulanase for detergent industry. The pulY103B gene (2217 bp) from Bacillus megaterium Y103 was cloned and expressed in Escherichia coli. PulY103B contained four conserved regions of glycoside hydrolase family (GH) 13 and the typical sequence of type I pullulanase. The optimal reaction conditions of PulY103B were pH 6.5 and 40 °C. In addition, it remained stable below 40 °C and over 80% of activity was retained at pH ranging from 6.0 to 8.5. The best substrate for the enzyme was pullulan. Furthermore, it exhibited activity toward wheat starch (36.5%) and soluble starch (33.4%) but had no activity toward amylose and glycogen. Maltotriose and maltohexaose were major pullulan hydrolysis products. Soluble starch and amylopectin were mainly hydrolyzed into maltotetraose. These results indicated that PulY103B is a novel type I pullulanase with transglycosylation activity via formation of α-1,4-glucosidic linkages. Moreover, PulY103B was strongly stimulated by nonionic detergents [viz, Tween 20 (10%), Tween 80 (1%), Triton X-100 (20%)] and commercial liquid detergents (3.0 g/L). Wash performance tests demonstrated that the mixture of PulY103B and detergent removed starch-based stains better than using detergent alone (p < 0.05). Therefore, this pullulanase has big potential as a detergent additive.

MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation.

Objective: Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the pathognomonic EWS-ETS chimeric transcripts and their corresponding oncoproteins. It has been suggested that the EWS-ETS oncogenic action can mediate microRNA (miRNA) processing. Importantly, small extracellular vesicles (sEVs), including those frequently referred to as exosomes have been shown to be highly enriched with tumor-derived small RNAs such as miRNAs. We hypothesized that ESFT-specific sEVs are enriched with certain miRNAs which could be utilized toward an exo-miRNA biomarker signature specific to this disease. Methods: We performed miRNAseq to compare both the exo-derived and cell-derived miRNA content from 8 ESFT, 2 osteosarcoma, 2 non-cancerous cell lines, and pediatric plasma samples. Results: We found that sEVs derived from ESFT cells contained nearly 2-fold more number of unique individual miRNAs as compared to non-ESFT samples. Quantitative analysis of the differential enrichment of sEV miRNAs resulted in the identification of 62 sEV-miRNAs (exo-miRNAs) with significant (P < .05) enrichment variation between ESFT and non-ESFT sEV samples. To determine if we could utilize this miRNA signature to diagnose ESFT patients via a liquid biopsy, we analyzed the RNA content of total circulating sEVs isolated from 500 µL plasma from 5 pediatric ESFT patients, 2 pediatric osteosarcoma patients, 2 pediatric rhabdomyosarcoma patients, and 4 non-cancer pediatric controls. Pearson's clustering of 60 of the 62 candidate exo-miRNAs correctly identified 80% (4 of 5) of pathology confirmed ESFT patients. Importantly, RNAseq analysis of tumor tissue from the 1 outlier, revealed a previously uncharacterized EWS-FLI1 translocation.Conclusions: Taken together, these findings support the development and validation of an exo-miRNA-based liquid biopsy to aid in the diagnosis and monitoring of ESFT.

Effect of alginate coatings incorporated with chitinase from 'Baozhu' pear on the preservation of cherry tomato during refrigerated storage.

The effects of edible coatings based on sodium alginate with 'Baozhu' pear chitinase on the quality of cherry tomatoes during refrigerated storage were evaluated. Cherry tomatoes inoculated with Fusarium oxysporum were coated and stored up to 21 days. All coatings with the chitinase significantly reduced F. oxysporum proliferation on cherry tomatoes during storage and extended the shelf life of cherry tomatoes effectively (p < .05). Results showed that alginate coatings with the chitinase could prevent weight loss, maintain firmness, and slow down the changes of titratable acidity and vitamin C (p < .05) in a dose-dependent manner. However, no significant differences were observed between T3 (1% alginate/0.15% 'Baozhu' pear chitinase/1% glycerin) and T4 (1% sodium alginate/0.3% 'Baozhu' pear chitinase/1% glycerin) (p > .05). Overall, alginate coating with 0.15% 'Baozhu' pear chitinase could be a promising method to maintain the quality of cherry tomatoes.

Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway.

Very little is known about how the material properties of protein condensates assembled via liquid-liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like condensates of the transcription factor TFEB exhibit low fusion propensity in vitro and in living cells. We directly measured the attraction force between droplets, and we characterized the interfacial tension, viscosity, and elasticity of TFEB condensates. TFEB condensates contain rigid interfacial boundaries that govern their interaction behaviors. Several small molecules, including Ro-3306, modify the material properties of TFEB condensates, increasing their size and fusion propensity. These compounds promote lysosomal biogenesis and function in a TFEB-dependent manner without changing its cytoplasmic-nuclear translocation. Ro-3306 promotes autophagy activity, facilitating degradation of toxic protein aggregates. Our study helps explain how protein condensates are maintained as physically separate entities and reveals that the material properties of TFEB condensates can be harnessed to modulate TFEB activity.

Marinobacter mangrovi sp. nov., isolated from mangrove sediment.

A novel marine bacterium, designated strain CHFG3-1-5T, was isolated from mangrove sediment sampled at Jiulong River estuary, Fujian, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CHFG3-1-5T belonged to the genus Marinobacter, with the highest sequence similarity to Marinobacter segnicrescens SS011B1-4T (97.6%), followed by Marinobacter nanhaiticus D15-8WT (97.5%), Marinobacter bohaiensis T17T (97.1%) and Marinobacter hydrocarbonoclasticus SP.17T (90.6%). The bacterium was Gram-stain-negative, facultative anaerobic, oxidase- and catalase-positive, rod-shaped and motile with a polar flagellum. Strain CHFG3-1-5T grew optimally at 32-37 °C, pH 6.0-8.0 and in the presence of 2.0-3.0% (w/v) NaCl. The G+C content of the chromosomal DNA was 61.1 mol%. The major respiratory quinone was determined to be Q-9. The principal fatty acids were C16 : 0, summed feature 3 (C16 : 1 ω7c/ω6c), C12 : 0, summed feature 9 (C17 : 1 iso ω9c and/or C16 : 0 10-methyl), C12 : 0 3-OH and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three phospholipids, one glycolipid and two aminolipids. The average nucleotide identity and digital DNA-DNA hybridization values among the genomes of strain CHFG3-1-5T and the reference strains were 73.4-79.4 and 19.6-22.4%, respectively. Like many other species reported in the genus Marinobacter, strain CHFG3-1-5T was able to oxidise iron. The combined genotypic and phenotypic data showed that strain CHFG3-1-5T represents a novel species within the genus Marinobacter, for which the name Marinobacter mangrovi sp. nov. is proposed, with the type strain CHFG3-1-5T (=MCCC 1A18306T=KCTC 82398T).

Stress analysis and experiment on a split-type ultra-high-pressure die for synthesizing diamond.

In order to obtain a higher pressure-bearing capacity and a larger sample volume and prolong the life of the high-pressure die, a novel high-pressure die for synthesizing gem-grade diamond is investigated with the finite element method. This device is the split-type die, and the cylinder is a combined type. Furthermore, this paper studies the stress distribution of the split-type cylinder and compares it with that of the traditional belt-type die. According to the simulation results, the split-type cylinder has much smaller stress than that of the belt-type cylinder, and it can bear much higher pressure. Meanwhile, the experimental tests also show that the high-pressure die with a split cylinder has a stronger pressure-bearing capacity than the belt-type die. Apart from that, the split-type cylinder has a better performance in easy manufacturing, strong pressure-bearing capacity, and replaceable performance.

SH-1028, An Irreversible Third-Generation EGFR TKI, Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer.

SH-1028 is an irreversible third-generation EGFR TKI. Both SH-1028 and osimertinib have a pyrimidine structure (a typical mutant-selective EGFR TKI structure). Compared with osimertinib, SH-1028 is modified on the indole ring, thus resulting in a more stable 6,7,8,9-tetrahydro-pyrrolo [1, 2-a] indol structure. In this study, we explored the anti-tumor effect of SH-1028 in vitro and in vivo, the inhibition of cell signal, such as EGFR and ERK phosphorylation, and verified the relationship between the pharmacokinetics and pharmacodynamic responses. Firstly, SH-1028 selectively inhibited EGFR sensitive and resistant mutations, with up to 198-fold more effective compared with wild-type EGFR cells. Then, in mouse xenograft models, oral administration of SH-1028 at a daily dose of 5 mg/kg significantly inhibited proliferation of tumor cells with EGFR sensitive mutation (exon 19 del) and resistant mutation (T790 M) for consecutive 14 days, with no TKI-induced weight loss. Moreover, SH-1028 exhibited good bioavailability, and was distributed extensively from the plasma to the tissues. The main metabolite of SH-1028, Imp3, was tested and showed no wild-type EGFR inhibition or off-target effects. In conclusion, SH-1028 is a new third-generation EGFR inhibitor that exhibits potent activity against EGFR sensitive and resistant (T790 M) mutations.

LPS-induced vein endothelial cell injury and acute lung injury have Btk and Orai 1 to regulate SOC-mediated calcium influx.

Patients with sepsis and sepsis-related complications have a high mortality. Endothelial cell dysfunction plays a central role in sepsis pathophysiological process. In sepsis patients, endothelial cell apoptosis is associated with intracellular calcium overload. Multiple functions in the apoptotic process have been found to be regulated by calcium signaling. Our previous work had proved that LPS-induced cell injury was associated with store-operated calcium (SOC) entry mediated by stromal interaction molecule-1 (STIM 1) in Human umbilical vein endothelial cells (HUVEC), but the underlying molecular mechanism has not been adequately defined. Here we report that the LPS-induced cell injury is related to the calcium overload in HUVEC. SOC entry mediated by calcium release-activated calcium modulator (Orai) 1 and transient receptor potential canonical (TRPC) 1 was associated with LPS-induced calcium overload and cell apoptosis. Bruton's tyrosine kinase (Btk)/Phospholipase C(PLC) γ/inositol 1,4,5-triphosphate receptor (IP3R) played a major role in regulating calcium overload in LPS-induced HUVEC. Knockdown of Btk markedly inhibited the expressions of Orai 1 and its downstream molecule IP3R but not that of TRPC1 in LPS-induced HUVEC. In mice, knockdown of Btk and Orai 1 inhibited LPS-induced calcium overload, pulmonary vascular endothelial cell (VEC) injury and acute lung injury. These findings demonstrated that Btk acts as a regulator of calcium-dependent signaling, especially in the Orai 1-mediated SOC entry of the LPS-induced VEC.

Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers.

PURPOSE: Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs). MATERIALS AND METHODS: We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and identified 619 proteins composing the core ESFT sEV proteome. We compared these core proteins to databases of common plasma-based proteins and sEV-associated proteins found within healthy plasma to identify proteins unique or enriched within ESFT. RESULTS: From these analyses, two membrane bound proteins with biomarker potential were selected, CD99/MIC2 and NGFR, to develop a liquid-based assay enriching of ESFT-associated sEVs and detection of sEV mRNA cargo (i.e., EWS-ETS transcripts). We employed this immuno-enrichment approach to diagnosis of ESFT utilizing plasma (250 µl) from both localized and metastatic ESFT pediatric patients and cancer-free controls, and showed significant diagnostic power [AUC = 0.92, p = 0.001 for sEV numeration, with a PPV = 1.00, 95% CI = (0.63, 1.00) and a NPV = 0.67, 95% CI = (0.30, 0.93)]. CONCLUSIONS: In this study, we demonstrate utilization of circulating ESFT-associated sEVs in pediatric patients as a source of minimally invasive diagnostic and potentially prognostic biomarkers.

Cloning and characterization of a novel amylopullulanase from Bacillus megaterium Y103 with transglycosylation activity.

OBJECTIVE: To obtain a novel pullulanase with synthetic ability from a microorganism and characterize its substrates specificity. RESULTS: A novel pullulanase, PulY103A, from Bacillus megaterium Y103 was purified, characterized and expressed in Escherichia coli. PulY103A contained the signature sequences of type I pullulanases and showed 94.7% identity with a type I pullulanase (BmPul) from B. megaterium WW1210, showing similar molecular weight (110.8 kDa) and optimal pH (6.5). However, PulY103A had an optimal temperature of of 45 °C and exhibited relatively higher activity toward amylose (48.3%) compared with pullulan (100%), soluble starch (67.5%), and amylopectin (23.1%). The thin-layer chromatography results showed that the major pullulan hydrolysis products were maltotriose and maltohexaose, which differed from those reported in other pullulanases. On the basis of enzyme specificity, PulY103A was an amylopullulanase, which presented transglycosylation activity by forming α-1,4-glucosidic linkages. CONCLUSIONS: A novel amylopullulanase with transglycosylation activity was characterized. The features of this enzyme suggested its potential to produce maltohexaose.

Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells.

One of the major risk factors for asthma development is exposure to environmental allergens. House dust mites (HDM) can induce DNA damage, resulting in asthma. Resveratrol (RES) produced by several plants, has anti­apoptotic properties and may affect a variety of biological processes. The aim of the present study was to investigate the protective role of RES against apoptosis in bronchial epithelial cells. C57BL/6J mice treated with HDM exhibited high levels of cell apoptosis, while RES significantly reversed this process. Induced DNA damage was more severe in the HDM group vs. the HDM combined with RES group. This result was confirmed by immunostaining and western blot analysis of the protein expression of the DNA damage­related gene γH2AX, which was highly induced by HDM. In addition, treatment with RES protected bronchial epithelial cells exposed to HDM from DNA damage. RES decreases reactive oxygen species levels to inhibit oxidative DNA damage in bronchial epithelial cells. Furthermore, compared with the HDM group, induced cell apoptosis could be attenuated by RES in the group of combined treatment with RES and HDM. A DNA repair inhibitor augmented DNA damage and apoptosis in bronchial epithelial cells, whereas RES significantly attenuated cell apoptosis through inhibiting DNA damage.

Lyn regulates epithelial-mesenchymal transition in CS-exposed model through Smad2/3 signaling.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is progressive and not fully reversible. Cigarette smoking is one of the most commonly and important risk factors for COPD, which contributes to airway remodeling, the outstanding pathological changes in COPD. One potential mechanism which might be important for airway remodeling is the process called epithelial-mesenchymal transition (EMT). However, the underlying molecular mechanisms of EMT in CS-induced COPD are still poorly understood. METHODS: Two Gene Expression Omnibus (GEO) datasets (GSE108134 and GSE5058) were combined to identify the key genes involved in COPD. Then, single-gene analysis of Lyn was performed. Lyn expression was confirmed in patients with COPD. 16HBE cells were treated with cigarette smoking extracts (CSE). Wild type (WT) C57BL/6 J mice and Lyn+/+ transgenic mice were exposed to CSE to establish CS-exposed model. Pathological changes were observed by hematoxylin-eosin staining. The expression levels of EMT markers were examined by using western blot and immunofluorescence. The expression and phosphorylation levels of Lyn and Smad2/3 were detected as well. RESULTS: The gain of mesenchymal markers vimentin and α-SMA with a concomitant loss of E-cadherin was observed in both in vivo and in vitro studies. Meanwhile, cigarette smoking extracts (CSE) induced EMT in 16HBE cells in a time- and dose- dependent manner. Furthermore, by analyzing GEO datasets and using molecular methods, we explored a kinase, Lyn, its expression correlated with the expression of E-cadherin, vimentin and α-SMA in CS-exposed model. Moreover, we found that EMT induced by CSE was regulated by activated Lyn through phosphorylation of Smad2/3. CONCLUSIONS: In summary, we found that Lyn regulates epithelial-mesenchymal transition in CS-exposed model through Smad2/3 signaling. As a kinase, Lyn is "druggable", and might provide a therapeutic opportunity for targeting EMT. Therefore, our research might provide a new method to treat COPD by targeting Lyn kinase specifically.

Method of distortion and pointing correction of a ground-based telescope.

Detection accuracy is an important performance indicator of ground-based telescopes and is affected mainly by pointing error, geometric distortion of the optical system, and parameter errors caused by machining error and installation error. To improve detection accuracy, a modified algorithm based on a simulated annealing algorithm is proposed in this paper; this algorithm is able to correct pointing, derive a geometric distortion solution, and re-estimate some parameters of telescopes simultaneously. The efficiency of the proposed method is verified by using the observation data of the telescope, whose aperture is 600 mm under two distortion models (the physical model and polynomial fitting model). The results show that the method presented in this paper can effectively solve the problem of nonconvergence of the distortion solution with a pointing error. The final angle error under the polynomial fitting model is 1.07″, and the pixel error is 0.06 pixels; the errors under the physical model are 1.08″ and 0.07 pixels. The correction effect under the two distortion models is basically the same, but the averaged operation speed based on the physical model is 19.45% faster.

Expert consensus on multidisciplinary therapy of colorectal cancer with lung metastases (2019 edition).

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

Microstructure, Tensile, and Creep Behaviors of Ti-22Al-25Nb (at.%) Orthorhombic Alloy with Equiaxed Microstructure.

This article investigates the tensile and creep behaviors of the Ti-22Al-25Nb (at.%) alloy with equiaxed microstructure. The experimental results show that the equiaxed microstructures are formed by isothermal forging in the α2 + B2 + O phase region, and then heat treating in α2 + B2 + O and B2 + O phase regions. The equiaxed particles are determined by isothermal forging and solution heat treating, and the acicular O phase is obtained by adjusting the aging temperature. The strengths of the alloy are sensitive to the thickness of the secondary acicular O phase. Increase in aging temperature improves strength and reduces the ductility. Deformation of the alloy mainly depends on the volume fraction and deformability of the B2 phase. During the high-temperature tensile deformation, the flow stress decreases with the increasing deformation temperature and increases with the increasing strain rate. The microstructure obtained by higher aging temperature (HT-840) has better creep resistance, due to the coarsening of the secondary acicular O phase.

Gastrointestinal stromal tumor (GIST) with liver metastases: An 18-year experience from the GIST cooperation group in North China.

Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.