AMHMDA: attention aware multi-view similarity networks and hypergraph learning for miRNA-disease associations identification.

In recent years, many experiments have proved that microRNAs (miRNAs) play a variety of important regulatory roles in cells, and their abnormal expression can lead to the emergence of specific diseases. Therefore, it is greatly valuable to do research on the association between miRNAs and diseases, which can effectively help prevent and treat miRNA-related diseases. At present, effective computational methods still need to be developed to better identify potential miRNA-disease associations. Inspired by graph convolutional networks, in this study, we propose a new method based on Attention aware Multi-view similarity networks and Hypergraph learning for MiRNA-Disease Associations identification (AMHMDA). First, we construct multiple similarity networks for miRNAs and diseases, and exploit the graph convolutional networks fusion attention mechanism to obtain the important information from different views. Then, in order to obtain high-quality links and richer nodes information, we introduce a kind of virtual nodes called hypernodes to construct heterogeneous hypergraph of miRNAs and diseases. Finally, we employ the attention mechanism to fuse the outputs of graph convolutional networks, predicting miRNA-disease associations. To verify the effectiveness of this method, we carry out a series of experiments on the Human MicroRNA Disease Database (HMDD v3.2). The experimental results show that AMHMDA has good performance compared with other methods. In addition, the case study results also fully demonstrate the reliable predictive performance of AMHMDA.

DLF-Sul: a multi-module deep learning framework for prediction of S-sulfinylation sites in proteins.

Protein S-sulfinylation is an important posttranslational modification that regulates a variety of cell and protein functions. This modification has been linked to signal transduction, redox homeostasis and neuronal transmission in studies. Therefore, identification of S-sulfinylation sites is crucial to understanding its structure and function, which is critical in cell biology and human diseases. In this study, we propose a multi-module deep learning framework named DLF-Sul for identification of S-sulfinylation sites in proteins. First, three types of features are extracted including binary encoding, BLOSUM62 and amino acid index. Then, sequential features are further extracted based on these three types of features using bidirectional long short-term memory network. Next, multi-head self-attention mechanism is utilized to filter the effective attribute information, and residual connection helps to reduce information loss. Furthermore, convolutional neural network is employed to extract local deep features information. Finally, fully connected layers acts as classifier that map samples to corresponding label. Performance metrics on independent test set, including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under curve, reach 91.80%, 92.36%, 92.08%, 0.8416 and 96.40%, respectively. The results show that DLF-Sul is an effective tool for predicting S-sulfinylation sites. The source code is available on the website https://github.com/ningq669/DLF-Sul.

FCCCSR_Glu: a semi-supervised learning model based on FCCCSR algorithm for prediction of glutarylation sites.

Glutarylation is a post-translational modification which plays an irreplaceable role in various functions of the cell. Therefore, it is very important to accurately identify the glutarylation substrates and its corresponding glutarylation sites. In recent years, many computational methods of glutarylation sites have emerged one after another, but there are still many limitations, among which noisy data and the class imbalance problem caused by the uncertainty of non-glutarylation sites are great challenges. In this study, we propose a new semi-supervised learning algorithm, named FCCCSR, to identify reliable non-glutarylation lysine sites from unlabeled samples as negative samples. FCCCSR first finds core objects from positive samples according to reverse nearest neighbor information, and then clusters core objects based on natural neighbor structure. Finally, reliable negative samples are selected according to clustering result. With FCCCSR algorithm, we propose a new method named FCCCSR_Glu for glutarylation sites identification. In this study, multi-view features are extracted and fused to describe peptides, including amino acid composition, BLOSUM62, amino acid factors and composition of k-spaced amino acid pairs. Then, reliable negative samples selected by FCCCSR and positive samples are combined to establish models and XGBoost optimized by differential evolution algorithm is used as the classifier. On the independent testing dataset, FCCCSR_Glu achieves 85.18%, 98.36%, 94.31% and 0.8651 in sensitivity, specificity, accuracy and Matthew's Correlation Coefficient, respectively, which is superior to state-of-the-art methods in predicting glutarylation sites. Therefore, FCCCSR_Glu can be a useful tool for glutarylation sites prediction and FCCCSR algorithm can effectively select reliable negative samples from unlabeled samples. The data and code are available on https://github.com/xbbxhbc/FCCCSR_Glu.git.

Identifying drug-target interactions via heterogeneous graph attention networks combined with cross-modal similarities.

Accurate identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are more and more popular in recent years. Conventional computational methods almost simply view heterogeneous networks which integrate diverse drug-related and target-related dataset instead of fully exploring drug and target similarities. In this paper, we propose a new method, named DTIHNC, for $\mathbf{D}$rug-$\mathbf{T}$arget $\mathbf{I}$nteraction identification, which integrates $\mathbf{H}$eterogeneous $\mathbf{N}$etworks and $\mathbf{C}$ross-modal similarities calculated by relations between drugs, proteins, diseases and side effects. Firstly, the low-dimensional features of drugs, proteins, diseases and side effects are obtained from original features by a denoising autoencoder. Then, we construct a heterogeneous network across drug, protein, disease and side-effect nodes. In heterogeneous network, we exploit the heterogeneous graph attention operations to update the embedding of a node based on information in its 1-hop neighbors, and for multi-hop neighbor information, we propose random walk with restart aware graph attention to integrate more information through a larger neighborhood region. Next, we calculate cross-modal drug and protein similarities from cross-scale relations between drugs, proteins, diseases and side effects. Finally, a multiple-layer convolutional neural network deeply integrates similarity information of drugs and proteins with the embedding features obtained from heterogeneous graph attention network. Experiments have demonstrated its effectiveness and better performance than state-of-the-art methods. Datasets and a stand-alone package are provided on Github with website https://github.com/ningq669/DTIHNC.

MVNN-HNHC:A multi-view neural network for identification of human non-histone crotonylation sites.

Crotonylation on lysine sites in human non-histone proteins plays a crucial role in biology activities. However, because traditional experimental methods for crotonylation site identification are time-consuming and labor-intensive, computational prediction methods have become increasingly popular in recent years. Despite its significance, crotonylation site prediction has received less attention in non-histone proteins than in histones. In this study, we proposed a Multi-View Neural Network for identification of Human Non-Histone Crotonylation sites, named MVNN-HNHC. MVNN-HNHC integrated multi-view encoding features and adaptive encoding features through multi-channel neural network to deeply learn about attribute differences between crotonylation sites and non-crotonylation sites from various aspects. In MVNN-HNHC, convolutional neural networks can obtain local information from these features, and bidirectional long short term memory networks were utilized to extract sequence information. Then, we employ the attention mechanism to fuse the outputs of various feature extraction modules. Finally, the fully connection network acted as the classifier to predict whether a lysine site was crotonylation site or non-crotonylation site. Performance metrics on independent test set, including sensitivity, specificity, accuracy, Matthews correlation coefficient, and area under the curve (AUC) values reach 80.06 %, 75.77 %, 77.06 %, 0.5203, and 0.7792, respectively. To verify the effectiveness of this method, we carry out a series of experiments and the results show that MVNN-HNHC is an effective tool for predicting crotonylation sites in non-histone proteins. The data and code are available on https://github.com/xbbxhbc/junjun0612.git.

A study of knowledge on Alzheimer's disease and attitudes of Chinese social residents toward Alzheimer's disease: A cross-sectional survey in China.

OBJECTIVE: Social residents become increasingly concerned about Alzheimer's dementia (AD) as a global public health crisis. China's AD population is the largest and growing fastest. However, no study has examined Chinese social residents' knowledge and attitudes concerning Alzheimer's illness. This study examined Chinese social residents' AD knowledge and attitudes using the Alzheimer's Disease Knowledge Scale (ADKS) and dementia attitudes scale (DAS). DESIGN: Cross-sectional survey. SAMPLE: 338 social residents over 18 years old from various Chinese regions were recruited using convenient sampling. MEASUREMENTS: The ADKS (Chinese) and the Dementia Attitude Scale (Chinese) were used to assess their knowledge and attitude regarding AD. RESULTS: A total of 328 respondents (97.04%) completed the survey. ADKS = 19.44 ± 3.33; DAS = 86.98 ± 12.7. Age and education levels can have a substantial impact on ADKS scores, and education levels can have a substantial impact on DAS scores. CONCLUSIONS: Low levels of awareness and acceptance of AD exist among Chinese residents. The results indicate that China must immediately implement comprehensive AD education for its social residents.

pQLyCar: Peptide-based dynamic query-driven sample rescaling strategy for identifying carboxylation sites combined with KNN and SVM.

Lysine carboxylation is one of the most crucial type of post-translation modification, which plays a significant role in catalytic mechanisms. Therefore, it is essential to study lysine carboxylation and explore its biological mechanism. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are much more convenience and faster. Therefore, it is urgent to establish an accurate carboxylation identification model. Herein we proposed a method, named pQLyCar for identification of lysine carboxylation using SVM as classifier. In pQLyCar, a peptide-based dynamic query-driven sample rescaling strategy (pDQD-SR) is proposed to address the class imbalance of training data, which builds a specific prediction model for each query sample. KNN algorithm calculates distance between samples according to original sequences instead of feature vectors. Information entropy is applied to select optimal size of sliding window and various types of sequence- and position-based features are incorporated for construction of feature space, including residues composition (RC), K-space and position-special amino acid propensity (PSAAP). Finally, the performance of pQLyCar is measured with a specificity of 96.49% and a sensibility of 99.59% using jackknife test method, which indicated that pQLyCar method can be a useful tool for prediction of lysine carboxylation sites.

Analysis and prediction of human acetylation using a cascade classifier based on support vector machine.

BACKGROUND: Acetylation on lysine is a widespread post-translational modification which is reversible and plays a crucial role in some biological activities. To better understand the mechanism, it is necessary to identify acetylation sites in proteins accurately. Computational methods are popular because they are more convenient and faster than experimental methods. In this study, we proposed a new computational method to predict acetylation sites in human by combining sequence features and structural features including physicochemical property (PCP), position specific score matrix (PSSM), auto covariation (AC), residue composition (RC), secondary structure (SS) and accessible surface area (ASA), which can well characterize the information of acetylated lysine sites. Besides, a two-step feature selection was applied, which combined mRMR and IFS. It finally trained a cascade classifier based on SVM, which successfully solved the imbalance between positive samples and negative samples and covered all negative sample information. RESULTS: The performance of this method is measured with a specificity of 72.19% and a sensibility of 76.71% on independent dataset which shows that a cascade SVM classifier outperforms single SVM classifier. CONCLUSIONS: In addition to the analysis of experimental results, we also made a systematic and comprehensive analysis of the acetylation data.

dForml(KNN)-PseAAC: Detecting formylation sites from protein sequences using K-nearest neighbor algorithm via Chou's 5-step rule and pseudo components.

Formylation is a type of post-translational modification that can occur on lysine sites, which plays an irreplaceable role in organism. To better understand the mechanism, it is necessary to identify formylation sites in proteins accurately. Computational method is popular because of its more convenience and higher speed than traditional experimental methods. However, no computational method has been proposed for prediction of lysine formylation. In this study, we developed a predictor named LFPred to identify lysine formylation sites using sequence features (including amino acid composition (AAC), binary profile features (BPF), and amino acid index (AAI)) combined K-nearest neighbor algorithm as classifier. We chose discrete window instead of continuous window according to information entropy. Besides, we took measure to select more reliable negative samples and address the severe imbalance between positive samples and negative samples. Finally, the performance of LFPred is measured with a specificity of 79.9% and a sensibility of 81.4% using jackknife test method, which indicated that our method can be a useful tool for prediction of lysine formylation sites.

Identifying N6-methyladenosine sites using extreme gradient boosting system optimized by particle swarm optimizer.

N6-methyladenosine (m6A) is the one of the most important RNA modifications, playing the role of splicing events, mRNA exporting and stability to cell differentiation. Because of wide distribution of m6A in genes, identification of m6A sites in RNA sequences has significant importance for basic biomedical research and drug development. High-throughput laboratory methods are time consuming and costly. Nowadays, effective computational methods are much desirable because of its convenience and fast speed. Thus, in this article, we proposed a new method to improve the performance of the m6A prediction by using the combined features of deep features and original features with extreme gradient boosting optimized by particle swarm optimization (PXGB). The proposed PXGB algorithm uses three kinds of features, i.e., position-specific nucleotide propensity (PSNP), position-specific dinucleotide propensity (PSDP), and the traditional nucleotide composition (NC). By 10-fold cross validation, the performance of PXGB was measured with an AUC of 0.8390 and an MCC of 0.5234. Additionally, PXGB was compared with the existing methods, and the higher MCC and AUC of PXGB demonstrated that PXGB was effective to predict m6A sites. The predictor proposed in this study might help to predict more m6A sites and guide related experimental validation.

Detecting Succinylation sites from protein sequences using ensemble support vector machine.

BACKGROUND: Lysine succinylation is a new kind of post-translational modification which plays a key role in protein conformation regulation and cellular function control. To understand the mechanism of succinylation profoundly, it is necessary to identify succinylation sites in proteins accurately. However, traditional methods, experimental approaches, are labor-intensive and time-consuming. Computational prediction methods have been proposed recent years, and they are popular because of their convenience and high speed. In this study, we developed a new method to predict succinylation sites in protein combining multiple features, including amino acid composition, binary encoding, physicochemical property and grey pseudo amino acid composition, with a feature selection scheme (information gain). And then, it was trained using SVM (Support Vector Machine) and an ensemble learning algorithm. RESULTS: The performance of this method was measured with an accuracy of 89.14% and a MCC (Matthew Correlation Coefficient) of 0.79 using 10-fold cross validation on training dataset and an accuracy of 84.5% and a MCC of 0.2 on independent dataset. CONCLUSIONS: The conclusions made from this study can help to understand more of the succinylation mechanism. These results suggest that our method was very promising for predicting succinylation sites. The source code and data of this paper are freely available at https://github.com/ningq669/PSuccE .

[Effects of Jinwu Jiangu recipe on IL-17/STAT3 signals in rheumatoid arthritis synoviocytes].

This paper aimed to investigate the effects of Jinwu Jiangu recipe total extract on the IL-17/STAT3 signals in rheumatoid arthritis synovial fibroblasts(RASF). The primary RASFs were cultured by tissue piece method in vitro， and divided into blank control group， Jinwu Jiangu recipe low dose group， Jinwu Jiangu recipe middle dose group， Jinwu Jiangu recipe high dose group， and tripterygium glycosides control group. They were then treated with corresponding serum free medium， different doses of Jinwu Jiangu recipe total extract(0.06， 0.6， 6.0 g·L⁻¹)， and tripterygium glycosides(0.03 g·L⁻¹) respectively for 24 hours. The gene expression levels of RORα， RORγt， and STAT3 mRNA were detected by polymerase chain reaction(PCR)， and the protein activity of IL-17R and pSTAT3 were measured by Western blot assay. The results showed that as compared with blank control group， the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA in RASF were significantly declined(P<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe total extract middle dose group and high dose group can down-regulate the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA(P<0.05)， and the effect was more obvious in high dose group(P<0.01). As compared with blank control group， the protein expression levels of IL-17R and pSTAT3 in each treatment group were obviously decreased(P<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe high dose group had more obvious effect in down-regulating the protein expression of pSTAT3(P<0.01). Therefore， Miao medicine Jinwu Jiangu recipe total extract can down-regulate the expressions of RORα， RORγt， and STAT3 mRNA， and inhibit the protein activity of IL-17R and pSTAT3 in RASF.

Identification of S-glutathionylation sites in species-specific proteins by incorporating five sequence-derived features into the general pseudo-amino acid composition.

As a selective and reversible protein post-translational modification, S-glutathionylation generates mixed disulfides between glutathione (GSH) and cysteine residues, and plays an important role in regulating protein activity, stability, and redox regulation. To fully understand S-glutathionylation mechanisms, identification of substrates and specific S-Glutathionylated sites is crucial. Experimental identification of S-glutathionylated sites is labor-intensive and time consuming, so establishing an effective computational method is much desirable due to their convenient and fast speed. Therefore, in this study, a new bioinformatics tool named SSGlu (Species-Specific identification of Protein S-glutathionylation Sites) was developed to identify species-specific protein S-glutathionylated sites, utilizing support vector machines that combine multiple sequence-derived features with a two-step feature selection. By 5-fold cross validation, the performance of SSGlu was measured with an AUC of 0.8105 and 0.8041 for Homo sapiens and Mus musculus, respectively. Additionally, SSGlu was compared with the existing methods, and the higher MCC and AUC of SSGlu demonstrated that SSGlu was very promising to predict S-glutathionylated sites. Furthermore, a site-specific analysis showed that S-glutathionylation intimately correlated with the features derived from its surrounding sites. The conclusions derived from this study might help to understand more of the S-glutathionylation mechanism and guide the related experimental validation. For public access, SSGlu is freely accessible at http://59.73.198.144:8080/SSGlu/.

PGlcS: Prediction of protein O-GlcNAcylation sites with multiple features and analysis.

As a widespread type of protein post-translational modification, O-GlcNAcylation plays crucial regulatory roles in almost all cellular processes and is related to some diseases. To deeply understand O-GlcNAcylated mechanisms, identification of substrates and specific O-GlcNAcylated sites is crucial. Experimental identification is expensive and time-consuming, so computational prediction of O-GlcNAcylated sites has considerable value. In this work, we developed a novel O-GlcNAcylated sites predictor called PGlcS (Prediction of O-GlcNAcylated Sites) by using k-means cluster to obtain informative and reliable negative samples, and support vector machines classifier combined with a two-step feature selection. The performance of PGlcS was evaluated using an independent testing dataset resulting in a sensitivity of 64.62%, a specificity of 68.4%, an accuracy of 68.37%, and a Matthew׳s correlation coefficient of 0.0697, which demonstrated PGlcS was very promising for predicting O-GlcNAcylated sites. The datasets and source code were available in Supplementary information.

Accurate in silico identification of protein succinylation sites using an iterative semi-supervised learning technique.

As a widespread type of protein post-translational modifications (PTMs), succinylation plays an important role in regulating protein conformation, function and physicochemical properties. Compared with the labor-intensive and time-consuming experimental approaches, computational predictions of succinylation sites are much desirable due to their convenient and fast speed. Currently, numerous computational models have been developed to identify PTMs sites through various types of two-class machine learning algorithms. These methods require both positive and negative samples for training. However, designation of the negative samples of PTMs was difficult and if it is not properly done can affect the performance of computational models dramatically. So that in this work, we implemented the first application of positive samples only learning (PSoL) algorithm to succinylation sites prediction problem, which was a special class of semi-supervised machine learning that used positive samples and unlabeled samples to train the model. Meanwhile, we proposed a novel succinylation sites computational predictor called SucPred (succinylation site predictor) by using multiple feature encoding schemes. Promising results were obtained by the SucPred predictor with an accuracy of 88.65% using 5-fold cross validation on the training dataset and an accuracy of 84.40% on the independent testing dataset, which demonstrated that the positive samples only learning algorithm presented here was particularly useful for identification of protein succinylation sites. Besides, the positive samples only learning algorithm can be applied to build predictors for other types of PTMs sites with ease. A web server for predicting succinylation sites was developed and was freely accessible at http://59.73.198.144:8088/SucPred/.

Hierarchical hypergraph learning in association-weighted heterogeneous network for miRNA-disease association identification.

MicroRNAs (miRNAs) play a significant role in cell differentiation, biological development as well as the occurrence and growth of diseases. Although many computational methods contribute to predicting the association between miRNAs and diseases, they do not fully explore the attribute information contained in associated edges between miRNAs and diseases. In this study, we propose a new method, Hierarchical Hypergraph learning in Association-Weighted heterogeneous network for MiRNA-Disease association identification (HHAWMD). HHAWMD first adaptively fuses multi-view similarities based on channel attention and distinguishes the relevance of different associated relationships according to changes in expression levels of disease-related miRNAs, miRNA similarity information, and disease similarity information. Then, HHAWMD assigns edge weights and attribute features according to the association level to construct an association-weighted heterogeneous graph. Next, HHAWMD extracts the subgraph of the miRNA-disease node pair from the heterogeneous graph and builds the hyperedge (a kind of virtual edge) between the node pair to generate the hypergraph. Finally, HHAWMD proposes a hierarchical hypergraph learning approach, including node-aware attention and hyperedge-aware attention, which aggregates the abundant semantic information contained in deep and shallow neighborhoods to the hyperedge in the hypergraph. Our experiment results suggest that HHAWMD has better performance and can be used as a powerful tool for miRNA-disease association identification. The source code and data of HHAWMD are available at https://github.com/ningq669/HHAWMD/.

SSKM_Succ: A Novel Succinylation Sites Prediction Method Incorporating K-Means Clustering With a New Semi-Supervised Learning Algorithm.

Protein succinylation is a type of post-translational modification (PTM) that occurs on lysine sites and plays a key role in protein conformation regulation and cellular function control. When training in computational method, it is difficult to designate negative samples because of the uncertainty of non-succinylation lysine sites, and if not handled properly, it may affect the performance of computational models dramatically. Therefore, we propose a new semi-supervised learning method to identify reliable non-succinylation lysine sites as negative samples. This method, named SSKM_Succ, also employs K-means clustering to divide data into 5 clusters. Besides, information of proximal PTMs and three kinds of sequence features (grey pseudo amino acid composition, K-space and position-special amino acid propensity) are utilized to formulate protein. Then, we perform a two-step feature selection to remove redundant features and construct the optimization model for each cluster. Finally, support vector machine is applied to construct a prediction model for each cluster. Promising results are obtained by this method with an accuracy of 80.18 percent for succinylation sites on the independent testing dataset. Meanwhile, we compare the result with other existing tools, and it shows that our method is promising for predicting succinylation sites. Through analysis, we further verify that succinylated protein has potential effects on amino acid degradation and fatty acid metabolism, and speculate that protein succinylation may be closely related to neurodegenerative diseases. The code of SSKM_Succ is available on the web https://github.com/yangyq505/SSKM_Succ.git.

A Novel Method for Identification of Glutarylation Sites Combining Borderline-SMOTE With Tomek Links Technique in Imbalanced Data.

Glutarylation is a type of post-translational modification that occurs on lysine residues. It plays an irreplaceable role in various cellular functions. Therefore, identification of glutarylation sites is significant for understanding the molecular mechanism of glutarylation. In this study, we proposed a method named DEXGB_Glu to identify lysine glutarylation sites using XGBoost as classifier which was optimized by differential evolution algorithm. Aiming at the imbalance between positive samples and negative samples, Borderline-SMOTE method was employed to synthesize positive samples, increasing their amount equal to negative samples. Then, Tomek links technique was applied to filter out noise data. Analysis of this method and its results showed that differential evolution algorithm obviously improved the performance and the combination of Borderline-SMOTE and Tomek links effectively solved the imbalance between positive samples and negative samples. Finally, the performance of this method was much better than other methods in prediction of glutarylation sites. The data and code are available on https://github.com/ningq669/DEXGB_Glu.

[Clinical Analysis on the Therapeutic Efficacy of Autologous Hematopoietic Stem Cell Transplantation in 56 Multiple Myeloma Patients].

OBJECTIVE: To evaluate the therapeutic efficacy and prognosis of autologous stem Hematopoietic cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. METHODS: A retrospective study was conducted for 56 patients diagnosed with MM and then received auto-HSCT in our hospital from December 2008 to September 2016. RESULTS: All the patients successfully underwent hematopoietic reconstruction without transplantation-related mortality (TRM). The complete response (CR) rate of all the patients after induction chemotherapy was 23.2% (13/56), while the CR rate of these patients with auto-HSCT increased to 78.6% (44/56) (P<0.01). The CR plus VGPR (very good partial response) rates of these 56 patients after induction chemotherapy and auto-HSCT were 53.6%（30/56）and 94.6%（53/56） respectively (P<0.01). The median progression-free survival (PFS) time and median overall survival (OS) time were 37 and 71 months, respectively. The median PFS time in the patients with induction therapy containing bortezomib was 37 months, however, the median OS time did not reach to 71 months; the median PFS (P<0.01) and the median OS (P<0.01) in the patients with the induction chemotherapy without bortezomib was 27 and 51 months, respectively. Univariate analysis demonstrated that the patients maintained CR or VGPR after auto-HSCT or with less than 6 cycles of induction chemotherapy significantly correlated with PFS (P<0.01). CONCLUSION: auto-HSCT can further increase the CR rate, prolong PFS and OS time. Sequential auto-HSCT after bortezomib-based therapy is the first line therapy for the transplant-eligible MM patients. Maintenance treatment is beneficial to the sustained CR+VGPR patients after auto-HSCT.

Activations of mitogen-activated protein kinase and nuclear factor-kappaB by mechanical stretch result in ventilation-induced lung injury.

Mechanical ventilation is an important therapeutic technique for patients with respiratory failure. Nonetheless, it may cause or worsen lung injury. The specific triggers for cytokine release and the cellular origins of the inflammatory mediators in ventilation-induced lung injury (VILI) have yet to be defined. With the development of cytomechanics, we can study the lung cell response to mechanical strain. The initial step is mechanosensation, including stretch-activated ionchannels and the ECM-integrin-cytoskeleton pathway. Several intracellular signaling pathways then are activated and eventually result in increased transcription of specific genes. Mitogen-activated protein kinase cascade, nuclear factor(NF)-kappaB, PKC are all activated by mechanical stretch. But the mechanisms regulating lung stretch-induced cytokine production are still unclear. I hypotheses mechanical stretch initiate specific genes transcription, then the cytokines stimulate the cell again. This formed a positive feed back loop, which caused VILI. These studies may lead to the identification of new targets for therapeutic interventions and help to develop less aggressive ventilation strategies for patients with acute respiratory failure.