GraphDPA: Predicting drug-pathway associations by graph convolutional networks.

Pathway-based drug discovery is a promising strategy for the discovery of drugs with low toxicity and side effects. However, identifying the associations between drug and targeting pathways is challenging for this method. The formation of various biomolecular interaction databases and the development of neural network technology provide new ways for the large-scale prediction of drug-pathway associations. This article proposes a new model called GraphDPA, which represents the drug and pathway-gene association as a graph. We use graph convolutional networks (GCN) to learn the features of the drug and pathway and predict the drug-pathway association. The results show that GraphDPA can predict drug-pathway associations with high accuracy, which verify the potential of the GCN in drug discovery.

Association between new onset type 1 diabetes and real-world antibiotics and neonicotinoids' exposure-related gut microbiota perturbation.

BACKGROUND: The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes (T1D) children and their associations as environmental triggers through gut microbiota shifts remained unknown. We thus investigated the antibiotics and neonicotinoids' exposure levels and their associations with gut microbiota in pediatric T1D. METHODS: Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited. Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry. Children were grouped according to the kinds of antibiotics' and neonicotinoids' exposures, respectively. The 16S rRNA of fecal gut microbiota was sequenced, and the correlation with urine antibiotics and neonicotinoids' concentrations was analyzed. RESULTS: The overall detection rates of antibiotics were 72.5% and 61.2% among T1D and healthy children, whereas the neonicotinoids detection rates were 70.6% and 52.2% (P = 0.044). Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D, with the odd ratios of 2.579 and 3.911. Furthermore, co-exposure to antibiotics and neonicotinoids was associated with T1D, with the odd ratio of 4.924. Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota. However, children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together. CONCLUSION: High antibiotics and neonicotinoids exposures were found in T1D children, and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera, which might increase the risk of T1D.

Effective use of sequence information to predict CRISPR-Cas9 off-target.

The CRISPR/Cas9 gene-editing system is the third-generation gene-editing technology that has been widely used in biomedical applications. However, off-target effects occurring CRISPR/Cas9 system has been a challenging problem it faces in practical applications. Although many predictive models have been developed to predict off-target activities, current models do not effectively use sequence pair information. There is still room for improved accuracy. This study aims to effectively use sequence pair information to improve the model's performance for predicting off-target activities. We propose a new coding scheme for coding sequence pairs and design a new model called CRISPR-IP for predicting off-target activity. Our coding scheme distinguishes regions with different functions in the sequence pairs through the function channel. Moreover, it distinguishes between bases and base pairs using type channels, effectively representing the sequence pair information. The CRISPR-IP model is based on CNN, BiLSTM, and the attention layer to learn features of sequence pairs. We performed performance verification on two data sets and found that our coding scheme can represent sequence pair information effectively, and the CRISPR-IP model performance is better than others. Data and source codes are available at https://github.com/BioinfoVirgo/CRISPR-IP.

AttCRISPR: a spacetime interpretable model for prediction of sgRNA on-target activity.

BACKGROUND: More and more Cas9 variants with higher specificity are developed to avoid the off-target effect, which brings a significant volume of experimental data. Conventional machine learning performs poorly on these datasets, while the methods based on deep learning often lack interpretability, which makes researchers have to trade-off accuracy and interpretability. It is necessary to develop a method that can not only match deep learning-based methods in performance but also with good interpretability that can be comparable to conventional machine learning methods. RESULTS: To overcome these problems, we propose an intrinsically interpretable method called AttCRISPR based on deep learning to predict the on-target activity. The advantage of AttCRISPR lies in using the ensemble learning strategy to stack available encoding-based methods and embedding-based methods with strong interpretability. Comparison with the state-of-the-art methods using WT-SpCas9, eSpCas9(1.1), SpCas9-HF1 datasets, AttCRISPR can achieve an average Spearman value of 0.872, 0.867, 0.867, respectively on several public datasets, which is superior to these methods. Furthermore, benefits from two attention modules-one spatial and one temporal, AttCRISPR has good interpretability. Through these modules, we can understand the decisions made by AttCRISPR at both global and local levels without other post hoc explanations techniques. CONCLUSION: With the trained models, we reveal the preference for each position-dependent nucleotide on the sgRNA (short guide RNA) sequence in each dataset at a global level. And at a local level, we prove that the interpretability of AttCRISPR can be used to guide the researchers to design sgRNA with higher activity.

Association of ß-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children.

BACKGROUND: In addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM. AIM: To investigate the association of ß-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study. METHODS: This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the ß-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile. RESULTS: The male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40-11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60-2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors. CONCLUSION: Besides insulin resistance, ß-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

ANMDA: anti-noise based computational model for predicting potential miRNA-disease associations.

BACKGROUND: A growing proportion of research has proved that microRNAs (miRNAs) can regulate the function of target genes and have close relations with various diseases. Developing computational methods to exploit more potential miRNA-disease associations can provide clues for further functional research. RESULTS: Inspired by the work of predecessors, we discover that the noise hiding in the data can affect the prediction performance and then propose an anti-noise algorithm (ANMDA) to predict potential miRNA-disease associations. Firstly, we calculate the similarity in miRNAs and diseases to construct features and obtain positive samples according to the Human MicroRNA Disease Database version 2.0 (HMDD v2.0). Then, we apply k-means on the undetected miRNA-disease associations and sample the negative examples equally from the k-cluster. Further, we construct several data subsets through sampling with replacement to feed on the light gradient boosting machine (LightGBM) method. Finally, the voting method is applied to predict potential miRNA-disease relationships. As a result, ANMDA can achieve an area under the receiver operating characteristic curve (AUROC) of 0.9373 ± 0.0005 in five-fold cross-validation, which is superior to several published methods. In addition, we analyze the predicted miRNA-disease associations with high probability and compare them with the data in HMDD v3.0 in the case study. The results show ANMDA is a novel and practical algorithm that can be used to infer potential miRNA-disease associations. CONCLUSION: The results indicate the noise hiding in the data has an obvious impact on predicting potential miRNA-disease associations. We believe ANMDA can achieve better results from this task with more methods used in dealing with the data noise.

[Clinical analysis and countermeasures of 739 cases treated in the emergency department of stomatology in general hospital during COVID-19 epidemic].

PURPOSE: In this paper, based on the age, sex, disease type, and consultation time of dental emergency during COVID-19 epidemic, a comprehensive analysis of dental emergency management and prevention and control of COVID-19 was conducted. METHODS: A total of 739 emergency dental cases were collected from January 29 2020 to February 28 2020. They were divided into 3 groups，including adolescents (≤18 years), young adults (18 ~ 60 years), and elderly ( ≥60 years old). The data was analyzed using SPSS 21.0 software package. RESULTS: The ratio of male to female was 1.24∶1. There were 655 emergency cases during the day and 84 cases during the night. The types of diseases included pericoronitis (15.83%), apical periodontitis (14.21%), pulpitis (13.40%), periodontitis (12.31%), oral mucosal disease (12.18%), Oral and maxillofacial trauma (10.55%), oral and maxillofacial space infection (8.39%), dental disease in children (5.41%), oral and maxillofacial tumors (2.84%), temporomandibular joint dislocations and disorders (1.76%), and others (3.11%). CONCLUSIONS: Under the epidemic situation of the new coronavirus, as one of the high-risk departments, it is of great significance to enhance the clinical emergency skills and ability of emergency treatment, improve patients' oral health awareness, address the diagnosis and treatment of essential diseases, for the improvement the quality of dental medical care and the prevention and control of COVID-19 epidemic.

Life-threatening complications after microvascular decompression procedure: Lessons from a consecutive series of 596 patients.

The microvascular decompression procedure (MVD) is widely utilized on patients with neurovascular compression syndromes, such as trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia, which have failed medical therapy. However, surgical complications are an ongoing problem. We retrospectively reviewed a total of 596 patients undergoing MVD in the Affiliated Hospital of Qingdao University from January 2008 to December 2018. Furthermore, we discussed the cases with life-threatening complications to determine the potential causes, aiming to achieve the goal of safer microvascular decompression. There were seven cases with life-threatening complications. Of those complications, one was cerebellar infarction with acute hydrocephalus, one was infarction of the cerebellum and the brain stem with acute hydrocephalus and serious intracranial infection, two were cerebellar haematoma, one was multiple haemorrhage with acute hydrocephalus, one was supratentorial subdural haematoma, and one was cerebellar swelling with acute hydrocephalus. After therapy, one patient died, one was in a persistent vegetative state, and five were discharged from the hospital upon recovery. In brief, MVD is a safe operation, and life-threatening complications accompanying MVD are rare, but require attention. The causes of some life-threatening complications are still not completely clear. Surgeons should continuously improve surgical techniques and perioperative care to reduce potential risks.

Altered Serum Amino Acid and Acylcarnitine Profiles in Hyperinsulinemic Hypoglycemia and Ketotic Hypoglycemia.

Background: In addition to inborn metabolic disorders, altered metabolic profiles were reported to be associated with the risk and prognosis of some non-metabolic diseases, while as a rare metabolic disease, the overall secondary metabolic spectrum in congenital hyperinsulinemic hypoglycemia (HH) is largely undetermined. Therefore, we investigated metabolic profiles in HH patients and used ketotic hypoglycemia (KH) patients as a control cohort to unveil their distinct metabolic features. Methods: A total of 97 hypoglycemia children, including 74 with hyperinsulinemic hypoglycemia and 23 with ketotic hypoglycemia, and 170 euglycemia control subjects were studied retrospectively. Clinical and biochemical data were collected. The normoglycemic spectra of amino acids and acylcarnitines were determined by liquid chromatography tandem mass spectrometry. The serum insulin and fatty acid concentrations during standardized fasting tests in hypoglycemia patients were also collected. Receiver operating characteristic curve analysis was performed to screen potential biomarkers. Results: Among the normoglycemic spectra of amino acids, blood valine (p < 0.001), arginine (p < 0.001), threonine (p = 0.001), glutamate (p = 0.002), methionine (p = 0.005), ornithine (p = 0.008), leucine (p = 0.014), alanine (p = 0.017), proline (p = 0.031), citrulline (p = 0.042), aspartate (p = 0.046), and glycine (p = 0.048) levels differed significantly among the three groups. Significantly decreased levels of long- (C14:1, p < 0.001; C18, p < 0.001), medium- (C8, p < 0.001; C10, p < 0.001; C10:1, p < 0.001), and short-chain (C4-OH, p < 0.001; C5OH, p < 0.001) acylcarnitines were found in the hyperinsulinemic hypoglycemia group. Hyperinsulinemic hypoglycemia children with focal lesions and diffuse lesions had similar amino acid and acylcarnitine spectra. C10:1 < 0.09 µmol/L, threonine > 35 µmol/L, and threonine/C10:1 > 440 showed sensitivities of 81.1, 66.2, and 81.1% and specificities of 72.7, 78.3, and 81.8%, respectively, in distinguishing HH from KH. Conclusions: We found significantly different altered serum amino acid and acylcarnitine profiles at normoglycemia, especially decreased C10:1 and increased threonine levels, between HH and KH children, which may reflect the insulin ketogenesis inhibition effect in HH patients; however, the detailed mechanisms and physiological roles remain to be studied in the future.

Clinical characteristics and beta-cell function of Chinese children and adolescents with type 2 diabetes from 2009 to 2018.

BACKGROUND: The limited available studies have unveiled different natural histories and prognosis associated with pediatric type 2 diabetes (T2D) and adult T2D. To date, data on the clinical features, metabolic profiles and beta-cell function characteristics are still limited in the Chinese pediatric T2D population. METHODS: A total of 56 children with T2D, 31 with prediabetes and 159 with obesity were recruited. Clinical characteristics, metabolic profiles, beta-cell function and insulin resistance were analyzed. RESULTS: The mean onset age of T2D was 12.35 ± 1.99 (7.9-17.8) years, and 7% of children were younger than 10 years; 55% of them were male, 57% had a family history of diabetes and 64% had classic symptoms, and 25% had a low or high birth weight. 89% of T2D patients were obese or overweight. A total of 58% of the patients with prediabetes were male. The fast serum C-peptide level was highest in the obesity group (P < 0.001), and there was no significant difference between the T2D and prediabetes groups. The mean homeostatic model of assessment of beta-cell function was the highest in the obesity group and was lowest in the T2D group (P < 0.001). The T2D group had the most serious lipid metabolism disorder, with the highest levels of total triglycerides, total cholesterol, and low density lipoprotein and the lowest high density lipoprotein level among the three groups. CONCLUSIONS: A younger onset age and greater male susceptibility were found in Chinese pediatric T2D patients, and there was a stepwise deterioration trend in beta-cell function among patients with obesity, prediabetes and T2D. Based on our results, together with the SEARCH study results, an early screening and intervention program for T2D is recommended in high-risk or obese Chinese pediatric populations starting at 7 years.

In situ generation of H2O2 using MWCNT-Al/O2 system and possible application for glyphosate degradation.

Hydrogen peroxide (H2O2), as a green oxidant, has been widely applied into advanced oxidation processes (AOPs) for the degradation of toxic organic pollutants. The in situ generation of H2O2 can not only improve the storage and transportation safety of H2O2 but also reduce the capital and operation costs. In the present work, a novel system, i.e., multi-walled carbon nanotube­aluminum (MWCNT-Al) composite was used to in situ generate H2O2 through micro-electrolysis. The MWCNT-Al composite was characterized and optimized. The accumulation concentration of H2O2 reached 947 mg/L at the initial pH of 9.0, the MWCNT-Al composite dosage of 8 g/L and oxygen gas flow rate of 400 mL/min after 60 min. The in situ generation of H2O2 was achieved by MWCNT-Al/O2 system, mainly owing to the direct contact between Al0 and MWCNT in MWCNT-Al composite, which accelerated the transfer of electrons from Al0 to O2, as well as the excellent electrocatalytic activity of MWCNT toward the two-electron reduction of oxygen. When H2O2 in situ generation technology was used in peroxone process (O3/H2O2 process) to degrade glyphosate in aqueous solution, the removal efficiency of TOC and total phosphorus was 68.35% and 73.27%, respectively. Finally, the possible mechanism of in situ generation of H2O2 in MWCNT-Al/O2 system was temporarily proposed.

[Genotyping and polymorphism analysis of cytochrome c oxidase subunit â gene of Pomacea canaliculata from Lincang City in Yunnan Province].

OBJECTIVE: To analyze the genetic diversity of Pomacea canaliculata based on the mitochondria DNA cytochrome c oxidase subunit Ⅰ (mtDNA COⅠ) gene as a molecular marker in Lincang City of Yunnan Province, so as to provide the scientific data for monitoring Angiostrongylus cantonensis in local areas. METHODS: The genotypes and polymorphisms of 38 specimens of P. canaliculata collected from Mengding Town of Lincang City were analyzed by sequencing COⅠ gene. The phylogenetic tree and genetic distances were produced based on the haplotypes from GenBank and the present study by using the neighbourjoining method with the software MEGA version 6.06. RESULTS: Totally 31 sequences were acquired in the present study and they produced 3 unique haplotypes. Haplotype 1 showed a higher frequency compared to the others and it accounted for 83.9 % (26/31). The data showed that the least genetic distances ranged from 0 to 0.052 between P. canaliculata and 3 haplotypes, as well as the largest genetic distances ranged from 0.021 to 0.239 between Pila conica and 3 haplotypes. Otherwise, the analysis of the phylogenetic trees based on COⅠ gene sequences of P. canaliculata indicated that all of 3 haplotypes clustered into one big clade with that from Japan (GenBank accession number: AB433769), China (GenBank accession number: KT313034) and USA (GenBank accession number: EU523129), which owned the closet relationship amongst them. Their genetic relationships were distantly related to the GenBank's reference sequences of P. insularum (GenBank accession number: EF514942), P. camena (GenBank accession number: EF515059) and so on. CONCLUSIONS: There is a P. canaliculata species in Lincang City of Yunnan Province as well as a high genetic diversity amongst the acquired 3 haplotypes in this study.

[Application and effect of enhanced recovery after surgery in early rehabilitation of oral cancer patients after operation].

PURPOSE: To explore the application and effect of enhanced recovery after surgery (ERAS) in early rehabilitation of oral cancer patients after operation. METHODS: Ninety cases of oral cancer admitted from January 2016 to December 2017 were randomly divided into two groups. 45 cases of oral cancer in the experimental group received ERAS nursing after operation, and another 45 patients received routine nursing after operation. The sleep duration, pain and halitosis 3 days after operation; the first time to get out of bed, the length of hospitalization; and the level of albumin and other laboratory indicators 1 and 3 days after operation were observed. SPSS 17.0 software package was used for statistical analysis. RESULTS: After 1 day and 3 day of ERAS intervention, the nutritional index of the experimental group was lower than that of the control group. The time of first ambulation and the length of hospitalization were shorter than those of the control group. The average sleep time 3 days after operation was longer than that of the control group. The incidence of halitosis, wound infection and moderate pain was lower than that of the control group. The difference was statistically significant (P<0.05). CONCLUSIONS: ERAS nursing after oral cancer surgery can improve the comfort of patients, enhance the clinical outcome, promote rapid recovery of patients, with good clinical application prospects.

Relationship between the Proportion of Tumor Infiltrating Lymphocytes in Tumor Mass and Postoperative Recurrence of Prostate Carcinoma / 昆明医科大学学报

Objective To investigate the relationship between proportion of Tumor infiltrating lymphocytes (TILs) in the prostate tumor mass and postoperative recurrence of prostate carcinoma in order to offer the theoretic as well as experimental basis for the prevention of postoperative recurrence in the prostate carcinoma.Methods The proportion of CD3+, CD8+, CD3+CD4+, CD3+CD8+ TILs cells of 81 PCa specimens underwent Radical prostatectomy were analyzed. The proportion of CD3+CD8+TILs in patients with recurrence of PCa within3 years after surgery (group A), within 35 years (group B) and without recurrence after 5 years (group C) was compared. Results The proportion of CD3+CD8+TILs was significantly lower in group A than that of in group B and C (P＜0.05), meanwhile, the proportion of CD3+CD8+TILs were significantly higher in group C than that in group A and B (P＜0.05), while the proportion of CD3+, CD8+, CD3+CD4+ in three groups had no significant difference (P＞0.05). Conclusion The proportion of CD3+CD8+TILs presented in the PCa specimen mass is relative to the postoperative recurrence of prostate cancer, which might be a biomarker for the surveillance of postoperative recurrence of PCa.

Genotyping and polymorphism analysis of cytochrome c oxidase subunit Ⅰgene of Pomacea canaliculata from Lincang City in Yunnan Province / 中国血吸虫病防治杂志

Objective To analyze the genetic diversity of Pomacea canaliculata based on the mitochondria DNA cytochrome c oxidase subunitⅠ(mtDNA COⅠ)gene as a molecular marker in Lincang City of Yunnan Province,so as to provide the scien-tific data for monitoring Angiostrongylus cantonensis in local areas. Methods The genotypes and polymorphisms of 38 speci-mens of P.canaliculata collected from Mengding Town of Lincang City were analyzed by sequencing COⅠgene.The phylogenet-ic tree and genetic distances were produced based on the haplotypes from GenBank and the present study by using the neighbour-joining method with the software MEGA version 6.06. Results Totally 31 sequences were acquired in the present study and they produced 3 unique haplotypes.Haplotype 1 showed a higher frequency compared to the others and it accounted for 83.9 % (26/31).The data showed that the least genetic distances ranged from 0 to 0.052 between P.canaliculata and 3 haplotypes,as well as the largest genetic distances ranged from 0.021 to 0.239 between Pila conica and 3 haplotypes.Otherwise,the analysis of the phylogenetic trees based on COⅠgene sequences of P.canaliculata indicated that all of 3 haplotypes clustered into one big clade with that from Japan(GenBank accession number: AB433769),China(GenBank accession number: KT313034)and USA(GenBank accession number:EU523129),which owned the closet relationship amongst them.Their genetic relationships were distantly related to the GenBank's reference sequences of P.insularum(GenBank accession number:EF514942),P.cam-ena(GenBank accession number: EF515059)and so on. Conclusion There is a P. canaliculata species in Lincang City of Yunnan Province as well as a high genetic diversity amongst the acquired 3 haplotypes in this study.

[Treatment of 48 cases of benign lower posterior tumor of the parotid gland with C-shaped small incision].

PURPOSE: To summarize the feasibility and advantages of C-shaped small incision for the treatment of benign lower posterior tumor of the parotid gland. METHODS: Forty-eight cases of benign lower posterior tumor of the parotid gland were treated with C-shaped small incision. The treatment outcomes were recorded and analyzed. RESULTS: The wound healed primarily in all 48 cases. The follow-up period was 1-5 years, and there was no recurrence of tumor and the shape of parotid region recovered well. The residual parotid tissue had certain secretory functions postoperatively. CONCLUSIONS: C-shaped small incision is an effective way of surgical treatment for lower posterior benign tumor of the parotid gland, which can reduce surgical trauma, shorten operation time, reduce facial scars, facial nerve injury, reduce tumor recurrence rate and preserve the function of the remaining parotid tissues.

[Protection Mechanism of Alpinetin on Pulmonary Microvascular Endothelial Cells Injury].

Objective To explore the protection mechanisms about Alpinetin to acute human pulmonary microvascular endothelial cells ( HPMECs ) injury. Methods Different concentration of LPS (0. 01,0. 1 ,1. ,10 mg/L) was applied to the HPMECs to induce acute HPMECs injury. The HPMECs mod- els (n =3) were intervened by Alpinetin(40,80,160,320 mg/L) . Normal HPMECs were selected as control group. The viability of HPMECs was observed,mRNA and protein expression of intercellular cell adhesion molecule-1 (ICAM-1) ,TNF-α,APQ-1 were detected. Results Compared with control group, the protein expression of ICAM-1 , TNF-a were increased, the protein and mRNA expression of APQ-1 and the vi- ability of HPMECs were decreased in model group (P <0. 05). Compared with model group,ICAM-1 and TNF-α protein expressions were significantly inhibited in Alpinetin (80,160 mg/L) group, the mRNA and protein expression of APQ-1 and the viability of HPMECs were significantly increased (P <0. 05, P < 0. 01). Conclusion Alpenitin could protect the HPMECs injury by down-regulated protein expression of ICAM-1, TNF-α and up-regulated the mRNA and protein expression of APQ-1.

DSEP: A Tool Implementing Novel Method to Predict Side Effects of Drugs.

Drug side effects, or adverse drug reactions, have become a focus of public health concern. Anticipating side effects before the drugs are granted marketing authorization for clinical use can help reduce health threats. An increasing need for methods and tools that facilitate side-effect prediction still remains. Here, we present DSEP, which is a tool that is able to analyze chemistry files to predict side effects of drugs that are under development and have not been included into any database. Meanwhile, DSEP provides three computational methods, one of which is a novel method proposed by us. The method can obtain higher AUC(0.8927) and AUPR(0.4143) scores than previous work. The advantage characteristic and method made DSEP a useful tool to predict potential side effects for a given drug or compound. We use DSEP to conduct uncharacterized drugs' side-effect prediction and confirm interesting results.

Prediction of drug's Anatomical Therapeutic Chemical (ATC) code by integrating drug-domain network.

Predicting Anatomical Therapeutic Chemical (ATC) code of drugs is of vital importance for drug classification and repositioning. Discovering new association information related to drugs and ATC codes is still difficult for this topic. We propose a novel method named drug-domain hybrid (dD-Hybrid) incorporating drug-domain interaction network information into prediction models to predict drug's ATC codes. It is based on the assumption that drugs interacting with the same domain tend to share therapeutic effects. The results demonstrated dD-Hybrid has comparable performance to other methods on the gold standard dataset. Further, several new predicted drug-ATC pairs have been verified by experiments, which offer a novel way to utilize drugs for new purposes effectively.