Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Objective To investigate the intervention of trans-theoretical model on the risk factors in the patients with prediabetes.Methods One hundred and twenty-two patients with pre-diabetes in a tertiary hospital of Zhengzhou City were selected and randomly assigned to control group and intervention group.The control group received the routine diabetic health education,while in addition to the routine health education,the intervention group was assisted by TTM interventional measures.The blood glucose,body mass index(BMI) and negative emotion were compared between the two groups.Results The blood glucose and BMI after intervention in the two groups were decreased,moreover the decrease level of fasting blood glucose and BMI in the intervention group was higher than that in the control group,and the difference was statistically significant(t=4.963、2.061,P＜0.05).The anxiety and depression emotion scores after intervention in the intervention group were [(3.47 ±1.07) and (0.30 ± 0.46)],before intervention were (7.74 ± 4.00) and(7.25 ± 4.50),The difference was statistically significant(P＜0.05),Moreover the anxiety and depression emotion scores after intervention in the intervention group were lower tghan those in the control group with statistical difference(t=3.300、2.054,P＜0.05).Conclusion The intervention measures based on TTM has significant advantage for controlling the risk factors of pre-diabetes and preventing diabetes than the conventional health education.

Objective To investigate the knowledge and influencing factors of diabetes in middle-aged and elderly patients with prediabetes, and to provide evidence for public education in those patients. Methods According to convenient sampling, the questionnaire survey was conducted in 234 middle-aged and elderly patients with prediabetes who had a physical examination in a class Ⅲ grade A hospital in Zhengzhou from July to December 2014.Results There were significant differences in knowledge points of diabetes, diet dimension and total points in middle-aged patients compared with elderly patients (P<0.05), however, there was no significant difference in risk factors, treatment and exercise knowledge dimension (P>0.05). The multivariable linear regression analysis showed that the main factors for knowledge were marital status and educational level in middle-aged participants, and educational level and family history of diabetes in elderly participants.Conclusions The knowledge of diabetes should be strengthened in middle-aged patients with prediabetes who have low education level and no spouse, and in elderly patients with low education level and no family history of diabetes.

Objective To explore the molecular mechanism of blood_stasis syndrome (BSS) by studying the changes of gene expression of endothelin (ET) and constit utive nitric oxide synthase (cNOS) in vascular endothelial cells (VEC) cultured w ith BSS rabbit serum. Methods ET_1 mRNA expression and cNOS mRNA expression were analyzed by semi_quantitative reverse transcription and polymerase chain re action method. Results ET_1 mRNA expression level was increased and cNOS mRN A expression level was decreased in VEC cultured with BSS rabbit serum (Group A) as compared with VEC cultured with normal rabbit serum (Group B) or without rab bit serum (Group C) (P