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.

Objective:To investigate the changes in retinal structure and microcirculation in the patients with high myopia(HM)and the non-HM individuals,and to elucidate the correlations between axial length(AL)and the related parameters.Methods:A total of 80 eyes from 40 patients with simple HM(non-pathological myopia)were enrolled as case group,while 80 eyes from 40 age-and sex-matched non-HM subjects were selected as control group.The best-corrected visual acuity(BCVA),AL,spherical equivalent(SE),and optical coherence tomography angiography(OCT A)examination were performed in all the subjects.OCTA examination was used to measure the vascular density of the superficial retinal capillary plexus(SCP),deep retinal capillary plexus(DCP),and radial peripapillary capillary(RPC),as well as central macular thickness(CMT),and the area and volume of the foveal avascular zone(FAZ)of the subjects in two groups.The differences in these parameters of the subjects between two groups were analyzed.The AL of the subjects in two groups was measured using a biometer,and its correlations with the parameters mentioned above were evaluated.Results:No statistically significant differences were observed in age or sex distribution between two groups(P＞0.05).Compared with control group,both SCP and DCP vessel densities acrossing the whole(excluding the foveal),parafoveal,and perifoveal regions of the macular retina of the patients in case group were significantly decreased(P＜0.05).Compared with control group,the RPC vessel densities in the optic disc region of the patients in case group were significantly decreased in the whole,peripapillary,peripapillary superior,and peripapillary inferior sectors(P＜0.001),while the RPC vessel density was increased inside the disc(P＜0.01).Compared with control group,the whole FAZ volume of the patients in case group was increased(P＜0.01),while the parafoveal and perifoveal CMT were decreased(P＜0.001).In case group,AL was negatively correlated with SCP vessel density(r=-0.642,P＜0.001),DCP vessel density(r=-0.388,P＜0.001),RPC vessel density(r=-0.639,P＜0.001),and CMT(r=-0.495,P＜0.001),but positively correlated with FAZ volume(r=0.580,P＜0.001);no significant correlation was found between AL and FAZ area(r=-0.062,P=0.587).Conclusion:The patients with HM may exhibit early reductions in SCP,DCP,and RPC vessel densities,thinning of the central retina,and increased FAZ volume.Furthermore,as AL increases,SCP,DCP,and RPC vessel densitiesas as well as CMT decreases,while FAZ volume increases,suggesting significant associations between AL and the parameters mentioned above.

Objective:A high performance liquid chromatography (HPLC) method was developed to determine the enzymatic activity of CD38 in blood, which was the major enzyme responsible for consuming nicotinamide adenine dinucleotide (NAD). Additionally, the study aimed to detect the differences in CD38 enzymatic activity among individuals of varying ages and health statuses.Methods:A 50 μl whole blood matrix and enzyme reaction substrate of 150 μl β-NAD at a concentration of 500 μmol/L were selected for the analysis. To eliminate the impact of endogenous β-NAD, the whole blood sample was pre-incubated at 37 ℃ for 20 minutes before adding the substrate. The reaction was terminated by perchloric acid (PCA) after incubation at 37 ℃ for 40 min. The change in product nicotinamide (NAM) before and after the enzymatic reaction was measured by HPLC to calculate the CD38 activity. The linearity, limit of detection, limit of quantification, precision, and stability of the method were evaluated. The CD38 enzymatic activities in 60 healthy volunteers and 30 colorectal cancer patients in blood were determined by the developed method.Results:Pre-incubation at 37 ℃ for 20 minutes eliminated the effect of endogenous β-NAD. The correlation coefficient of NAM was 0.999 in the concentration range of 0.1-3.2 μmol/L, with limit of detection of 0.5 nmol/L and limit of quantification of 2.1 nmol/L. The average within-run imprecision ( CV) and total CV were 3.22%-4.03% and 2.91%-4.70%, respectively. The recovery rate ranged from 94.82% to 96.81%. The CD38 activity of whole blood was stable by storage at 4 ℃ for 48 hours, storage at room temperature for 8 hours, thawing of frozen whole blood at room temperature for 2 hours, or repeated freeze-thawing three times. NAM, NAD standards, and pre-treatment samples were stable after 48 hours at 4 ℃ and 8 hours at room temperature. CD38 activity gradually decreased with increasing concentration of the added CD38 inhibitor 4-aminoquinoline derivative (78c). Measurement of 60 healthy physical examination population samples showed significantly higher CD38 enzyme activity in the elderly group than that in the young group ( t=-2.776, P=0.007) and measurement of 30 colorectal cancer patients showed significantly higher CD38 enzyme activity than that in healthy people ( t=-2.572, P=0.012). Conclusion:The established HPLC method for determining CD38 enzymatic activity is characterized by its simplicity, efficiency, accuracy, and reproducibility. This technique serves as a valuable tool for investigating aging and aging-related diseases.

ObjectiveTo observe the recovery of proprioception of the affected ankle over time after lateral ankle sprain accepting routine rehabilitation. MethodsFrom June, 2020 to June, 2022, 18 patients with lateral ankle sprain in Kunshan Rehabilitation Hospital underwent routine rehabilitation for twelve weeks. They were measured active and passive position sense of bilateral ankles using an isokinetic dynamometer before treatment, and four, eight and twelve weeks after treatment, respectively. ResultsThe active presentation difference of affected ankle reduced after treatment (F = 22.533, P < 0.001), but it was more than that of the healthy ankle at the same time (t > 4.419, P < 0.001). No significant improvement was found in passive presentation difference of affected ankle after treatment (F = 1.175, P > 0.05), and it was not significantly different from those of the healthy ankle at the same time (|t| < 0.646, P > 0.05). ConclusionProprioception of affected ankle has been impaired after lateral ankle sprain, and it can be recovered after rehabilitation, but cannot achieve the healthy level even after three months of training. Passive position sense as an index of proprioception needs more researches.

Objective To optimize the experimental system of dual molecular beacon to rapidly detect My-cobacterium tuberculosis and its resistant strains.Methods Fluorescence quantitative PCR was carried out by selecting different magnesium ion concentration,annealing temperature and primer concentration respectively. Finally,the optimum reaction conditions were obtained.Results In order to ensure the efficiency of amplifica-tion and no non-specific amplification,the final selection of the best conditions were as follows,the concentra-tion of Mg2+was 3.0 mmol/L,annealing temperature was 60 ℃,and the concentration of primers was 0.3 mmol/L.Conclusion The optimal condition of dual molecular beacon experiment was established,which en-sured that the detection of Mycobacterium tuberculosis by molecular beacon quantitative PCR had the advanta-ges,such as simple operation,rapid speed,high sensitivity(the minimum detection limit was 1 CFU/mL)and specificity(only Mycobacterium tuberculosis complex including drug-resistant strains could be detected),good reproducibility(coefficient of variation was < 5%)and other advantages.The study provides the necessary conditions for the dual molecular beacon detection of Mycobacterium tuberculosis.

Objective To evaluate the short-term effect of Pipeline embolization device (PED)for the treatment of unruptured wide-necked intracranial aneurysms. Methods From October 2015 to September 2016,15 consecutive patients with unruptured wide-necked intracranial aneurysm (aneurysm neck and aneurysm body ratio ≥0. 5)treated with PED at the Department of Neurosurgery,the Second Affiliated Hospital of Nanchang University were enrolled retrospectively. Their clinical and imaging data were analyzed. Kamran scale was used to evaluate the embolization rate of aneurysms and the changes of the parent arteries. DSA examination was performed again at 6 -12 months after operation. Results Fifteen PED were implanted in 15 patients with unruptured wide-necked intracranial aneurysms,including 13ophthalmic artery aneurysms,1 posterior communicating artery aneurysm,and 1 cavernous sinus aneurysm. The technical success rate was 100% . Immediately after PED implantation,Karman rating of 15 cases were aneurysm grade 2 embolization,parent artery grade A (grade 2a). DSA examination was performed again at 6 - 12 months after operation showed that 14 patients were aneurysm grade 4,parent artery was grade A (grade 4a). One patient (ophthalmic artery aneurysm)underwent the second DSA examinations at 6 and 12 months after operation showed that the residual development of aneurysms. The aneurysm embolization was grade 3, and the parent artery was grade A (grade 3a). No branch artery occlusion was observed. Non of them had neurological deficit. The modified Rankin scale score was 0 in all 15 patients. Conclusion The use of PED in the treatment of unruptured wide-necked intracranial aneurysms has a higher occlusion rate. Its long-term effect still needs further follow-up.

Objective To study the influence of pregnant rats' prenatal chronic stress (PS) on learning and memory of their offspring rats and its possible molecular mechanisms.Methods Pregnant females were individually restrained for 45 min 3 times a day during pregnancy from day 14 to day 21.Control pregnant females were left undisturbed in their home cages.The rat offsprings were randomly assigned to PS group or control group.Males and females were kept for the study separately.The learning and memory of the developing rat offspring in the Morris water maze were examined.The basal levels of corticosterone (COR) and adreno-cortico-tropic-hormone (ACTH) were analyzed by using radioimmunoassay.The Golgi-Cox impregnation technique was used to compare density and morphology of the CA1 hippocampal dendritic spines.Results The escape latency (EL) to find the platform in the control group was significantly less than that in the PS group in female rat offspring (F =4.533,P ＜ 0.05),and the difference was statistically significant on the 5th day (t =2.788,P ＜ 0.01).EL to find the platform in the control group was significantly less than that in the PS group in male rat offspring (F =6.101,P ＜0.05),and the difference was statistically significant on the second day (t =3.051,P ＜ 0.01).In the space exploration experiments of the water maze,the retention time observed for the control group and the PS group in the goal quadrant was similar(P ＞ 0.05).The basal levels of the serum COR in the PS group were higher than those in the control group of female rat offspring(t =3.658,P ＜ 0.01) and the basal levels of the serum ACTH in the PS group were higher than those in the control group of male rat offsprings(t =2.319,P ＜ 0.05).A simplified pattern was observed in the CA1 hippocampal dendritic spines in the PS group,showing a less extent of dendritic arborization and the density was significantly lower than that in the control group(t =-3.072,P ＜ 0.01).Conclusions Altered function of the hypothalamic-pituitary-adrenal axis in the offspring mediates the cognitive alterations observed following prenatal stress should to be associated with the lower density and simplified pattern of CA1 dendritic spines.