Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases, and its diagnosis heavily relies on imaging biomarkers. This paper integrates core pathological markers, such as amyloid β (Aβ)-positron emission tomography (PET), tau-PET, structural magnetic resonance imaging, and fluorodeoxyglucose-PET, with the latest advancements in novel imaging biomarkers, including inflammation, synaptic imaging, and cerebrovascular injury-related markers, based on the Aβ proteinopathy, tau proteinopathy, neurodegeneration, inflammation, α-synuclein and vascular brain injury biomarkers (AT 1T 2NISV) framework proposed by the 2024 Alzheimer′s Association diagnostic guidelines. With the development of machine learning and artificial intelligence technologies, future research should focus on enhancing the specificity of imaging biomarkers and developing precise diagnostic models for comorbidities to better address the heterogeneity and complex pathological features of AD.

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.

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.

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases, and its diagnosis heavily relies on imaging biomarkers. This paper integrates core pathological markers, such as amyloid β (Aβ)-positron emission tomography (PET), tau-PET, structural magnetic resonance imaging, and fluorodeoxyglucose-PET, with the latest advancements in novel imaging biomarkers, including inflammation, synaptic imaging, and cerebrovascular injury-related markers, based on the Aβ proteinopathy, tau proteinopathy, neurodegeneration, inflammation, α-synuclein and vascular brain injury biomarkers (AT 1T 2NISV) framework proposed by the 2024 Alzheimer′s Association diagnostic guidelines. With the development of machine learning and artificial intelligence technologies, future research should focus on enhancing the specificity of imaging biomarkers and developing precise diagnostic models for comorbidities to better address the heterogeneity and complex pathological features of AD.

Ischemic stroke(IS)is a severe cerebrovascular disease that seriously endangers human health.Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine.In recent years,trimethylamine N-oxide(TMAO)as a gut microbiota metabolite has received widespread attention in cardiovascular diseases.Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis,atrial fibrillation,hypertension,and type 2 diabetes.TMAO exacerbates neurological damage in IS patients,increases the risk of IS recurrence,and is an independent predictor of post-stroke cognitive impairment(PSCI)in patients.Current research suggests that the mechanisms of TMAO action include endothelial dysfunction,promoting of foam cell formation,influence on cholesterol metabolism,and enhancement of platelet reactivity.Lowering plasma TMAO levels through the rational use of traditional Chinese medicine,dietary management,vitamins,and probiotics can prevent and treat IS.

Objective: To evaluate the prevalence and consistency of screening myopia, non-cycloplegic myopia and cycloplegic myopia in children and adolescents, and to provide references for exploring the factors affecting the consistency of different definition methods. Methods: A total of 3 868 children and adolescents aged 6 to 17 years from seven schools were included in a school based cross sectional study in Shandong Province in September 2020. The prevalence of screening myopia, non cycloplegic refraction, and cycloplegic refraction at different ages and all children and adolescents were analyzed. With cycloplegic spherical equivalent ≤-0.50 D as the gold standard for myopia, and Kappa test and area under the ROC curve were used to evaluate the consistency. Results: The prevalence of cycloplegic myopia and screening myopia were 36.7% and 38.3% among children and adolescents. The prevalence of non cycloplegic myopia was 62.4%, which was significantly higher than screening myopia and cycloplegic myopia two methods in primary and junior high schools. Among 3 868 subjects, there were 3 628 (93.8%) subjects with screening myopia and 2 862 (74.0%) subjects with non cycloplegic myopia who were consistent with the gold standard for myopia. The Kappa values of screening myopia and non cycloplegic myopia were 0.87 and 0.51, and the area under the ROC curve was 0.94 (95% CI =0.93-0.95) and 0.79 (95% CI =0.78-0.81). Compared with other groups, children and adolescents aged 8 to 17 years, in junior or high school, urban residence, better presenting distance visual acuity, and astigmatism ≤1.50 D had a higher consistency in the application of screening myopia ( P <0.05). Conclusion The consistency between screening myopia and cycloplegic myopia is high, and the consistency between non cycloplegic objective myopia is low.

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 explore the effect of hallux nail flap design assisted with 3D printing in reconstruction of thumb defect in degloving injury.Methods:From January 2020 to March 2022, 16 patients with thumb defect caused by degloving injury with intact digit flexor and extensor tendons were treated. The patients were 11 males and 5 females, aged 20 to 52 years old, with an average age of 31 years old. The injured patient's hands were firstly scanned by CT and the 3D models were created to map the profile of the tissues required for reconstruction. Photopolymer templates for the defects in thumb were then 3D printed. The printed templates were put on the great toes and accordingly the hallux nail flaps were designed and harvested. The degloving wound of thumb was repaired by the hallux nail flap. Donor sites were repaired with artificial dermis in 6 patients and with ilioinguinal flaps in 10 patients. The effect of surgery was observed at outpatient clinic during postoperative follow-up. The survival of the hallux nail flap and the recovery of the donor site were observed. Function recovery were evaluated according to the Evaluation Standard of Finger Replantation and Reconstruction of Hand Surgery Society of Chinese Medical Association.Results:All the harvested hallux nail flaps matched with the profiles of recipient sites. All the hallux nail flaps survived over 4 to 30 months of follow-up, in an average of 16 months. Appearance of all hallux nail flaps was similar to normal thumbs, with good fingerprint and nails. Sensation recovery were S 3-S 4, with TPD at 4-7 mm. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 15 thumbs were excellent and 1 was good. Conclusion:Application of 3D printing assisted hallux nail flap transfer in reconstruction of defect of thumb in degloving injury can precisely design and harvest the required tissue and minimise a damage to the donor great toe. It improves the appearance of thumb as well as patient satisfaction. It is practical in reconstruction of the defect of thumb in degloving injury.

Objective: Establish a murine model for hyperuricemia (HU) and periodontitis to explore whether there is correlation between them and provide a basis for periodontal treatment. Methods: Fourteen male KM mice were divided into 2 groups; the HU group (n=7) was fed food supplemented with potassium oxonate and uric acid, the NC group (n=7) was fed standard food, and the induction period was 35 days. On the 25th day, the molars on one side were ligated to induce periodontitis (P side), while the opposite was true for the control (C side). Baseline and terminal serum uric acid (UA) levels were detected, and alveolar bone resorption was analyzed by micro-CT. Results: The serum UA level of HU mice was (112.94 ± 26.82 )mol/L, that of the NC group was (72.21 ± 19.95) μmol/L, and the difference in UA level was statistically significant (P < 0.05). The P side bone volume fractions of the HU and NC groups were( 29.01 ± 11.09)% and (29.56 ± 15.27)%, respectively, which were not significantly different (t=-0.072, P=0.944). The P side bone mineral densities of the HU and NC groups were(0.53 ± 0.16) g/cm3 and (0.52 ± 0.14) g/cm3, respectively, which were not significantly different (t=0.038, P=0.970). Additionally, there was no correlation between HU or serum UA and alveolar bone resorption (P > 0.05). Conclusion This research established a murine model for HU and periodontitis, but based on micro-CT analysis of alveolar bone, no relationship between HU or UA levels and periodontitis was found.