Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

Objective:To identify the clinical characteristics and pathogenic gene of a Chinese Han family with achromatopsia (ACHM).Methods:The method of pedigree investigation was adopted.A Chinese Han ACHM family was recruited in Peking Union Medical College Hospital form July 2010 to July 2019, including 5 members of 2 generations.There were 2 patients and 3 phenotypically normal individuals.The medical history was collected and comprehensive ophthalmic examinations were performed, including visual acuity, colour vision, color fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG).Genomic DNA was extracted from peripheral blood sample from the patients and family members.Pathogenic variant was screened by whole exome sequencing (WES) and verified by Sanger sequencing and co-segregation analysis.The variant was annotated with the 1000 Genomes, Human Gene Mutation Database (HGMD), ExAC, ClinVar and OMIM databases to detect the single nucleotide polymorphism and whether it had been reported previously.The pathogenicity of the variant was evaluated according to the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG).This study adhered to the Declaration of Helsinki.The study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (No.JS-2059).Written informed consent was obtained from the guardians of juvenile patients.Results:There was consanguinity between the proband's parents and this family was consistent with autosomal recessive inheritance.Both male patients presented the reduction of visual acuity accompanied with photophobia and color blindness since childhood.Barely visible foveal light reflex in fundus images, hypofluorescence of foveal areas in FAF images, foveal defect with disruption of ellipsoid zone and interdigitation zone in OCT images were found in both patients.Central scotoma with or without peripheral visual field defects was detected.Generally normal scotopic 0.01, 3.0 and 10.0 responses, decreased oscillatory potentials amplitudes, no photopic 3.0 and 30 Hz flicker responses were observed.No sign of progression was found during the 9-year follow-up.It was confirmed that both patients carried a novel homozygous disease-causing variant c. 947insA (p.Asn316Lysfs*46) in ATF6 gene.Their mother had the heterozygous variant.The unaffected brother did not carry the variant.This family was consistent with co-segregation.This variant was labeled as pathogenic according to the ACMG standards and guidelines. Conclusions:A novel variant c.947insA (p.Asn316Lysfs*46) in ATF6 gene is the pathogenic variant of this achromatopsia family.This is the first time that this variant has been reported.

Objective:To assess the shielding requirements of low energy X-ray intraoperative radiotherapy room under the domestic and foreign standards and guidelines, to measure the sured transmission factors for a range of shielding materials, the ambient dose equivalent rate around concerned positions and the shielding effect of protective devices, so as to provide references for shielding design of such radiotherapy units and applications of radiological protection devices.Methods:The required shielding thicknesses for a treatment room with INTRABEAM intraoperative radiotherapy system were calculated under the Chinese national standard GBZ 121, IPEM report No. 75 and NCRP report No. 151, respectively. The transmission factors for a range of shielding materials including solid water slab, shielding sheet and shielding apron were measured. Moreover, the ambient dose equivalent rates were measured under the simulated working conditions and the shielding effectiveness of a lead screen was evaluated.Results:The required lead thicknesses calculated under different standards and guidelines were less than 0.6 mm for all the concerned points, with the differences at sub-millimeter level. The low energy X-rays generated by this equipment attenuated rapidly in the shielding materials. The measured transmission factors of 0.05 mm lead equivalent shielding sheet and 0.25 mm lead equivalent shielding apron were 0.068 and 0.003 8, respectively. When the radiation was delivered using spherical applicator without any attenuation, the ambient dose equivalent rates at 1 m and 2 m from the X-ray source were 10.7 and 2.6 mSv/h, respectively. The corresponding measurement values decreased to 3.8 and 0.9 μSv/h, respectively, when the spherical applicator was inserted into a small water tank. Meanwhile, the ambient dose equivalent rate at 2 m was reduced to the background level when using protective screen.Conclusions:The shielding requirements for a low energy X-ray intraoperative radiotherapy facility are minimal, with low effective energy of X-rays generated by this equipment, but the dose rate close to the unshielded radiation source is high. The shielding scheme of treatment room should be optimized in design and the protective device should be used in a reasonable way.

Objective:To access the genetic defects and clinical characteristics of patients with KCNV2-associated cone dystrophy. Methods:Three pedigrees with KCNV2-associated cone dystrophy were recruited in Peking Union Medical College Hospital from August 2017 to December 2019.Peripheral blood from each patient and their parents was collected, and genomic DNA was extracted.Targeted exome capture plus next-generation sequencing (NGS) was used to detect the candidate variants.Suspected causative variants were validated by Sanger sequencing and segregation analysis.Comprehensive ocular examinations were performed, including vision acuity, colour vision, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG). This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and adhered to the tenets of the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination. Results:Three probands from three unrelated Chinese families were confirmed carrying biallelic KCNV2 disease-causing variants.Two patients harbored compound heterozygous variants and one patient with history of consanguinity was identified carrying homozygous variant.Five novel variants in the KCNV2 gene were identified, including p. T121M, p.R244C, p.C199Y, p.M250R and p. L171Pfs*201.All patients enrolled in this study were male with age of 25, 16 and 2 years old, respectively.Three affected individuals complained of vision loss and photophobia and two patients demonstrated reduced color perception and nystagmus.Macular discoloration (bull's eye maculopathy or gold foil macular reflex) was observed in fundus photographs.Macular hypofluorescence was illustrated in FAF imaging, which accompanying a broad hyperfluorescent ring surrounding the central atrophy or not.Macular thinning with loss of the inner segment ellipsoid zone was noted in OCT images, and the disruption was more profound in older patients.Central scotoma with or without peripheral visual field defects was observed in perimetry.Severe cone function loss and variable scotopic rod impairment were demonstrated in ERG, whereas a broad a-wave trough response to scotopic bright flash stimulation was noted. Conclusions:Patients with KCNV2-associated cone dystrophy show a characteristic ERG manifestation.ERG results and KCNV2 variants in Chinese patients differ from those in foreigners.