With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To study the effect of phonetic training on lateral articulation in preschool patients with functional articulation disorders(FAD).Methods A total of 45 FAD patients from June 2022 to December 2022 were selected as the control group,and 45 FAD patients from January 2023 to March 2023 were selected as the ob-servation group.The patients in the observation group were given basic function training,tongue force point train-ing,correct ventilation training,computer speech lab(CSL)visual feedback training,family synchronization train-ing,family continuation training and other voice training measures.Forty-five patients in the control group did not receive speech training,and routine guidance was implemented.Speech assessment was carried out on patients in the observation group at the end of the speech training class and patients in the control group at the time of return visit,and the number of lateral articulation words between the two groups was compared.Results Within the group com-parison,after 10～50 hours of targeted language training,the number of words of lateral articulation in the observa-tion group decreased from 95.16±7.82 before training to 17.60±3.45,and the difference was statistically signifi-cant(t=70.871,P＜0.01).In the control group,the number of words of lateral structure decreased from 94.29±8.50 at the time of visit to 82.96±8.43 at the time of return visit,and the difference was statistically significant(t=9.849,P＜0.01).For comparison between groups,there was no statistical difference in the number of words of lateralized phonation between the two groups before voice training(t=0.504,P=0.616).The number of words of lateralized phonation in the observation group after training was significantly less than that in the control group after follow-up visit,and the difference was statistically significant(t=48.131,P＜0.01).Conclusion The lateral artic-ulation of preschool FAD patients has a certain tendency of self-healing.Based on the mechanism of lateral articula-tion,targeted phonetic training for preschool FAD patients is an effective measure to correct the lateral articulation of FAD.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease globally,with only one Food and Drug Administration(FDA)-approved drug for its treatment.Given MASLD's complex pathophysiology,ther-apies that simultaneously target multiple pathways are highly desirable.One promising approach is dual-modulation of the famesoid X receptor(FXR),which regulates lipid and bile acid metabolism.However,FXR agonists alone are insufficient due to their limited anti-inflammatory effects.This study aimed to dto identify natural products capable of both FXR activation and inflammation inhibition to provide a comprehensive therapeutic approach for MASLD.Potential FXR ligands from the Natural Product Library were predicted via virtual screening using the Protein Preparation Wizard module in Schrodinger(2018)for molecular docking.Direct binding and regulation of candidate compounds on FXR were analyzed using surface plasmon resonance(SPR)binding assay,reporter gene ana-lysis,and reverse transcription-polymerase chain reaction(RT-PCR).The anti-inflammatory properties of these compounds were eval-uated in AML12 cells treated with tumor necrosis factor-alpha(TNF-α).Dual-function compounds with FXR agonism and inflamma-tion inhibition were further identified in cells transfected with Fxr siRNA and treated with TNF-α.The effects of these dual-function compounds on lipid accumulation and inflammation were evaluated in cells treated with palmitic acid.Results revealed that 17 natural products were predicted via computational molecular docking as potential FXR agonists,with 15 exhibiting a strong affinity for FXR recombinant protein.Nine isoflavone compounds significantly enhanced FXR reporter luciferase activity and the mRNA expressions of Shp and Ostb.Structure-activity relationship analysis indicated that introducing isopropyl or methoxy groups at the C7 position or a methoxy group at the C6 position could enhance the agonistic efficacy of isoflavones.Three compounds(2,6,and 8)were identified as dual-function natural products functioning as FXR agonists and inflammatory inhibitors,while one compound(12)acted as an FXR agonist to inhibit inflammation.These natural products protected hepatocytes against palmitic acid-induced lipid accumulation and in-flammation.In conclusion,compounds 2,6,and 8(genistein,biochanin A,and 7-methoxyisoflavone,respectively)were identified as dual-function bioactive products that transactivate FXR and inhibit inflammation,serving as potential candidates or lead compounds for MASLD therapy.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*

Objective To investigate the potential risk factors for mild cognitive impairment (MCI) in the elderly population in the community, and to provide a basis for the primary prevention of MCI. Methods A cross-sectional study of elderly population in communities of Shanghai, China was conducted. A total of 368 subjects including both males and females, aged 65-80 years old, were selected to complete the mini-mental state examination (MMSE), basic information questionnaires, and physical examinations. Logistic regression analysis was used to analyze the potential risk factors of MCI. Results Of the 368 subjects participating in the study, 53 were found to have MCI and the prevalence rate was 14.4%. Univariate analysis found that older age, low education, no folic acid supplementation, stroke, osteoporosis and hyperlipidemia were risk factors of MCI. Multiple logistic regression analysis showed that advanced age [OR=1.146 (95%CI: 1.052-1.249)] and osteoporosis [OR=2.371 (95%CI: 1.042-5.396)] were the independent risk factors for MCI, while higher education [OR=0.073 (95%CI: 0.011-0.478)] was a protective factor. Age influenced all the aspects of MMSE scores (all P values <0.05). In addition, the analysis of the results suggested that subjects with regular folic acid supplementation got higher MMSE scores, especially in the aspect of language and praxis (P=0.002). On the contrary, patients with osteoporosis had lower attention and computing power scores (P=0.022). Conclusion The prevalence of MCI increased with age. Low education and osteoporosis may be the independent risk factors for MCI in the elderly population. Although no association was observed between folic acid supplementation and MCI, folic acid supplementation could improve the performance of language and praxis.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Objective To investigate the value of color Doppler ultrasonography in the differential diagnosis of benign and malignant testicular tumors in children. Methods The sonographic findings of 63 children pathologically confirmed testicular tumors were retrospectively analyzed.All children were divided into benign group and malignant group according to pathologic diagnosis. The tumor size,shape,border, echo texture,calcification and color blood flow were compared between two groups. Logistic regression analysis was employed to predict sonographic features of benign and malignant testicular tumors.Receiver operating curve (ROC) was employed to assess the diagnostic performance of sonographic features. Results Among the 63 cases of pediatric testicular tumors,42 cases were histologically confirmed as benign testicular tumors (66.7% ),and the rest 21 cases were malignant testicular tumors (33.3% ). The maximum diameter of tumor in benign tumors was significantly smaller than that in malignant tumors[(1.75 ± 0.75) cm vs (2.90 ± 1.22)cm,P =0.000].In the sonographic features,malignant testicular tumors were more likely to present with solid masses,and benign testicular tumors were more likely to be cystic or cystic-solid ( P =0.024).Calcification was more common in benign tumors than that in malignant tumors ( P =0.000).Compared with benign tumors,malignant tumors had increased blood flow on color Doppler images ( P =0.000).Logistic regression analysis indicated that flow grade was the independent prognostic factors for malignant tumor. By using Alder grade of 2 or above as threshold,the sensitivity,specificity and accuracy were 95.2%,78.6% and 84.1%,respectively. Conclusions The sonographic features vary between benign and malignant testicular tumors. Blood flow is the independent factors for predicting malignant tumor. Color Doppler ultrasonography is an important method for differential diagnosis of testicular tumors in children.

Objective To investigate the value of ultrasound in assessing leuprorelin treatment response of girls with central precocious puberty . Methods Forty girls with central precocious puberty scheduled for leuprorelin treatment were enrolled . Ultrasound examination as well as the serum hormone level test of luteinizing hormone ( LH) and follicle stimulating hormone ( FSH) were performed prior to the treatment ,after 3 and 9 months of treatment . The correlation between uterine volume ,ovarian volume and hormone levels were analyzed . Results After 3 and 9 months of leuprorelin treatment ,both the volumes of uterus and ovary and the levels of LH and FSH were significant reduced ( all P < 0 .05) . After 3 months of leuprorelin treatment ,the reduction rate in ovarian volume was positively correlated with the reduction rate of LH and FSH ( r = 0 .335 , P = 0 .034 ; r = 0 .334 , P = 0 .035) . No correlation was found between the reduction rate of uterine volume and hormone level changes ( r = 0 .110 , P = 0 .501 ; r = 0 .257 , P =0 .109) . After 9 months of treatment ,the ovarian volume reduction rate was positively correlated with the reduction rate of LH and FSH ( r = 0 .327 , P = 0 .039 ; r = 0 .356 , P = 0 .024) ,and the uterine volume reduction rate was positively correlated with the reduction rate of LH and FSH ( r = 0 .439 , P = 0 .005 ;r =0 .433 , P = 0 .005 ) . Conclusions Leuprorelin could effectively inhibit hormone release and gonadal development in girls with central precocious puberty . Ultrasound examination , as a noninvasive and convenient method ,could dynamically monitor the volume changes of uterus and ovary ,thus reflect the development of gonadal development directly and the changes of hormone level indirectly . It could be used as a routine outpatient follow-up method after central precocious medicine treatment .