Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Demyelination and remyelination play key roles in spinal cord injury (SCI), affecting the recovery of motor and sensory functions. Research in rodent models is extensive, but the study of these processes in non-human primates is limited. Therefore, our goal was to thoroughly study the histological features of demyelination and remyelination after contusion injury of the cervical spinal cord in Macaca fascicularis. In a previous study, we created an SCI model in M. fascicularis by controlling the contusion displacement. We used Eriochrome Cyanine staining, immunohistochemical analysis, and toluidine blue staining to evaluate demyelination and remyelination. The results showed demyelination ipsilateral to the injury epicenter both rostrally and caudally, the former mainly impacting sensory pathways, while the latter primarily affected motor pathways. Toluidine blue staining showed myelin loss and axonal distension at the injury site. Schwann cell-derived myelin sheaths were only found at the center, while thinner myelin sheaths from oligodendrocytes were seen at the center and surrounding areas. Our study showed that long-lasting demyelination occurs in the spinal cord of M. fascicularis after SCI, with oligodendrocytes and Schwann cells playing a significant role in myelin sheath formation at the injury site.
Animals ; Spinal Cord Injuries/physiopathology* ; Demyelinating Diseases/etiology* ; Remyelination/physiology* ; Macaca fascicularis ; Disease Models, Animal ; Myelin Sheath/pathology* ; Oligodendroglia/pathology* ; Schwann Cells/pathology* ; Female ; Spinal Cord/pathology* ; Axons/pathology*

Objective:By analyzing the genetic risk of triglyceride-glucose index(Tyg)and insulin resistance(IR)for cardiovascular disease(CVD), to elucidate the extent to which the contribution of Tyg to the risk of CVD development is influenced by IR genetic risk.Methods:In this study, we selected data from a cohort of elderly people in the Kunshan community, screened 7, 385 individuals with both clinical and genomic data, and calculated the polygenic risk score of insulin resistance(IRPRS)for each participant based on publicly available IR genome-wide association data, and assessed the effect of genetic risk and Tyg level on the risk of developing CVD using a multivariate Cox proportional risk model.Calculating interactions to assess the effects of genetic risk and Tyg levels on the risk of developing CVD, the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD were assessed using a multivariate Cox proportional risk model, and subgroup analyses were performed for gender to assess the effects of Tyg tertile grouping and IRPRS on the risk of developing CVD by gender.Results:In the univariate Cox model, Q3 and IRPRS with the highest TYG levels were significantly associated with the risk of CVD, respectively( HR=1.59, 95% CI: 1.33-1.89; P<0.001; HR=1.61, 95% CI: 1.18-2.20; P=0.003).After adjusting for multiple confounders, the Q3 Group with the highest TYG level was still significantly associated with the risk of CVD( HR=1.28, 95% CI: 1.05-1.57; P=0.014), the Association of TYG with the risk of CVD did not change significantly( HR=1.29, 95% CI: 1.05-1.57; P=0.014).We conducted a subgroup analysis by sex and found that among older men, 13, the highest levels of TYG and IRPRS were significantly associated with CVD risk, respectively( HR=1.70, 95% CI: 1.31.2.20; P<0.001; HR=1.98, 95% CI: 1.24-3.15; P=0.004).After adding IRPRS to the model, the Association of TYG with the risk of CVD remained unchanged( HR=1.69, 95% CI: 1.31-2.19; P<0.001).After adjusting for various confounders, Tyg remained significantly associated with the risk of CVD( HR=1.39, 95% CI: 1.04-1.88; P=0.028), the results showed that TYG remained significantly associated with the risk of CVD( HR=1.41, 95% CI: 1.05-1.90; P=0.023), and the association did not decrease.No Association of IRPRS with CVD risk was found in older women. Conclusions:IRPRS and TYG are the risk factors of CVD, and diet, exercise, drugs and other external factors on TYG are the main risk factors of CVD.For individuals with high genetic factors, the risk of CVD can still be reduced by lifestyle adjustments such as diet, exercise and drug intervention.

Objective The study aimed to investigate the predictive efficacy of contrast-enhanced ultrasound combined with telomerase reverse transcriptase(TERT)promoter mutation in constructing nomogram model for the prediction of concomitant cervical lymph node metastasis(CLNM)in papillary thyroid microcarcinoma(pTMC).Methods A total of 202 patients with pTMC who underwent partial or total thyroidectomy+lymph node dissection at our hospital from January 2021 to March 2024 were selected.Then,they were divided into the CLNM group(97 patients)and the non-CLNM group(105 patients)according to whether they had concomitant CLNM on postoperative pathological examination.General data and ultrasound(conventional ultrasound and contrast-enhanced ultrasound)characteristics were collected from all patients with pTMC,and Sanger sequencing was used to detect TERT promoter mutations.The influencing factors of pTMC complicated by CLNM were analyzed by single-factor and multifactorial unconditional logistic regression;the nomogram model of pTMC complicating CLNM with contrast-enhanced ultra-sound combined with TERT promoter mutation was constructed by RStudio 4.4.1 software,and the consistency and net benefit of the nomogram model were evaluated by using calibration curves,decision curves,and C-indexes,and the Hosmer-Lemeshow test for goodness of fit of the nomogram model;The predictive efficiency of the nomogram model constructed by combining contrast-enhanced ultrasound and TERT promoter mutation for pTMC complicated by CLNM was evaluated by plotting receiver operating characteristic(ROC)curves using MedCalc22.023 software.Results After postoperative pathological examination,the incidence of CLNM in 202 patients with pTMC was 48.02%(97/202).Univariate analysis showed that thyroglobulin antibodies,number of lesions,aspect ratio,micro-calcifications,enhancement time,enhancement mode,enhancement intensity,capsular continuity,and TERT promoter mutations were associated with pTMC complicating CLNM(P<0.05).Multifactorial unconditional logistic regression showed that multifocal tumours(OR=3.487,95%CI:1.641～7.406,P=0.001),microcalcifications(OR=4.484,95%CI:2.113～9.516,P<0.001),equal or high enhancement(OR=3.187,95%CI:1.460～6.957,P=0.004),disruption of peritoneal continuity(OR=2.201,95%CI:1.051～4.608,P=0.036),and TERT promoter mutation positivity(OR=4.460,95%CI:2.132～10.103,P<0.001)were the independent risk factors for pTMC complicating CLNM.A contrast-enhanced ultrasound combined TERT promoter mutation nomogram model was constructed based on independent risk factors for pTMC complicating CLNM[Logit(p)=-4.486+1.350×number of foci+1.399×microcalcifications+2.124×intensity of enhancement+1.524×capsular continuity+2.175×TERT promoter mutations].The C-index of this nomogram model was 0.899(95%CI:0.893～0.905),the calibra-tion curve alignment was close to the ideal curve,the decision curve was higher than the two extreme curves,and the Hosmer-Lemeshow test showed a P>0.05.The ROC curve analysis showed that the nomogram model constructed with contrast-enhanced ultrasound combined with TERT promoter mutations predicted CLNM in pTMC with an area under the curve of 0.899.This was significantly higher than the area under the curves for contrast-enhanced ultra-sound alone(0.857)and TERT promoter mutations alone(0.697)(P<0.05).Conclusion The contrast-enhanced ultrasound combined with TERT promoter mutations to construct a nomogram model has high predictive efficiency for pTMC complicating CLNM.

With the rapid development of mobile internet technology, mobile health application (mHealth APP) are increasingly widely used in the field of health management and have been proven to play an important role in the management of chronic diseases. Solid organ transplant recipients face complex health management needs after surgery, including postoperative follow-up, medication management, prevention and treatment of complications and comorbidities, and lifestyle adjustment. mHealth APP can provide solid organ transplant recipients with convenient self-management tools. Although some progress has been made in this field, there are still many challenges, such as insufficient user experience, technological dependence, and data security risks. Therefore, this article discusses the development process, main functions and current application status of mHealth APP, and analyzes its advantages in improving the self-management ability of solid organ transplant recipients, promoting doctor-patient communication and reducing the incidence of complications. At the same time, based on the practical experience of author’s team in developing the “TransMate” mHealth APP, we propose the directions that mHealth APPs should focus on in the future, in order to provide more effective support and services for the health management of solid organ transplant recipients.

AIM:To investigate the influencing factors of dry eye in elderly people aged over 60 years, and to construct a risk nomogram prediction model, so as to provide a reference for the identification of high-risk individuals and the development of preventive strategies.METHODS:A convenience sampling method was used to select 301 people aged over 60 years who attended the ophthalmology outpatient clinic or were hospitalized at the Second Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. They were divided into a dry eye group(n=173)and a non-dry eye group(n=128)based on the presence or absence of dry eye. Data from the two groups were compared and a risk prediction model was constructed.RESULTS:Gender, hypertension, meibomian gland dysfunction, frequent use of eye drops, frequent use of electronic products, and frequent exposure to dry environments were significant influencing factors for the occurrence of dry eye in people aged over 60 years(all P<0.05). The nomogram prediction model demonstrated excellent discrimination(AUC=0.86, 95% CI: 0.81-0.90). The calibration curve showed good fit with the ideal curve, indicating high predictive accuracy. The Hosmer-Lemeshow test yielded a P-value of 0.424. The sensitivity was 73% and the specificity was 86%.CONCLUSION:The nomogram predictive model for the risk of dry eye in elderly people aged over 60 years constructed in this study showed good discrimination and calibration. It can serve as an intuitive and effective clinical risk assessment tool, providing a basis for the early identification of high-risk populations and the development of individualized intervention strategies.

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Objective To observe the value of multi-sequence magnetic resonance imaging(MRI)radiomics in predicting the efficacy of concurrent chemoradiotherapy(CCRT)in locally advanced cervical squamous cell carcinoma(CSCC)patients.Methods Clinical data of 100 CSCC patients underwent CCRT treatment were selected.In order to better validate the performance of the model,patients were randomly divided into the training set(70 cases)and the validation set(30 cases)in a 7∶3 ratio.According to the efficacy criteria for solid tumors,patients were divided into the complete response(CR)group(n=16)and the partial response(PR)group(n=14).Examination images of cross-sectional DWI,T2WI and enhanced T1WI were collected from all patients before treatment.ITK-SNAP software package combined with three sequences were used to outline ROI,and the open source software PyRadiomics was used to extract image omics features.For MRI omics features,the minimum redundancy maximum correlation(mRMR)algorithm was used to analyze and screen out the first 30 main features,and then the minimum absolute contraction and selection method(Lasso)based on 10-fold cross-validation was used to reduce dimensionality to screen the non-zero coefficient features.According to the weighting coefficient of Lasso-Logistic regression model in the training set,patient omics labels were calculated.Logistic regression analysis was used to construct a prediction model based on DWI,T2WI and T1WI sequence prediction models and multiple sequenomics labels.Receiver operating characteristic(ROC)curves evaluated the predictive value of each omics model for CCRT treatment in patients with locally advanced CSCC.Results There were 38 cases in the CR group and 32 cases in the PR group in the training set.There were 16 cases in the CR group and 14 cases in the PR group in the validation set.There were no significant differences in patient age,FIGO stage,differentiation degree,maximum lesion diameter and menstrual status between the CR group and the PR group in the training and validation sets.A total of 851 imaging features were extracted from the ROI target area.After the first 30 features were retained by mRMR algorithm,3 CR-related features were selected from the 851 imaging omics features of each individual sequence by Lasso algorithm and 10-fold cross-validation.Eight CR related features were selected from 2 553 features after the combination of the three sequences.ROC curve results showed that in the training set and validation set,the AUC of multiple sequences combined to predict the therapeutic effect of CCRT in patients with locally advanced CSCC was 0.971 and 0.946,respectively,which was higher than that of T1WI,T2WI and DWI single sequence prediction(training set Z=2.683,2.046,2.817,P＜0.05;verification set Z=2.075,2.117,2.005,P＜0.05).Conclusion The multi sequence MRI radiomics model has high predictive value for the efficacy of CCRT treatment in locally advanced CSCC patients.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.