Impact of Social Determinants of Health on Self-Perceived Resilience: An Exploratory Study of Two Cohorts of Adults with Congenital Heart Disease

Social determinants of health(SDOH)affect quality of life.We investigated SDOH impacts on self-perceived resilience among people with adult congenital heart disease(ACHD).Secondary analysis of data from two com-plementary studies:a survey study conducted May 2021–June 2022 and a qualitative study conducted June 2020–August 2021.Resilience was assessed through CD-RISC10 score(range 0–40,higher scores reflect greater self-perceived resilience)and interview responses.Sociodemographic and SDOH(education,employment,living situa-tion,monetary stability,financial dependency,area deprivation index)data were collected by healthcare record review and self-report.We used linear regression with robust standard errors to analyze survey data and performed a thematic analysis of interview data.Survey participants(N=127)mean age was 42±14 years;51%were female,87%white.ACHD was moderate(75%)or complex(25%);41%functional class C or D.Resilience(mean 30±7)varied by monetary stability:compared to people with difficulty paying bills,resilience was 15.0 points higher(95%CI:6.9–23.1,p<0.001)for people reporting having enough money and 14.2 points higher(95%CI:5.9–22.4,p=0.001)for those reporting just enough money.Interview participants’(N=25)mean age was 32 years(range 22–44);52%were female,72%white.ACHD was moderate(56%)or complex(44%);76%functional class C or D.Participants discussed factors affecting resilience aligned with each of the major SDOH,prominently,economic stability and healthcare access and quality.Financial stability may be important for supporting self-perceived resi-lience in ACHD.This knowledge can inform the development of resilience interventions for this population.

Loss to Specialized Cardiology Follow-Up in Adults Living with Congenital Heart Disease

Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care centers.Much less is understood about the loss to follow-up(LTF)after a successful transition.This is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature mortality.Aims:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)centre.Methods:Patients with moderate or highly complex CHD and gaps in care of>3 years(defined as LTF)were identified from a comprehensive ACHD data-base.Structured telephone interviews examined current care and barriers to clinic attendance.Results:Overall,407(22%)of ACHD patients(n=1842)were LTF.The mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were uncontactable.Compared to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful transition.This Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to follow-up.This study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.

Adults with Congenital Heart Disease during the COVID-19 Era:One-Year Tertiary Center Experience

Background:Adult patients with congenital heart disease(ACHD)might be at high risk of Coronavirus disease-2019(COVID-19).This study aimed to report on a one-year tertiary center experience regards COVID-19 infection in ACHD patients.Methods:This is a one-year(March-2020 to March-2021)tertiary-center retrospective study that enrolled all ACHD patients;COVID-19 positive patients’medical records,and management were reported.Results:We recorded 542 patients,205(37.8%)COVID-19-positive,and 337(62.2%)COVID-19-negative patients.Palliated single ventricle and Eisenmenger syndrome patients were more vulnerable to COVID-19 infection(P<0.05*).Cardiovascular COVID-19 complications were arrhythmias in 47(22.9%)patients,heart failure in 39(19.0%)patients,cyanosis in 12(5.9%)patients,stroke/TIA in 5(2.4%)patients,hypertension and infective endocarditis in 2(1.0%)patients for each,pulmonary hypertension and pulmonary embolism in 1(0.5%)patient for each.11(5.4%)patients were managed with home isolation,147(71.7%)patients required antibiotics,32(15.6%)patients required intensive care unit(ICU),8(3.9%)patients required inotropes,7(3.4%)patients required mechanical ventilation,and 2(1.0%)patients required extracorporeal membrane oxygenation(ECMO).Thromboprophylaxis was given to all 46(22.4%)hospitalized patients.American College of Cardiology/American Heart Association classification revealed that complex lesions,and FC-C/D categories were more likely to develop severe/critical symptoms,that required mechanical ventilation and ECMO(P<0.05*).Mortality was reported in 3(0.6%)patients with no difference between groups(P=0.872).193(35.6%)patients were vaccinated.Conclusions:COVID-19 infection in ACHD patients require individualized risk stratification and management.Eisenmenger syndrome,single ventricle palliation,complex lesions,and FC-C/D patients were more vulnerable to severe/critical symptoms that required ICU admission,mechanical ventilation,and ECMO.The vaccine was mostly tolerable.

Stable ischemic heart disease in the older adults

1 Introduction Ischemic heart disease is caused by atherosclerotic and/or thrombotic obstruction of coronary arteries. Clinical spec- trum of ischemic heart disease expands from asymptomatic atherosclerosis of coronary arteries to acute coronary syn- dromes （ACS） including unstable angina, acute myocardial infarction （non-ST elevation myocardial infarction and ST elevation myocardial infarction）. Stable ischemic heart dis- ease （SIHD） refers to patients with known or suspected SIHD who have no recent or acute changes in their symp- tomatic status, suggesting no active thrombotic process is underway.

Atrial tachyarrhythmia in adult congenital heart disease

The adult congenital heart disease (ACHD) population continues to grow and most cardiologists, emergency room physicians and family doctors will intermittently come into contact with these patients. Oftentimes this may be in the setting of a presentation with atrial tachyarrhythmia; one of the commonest late complications of ACHD and problem with potentially serious implications. Providing appropriate initial care and ongoing management of atrial tachyarrhythmia in ACHD patients requires a degree of specialist knowledge and an awareness of certain key issues. In ACHD, atrial tachyarrhythmia is usually related to the abnormal anatomy of the underlying heart defect and often occurs as a result of surgical scar or a consequence of residual hemodynamic or electrical disturbances. Arrhythmias significantly increase mortality and morbidity in ACHD and are the most frequent reason for ACHD hospitalization. Intra-atrial reentrant tachycardia and atrial fibrillation are the most prevalent type of arrhythmia in this patient group. In hemodynamically unstable patients, urgent cardioversion is required. Acute management of the stable patient includes anticoagulation, rate control, and electrical or pharmacological cardioversion. In ACHD, rhythm control is the preferred management strategy and can often be achieved. However, in the long-term, medication side-effects can prove problematic. Electrophysiology studies and catheter ablation are important treatments modalities and in certain cases, surgical or percutaneous treatment of the underlying cardiac defect has a role. ACHD patients, especially those with complex CHD, are at increased risk of thromboembolic events and anticoagulation is usually required. Female ACHD patients of child bearing age may wish to pursue pregnancies. The risk of atrial arrhythmias is increased during pregnancy and management of atrial tachyarrhythmia during pregnancy needs specific consideration.

Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmpl- Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmpl gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmpl-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmpl-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra. Confirming the utility of Dmpl-Cre in the gastrointestinal mesenchyme, deletion of Bmprla with Dmpl-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmpl-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

Xiaoyu Jiangzhi capsule protects against heart failure via Ca^(2+)/CaMKII signaling pathways in mice

Objective: Heart failure(HF), a worldwide health condition, is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM) Xiaoyu Jiangzhi capsule(XYC) has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation. This study explores the effects of XYC on heart failure(HF) and its detailed mechanisms.Methods: Isoproterenol(ISO, 30 mg/kg) was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old, 20-30 g male mice. We then compared the CON(control) group, ISO(HF model)group, MET(metoprolol) group, and XYC group. Cardiac systolic function and left wall thickness were evaluated by echocardiograph. Using western blot analysis, we detected the proteins of calmodulin dependent protein kinase Ⅱ(Ca MKII) and sarco/endoplasmic reticulum Ca^(2+)-ATPase(Serca). Furthermore, ts A201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2) were detected by patch clamp experiments.Results: XYC reduced HF, inhibiting the protein expression of Ca MKII, but Serca did not change significantly. Moreover, XYC inhibited the peak amplitude of the hCaV1.2 current, depolarizing shifted the activation curve 27.6 mV, and shifted the inactivation curve toward a positive potential 17.6 mV. The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion: XYC could inhibit ISO-induced HF by reducing the Ca^(2+)/Ca MKII signaling pathway in mice.

Perioperative Nursing for Adult Congenital Heart Disease with Severe Pulmonary Arterial Hypertension

Objectives: To explore the main points of perioperative nursing for adult congenital heart disease with severe pulmonary arterial hypertension. Methods: A retrospective study of 13 patients with congenital heart disease and severe pulmonary arterial hypertension who admitted to the perioperative period of care from January 2018 to December 2019. To prevent perioperative complications of the patients, the focus is on respiratory and circulatory system care, followed by blood coagulation monitoring, digestive system protection and psychological care. Results: All 13 patients passed the perioperative period and were discharged from ICU. Conclusion: Adult congenital heart disease with severe pulmonary arterial hypertension has high perioperative risk, respiratory and circulatory system care is the key.

Heart Transplantation for Adult Congenital Heart Disease:Overview and Special Considerations

With improvements in their surgical and medical management,the number of patients with congenital heart disease(CHD)reaching adulthood has increased over the last decade.As the population of adult CHD patients continues to rise,an increasing number of these patients will require evaluation for heart transplantation.It is important to recognize advanced heart failure and other associated complications early in this cohort of complex patients for early referral to an adult CHD specialist.As these patients present with unique challenges because of their multiple comorbidities and complex anatomy,there needs to be a careful selection process for transplantation to optimize the utilization of donor organs.

Depression in Adults with Congenital Heart Disease:Prevalence,Prognosis,and Intervention

Data on the prevalence of depression in adult congenital heart disease(ACHD)patients differ widely.We aim to summarize the best available information on the prevalence of depression,its prognostic impact,and psychiatric interventions for depressed ACHD patients.We reviewed references in relevant publications up to October 17,2017.For homogeneity of data,studies in which depression was independently assessed in patients aged 18 years or older or with a mean/median age older than 18 years were included.Retrospective and postoperative evaluation studies were excluded.Twenty publications met these criteria.Study samples included ACHD patients followed up at ACHD-specialized hospitals in 13 countries.The prevalence of depression differed widely,ranging from 6 to 69%.Depression has been shown to be an independent predictor of adverse clinical outcomes.It is also frequently associated with other prognostic variables(i.e.,poor functional class,unfavorable perceived health status,and low quality of life).Currently,no randomized clinical trials on psychiatric interventions in ACHD are available.In summary,depression is highly prevalent in ACHD patients,yet it is often unrecognized and untreated.The adverse prognostic impact of depression calls for specialized psychiatric interventions,for which more research is needed in the ACHD patient population.

Stable Ischemic Heart Disease in the Older Adult

Demographic trends worldwide show a progressively aging population and an increase in the overall medical complexity of elderly patients with cardiovascular disease.Elderly patients,especially those aged 75 or older,are relatively underrepresented in many of the clinical trials that helped create major society guidelines for evaluation and management of ischemic heart disease.Consequently,risk benefi t ratios of a guideline-based approach in these patients are not well defi ned,especially with regards to pharmacotherapies and percutaneous coronary interventions.In this article we offer a practical approach to defi ning the elderly population,and provide an evidenced based review of the diagnostic and therapeutic implications of advanced age in the evaluation and management of ischemic heart disease.

Emotions,Perceptions and Health Behaviors of Adult Congenital Heart Disease Patients during COVID-19 in New York City

Background:Adults with congenital heart disease(ACHD)have increased prevalence of mood and anxiety disorders.There are limited data regarding the influence of the COVID-19 pandemic on the mental health and health behaviors of these patients.Objective:The purpose is to evaluate the perceptions,emotions,and health behaviors of ACHD patients during the COVID-19 pandemic.Methods:In this cross-sectional study of ACHD patients,we administered surveys evaluating self-reported emotions,perceptions and health behaviors.Logistic regressions were performed to determine the adjusted odds of displaying each perception,emotion and health behavior based on predictor variables.Results:Ninety-seven patients(mean age 38.3 years,46.4%female,85.6%moderate or complex lesion)completed the survey.The majority of patients reported feeling moderately or very sad(63.1%),and 48.4%of patients identified themselves as feeling moderately or very anxious.The majority of patients perceived their risk of COVID-19 as moderate or high.Females were more likely to report feeling sad and anxious(95%CI 1.06–10.96,p-value 0.039,and 95%CI 1.44–15.30,p-value=0.012,respectively),and were associated with higher odds of having a perceived increased risk of COVID-19(95%CI 1.33–10.59,p-value 0.012).There was no association between ACHD anatomic or physiologic classification and perceptions,emotions and health behaviors.Conclusions:Females were more likely to report feeling sad,anxious and an increased risk of COVID-19 in comparison to males.These findings indicate the need for mental health support and promotion of health behaviors during the pandemic amongst all ACHD patients,regardless of underlying condition.

The Effect of Circuit Training on Resting Heart Rate Variability, Cardiovascular Disease Risk Factors and Physical Fitness in Healthy Untrained Adults

The purpose of the present study was to examine the effect of circuit training (CT) on resting heart rate variability (HRV) and other cardiovascular disease (CVD) risk factors such as blood lipids and blood glucose and on fitness components. Twenty-four healthy untrained adults (age 26.5 ± 5.1 years;height 1.67 ± 8.4 m;weight 66.8 ± 15.1 kg;26.3% ± 5.2%;maximum oxygen uptake (VO2max) 48.5 ± 10.0 ml.kg-1.min-1) were assigned to either CT (n = 12) involving bodyweight exercises, or control (CON, n = 12) groups. Prior to the start and following the end of the six-week training period, time-, frequency-domain and nonlinear measures of resting HRV, arterial blood pressure, body composition, fasting blood lipids, lipoproteins and glucose, VO2max, upper body muscular endurance (UBME) and abdominal and hip flexor (AHFME), back strength (BS) and handgrip were assessed. None of the resting HRV measures (P > 0.05) were affected by the CT intervention. However, diastolic blood pressure decreased (P = 0.03), lean body weight (P = 0.03) increased, VO2max (P = 0.03), UBME (P = 0.001), AHFME (P = 0.04), and BS (P = 0.03) were significantly higher following CT, whereas the other variables were not influenced by the CT. Six-week of CT involving bodyweight exercises has no significant impact on resting HRV. However, this type of training might decrease the risk for development of CVD by reducing arterial blood pressure and by improving body composition, aerobic capacity, muscular endurance and strength.

Comparative Assessment of Melatonin-Afforded Protection in Liver, Kidney and Heart of Male Mice against Doxorubicin Induced Toxicity

Melatonin (MEL) was investigated for protection against the anthracycline antibiotic doxorubicin (Dox) that is well known for its oxidative damage to various body organs. It was aimed to have a comparison of this protection to heart, liver and kidney in the treated subjects. In this study, groups of mice were treated with Dox and melatonin and their individual or combined effects were evaluated by assessing lipidperoxidation, non-protein sulfhydryls (NP-SH) and nitrate/nitrite (NO) contents in these tissues. Plasma aminotransferases, LDH and CK-MB enzyme activities were measured. Moreover, these tissues were subject to histopathological assessment. MEL co-treatment significantly prevented any rise in lipidperoxides more significantly in heart and liver as compared to kidney. In tandem, MEL prevented a decline in GSH that was observed by Dox alone in liver and kidney. Dox significantly increased total NO levels in all the tissues. Melatonin at both dose levels could not afford protection against nitrosative stress. MEL in combination treatment provided significant

Emotional Support and Well-Being of Adults with Congenital Heart Disease (ACHD): Contributions of a Specialist Nursing Service

Living with a congenital heart condition can require a daunting and uncertain patient journey during which the support of a specialist nursing service is vital. A descriptive, cross-sectional evaluation completed over two years, utilised a postal questionnaire to investigate patient’s satisfaction with aspects of service. Qualitative responses to open questions on satisfaction with emotional support (n = 103) and contributions to well-being (n = 90) were analysed using a framework approach which identified eight themes. Professional knowledge and expertise, service accessibility, caring attributes, enabling patients to cope with anxiety, depression and meeting changing needs contributed positively to both patient well-being and emotional support. Family support was influential on emotional support alone, whilst mediating medical liaison exerted an impact on well-being by enhancing feelings of security. In conclusion, the specialist nursing service contributed positively to well-being and emotional support of patients and thereby to selective aspects of continuity of care.

Prevalence and prognostic implications of sarcopenia in older patients with coronary heart disease

Background Sarcopenia is a progressive and generalized skeletal muscle disorder that is associated with an increased likelihood of adverse outcomes, including falls, fractures, physical disability, and mortality. However, there have been few systematic studies of the prevalence and prognostic values of sarcopenia in older patients with coronary heart disease(CHD). This study aimed to investigate the prevalence of sarcopenia in hospitalized older patients with CHD, and to prospectively evaluate the effect of sarcopenia on the short-term prognosis of these patients. Methods Patients aged ≥ 65 years, with the diagnosis of CHD from Peking Union Medical College Hospital between December 2017 and November 2018, were included. Sarcopenia was diagnosed according to consensus of the Asian Working Group for Sarcopenia in 2014. Follow-up items included unscheduled return visits, occurrence of major adverse cardiac and cerebral events (MACCE), and all-cause mortality. The MACCE-free survival curve of sarcopenic and non-sarcopenic older patients with CHD was estimated by the Kaplan-Meier method. Cox regression analysis was used to analyze the association between sarcopenia and an unscheduled return visits, MACCE, and all-cause mortality. Results A total of 345 older patients with CHD were enrolled in the study, with a median age of 74 years. Among the patients, 78 (22.6%) were diagnosed with sarcopenia. During the follow-up time, there were significantly more unscheduled return visits in sarcopenic patients than in non-sarcopenic patients (34.2% vs. 21.8%,χ^2 = 4.418, P = 0.036), while there was no significant difference in the occurrence of MACCE (χ^2 = 2.869, P = 0.09) or all-cause mortality (χ^2 = 1.673, P = 0.196) between these patient groups. The Kaplan-Meier curve showed that the MACCE-free survival time of sarcopenic patients was significantly shorter than that in non-sarcopenic patients (χ^2 = 4.102, P = 0.043). After adjusting for sex, age, and the Charlson comorbidity index, sarcopenia was not an independent risk factor of unscheduled return visits (HR = 1.002, 95% CI: 0.556–1.807). However, the complication of anxiety and depression was an independent risk factor (HR = 1.876, 95% CI: 1.012–3.477, P = 0.046) for unscheduled return visits in older patients with CHD. Conclusions There is a high prevalence of sarcopenia among hospitalized older adults with CHD. A shorter MACCE-free survival time and more unscheduled return visits are found in sarcopenic older patients with CHD. Clinicians should pay more attention to the functional status of older patients with CHD, as well as identification and management of geriatric syndromes.

Effects of functional training on geometric indices of heart rate variability

Background： Geometric methods provide an analysis of autonomic modulation using the geometric properties of the resulting pattern, and represent an interesting tool in the analysis of heart rate variability （HRV）. The aim of this study was to evaluate the impact of functional training on cardiac autonomic modulation in healthy young women using the geometric indices of HRV. Methods： Data were analyzed from 29 women, and were stratified into a functional training group （FTG, n = 13; 23.00 ± 2.51 years; 21.90± 2.82 kg/m2） and a control group （CG, n = 16; 20.56 ± 1.03 years; 22.12±3.86 kg/m2）. The FTG received periodized functional training for 12 weeks. The cardiac autonomic modulation of both groups was evaluated before and after this training, and a qualitative analysis was performed using the Poincar6 plot. Results： There was a significant increase in the difference of the triangular index （RRTri）, SDI, SD2, and RR intervals in the FTG as compared to the CG, and the qualitative analysis from the Poincar6 plot showed an increase in the dispersion of beat-to-beat and long-term RR intervals in the functional group after training. No changes were observed in the triangular interpolation of RR interval histogram （TINN） or SD1/SD2. Conclusion： Functional training had a beneficial impact on autonomic modulation, as characterized by increased parasympathetic activity and overall variability, thus highlighting the clinical usefulness of this type of training.

Influencing factors of fatigue in young and middle-aged patients with coronary heart disease:a cross-sectional study

Objective:To examine the present state of fatigue in young and middle-aged patients with coronary heart disease(CHD)and to identify the elements that may be affecting it.Methods:From December 2020 to June 2021,240 young and middle-aged patients with CHD who were being treated in the cardiology department of a tertiary care hospital in Suzhou were chosen using a convenience sampling method in order to gather data on the patients’sociodemographic status,fatigue,social support,and stress.Results:Of the 240 disseminated questionnaires,220 valid responses were returned,resulting in an effective recovery rate of 91.67%.The frequency of exhaustion was 51.8%,and the fatigue score was(5.27±2.77).The stress score was(11.15±3.36),while the overall social support score was(39.13±4.72).Binary logistic regression analysis indicated that age,exercise,staying up late,stress,social support,high-sensitivity troponin T,high-density lipoprotein,and ejection fraction were independent risk factors for fatigue in young and middle-aged patients with CHD(P<0.05).Conclusions:Fatigue is more prevalent in young and middle-aged patients with CHD.Clinical nurses can create a unique management plan for patients based on their lifestyle and behavioral patterns,stress levels,social support,and clinical signs to reduce fatigue.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.