OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control. Methods: T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability. Conclusion The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Objective:To explore the potential profile characteristics and influencing factors of rehabilitation motivation in elderly patients with first stroke, so as to provide reference for promoting precise rehabilitation mode.Methods:A convenience sampling method was employed to conduct a cross-sectional survey of elderly patients with first stroke admitted to the Huanhu Hospital Affiliated to Tianjin Medical University from October 2024 to March 2025. The survey utilized a general information questionnaire, the Motivation in Stroke Patients for Rehabilitation Scale, the Perceived Social Support Scale (PSSS), the Exercise Adherence Questionnaire (EAQ), and the Stroke Stigma Scale (SSS). Potential categories of rehabilitation motivation among elderly patients with first stroke were identified using latent profile analysis, and the influencing factors of these potential categories were explored using the ordered multinomial Logistic regression.Results:A total of 290 survey questionnaires were distributed, and 281 valid questionnaires were collected, with an effective response rate of 96.9%(281/290). Among 281 elderly patients with first stroke, there were 152 males and 129 females, with an age of (68.68 ± 6.89) years. The score of the Motivation in Stroke Patients for Rehabilitation Scale was 56.00 (36.00, 68.00) points. Rehabilitation motivation among elderly patients with first stroke could be categorized into three groups: low motivation-lack of family support and unclear goals group (44.1%, 124/281), moderate motivation-social reintegration driven but insufficient behavior group (41.3%, 116/281), and high motivation autonomous planning adaptation and value internalization group (14.6%, 41/281). The ordered multinomial Logistic regression analysis showed that compared to patients aged ≥80 years, patients aged 60-69 years were less likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.231, P<0.05). Compared to patients with a per capita monthly income of ≥5 001 yuan, patients with a per capita monthly income of 3 001-5 000 yuan were more likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=2.340, P<0.05). Compared to heavily dependent patients, patients who were completely independent ( OR=0.160, P<0.05), mildly dependent ( OR=0.155, P<0.01), and moderately dependent ( OR=0.211, P<0.05) were less likely to belong to the high motivation autonomous planning adaptation and value internalization group. The higher the EAQ score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.139, P<0.01). The higher the PSSS score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.108, P<0.01). The higher the SSS score, the less likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.787, P<0.01). Conclusions:Healthcare professionals can develop targeted intervention strategies based on the characteristics and influencing factors of patients' different rehabilitation motivations, thereby enhancing their rehabilitation motivation and promoting patient recovery.

Objective:To explore the potential categories of internal ability of elderly patients with ischemic stroke, identify the influencing factors and propose corresponding nursing interventions.Methods:This was a cross-sectional study. From January 2025 to May 2025, the elderly patients with ischemic stroke in Tianjin Huanhu Hospital were selected by convenient sampling method. The general information questionnaire, the Internal Capacity Assessment Scale for the Older People, the Health Literacy Scale for stroke patients and the Perceived Social Support Scale were used to investigate. To determine latent categories of patients' intrinsic capacity, potential profile analysis was employed. Subsequently, multivariable Logistic regression examined factors associated with these categories.Results:A total of 260 survey questionnaires were distributed, and 256 valid questionnaires were finally collected, with an effective response rate of 98.46% (256/260). Among of them, there were 166 males and 90 females, aged 68.00 (63.00, 74.00) years.The intrinsic ability of elderly patients with ischemic stroke could be divided into three potential categories: low sensation-low exercise group (27.0%, 69/256), relatively stable intrinsic ability group (37.5%, 96/256) and low cognition-low psychology group (35.5%, 91/256). Multivariable Logistic regression showed that advanced age (compared to the low sensation-low exercise group, OR=0.902; compared to the relatively stable intrinsic ability group, OR=0.813), smoking (compared to the low sensation-low exercise group, OR=0.459; compared to the relatively stable intrinsic ability group, OR=0.442), the lower the Barthel index (compared to the low sensation-low exercise group, ≤40 points with OR=0.157; 41-60 points with OR=0.285) were more likely to enter the low cognition-low psychology group (all P<0.05); other chronic disease types ≤1 (compared to the low cognition-low psychology group, OR=2.630), higher health literacy scores (compared to the low cognition-low psychology group, OR=1.033) were more likely to enter the relatively stable intrinsic ability group (both P<0.05); and stroke frequency was the first occurrence (compared to the low cognition-low psychology group, OR=2.725) was more likely to enter the low sensation-low exercise group ( P<0.05). Conclusions:In older adults with ischemic stroke, the characteristics of intrinsic ability are clearly categorized. To enhance patient outcomes, healthcare professionals are advised to tailor nursing interventions based on the unique features and specific influencing factors associated with each potential category.

Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.

Background and Aims:Centrally located breast cancer(CLBC),due to its proximity to the nipple-areolar complex,has long been treated primarily with mastectomy,while the oncologic safety of breast-conserving surgery(BCS)remains controversial.This study,based on a large-scale database combined with a real-world cohort,compared the survival outcomes of BCS and mastectomy to evaluate the feasibility and oncologic safety of BCS in CLBC patients.Methods:Data of 10 325 female CLBC patients diagnosed between 2010 and 2015 were extracted from the SEER database,including 5 601 patients who underwent BCS and 4 724 who underwent mastectomy.Propensity score matching(PSM)yielded 1 951 matched pairs,and disease-specific survival(DSS)and overall survival(OS)were compared between groups.Cox regression analyses were performed to identify prognostic factors,and subgroup analyses were conducted.Additionally,an independent validation cohort from Xiangya Hospital,Central South University(2015-2016)included 221 BCS and 636 mastectomy patients,with OS and progression-free survival(PFS)assessed.Results:After PSM,baseline characteristics between groups were well balanced.Kaplan-Meier analysis demonstrated no significant differences in DSS or OS between BCS and mastectomy,and 5-,7-,and 10-year OS rates were comparable(all P＞0.05).Subgroup analyses revealed equivalent outcomes for BCS and mastectomy in patients with T1/T2 disease,different HER2 statuses,and those receiving chemotherapy,while in patients receiving radiotherapy,BCS showed significantly better DSS and OS than mastectomy(both P＜0.05).Multivariate Cox regression identified T,N,and M stage,histologic grade,molecular subtype,ER/PR status,and chemotherapy as independent prognostic factors(all P＜0.05),whereas surgical type was not(P＞0.05).The validation cohort confirmed the SEER findings,with no significant differences in OS or PFS between the two groups(both P＞0.05).Conclusions:BCS provides DSS and OS comparable to mastectomy in CLBC patients and may confer additional survival benefits when combined with radiotherapy.These findings suggest that CLBC should not be considered a contraindication to BCS,supporting BCS as a feasible and safe surgical strategy that offers valuable evidence for individualized clinical decision-making and may help improve patients' quality of life.

Objective:To explore the potential profile characteristics and influencing factors of rehabilitation motivation in elderly patients with first stroke, so as to provide reference for promoting precise rehabilitation mode.Methods:A convenience sampling method was employed to conduct a cross-sectional survey of elderly patients with first stroke admitted to the Huanhu Hospital Affiliated to Tianjin Medical University from October 2024 to March 2025. The survey utilized a general information questionnaire, the Motivation in Stroke Patients for Rehabilitation Scale, the Perceived Social Support Scale (PSSS), the Exercise Adherence Questionnaire (EAQ), and the Stroke Stigma Scale (SSS). Potential categories of rehabilitation motivation among elderly patients with first stroke were identified using latent profile analysis, and the influencing factors of these potential categories were explored using the ordered multinomial Logistic regression.Results:A total of 290 survey questionnaires were distributed, and 281 valid questionnaires were collected, with an effective response rate of 96.9%(281/290). Among 281 elderly patients with first stroke, there were 152 males and 129 females, with an age of (68.68 ± 6.89) years. The score of the Motivation in Stroke Patients for Rehabilitation Scale was 56.00 (36.00, 68.00) points. Rehabilitation motivation among elderly patients with first stroke could be categorized into three groups: low motivation-lack of family support and unclear goals group (44.1%, 124/281), moderate motivation-social reintegration driven but insufficient behavior group (41.3%, 116/281), and high motivation autonomous planning adaptation and value internalization group (14.6%, 41/281). The ordered multinomial Logistic regression analysis showed that compared to patients aged ≥80 years, patients aged 60-69 years were less likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.231, P<0.05). Compared to patients with a per capita monthly income of ≥5 001 yuan, patients with a per capita monthly income of 3 001-5 000 yuan were more likely to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=2.340, P<0.05). Compared to heavily dependent patients, patients who were completely independent ( OR=0.160, P<0.05), mildly dependent ( OR=0.155, P<0.01), and moderately dependent ( OR=0.211, P<0.05) were less likely to belong to the high motivation autonomous planning adaptation and value internalization group. The higher the EAQ score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.139, P<0.01). The higher the PSSS score, the more likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=1.108, P<0.01). The higher the SSS score, the less likely patients were to belong to the high motivation autonomous planning adaptation and value internalization group ( OR=0.787, P<0.01). Conclusions:Healthcare professionals can develop targeted intervention strategies based on the characteristics and influencing factors of patients' different rehabilitation motivations, thereby enhancing their rehabilitation motivation and promoting patient recovery.