ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

OBJECTIVE: To observe the clinical efficacy of auricular electroacupuncture for post-stroke dysphagia in the pharyngeal phase. METHODS: Eighty-two patients with post-stroke dysphagia in the pharyngeal phase were randomized into an auricular electroacupuncture group (41 cases) and a swallowing electrical stimulation group (41 cases, 1 case dropped out). In the auricular electroacupuncture group, electroacupuncture was applied at auricular points, i.e. Xin (CO₁₅) and Yanhou (TG₃), using disperse-dense wave, in frequency of 2 Hz/10 Hz, 30 min a time. In the swallowing electrical stimulation group, swallowing electrical stimulation was delivered for 30 min a time. Both groups were treated once daily for 4 weeks. The functional oral intake scale (FOIS) grade, as well as the hyolaryngeal complex displacement, the pharyngeal constriction rate (PCR) and the pharyngeal delay time (PDT) under video fluoroscopic study of swallowing (VFSS) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: Compared before treatment, the FOIS grade was improved (P<0.01), the forward and upward displacement amplitude of hyoid bone and thyroid cartilage was increased (P<0.05), and the PCR and PDT were decreased (P<0.05) after treatment in the two groups. After treatment, compared with the swallowing electrical stimulation group, the FOIS grade was superior (P<0.01), the upward displacement amplitude of hyoid bone and thyroid cartilage was larger (P<0.05) and the PCR and PDT were lower (P<0.05) in the auricular electroacupuncture group. The total effective rate was 85.4% (35/41) in the auricular electroacupuncture group, which was higher than 62.5% (25/40) in the swallowing electrical stimulation group (P<0.05). CONCLUSION Auricular electroacupuncture can effectively trigger pharyngeal initiation and improve post-stroke dysphagia in the pharyngeal phase.
Humans ; Electroacupuncture ; Male ; Deglutition Disorders/etiology* ; Female ; Middle Aged ; Aged ; Stroke/physiopathology* ; Pharynx/physiopathology* ; Acupuncture, Ear ; Acupuncture Points ; Deglutition ; Treatment Outcome ; Adult

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major health concern, and lipoprotein(a) (Lp(a)) is an independent risk factor. However, there is limited evidence regarding Lp(a) and the risk of ASCVD in Asian populations. This study aimed to assess the predictive value of changes in coronary artery calcification (CAC) for ASCVD risk associated with Lp(a) level. Methods: Participants (n=2,750) were grouped according to their Lp(a) levels, and the association between Lp(a) and CAC progression was examined. CAC progression was defined as the occurrence of incident CAC or a difference ≥2.5 between the square root (√) of baseline and follow-up coronary artery calcium scores (CACSs) (Δ√transformed CACS). To adjust for differences in follow-up periods, Δ√transformed CACS was divided by the follow- up period (in years). Results: Over an average follow-up of 3.07 years, 18.98% of participants experienced CAC progression. Those with disease progression had notably higher Lp(a) levels. Higher Lp(a) tertiles correlated with increased baseline and follow-up CACS, CAC progression (%), and Δ√transformed CACS. Even after adjustment, higher Lp(a) levels were associated with CAC progression. However, annualized Δ√transformed CACS analysis yielded no significant results. Conclusion This study demonstrated an association between elevated Lp(a) levels and CAC progression in a general population without ASCVD. However, longer-term follow-up studies are needed to obtain meaningful results regarding CAC progression. Further research is necessary to utilize Lp(a) level as a predictor of cardiovascular disease and to establish clinically relevant thresholds specific to the Korean population.

Percutaneous endoscopic gastrostomy (PEG) has become a standard method for enteral nutrition in patients with swallowing difficulties due to various medical conditions, including neurodegenerative diseases, stroke, and malignancies. While nutrition by PEG is superior to nasogastric nutrition in terms of patient comfort, long-term use, and nutritional efficiency, it requires selection of target patients, appropriate insertion methods, and appropriate management of complications. Appropriate use of prophylactic antibiotics can reduce wound infection and proper management of tube can reduced the possibility of complications such as tube malfunction and buried bumper syndrome. Even though most complications arising from PEG are not severe, we should do careful monitoring because sometimes life-threatening events which need surgical treatment or intensive medical care can be happened. Therefore, it is necessary to understand the indications of PEG, to properly select the method of insertion, and to know about complications that may occur during or after the PEG.

It is difficult to determine a cause of bile duct stricture and dilatation. Eosinophilic cholangitis, a rare benign condition, may be one cause of bile duct stricture and dilatation. It can be evaluated using various methods of histopathology, radiographs, endoscopy, and hematologic findings. Treatment generally involves steroid therapy which can lead to improvement. This case report will discuss eosinophilic cholangitis, emphasizing that while it can easily be overlooked but should be considered in differential diagnoses.