Abnormal Function Research Articles

Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality

Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality

Multimodal abnormalities of brain function in chronic low back pain: a systematic review and meta-analysis of neuroimaging studies

ObjectivesNeuroimaging investigations into chronic low back pain (CLBP) have detected functional abnormalities across a spectrum of brain regions, yet the findings have often been inconsistent. In this meta-analysis, we integrated the existing data, delineating a pattern of coherent results from the encompassed studies.MethodsA systematic search of neuroimaging studies investigating the brain activity differences between CLBP and Healthy controls (HCs) was conducted in seven databases up to December 22, 2024. An anisotropic effect-size signed differential mapping (AES-SDM)-based meta-analysis was carried out to report the results and perform a multimodal analysis.ResultsA total of 20 publications reporting on 24 experiments in this meta-analysis. The ReHo meta-analysis showed abnormal spontaneous activity of left inferior temporal gyrus (ITG), left superior frontal gyrus (SFG), right middle frontal gyrus (MFG), right precuneus, right fusiform gyrus and bilateral postcentral gyrus (PoCG) in CLBP patients. The ALFF meta-analysis demonstrated functional alterations in the right rolandic operculum (extending to the right insula and right IFG), left ITG, left middle occipital gyrus (MOG), left paracentral lobule, left PoCG and bilateral cuneus cortex in CLBP patients. The results of the functional group meta-analysis revealed that patients with CLBP displayed new decreased functional activity in the right thalamus, right precentral gyrus (PreCG) and right lingual gyrus.ConclusionPatients with CLBP exhibit extensive multimodal functional neuroimaging abnormalities, involving brain regions related to pain perception, emotional processing, cognitive functions, and both the visual and motor cortices. These meta-analysis findings might provide a valuable reference for the identification of potential therapeutic targets for CLBP in the brain.

Ultrasonic characteristics of inserted central catheter related fibroblastic sleeve

This study was aimed to summarize the ultrasonic characteristics of inserted central catheter (ICC) related fibroblastic sleeve, providing theoretical basis for its early diagnosis. Clinical and ultrasonic data of patients with ICC confirmed by pathology to have fibroblastic sleeves in our hospital from June 4, 2020 to April 1, 2024 were collected. All ICCs were made of polyurethane. Patients required the ultrasound evaluation due to local swelling and pain, abnormal coagulation function, lack of response to flushing of saline and heparin, or before extubation. The ultrasonic characteristics of fibroblastic sleeve such as its starting point, shape, thickness, internal echo, number of layers, relationship to the catheter, and presence or absence of thrombosis were analyzed. After the removal of the ICC, there was a membrane-like structure adhesion on the surface of the catheter, which was composed of endothelial cells, smooth muscle cells, collagen and fibrous connective tissues. A total of 95 patients with pathologically confirmed fibroblastic sleeve were present, of which 44 patients had only fibroblastic sleeves (46.32%) and 51 patients had fibroblastic sleeves with thrombi (53.68%). The fibroblastic sleeve originated from the site where the catheter contacted the vein wall and extended in a distal direction, with a thickness ranged between 0.7 and 5.6 mm. With the pathological results as the gold standard, the optimal cut-off value for the diagnosis of fibroblastic sleeve with thrombosis was 2.58 mm, and the sensitivity and specificity of the diagnosis were 95.45% and 96.08%. Compared to echogenicity of the catheter wall, hyperechoic or isoechoic fibroblastic sleeves were observed in 89 patients, while hypoechoic fibroblastic sleeves were observed in 6 patients. There were significant differences in the location of catheterization and duration of catheterization between the single-layer group and the double-layer group (P < 0.05). Fibroblastic sleeves were tightly attached to the catheter walls in 78 patients and loosely attached to the catheter walls in 17 patients, with significant differences in the location of catheterization and duration of catheterization (P < 0.05). ICC-related fibroblastic sleeves have specific ultrasonic characteristics. Understanding these ultrasonic characteristics can provide a reliable basis for their early diagnosis and timely treatment.

Dexamethasone in critical coronavirus disease-2019 cases: Insights from a cross-sectional study

Objective: The objective of the study is to describe the clinical and laboratory characteristics of critically ill coronavirus disease-2019 (COVID-19) patients treated with dexamethasone in an intensive care unit (ICU) to provide a support tool for clinical decision-making. Design: A survey was conducted among hospitalized patients from November 2020 to March 2021, with data collected through patient interviews, medical records, and laboratory tests. Setting: This is a large hospital serving as a reference center for COVID-19 care in Bahia, Brazil. Patients: A convenience sample of 22 patients admitted to the COVID-19 ICU who signed informed consent to participate in the study. Methods: A cross-sectional study of patients admitted to the ICU with COVID-19. Data were analyzed using statistical methods. Results: The most common comorbidities among patients were hypertension (54%), diabetes (36%), and cardiovascular disease (27%). Among the deaths recorded, 55% of patients had hypertension, 44% had diabetes and/or required insulin therapy, 33% had a history of cardiovascular disease (including atrial fibrillation and congestive heart failure), and 22% had a history of stroke. Renal dysfunction (elevated creatinine); liver function abnormalities (increased alanine aminotransferase and aspartate aminotransferase); and elevated levels of ferritin, fibrinogen, and D-dimer were identified as potential indicators of disease progression. Among these factors, only elevated creatinine demonstrated a statistically significant association with an increased mortality risk. Conclusion: These findings provide a better understanding of the clinical course of severe acute respiratory syndrome coronavirus 2 infections and suggest that laboratory medicine is crucial in supporting clinical decision-making and advancing scientific and healthcare knowledge during the early phases of the COVID-19 pandemic. Relevance for patients: Identifying key risk factors, such as renal dysfunction, can improve early intervention and personalized treatment for critically ill COVID-19 patients.

Serum uric acid/creatinine ratio and 1-year stroke recurrence in patient with acute ischemic stroke and abnormal renal function: results from the Xi'an stroke registry study of China

BackgroundThe relationship between abnormal renal function and serum uric acid levels in patients with acute ischemic stroke (AIS) remains insufficiently explored. Although uric acid is associated with cardiovascular and cerebrovascular risk, the specific link between normalized serum uric acid (SUA/SCr) and stroke recurrence in patients with impaired renal function has not been well studied. This study aims to fill this gap by investigating the association between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function.MethodsThis study utilized the ratio of serum uric acid (SUA) to serum creatinine (SCr) to represent SUA levels normalized for renal function. Abnormal Renal function was defined by the estimated glomerular filtration rate (eGFR) &amp;lt; 90 mL/min/1.73 m2. Multivariable Cox regression, curve fitting, and stratified analyses were employed to assess the relationship between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function, considering SUA/SCr as both a continuous variable and in quartiles (Q1–Q4).ResultsOf 1,932 enrolled patients (65.3% male; mean age 66.7 ± 11.3 years), each unit of increase in SUA/SCr was associated with a 17% decrease in 1-year stroke recurrence (HR = 0.83, 95% CI 0.73 to 0.96, P = 0.009). Compared to Q1, the Q2 and Q4 groups showed significantly reduced risk in 1-year stroke recurrence (Q2: HR = 0.46, 95% CI 0.27 to 0.79, P = 0.005; Q4: HR = 0.47, 95% CI 0.27 to 0.81, P = 0.007), with a significant trend across all quartiles (P = 0.01 for trend tests). Curve fitting revealed a negative but non-linear correlation. Subgroup analyses showed that in patients with eGFR &amp;lt; 60 ml/min/1.73 m2, Q4 had significantly lower 1-year stroke recurrence risk than Q1 (HR = 0.19, 95% CI 0.04 to 0.86, P = 0.031).ConclusionLow SUA/SCr independently predicts 1-year stroke recurrence in patients with AIS and abnormal renal function, particularly in those with eGFR &amp;lt; 60 mL/min/1.73 m2.

Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Currently, it has shown a trend of earlier onset, with most patients experiencing a progressive decline in cognitive function following the disease's onset, which places a heavy burden on society and family. Since no drug cure for AD exists, exploring new ways for its treatment and prevention has become critical. Early vascular damage is an initial trigger for neuronal injury in AD, underscoring the importance of vascular health in the early stages of the disease. Patients with early AD experience abnormal blood-brain barrier transport of amyloid-β (Aβ) peptides, with excess Aβ being deposited in the cerebral vasculature. The toxic effects of Aβ lead to abnormalities in cerebrovascular structure and function. Fibroblast growth factor21 (FGF21) is an endocrine factor that positively regulates energy homeostasis and glucose-lipid metabolism. Notably, it is one of the effective targets for metabolic disease prevention and treatment. Recent studies have found that FGF21 has anti-aging and vasoprotective effects, with receptors for FGF21 present in the brain. Exercise stimulates the liver to produce large amounts of FGF21, which enters the blood-brain barrier with the blood to exert neurovascular protection. Therefore, we review the biological properties of FGF21, its role in the cerebrovascular structure and function in AD, and the mechanism of exercise-regulated FGF21 action on AD-related cerebrovascular changes, aiming to provide a new theoretical basis for using exercise to ameliorate degenerative neurological diseases.

Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto’s thyroiditis and Graves’ disease. Long COVID may disrupt the hypothalamic–pituitary–adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.

Gut microbiota and atrial cardiomyopathy

Atrial cardiomyopathy is a multifaceted heart disease characterized by structural and functional abnormalities of the atria and is closely associated with atrial fibrillation and its complications. Its etiology involves a number of factors, including genetic, infectious, immunologic, and metabolic factors. Recent research has highlighted the critical role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, and this is consistent with the gut–heart axis having major implications for cardiac health. The aim of this work is to bridge the knowledge gap regarding the interactions between the gut microbiota and atrial cardiomyopathy, with a particular focus on elucidating the mechanisms by which gut dysbiosis may induce atrial remodeling and dysfunction. This article provides an overview of the role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, including changes in the composition of the gut microbiota and the effects of its metabolites. We also discuss how diet and exercise affect atrial cardiomyopathy by influencing the gut microbiota, as well as possible future therapeutic approaches targeting the gut–heart axis. A healthy gut microbiota can prevent disease, but ecological dysbiosis can lead to a variety of symptoms, including the induction of heart disease. We focus on the pathophysiological aspects of atrial cardiomyopathy, the impact of gut microbiota dysbiosis on atrial structure and function, and therapeutic strategies exploring modulation of the microbiota for the treatment of atrial cardiomyopathy. Finally, we discuss the role of gut microbiota in the treatment of atrial cardiomyopathy, including fecal microbiota transplantation and oral probiotics or prebiotics. Our study highlights the importance of gut microbiota homeostasis for cardiovascular health and suggests that targeted interventions on the gut microbiota may pave the way for innovative preventive and therapeutic strategies targeting atrial cardiomyopathy.

Efficacy and safety assessment of propranolol tablets vs. oral solution for infantile hemangioma: a retrospective study in China

BackgroundPropranolol for infantile hemangiomas (IHs) is effective and relatively safe. However, propranolol has different formulations and there is no consensus on the optimal formulation for IHs. The propranolol oral solution was not used in China until 2022.ObjectiveTo evaluate the efficacy and safety of propranolol tablets and an oral solution in infants with high-risk IH.MethodsA retrospective cohort study was conducted involving 234 consecutive patients with a clinical diagnosis of high-risk IH who were treated with propranolol between August 2018 and February 2023 (propranolol tablets, 168 patients; propranolol oral solution, 66 patients). All patients were assessed in the hospital at the initiation of treatment and in the outpatient setting during treatment. The Hemangioma Activity and Severity Index was used to monitor the clinical activity of the hemangioma after propranolol treatment.ResultsBased on the Hemangioma Activity and Severity Index, 66.52% and 69.15% improvement occurred in the propranolol tablet and oral solution groups, respectively. 23.21% of patients in the propranolol tablet group and 42.42% in the oral solution group achieved &amp;gt;75% score improvement (X2 = 8.557; P = 0.003). Adverse reactions occurred in 34 (20.24%) and 11 patients (16.67%) in the propranolol tablet and oral solution groups, respectively. The most common adverse reaction in the propranolol tablet group was liver function abnormalities due to mild elevation of liver enzymes (X2 = 4.09; P = 0.045).ConclusionBoth propranolol tablets and oral solution had positive efficacy in patients with high-risk IHs, but more patients in the propranolol oral solution group achieve &amp;gt;75% score improvement compared to the propranolol tablet group. No life-threatening adverse reactions occurred in either group but liver function abnormalities were more likely to occur in patients treated with propranolol tablets.

Protective Factors Associated with Normal Lymphatic Function After Axillary Lymph Node Dissection for Breast Cancer Treatment.

Risk factors associated with developing lymphedema following axillary lymph node dissection (ALND) are well-described in the literature. However, lymphedema diagnosis criteria is arbitrary and can vary between studies. This study instead aims to identify protective factors associated with normal lymphatic function after ALND for treatment of breast cancer. This was a prospective study of women treated with unilateral ALND for breast cancer between 2020 and 2023. Patients with normal lymphatic function were defined as meeting all of four criteria: <10% arm volume change from baseline, <10 bioimpedance change from baseline, no compression use, and Stage 0 on ICG lymphography at one year follow-up. All other patients were classified as having abnormal lymphatic function. Univariable and multivariable logistic regression were used to examine variables possibly associated with normal lymphatic function. Of 150 patients with 1-year follow-up, 39 patients (26%) had normal lymphatic function and 111 patients (74%) had abnormal lymphatic function. On multivariable analysis, immediate lymphatic reconstruction (ILR) and younger age were significantly associated with normal lymphatic function. The odds of normal lymphatic function in patients who had ILR were 2.79 times higher than that of patients who did not undergo ILR (odds ratio [OR] = 2.79, 95% confidence interval [CI] = 1.23-6.69, p = 0.017). Meanwhile, increased age was associated with decreased odds of normal lymphatic function (OR = 0.93, 95% CI = 0.89-0.97, p = 0.001). Immediate lymphatic reconstruction and younger age are significantly associated with normal lymphatic function 1 year after ALND. These findings suggest that undergoing ILR may be protective against developing breast cancer-related lymphedema.

Microstructural maturation of the splenium of corpus callosum and cognitive and motor outcome in very preterm infants

Introduction: Common brain injuries of preterm infants do not entirely explain the incidence of neurodevelopmental impairment observed in this population. Evidence suggests an association with microstructural maturation of the splenium of corpus callosum. This study aimed to investigate a correlation between microstructural maturation of the splenium of corpus callosum and neurodevelopmental outcome in very preterm infants. Method: In a cohort study of 373 very preterm infants, we used fractional anisotropy (FA) and apparent diffusion coefficient (ADC) derived from diffusion tensor imaging at term equivalent age (TEA) to quantitatively reflect microstructural maturation of the splenium of corpus callosum, and standardized follow-up assessments of cognitive and motor function at 24 months corrected age and five years chronological age. Correlation was tested by Spearman rank´s correlation coefficients and multivariate regression analysis. Results: At 24 months, we found significantly lower FA and higher ADC values in infants with abnormal mental indices, psychomotor developmental indices and fine motor function. Scores of all three correlated positively with FA and negatively with ADC. Aged five years, lower FA values correlated significantly with abnormal overall motor function, and higher ADC values correlated significantly with abnormal full scale intelligence quotient (FSIQ) and overall motor function. Scores of FSIQ, overall and fine motor function correlated negatively with ADC. Conclusion: The results emphasize an association between microstructural maturation of the splenium of corpus callosum at TEA and neurodevelopmental outcome, and suggest that ADC may be more strongly linked to these outcomes than FA, especially in the long-term.

Benzimidazole Fungicide Carbendazim Induces Gut Inflammation through the TLR5/NF-κB Pathway in Grass Carp.

Fungicides have been increasingly used across various sectors, including agriculture and textiles. The biocidal properties of fungicides may negatively impact the stability of intestinal microbiota, thereby posing a threat to intestinal health. In this study, we investigated the mechanisms of intestinal damage and functional abnormalities in grass carp following a 42-day exposure to the widely used fungicide carbendazim at environmentally relevant concentrations (0.2 to 20 μg/L). Histopathological observations, mRNA and protein expression analyses, biochemical analysis, quantification of short-chain fatty acids (SCFAs), cytokines, lipopolysaccharide (LPS), and 16S ribosomal ribonucleic acid (rRNA), as well as internal transcribed spacer (ITS) sequencing, were performed. At environmentally relevant concentrations, carbendazim strongly induced intestinal inflammation, leading to increased transcriptional and translational levels of genes involved in the toll-like receptor five (TLR5)/nuclear factor kappa B (NF-κB) pathway, including TLR5, NF-κB, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNFα). Additionally, carbendazim damaged intestinal barriers and reduced the expression of tight junction proteins (e.g., occludin and zonula occludens-1/2), goblet cells, and immunoglobulin M levels, while also disrupting the gut microbiome, leading to intestinal metabolic disorders, particularly decreases in SCFAs and increases in LPS. Treatment with the TLR5 antagonist TH1020 mitigated intestinal inflammation caused by carbendazim, subsequently improving mechanical barrier function. Overall, our findings provide new insights into the toxicological mechanisms underlying intestinal damage caused by carbendazim in grass carp, indicating that carbendazim poses a significant threat to nontarget organisms. Given its widespread detection in the environment, these results underscore the substantial ecological risks to the gut health of fish living in carbendazim-contaminated water bodies.

Effect of baseline geriatric and quality of life assessments on treatment outcomes in ECOG-ACRIN EA2186 (GIANT): A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer.

676 Background: Data is lacking to guide the care of vulnerable older adults (OA) with newly diagnosed metastatic pancreatic adenocarcinoma (mPDAC). EA2186 trial demonstrated poor outcomes among vulnerable OA with mPDAC treated with dose-reduced chemotherapy. To understand the factors driving treatment outcomes in this patient population, we analyzed the correlation between baseline geriatric and quality of life (QOL) assessments and treatment outcomes. Methods: Vulnerable OA ≥70 yo with mPDAC, ECOG PS 0-2 were enrolled. Vulnerability was defined by screening geriatric assessment (GA) demonstrating mild abnormalities in function, comorbidities, cognition, or age≥80y. Pts were randomized to Arm A: Gemcitabine (1000mg/m2) + Nab-Paclitaxel (125mg/m2) q14 days or Arm B: 5-Fluorouracil (2400mg/m2 46hr) + Leucovorin (400mg/m2) + Liposomal Irinotecan (50mg/m2) q14 days. GA and QOL evaluations were completed at baseline and 3 time points. Secondary endpoints of the study included evaluating the correlation between baseline GA, QOL and treatment outcomes. Regression models were used to evaluate the associations between baseline GA and QOL factors, survival and grade 3 or higher toxicity, with 80% power to detect doubling in grade 3 toxicity for GA/QOL measures. Results: 176 pts (88 per arm) enrolled with median age 77 (range 70-90), 24% ECOG-0, 64% ECOG-1 and 12% ECOG-2. Pts were deemed vulnerable by cognition (46%), age (36%) or comorbidities (31.4%), with 35% meeting vulnerability criteria in ≥2 domains. No significant difference was seen in median OS (4.7 vs. 4.4 months; p=0.72) or ≥grade 3 toxicity rate (45.6% vs. 58.7%; p=0.10) between arms A and B, respectively. Strong correlation was found between OS and baseline instrumental activities of daily living score (HR 0.84; p=0.02), nutritional scores (HR 0.82; p&lt;0.0001), depression scores (HR 1.07; p=0.02), and scores of all QOL measures (HR 0.98; p&lt;0.0001). No correlation was found between OS and comorbidity, cognition, and Activities of Daily Living scores. After adjustment for age and PS, only baseline WBC level (OR=0.35; p=0.0054), and depression scores (OR=1.20 per score unit; p=0.021) and to a lesser extent FACT-G score (OR=0.98 per score unit; p=0.061) were found to correlate with rates of ≥grade 3 toxicity. Conclusions: Baseline GA and QOL factors among vulnerable older adults with mPDAC correlate strongly with survival and treatment tolerance. Supportive care to address these factors may favorably affect outcomes in this patient population. Clinical trial information: NCT04233866 .

Parathyroid Hormone Fluctuations During Thyroid and Parathyroid Surgery.

Stress hormone levels such as cortisol and epinephrine increase with general anesthesia (GA) and surgery. Parathyroid hormone (PTH) has been shown to increase with GA in those undergoing parathyroidectomy (PT) with abnormal parathyroid function, but there are conflicting reports of it in those with normal parathyroid function. In this study, we aim to determine the effects of anesthetic and surgical stress on those with abnormal parathyroid function undergoing PTs as well as those with normal parathyroid function undergoing unilateral/total thyroidectomies (UTs/TTs). Prospective study. Single tertiary academic center. Patients undergoing TT, UT, and PT were studied. PTH was measured consecutively during the preoperative, postanesthetic induction before incision, intraoperative, and postoperative periods. One hundred sixty patients were included, with 77 and 31 undergoing TT and UT, respectively, and 52 undergoing PT. Mean PTH levels were significantly higher following induction and intubation across all groups (TT: 139.2 vs 65.1 pg/mL, 113.8% increase; UT: 130.4 vs 57.1 pg/mL, 128.4% increase; PT: 219.6 vs 163.7 pg/mL, 34.1% increase) and remained elevated until excision (TT: 131.8 pg/mL; UT: 124.9 pg/mL; PT: 228.7 pg/mL). Following UT, mean PTH declined to preoperative levels by 1 hour postexcision. Compared to thyroidectomy groups, PTH in the PT group showed more variable responses to anesthesia induction. PTH consistently increases in response to anesthetic and surgical stress in adults undergoing UT and TT with normal preoperative parathyroid function. In contrast, those with hyperparathyroidism demonstrated variable changes.

Involvement of mitochondrial dysfunction and oxidative stress in the nephrotoxicity induced by high-fat diet in Sprague-Dawley rats.

The prevalence of obesity-associated kidney injury has increased, yet the precise extent of the injury and its underlying mechanisms remain unclear. This study used a Sprague-Dawley (SD) rat model to simulate human exposure scenarios, with the objective of investigating the involvement of mitochondria in obesity-induced renal toxicity. Biochemical analysis revealed significant increases in serum creatinine, cystatin C, urinary protein, urinary microalbumin, and urinary α1-microglobulin levels in rats fed a high-fat diet, indicating a notable decline in glomerular filtration function. Histopathological examination showed mild to moderate degeneration in renal tubular epithelial cells, slight glomerular enlargement, fusion and disappearance of pedunculated cell, and decreased electron density of mitochondrial matrix and cristae, indicating the impaired filtration function of kidney. Furthermore, the study found reduced mitochondrial membrane potential and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels, signifying elevated mitochondrial oxidative stress in the kidneys of high-fat diet-fed rats. Additionally, a decrease in the number of mitochondrial proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein-2 (UCP-2)-positive cells, as well as reduced protein expression levels in the mitochondria, suggests a reduced renal mitochondrial resistance to oxidative stress. Collectively, these findings indicate that a high-fat diet triggers abnormalities in both renal filtration and structural functionality in SD rats. The observed reduction in renal mitochondrial density and the elevation in oxidative stress levels could potentially serve as underlying mechanisms.

Innovations in acute and chronic pain biomarkers: enhancing diagnosis and personalized therapy.

Pain affects millions worldwide, posing significant challenges in diagnosis and treatment. Despite advances in understanding pain mechanisms, there remains a critical need for validated biomarkers to enhance diagnosis, prognostication, and personalized therapy. This review synthesizes recent advancements in identifying and validating acute and chronic pain biomarkers, including imaging, molecular, sensory, and neurophysiological approaches. We emphasize the emergence of composite, multimodal strategies that integrate psychosocial factors to improve the precision and applicability of biomarkers in chronic pain management. Neuroimaging techniques like MRI and positron emission tomography provide insights into structural and functional abnormalities related to pain, while electrophysiological methods like electroencepholography and magnetoencepholography assess dysfunctional processing in the pain neuroaxis. Molecular biomarkers, including cytokines, proteomics, and metabolites, offer diagnostic and prognostic potential, though extensive validation is needed. Integrating these biomarkers with psychosocial factors into clinical practice can revolutionize pain management by enabling personalized treatment strategies, improving patient outcomes, and potentially reducing healthcare costs. Future directions include the development of composite biomarker signatures, advances in artificial intelligence, and biomarker signature integration into clinical decision support systems. Rigorous validation and standardization efforts are also necessary to ensure these biomarkers are clinically useful. Large-scale collaborative research will be vital to driving progress in this field and implementing these biomarkers in clinical practice. This comprehensive review highlights the potential of biomarkers to transform acute and chronic pain management, offering hope for improved diagnosis, treatment personalization, and patient outcomes.

Abstract TP332: Assessing the Role of Thyroid Function in Ischemic Stroke: A Retrospective Analysis Across TOAST Classification

Introduction: Subclinical hyperthyroidism has been linked to an increased risk of atrial fibrillation, which elevates the likelihood of cardioembolism, cryptogenic stroke (CS), and embolic stroke of undetermined source (ESUS). However, the broader relationship between thyroid function abnormalities and acute ischemic stroke remains uncertain. This study aims to investigate whether patients with acute ischemic stroke due to cardioembolism, CS, or ESUS are more likely to have abnormal thyroid-stimulating hormone (TSH) levels compared to those with ischemic strokes from other etiologies, as classified by the TOAST criteria. Methods: Utilizing data from the Get With The Guidelines Database, we conducted a retrospective chart review of patients admitted to our single comprehensive stroke center, diagnosed with an acute ischemic stroke between August 2022 and January 2023. The Kruskal-Wallis rank sum test was employed to assess differences in TSH, Free T4, and, if available, one year follow-up TSH levels among patients with ischemic stroke etiologies of small vessel disease, large artery atherosclerosis, cardioembolism, CS, and ESUS. Results: A total of 211 patients were included in the analysis, the distribution of stroke etiologies included 33 (16%) with small vessel disease, 51 (24%) with large artery atherosclerosis, 77 (36%) with cardioembolism, 13 (6.2%) with an undetermined/cryptogenic etiology, and 25 (12%) with ESUS. The majority of patients had normal TSH levels, accounting for 82% of the total cohort, the overall mean TSH level was 2.52 (reference range 0.27-4.2uIU/mL). No significant differences were observed in the mean TSH (p = 0.066), Free T4 (p = 0.13), or follow-up TSH (p = 0.79) levels across each stroke subtype. Conclusions: Our findings suggest that thyroid function does not significantly differ across the various etiologies of acute ischemic stroke, as classified by TOAST criteria. While further large-scale studies are warranted, our results indicate that routine evaluation of thyroid function may not be essential in the determination of stroke etiology.

Preliminary results of benmelstobart plus anlotinib combined with SOX in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with low PD-L1 expression: A single-arm, multicenter phase II clinical trial.

444 Background: First-line chemotherapy for advanced HER2-negative gastric/gastroesophageal (G/GEJ) adenocarcinoma has limited efficacy. PD-1 inhibitors plus chemotherapy show promise but need improvement, especially for patients (pts) with low PD-L1 expression. Anlotinib, a multi-targeted TKI for tumor angiogenesis/proliferation, is approved in China. This study aims to evaluate the efficacy and safety of benmelstobart a PD-L1 blockade) in combination with anlotinib and SOX (S-1 plus oxaliplatin) as a first-line regimen for advanced G/GEJ adenocarcinoma in patients with low PD-L1 expression, Preliminary findings will be reported promptly. Methods: Pts with HER2-negative, unresectable, locally advanced, or metastatic G/GEJ adenocarcinomas and a PD-L1 Combined Positive Score (CPS) &lt; 5, who had not received prior systemic therapy were included. They received benmelstobart (1200mg, iv, d1, q3w) combined with anlotinib (10mg, po, d1~14, q3w), oxaliplatin (130mg/m 2 , d1, iv, q3w) and S-1 (40mg, po, bid, d1~14, q3w) for 6 cycles as initial therapy. Maintenance therapy with benmelstobart (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) followed for non-progressive diseaseuntil PD or unacceptable toxicity occurred. Tumor responses were evaluated by RECIST 1.1 criteria. The target sample size was 37, with ORR as the primary endpoint, and safety, DCR, DoR, PFS, and 1-year OS rate as secondary endpoints. Results: From Jun 2023 to Sep 2024, 28 pts were enrolled and 27 were available for efficacy and safety evaluation. The patients’ characteristics were as follows; median age (range): 59 (38-77) years, Male/Female: 19 (70%)/8 (30%), ECOG PS 0/1: 2 (7%)/25 (93%), Surgical history yes/no: 6 (22%)/21 (78%), CPS: ＜1/ ≥1: 4 (15%)/23 (85%), respectively. In the response assessment, 19 PR (70.4%), 6 SD (22.2%), and 2 NE (7.4%) were observed, yielding an ORR of 70.4% (95% CI: 49.8-86.2) and DCR of 92.6% (95% CI: 75.7-99.1). As of September 17, 2024, 6 of 27 patients discontinued (3 due to PD, 3 voluntary), leaving 21 ongoing. The longest DoT was 15.08 months, and the median PFS was not reached. Common TEAEs ≥10% included thrombocytopenia (37%), anemia (33%), leukopenia (22%), HFS (19%), fatigue (15%), liver function abnormalities (15%), and appetite loss (11%). Grade ≥3 TEAEs were thrombocytopenia (4%) and anemia (4%). Conclusions: Preliminary findings indicate that the combination of benmelstobart and anlotinib with the SOX regimen as a first-line treatment for advanced G/GEJ adenocarcinoma with low PD-L1 expression demonstrates promising therapeutic efficacy and tolerable adverse events. Further validation of these results in a larger, consecutive patient population is warranted. Clinical trial information: ChiCTR2400085396.

Abstract WMP16: Impaired Neurocognitive Domains Related To Quantitative Brain Functional Abnormalities In Patients With Unilateral Asymptomatic Middle Cerebral Artery Stenotic-occlusive Disease

Abstract WMP16: Impaired Neurocognitive Domains Related To Quantitative Brain Functional Abnormalities In Patients With Unilateral Asymptomatic Middle Cerebral Artery Stenotic-occlusive Disease

Abstract 27: The Brain-behaviour Mechanisms of Impaired Linguistic and Cognitive Function Impairments in Stroke Patients with Aphasia

Introduction: The combination of verbal and non-verbal cognitive dysfunction in post-stroke aphasia (PSA) patients may ultimately affect social interactions. However, the underlying neural mechanisms of both verbal and non-verbal cognitive impairment remain unclear. This study aimed to investigate the activity and functional abnormalities of local and remote brain regions and their relationship with cognitive behaviour, to provide more effective guidance in future clinical therapy. Methods: We recruited 46 PSA patients and 40 normal controls(NCs) matched for general characteristics in this study and evaluated their verbal and non-verbal cognitive functions. Functional magnetic resonance imaging(fMRI) was used to examine the fractional amplitude of low-frequency fluctuations(fALFF), regional homogeneity(ReHo), and functional connectivity(FC) in PSA patients. Independent two-sample t-tests were used to identify differences in these measures between two groups. Moreover, partial correlation analyses were performed to determine the correlation between FC from the affected brain regions and language and cognitive performance in PSA patients. Results: This study revealed that PSA patients presented significantly lower fALFF and ReHo values in right cerebellum superior (CRBL.Superior.R), left thalamus(THA.L), and left middle frontal gyrus(MFG.L). Moreover, the FC in the MFG.L-left inferior frontal gyrus, orbital part was significantly lower among PSA patients and was positively correlated with language and cognitive performance(p&lt; 0.05). The CRBL. Superior. R-left caudate nucleus and right lenticular nucleus FC were also decreased and were associated with cognitive function(p&lt; 0.05). In addition, PSA patients were further divided into fluent and nonfluent groups. The results revealed that nonfluent patients performed worse in verbal and non-verbal cognitive performance(p&lt; 0.05) and had weaker performance in the THA.L and left supplementary motor area FC(p&lt; 0.001). Conclusions: This study provides new evidence that abnormal neural activity and functional connectivity within specific brain regions may play crucial roles in language and cognitive processing. The underlying mechanisms of impaired linguistic function accompanied by decline in cognition may be a partial overlap between language and cognitive-related brain networks. In future, combining cognitive and linguistic functions and designing a comprehensive treatment plan will be the focus of rehabilitation.