The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

This study aims to elucidate the role and mechanism of clematichinenoside AR(CAR) in protecting bone marrow mesenchymal stem cells(BMSCs) from hypoxia-induced apoptosis. BMSCs were isolated by the bone fragment method and identified by flow cytometry. Cells were cultured under normal conditions(37℃, 5% CO_2) and hypoxic conditions(37℃, 90% N_2, 5% CO_2) and treated with CAR. The BMSCs were classified into eight groups: control(normal conditions), CAR(normal conditions + CAR), hypoxia 24 h, hypoxia 24 h + CAR, hypoxia 48 h, hypoxia 48 h + CAR, hypoxia 72 h, and hypoxia 72 h + CAR. The cell counting kit-8(CCK-8) assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) were employed to measure cell proliferation and apoptosis, respectively. The number of mitochondria and mitochondrial membrane potential were measured by MitoTracker®Red CM-H2XRo staining and JC-1 staining, respectively. The level of reactive oxygen species(ROS) was measured with the DCFH-DA fluorescence probe. The protein levels of B-cell lymphoma-2 associated X protein(BAX), caspase-3, and optic atrophy 1(OPA1) were determined by Western blot. The results demonstrated that CAR significantly increased cell proliferation. Compared with the control group, the hypoxia groups showed increased apoptosis rates, reduced mitochondria, elevated ROS levels, decreased mitochondrial membrane potential, upregulated expression of BAX and caspase-3, and downregulated expression of OPA1. In comparison to the corresponding hypoxia groups, CAR intervention significantly decreased the apoptosis rate, increased mitochondria, reduced ROS levels, elevated mitochondrial membrane potential, downregulated the expression of BAX and caspase-3, and upregulated the expression of OPA1. Therefore, it can be concluded that CAR may exert an anti-apoptotic effect on BMSCs under hypoxic conditions by regulating OPA1 to maintain mitochondrial homeostasis.
Mesenchymal Stem Cells/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Hypoxia/drug effects* ; Homeostasis/drug effects* ; Reactive Oxygen Species/metabolism* ; Rats, Sprague-Dawley ; Membrane Potential, Mitochondrial/drug effects* ; Saponins/pharmacology* ; Caspase 3/genetics* ; Male ; bcl-2-Associated X Protein/genetics* ; Bone Marrow Cells/metabolism* ; Cell Proliferation/drug effects* ; Protective Agents/pharmacology* ; Cells, Cultured

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the effects of melatonin(MT)on spinal cord ischemia reperfusion injury(SCIRI)and its possible mechanisms in rats.Methods:Forty-two 6-week-old male Sprague Dawley rats were selected for the study and randomly divided into three groups:① Sham group(Sham group,n=14);② model group(model/SCIRI group,n=14);and ③ treatment group(MT group,n=14).Neurological function analysis was used to assess the motor conditions of rats in each group.Nissl staining and hematoxylin eosin(HE)staining were used to observe the number and morphology of neurons in each group,and TUNEL staining was used to evaluate the occurrence of apoptosis of neurons in each group.The expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),gasdermin D(GSDMD),the N-terminal fragment of gasdermin D(GSDMD-N),and cysteine proteinase 1(caspase-1)were evaluated using immunofluorescence,immunohistochemistry staining,and Western blot analysis.Results:Compared with the sham operation group,the neurological function score of the model group was significantly decreased,while the neurological function score of the treatment group was higher than that of the model group(P＜0.05).The model group had fewer Nissl corpuscles compared with that in the sham operation group and abnormal neuronal morphology(P＜0.05).Compared with the model group,the treatment group had a rise in the number of Nissl corpuscles and restored neuronal morphology(P＜0.05).Compared with the Sham group,the number of apoptotic neurons increased in the model group,and the protein expression levels of NLRP3,ASC,GSDMD,and caspase-1 increased(P＜0.05).Compared with the model group,The number of apoptotic neurons and the protein expressions of NLRP3,ASC,GSDMD and caspase-1 in the treatment group were significantly decreased(P＜0.05).Conclusions:MT may alleviate spinal cord ischemia-reperfusion injury by inhibiting pyroptosis in neurons.

Objective:To investigate the effects of melatonin(MT)on spinal cord ischemia reperfusion injury(SCIRI)and its possible mechanisms in rats.Methods:Forty-two 6-week-old male Sprague Dawley rats were selected for the study and randomly divided into three groups:① Sham group(Sham group,n=14);② model group(model/SCIRI group,n=14);and ③ treatment group(MT group,n=14).Neurological function analysis was used to assess the motor conditions of rats in each group.Nissl staining and hematoxylin eosin(HE)staining were used to observe the number and morphology of neurons in each group,and TUNEL staining was used to evaluate the occurrence of apoptosis of neurons in each group.The expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),gasdermin D(GSDMD),the N-terminal fragment of gasdermin D(GSDMD-N),and cysteine proteinase 1(caspase-1)were evaluated using immunofluorescence,immunohistochemistry staining,and Western blot analysis.Results:Compared with the sham operation group,the neurological function score of the model group was significantly decreased,while the neurological function score of the treatment group was higher than that of the model group(P＜0.05).The model group had fewer Nissl corpuscles compared with that in the sham operation group and abnormal neuronal morphology(P＜0.05).Compared with the model group,the treatment group had a rise in the number of Nissl corpuscles and restored neuronal morphology(P＜0.05).Compared with the Sham group,the number of apoptotic neurons increased in the model group,and the protein expression levels of NLRP3,ASC,GSDMD,and caspase-1 increased(P＜0.05).Compared with the model group,The number of apoptotic neurons and the protein expressions of NLRP3,ASC,GSDMD and caspase-1 in the treatment group were significantly decreased(P＜0.05).Conclusions:MT may alleviate spinal cord ischemia-reperfusion injury by inhibiting pyroptosis in neurons.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Lung cancer is the leading cause of cancer-related deaths worldwide, especially non-small cell lung cancer (NSCLC). With the popularization of low-dose CT and the improvement of people’s awareness of physical examinations, the number of detected pulmonary nodules is gradually increasing, and there is a greater demand for standardized diagnostic and treatment guidelines. On April 23, 2024, the National Comprehensive Cancer Network updated its clinical practice guidelines for NSCLC to the version 5. Compared with the version 5 in 2023, the version 5 in 2024 updates focus on diagnostic evaluation, perioperative systemic therapy, treatment of advanced NSCLC, and molecular marker testing, which will be interpreted in this article with the aim of providing the latest guidance and reference for the diagnosis and treatment of lung cancer in China.