OBJECTIVE: To observe the effects of Tiaoshu Anshen (regulating the hinge and calming the mind) acupuncture on sleep quality and serum levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) in patients with chronic insomnia. METHODS: A total of 58 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 29 cases in each group. Tiaoshu Anshen acupuncture was applied at Baihui (GV20) and bilateral Shenmen (HT7), Sanyinjiao (SP6), Benshen (GB13) in the acupuncture group, once a day, 1-day interval was taken after 6 consecutive days of treatment. Estazolam tablet was given orally before bed in the medication group, 1 mg each time. The 4-week treatment was required in both groups. Before and after treatment, the sleep quality was assessed by Pittsburgh sleep quality index (PSQI) and polysomnography (PSG), the serum levels of 5-HT and DA were detected by ELISA. RESULTS: After treatment, the item scores and total scores of PSQI were decreased compared with those before treatment in the two groups (P<0.05); in the acupuncture group, the scores of sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorders and total score of PSQI were lower than those in the medication group (P<0.05). After treatment, the total sleep time (TST) was prolonged (P<0.05), the sleep latency (SL) and wake after sleep onset (WASO) were shortened (P<0.05), the sleep efficiency (SE%), percentage of non-rapid eye movement stage 3 (N3%), percentage of rapid eye movement stage (REM%) and serum levels of 5-HT were increased (P<0.05) compared with those before treatment; the percentage of non-rapid eye movement stage 1 (N1%), percentage of non-rapid eye movement stage 2 (N2%) and serum levels of DA were decreased (P<0.05) compared with those before treatment in the two groups. After treatment, in the acupuncture group, TST was longer, while SL and WASO were shorter than those in the medication group (P<0.05), SE%, N3%, REM% and serum level of 5-HT were higher, while N1%, N2% and serum level of DA were lower than those in the medication group (P<0.05). CONCLUSION Tiaoshu Anshen acupuncture may improve the sleep quality by regulating the serum neurotransmitter levels i.e. 5-HT and DA in patients with chronic insomnia.
Humans ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Male ; Acupuncture Therapy ; Female ; Middle Aged ; Adult ; Serotonin/blood* ; Sleep Quality ; Acupuncture Points ; Dopamine/blood* ; Aged ; Neurotransmitter Agents/blood* ; Young Adult

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

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

OBJECTIVE: To elucidate the predictive value of norepinephrine equivalence (NEE) score on the 28-day death risk in patients with sepsis and provide evidence for its application in the diagnosis and treatment of sepsis and septic shock. METHODS: A retrospective cohort study was conducted based on the data of patients with sepsis from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). The patients who received vasoactive agents within 6 hours after the diagnosis of sepsis or septic shock were enrolled, and they were divided into survival and non-survival groups based on their 28-day outcomes. The baseline characteristics, vital signs, and treatment data were collected. Multivariate Cox regression analysis was performed to identify factors influencing the 28-day death risk. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of various parameters on the 28-day death risk of septic patients. Kaplan-Meier survival curve was used to evaluate cumulative survival rate in patients classified by different quantitative parameters based on the cut-off values obtained from ROC curve analysis. RESULTS: A total of 7 744 patients who met the Sepsis-3 diagnostic criteria and received vasopressor treatment within 6 hours post-diagnosis were enrolled, of which 5 997 cases survived and 1 747 died, with the 28-day mortality of 22.6%. Significant differences were observed between the two groups regarding age, gender, height, body weight, race, type of intensive care unit (ICU), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, Charlson comorbidity index (CCI) score, underlying comorbidities, and vital signs. Compared with the survival group, the non-survival group had poorer blood routine, liver and kidney function, coagulation function, blood gas analysis and other indicators. Multivariate Cox regression analysis revealed that age > 65 years old [hazard ratio (HR) = 0.892, 95% confidence interval (95%CI) was 0.801-0.994, P = 0.039] and male (HR = 0.735, 95%CI was 0.669-0.808, P < 0.001) were protective factors for 28-day death in patients with sepsis, and NEE score (HR = 1.040, 95%CI was 1.021-1.060, P < 0.001), shock index (HR = 1.840, 95%CI was 1.675-2.022, P < 0.001), APACHE II score (HR = 1.076, 95%CI was 1.069-1.083, P < 0.001), SOFA score (HR = 1.035, 95%CI was 1.015-1.056, P < 0.001), and CCI score (HR = 1.135, 95%CI was 1.115-1.155, P < 0.001) were independent risk factors for 28-day death in septic patients. ROC curve analysis showed that the area under the ROC curve (AUC) of NEE score for predicting the 28-day death risk of septic patients was 0.743 (95%CI was 0.730-0.756), which was comparable to the predictive value of APACHE II score (AUC = 0.742, 95%CI was 0.729-0.755) and ratio of mean arterial pressure (MAP)/NEE score (MAP/NEE; AUC = 0.738, 95%CI was 0.725-0.751, both P > 0.05), and better than SOFA score (AUC = 0.609, 95%CI was 0.594-0.624), CCI score (AUC = 0.658, 95%CI was 0.644-0.673), shock index (AUC = 0.613, 95%CI was 0.597-0.629) and ratio of diastolic blood pressure (DBP)/NEE score (DBP/NEE; AUC = 0.735, 95%CI was 0.721-0.748, all P < 0.05). According to the cut-off values of APACHE II and NEE scores obtained from ROC curve analysis, the patients were stratified for Kaplan-Meier survival curve analysis, and the results showed that the 28-day cumulative survival rate in the septic patients with an APACHE II score ≤ 22.5 was significantly higher than that in those with an APACHE II > 22.5 (Log-Rank test: χ² = 848.600, P < 0.001), and the 28-day cumulative survival rate in the septic patients with an NEE score ≤0.120 was significantly higher than that in those with an NEE score > 0.120 (Log-Rank test: χ² = 832.449, P < 0.001). CONCLUSIONS NEE score is an independent risk factor for 28-day death in septic patients who received vasoactive treatment within 6 hours of diagnosis and possesses significant predictive value. It can be used for severity stratification in sepsis management.
Humans ; Retrospective Studies ; Sepsis/diagnosis* ; Male ; Female ; Norepinephrine/therapeutic use* ; Middle Aged ; Aged ; Prognosis ; Predictive Value of Tests ; Shock, Septic/mortality* ; Adult ; ROC Curve ; Risk Factors ; Survival Rate ; Aged, 80 and over

Traumatic brain injury (TBI), as a significant central nervous system damage disease with high frequency in the world, leads to a huge number of patients with impaired health and lower quality of life every year. Lung injury is a common and dangerous consequence, which dramatically raises the mortality of patients. Discovering the pathophysiology of lung injury after TBI and discovering viable therapeutic targets has become an important need for clinical diagnosis and therapy. Neurotransmitters, as the fundamental chemical agents of the nervous system for signal transmission, not only govern neuronal activity and apoptosis in TBI but also significantly influence the pathophysiological mechanisms of lung injury subsequent to TBI. The imbalance is intricately linked to the onset and progression of lung damage. This paper systematically reviews the clinical characteristics and predominant pathogenesis of lung injury following TBI, emphasizing the role of key neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh), in lung injury post-TBI. It examines their influence on inflammatory response, vascular permeability, and pulmonary circulation function. Additionally, the paper evaluates the research advancements and potential applications of targeted therapeutic strategies for various neurotransmitter systems, such as receptor antagonists, transporter inhibitors, and neurotransmitter analogues. This research aims to offer a theoretical framework for clarifying the neural regulatory mechanisms of lung injury following TBI and to establish a basis for the development of novel therapeutic strategies and enhancement of the prognosis of the patients.
Humans ; Brain Injuries, Traumatic/metabolism* ; Neurotransmitter Agents/metabolism* ; Lung Injury/metabolism* ; gamma-Aminobutyric Acid/metabolism* ; Glutamic Acid/metabolism* ; Norepinephrine/metabolism* ; Dopamine/metabolism* ; Acetylcholine/metabolism*

Blood biochemical indicators are an important basis for the diagnosis and treatment by doctors. The performance of related instruments, the qualification of operators, the storage method and time of blood samples and other factors will affect the accuracy of test results. However, it is difficult to meet the clinical needs of rapid detection and early screening of diseases with currently available methods. Point-of-care testing (POCT) is a new diagnostic technology with the characteristics of instant, portability, accuracy and efficiency. Microfluidic chips can provide an ideal experimental reaction platform for POCT. This paper summarizes the existing detection methods for common biochemical indicators such as blood glucose, lactic acid, uric acid, dopamine and cholesterol, and focuses on the application status of POCT based on microfluidic technology in blood biochemistry. It also summarizes the advantages and challenges of existing methods and prospects for development. The purpose of this paper is to provide relevant basis for breaking through the technical barriers of microfluidic and POCT product development in China.
Humans ; Point-of-Care Testing ; Lactic Acid/blood* ; Microfluidic Analytical Techniques/methods* ; Blood Glucose/analysis* ; Point-of-Care Systems ; Blood Chemical Analysis/instrumentation* ; Uric Acid/blood* ; Cholesterol/blood* ; Dopamine/blood* ; Microfluidics/methods*

The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI ( n = 40), H2RA ( n = 31), or control group ( n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION www.chictr.org.cn (ChiCTR2000029552).
Humans ; Proton Pump Inhibitors/therapeutic use* ; Acute Coronary Syndrome/microbiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Male ; Middle Aged ; Histamine H2 Antagonists/therapeutic use* ; Aged ; Single-Blind Method

The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals