Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

Objective To observe the clinical efficacy and safety of esketamine injection combined with sufentanil injection for patient-controlled intravenous analgesia(PCIA)after fracture surgery in children.Methods Children scheduled for elective limb fracture incision and internal fixation were randomly divided into control group and treatment group.The control group was given 2 μg·kg-1 sufentanil for PCIA;the treatment group was given 1.0 mg·kg-1 esketamine combined with 1.5 μg·kg-1 sufentanil for PCIA.Background dose of 2 groups:2 mL·h-1,single dose of 2 mL each time,locking time of 15 min,total volume of 100 mL.The facial expression,leg movement,mobility,crying,consolability scale(FLACC)scores and Ramsay sedation scores,analgesic drug consumption and PCIA compression times within 48 h after operation,and adverse drug reactions were compared between the two groups at different time points after operation.Results Forty subjects enrolled in the treatment group,1 dropped out,and 39 were finally included in the statistical analysis;40 subjects enrolled in the control group,2 dropped out,and 38 were finally included in the statistical analysis.After treatment,the FLACC scores of treatment group at 2,4,6,12,24 and 48 h after operation were(4.75±0.93),(2.50±0.97),(1.75±0.93),(2.06±1.18),(1.13±0.62)and(0.50±0.63)points,which in control group were(6.13±1.13),(3.80±1.21),(2.87±0.64),(3.47±1.13),(1.87±0.92)and(1.27±0.80)points,and there were significant differences in the two groups(all P＜0.05).The Ramsay sedation scores of treatment and control groups at 2 hours after operation were(2.25±0.45)and(1.47±0.52)points;the number of effective PCIA compressions within 24 hours was 4.25±3.94 and 8.13±5.71;the amount of analgesic drugs used within 24 hours after surgery was(52.38±9.11)and(61.47±12.82)mL;the amount of analgesic drugs used within 48 hours after surgery was(88.81±14.31)and(94.60±5.93)mL,respectively;and the differences were statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly dizziness,nausea and vomiting.The total incidences of adverse drug reactions in treatment and control groups were 53.85％and 84.21％with significant difference(P＜0.05).Conclusion Esketamine injection combined with sufentanil injection can reduce postoperative pain intensity,improve analgesic sedation effect and reduce the incidence of adverse reactions of analgesic pump after fracture surgery in children.

ObjectiveTo evaluate the dynamic disinfection effect of the upper-room 222 nm ultraviolet radiation on the air in different areas of the emergency department, and to provide references for a new solution of air disinfection that man-machine coexisted in the medical and healthcare institutions. MethodsThe upper-room 222 nm ultraviolet radiation air sterilizers were installed at a height of 2.3‒2.6 m from the ground in the observation room, computed tomography (CT) scanning room, rescue room and consulting room of the emergency department in Beijing Tiantan Hospital, Capital Medical University . The test area was divided into a 222 nm ultraviolet group and a control group according to whether the 222 nm ultraviolet germicidal air disinfection was conducted or not. The experimental group started air disinfection at8:00 a.m., and the air sampling was conducted from 9:00 a.m. to 16:00 p.m., with a 10 min sampling interval of every 1 hour. While the control group only collected air sample with the same air sampling method used in the experimental group, without air disinfection. The air microbial sampler with six-level sieve impingement was used for the air sampling, and the differences in the total number of airborne bacterial colonies were compared between the two groups. ResultsA total of 128 air samples were collected in the trial, of which 64 were from the experimental group and 64 from the control group. The total number of airborne bacterial colonies in the experimental group was lower than that in the control group (all P<0.001), and was maintained at a lower level throughout the entire period. The killing rate of 222 nm ultraviolet radiation to airborne microorganisms was approximately 55.76% to 76.33% in different sampling areas. The qualified rates of the total number of dynamic airborne bacterial colonies in the observation room, rescue room and consulting room were improved from 12.50%, 37.50% and 25.00% to 81.25%, 100.00% and 100.00%, respectively (all P<0.001). Over 62.50% of the time, the air quality in the consulting room and CT room in the 222 nm ultraviolet group met the environment standards for airborne bacterial colony criteria of class Ⅰ or class Ⅱ. ConclusionThe upper-room222 nm ultraviolet radiation germicidal disinfection can effectively reduce the total number of airborne bacterial colonies and improve the environment for emergency department, and the continuous using of it is helpful for keeping the air safe and clean.

Objective To assess the effects of temperature and rainfall on the incidence of cardiovascular and cerebrovascular diseases (CVD) in Guiyang. Methods Using daily CVD incidence data and temperature and rainfall data in Guiyang City from September 2021 to August 2022, a distributed lag non-linear model was used to explore the nonlinear relationship between meteorological and environmental factors and CVD incidence. Results The risk of CVD was higher under cold (average, minimum, and maximum temperatures <2.1 ℃, 1.6 ℃, and 4.2 ℃, respectively) and hot (maximum temperature>32.5 ℃) effects, and the cumulative lag effect reached its maximum at 10 and 17 days, respectively. The risk of CVD increased sharply when there was a small diurnal temperature (<6.9 ℃), sudden drop in temperature (over 6.1 ℃), and heating (over 2.4 ℃ in 24 hours). The incidence risk of CVD was high when the daily rainfall exceeded 21.5 mm and the continuous rainy days exceed 5.7 days. The risk in rainstorm was 0.81 higher than that in heavy rain. Continuous absence of rain helped to prevent CVD patients from developing symptoms. Conclusion Meteorological environments such as hot and cold weather, dramatic change in temperature, significant rainfall and continuous rainfall have an impact on the incidence of CVD. It is necessary to consider the changes of the meteorological environment during the prevention and control of CVD.

Objective:Migraine and tremor share some genetic mutation sites,and clinical studies have also confirmed their correlation.This study aims to explore the clinical and electrophysiological characteristics of migraine patients with concomitant tremor,and to analyze the relevant influential factors of tremor occurrence. Methods:We retrospectively analyzed the clinical data of 217 migraine patients who visited the Third Affiliated Hospital of Qiqihar Medical University from June 2022 to October 2023.The Clinical Rating Scale for Tremor(CRST),Numerical Rating Scale(NRS),Generalized Anxiety Disorder-7(GAD-7),and Patient Health Questionnaire-9(PHQ-9)were respectively used to assess the tremor symptoms,degree of headache,anxiety,and depression of patients.All patients underwent routine head MR scanning and electromyography examination,and were divided into a migraine with tremor group and a migraine without tremor group based on the electromyogram examination. Results:The migraine with tremor group and the migraine without tremor group were included 52 patients(23.96%)and 165 patients(76.04%),respectively.Compared with the migraine without tremor group,the migraine with tremor group had a longer course and duration of headache,higher frequency of headache attacks,higher NRS score,GAD-7 score,and PHQ-9 score,and fewer weekly physical exercises.The differences were statistically significant(all P<0.05).There were no statistically significant differences in the presence or absence of prodromal headache and white matter hyperintensities(WMHs)between the 2 groups(both P>0.05).The evaluation results of the CRST showed that out of 217 migraine patients,39 patients(17.97%)were accompanied by tremors.The electromyographic results showed that all 52 migraine patients with tremors had upper limb tremors,including 28 migraine patients with postural tremors and 24 migraine patients with static tremors.Compared with the migraine patients with static tremors,the migraine patients with postural tremors had lower average frequency,peak frequency,and headache onset frequency(all P<0.05).Multiple linear regression analysis showed that frequency of physical exercise,duration of illness,frequency of headache attacks,NRS score,GAD-7 score,and PHQ-9 score were risk factors for migraine patients with concomitant tremors(all P<0.05). Conclusion:Patients with migraine mainly experience upper limb postural tremors.Reduced physical exercise,long course of disease,long duration of headache,frequent headache attacks,severe headache,anxiety,and depression are risk factors for migraine patients with concomitant tremors.

Objective:To explore the effect of family empowerment model on the improvement of swallowing care ability and care preparedness of primary caregivers of first-episode stroke dysphagia patients, further to explore its impact on patients′s wallowing function and life quality.Methods:This study was a randomized controlled study. From January 2021 to December 2022, 80 main caregivers of patients with dysphagia caused by manual stroke admitted to the Department of Acupuncture and Moxibustion, Shenzhen Hospital of Traditional Chinese Medicine were selected as the research objects, and 40 cases in the control group and 40 cases in the observation group were selected by random number table method. The control group were treated with conventional nursing care of first-episode stroke dysphagia patients in the acupuncture and moxibustion Department. On the basis of the conventional care in the control group, the observation group were treated with family empowerment model intervention for 14 days and was followed up for 28 days. Primary caregivers′ swallowing care ability, Caregiver Preparedness Scale (CPS), patients′ swallowing function rate, Swallowing Related Quality of Life (SWALQOL) were used to evaluate the effects before intervention and at the end of intervention.Results:There were 18 males and 19 females primary caregivers in the control group, aged (55.61 ± 7.43) years old. There were 18 males and 21 females primary caregivers in the observation group, aged (58.23 ± 8.22) years old. The swallowing care ability score showed a statistically significant difference between the observation group (143.47 ± 3.96) and the control group (107.74 ± 1.43) ( t=-26.76, P<0.05). After intervention, the caregiver preparedness scale was (26.11 ± 3.81) in the observation group, and (18.35 ± 4.54) in the control group, and the difference was statistically significant ( t=-4.11, P<0.05).The patients′ swallowing function rate and SWALQOL score were respectively 97.44% (38/39) and (91.41 ± 8.08) points in the observation group, and 72.97% (27/37) and (80.33 ± 4.21) points in the control group, and the difference was both statistically significant ( χ2=10.76, t=-2.54, both P<0.05). Conclusions:The implementation of family empowerment model could enhance the swallowing care ability and care preparedness of primary caregivers of the first-episode stroke dysphagia patients, which could further improve patients′ swallowing function and life quality.