BackgroundMonitoring the blood concentrations of antipsychotic drugs and their metabolites can guide the adjustment of clinical treatment plans， improving therapeutic efficacy while reducing adverse effects. However， there is currently a lack of a method that can accurately and efficiently quantitatively detect multiple antipsychotic drugs and their metabolites. ObjectiveTo establish a ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. MethodsUsing UPLC-MS/MS technology， protein precipitation method was employed for sample pretreatment. An Agela Technologies Durashell C₈ chromatographic column （50 mm×3.0 mm， 5 μm） was selected for chromatographic separation with gradient elution. The flow rate was 0.4 mL/min， and the total analysis time was 5 minutes. The column temperature was 40℃. The mass spectrometry detection was carried out in the multiple reaction monitoring （MRM） mode， and the isotope internal standard method was used for quantification. ResultsThe relative standard deviation （RSD） of the internal standard normalization matrix effect factor for 12 antipsychotic drugs and their main metabolites at low and high quality concentrations was all less than 15%. The extraction recovery rate was 85% to 115%. They showed good linear relationships within their respective standard curve ranges （r>0.995）. At low， medium， and high quality concentrations， the accuracy was 85.24% to 114.71%， and the RSD of intra-batch and inter-batch precision was all ≤14.15%， with good stability. ConclusionAll the analytical performance indicators of this method meet the verification requirements， providing an analytical means for the quantitative detection of antipsychotic drugs and their main metabolites in human serum. ［Funded by The Third Batch of Science and Technology Projects in Chaozhou City in 2023 （number， 202303GY02）］

The liver is a vital metabolic organ sustaining human life activities， and its dysfunction is closely associated with various liver diseases. In recent years， an increasing number of studies have shown that semaphorins （SEMA） play a significant role in pathological processes such as immune inflammatory response， tumor progression， and fibrosis in liver diseases by interacting with their receptors plexins and neuropilins. This article reviews the expression， functions， and molecular mechanisms of different SEMA in viral hepatitis， hepatocellular carcinoma， liver fibrosis， nonalcoholic fatty liver disease， and hepatic ischemia-reperfusion injury， and it also explores the potential application value of SEMA in the diagnosis and treatment of liver diseases， in order to provide new ideas for precise diagnosis and targeted treatment of liver diseases.

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

Objective: To construct an evaluation index system of cervical cancer prevention and control literacy, so as to provide an assessment tool for cervical cancer prevention and control literacy. Methods: The preliminary framework for cervical cancer prevention and control literacy was designed based on literature review. Twenty-one experts with both theoretical and practical experience in cervical cancer prevention and control were invited to participate in two rounds of Delphi consultation. The weights of indicators were determined by the percentage weighting method and product method, and the response rate, authority level, opinion concentration degree, and coordination degree of experts were evaluated. Results: Twenty-one experts participated in the consultation, including 3 males and 18 females. There were 11 experts with a doctor's degree, 7 with a master's degree and 3 with a bachelor's degree. All of them had senior professional titles and had more than 10 years of working experience. The recovery rates of the two rounds of consultations were 100.00% and 95.24%, the authority coefficients were 0.963 and 0.948, and Kendall's coefficients of concordance were 0.175 and 0.148 (both P<0.05), respectively. The final cervical cancer prevention and control literacy evaluation index system included 3 primary indicators (basic knowledge and concepts: 0.334; healthy lifestyle and behaviors: 0.338; basic skills: 0.328), 12 secondary indicators, with "capability to accurately acquire, comprehend, evaluate and apply health information" having the highest weight (0.166), and 51 tertiary indicators, with "HPV vaccination" (0.086), "consulting on relevant issues" (0.082), and "expressing personal perspectives" (0.080) having relatively higher weights. Conclusion The evaluation index system of cervical cancer prevention and control literacy serves as a valid assessment tool for women of appropriate age, providing the reference for developing targeted health education to enhance cervical cancer prevention and control literacy.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Objective To study the gradient damage pattern of cochlear explants hair cells induced by genta-micin in vitro culture.Methods After diluting gentamicin to concentrations of 0 mM,0.1 mM,0.5 mM,1.0 mM,1.5 mM,and 3.0 mM in culture medium,the cochlear basement membrane was cultured in vitro(10 cochlea in each group).After 24 hours,FITC-conjugated phalloidin staining was used to specifically display the static cilia of cochlear hair cells.The morphology and quantity of hair cells in the cochlear basement membrane were observed under a fluorescence microscope.After 12 hours,24 hours,and 36 hours(10 cochlea in each group),Rhodamine was used to label the accumulation of 0.5 mM gentamicin content at different positions in cochlear ex-plants.Results After culturing the cochlear basement membrane with different concentrations of gentamicin for 24 hours,0.1 mM gentamicin had little damage to cochlear hair cells,with no significant difference.Gentamicin at concentrations of 0.5 mM,1.0 mM,1.5 mM,and 3.0 mM caused damage to cochlear hair cells,with the most se-vere damage occurring in the basal gyrus hair cells and gradually progressing towards the apical gyrus hair cells.The accumulation of gentamicin first occurred in the outer hair cells of the basal gyrus,and gradually spread towards the inner hair cells of the basal gyrus and the inner and outer hair cells of the parietal gyrus with increasing culture time.The degree of damage gradually worsened with the increase of gentamicin dosage,and the damage was significant and concentration time dependent.Conclusion Through the in vitro culture method of rat cochlear explants,it was found that gentamicin could cause gradient damage to hair cells in cochlear explants.

BACKGROUND:Activation of nuclear factor-κB/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling leads to endothelial dysfunction,oxidative stress,and plays a key role in the initiation of lipid metabolism disorders and arteriosclerosis.However,currenty,the effect of walnut oil and peanut oil on skeletal muscle inflammatory factors in arteriosclerotic rats remains unclear.OBJECTIVE:To discuss the effect and mechanism of walnut oil and peanut oil on atherosclerosis.METHODS:Forty 8-week-old SD male rats were randomly divided into normal control group(n=10)and high fat group(n=30)after 1 week of adaptive feeding.The atherosclerosis model was established by high-fat diet combined with vitamin D3 injection.The rats with successful modeling were randomly divided into model group(n=10),peanut oil group(n=8)and walnut oil group(n=8).The latter two groups were gavaged with peanut oil or walnut oil for 4 weeks(5 days/week,1.2 g/kg per day).After the intervention,ELISA was used to detect the related indexes of blood lipids in rats.The morphological changes of aorta were observed by hematoxylin-eosin staining.The RT-qPCR and western blot assay were used to detect nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,interleukin-18 mRNA and nuclear factor-κB,NLRP3,interleukin-1β protein expression levels in skeletal muscle.The protein expressions of nuclear factor-κB and NLRP3 were detected by immunofluorescence immunohistochemical staining.RESULTS AND CONCLUSION:(1)Compared with the normal control group,the aortic wall of rats in the model group was thickened,the damage and lipid precipitation were more serious,the blood lipid levels and arteriosclerosis index were significantly increased(P＜0.01).The mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18,and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly increased(P＜0.01).(2)Compared with model group,the vulnerable area of aortic tissue in peanut oil group and walnut oil group was significantly reduced,the levels of total cholesterol,triglyceride,low density lipoprotein cholesterol in serum,and atherosclerosis index were decreased(P＜0.01),and the mRNA expressions of nuclear factor-κB,NLRP3,Caspase-1,interleukin-1β,and interleukin-18 and the protein expressions of nuclear factor-κB,NLRP3,and interleukin-1β in skeletal muscle were significantly decreased(P＜0.01 or P＜0.05).(3)Compared with peanut oil group,the serum total cholesterol,triglyceride,and low density lipoprotein cholesterol levels in walnut oil group were significantly decreased(P＜0.01 or P＜0.05),and the mRNA levels of nuclear factor-κB,NLRP3,Caspase-1,interleukin-18,and the protein levels of nuclear factor-κB,NLRP3,interleukin-1β decreased significantly in skeletal muscle(P＜0.01 or P＜0.05).It is concluded that both peanut oil and walnut oil have ameliorative effect on atherosclerotic damage,which may be related to nuclear factor-κB/NLRP3 signaling pathway,and walnut oil has better ameliorative effect than peanut oil.

When patients with malignant tumors are in the terminal stage of life, palliative care centered on the patient and their family plays a crucial role in improving the quality of life for advanced cancer patients and their families. As the core practitioners of palliative care, oncology nurses' cognition and practice of palliative care are closely related to the quality of palliative care for cancer patients. This paper analyzes the current state and influencing factors of the cognition and practice of palliative care from the perspective of oncology nurses and proposes improvement strategies, aiming to provide a reference for nursing managers to formulate targeted improvement programs and improve relevant systems.