Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

α7 nicotinic acetylcholine receptor(α7nAChR)is widely expressed in the central nervous system and immune system,and plays a neuro-immunoregulatory role.On the one hand,α7nAChR is involved in the transmission of neurotransmitters,the conduction of excitatory signals and the maintenance of synaptic plasticity,which is of great significance for maintaining the normal and stable neurocognitive function.On the other hand,as an important part of the cholinergic anti-inflammatory pathway,α7nAChR is involved in the regulation of physiological and pathological processes such as inflammatory response,oxidative stress,apoptosis and autophagy in the central system,and plays an immunomodulatory and neuroprotective role,thus being potential target for improving perioperative neurocognitive function.This article reviews the biological characteristics of α7nAChR and its effect on perioperative neurocognitive function,in order to provide ideas and methods for clinical improvement of perioperative neurocognitive function in surgical patients.

Objective Analyze the temporal trend of ischemic stroke(IS)mortality among the residents of Tengzhou City of Shandong Province during the period of hypertension control from 2013 to 2021.Methods On January 1,2013,Tengzhou City,Shandong Province,began its hypertension control program.The IS mortality rate was calculated using the mortality data from January 1,2013 to December 31,2021,and analyzed for its time trend among residents with different characteristics.The registered population was derived from the Public Security Bureau of Tengzhou City,Shandong Province,and the age and sex standardized mortality rate was calculated using the data of China's 7th population census in 2020.The Chi-square test was used to compare the differences in mortality rate,and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate.Results The overall crude and standardized mortality rates of IS in Tengzhou showed a temporal trend from 2013 to 2021(Z values were 12.647,7.305,respectively;all P＜0.001),and decreased by 23.77％and 30.99％(Z values were-7.393,-9.975,respectively;all P＜0.001)respectively in 2021 compared with 2019.The crude mortality rate of IS in male increased by 13.27％in 2019 compared with 2017,while the crude and standardized mortality rate in female decreased by 16.39％and 19.49％in 2018 compared with 2017,respectively,with statistical significance(x2 values were 7.160,9.789,and 15.109,respectively;all P＜0.05).Except the crude mortality rates in 2013 and 2015,the crude mortality rates and standardized mortality rates for males in other years were all higher than those for females,with statistically significant differences(x2 values:25.816-124.040,all P＜0.001).The crude mortality rate for IS increased with age in all years(Z values:42.604-61.025,all P＜0.001).The proportion of IS deaths among those aged≥65 was 85.85％.The overall crude mortality rates of the age group of male 45-54 years old showed a temporal trend from 2013 to 2021(Z=3.035,P＜0.01),while females in the same age group did not show a temporal trend(P＞0.05).The IS mortality rate in urban areas decreased from 62.61 per 100 000 in 2013 to 54.00 per 100 000 in 2021(Z=-2.097,P＜0.05).The rural areas increased by 213.15％in 2019 compared with 2013 and decreased by 22.75％in 2021 compared with 2019(Z values were 19.074,-6.390,respectively;all P＜0.001).Conclusions The IS mortality rate in Tengzhou City showed a decreasing trend in urban areas from 2013 to 2021,and a decreasing trend in rural areas after 2019.Compared to females,there is a trend of younger mortality among males in the age range of 45-54.Males and rural IS patients should be given special attention.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

AIM To investigate the purification process for esculin,fraxin,esculetin and fraxetin in Fraxini Cortex by macroporous resin.METHODS Static adsorption experiment was applied to screening resin model,single factor test was adopted in the optimization of purification process,UPLC-QTOF-MS/MS was used for identifying main components,after which heatmap was drawn.RESULTS The optimal resin model was ADS-5.The optimal purification process was determined to be 1.1 BV for loading amount,0.75 g/mL for loading concentration,2 BV pure water for washing impurity,and 4 BV 25%ethanol for eluting effective constituents,coumarins demonstrated the total transfer rate,purity and yield of 84.42%,53.28%and 4.79%,respectively.Total 37 constituents were identified,among which coumarins and phenylethanol glycosides were mainly concentrated in 25%ethanol eluent,organic acids,iridoids and flavonoids were mainly concentrated in 95%ethanol eluent.CONCLUSION This stable,feasible and accurate method can characterize the distribution patterns of coumarins in Fraxini Cortex in different eluents of macroporous resin,which provides guidance for further related pharmaceutical research.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of coronary heart disease patients with angina pectoris after percutaneous coronary intervention(PCI). The basic elements of these RCTs, including sample size and estimation method, randomizing scheme, allocation concealment, blind method implementation, data integrity, statistical method, TCM syndrome, intervention measures, treatment course, follow-up time, and outcome indicators, were analyzed to provide reference for the design of future RCT and the clinical application of TCM in treating angina pectoris after PCI. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese Clinical Trial Registry were searched for the RCT about TCM treatment of coronary heart disease patients with angina pectoris after PCI according to pre-defined criteria, with the time interval from inception to January 31, 2024. A total of 188 RCTs were included, of which 184 were clinical research articles and 4 were clinical trial registration schemes. These RCTs involved a total of 15 521 patients, with an average sample size of 83 patients and a maximum sample size of 248 patients. Among them, 126 RCTs reported TCM syndromes, the top three of which were Qi deficiency and blood stasis(38.89%), phlegm combined with stasis(17.46%), and Qi stagnation and blood stasis(9.52%). The control group received guideline-directed medical therapy(GDMT) or GDMT combined with placebo, and the treatment group received GDMT combined with TCM. The treatment mainly lasted for 4-8 weeks, most of the RCTs did not set the follow-up period or the follow-up period was unknown. A total of 160 outcome indicators were used, with the total frequency of 1 348. According to functional attributes, the outcome indicators can be categorized into 6 groups: symptoms/signs(403, 29.90%), TCM syndromes/symptoms(182, 13.50%), physical and chemical examination(468, 34.72%), quality of life(89, 6.60%), long-term prognosis(5, 0.37%), and safety evaluation(201, 14.91%). The clinical trial design of TCM intervention in angina pectoris after PCI of coronary heart disease is becoming more and more rigorous, while it remains to be improved. It is expected that more clinical trial schemes with rigorous design and taking into account the TCM advantages can be adopted in the future to provide a basis for the TCM treatment of angina pectoris after PCI of coronary heart disease.
Humans ; Randomized Controlled Trials as Topic ; Angina Pectoris/drug therapy* ; Coronary Disease/drug therapy* ; Percutaneous Coronary Intervention ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Treatment Outcome ; Female

Based on the differences in the protective effects of fresh Panax ginseng and its processed products on myocardial ischemia in mice, this study identified the advantageous aspects of fresh P. ginseng. By using network pharmacology combined with cell model validation, the molecular mechanisms of fresh P. ginseng in regulating the FoxO signaling pathway were preliminarily revealed. A mouse model of myocardial ischemia was established via intraperitoneal injection of isoproterenol hydrochloride(ISO). The comparison of the protective effects of fresh P. ginseng and its processed products on myocardial ischemia indicated that fresh P. ginseng had a more pronounced effect in reducing lipid peroxidation and alleviating myocardial ischemia in mice. On this basis, network pharmacology research was conducted, showing that fresh P. ginseng contained 19 dominant active ingredients and 38 key targets, including albumin(ALB), serine/threonine protein kinase(AKT1), epidermal growth factor receptor(EGFR), extracellular signal-regulated kinases(ERK1/2), and mitogen-activated protein kinase(P38). Fresh P. ginseng could regulate various biological functions such as cell proliferation, apoptosis, inflammation, and oxidative stress through signaling pathways including Ras, FoxO, IL-17, and Rap1, thereby protecting cardiomyocytes. Among them, the FoxO signaling pathway was identified as a characteristic pathway for fresh P. ginseng. It was further discovered that the dominant active components of fresh P. ginseng, such as ginsenoside Re, ginsenoside Rg_1, and β-elemene, could regulate this pathway through targets such as AKT, JNK, EGFR, and P38. Biological validation results showed that ginsenoside Re, ginsenoside Rg_1, and β-elemene could enhance cell viability, reduce lactate dehydrogenase(LDH) content, and decrease reactive oxygen species(ROS) levels in the cell supernatant. Target validation results indicated that ginsenoside Rg_1 and β-elemene significantly down-regulated the expression of EGFR protein in the FoxO signaling pathway, while ginsenoside Re and β-elemene significantly down-regulated the expression of ERK1/2 and P38 proteins. This study revealed the advantageous mechanisms of fresh P. ginseng in protecting against myocardial ischemia, providing a theoretical basis for the further development of fresh P. ginseng and related products.
Panax/chemistry* ; Animals ; Mice ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Myocardial Ischemia/genetics* ; Male ; Forkhead Transcription Factors/metabolism* ; Humans ; Apoptosis/drug effects* ; Oxidative Stress/drug effects*