Electroencephalography (EEG) is a non-invasive neurophysiological monitoring technique. It records the electrical activity of the cerebral cortex using electrodes placed on the scalp surface. Owing to its high safety, portability, and millisecond-level temporal resolution, EEG has been widely utilized in a variety of fields, including clinical diagnosis, brain-computer interfaces (BCIs), and cognitive neuroscience research. However, due to its microvolt-level amplitude, EEG is highly susceptible to various artifacts, including electrooculographic (EOG), electrocardiographic (ECG), electromyographic (EMG), and power line interference (PLI). These artifacts can obscure genuine neural activity and introduce spurious electrophysiological features. Consequently, they may compromise EEG signal quality, thereby reducing the reliability of downstream analyses. To address this issue, numerous EEG artifact removal methods have been developed, including both traditional denoising techniques and deep learning-based approaches. Traditional EEG denoising methods have long served as the primary solutions for artifact removal. Representative approaches include filtering, regression, and blind source separation. Although these methods have demonstrated effectiveness in specific scenarios, they suffer from several inherent limitations. Filtering assumes that artifacts and EEG signals can be separated in the frequency domain, but many artifacts, such as EOG and EMG, overlap with EEG spectra, which may lead to the loss of valuable neural information. Regression methods require high-quality artifact references to estimate and subtract contaminations, limiting their effectiveness in reference-free scenarios. Blind source separation can remove artifacts without external references, but it typically requires the number of EEG channels to exceed the number of sources, restricting its application in single- or low-channel EEG recordings. Deep learning-based EEG denoising methods address these limitations effectively. First, they learn the nonlinear mapping between contaminated and clean EEG directly from data in an end-to-end manner. This approach does not rely on assumptions about spectral separability, thereby preserving neural activity more completely. Second, the reference information is incorporated during the training phase, allowing the trained model to perform artifact removal independently without external references. Third, deep learning models can be flexibly designed to accommodate various recording setups, achieving robust denoising for both high-density and single-channel EEG. Collectively, these advantages enable deep learning-based methods to overcome the main challenges of traditional approaches, providing more accurate and reliable EEG signal recovery. The superior denoising performance of deep learning-based EEG denoising methods has attracted increasing attention in EEG artifact removal research. As a result, many deep learning-based denoising methods have been developed and successfully applied in neural engineering areas. However, a systematic review of the techniques and applications in this field is still lacking. To address this gap, this paper reviews recent advances in deep learning-based EEG denoising from four perspectives: technical principle, benchmark dataset, denoising model, and evaluation method. Representative applications in neural signal analysis and BCI decoding are also summarized. Furthermore, the advantage, existing challenge, and future research direction of deep learning-based EEG denoising are discussed. This review aims to provide valuable theoretical insights and technical guidance for researchers. It is also expected to promote further advances and broader applications of deep learning-based EEG denoising techniques.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome types with endoscopic features and pathological types of gastric polyps.Methods A total of 1 746 patients with gastric polyps admitted to the Department of Spleen and Stomach Diseases,Dongguan Hospital of Guangzhou University of Chinese Medicine were enrolled.The clinical data of the patients were collected,including gender,age,information obtained by four diagnostic methods of TCM,and pathological types and predilection sites of gastric polyps as well as their number and size.The distribution of TCM syndromes in the patients with gastric polyps and their correlation with endoscopic features and pathological types of the polyps were analyzed.Results(1)Of the 1 746 patients,1 107(63.40%)were female and 639(36.60%)were male,with the male to female ratio being 1∶1.73.The incidence of gastric polyps was positively correlated with the age(P＜0.01):the older the age,the higher the incidence rate.The middle-aged and elderly people were the predilection population for gastric polyps,and the patients aged over 40 years old accounted for 87.40%.(2)The TCM syndrome types of patients with gastric polyps were predominated by spleen-stomach qi deficiency syndrome(418 cases,23.94%),and then came cold-damp obstruction syndrome(394 cases,22.57%),damp-heat in the spleen and stomach syndrome(353 cases,20.22%),qi stagnation and phlegm obstruction syndrome(311 cases,17.81%)and phlegm blended with blood stasis syndrome(70 cases,15.46%).(3)There was a statistically significant difference in the distribution of TCM syndromes between the genders(P＜0.01):spleen-stomach qi deficiency syndrome,cold-damp obstruction syndrome,qi stagnation and phlegm obstruction syndrome and phlegm blended with blood stasis syndrome were more common in the female,while damp-heat in the spleen and stomach syndrome was more common in the male.The distribution of TCM syndromes varied in different age groups(P＜0.01):patients aged over 30 years old were more likely to suffer spleen-stomach qi deficiency syndrome,patients aged 30-39 and 40-49 years old were more likely to suffer damp-heat in the spleen and stomach syndrome,patients aged 50-59 years old were more likely to suffer qi stagnation and phlegm obstruction syndrome,and patients aged 60 years old or above were more likely to suffer cold-damp obstruction syndrome.(4)The pathological types of gastric polyps were predominated by fundus gland polyps(1 327 cases,76.00%),followed by hyperplastic polyps(266 cases,15.23%),inflammatory polyps(146 cases,8.36%),and adenomatous polyps(7 cases,0.40%).There was a statistically significant difference in the distribution of TCM syndromes among various pathological types(P＜0.01):fundus gland polyps were common in the patients with spleen-stomach qi deficiency syndrome,hyperplastic polyps were common in the patients with qi stagnation and phlegm obstruction syndrome,inflammatory polyps were common in the patients with cold-damp obstruction syndrome,and adenomatous polyps were common in the patients with phlegm blended with blood stasis syndrome.(5)Gastric polyps were characterized by multiple polyps(1 120 cases,64.15%),single polyp was rare(626 cases,35.85%).The distribution of TCM syndromes varied in the patients with different number of polyps(P＜0.05):patients with multiple polyps were predominated by spleen-stomach qi deficiency syndrome(25.45%),patients with single polyp were predominated by damp-heat in the spleen and stomach syndrome(24.28%).(6)Gastric polyps frequently appeared in the gastric body and gastric fundus,with the diameter being or less than 0.5 cm.And the differences of the distribution of TCM syndromes in the patients with various favored sites and polyp size were not statistically significant(P＞0.05).Conclusion TCM syndrome types of patients with gastric polyps are correlated with gender and age of the patients and with the pathological types and number of gastric polyps.The incidence is positively correlated with the age,and middle-aged and elderly people are the predilection population of gastric polyps.The female incidence is significantly higher than that of the male,and damp-heat in the spleen and stomach syndrome is more common in the male while the rest of syndrome types are more common in the female.The patients with gastric fundus gland polyps usually suffer spleen-stomach qi deficiency syndrome,patients with hyperplastic polyps usually suffer qi stagnation and phlegm obstruction syndrome,patients with inflammatory polyps usually suffer cold-damp obstruction syndrome,and patients with adenomatous polyps usually suffer phlegm blended with blood stasis syndrome.

Objective:To explore the relationship between the Prognostic Nutritional Index (PNI) and the HALP score with the prognosis of patients with middle-to-advanced prostate cancer. Methods:A total of 168 patients with middle-to-advanced prostate cancer admitted to three comprehensive tertiary hospitals were observed from 2013 to 2018. Patient medical records were reviewed,and overall survival (OS) and progression-free survival (PFS) were followed up. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) and the optimal cut-off value of PNI and HALP scores for predicting patients' prognosis. The Kaplan-Meier method was used to draw survival curves,and the Log-rank test and Cox regression were used to analyze the influencing factors of patient OS and PFS. Results:The follow-up period was 55 (38.5,63) months,with 87 deaths (51.79％) during this period. The median OS and PFS times were 50 months and 45 months,respectively. The 3-year OS and PFS survival rates were 72.02％ and 64.29％,respectively. The areas under the ROC curve for predicting patients' prognosis with PNI and HALP scores were 0.912 and 0.828,respectively,with optimal cut-off values of 46.3 and 31.64 (P<0.05). Multivariate Cox regression showed that PNI<46.3,HALP score<31.64,and age ≥ 60 years were risk factors for OS with HR (95％ CI) of 6.016 (3.273～11.056),2.537 (1.531～4.205),and 1.776 (1.221～2.967),respectively (P<0.05). AJCC stage Ⅳ,PNI<46.3,and HALP<31.64 were risk factors for PFS with HR (95％ CI) of 2.777 (1.381～5.419),5.940 (3.245～10.872),and 2.481 (1.498～4.109),respectively (P<0.05). Conclusion:PNI and HALP scores can predict the prognosis of patients with middle-to-advanced prostate cancer.

OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis/drug effects* ; Apoptosis Regulatory Proteins/immunology* ; Autophagy/immunology* ; bcl-2-Associated X Protein/immunology* ; Bortezomib/therapeutic use* ; Burkitt Lymphoma/immunology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Drug Therapy, Combination ; Proto-Oncogene Proteins c-akt ; Proto-Oncogene Proteins c-bcl-2 ; Receptors, CXCR/immunology* ; RNA, Messenger ; TOR Serine-Threonine Kinases ; Xanthones/therapeutic use*

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg^-1•d^-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg^-1•d^-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.
Animals ; Rats ; Rats, Sprague-Dawley ; Propionates ; Serotonin ; Depression/therapy* ; Electroacupuncture ; Fatty Acids, Volatile ; Stroke/complications* ; Acetic Acid ; Butyric Acid ; Water

Humans ; East Asian People ; External Fixators ; Fracture Fixation/methods* ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; China ; Minimally Invasive Surgical Procedures/methods*

Aim To investigate the effect of terpinene 4-alcohol(T4O)on the malignant behavior of colorectal cancer cell RKO and HCT116 and the underlying mechanism. Methods RKO and HCT116 cells were treated with 0, 1, 2, 4 μmol·L-1 T4O and 4 μmol·L-1 5-Fu, respectively. The proliferation, clonal formation, apoptosis, cell cycle, migration and invasion of RKO and HCT116 cells were detected by CCK-8, colony formation, flow cytometry, wound healing and Transwell assay; the expressions of E-Cadherin, N-Cadherin, p21, CyclinB1 and cleaved-Caspase7 in each group of cells were detected by Western blot. Based on pharmacophore, the target of T4O was analyzed and then the effects of T4O on the expression and degradation rate of NR3C1 were explored. NR3C1 knockdown cells were constructed, and the effects of NR3C1 knockdown on the proliferating and migrating inhibition induced by T4O were detected by wound healing and CCK-8 assay. Results T4O significantly inhibited the proliferation, colony formation, migration and invasion of RKO and HCT116 cells, as well as induced apoptosis and G1 phase arrest(P all <0. 05). The effect of T4O was better than that induced by 5-Fu with the same dose. T4O obviously reduced N-Cadherin and Cyclin B1 expression, and elevated the E-Cadherin, p21 and cleaved-Caspase7 expression(P all <0. 05). A total of 10 targets of T4O were discovered, among which NR3C1 had the highest binding score. After T4O treatment, NR3C1 level in cells increased obviously, and the degradation rate decreased markedly(P<0.05). NRC3C1 knockdown significantly relieved the inhibitory effects of T4O on cell prolfieration and migration(P<0.05). Conclusion T4O can inhibit the malignant behavior of colorectal cancer cells RKO and HCT116 by maintaining the stability of NR3C1 protein.

Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.
Electrocardiography ; Female ; Heart ; Humans ; Long QT Syndrome ; Male ; Retrospective Studies ; Sympathectomy/methods*