Closed-loop neuromodulation, especially using the phase of the electroencephalography (EEG) rhythm to assess the real-time brain state and optimize the brain stimulation process, is becoming a hot research topic. Because the EEG signal is non-stationary, the commonly used EEG phase-based prediction methods have large variances, which may reduce the accuracy of the phase prediction. In this study, we proposed a machine learning-based EEG phase prediction network, which we call EEG phase prediction network (EPN), to capture the overall rhythm distribution pattern of subjects and map the instantaneous phase directly from the narrow-band EEG data. We verified the performance of EPN on pre-recorded data, simulated EEG data, and a real-time experiment. Compared with widely used state-of-the-art models (optimized multi-layer filter architecture, auto-regress, and educated temporal prediction), EPN achieved the lowest variance and the greatest accuracy. Thus, the EPN model will provide broader applications for EEG phase-based closed-loop neuromodulation.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Machine Learning ; Signal Processing, Computer-Assisted ; Male ; Adult ; Neural Networks, Computer ; Brain Waves/physiology*

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective To investigate the clinical symptoms and psychological health status of migraine patients.Methods A total of 120 migraine patients admitted to Xingtai People's Hospital from September 14,2022 to July 30,2023 were selected and divided into mild pain group(0-3 points,51 cases),moderate pain group(4-6 points,48 cases),and severe pain group(7-10 points,21 cases)according to numerical rating scale.General clinical data,headache impact test-6(HIT-6),patient health questionnaire-9(PHQ-9),generalized anxiety disorder(GAD-7)and Pittsburgh sleep quality index(PSQI)were collected.Results The scores of HIT-6,PHQ-9,GAD-7,and PSQI of migraine patients were(56.33±11.30)points,(3.38±1.51)points,(3.01±0.58)points,and(4.73±0.78)points,respectively.There were statistically significant differences in the duration and total number of headache attacks among three groups(P＜0.05).With the aggravation of headache degree,the duration of headache attacks increased and the number of attacks increased.There were statistically significant differences in the scores of HIT-6 and GAD-7 among three groups(P＜0.05),and the scores of HIT-6 and GAD-7 increased with the aggravation of headache.Conclusion There are differences in the daily life impact,anxiety,pain duration and frequency of migraine in patients with different degrees of migraine.

Objective:To study the effects and the related molecular mechanisms of miR-148a-3p on the proliferation,invasion and migration of salivary adenoid cystic carcinoma SACC-LM cells.Methods:miR-148a-3p mimics and inhibitors,siRNA targeting EG-FR and their corresponding controls were transfected into SACC-LM cells.Bioinformatics was used to predict the potential target genes of miR-148a-3p.EGFR and miR-148a-3p mRNA expression levels were examined by qRT-PCR and the protein levels of EG-FR were detected by Western blotting.CCK-8,scratch,and Transwell assays were used to study the proliferation,migration,and invasion of SACC-LM cells,respectively.The direct targeting relationship between miR-148a-3p and EGFR was examined by using the double luciferase reporter gene assay.Statistical analysis of the data was performed by SPSS 22.0 software.Results:Overexpres-sion or inhibition of miR-148a-3p significantly inhibited or promoted the proliferation,invasion and metastasis of SACC-LM cells re-spectively(P＜0.05).Bioinformatics and double luciferase assay showed that miR-148a-3p directly targeted and regulated the expres-sion of EGFR(P＜0.001).Downregulation of EGFR inhibited the proliferation,migration and invasion of SACC-LM cells(P＜0.05)and partially reversed the promoting effect of miR-148a-3p inhibition(P＜0.05).Conclusion:The downregulation of miR-148a-3p leads to the abnormally high expression of its target gene EGFR,and promotes the proliferation,invasion,and migration of salivary adenoid cystic carcinoma cells.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

OBJECTIVE To conduct rapid health technology assessment （HTA） of ulinastatin （UTI）， and to evaluate the efficacy， safety and cost-effectiveness of UTI in the treatment of acute pancreatitis （AP）. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang database， CBM and official websites of HTA institutions， the systematic review （SR）/meta-analysis， economic evaluation and HTA reports of UTI in the treatment of AP were collected from the inception to Apr. 2024. Two researchers independently conducted screening， quality evaluation and data extraction according to the admission and exclusion criteria， and descriptive analysis was adopted to analyze and summarize the data. RESULTS A total of 19 studies were included， involving 15 SR/meta-analysis and 4 economic studies， and no HTA report was retrieved. In the treatment of AP， UTI showed clear advantages over conventional treatment alone in terms of improving the overall effective rate， shortening the recovery time of amylase， reducing the time required to relieve abdominal pain and distension， lowering the mortality rate， and decreasing the average hospital stay. Compared to other positive drugs （carbendate mesylate， octreotide， somatostatin， etc.）， its efficacy is similar， with a favorable safety profile. As far as the current research was concerned， UTI had obvious economic advantages over other positive drugs. CONCLUSIONS UTI is safe and effective in the treatment of AP， and has economic advantages.

ObjectiveTo explore the clinical efficacy of compound Wufengcao liquid （CWL） on tuberculous ulcer and the influence on macrophage polarization. Method① Clinical experiment： A total of 145 patients with tuberculous ulcer who were treated in Nanjing Integrated Traditional Chinese and Western Medicine Hospital were randomized into observation group， control group Ⅰ， and control group Ⅱ according to the random number table method. In addition to the basic anti-tuberculosis chemotherapy， CWL， Kangfuxin liquid， and isoniazid solution （local external application） were respectively used in the observation group， control group Ⅰ， and control group Ⅱ. The treatment lasted 4 weeks for each group. The total effective rate in wound healing， traditional Chinese medicine（TCM） syndrome score， and histopathological morphology of wound were observed and the expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in wound tissue was measured. ② Cell experiment： RAW264.7 cells were cultured in DMEM （10% fetal bovine serum， 1% double-antibody solution） in a cell incubator （37 °C， 5% CO₂）. Phorbol 12-myristate 13-acetate （PMA） was used to induce the differentiation of RAW264.7 cells into macrophages. Lipopolysaccharide （LPS） was employed to stimulate polarization of macrophages into M1 type and interleukin-4 （IL-4） to induce the polarization into M2 type. Kangfuxin solution， isoniazid solution， and CWL were respectively applied to the above cell model for 36 h. The cell supernatant was collected and centrifuged. Western blot was used to detect the protein expression of tumor necrosis factor-α （TNF-α）， transforming growth factor-β （TGF-β）， iNOS， and Arg-1， and flow cytometry （FCM） to detect the expression of CD86 and CD206. Result①Clinical experiment： The total effective rate in the CWL group ［98.0% （48/49）］ was higher than that in the control group Ⅰ ［87.5% （42/48）， χ²=3.962， P<0.05］ and control group Ⅱ ［83.3% （40/48）， χ²=6.162， P<0.05］. After 28 days of treatment， compared with control group Ⅰ and control group Ⅱ， CWL decreased the TCM syndrome score （P<0.05） and obviously improved the histopathological morphology of the wound. Immunohistochemistry results showed that the iNOS expression in local focus tissue was lower （P<0.05） and the expression of Arg-1 was higher （P<0.05， P<0.01） in the CWL group than in the control group Ⅰ and control group Ⅱ after 28 days of treatment. ② Cell experiment： Western blot assay showed that the expression of iNOS and TNF-α in LPS group increased compared with that in the M0 group （P<0.01） and the expression in the LPS+ isoniazid group， LPS+ Kangfuxin group， and LPS+CWL group was lower than that in the LPS group （P<0.05）. The expression of iNOS in LPS+Kangfuxin group and LPS+ CWL group was lower than that in the LPS+isoniazid group （P<0.05， P<0.01）， and the expression of TNF-α in LPS+ CWL group was lower than that in LPS+isoniazid group （P<0.01）. The expression of TNF-α in LPS+ CWL group decreased compared with that in the LPS+ Kangfuxin group （P<0.05）. The expression of Arg-1 and TGF-β in IL-4 group was higher than that in the M0 group （P<0.01）， and the expression in the IL-4+isoniazid group， IL-4+Kangfuxin group， and IL-4+ CWL group was higher than that in the IL-4 group （P<0.05）. The expression of Arg-1 and TGF-β in the IL-4+ Kangfuxin group and IL-4+CWL group was higher than that in the IL-4+isoniazid group （P<0.05， P<0.01）， and the expression was higher in the IL-4+CWL group than in the IL-4+Kangfuxin group （P<0.05， P<0.01）. The FCM result showed that the expression of CD86 and CD206 in LPS group and IL-4 group was higher than that in M0 group （P<0.01）. CD86 expression in LPS+isoniazid group， LPS+ Kangfuxin group， and LPS+CWL group was lower than that in the LPS group （P<0.01）. The expression of CD86 in LPS+Kangfuxin group and LPS+ CWL group increased compared with that in the LPS+isoniazid group （P<0.01）， and the expression was higher in the LPS+ CWL group than in the LPS+Kangfuxin group （P<0.01）. CD206 expression in IL-4+ isoniazid group， IL-4+Kangfuxin liquor group， and IL-4+ CWL group was increased compared with that in the IL-4 group （P<0.01）. CD206 expression in IL-4+Kangfuxin liquid group and IL-4+ CWL group was decreased compared with that in the IL-4+isoniazid group （P<0.01）. CD206 expression in IL-4+CWL group was lower than that in the IL-4+ Kangfuxin group （P<0.05）. ConclusionCWL can promote the healing of tuberculous ulcers， and the mechanism is that it inhibits the expression of iNOS， TNF-α， and CD86 and promotes the expression of Arg-1， TGF-β， and CD206， thereby regulating M1/M2 polarization balance.

Objective:To explore the effect of mixed reality (MR) application in the reconstruction of mandibular defects.Methods:Eighteen patients with mandibular defects were enrolled in this study, including 10 male patients and 8 female patients, whose age ranged from 27 to 45 years, and the mean age was 35.4 years. All the patients were from the Stomatological Hospital of the Fourth Military Medical University, during October 2019 to May 2021. Fibular flaps were used for the reconstruction of the mandibular defects. The patients were randomly divided into three groups, six in each group. In group one, MR-guided mandibular defect repair and reconstruction technique was used. In group two, 3D printed guide-assisted mandibular defect repair and reconstruction technique was used, and in the control group, traditional jaw defect repair and reconstruction technique was used. All the procedures were performed by the same team. Cone beam computed tomography (CBCT) was used for analysis of surgical accuracy, and questionnaires were used to evaluate the outcome of medical communication, occlusal relationship, appearance restoration, and medical experience satisfaction.Results:The mean surgical errors in the group one and group two were (1.75±0.44) mm and (1.81±0.16) mm respectively, which were both significantly lower than that in the control group (3.05±0.83) mm ( tMR=3.38, t3D=3.56, P<0.01). The medical communication (4.60±0.35, 4.52±0.28, tMR=2.90, t3D=2.77, P<0.05), occlusal relationship (4.17±0.32, 4.28±0.39, tMR=3.07, t3D=3.29, P<0.05), and medical experience satisfaction scores (4.26±0.45, 4.25±0.67, tMR=2.50, t3D=2.26, P<0.05) in the experimental groups were significantly higher than those in the control group (4.02±0.34, 3.58±0.33, 3.56±0.32, respectively). There was no significant difference in the satisfaction of appearance recovery among all the groups ( P>0.05). Conclusions:MR-guided mandibular repair and reconstruction surgery has high accuracy and is also beneficial to the recovery of occlusal relationship and medical communication.

Objective:To evaluate the effect of mixed reality (MR) in the standardized resident training on oral and maxillofacial-head and neck tumor surgery.Methods:Twenty resident doctors, who received standardized training in the department of maxillofacial oncology of our hospital, were randomly divided into experimental group and control group. The MR teaching method was used in the experimental group, while the traditional teaching method was used in the control group. The teaching effect was evaluated by theoretical and operational tests and a questionnaire survey. Statistical analysis was performed with the SPSS 24.0 software. Statistical comparisons were performed by the Students' t-test or the Wilcoxon rank correlation test. Results:The theoretical test results showed that the scores of the experimental group were significantly higher than those of the control group (85.30±3.59 vs. 80.20±5.63, t = 2.41, P = 0.027). The operational test results showed that the scores of the experimental group were significantly higher than those of the control group (89.20±5.07 vs. 82.30±6.36, t = 2.68, P = 0.015). The questionnaire survey results showed that the MR teaching helped to easily acquire the knowledge of head and neck anatomy and operation skills. Besides, the doctors in the experimental group were more active and glad to communicate with others than those in the control group. In addition, the MR teaching method improved the learning interest of doctors. The doctors in the experimental group were more satisfied with the teaching effect than those in the control group, and they recommended that the MR teaching method be used in clinical training and teaching on oral and maxillofacial-head and neck tumor surgery. Conclusion:MR teaching can help doctors understand and master the knowledge of head and neck anatomy and operation skills and improve their learning interest, achieving a good teaching effect, so it has important application value in the standardized resident training on oral and maxillofacial-head and neck tumor surgery.