1.Applications of EEG Biomarkers in The Assessment of Disorders of Consciousness
Zhong-Peng WANG ; Jia LIU ; Long CHEN ; Min-Peng XU ; Dong MING
Progress in Biochemistry and Biophysics 2025;52(4):899-914
Disorders of consciousness (DOC) are pathological conditions characterized by severely suppressed brain function and the persistent interruption or loss of consciousness. Accurate diagnosis and evaluation of DOC are prerequisites for precise treatment. Traditional assessment methods are primarily based on behavioral scales, which are inherently subjective and rely on observable behaviors. Moreover, traditional methods have a high misdiagnosis rate, particularly in distinguishing minimally conscious state (MCS) from vegetative state/unresponsive wakefulness syndrome (VS/UWS). This diagnostic uncertainty has driven the exploration of objective, reliable, and efficient assessment tools. Among these tools, electroencephalography (EEG) has garnered significant attention for its non-invasive nature, portability, and ability to capture real-time neurodynamics. This paper systematically reviews the application of EEG biomarkers in DOC assessment. These biomarkers are categorized into 3 main types: resting-state EEG features, task-related EEG features, and features derived from transcranial magnetic stimulation-EEG (TMS-EEG). Resting-state EEG biomarkers include features based on spectrum, microstates, nonlinear dynamics, and brain network metrics. These biomarkers provide baseline representations of brain activity in DOC patients. Studies have shown their ability to distinguish different levels of consciousness and predict clinical outcomes. However, because they are not task-specific, they are challenging to directly associate with specific brain functions or cognitive processes. Strengthening the correlation between resting-state EEG features and consciousness-related networks could offer more direct evidence for the pathophysiological mechanisms of DOC. Task-related EEG features include event-related potentials, event-related spectral modulations, and phase-related features. These features reveal the brain’s responses to external stimuli and provide dynamic information about residual cognitive functions, reflecting neurophysiological changes associated with specific cognitive, sensory, or behavioral tasks. Although these biomarkers demonstrate substantial value, their effectiveness rely on patient cooperation and task design. Developing experimental paradigms that are more effective at eliciting specific EEG features or creating composite paradigms capable of simultaneously inducing multiple features may more effectively capture the brain activity characteristics of DOC patients, thereby supporting clinical applications. TMS-EEG is a technique for probing the neurodynamics within thalamocortical networks without involving sensory, motor, or cognitive functions. Parameters such as the perturbational complexity index (PCI) have been proposed as reliable indicators of consciousness, providing objective quantification of cortical dynamics. However, despite its high sensitivity and objectivity compared to traditional EEG methods, TMS-EEG is constrained by physiological artifacts, operational complexity, and variability in stimulation parameters and targets across individuals. Future research should aim to standardize experimental protocols, optimize stimulation parameters, and develop automated analysis techniques to improve the feasibility of TMS-EEG in clinical applications. Our analysis suggests that no single EEG biomarker currently achieves an ideal balance between accuracy, robustness, and generalizability. Progress is constrained by inconsistencies in analysis methods, parameter settings, and experimental conditions. Additionally, the heterogeneity of DOC etiologies and dynamic changes in brain function add to the complexity of assessment. Future research should focus on the standardization of EEG biomarker research, integrating features from resting-state, task-related, and TMS-EEG paradigms to construct multimodal diagnostic models that enhance evaluation efficiency and accuracy. Multimodal data integration (e.g., combining EEG with functional near-infrared spectroscopy) and advancements in source localization algorithms can further improve the spatial precision of biomarkers. Leveraging machine learning and artificial intelligence technologies to develop intelligent diagnostic tools will accelerate the clinical adoption of EEG biomarkers in DOC diagnosis and prognosis, allowing for more precise evaluations of consciousness states and personalized treatment strategies.
2.Effect of Sargassum and Glycyrrhizae Radix et Rhizoma Incompatible Pair with Haizao Yuhutang on Oxidative Stress in Liver of Goiter Rats
Xiao DONG ; Yi TIAN ; Xiaoqing LIU ; Can CAO ; Wenyong LIAO ; Xiangnan XU ; Meijing WU ; Haiyan LIU ; Shaohong CHEN ; Xue YU ; Angran FAN ; Linlin XIU ; Gansheng ZHONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):37-45
ObjectiveTo observe the effects of Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the Haizao Yuhutang (HYT) on oxidative stress in the liver of goiter rats under the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020. MethodA total of 128 male Wistar rats were randomly divided into a blank group, a model group, a euthyrox group (20 μg·kg-1), a HYT group (12.06 g·kg-1), a HYT without Sargassum (HYT-H) group (9.90 g·kg-1), a HYT without Glycyrrhizae Radix et Rhizoma (HYT-G) group (10.26 g·kg-1), a HYT without Sargassum and Glycyrrhizae Radix et Rhizoma (HYT-HG) group (8.10 g·kg-1), and a Sargassum and Glycyrrhizae Radix et Rhizoma (HG) group (3.96 g·kg-1). The blank group was given deionized water by gavage, and the others were given propylthiouracil (PTU) to replicate the goiter pathological model. Euthyrox was taken as a positive control drug, and the rest of the Chinese medicine groups were given the corresponding decoction by gavage, the material was collected 12 hours after the last dose. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), reactive oxygen species (ROS) in liver tissue were detected in each group. The pathological changes in the liver were observed via hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to detect the mRNA expressions of Kelch-like Ech-associated protein 1 (Keap1), nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), p53 and Caspase-3 in liver tissues. Western blot was adopted to detect the protein expressions of Nrf2 and HO-1 in liver tissues in oxidative stress-related signaling pathways. ResultCompared with control group, the model group showed significantly increased serum ALT level and contents of MDA and ROS in liver tissues (P<0.05, P<0.01), significantly reduced activities of SOD and GSH-Px in the liver (P<0.01), significantly increased mRNA expression of Keap1 (P<0.01), and significantly decreased mRNA and protein expressions of Nrf2 and HO-1 (P<0.05, P<0.01). Compared with the model group, the HYT group manifested significantly reduced serum levels of AST, ALT, and ALP (P<0.05, P<0.01), significantly reduced contents of MDA and ROS in liver tissue (P<0.01), significantly increased the activities of SOD and GSH-Px (P<0.01), significantly decreased mRNA expressions of Keap1, p53, and Caspase-3 (P<0.01), and significantly increased mRNA and protein expressions of Nrf2 and HO-1 (P<0.05, P<0.01). ConclusionUnder the condition of 2 times the dose limit of the Pharmacopoeia of the People's Republic of China 2020, Sargassum and Glycyrrhizae Radix et Rhizoma incompatible pair with the HYT on oxidative stress in the liver of goiter rats had different effects. The HYT that contains Sargassum and Glycyrrhizae Radix et Rhizoma has a protective effect on the liver of goiter rats, and the effect is better than that of the HG group, the euthyrox group, and the incomplete groups. Its mechanism may be related to activating the Nrf2/HO-1 signaling pathway to alleviate liver oxidative stress and inhibiting the p53/Caspase-3 signaling pathway to reduce hepatocyte apoptosis.
3.Effects of esketamine combined with sufentanil on postoperative analgesia and depression after hip arthroplasty
Jun-Jun HE ; Hong WANG ; Yuan-Yuan HU ; Lan XU ; Jing-Jing WU ; Qun CHEN ; Zhi-Peng DONG ; Li-Li ZHONG
Journal of Regional Anatomy and Operative Surgery 2024;33(3):268-271
Objective To evaluate the effects of ketamine combined with sufentanil on postoperative analgesia and depression in patients undergoing hip arthroplasty.Methods A total of 60 patients who underwent elective hip arthroplasty were selected and divided into the S group,the SK1 group and the SK2 group according to the patient-controlled intravenous analgesia regimen,with 20 cases in each group.Patients in the S group were received 2 μg/kg of sufentanil for postoperative analgesia,patients in the SK1 group were received 1 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia,and patients in the SK2 group were received 2 mg/kg of esketamine and 2 μg/kg of sufentanil for postoperative analgesia.At 1,4,24,and 48 hours after surgery,the analgesic effect of patients was evaluated using the numeric rating scale(NRS),and the sedation effect of patients was evaluated using the Ramsay sedation score.Depression of patients before and 48 hours after surgery was assessed by self-rating depression scale(SDS).The adverse reactions such as nausea and vomiting,dizziness and headache,respiratory depression,and mental symptoms within 48 hours after surgery of patients were recorded.Results The NRS scores 1,4,and 24 hours after surgery of patients in the SK1 group and the SK2 group were lower than those in the S group(P<0.05);there was no statistically significant difference in the NRS scores 48 hours after surgery of patients among the three groups(P>0.05);there was no statistically significant difference in the NRS scores at different postoperative points of patients between the SK1 and SK2 groups(P>0.05).The SDS scores 48 hours after surgery of patients in each group were lower than those before surgery(P<0.05).There was no statistically significant difference in the Ramsay scores at different postoperative points of patients among the three groups(P>0.05).The incidence of adverse reactions 48 hours after surgery in the SK2 group was higher than those in the S group and the SK1 group(P<0.05).Conclusion Using 1 mg/kg of esketamine combined with 2 μg/kg of sufentanil after hip arthroplasty has a good analgesic effect without obvious increase of adverse reactions or significant effect on improving depression of patients.
4.Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge. and Carthamus tinctorius L.
Linying Zhong ; Ling Dong ; Jing Sun ; Jie Yang ; Zhiying Yu ; Ping He ; Bo Zhu ; Yuxin Zhu ; Siyuan Li ; Wenjuan Xu
Journal of Traditional Chinese Medical Sciences 2024;11(1):44-54
Objective:
To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation.
Methods:
Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets.
Results:
Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3.
Conclusion
The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.
5.A Method for Developing Implementation Strategies to Address Implementation Barriers: the CFIR-ERIC Matching Tool
Wanqing HUANG ; Dongmei ZHONG ; Siyuan LIU ; Yunyun XIE ; Jiangyun CHEN ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1182-1191
Implementation strategies are targeted interventions aimed at promoting the adoption, implementation, and sustainment of research findings or evidence-based practices in routine healthcare. If implementation strategies can precisely match implementation barriers and facilitators, the likelihood of successful implementation will increase. The CFIR-ERIC matching tool, which can match corresponding ERIC implementation strategies based on CFIR barriers, is a convenient and direct tool for developing implementation strategies. This paper provides a detailed overview of the origins and development of the CFIR-ERIC matching tool, outlines its contents and usage, and illustrates how to apply the tool to develop implementation strategies by using a brief smoking cessation intervention project as an example. The paper also discusses the advantages and limitations of using this tool for developing implementation strategies, with the aim of providing methodological reference for other researchers.
6.Visual analysis of research hotspots and development trends of Polygoni Multiflori Radix(processed)based on CiteSpace
Fang TANG ; Li-Yuan QU ; Bo-Hong CEN ; Ping WANG ; Dong-Mei SUN ; Zhong-Yuan XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1363-1367
Objective This study aims to explore the research hotspots and trends of Polygoni Multiflori Radix(processed)and provide a reference for follow-up research by bibliometric visualization analysis.Methods Relevant Polygoni Multiflori Radix literatures were collected through databases such as PubMed,Web of Science and China National Knowledge Infrastructure.Use CiteSpace 6.1.R6 software to do bibliometric analysis on the number and years of articles,research fields,countries/regions,institutions,authors,keywords,co-citation references,and build visual maps.Results A total of 1 517 literatures(1 131 Chinese literatures and 386 English literatures)were searched through databases in this review.We therefore conducted a quantitative analysis of accessible literature published over the last 30 years found that a very modest upward trend in publication volume from Chinese and a notable increase in publication over the world.Among the author teams,there was some cooperation,and the author team with the most published papers cooperated more closely,such as XIAO Xiao-he and WANG Jia-bo's team.In particular reducing toxicity and increasing efficiency by processing,and the toxicity and the rationalusage of Polygoni Multiflori Radix were a main research direction for nearly ten years.Meanwhile,through the co-occurrence analysis of keywords,we constructed and visualized a keyword network to explore the hotspots and future directions of Polygoni Multiflori Radix.We clearly found that effective and toxic homologous components,molecular mechanisms and early warning surveillance of hepatotoxicity might be the next topics for Polygoni Multiflori Radix.Conclusion The research on the homologous chemical components of Polygoni Multiflori Radix(processed)has been very active.The research on the conversion relationship and mechanism of homologous components of Polygoni Multiflori Radix(processed)and the mechanism of hepatotoxicity will be the research focus and development trend in this field.
7.Comparison of clinical efficacies among three surgical methods in treating stage Ⅲ Kümmell disease without neurological symptoms
Xudong MENG ; Jiongbiao ZHONG ; Chao DONG ; Yin XU ; Jiafu LI
Chongqing Medicine 2024;53(16):2512-2519
Objective To compare the clinical efficacies among three surgical methods in the treatment of stage Ⅲ Kümmell's disease without neurological symptoms.Methods A total of 71 patients with stage Ⅲ Kümmell's disease without neurological symptoms admitted and treated in the orthopedics department of Af-filiated Yueyang Hospital of Hunan Normal University from September 2019 to April 2022 were selected and divided into three groups:29 cases in the percutaneous vertebroplasty (PVP) group (group A),19 cases in the percutaneous pedicle screw+lesioned vertebral PVP group (group B) and 21 cases in the percutaneous bone cement screw combined with lesioned vertebral PVP group (group C) according to the operation methods.The imaging,perioperative and follow-up indexes were compared among the three groups.Results All patients successfully completed the operation,no serious complications occurred after operation,and the follow-up time was more than 1 year.The sagittal position index (SI value) in the affected vertebra,visual analogue scale (VAS) score and Oswestry Disability Index (ODI) score at each time point (postoperative 1,3 months,1 year) after surgery in the group A were improved compared with before operation (P<0.05).The affected vertebra SI value,kyphosis Cobb angle,spinal canal stenosis rate,VAS score and ODI score at postoperative time points in the group B and C were improved compared with before operation (P<0.05).The affected ver-tebra SI value,kyphosis Cobb angle,spinal canal stenosis rate and ODI score at postoperative time points in the group B and C all were superior to those in the group A (P<0.05),while the affected vertebra SI value,kyphosis Cobb angle and spinal canal stenosis rate in postoperative 1 year in the group C were superior to those in the group B (P<0.05).The operative time,intraoperative bleeding volume,postoperative hospitaliza-tion duration and affected vertebral cement injection volume in the group A were significantly less than those in the group B and C (P<0.05).The operation time in the group B was less than that in the group C (P<0.05).Conclusion The three surgical methods for the treatment of stage Ⅲ Kümmell's disease without neu-rological symptoms all could relieve the symptoms and restore the function.The two surgical methods of pedi-cle screw reduction could more effectively restore the height of the affected vertebra,correct kyphosis malfor-mation and improve spinal stenosis than PVP alone.The pedicle screw has more advantages in maintaining mechanical support and stability after bone cement reinforcement.
8.FAN Rui-Qiang's Experience in Differentiating and Treating Urticaria
Jin-Feng AI ; Dong-Jun ZHONG ; Xu KANG ; Rui-Qiang FAN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1607-1611
Urticaria is a common allergic skin disease.Professor FAN Rui-Qiang believes that the main pathogenesis of urticaria is due to endowment intolerance,and wind-pathogen is the main pathogenic factor.The patients of Lingnan area are prone to be attacked by dampness interweaved with heat.The common syndrome patterns of urticaria are wind-damp heat syndrome,spleen deficiency and dampness accumulation syndrome,and disharmony between nutritive qi and defensive qi syndrome.For the treatment of urticaria by stages,the differentiation of deficiency and excess is stressed.Acute urticaria usually manifests as excess syndrome,and chronic urticaria often manifests as deficiency syndrome or deficiency interweaved with excess syndrome.For the treatment of urticaria patients with excess syndrome,therapies of clearing heat and removing dampness,and dispelling wind and relieving itching are recommended,and the modified prescription of Soufeng Lishi Decoction is usually adopted.For the treatment of urticaria patients with deficiency interweaved with excess syndrome,simultaneous treatment of symptoms and root causes should be performed,therapies of invigorating spleen,resolving dampness and relieving itching are recommended,and the modified prescription of Duopi Decoction is adopted.For the treatment of urticaria patients with deficiency syndrome,therapies of regulating nutritive qi and defensive qi,and expelling wind to relieve itching are recommended,and the modified prescription of Yupingfeng Powder plus Guizhi Decoction is adopted.The high-frequency Chinese medicinals for the treatment of urticaria treated by Professor FAN Rui-Qiang are Saposhnikoviae Radix,Cynanchi Paniculati Radix et Rhizoma,Schizonepetae Spica,Glycyrrhizae Radix et Rhizoma,Albiziae Cortex,Artemisiae Scopariae Herba,Paeoniae Radix Alba,Forsythiae Fructus,Tribuli Fructus,Houttuyniae Herba,Rehmanniae Radix,Dictamni Cortex,Atractylodis Rhizoma,Poria,and Astragali Radix.Professor FAN Rui-Qiang's clinical medication is flexible,and aims to reduce recurrence and improve the quality of life of urticaria patients.
9.Effect and mechanism of proteasome inhibitor MG132 on memory impairment caused by chronic hypoxia in mice
Hua-Ping DONG ; Peng LI ; Xiao-Xu LI ; Si-Min ZHOU ; Heng XIAO ; Jia-Xin XIE ; Pei HUANG ; Yu WU ; Zhi-Feng ZHONG
Medical Journal of Chinese People's Liberation Army 2024;49(4):449-458
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.
10.A case report of primary Müllerian adenosarcoma of the ovary and literature review
Tao PU ; Fang-Fang ZHONG ; Xiao-Yan ZHANG ; Dong-Dong SHI ; Cong-Jian XU ; Hong-Yuan JIANG ; Ling-Ling FAN
Fudan University Journal of Medical Sciences 2024;51(5):850-856
This article reports a case of primary Müllerian adenosarcoma(MA)of the ovary admitted to the Obstetrics and Gynecology Hospital,Fudan University in 2022,reviews the literature on this rare disease,and shares the experience of its diagnosis and treatment.The patient was a 29-year-old unmarried woman who underwent laparoscopic resection of an ovarian lesion in another hospital.Intraoperatively,it was observed that"the right ovary was enlarged with a cauliflower-shaped mass at the lower pole,measuring about 11 cm×8 cm,unencapsulated,with a fish-like texture,which was completely excised and sent for examination."Postoperative consultation with a(tertiary)hospital in Beijing and our pathology department suggested the diagnosis of ovarian adenosarcoma.Therefore,we performed a comprehensive staged surgery for the patient,i.e.,laparoscopic right salpingo-oophorectomy,cystectomy of the left ovary,omentectomy,multiple peritoneal biopsies,and hysteroscopic resection of cervical canal lesions.The patient received four cycles of postoperative chemotherapy with paclitaxel and ifosfamide.After chemotherapy,the patient has been regular followed up and showed no signs of recurrence during the almost 2-year postoperative follow-up period.


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