1.Physical factors and action mechanisms affecting osteogenic/odontogenic differentiation of dental pulp stem cells
Yuting SUN ; Jiayuan WU ; Jian ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(7):1531-1540
BACKGROUND:Dental pulp stem cells are one of the stem cells with great potential in oral and maxillofacial tissue engineering.Compared with mesenchymal stem cells,dental pulp stem cells have the advantages of convenient collection,less ethical problems and higher potential of proliferation and differentiation.Currently,except for biochemical factors,physical stimulation also plays a critical role in the osteogenic/odontogenic differentiation of dental pulp stem cells. OBJECTIVE:To review the relevant physical factors and the possible signaling pathway affecting the osteogenic/odontogenic differentiation of dental pulp stem cells to find the optimal induction conditions affecting their differentiation. METHODS:PubMed and CNKI databases were searched for relevant articles using"dental pulp stem cells(DPSCs),osteogenesis differentiation,odontoblastic differentiation,hypoxia,mechanical force,laser therapy,magnetic fields,microgravity"as English and Chinese search terms.Seventy-nine articles regarding physical factors affecting osteogenic/odontogenic differentiation of dental pulp stem cells were selected for the review. RESULTS AND CONCLUSION:(1)Direct or indirect physical signals in the microenvironment have shown broad application prospects in regulating the directed differentiation of stem cells.Many related physical factors,for example,hypoxia,mechanical stimulation(dynamic hydrostatic pressure,mechanical tension,shear force,etc.),laser,microgravity,and magnetic field,have positive influences on the osteogenic/odontogenic differentiation of dental pulp stem cells.Owing to the complex mechanical environment of stomatognathic system,mechanical stimulation is a key physical factor in changing cellular environment and is also a frontier in tissue engineering.It will provide new ideas for investigating the response of dental pulp stem cells to the mechanical environment in the diagnosis and treatment of oral diseases.(2)Because this field is relatively"young",the parameters of equipment have not been unified and the relevant results are not consistent.The optimal induction parameters and conditions of related physical factors should be further explored and optimized.(3)Scaffold material,one of the three elements of tissue engineering,plays a role in promoting the osteogenic/odontogenic differentiation of dental pulp stem cells,and promotes the development of materials science and clinical technology.(4)The signaling pathways involve Notch,Wnt,MAPK,etc.The biological basis of regulating the behavior of dental pulp stem cells is not clear.The specific mechanism will be further explored in the future to provide new ideas for dental pulp regeneration and bone tissue engineering under the influence of physical factors.
2.Construction of management index system for rational drug use of key monitoring drugs
Mingxiong ZHANG ; Wanying QIN ; Jian HUANG ; Dan WANG ; Li LI ; Yinghui BU ; Ming YAN ; Kejia LI
China Pharmacy 2025;36(7):784-788
OBJECTIVE To establish management index system for rational drug use of key monitoring drugs, and provide reference for the management of key monitoring drugs in the hospitals. METHODS First, the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next, using a modified Delphi method, twenty experienced experts from the fields of pharmacy, medical practice, healthcare insurance, and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient, authority coefficient, degree of opinion concentration, and degree of coordination, the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level, second-level and third-level indicators, the authority coefficients of experts were 0.89, 0.86 and 0.87, and coordination coefficients of the experts in importance score were 0.300 (P< 0.05), 0.125 (P<0.05) and 0.139 (P<0.05), respectively. The average score for the importance of all indicators reached over 3.5, in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26, the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation, final version of the management index system established in this study, including two first-level indicators (drug procurement and use, and rational drug use), five second-level indicators (such as the accessibility, cost-effectiveness) and twenty third-level indicators (such as the number of specifications purchased for key monitored drugs, the increase in the cost of key monitored drugs). CONCLUSIONS The management index system established in this study possesses high reliability and strong operability, and may provide a reference for the management of key monitoring drugs in the hospitals.
3.Protective Effect and Mechanism of Anmeidan against Neuronal Damage in Rat Model of Sleep Deprivation Based on Hippocampal Neuroinflammation
Guangjing XIE ; Zixuan XU ; Junlu ZHANG ; Jian ZHANG ; Jing XIA ; Bo XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):65-71
ObjectiveTo investigate the effects of Anmeidan (AMD) on neuroinflammation in the hippocampus of sleep-deprived rats. MethodsSD rats were randomly divided into four groups (n = 10 per group): control group, model group, AMD group, and melatonin group. A sleep deprivation model was established using the modified multiple platform water environment method. The AMD group received AMD at a dose of 18.18 g·kg-1·d-1, the melatonin group received melatonin at 100 mg·kg-1·d-1, and the control and model groups were given an equal volume of pure water. All treatments were administered by gavage for four weeks. Spontaneous activity was assessed using an animal behavior video system. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Hippocampal pyramidal neuron morphology was examined using hematoxylin-eosin (HE) staining, and ultrastructural changes of hippocampal neurons were observed via transmission electron microscopy. Immunofluorescence was used to detect the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus. Western blot analysis was performed to measure the expression of nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), NOD-like receptor protein 3 (NLRP3), and Caspase-1 proteins. ResultsCompared with the control group, the model group showed a significant increase in activity duration and frequency (P<0.01), increased hippocampal pyramidal cell structural damage and decreased cell count, aggravated hippocampal ultrastructural damage, mitochondrial cristae disruption, and exacerbated vacuolization. The expression of p-NF-κB p65, NLRP3, and Caspase-1 proteins was upregulated, serum IL-1β, IL-6, and TNF-α levels were significantly elevated (P<0.01), and the fluorescence intensity of BDNF and NGF proteins was significantly reduced (P<0.01). Compared with the model group, the AMD group showed a significant reduction in activity duration and frequency (P<0.01), increased hippocampal pyramidal cell count with reduced structural damage, alleviated hippocampal ultrastructural damage, significantly downregulated p-NF-κB p65, NLRP3, and Caspase-1 protein expression (P<0.01), decreased serum IL-1β, IL-6, and TNF-α levels (P<0.01), and significantly increased the fluorescence intensity of BDNF and NGF proteins (P<0.01). ConclusionAnmeidan alleviates hippocampal neuronal damage in sleep-deprived rats, potentially by downregulating the NLRP3 signaling pathway, reducing inflammatory cytokine release, and increasing neurotrophic factor levels.
4.Correlation Between Quality of Life and Traditional Chinese Medicine Syndromes in Patients with Myasthenia Gravis
Yibin ZHANG ; Qi LU ; Baitong WANG ; Yixun QI ; Hanying XU ; Peng XU ; Meijin SONG ; Peixi ZHAO ; Zhiguo LYU ; Jian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):275-281
ObjectiveThis study aimed to explore the correlation between the quality of life (QOL) and different traditional Chinese medicine (TCM) syndromes in patients with myasthenia gravis (MG), identifying potential influencing factors to provide new insights for clinical interventions and improving the QOL of patients with MG. MethodsA questionnaire survey was conducted on 93 adults with MG who visited the Department of Neurology at the Affiliated Hospital of Changchun University of Chinese Medicine from March 2023 to January 2024. Statistical analysis was performed on the clinical data collected using SPSS 24.0 software. ResultsAmong the 93 patients with MG, the average score for myasthenia gravis quality of life-15 (MGQOL-15) was 17.65±6.27, and that for the 36-item short form health survey (SF-36) was (106.13±11.83) scores. The QOL was rated as good for 16 patients and moderate for 77 patients. There were no statistically significant differences in the scores of MGQOL-15, SF-36, and their individual scales by gender or education level. Age showed statistically significant differences in MGQOL-15 and the role physical (RP) scale (P<0.05), and occupational type showed significant differences in the vitality (VT) scale (P<0.01). The Myasthenia Gravis Foundation of America (MGFA) classification had statistical significance on the total SF-36 score (P<0.01), VT scale (P<0.01), role emotional (RE) scale (P<0.05), social functioning (SF) scale (P<0.05), and physical functioning (PF) scale (P<0.01). Among patients with different TCM syndromes, there were significant differences in MGQOL-15 scores (F=4.919, P<0.01). Moreover, significant differences were observed in SF-36 scores (P<0.01), VT scale (P<0.01), RE scale (P<0.05), mental health (MH) scale (P<0.01), and SF scale (P<0.05). ConclusionFactors affecting the QOL of patients with MG include age, occupational type, and clinical classification of MG. Specifically, a greater impact on the QOL of older patients is observed, while physical laborers have a poorer QOL compared to non-physical laborers. Patients classified as MGFA type Ⅱ and higher have a poorer QOL. Additionally, there is a potential correlation between the QOL and TCM syndromes, with patients presenting with spleen and kidney Qi deficiency having a lower QOL than those with spleen and stomach Qi deficiency or Qi and Yin deficiency, which is particularly evident in the VT, RE, MH, and SF scales.
5.Analysis of surgical outcomes of congenital cataract treated with different surgical approaches and minimally invasive techniques
Weijie ZHANG ; Hong YAN ; Jian ZHANG
International Eye Science 2025;25(5):775-780
Congenital cataract is a leading cause of childhood blindness worldwide. By inducing visual impairment from birth, it disrupts the normal development of the visual system and profoundly impacts patients' quality of life. Therefore, timely diagnosis and the implementation of effective, safe interventions, particularly during the critical period of visual development, are of paramount clinical importance. Cataract extraction is a cornerstone therapeutic intervention. The success of the surgery, as well as postoperative visual recovery and the incidence of complications in pediatric patients, largely depends on the selected surgical approach and instrumentation. Surgical approaches are primarily categorized into the anterior approach(via corneal or limbal incision)and the posterior approach(via pars plana). Surgical instruments are typically classified by the gauge of the vitreous cutter, such as 20 G, 23 G, and 25 G. The choice of surgical approach not only directly influences the incidence of postoperative complications but also significantly impacts visual recovery. This article reviews and analyzes these critical aspects to provide valuable guidance for clinical practice.
6.Trends in global burden due to visceral leishmaniasis from 1990 to 2021 and projections up to 2035
Guobing YANG ; Aiwei HE ; Yongjun LI ; Shan LÜ ; Muxin CHEN ; Liguang TIAN ; Qin LIU ; Lei DUAN ; Yan LU ; Jian YANG ; Shizhu LI ; Xiaonong ZHOU ; Jichun WANG ; Shunxian ZHANG
Chinese Journal of Schistosomiasis Control 2025;37(1):35-43
Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/105, 95% UI: (1.49/105, 4.07/105)], prevalence [0.64/105, 95% UI: (0.37/105, 1.02/105)], mortality [0.51/105, 95% UI: (0, 1.80/105)] and DALYs rates of VL [33.81/105, 95% UI: (0.06/105, 124.09/105)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/105, 95% UI: (0.45/105, 0.72/105); 0.14/105, 95% UI: (0.11/105, 0.18/105)] than among women [0.27/105, 95% UI: (0.21/105, 0.33/105); 0.06/105, 95% UI: (0.05/105, 0.08/105)], and the highest mortality of VL was found among children under 5 years of age [0.24/105, 95% UI: (0.08/105, 0.66/105)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/105, 0.03/105, 0.02/105 and 1.44/105 in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.
7.Management status and influencing factors of disease stabilization in patients with severe mental disorders in Luzhou City, Sichuan Province
Xuemei ZHANG ; Bo LI ; Benjing CAI ; Youguo TAN ; Bo XIANG ; Jing HE ; Qidong JIANG ; Jian TANG
Sichuan Mental Health 2025;38(2):131-137
BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden, which has garnered significant national attention and prompted their inclusion in public health project management systems. However, credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City, Sichuan Province, remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City, Sichuan Province, and to analyze influencing factors of disease stabilization among patients under standardized care, so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023, data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City, the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017, respectively, which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022, the regular medication adherence rate was 71.80% for schizophrenia, 55.26% for paranoid psychosis, and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization: age of 18~39 years (OR=0.613, 95% CI: 0.409~0.918), age of 40~65 years (OR=0.615, 95% CI: 0.407~0.931), urban residence (OR=0.587, 95% CI: 0.478~0.720), and regular medication adherence (OR=0.826, 95% CI: 0.702~0.973). Risk factors for disease fluctuation included poor (OR=1.712, 95% CI: 1.436~2.040), non-inclusion in care-support programs (OR=1.928, 95% CI: 1.694~2.193), non-participation in community rehabilitation (OR=2.255, 95% CI: 1.930~2.634), and intermittent medication adherence (OR=3.893, 95% CI: 2.548~5.946). ConclusionThe stability rate, standardized management rate, and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age, household registration status, economic condition, medication compliance, and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. [Funded by Luzhou Science and Technology Plan Project (number, 2022-ZRK-186)]
8.Application of three-dimensional fluid-attenuated inversion recovery sequence using artificial intelligence-assisted compressed sensing technique in intravenous gadolinium contrast-enhanced magnetic resonance imaging of inner ear
Kai LIU ; Jian WANG ; Huaili JIANG ; Shujie ZHANG ; Di WU ; Xinsheng HUANG ; Mengsu ZENG ; Menglong ZHAO
Chinese Journal of Clinical Medicine 2025;32(2):212-217
Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P<0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P<0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P<0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.
9.Analysis of Treatment of Diabetic Kidney Disease with Modified Buyang Huanwutang Based on 5hmC-Seal Sequencing Technology
Baixin ZHEN ; Haoyu CHEN ; Duolikun MAIMAITIYASEN ; Xuehui LI ; Hong XIAO ; Xiaxuan LI ; Kuerban SUBINUER ; Lei ZHANG ; Hangyu CHEN ; Jian LIN ; Linlin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):208-217
ObjectiveTo improve the therapeutic effect of Buyang Huanwutang(BYHW) on diabetic kidney disease (DKD) and explore new methods for developing new Chinese medicine decoctions,we utilized 5-hydroxymethylcytosine (5hmC)-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus (DM) patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA (cfDNA) in the patients’ plasma was sequenced. After data processing and screening, we performed temporal clustering analysis to select a DKD 5hmC gene set, which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM), and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction (PPI) network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed on non-common DKD genes, and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes, and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass, random blood glucose, urinary microalbumin (mALB), serum creatinine (Scr), and blood urea nitrogen (BUN) and by hematoxylin-eosin staining, periodic acid-Schiff staining, Masson staining, immunofluorescence assay, and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes, of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 (IL-6), Toll-like receptor 4 (TLR4), lactotransferrin (LTF), lipoprotein lipase (LPL), and sterol regulatory element-binding transcription factor 1 (SREBF1). Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes, among which TBC1 domain family member 5 (TBC1D5), RAD51 paralog B (RAD51B), and proteasome 20S subunit alpha 6 (PSMA6) had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine, glycine, myristicin, serine, and tyrosine, corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus, Ginseng Radix et Rhizoma, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Isatidis Radix, Glehniae Radix, Ophiopogonis Radix, Allii Sativi Bulbus, Isatidis Folium, and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory, the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice, with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions, potentially offering new perspectives for the exploration of these prescriptions
10.Characteristic Expression of Multiple Neurotransmitters Oscillation Imbabance in Brains of 1 028 Patients with Depression
Anqi WANG ; Xuemei QING ; Yanshu PAN ; Pingfa ZHANG ; Ying ZHANG ; Jian LI ; Cheng ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):278-286
ObjectiveTo analyze the characteristic expression patterns of six neurotransmitters including 5-hydroxytryptamine (5-HT), dopamine (DA), acetylcholine (ACh), norepinephrine (NE), inhibitory neurotransmitter (INH), and excitatory neurotransmitter (EXC) in the whole brain and different brain regions of depression patients by Search of Encephalo Telex (SET), providing new ideas for the study of heterogeneous etiology of depression. Methods(1) A retrospective study was conducted on supra-slow signals of EEG fluctuations in 1 028 patients with depression. The SET system was used to obtain the expression information of six neurotransmitters in the whole brain and 12 brain regions: left frontal region (F3), right frontal region (F4), left central region (C3), right central region (C4), left parietal region (P3), right parietal region (P4), left occipital region (O1), right occipital region (O2), left anterior temporal region (F7), right anterior temporal region (F8), left posterior temporal region (T5), and right posterior temporal region (T6). The expression information of each neurotransmitter was compared with the normal model, and it was found that single neurotransmitter was in one of three states: increased, decreased, or normal expression. The simultaneous expression states of six neurotransmitters in the brain space were referred to as the expression pattern of multiple neurotransmitters. (2) A MySQL database was established to analyze the actual expression patterns of different neurotransmitters in the whole brain of patients with depression. (3) Factor analysis was conducted to further analyze the characteristic rules of 78 variables of neurotransmitters in the whole brain and 12 brain regions in depression patients. Results(1) The expression of single neurotransmitters in the whole brain and different brain regions of the total depression population showed one of three expression states (increased/decreased/normal), being normal in the majority. The decreased and increased expression of 5-HT, ACh, DA, INH, EXC, and NE in the whole brain occurred in 6% and 25%, 31% and 17%, 36% and 9%, 15% and 31%, 32% and 14%, and 22% and 22%, respectively. (2) The antagonizing pairs of neurotransmitters (EXC/INH, DA/5-HT, and ACh/NE) showed significant antagonistic relationships in the whole brain and different brain regions, with a strong negative correlation between EXC and INH (P<0.01, |r| values ranging from 0.69 to 0.76), a strong negative correlation between DA and 5-HT (P<0.01, |r| values ranging from 0.83 to 0.90), and a moderate negative correlation between ACh and NE (P<0.01, with |r| values ranging from 0.56 to 0.66). Meanwhile, non-antagonizing pairs of neurotransmitters in the whole brain and different brain regions also showed correlations, with DA/NE (P<0.01, |r| values ranging from 0.38 to 0.46) and NE/EXC (P<0.01, |r| values ranging from 0.56 to 0.61) showing weak and moderate negative correlations, respectively, and DA/EXC showing a weak positive correlation (P<0.01, |r| values ranging from 0.38 to 0.47). (3) The six neurotransmitters in the 1 028 patients with depression presented a total of 170 expression patterns in the whole brain. The top 30 expression patterns were reported in this paper, with a cumulative rate of 60.60%, including patterns ① INH+/5-HT-/ACh+/DA+/NE-/EXC- (9.05%), ② INH+/5-HT-/ACh↓/DA+/NE-/EXC- (4.57%), and ③ INH+/5-HT-/ACh+/DA+/NE↓/EXC- (3.31%). That is, the proportion of depression patients with normal levels of all the six neurotransmitters was 9.05%, and the patients with at least one neurotransmitter abnormality accounted for 91.95%. (4) The factor analysis extracted 22 common factors from 78 variables in the whole brain and different brain regions. These common factors showed the absolute values of loadings ranging from 0.32 to 0.86 and the eigenvalues (F) ranging from 1.03 to 13.43, with a cumulative contribution rate of 76.82%. The characteristic expression patterns included ① AChP3↓/AChW↓/AChC3↓/AChF3↓/AChO1↓/AChT5↓/AChF7↓/NEP3↑/NEW↑/NEC3↑/NEF3↑/NEO1↑/NET5↑/NEF7↑ (F=13.43, whole brain), ② 5-HTO2↑/DAO2↓/5-HTP4↑/DAP4↓/5-HTW↑/DAW↓/5-HTC4↑/DAC4↓ (F=5.94), and ③ EXCF4↓/DAF4↓/NEF4↑/INHF4↑/5-HTF4↑/AChF4↓ (F=5.33). ConclusionThe actual 170 expression patterns of 6 neurotransmitters in the whole brain of 1 028 depression patients indicate that depression is a heterogeneous disease with individualized characteristics. The 22 characteristic expression patterns in the whole brain and 12 brain regions verify the pathogenesis hypothesis of multi-neurotransmitters oscillation imbalance in brains of depression patients. In summary, this study provides new guidance for the etiology, diagnosis, and treatment of depression and establishes a methodological foundation for the effectiveness evaluation of individualized treatment of depression by traditional Chinese medicine based on the objective biological markers.

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