1.Clinical and pathological features of intrahepatic intraductal papillary neoplasm of the bile duct: An analysis of four cases
Ying ZHANG ; Qing CAO ; Kaige WANG ; Fan JIA ; Yungang ZHANG
Journal of Clinical Hepatology 2026;42(7):1656-1660
ObjectiveTo investigate the clinical and pathological features of intrahepatic intraductal papillary neoplasm of the bile duct (IPNB), and to improve the understanding, diagnosis, and treatment of this disease. MethodsA retrospective analysis was performed for four patients who underwent surgical resection in Beijing Chaoyang Hospital, Capital Medical University, from January 2010 to December 2025 and were diagnosed with intrahepatic IPNB based on pathological examination. The clinical, imaging, and pathological features of these patients were summarized, and a literature review was performed for related articles in China and globally. ResultsAmong the four patients, there were three female patients and one male patient, with a median age of 65 years, and clinical manifestations included jaundice, abdominal pain or diarrhea, and asymptomatic findings on physical examination. The main imaging manifestation was bile duct dilatation or solid-cystic space-occupying lesion. Pathological typing revealed one case each of the gastric, intestinal, pancreatobiliary, and oncocytic types, and there was one patient with low-grade intraepithelial neoplasia and three patients with high-grade intraepithelial neoplasia, among whom one patient also had invasive carcinoma. ConclusionIntrahepatic IPNB is a rare precancerous lesion of the liver with diverse clinical, imaging, and pathological manifestations, and radical surgical resection remains the cornerstone of treatment.
2.Radiation environment monitoring and evaluation at application sites of online elemental analyzers in cement enterprises
Lun CUI ; Wenbin PENG ; Ying ZHANG ; Hua YANG ; Huijun YU ; Qing CHANG ; Mingfa XU
Chinese Journal of Radiological Health 2025;34(3):408-413
Objective To systematically evaluate the radiation impact of radioactive sources used in online elemental analyzers in cement enterprises on the surrounding environment, and to provide a scientific basis for radiation monitoring and safety management at the application sites of this type of radioactive sources. Methods A statistical analysis was conducted on 15 cement enterprises in Guangxi Province using online elemental analyzers with 252Cf as the radioactive source. On-site investigation of radiation safety management and on-site monitoring of radiation environment were performed, followed by an evaluation based on the collected data. Results Although the gamma radiation ambient dose equivalent rate and neutron ambient dose equivalent rate increased around the sites using online elemental analyzers with 252Cf as the radioactive source, they all met the requirements of the Radiological Health Protection Requirements for Instruments with Sealed Sources (GBZ 125—2009). Conclusion Under the current usage and management conditions, the application of this type of radioactive sources has controllable radiation impact on the surrounding environment, and will not pose a threat to public health and environmental safety. However, continuous strengthening of radiation safety management measures and regular radiation monitoring work are still needed to ensure the safe use of radioactive sources, further reducing potential radiation risks and providing strong guarantees for the safe application of radioactive sources in online elemental analyzers in cement enterprises.
3.Prevalence and influencing factors of overweight and obesity among primary school students in a community of Fengxian District, Shanghai, 2023
Xinxing ZHANG ; Qing LIU ; Ying WU ; Wanhong HE ; Chunlei PAN
Shanghai Journal of Preventive Medicine 2025;37(8):687-691
ObjectiveTo analyze the prevalence and influencing factors of overweight and obesity among primary school students in a community of Fengxian District, Shanghai, and to provide references for formulating prevention and control strategies against overweight and obesity. MethodsData on height and weight of all primary school students in a community in Fengxian District, Shanghai, in 2023 were obtained by physical examination, and 1 759 primary school students were included according to the entry criteria. Overweight and obesity were determined using body mass index (BMI). Additionally, a questionnaire survey was performed to 1 045 students to collect their demographic characteristics, dietary behaviors, dietary habits, sleep and physical activity information. Chi-square test and logistic regression analysis were used to analyze the influencing factors of overweight and obesity. ResultsIn 2023, among the 1 759 primary school students in the community in Fengxian District, 923 (52.47%) were male and 836 (47.53%) were female, with an overweight/obesity detection rate of 28.08%. The detection rate of overweight and obesity was 33.37% in males and 22.25% in females, which was significantly higher in males than that in females (χ2=26.845, P<0.001). Students aged 10‒12 years had a higher overweight/obesity detection rate (32.55%) than those aged 6‒<10 years (26.53%), and the difference was statistically significant (χ2=10.925, P<0.001). Logistic regression analysis revealed that being female, with young age, parental education level of bachelor’s degree and above, a high global dietary recommendation healthy (GDR-healthy) score, preference for vegetables and sweeter home-cooked meals, and a slow eating speed were negatively correlated with overweight/obesity. Whereas, parental overweight and obesity, binge eating, and a faster eating pace than same-age, same-gender peers may be positively correlated with overweight/obesity. ConclusionThe detection rate of overweight and obesity among primary school students in the community in Fengxian District of Shanghai is higher than the national level. Gender, age, parental BMI, parental education level, dietary behaviors and habits are the main influencing factors of overweight/obesity among primary school students.
4.Exploration of pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in treatment of gouty arthritis based on UPLC-Q-Exactive Orbitrap-MS technology and network pharmacology.
Yan XIAO ; Ting ZHANG ; Ying-Jie ZHANG ; Bin HUANG ; Peng CHEN ; Xiao-Hua CHEN ; Ming-Qing HUANG ; Xue-Ting CHEN ; You-Xin SU ; Jie-Mei GUO
China Journal of Chinese Materia Medica 2025;50(2):444-488
Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use*
;
Network Pharmacology
;
Arthritis, Gouty/metabolism*
;
Chromatography, High Pressure Liquid/methods*
;
Humans
;
Mass Spectrometry/methods*
;
Protein Interaction Maps/drug effects*
5.Effect of Yuxuebi Tablets on mice with inflammatory pain based on GPR37-mediated inflammation resolution.
Ying LIU ; Guo-Xin ZHANG ; Xue-Min YAO ; Wen-Li WANG ; Ao-Qing HUANG ; Hai-Ping WANG ; Chun-Yan ZHU ; Na LIN
China Journal of Chinese Materia Medica 2025;50(1):178-186
In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics*
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Pain/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Animals
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Mice
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Freund's Adjuvant/pharmacology*
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Ibuprofen
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Pain Threshold/drug effects*
;
Hyperalgesia/genetics*
;
Ganglia, Spinal
;
Interleukin-10/genetics*
;
Transforming Growth Factor beta/genetics*
;
Reverse Transcriptase Polymerase Chain Reaction
;
Tablets
;
Receptors, G-Protein-Coupled
6.Berberine promotes expression of AQP4 in astrocytes by regulating production of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance.
Xue-Ling LIN ; Ying LI ; Meng-Qing GUO ; Yan-Jun ZHANG ; Qing-Sheng YIN ; Peng-Wei ZHUANG
China Journal of Chinese Materia Medica 2025;50(3):768-775
This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans
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MicroRNAs/metabolism*
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Berberine/pharmacology*
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Hep G2 Cells
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Exosomes/genetics*
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Aquaporin 4/metabolism*
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Insulin Resistance
;
Astrocytes/drug effects*
7.Randomized, double-blind, parallel-controlled, multicenter, equivalence clinical trial of Jiuwei Xifeng Granules(Os Draconis replaced by Ostreae Concha) for treating tic disorder in children.
Qiu-Han CAI ; Cheng-Liang ZHONG ; Si-Yuan HU ; Xin-Min LI ; Zhi-Chun XU ; Hui CHEN ; Ying HUA ; Jun-Hong WANG ; Ji-Hong TANG ; Bing-Xiang MA ; Xiu-Xia WANG ; Ai-Zhen WANG ; Meng-Qing WANG ; Wei ZHANG ; Chun WANG ; Yi-Qun TENG ; Yi-Hui SHAN ; Sheng-Xuan GUO
China Journal of Chinese Materia Medica 2025;50(6):1699-1705
Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent
;
Child
;
Child, Preschool
;
Female
;
Humans
;
Male
;
Double-Blind Method
;
Drugs, Chinese Herbal/therapeutic use*
;
Tic Disorders/drug therapy*
;
Treatment Outcome
8.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
9.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.
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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