1.Visualization analysis of the international standard ISO/TC 249 for traditional Chinese medicine
ZHAO Shuting ; ZHONG Yanmei ; HU Yuanzhang ; SUN Tao ; WU Chunjie ; WEN Chuanbiao
Digital Chinese Medicine 2022;5(2):103-111
Objective This study proposes to visually review the current situation and progress of standards sets by the International Organization for Standardization/Technical Committee on Traditional Chinese Medicine (ISO/TC 249). The review aims to explore the development strategies of the standards, which will exhibit the considerable impact on the economy, trade and exchanges, and cooperation in the area of traditional Chinese medicine (TCM). Methods ISO/TC 249 standards were searched on the ISO website, and their title, proposed time, current stage, scope, and classification were obtained for further summarization. Gephi was utilized to portray the co-occurrence network graph of the ISO/TC 249 standards subject. Results In ISO/TC 249, there were 116 standards, including 81 published standards and 35 developing standards by April 30, 2022. Two withdrawal standards were published after revision, which were not counted in the total standards. The number of published standards has been increasing since the first standard was published in 2014, whose title was “Sterile acupuncture needles for single use”. Among these standards, 17.24% (20/116) standards were in review, 56.03% (65/116) in publication, 3.45% (4/116) in approval, 5.17% (6/116) in enquiry, 3.45% (4/116) in committee, and 14.66% (17/116) in preparation, respectively. With 116 standards, most of the research focused on the medicament, as its classification of the International Classification for Standards (ICS) showed the proportion reaching 49.54%. The network analysis data revealed that the top five most frequent words were “materials” “root” “requirements” “products” and “system”, after removing the noise data, such as prepositions, conjunctions, and pronouns. Additionally, the word “system” co-exists with the terms “computerized” “coding” “image” “tongue” and “analysis”; the word “requirement” co-exists with “manufacturing” “decoction” “process” and “materials”; whereas the word “devices” co-exists with “pulse” “electric” “skin” and “measurement”. Conclusion With the increased diversification and complexity of problems, the development of standards is also oriented to multidisciplinary fields to cultivate the interdisciplinary talents, and especially the international standardization talents of compound TCM. Multi-angle analysis, formulation, and demonstration of standards, in line with industry needs in different disciplines, enhance the availability of standards and the ability to serve the industry.
2.MEDICLOUD: a holistic study on the digital evolution of medical data
Astha Modi ; Nandish Bhayani ; Samir Patel ; Manan Shah
Digital Chinese Medicine 2022;5(2):112-122
The Corona Virus Disease 2019 (COVID-19) pandemic has taught us many valuable lessons regarding the importance of our physical and mental health. Even with so many technological advancements, we still lag in developing a system that can fully digitalize the medical data of each individual and make it readily accessible for both the patient and health worker at any point in time. Moreover, there are also no ways for the government to identify the legitimacy of a particular clinic. This study merges modern technology with traditional approaches, thereby highlighting a scenario where artificial intelligence (AI) merges with traditional Chinese medicine (TCM), proposing a way to advance the conventional approaches. The main objective of our research is to provide a one-stop platform for the government, doctors, nurses, and patients to access their data effortlessly. The proposed portal will also check the doctors’ authenticity. Data is one of the most critical assets of an organization, so a breach of data can risk users' lives. Data security is of primary importance and must be prioritized. The proposed methodology is based on cloud computing technology which assures the security of the data and avoids any kind of breach. The study also accounts for the difficulties encountered in creating such an infrastructure in the cloud and overcomes the hurdles faced during the project, keeping enough room for possible future innovations. To summarize, this study focuses on the digitalization of medical data and suggests some possible ways to achieve it. Moreover, it also focuses on some related aspects like security and potential digitalization difficulties.
3.Ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris based on data mining
WANG Chaoping ; LUO Jing ; WAN Qiang ; CAO Meifang ; ZHA Qinglin ; LEI Zhiqiang ; Abid Naeem ; YANG Ming
Digital Chinese Medicine 2022;5(2):123-140
Objective To explore ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris, and to provide new ideas for the clinical treatment. Methods With “angina pectoris” as the key word, ancient books prescriptions and Chinese patent medicines related to angina pectoris were collected from China National Knowledge Infrastructure (CNKI), Traditional Chinese Medicine Database System, Chinese Medicine Prescription Database, New National Proprietary Chinese Medicine (2nd edition), and Chinese Pharmacopoeia (2020 edition) from January 1, 2015 to December 31, 2021. Core high-frequency aromatic Chinese medicines were defined, and their potential medication rules were analyzed and summarized. Microsoft Access 2010 was used for data management. Data analysis software, including Excel and IBM SPSS Modeler 18.0 were used for drug association rule analysis, and Cytoscape 3.7.2 for visual display. Results There were 67 ancient books prescriptions and 258 Chinese patent medicines containing aromatic Chinese medicines treating angina pectoris collected from relevant databases. In ancient books prescriptions, there were nine aromatic Chinese medicines with the frequency ≥10, and the most commonly used medicine was Danggui (Angelicae Sinensis Radix), followed by Chenpi (Citri Reticulatae Pericarpium). There were 33 aromatic Chinese medicines with the frequency ≥10 in Chinese patent medicines, and the most commonly used medicine was Danshen (Salviae Miltiorrhizae Radix et Rhizoma), followed by Chuanxiong (Chuanxiong Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma). In ancient books prescriptions, the medicines mainly belonged to intenal-warming medicines, Qi-regulating medicines, and blood circulation promoting and blood stasis removing medicines. There were eight medicine pairs with confidence equal to 100% in ancient books prescriptions, the most frequently used pairs were Chuanxiong (Chuanxiong Rhizoma) + Danggui (Angelicae Sinensis Radix), and Xiangfu (Cyperi Rhizoma) + Chenpi (Citri Reticulatae Pericarpium). In Chinese patent medicines, the aromatic Chinese medicine Chuanxiong (Chuanxiong Rhizoma) could be combined with many other Chinese medicines, among which the Confidence and Support of Chuanxiong (Chuanxiong Rhizoma) + Danshen (Salviae Miltiorrhizae Radix et Rhizoma) were at a high level. Conclusion Aromatic Chinese medicines for the treatment of angina pectoris of coronary heart disease are mainly warm, and the flavors are mainly pungent, sweet, and bitter. They mainly access to the liver, gallbladder, and pericardium meridians. The treatment of angina pectoris of coronary heart disease mainly focuses on warming heart pulse, and promoting blood circulation and removing blood stasis.
4.Intra-set correlation analysis of medical records of thyroid cancer treated by traditional Chinese medicine Master ZHOU Zhongying
XU Ziyuan ; ZHU Yao ; LU Ming ; ZHOU Zhongying
Digital Chinese Medicine 2022;5(2):141-153
Objective Based on intra-set correlation analysis, this paper deconstructs the clinical medical records of traditional Chinese medicine (TCM) Master ZHOU Zhongying in treating thyroid cancer, and analyzes the experience in “mechanism-syndrome-medicine-prescription” for thyroid cancer. Methods Through Medcase data processing platform, based on Frequent Pattern (FP)-Growth enhanced correlation analysis algorithm, the medical records of Professor ZHOU Zhongying for the treatment of thyroid cancer from June 1, 2001 to February 28, 2015 were analyzed within the set. Results This study involved 43 medical records, 43 patients, and 167 visits. After processing intra-set correlations, 28 groups of highly correlated symptoms, 21 groups of highly correlated tongue images, 10 groups of highly correlated pulse conditions, 28 groups of highly correlated pathogenesis, 34 groups of highly correlated herbs, and 26 groups of highly correlated western medicine diagnosis were selected. Professor ZHOU Zhongying treats thyroid cancer according to syndrome differentiation. Symptoms with more association rules included neck swelling, neck pain, cough, and dry mouth; tongue images with more association rules included dark purple tongue, dark red tongue, and fissured tongue; pulse conditions with more association rules were wiry pulse, thready pulse, small pulse, and slippery pulse; the pathogenesis with more association rules was phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin; herbs with more association rules were Chaihu (Bupleuri Radix), Zeqi (Sun Euphoribiae Herb), and Tiandong (Asparagi Radix); western medicine diagnosis with more association rules included thyroid cancer, insomnia, and chronic gastritis. Conclusion Thyroid cancer mostly presents as deficiency in origin and excess in manifestations. The basic pathogenesis is phlegm and blood stasis, damp-heat accumulation, and impairment of both Qi and Yin, which are closely related to liver, kidney, and spleen. Professor ZHOU Zhongying adopts both attack and supplement approaches as the general treatment principle, with a strong emphasis on regulating Qi and relieving depression, eliminating phlegm and resolving stagnation, eliminating dampness and turbidity, clearing fire and destroying poison, moistening dryness and softening hard mass, invigorating Qi and nourishing Yin, and paying attention to nourishing liver and kidney, invigorating spleen and stomach, while protecting the heart and lungs.
5.Traditional Chinese medicine Master XIONG Jibo’s medication experience in treating arthralgia syndrome through data mining
DENG Wenxiang ; ZHANG Jidong ; ZHANG Wenan ; HE Qinghu
Digital Chinese Medicine 2022;5(2):154-168
Objective This study aimed to examine and propagate the medication experience and group formula of traditional Chinese medicine (TCM) Master XIONG Jibo in diagnosing and treating arthralgia syndrome (AS) through data mining. Methods Data of outpatient cases of Professor XIONG Jibo were collected from January 1, 2014 to December 31, 2018, along with cases recorded in A Real Famous Traditional Chinese Medicine Doctor: XIONG Jibo's Clinical Medical Record 1, which was published in December 2019. The five variables collected from the patients’ data were TCM diagnostic information, TCM and western medicine diagnoses, syndrome, treatment, and prescription. A database was established for the collected data with Excel. Using the Python environment, a customized modified natural language processing (NLP) model for the diagnosis and treatment of AS by Professor XIONG Jibo was established to preprocess the data and to analyze the word cloud. Frequency analysis, association rule analysis, cluster analysis, and visual analysis of AS cases were performed based on the Traditional Chinese Medicine Inheritance Computing Platform (V3.0) and RStudio (V4.0.3). Results A total of 610 medical records of Professor XIONG Jibo were collected from the case database. A total of 103 medical records were included after data screening criteria, which comprised 187 times (45 kinds) of prescriptions and 1 506 times (125 kinds) of Chinese herbs. The main related meridians were the liver, spleen, and kidney meridians. The properties of Chinese herbs used most were mainly warm, flat, and cold, while the flavors of herbs were mainly bitter, pungent, and sweet. The main patterns of AS included the damp heat, phlegm stasis, and neck arthralgia. The most commonly used herbs for AS were Chuanniuxi (Cyathulae Radix), Huangbo (Phellodendri Chinensis Cortex), Cangzhu (Atractylodis Rhizoma), Qinjiao (Gentianae Macrophyllae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangqi (Astragali Radix), and Chuanxiong (Chuanxiong Rhizoma). The most common effect of the herbs was “promoting blood circulation and removing blood stasis”, followed by “supplementing deficiency (Qi supplementing, blood supplementing, and Yang supplementing)”, and “dispelling wind and dampness”. The data were analyzed with the support ≥ 15% and confidence = 100%, and after de-duplication, five second-order association rules, 39 third-order association rules, 39 fourth-order association rules, and two fifth-order association rules were identified. The top-ranking association rules of each were “Cangzhu (Atractylodis Rhizoma) → Huangbo (Phellodendri Chinensis Cortex)” “Cangzhu (Atractylodis Rhizoma) + Chuanniuxi (Cyathulae Radix) → Huangbo (Phellodendri Chinensis Cortex)” “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) + Gancao (Glycyrrhizae Radix et Rhizoma) → Qinjiao (Gentianae Macrophyllae Radix)” and “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) +Gancao (Glycyrrhizae Radix et Rhizoma) + Huangbo (Phellodendri Chinensis Cortex) → Qinjiao (Gentianae Macrophyllae Radix)”, respectively. Five clusters were obtained using cluster analysis of the top 30 herbs. The herbs were mainly drying dampness, supplementing Qi, and promoting blood circulation. The main prescriptions of AS were Ermiao San (二妙散), Gegen Jianghuang San (葛根姜黄散), and Huangqi Chongteng Yin (黄芪虫藤饮). The herbs of core prescription included Cangzhu (Atractylodis Rhizoma), Chuanniuxi (Cyathulae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangbo (Phellodendri Chinensis Cortex), Mugua (Chaenomelis Fructus), Qinjiao (Gentianae Macrophyllae Radix), Danggui (Angelicae Sinensis Radix), and Yiyiren (Coicis Semen). Conclusion Clearing heat and dampness, relieving collaterals and pain, and invigorating Qi and blood are the most commonly used therapies for the treatment of AS by Professor XIONG Jibo. Additionally, customized NLP model could improve the efficiency of data mining in TCM.
6.Screening influencing factors of blood stasis constitution in traditional Chinese medicine
ZHOU Xiaoying ; YANG Shengwen ; OU Jintao ; WANG Zhuo ; WANG Guangrong ; LUO Yue
Digital Chinese Medicine 2022;5(2):169-177
Objective To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine (TCM) constitution identification. Methods Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors (gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors (sleep time, age, and mother's age at birth) on the constitution of the two groups were analyzed. In the single-factor analysis, the Pearson's chi-square test was selected for the categorical variable, and the independent sample t test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution; the binary logistic stepwise regression method was selected for the multi-factor analysis. Results The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson's chi-square test yielded significant differences (P < 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples t test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations (P < 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types (P > 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution (P < 0.05). Conclusion Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.
7.Mechanisms of Dihuang (Rehmanniae Radix) in treating diabetic nephropathy complicated with depression based on network pharmacology
LEI Xing ; CHEN Qingyao ; WANG Xiaoping ; XU Jie ; GAO Yazhen ; LIN Qiaohong ; YE Zuwen ; ZHANG Jieyan ; SI Qin ; WANG Fang
Digital Chinese Medicine 2022;5(2):178-188
Objective To predict the molecular mechanism of Dihuang (Rehmanniae Radix) in the treatment of diabetic nephropathy (DN) complicated with depression based on network pharmacology. Methods The components of Dihuang (Rehmanniae Radix) were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and relevant literature. The component targets were detected by combining the SwissTargetPrediction and PubChem databases. Disease targets were collected from the Therapeutic Target Database (TTD), DisGeNET, and Ensembl databases with “diabetic nephropathy” and “depression” as keywords. The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape 3.7.2. The co-expression genes of the key targets were collected based on the COXPRESdb 7.3. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for potential targets using R language. Target-component docking was verified and evaluated using Discovery Studio 4.5. Results According to the databases and literature reports, Dihuang (Rehmanniae Radix) contained 65 active components, and had 155 related targets for the treatment of DN complicated with depression. PPI screening showed that the key targets included serine/threonine protein kinase 1 (AKT1), signal transducer and activator transcription 3 (STAT3), interleukin 6 (IL-6), mitogen-activated protein kinase 1 (MAPK1), and vascular endothelial growth factor A (VEGFA), etc. GO enrichment analysis mainly involved biological processes, such as lipid metabolism, protein secretion regulation, cell homeostasis, and phosphatidylinositol 3 kinase activity. KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements, insulin resistance (IR), neurotrophin signal path, Toll-like receptor signaling pathway, relaxin signaling pathway, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), etc. Molecular docking showed that the target had high affinity for stachyose, manninotriose, verbascose, nigerose, etc. Conclusion Based on network parmacology, this study preliminarily predict the effects of Dihuang (Rehmanniae Radix) in treating DN complicated with depression by regulating inflammation, glucose metabolism, nution nerve, etc.
8.Extraction process in Chuantieling (CTL) based on the quality by design (QbD) concept
LI Ya ; LI Zirui ; GUO Zhihua
Digital Chinese Medicine 2022;5(2):189-198
Objective This study aimed to design and optimize the water extraction process for Chuantieling (喘贴灵, CTL) based on the concept of quality by design (QbD). Methods The single-factor experiments were used to select the best experimental points of CTL water extraction. On this basis, the transfer rate of ephedrine hydrochloride and sinapine thiocyanate, and the yield of the extract were evaluated as the evaluation indicators. The liquid-solid ratio, extraction time, and pH value were selected as the main factors to carry out the Box-Behnken design (BBD). A mathematical model of the critical process parameters (CPPs) and critical quality attributes (CQAs) was established, the interaction between CQAs and CPPs was examined, and the CTL extraction process design space was established and optimized, which guaranteed the stability of the process. The high performance liquid chromatography (HPLC) was used to analyze the main active compounds in the CTL extract. Results Through single-factor experiments, the best experimental parameters were found to be a liquid-solid ratio of 8∶1, extraction time of 90 min, pH value of 4, and extraction times of three. The experimental variance analysis results of the BBD showed that the P value of the regression model was less than 0.05, and the lack-of-fit value was greater than 0.01, indicating that the constructed model had good predictive ability. The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation. In the production situation, the best extraction process was nine times of water addition, 72 min of extraction time, and 4.5 of pH value. The HPLC results showed that the peak areas of ephedrine hydrochloride, sinapine thiocyanate, tetrahydropalmatine, methyl eugenol, cinnamaldehyde, and 6-gingerol in the CTL extract accounted for 0.94%, 14.32%, 0.78%, 31.23%, 0.34%, and 0.44% of the total peak area, respectively. Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations, ensuring the stability of the process.
9.Preventive and therapeutic effects of Aerva lanata (L.) extract on ethylene glycol-induced nephrolithiasis in male Wistar albino rats
Ankul Singh S, Chitra Vellapandian, Gowri Krishna
Digital Chinese Medicine 2022;5(2):199-209
Objective Nephrolithiasis is a common urological disease. This study aims to evaluate the preventive and therapeutic effects of hydro-alcoholic extract of Aerva lanata (L.) roots (HAEAL) on ethylene glycol-induced nephrolithiasis in rats. Methods Fifty grams of shade-dried coarsely powdered Aerva lanata (L.) root was successively extracted with organic solvents in increasing order of polarity [petroleum ether (60 −80 °C), chloroform, and ethanol] using a Soxhlet apparatus, and then concentrated. Physical tests including nature, color, odor, and texture were performed on the herbal suspension. In vitro nephrolithiasis assessment was performed by nucleation assay, aggregation assay, and crystal growth assay. Thirty adult male Wistar albino rats were randomly divided into five groups (six rats in each group). Group 1: negative control group without induction or treatment till day 28. Group 2: positive control group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and mixed with distilled water till day 28. Group 3: standard group receiving a daily oral solution of 0.75% ethylene glycol till day 14 and Cystone (750 mg/kg) from day 15 to day 28. Group 4: low dose HAEAL group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and 400 mg/kg HAEAL from day 15 to day 28 (1 mL per day). Group 5: high dose HAEAL group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and 800 mg/kg HAEAL from day 15 to day 28 (1 mL per day). Urine (urine volume, pH value, appearance, odor, and turbidity) examination and serum test were performed. On day 29, the kidneys were dissected, and histopathology examination was performed to determine the degree of tubular injury. Results The suspension showed stability and aroma with no turbidity at room temperature. The suspension did not show changes in color and odor until day 3, indicating that the preparation was stable for 72 h. Body weight decreased in the positive control group indicating stone formation and changes in water intake. Both standard and HAEAL treatments restored the body weight to normal levels after treatment, indicating the beneficial effects of the treatment. Histopathological examination revealed no significant findings in the negative control group, whereas the positive control group showed inflammation in the kidney parenchyma. Compared with positive control group, there was increase in urine volume and excretion of urinary constituents such as calcium and oxalate (P < 0.01) as well as improved clearance rate (P < 0.05) in HAEAL treatment groups, in addition, the urine pH value of HAEAL groups was increased. Conclusion HAEAL reduced nephrolithiasis formation and had a diuretic effect, which could be used to promote the expulsion of stones. Further studies are needed to enhance the stability of the suspension for the production of better pharmaceutical formulations.
10.Protective effects of Zuogui Jiangtang Jieyu Formula on hippocampal neurons in rats of diabetes complicated with depression via the TRP/KYN metabolic pathway
LING Jia ; LIU Jian ; JIN Shi ; ZOU Manshu ; JIANG Yajie ; WANG Yuhong
Digital Chinese Medicine 2022;5(2):210-221
Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZGJTJYF) on hippocampal neurons in rats of diabetes complicated with depression (DD) via the TRP/KYN metabolic pathway. Methods (i) In vivo experiments: 60 specified pathogen free (SPF) grade male Sprague-Dawley (SD) rats were randomly divided into six groups with 10 rats in each groups: control, DD model, positive (1.8 mg/kg fluoxetine + 0.18 g/kg metformin), high-dose ZGJTJYF (ZGJTJYF-H, 40.500 g/kg ZGJTJYF), middle-dose ZGJTJYF (ZGJTJYF-M, 20.250 g/kg ZGJTJYF), and low-dose ZGJTJYF (ZGJTJYF-L, 10.125 g/kg ZGJTJYF) groups. Except for the control group, other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin (STZ) and four weeks of chronic unpredictable mild stress (CUMS). All drug administration groups were treated by gavage during CUMS modeling, and the control and model groups were given equal amount of distilled water. After four weeks, the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF. Moreover, the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF. Changes in 5-hydroxytryptamine (5-HT) level were detected via high-performance liquid chromatography with electrochemical detection (HPLC-ECD); the levels of tryptophan (TRP), kynurenine (KYN), and indoleamine 2,3-dioxygenase (IDO) in the hippocampus were detected using enzyme-linked immunosorbent assay (ELISA); the protein expression levels of synaptophysin (SYN) and postsynaptic density material-95 (PSD-95) were detected via immunohistochemistry (IHC); and the protein expression levels of N-methyl-D-aspartate receptor (NR) 2A and NR2B were detected using Western blot. (ii) In vitro experiments: five SPF grade SD pregnant rats (E16 – 18) were used to obtain primary hippocampal neurons (Ne), six SD new-born rats were used to collected primary astrocytes (As) and microglia (MG), and to establish a Ne-As-MG co-culture system. All co-culture systems were divided into six groups: control (PBS), model [150 mmol/L glucose + 200 μmol/L corticosterone (G&P) + PBS], blank (G&P + blank serum), positive (G&P + positive drug-containing serum), ZGJTJYF (G&P + ZGJTJYF serum), and 1-methyl-D-tryptophan (1-MT, IDO inhibitor) (G&P + 1-MT) groups. After 18 h of intervention by corresponding treatment, immunofluorescence was used to analyze the protein expression levels of SYN, PSD-95, NR2A, and NR2B; ELISA was performed to measure the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α , and TRP/KYN metabolic pathway-related factors [TRP, KYN, kynurenine acid (KYNA), quinolinic acid (QUIN)]. Results (i) In vivo experimental