1.Active Ingredients of Bupleuri Radix in Treatment of Central Nervous System: A Review
Shuhuan YANG ; Xin JIANG ; Runda YUAN ; Fang LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):325-334
Diseases of the central nervous system have become a growing global health concern. At present, there are many adverse reactions in the treatment with Western medicine. In contrast, traditional Chinese medicine has shown unique efficacy and rich clinical practice accumulation in diseases of the central nervous system. As a traditional Chinese medicine, Bupleuri Radix has played an important role in the treatment of neurological diseases through multi-target regulation, multi-pathway intervention, and multi-pathway mechanism of action. In recent years, with the in-depth study of the pharmacological effects of Bupleuri Radix, it has been found that the active ingredients such as saikosaponin, baicalin, quercetin, and kaempferol in Bupleuri Radix can be used as the main material basis for the treatment of neurological diseases. The results of this study showed that in neurodegenerative diseases, active ingredients of Bupleuri Radix can inhibit β-amyloid (Aβ) deposition and abnormal phosphorylation of microtubule-associated protein (Tau protein) in Alzheimer's disease, regulate the nuclear factor-κB/nuclear factor E2 related factor 2 (NF-κB/Nrf2) pathway to play the anti-inflammatory role, and alleviate α-Synuclein (α-Syn) aggregation and mitochondrial damage in Parkinson's disease. In epilepsy, depression, and cerebral ischemia, they can improve symptoms by regulating neurotransmitters, oxidative stress, and apoptosis pathways, and inhibit brain glioma proliferation. However, the mechanism of action has not been fully elucidated, and the complexity of compound components and poor blood-brain barrier penetration limit their clinical application. In the future, it is necessary to integrate multi-omics, network pharmacology, and nano-delivery technologies, focus on the optimization of active ingredient group compounds and the precise guidance of biomarkers, accelerate the development of innovative therapies for Alzheimer's disease, Parkinson's disease, and other diseases for laying a solid theoretical foundation for further development and application and inspiring new research ideas.
2.Comparative analyses of the detection performance of five multiplex polymerase chain reaction nucleic acid detection kits for respiratory pathogens
Fang YUAN ; Lei BI ; Jiajing LIU ; Huanru WANG ; Jun FENG ; Yuan ZHUANG ; Min CHEN ; Zheng TENG
Shanghai Journal of Preventive Medicine 2026;38(2):165-169
ObjectiveTo evaluate the detection specificity for clinical samples and the detection capability for standard substances of five commercially available multiplex polymerase chain reaction (PCR) nucleic acid detection kits (hereinafter referred to as the kits) for respiratory pathogens, and to provide a reference for selecting appropriate detection kits for multi-pathogen nucleic acid testing of respiratory infections. MethodsA total of 60 respiratory pathogen-positive clinical samples with known redults were selected and tested using the five kits (labeled as A, B, C, D, and E). The detection rates and Kappa coefficients were calculated to evaluate the consistency between the results from these kits and those from single-pathogen PCR kits. According to the limit of detection (LOD) provided by the kits, standard substances of respiratory pathogens (including 12 types such as influenza virus, Mycoplasma pneumoniae, and Bordetella pertussis) were diluted to four concentrations (250, 500, 1 000, and 2 000 copies·mL⁻¹). All five kits were used for detection to evaluate their respective detection capabilities. ResultsCompared with the results from single-pathogen PCR kits, the five tested kits demonstrated good consistency (all Kappa >0.80). Among them, Kit A had the highest detection rate (100.00%), followed by Kits C and E (98.33%), and then Kits B and D (95.00%). All five kits showed a relatively low false negative rate (FNR) for samples with a cycle threshold (Ct) value ≤35 (≤2.38%). However, for samples with Ct values>35, the FNR increased accordingly(average FNR=6.67%, P=0.029). Kit C exhibited the highest detection sensitivity for the tested standard substances (average LOD: 458.33 copies·mL⁻¹), followed by Kit D, then Kits A/E, and finally Kit B. ConclusionThe five multiplex PCR kits showed good consistency with single-pathogen detection results, but each had its own performance emphasis. Kit A, with the highest detection rate and high throughput, is suitable for targeted viral screening. Kit B, covering the broadest pathogen spectrum (including fungi/bacteria), is suitable for comprehensive respiratory pathogen screening. Kits C, D and E, are applicable for rapid detection. It is important to note that the detection efficacy of all kits decreases for low viral load samples with Ct values >35. In practical application, selection should be based on specific screening objectives, throughput requirements, and sample types.
3.Influencing factors for calcium salt deposition in patients with alveolar echinococcosis
Zitong XIONG ; Zhiyi LIN ; Yanxin HUANG ; Fuzhong FANG ; Zhengzhan WU ; Zirui XIN ; Chunxia HU ; Jiayu ZHOU ; Yuan YAO ; Hongwei ZHANG
Journal of Clinical Hepatology 2026;42(2):372-379
ObjectiveTo investigate the imaging features of calcium salt deposition and serological markers in patients with alveolar echinococcosis through a retrospective analysis, as well as independent risk factors for the degree of calcium salt deposition in lesions, and to provide a basis for assessing disease process. MethodsA retrospective analysis was performed for the imaging and clinical data of 107 patients with alveolar echinococcosis who were admitted to The First Affiliated Hospital of Shihezi University from December 2023 to June 2025, and according to the volume of calcium salt deposition, they were divided into non-deposition group with 16 patients, mild deposition group with 52 patients, moderate deposition group with 16 patients, and severe deposition group with 23 patients. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups, and the χ2 test or Fisher’s exact test was used for comparison of categorical data between groups. The four groups were further combined into the low deposition group (no/mild deposition) and the high deposition group (moderate/severe deposition). A binary logistic regression analysis was used to investigate the independent influencing factors for calcium salt deposition, and a predictive model was established. The receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model, and the Bootstrap method was used for internal validation. ResultsThere were significant differences between the four groups in sex distribution, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.05). The univariate analysis showed that there were significant differences between the four groups in sex, involvement of other sites, white blood cell count, lymphocyte percentage, fibrinogen, alanine aminotransferase, albumin, creatinine, uric acid, sodium ion, chloride ion, and calcium ion (all P<0.1). The multi-collinearity diagnosis showed that the VIF values for all continuous variables ranged from 1.104 to 1.760, suggesting that collinearity did not affect modeling. An ordinal logistic regression model was established based on sex, involvement of other sites, calcium ion, lymphocyte percentage, and uric acid. The multivariate analysis showed that lymphocyte percentage (odds ratio [OR]=1.106, 95% confidence interval [CI]: 1.041 — 1.174, P=0.001) and blood calcium level (OR=0.005, 95%CI: 0.000 —0.230, P=0.007) were independent influencing factors for the degree of calcium salt deposition. The regression equation was established as Logit(P)=8.231 + 0.100 × lymphocyte percentage -5.344 × calcium ion. The ROC curve analysis showed that the model had an area under the ROC curve of 0.716, with a Youden index of 0.353, a sensitivity of 1.000, and a specificity of 0.353. The Hosmer-Lemeshow test showed that the model had poor calibration (χ2=20.688, P=0.008). The Bootstrap method with 1000 repeated samples showed that the estimated values of lymphocyte percentage (OR=1.106, 95%CI: 1.049 — 1.186, P=0.002) and calcium ion (OR=0.005, 95%CI: 0.000 — 0.214, P=0.010) were consistent with the original model, and the confidence intervals did not include 1, which further supported the reliability of the model. ConclusionBoth lymphocyte percentage and blood calcium level are independent influencing factors for calcium salt deposition in alveolar echinococcosis, and the degree of calcium salt deposition in alveolar echinococcosis lesions increases with the reduction in blood calcium level and the increase in lymphocyte percentage.
4.Establishment and stress analysis of a finite element model for adolescent cervical disc herniation
Yuxin ZHAO ; Liang LIANG ; Feng JIN ; Yangyang XU ; Zhijie KANG ; Yuan FANG ; Yujie HE ; Xing WANG ; Haiyan WANG ; Xiaohe LI
Chinese Journal of Tissue Engineering Research 2025;29(3):448-454
BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.
5.Analysis of the evaluation mechanism and methodology of clinical comprehensive evaluation cases of drugs in China
Yuan QIAO ; Fangyi MA ; Yubei HAN ; Mingyue ZHAO ; Minghuan JIANG ; Yu FANG
China Pharmacy 2025;36(2):146-153
OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China, and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI, Wanfang Data, PubMed and Web of Science were systematically searched, and the retrieval time was from the inception to December 31st, 2023. The summary and analysis were performed from the aspects of theme selection, indicator system construction, evaluation methods, comprehensive decision-making, quality control, etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs, Chinese patent medicines, cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8, all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making, quality control, or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However, there are still issues and challenges such as incomplete evaluation methods and standards, few cases of evaluation results being converted into decision-making, and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored; when the evidence-based basis is insufficient, real-world research should be conducted as much as possible, so as to accelerate the policy transformation of evaluation results.
6.Analysis of the evaluation mechanism and methodology of clinical comprehensive evaluation cases of drugs in China
Yuan QIAO ; Fangyi MA ; Yubei HAN ; Mingyue ZHAO ; Minghuan JIANG ; Yu FANG
China Pharmacy 2025;36(2):146-153
OBJECTIVE To sort out the evaluation mechanism and methodology of published cases of comprehensive clinical evaluation of drugs in China, and provide a reference for promoting standardized comprehensive clinical evaluation of drugs and strengthening policy transformation in China. METHODS Clinical comprehensive evaluation cases of drugs published in China from CNKI, Wanfang Data, PubMed and Web of Science were systematically searched, and the retrieval time was from the inception to December 31st, 2023. The summary and analysis were performed from the aspects of theme selection, indicator system construction, evaluation methods, comprehensive decision-making, quality control, etc. RESULTS A total of 143 pieces of literature were ultimately included from 2014 to 2023. The number of publications has shown a rapid upward trend since 2019. The subjects of the evaluation cases were mainly pediatric drugs, Chinese patent medicines, cardiovascular drugs and anti-tumor drugs. The evaluation dimensions were between 3-8, all involving safety and effectiveness dimensions. Most cases adopted rapid evaluation methods based on literature review and expert interviews/questionnaire surveys with less emphasis on real-world research. Most cases did not involve comprehensive decision-making, quality control, or policy transformation. CONCLUSIONS The clinical comprehensive evaluation of drugs in China has made rapid progress under the guidance of national policies. However, there are still issues and challenges such as incomplete evaluation methods and standards, few cases of evaluation results being converted into decision-making, and a lack of quality control mechanisms. It is suggested that standardized evaluation paths and quality control mechanisms should be explored; when the evidence-based basis is insufficient, real-world research should be conducted as much as possible, so as to accelerate the policy transformation of evaluation results.
7.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
8.Relation between parental psychological control and depressive symptoms among secondary school students: the pathway of negative perfectionism and academic stress
Haiping ZENG ; Qiang ZHOU ; Yuan FANG ; Hongli NIU ; Yanzhen REN
Sichuan Mental Health 2025;38(1):71-77
BackgroundDepression is a prevalent emotional problem in adolescents, and parental psychological control is an important predictor of adolescent depression. However, existing research on the acting mechanism between the two is not adequate. ObjectiveTo explore the pathway of negative perfectionism and academic stress between parental psychological control and depressive symptoms among secondary school students, so as to provide references for reducing the incidence risk of depression in such population. MethodsFrom February to April 2023, 1 100 students across 2 middle schools and 2 high schools in Zhongshan city were selected as subjects. The survey was conducted adopting Parental Psychological Control Questionnaire, Chinese Frost Multidimensional Perfectionism Scale (CFMPS), sense of academic stress subscale in Mental Health Inventory of Middle School Student (MMHI-60) and Center for Epidemiological Studies-Depression Scale (CES-D). Spearman correlation analysis was adopted to examine the correlation between scores of all scales above, and Amos 24.0 was used to test the mediating path of negative perfectionism and academic stress between parental psychological control and depressive symptoms among secondary school students. ResultsAmong the 1 009 valid questionnaires withdrew (91.73% of the total), 261 students were detected to have depressive symptoms (25.87%). As the results of Spearman correlation analysis showed, the scores of the Parental Psychological Control Questionnaire, score of negative perfectionism dimension in CFMPS, score of sense of academic stress subscale in MMHI-60 and CES-D score were positively correlated with each other (r=0.323~0.644, P<0.05 or 0.01). The direct effect value of parental psychological control on depressive symptoms in secondary school students was 0.128 (95% CI: 0.061~0.201), accounting for 31.37% of the total effect. Negative perfectionism and academic stress played independently as intermediatory roles between parental psychological control and depressive symptoms in secondary school students, and the indirect effect values were 0.099 (95% CI: 0.068~0.133) and 0.100 (95% CI: 0.060~0.143), accounting for 24.27% and 24.51% of the total effect, respectively. Negative perfectionism and academic stress acted combinedly as the chain effect pathway between parental psychological control and depressve symptoms in secondary school students, with the indirect effect value of 0.081 (95% CI: 0.060~0.106) accounting for 19.85% of the total effect. ConclusionParental psychological control can affect the depressive symptoms among secondary school students directly, and through independent or chain paths of negative perfectionism and academic stress indirectly. [Funded by Zhongshan Social Welfare Technology Research Project (number, 2022B1060)]
9.Value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices with significant portal hypertension in compensated hepatitis B cirrhosis
Cheng LIU ; Jiayi ZENG ; Mengbing FANG ; Zhiheng CHEN ; Bei GUI ; Fengming ZHAO ; Jingkai YUAN ; Chaozhen ZHANG ; Meijie SHI ; Yubao XIE ; Xiaoling CHI ; Huanming XIAO
Journal of Clinical Hepatology 2025;41(2):263-268
ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled, and according to the presence or absence of esophageal and gastric varices under gastroscopy, they were divided into esophageal and gastric varices group (GOV group) and non-esophageal and gastric varices group (NGOV group). Related data were collected, including age, sex, imaging findings, and laboratory markers. The chi-square test was used for comparison of categorical data between groups; the least significant difference t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of five scoring models, i.e., fibrosis-4 (FIB-4), LOK index, LPRI, aspartate aminotransferase-to-platelet ratio index (APRI), and aspartate aminotransferase/alanine aminotransferase ratio (AAR). The binary logistic regression method was used to establish a combined model, and the area under the ROC curve (AUC) was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group, the GOV group had a significantly higher age (52.64±1.44 years vs 47.96±1.68 years, t=0.453, P<0.05) and significantly lower levels of alanine aminotransferase [42.00 (24.00 — 17.00) U/L vs 82.00 (46.00 — 271.00) U/L, Z=-3.065, P<0.05], aspartate aminotransferase [44.00 (32.00 — 96.00) U/L vs 62.00 (42.50 — 154.50) U/L,Z=-2.351, P<0.05], and platelet count [100.00 (69.00 — 120.00)×109/L vs 119.00 (108.50 — 140.50)×109/L, Z=-3.667, P<0.05]. The ROC curve analysis showed that FIB-4, LOK index, LPRI, and AAR used alone had an accuracy of 0.667, 0.681, 0.730, and 0.639, respectively, in the diagnosis of esophageal and gastric varices (all P<0.05), and the positive diagnostic rates of GOV were 69.97%, 65.28%, 67.33%, and 58.86%, respectively, with no significant differences in AUC values (all P>0.05), while APRI used alone had no diagnostic value (P>0.05). A combined model (LAF) was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%, with a significantly higher AUC than FIB-4, LOK index, LPRI, and AAR used alone (Z=-2.773,-2.479,-2.206, and-2.672, all P<0.05). ConclusionFIB-4, LOK index, LPRI, and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension, and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy, which provides a certain reference for clinical promotion and application.
10.Xiaoyaosan Regulates HPT Axis in Rat Model with Syndrome of Liver Depression and Spleen Deficiency via CGA/GPX2/TSHβ Pathway for Thyroid Hormone Synthesis
Fang WANG ; Ruxin YUAN ; Lingjin FAN ; Zongli CHEN ; Huaye XIAO ; Liqiang YANG ; Xiaohong LI ; Chuncheng ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):1-10
ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit (CGA)/glutathione peroxidase 2 (GPX2)/thyroid-stimulating hormone β-subunit (TSHβ) pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups: normal, model, high-dose (16.7 g·kg-1), medium-dose (8.35 g·kg-1), and low-dose (4.175 g·kg-1) Xiaoyaosan, and fluoxetine (0.001 8 g·kg-1) groups, with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension, respectively. After modeling, hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine (T3), tetraiodothyronine (T4), and thyroid-stimulating hormone (TSH) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of TSH receptor (TSHR) in the thyroid tissue, thyrotropin-releasing hormone receptor (TRHR) and TSHβ in the pituitary tissue, and thyrotropin-releasing hormone (TRH), CGA, GPX2, and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group, the model group showed significant atrophy and irregularity of thyroid follicles, a marked reduction in colloid secretion, extensive vacuolar degeneration of adenocytes in the anterior pituitary, lowered serum levels of T3, T4, and TSH (P<0.01), and down-regulated mRNA and protein levels of TSHR in the thyroid tissue, TRHR and TSHβ in the pituitary tissue, and TRH, CGA, GPX2, and TSHβ in the hypothalamic tissue (P<0.01). Compared with the model group, high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue, outperforming the low-dose Xiaoyaosan group. Moreover, they elevated the serum levels of T3, T4, and TSH (P<0.05, P<0.01). The serum TSH level was also elevated in the low-dose Xiaoyaosan group (P<0.05). The mRNA and protein levels of TSHR in the thyroid, TRHR and TSHβ in the pituitary, and TRH, CGA, GPX2, and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups (P<0.05, P<0.01). Additionally, the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group (P<0.01). In the fluoxetine group, the mRNA and protein levels of TSHR in the thyroid, TRHR in the pituitary, and TRH, CGA, and GPX2 in the hypothalamus were up-regulated (P<0.05, P<0.01). ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

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