1.Value of immunoglobulin G/immunoglobulin M ratio in predicting the prognosis of patients with initially unresectable hepatocellular carcinoma treated by transcatheter arterial chemoembolization combined with tyrosine kinase inhibitor and programmed cell death protein-1 inhibitor
Xingzhi LI ; Wei LUO ; Yuan FENG ; Yu CAI ; Xiaohong LIU ; Feixiang WU ; Yong PENG
Journal of Clinical Hepatology 2026;42(1):117-124
ObjectiveTo investigate the association between immunoglobulin G (IgG)/immunoglobulin M (IgM) ratio and prognosis in patients with initially unresectable hepatocellular carcinoma (iuHCC) receiving TTP triple therapy with transcatheter arterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein-1 (PD-1) inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, from November 2019 to December 2022, and according to IgG/IgM ratio, they were divided into high IgG/IgM group (IgG/IgM ratio >13.23) and low IgG/IgM group (IgG/IgM ratio ≤13.23). The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis, and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival (OS). ResultsThe 151 patients had a median OS of 26.7 months (95% confidence interval [CI]: 19.8-not reached) and a median progression-free survival of 12.5 months (95%CI: 10.4 — 15.8). The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group (all P>0.05). There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group (20.6 months vs not reached, P=0.016). In both the high IgG/IgM group and the low IgG/IgM group, salvage hepatectomy was significantly associated with the improvement in OS (χ2=8.297 and 10.307, both P<0.05). The multivariate analysis showed that high IgG/IgM ratio (hazard ratio [HR]=1.799, 95%CI: 1.077 — 3.006, P=0.025), baseline alpha-fetoprotein >400 ng/mL (HR=1.762, 95%CI: 1.017 — 3.050, P=0.043), and BCLC stage (HR=2.265, 95%CI: 1.212 — 4.232, P=0.010) were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy, and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.
2.Mechanism of Sangpi Zhike Prescription in Treating Cough After Respiratory Syncytial Virus Infection Based on "Lung-intestine Co-treatment" Theory
Chuang SUO ; Xiaohong BAI ; Zhitong YU ; Xue GONG ; Chan XIU ; Qihui LYU ; Zhihui LIU ; Kelin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):126-137
ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus (RSV) infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man(OMIM) databases. Protein-protein interaction (PPI) networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established: 10 as the normal group, and the remaining mice were infected with RSV via slow nasal drip of RSV suspension, with cough induced using capsaicin solution. After modeling, mice were divided into a model group, a Montelukast Sodium group (1 mg·kg-1·d-1), and low, medium, and high dose groups of Sangpi Zhike prescription (4.875,9.75,and 19.5 g·kg-1·d-1), with 10 mice per group. From day 14 after RSV infection, the normal and model groups received saline via gavage, while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated (p)-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction(Real-time PCR) detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2, p-ERK1/2, p-c-Fos protein levels, and inflammatory cytokines interleukin(IL)-4 and (TNF)-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription, with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF, Fos, and Jun. KEGG enrichment revealed 179 pathways, primarily mitogen-activated protein kinase(MAPK), cancer, TNF, and IL-17 signaling pathways. Animal experiments showed that, compared to those of the normal group, the lung tissue sections of the model group showed typical inflammatory damage, infiltration of inflammatory cells, rupture of alveolar septa, extensive alveolar fusion, and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased (P<0.01), and the expression level of ERK1/2 mRNA was significantly elevated (P<0.01). The levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α along the ERK pathway were significantly increased (P<0.05, P<0.01). Compared to the model group, Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation, decreased p-ERK1/2/ERK1/2 ratios (P<0.05,P<0.01), lower ERK1/2 mRNA levels, and downregulated ERK pathway proteins (P<0.05,P<0.01). ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2, p-MEK1/2, p-ERK1/2, p-c-Fos, IL-4, and TNF-α on ERK pathway components, thereby mitigating lung and intestinal pathological damage.
3.The mechanism and clinical characteristics in comorbidity of autoimmune liver diseases and autoimmune thyroid diseases
Yinghui RAN ; Wei LU ; Fumei YANG ; Xiaohong LI ; Rong ZHU
Journal of Clinical Hepatology 2026;42(2):432-437
Autoimmune liver diseases (AILD) are a group of chronic liver diseases caused by abnormal activation of the immune system, mainly including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, IgG4-related sclerosing cholangitis, and overlap syndrome. Clinical studies have shown that patients with AILD are often comorbid with thyroid diseases, especially autoimmune thyroid diseases (AITD), such as Graves’ disease and Hashimoto’s thyroiditis. This article systematically reviews the epidemiological association, potential shared pathogenesis, and overlapping features between AILD and thyroid diseases. A deeper understanding of the immunological links between AILD and AITD may provide a theoretical basis for precision medicine and future research.
4.Acellular dermal matrix hydrogel promotes skin wound healing in rats
Xiaohong LIU ; Tian ZHAO ; Yunping MU ; Wenjin FENG ; Cunsheng LYU ; Zhiyong ZHANG ; Zijian ZHAO ; Fanghong LI
Chinese Journal of Tissue Engineering Research 2026;30(2):395-403
BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.
5.Acellular dermal matrix hydrogel promotes skin wound healing in rats
Xiaohong LIU ; Tian ZHAO ; Yunping MU ; Wenjin FENG ; Cunsheng LYU ; Zhiyong ZHANG ; Zijian ZHAO ; Fanghong LI
Chinese Journal of Tissue Engineering Research 2026;30(2):395-403
BACKGROUND:Promoting skin wound healing is a huge challenge facing global public health.To promote faster and higher-quality wound healing,it is necessary to explore more advantageous dressings to address this problem.OBJECTIVE:To investigate the hemostatic properties of acellular dermal matrix hydrogel and its effect on skin wound healing.METHODS:(1)Acellular dermal matrix hydrogel was prepared,and the differences in microscopic morphology and main components between it and acellular dermal matrix were analyzed.(2)Acellular dermal matrix hydrogel and chitosan hydrogel were used to cover the femoral artery puncture site of rats,and the bleeding quality and coagulation time were recorded.Acellular dermal matrix hydrogel and chitosan hydrogel were mixed with rat anticoagulated blood,and the coagulation index within 30 minutes was detected.(3)A full-thickness skin defect model with a diameter of 12 mm was made on the back of 18 SD rats,and they were randomly divided into 3 groups,with 6 rats in each group:the model group used PBS to clean the wound,and the control group and the experimental group used chitosan hydrogel and acellular dermal matrix hydrogel to cover the wound,respectively.The hydrogel dressing was changed every day,and the treatment was continued for 14 days,and the wound healing was observed.On day 3 after modeling,immunofluorescence staining of inducible nitric oxide synthase(M1 macrophages)and CD206(M2 macrophages)was performed on the wound surface.On day 14 after modeling,hematoxylin-eosin staining,Masson staining,and CD31 immunohistochemical staining were performed on the wound surface.RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the acellular dermal matrix hydrogel had a porous structure,and the Fourier transform infrared spectrum showed that it had the same main components as the acellular dermal matrix.(2)Both acellular dermal matrix hydrogel and chitosan hydrogel had obvious hemostatic ability in vivo.In the in vitro coagulation experiments,the coagulation index of acellular dermal matrix hydrogel was significantly higher than that of chitosan hydrogel.(3)In the rat skin full-thickness defect model,both acellular dermal matrix hydrogel and chitosan hydrogel could improve the wound healing rate.Hematoxylin-eosin and Masson staining results showed that acellular dermal matrix hydrogel could reduce the infiltration of inflammatory cells in the center of the wound.Both acellular dermal matrix hydrogel and chitosan hydrogel could decrease scar width and increase collagen deposition rate.CD31 immunohistochemical staining results showed that both hydrogels could promote angiogenesis in the wound site.Immunofluorescence staining results showed that both hydrogels could reduce the proportion of M1 macrophages and increase the proportion of M2 macrophages,and the effect of acellular dermal matrix hydrogel was stronger than that of chitosan hydrogel.(4)The results show that the acellular dermal matrix hydrogel has good hemostatic properties and the ability to promote wound healing.
6.Application Value and Pathways of Traditional Chinese Medicine Constitution Theory in Elderly Health Management
Zhuqing LI ; Meiqing LI ; Xiaohong ZHENG
Journal of Traditional Chinese Medicine 2026;67(10):1052-1056
Traditional Chinese medicine (TCM) constitution theory, with its focus on individualized diagnosis and treatment, provides the theoretical foundation and practical pathways for the prevention and control of comorbidities in the elderly, mental health interventions, and rehabilitation for functional impairment, based on the principle of "treating different diseases with the same approach and preventing multiple diseases simultaneously". Addressing the current issues of insufficient accuracy in identifying elderly constitutions and a lack of targeted prevention and treatment strategies, this paper proposes the construction of a precision identification system characterized by data-driven, dynamic tracking, and human-machine collaboration. It also establishes a dynamic regulatory framework based on classification-based foundation, grad-based quantification, and tiered collaboration. These approaches aim to expand the application of TCM constitution theory in promoting elderly health promotion.
7.Application of frontal electroencephalogram in assessment of anxiety, depression,and sleep quality in adolescents with emotional disorders
Ying YANG ; Haiting XU ; Weigang PAN ; Xinpeng XU ; Siyuan LIU ; Xiaohong LI
Sichuan Mental Health 2026;39(2):112-118
BackgroundEmotional disorders in adolescents have emerged as a prominent issue in recent years. Current mainstream clinical assessment approaches for such conditions predominantly rely on interviews and rating scales, which are limited by inherent drawbacks such as high subjectivity and recall bias. Accordingly, there exists an urgent clinical need for the development of objective, quantifiable auxiliary diagnostic tools.In previous studies, frontal electroencephalography (EEG) has demonstrated significant value in assessing depressive and anxiety. However, the lack of standardized quantitative metrics and intuitive visual analytical approaches has severely restricted clinical interpretability of EEG data and diminished patient engagement. To address these key limitations, the present study proposes an innovative analytical framework that converts frontal EEG signals into quantifiable visual metrics to enhance clinical comprehension and acceptance. ObjectiveTo explore the value of frontal EEG in assessing anxiety, depression, and sleep quality in adolescents with emotional disorders, with the aim of providing objective auxiliary tools for clinical diagnosis and assessment of adolescents with emotional disorders. MethodsThis cross-sectional study recruited 105 adolescents aged 12-18 years who visited the outpatient department of a specialized mental hospital in Beijing from April 2023 to April 2024. All participants met the diagnostic criteria for mood (affective) disorders or anxiety disorders in the International Classification of Diseases, tenth edition (ICD-10). Frontal EEG signals were collected within a big data analytics-driven framework and further processed by EEG system to generate six quantitative cerebral function indices, namely brain load, tension and excitement, emotional stress, sleepiness index, cerebral vitality, and cerebral fatigue. In addition, validated standardized scales, including the Self-rating Anxiety Scale (SAS), the Self-rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI), were administered for anxiety, depressive symptoms, and sleep quality, respectively. ResultsIn adolescent patients with emotional disorders, the SAS score exhibited significant positive correlations with brain load (rs=0.328, P<0.01), emotional stress (rs=0.341, P<0.01), and cerebral fatigue (rs=0.286, P<0.01). The SDS score was positively correlated with brain load (rs=0.275, P<0.01), emotional stress (rs=0.241, P<0.05), and cerebral fatigue (rs=0.311, P<0.01), while showing a significant negative correlation with cerebral vitality (rs=-0.212, P<0.05). Additionally, the PSQI total score demonstrated positive correlations with brain load (rs=0.340, P<0.01), emotional stress (rs=0.322, P<0.01), and cerebral fatigue (rs=0.229, P<0.05). ConclusionFrontal EEG-derived indices, including brain load, emotional stress, cerebral fatigue and cerebral vitality, may serve as objective markers for reflecting anxiety, depression, and sleep quality in adolescents with emotional disorders. [Funded by Beijing High level Innovation and Entrepreneurship Talent Support Program (number, 202504841041); Horizontal Joint Project]
8.Evaluation of CARIFS Score and Negative Antigen Conversion Rate of Qingxuan Daozhi Formula in Treatment of Influenza in Children (Heat Accumulation in Lung and Stomach Syndrome):A Multi-center Randomized Controlled Clinical Study
Jing WANG ; Liqun WU ; Tiegang LIU ; Yongning CAO ; Jing QIU ; Jing LI ; Huaqing TAN ; Ying ZHANG ; Xulei GOU ; Jia WANG ; Jing LI ; Haipeng CHEN ; Xueying QIN ; Yuanshuo TIAN ; Yang WANG ; Chen BAI ; Zhendong WANG ; Qianqian LI ; He YU ; Xueyan MA ; Fei DONG ; Lin JIANG ; Yingqi XU ; Jianping LIU ; Xiaohong GU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):188-196
ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome). MethodsThrough a multi-center randomized controlled methodology design,confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals,such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days,and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale (CARIFS) and the incidence of complications,severe cases, and critical cases. Follow-up observation was conducted on the day of enrollment,48 hours after medication,72 hours after medication, and (6+1) d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group (90 cases) or the control group (90 cases). All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was (5.29±1.25) d,and that in the control group was (5.40±1.68) d,without a statistically significant difference. After five days of intervention,52 cases in the experimental group and 51 cases in the control group converted to negative,without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention,there were statistically significant differences between the experimental group and the control group in three dimensions, including headache,muscle soreness, and the need for extra care (P<0.05). On the (6+1) days after the intervention,the differences in both the experimental group and the control group were statistically significant in 10 dimensions, including sore throat,bad sleep,uncomfortable feeling,poor spirit and fatigue,crying more than usual,the need for extra care,symptom,function,influence on parents,and total score (P<0.05). The comparison results within the group in the dimensional scores of symptom, function, and influence on parents,as well as the CARIFS total score showed that with the delay of follow-up time,scores of both groups decreased significantly,with a statistically significant difference (P<0.01). Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention,the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up,the mean score of the experimental group was lower than that of the control group,with no statistically significant difference. In terms of the incidence of complications,severe cases, and critical cases, there were no complications,severe cases, and critical cases in the two groups,without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children (heat accumulation in the lung and stomach syndrome) are not inferior to Oseltamivir Phosphate granules, and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children (heat accumulation in the lung and stomach syndrome).
9.Association between triglyceride glucose-body mass index and new-onset metabolic dysfunction-associated fatty liver disease
Xiaohong XIANG ; Yang LI ; Bo LI ; Mei WEI ; Zhongfang ZHOU ; Suqiong HUANG
Journal of Clinical Hepatology 2026;42(4):840-847
ObjectiveTo investigate the association between serum fasting triglyceride glucose-body mass index (TyG-BMI) and new-onset metabolic dysfunction-associated fatty liver disease (MAFLD) within 10 years. MethodsA retrospective analysis was performed for the data of individuals who underwent physical examination in The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University in 2013, 2018, and 2023 and were not diagnosed with MAFLD in 2013, and a total of 1 340 valid subjects were enrolled according to the inclusion and exclusion criteria. The gbmt package in R 4.3.0 was used to construct the dynamic change trajectory model of TyG-BMI, and four different TyG-BMI trajectory groups were determined, i.e., the low-level group (n=352), the medium-level group (n=517), the high-level group (n=314), and the extremely high-level group (n=157). The data on general information and blood biochemical parameters were collected from all subjects and were then compared between groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data with heterogeneity of variance between multiple groups. The Cox regression analysis was used to investigate the association between different TyG-BMI trajectories and the risk of MAFLD, and the receiver operating characteristic (ROC) curve was used to assess the value of TyG-BMI in the diagnosis of MAFLD. ResultsThe cumulative incidence rate of MAFLD increased with the increase in the level of TyG-BMI trajectory, with a cumulative incidence rate of 4.83% in the low-level group, 29.98% in the medium-level group, 61.15% in the high-level group, and 83.44% in the extremely high-level group (P<0.001), and the cumulative incidence rate of MAFLD in men was significantly higher than that in women (51.34% vs 20.67%, P<0.001). The multivariate Cox regression analysis showed that increases in the levels of TyG-BMI trajectory, uric acid, diastolic blood pressure, hemoglobin, and alanine aminotransferase were independent risk factors for the onset of MAFLD (all P<0.05), while the increase in high-density lipoprotein cholesterol was an independent protective factor against MAFLD (P<0.001). After adjustment for confounding factors, the medium-, high-, and extremely high-level groups had a hazard ratio of 4.430 (95% confidence interval [CI]: 2.660 — 7.377, P<0.001), 6.937 (95%CI: 4.110 — 11.708, P<0.001), and 7.989 (95%CI: 4.616 — 13.827, P<0.001), respectively. The ROC curve analysis showed that TyG-BMI had the highest diagnostic value, with an area under the ROC curve of 0.859 (95%CI: 0.840 — 0.879), a sensitivity of 79.8%, and a specificity of 76.3%. ConclusionThe risk of MAFLD increases with the increase in the level of TyG-BMI trajectory, and TyG-BMI can be used as a predictive indicator for MAFLD.
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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