1.Exploring Mechanism of Anti-atherosclerosis Effect of Huangqi Chifengtang Based on AMPK/PPARα Signaling Pathway and NLRP3 Inflammasome
Yuqin LIANG ; Jie LIU ; Chi ZHANG ; Pingping CHEN ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):131-139
ObjectiveTo explore the improving effect of Huangqi Chifengtang(HCT) on atherosclerosis(AS), and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor α(PPARα) signaling pathway and nucleotide-binding oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome. MethodsEight C57BL/6J mice were set as the normal group, and 32 ApoE-/- mice were randomly divided into the model group, the positive drug group(atorvastatin, 5 mg·kg-1·d-1), HCT low- and high-dose groups(1.95, 3.90 g·kg-1·d-1). ApoE-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling, they were orally administered corresponding dose of drugs for 28 days, while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin(HE) staining was used to observe the pathological status of the aorta and liver in mice, Biochemical testing and enzyme-linked immunosorbent assay(ELISA) were used to detect the levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), C-reactive protein(CRP), interleukin(IL)-1β, IL-18 in the serum, as well as superoxide dismutase(SOD), malondialdehyde(MDA), and reduced glutathione(GSH) in the liver. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to measure the mRNA expression levels of NLRP3, apoptosis-associated speck-like protein(ASC), cysteinyl aspartate specific proteinase-1(Caspase-1), Toll-like receptor 4(TLR4) in the aorta, and fatty acid synthase(FAS), stearoyl-CoA desaturase 1(SCD1), PPARα, and carnitine palmitoyltransferase 1A(CPT1A) in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3, Caspase-1, and ASC in the aorta, and Western blot was used to measure the protein expressions of AMPK, p-AMPK, sterol regulatory element binding protein-1c(SREBP-1c), CPT1A, and FAS in the liver. ResultsCompared with the normal group, the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver, the levels of TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum were significantly increased(P<0.01), and the mRNA and protein expressions of aortic TLR4, NLRP3, Caspase-1 and ASC were significantly upregulated(P<0.01). The levels of SOD and GSH in the liver were significantly reduced, while the level of MDA was significantly increased(P<0.01). The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated, while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced, while the expressions of SREBP-1c and FAS proteins were significantly increased(P<0.01). Compared with the model group, the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC, LDL-C, AST, IL-1β and IL-18 in the serum of the low-dose HCT group, as well as TC, TG, LDL-C, AST, ALT, IL-1β, IL-18 and CRP in the serum of the high-dose HCT group, were significantly reduced(P<0.01). The mRNA expressions of TLR4, NLRP3 and Caspase-1 in the aorta of the low-dose HCT group, as well as TLR4, NLRP3, Caspase-1 and ASC in the aorta of the high-dose HCT group, were significantly downregulated(P<0.01). The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group, as well as NLRP3, Caspase-1 and ASC in the high-dose HCT group, were significantly downregulated(P<0.01). The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased, while the level of MDA in the high-dose HCT group was significantly decreased(P<0.05, P<0.01). In the HCT-treated group, the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated, while the mRNA expressions of PPARα and CPT1A were significantly downregulated, the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased, while the protein expressions of SREBP-1c and FAS were significantly decreased(P<0.05, P<0.01). ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses, thereby reducing hepatic lipid deposition and AS plaque formation.
2.Advances in the JAK2/STAT3 signaling pathway and its inhibitors in diffuse large B cell lymphoma
Chuanyang LU ; Qiuni CHEN ; Yuye SHI ; Yuan DENG ; Tingting JI ; Zhengyuan LIU ; Chunling WANG ; Liang YU
China Pharmacy 2026;37(5):682-688
Abnormal activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). In recent years, inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors (e.g., ruxolitinib) and STAT3 inhibitors (direct small-molecule inhibitors, the antisense oligonucleotide, and proteolysis targeting chimeras, etc.) in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile, the development of novel drug delivery systems has significantly enhanced the stability, bioavailability, and targeting ability of the compounds. Furthermore, JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies (such as combinations with B-cell receptor signaling pathway inhibitors, immunomodulators, or other targeted drugs). However, current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL, and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.
3.Relationship between family functioning and non-suicidal self-injury behaviors in adolescents with depressive disorders
Tongxing MA ; Zilong SONG ; Yingyi CHEN ; Xinzhu ZHENG ; Junsong LIANG ; Liping LIU
Sichuan Mental Health 2026;39(1):14-20
BackgroundFamily functioning is one of the factors influencing non-suicidal self-injury (NSSI) behaviors in adolescents with depressive disorders. Previous studies have treated family functioning as a unitary construct, which may obscure the differential impacts of specific dimensions on NSSI behaviors. ObjectiveTo explore the relationships between various dimensions of family functioning and NSSI behaviors in adolescents with depressive disorders, aiming to provide precise targets for family-based interventions for adolescents with depressive disorders who exhibit NSSI behaviors. MethodsIn this cross-sectional study, 217 adolescent patients who were treated at the outpatient or inpatient department of The First Psychiatric Hospital of Harbin from January to July 2025 and met the diagnostic criteria for depressive disorders as stipulated in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were included as the research subjects. Assessments included a self-designed questionnaire, the Hamilton Depression Scale-17 item (HAMD-17), and the Family Assessment Device (FAD). Univariate Logistic regression analysis was employed to investigate the association between each dimension of family functioning and the NSSI behaviors, and multivariate Logistic regression was used to test the independent effect of each dimension of family functioning on the NSSI behaviors. ResultsA total of 204 cases (94.01%) of adolescent patients with depressive disorders completed the valid questionnaire survey. Among them, 134 cases (65.69%) exhibited NSSI behaviors (NSSI group), and 70 cases (34.31%) did not exhibit NSSI behaviors (non-NSSI group). Compared with the non-NSSI group, the NSSI group had a higher HAMD-17 score [(20.97±7.50) vs. (17.79±6.95), t=8.705, P=0.004], a higher FAD total score [(155.68±21.84) vs. (148.87±22.72), t=4.348, P=0.038], and a higher problem-solving dimension score [(2.54±0.49) vs. (2.34±0.51), t=7.399, P=0.007]. All the differences were statistically significant. The results of the Logistic regression analysis showed that the FAD total score (OR=1.014, 95% CI: 1.001–1.028, P=0.041) and the problem-solving dimension score (OR=2.241, 95% CI: 1.228–4.090, P=0.009) were both risk factors for NSSI behaviors. After adjusting for gender, age, residence, educational level, monthly family income, and whether being an only child, the correlation between the FAD total score and NSSI behaviors was not statistically significant (OR=1.010, 95% CI: 0.995–1.025, P=0.185), while the correlation between the FAD problem-solving dimension score and NSSI behaviors remained statistically significant (OR=2.000, 95% CI: 1.028–3.889, P=0.041). ConclusionImpaired problem-solving capacity within family functioning may constitute a risk factor for NSSI behaviors in adolescents with depressive disorders. [Funded by Research Project of Heilongjiang Provincial Health Commission (number, 20240303090148, 20230303090154)]
4.Relationship between non-suicidal self-injury behaviors, impulsivity, and emotional regulation in adolescents with depressive disorder
Mingfei ZHANG ; Xinyu CHEN ; Fang LIANG ; Zhe CHEN ; Lu QIAN ; Zhijia LI
Sichuan Mental Health 2026;39(1):21-26
BackgroundAdolescents with depressive disorder often engage in non-suicidal self-injury (NSSI) behaviors, which severely impacts their physical and mental health. Impulsivity and emotional regulation are key factors influencing NSSI behaviors. However, research on the mechanisms through which impulsivity and emotional regulation affect NSSI behaviors in adolescent depressive disorder patients with NSSI remains insufficient, limiting the development of effective intervention strategies. ObjectiveTo explore the differences in impulsivity and emotion regulation abilities between adolescent patients with depressive disorder accompanied by and without NSSI behaviors, and to analyze the association between NSSI behaviors and impulsivity and emotion regulation abilities in adolescent patients with depressive disorder accompanied by NSSI behaviors. MethodsA total of 184 adolescents hospitalized in the child and adolescent psychiatry department of Wuxi Mental Health Center from October 2023 to August 2024, who met the diagnostic criteria for depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), were consecutively enrolled as study subjects. Based on the diagnostic criteria for NSSI in DSM-5, patients were divided into NSSI group (n=108) and non-NSSI group (n=76). The Barratt Impulsiveness Scale-11 (BIS-11), the Emotion Regulation Questionnaire (ERQ), the Adolescent Self-Harm Questionnaire, and the Positive and Negative Suicide Ideation (PANSI) were used for assessment. Spearman correlation analysis was employed to explore the correlation between the scores of the Adolescent Self-Harm Questionnaire and the scores of BIS-11 and ERQ in the NSSI group. Multiple regression analysis was conducted to examine the effects of impulsivity and emotion regulation on NSSI behaviors in the NSSI group. ResultsCompared to the non-NSSI group, the NSSI group showed significantly higher scores in BIS-11 non-planned impulsivity (Z=-4.181, P<0.05), action impulsivity (t=4.944, P<0.05), cognitive impulsivity (Z=-3.392, P<0.05), and total score (t=4.763, P<0.05), and lower scores in the cognitive reappraisal of ERQ (t=-4.094, P<0.05) and total score (Z=-2.299, P<0.05), and higher scores in the expression inhibition of ERQ (Z=-3.019, P<0.05). The correlation analysis results showed that the score of the adolescent self-harm questionnaire in the NSSI group was positively correlated with the behavioral impulsivity factor score in the BIS-11 (r=0.434, P<0.05). Multiple regression analysis indicated that action impulsivity factor was a significant correlate of self-injury behaviors in the NSSI group (B=0.855, P<0.05), explaining 22.30% of the total variance. ConclusionAdolescent patients with depressive disorder accompanied by NSSI behaviors exhibit higher levels of impulsivity and poorer emotional regulation abilities. Action impulsivity may play a significant role in the mechanism of NSSI behaviors. [Funded by Wuxi Municipal Health Commission Research Project (number, Q202320)]
5.Preoperative evaluation of lung function in patients with lung cancer using two-phase dual-energy CT perfusion imaging
Lifang LING ; Yizhen JIA ; Qinmin HAO ; Wenzheng XU ; Zhibo WANG ; Jun WANG ; Liang CHEN ; Mei YUAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):79-86
Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P<0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.
6.The effect of body mass index and inferior pulmonary ligament division on the residual lung expansion after right upper lobectomy: A retrospective cohort study in a single center
Guang MU ; Wenhao ZHANG ; Hongchang WANG ; Yan GU ; Chenghao FU ; Wentao XUE ; Shiyuan XIE ; Tong WANG ; Ke WEI ; Yang XIA ; Liang CHEN ; Jun WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):261-266
Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2<BMI≤23 kg/m2), a group B (23 kg/m2<BMI≤29 kg/m2) and a group C (BMI>29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.
7.Association between random urine electrolytes and hypertension in children and adolescents
Chinese Journal of School Health 2026;47(3):314-318
Objective:
To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions.
Methods:
In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension.
Results:
At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ).
Conclusion
The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.
8.Analysis of knowledge awareness and associated factors of chikungunya fever among medical college students in Baise City
Chinese Journal of School Health 2026;47(3):347-350
Objective:
To understand the awareness of chikungunya fever knowledge and its related factors among medical college students in Baise City, so as to provide a scientific basis to offer relevant courses and special education.
Methods:
From July to August 2025, 7 286 enrolled medical students were selected by a sampling method from a medical college in Baise City to participate in the questionnaire survey. The questionnaire covered epidemiological characteristics, clinical symptoms, and prevention/control knowledge of chikungunya fever. Statistical analyses including the Chi quare test and multivariate Logistic regression models were performed.
Results:
The overall awareness rate of chikungunya fever knowledge among the medical students was 18.89%. Among the knowledge items, the awareness rate of "the high incidence season" was the highest (84.05%), while that of "the infectious period" was the lowest (17.80%). Multivariate Logistic regression analysis showed that medical students with female (a OR= 1.37 , 95%CI =1.20- 1.57 ), the age for over 25 years old (a OR=1.76, 95%CI =1.05-2.93), whose father had a middle school educational level (a OR=1.18, 95%CI =1.05-1.31), and majored in preventive medicine (a OR=1.54, 95%CI =1.10-1.67) had relatively higher awareness rates of chikungunya fever knowledge (all P <0.05). In contrast, students of Zhuang ethnicity (a OR= 0.87 , 95%CI =0.76-0.98) and majoring in nursing (a OR=0.74, 95%CI =0.61-0.91) or pharmacy (a OR=0.70, 95%CI =0.52-0.95) had relatively lower awareness rates (all P <0.05).
Conclusions
The awareness rate of chikungunya fever related knowledge among medical college students in Baise City is relatively low. Schools should take targeted publicity measures to improve medical students awareness.
9.Relationship of non-suicidal self-injury behavior with serum lipid levels and thyroid function among college students with depression
CHEN Lu, YANG Zhiqiang, CAO Xiaoping, ZHAO Yanxia, LIANG Shaoying, LUO Yi, LI Hongyu
Chinese Journal of School Health 2026;47(3):394-397
Objective:
To explore the relationship between non suicidal self injury (NSSI) behavior and serum lipid levels as well as thyroid function among college students with depression.
Methods:
A total of 169 college students with depression in the psychiatry departments of tertiary hospitals (grade 3A and 3B) in Ningbo from December 2023 to April 2025 were selected. The Adolescent Self injury Scale (ASIS) was used to assess the presence of NSSI, and participants were accordingly divided into a NSSI group ( n =51) and a non NSSI group ( n =118). General demographic data (including gender, age, and family situation) were collected from both groups. Blood tests were performed to measure lipid profiles [triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C)] and thyroid hormones [triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH)]. Multivariate Logistic regression was employed to analyze risk factors for NSSI, and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of serum lipid and thyroid hormone levels for NSSI occurrence in college students with depression.
Results:
The levels of TC, LDL-C, and TSH in the NSSI group were (4.02±0.73) mmol/L, (2.32±0.36) mmol/L, and (6.57±1.95) mU/L , which were significantly higher than those in the non NSSI group [(3.41±0.56) mmol/L, (2.00±0.27) mmol/L, and ( 4.48± 1.09) mU/L, respectively] ( t =5.32, 5.60, 7.20, all P <0.05). Logistic regression analysis revealed that college students from single parent/reconstituted families, those who had experienced school bullying, and those with higher levels of TC, LDL-C, and TSH had a significantly increased risk of engaging in NSSI ( OR =5.22, 6.12, 5.90, 83.64, 3.64, all P <0.05). ROC curve analysis demonstrated that the combined detection of TC, LDL-C, and TSH had high diagnostic efficacy for predicting NSSI in college students with depression, with a sensitivity of 86.3% and a specificity of 94.9%.
Conclusions
NSSI behavior in college students with depression is associated with serum lipid levels and thyroid function. These biomarkers may serve as useful reference indicators for assessing the conditions of these patients.
10.Therapeutic effect and mechanism of modified Chaihu Shugan Powder on a mouse model of gallbladder cholesterol stone with liver depression syndrome
Zhaoyan LI ; Heying WANG ; Renjie LIANG ; Yichun WANG ; Huiping CHEN ; Li MIN
Journal of Clinical Hepatology 2026;42(2):387-399
ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone (CS) with liver depression syndrome, and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress (CUMS) to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group (6 mice fed a normal diet) and CS group (39 mice fed a high-fat lithogenic diet). After CS modeling, the CS group was further randomly divided into four subgroups of CS group, CS liver depression group, traditional Chinese medicine group (treated with modified Chaihu Shugan Powder), and Western medicine group (treated with ursodeoxycholic acid), with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet, and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin (CCK), liver function parameters, and blood lipid profiles were measured; HE staining was performed for liver and gallbladder tissue; qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 (TGR5) and glucagon-likepeptide-1/2 (GLP-1/2) in the intestine and TGR5 and glucagon-like peptide-2 receptor (GLP-2R) in gallbladder; metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group, the CS group showed significant gallstone formation, bile turbidity, hepatic steatosis, abnormal gallbladder wall structure, and significant increases in anxiety- and depression-like behaviors based on behavioral tests; significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase, aspartate aminotransferase, and low-density lipoprotein and significant reductions in the level of total bile acid (TBA) in bile and the serum levels of CCK and high-density lipoprotein (HDL) (all P<0.05); significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder (all P<0.05); significant changes in multiple bile acid components in intestinal contents (all P<0.05). Compared with the CS group, the CS liver depression group had further aggravation of pathological and behavioral manifestations, changes in bile acid composition, significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine, and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder (all P<0.01). Compared with the CS liver depression group, both treatment groups had an improvement in gallbladder morphology, alleviation of stones and liver injury, and recovery of liver function and blood lipid levels, as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder (all P<0.05); the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid (GDCA), tauro-α-muricholic acid (T-α-MCA), and taurochenodeoxycholic acid (TCDCA) (all P<0.05), while the Western medicine group showed significant increases in taurohyodeoxycholic acid, T-α-MCA, TCDCA, GDCA, and glycoursodeoxycholic acid (all P<0.05). Compared with the Western medicine group, the traditional Chinese medicine group had significantly greater behavioral improvements, significantly higher levels of TBA in bile and serum HDL (both P<0.01), significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder, and a significant reduction in the mRNA expression level of TGR5 in the intestine (all P<0.01), as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid, taurohyodeoxycholic acid, TCDCA, and taurolithocholic acid (all P<0.05). ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis, thereby exerting the therapeutic effect of soothing the liver, resolving depression, moving Qi, and promoting bile flow.


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