1.Renal Protective Mechanism of Danggui Shaoyaosan in db/db Mice Based on RhoA/ROCK/NF-κB Signaling Pathway
Luyu HOU ; Yuanyuan ZHANG ; Wenjing SHI ; Shilong GUO ; Zixuan WANG ; Linlin ZHENG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):30-38
ObjectiveTo investigate whether Danggui Shaoyaosan (DSS) inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway, thereby delaying the progression of diabetic kidney disease (DKD) and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group, and forty 8-week-old db/db mice were randomly divided into the model group, DSS low-dose group (8.39 g·kg-1), DSS medium-dose group (16.77 g·kg-1), DSS high-dose group (33.54 g·kg-1), and irbesartan group (0.025 g·kg-1), with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration, changes in body weight, fasting blood glucose (FBG), and 24 hour urinary protein (24 h UTP) were observed. After 12 consecutive weeks of administration, hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species (ROS) in renal tissue were detected using the dihydroethidium (DHE) method. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were determined. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of RhoA, ROCK1, and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of fibronectin (FN), Collagen Ⅳ(Col Ⅳ), transforming growth factor-β1 (TGF-β1), RhoA, ROCK, and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed significantly increased body weight, FBG, and 24 h UTP levels (P<0.01), elevated serum IL-1β and IL-6 levels, enlarged glomerular volume, diffuse mesangial expansion, increased mesangial matrix, and marked collagen fiber proliferation in renal tissues. SOD activity was decreased, while MDA, ROS, RhoA, ROCK1, and NF-κB p65 mRNA expression levels were increased (P<0.01), and the protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 were also elevated (P<0.01). Compared with the model group, the DSS low-, medium-, and high-dose groups and the irbesartan group showed reductions in body weight, FBG, and 24 h UTP, decreased serum IL-1β and IL-6 levels, varying degrees of improvement in renal histopathology, increased SOD activity, decreased MDA levels, reduced ROS expression, and significantly downregulated RhoA, ROCK1, and NF-κB p65 mRNA expression (P<0.05, P<0.01), as well as reduced protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 (P<0.05, P<0.01). ConclusionDSS can alleviate oxidative stress and inflammation, reduce extracellular matrix deposition, and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway, thereby exerting a therapeutic effect on DKD.
2.Molecular Mechanism of Danshen Tongluo Formula in Intervention of Coronary Artery Disease-dominated Panvascular Disease
Jiawen CHENG ; Chao LIU ; Jie WANG ; Yongmei LIU ; Wenjing LIAN ; Chengzhi HOU ; Chenyang ZHU ; Cheng MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):86-93
ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group, a model group, and a Danshen Tongluo formula (28 mg·kg-1·d-1) group. The efficacy was evaluated by examining the cardiac ultrasound, determination of the plasma level of N-terminal pro-brain natriuretic peptide, and pathological staining. After single-cell sequencing, SingleR package, public datasets, and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis, and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level (P<0.05), ameliorated myocardial cell damage and fibrosis, and increase left ventricular ejection fractions (LVEF) in the rat model of heart failure after myocardial infarction(P<0.05). Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells, venous endothelial cells, and capillary-arterial endothelial cells, while reducing the proportion of capillary-venous endothelial cells. In addition, this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells, while downregulating Mif-(CD74+CXCR44) signaling in endothelium-M1 macrophages and Mif-(CD74+CD44) signaling in endothelium-M2 macrophages. It reduced the citric acid cycle, oxidative phosphorylation, and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells, venous endothelial cells, and venous capillary endothelial cells can all regulate oxidative phosphorylation, cell adhesion molecules, and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.
3.Regulatory effect mechanism of Eucommia ulmoides on postpartum depression in rats
Yujie LI ; Wenjing CHEN ; Lan ZHANG ; Yingzhen WU ; Yongjie XU ; Xiaolan WANG ; Junlin HOU ; Liping YANG
China Pharmacy 2024;35(11):1303-1308
OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group, postpartum depression group, and low-dose and high-dose groups of E. ulmoides (1.34, 2.68 g/kg, calculated by crude drug), with 10 rats in each group. Except for the normal group, the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy; at the same time of modeling, the administration groups were given relevant medicine intragastrically, while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test, Morris water maze test and sucrose preference test. Additionally, the levels of corticosterone (CORT) in serum, corticotropin releasing factor (CRF) and urocortin (UCN) in hypothalamus, and adrenocorticotropic hormone (ACTH) in hypophysis were detected; meanwhile, the protein expressions of CRF receptor 1 (CRFR1), CRFR2, and voltage-dependent anion channel 1 (VDAC1) in hippocampal tissue were measured; the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined, and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group, the high-dose group of E. ulmoides showed improvements in appetite, mental state, and hair color in rats; their body weight had increased; the scores of vertical movement, horizontal movement and self-sorting significantly increased; from the 2ed to 4th day avoidance latency significantly shortened, and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目(No.82204789) significantly increased/prolonged (P<0.05); the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum (P<0.05); the levels of CRF, UCN, ACTH and CORT, phagocytic rate, protein expressions of CRFR2 and VDAC1, and the proportion of apoptosis cells in hippocampal tissue were decreased significantly (P<0.05); the proportion of JC-1 high potential cells significantly increased (P<0.05), and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis, decreasing the expression of CRFR2, thereby inhibiting the expression of VDAC1, and decreasing the apoptosis of neuronal cells.
4.Regulatory effect mechanism of Eucommia ulmoides on postpartum depression in rats
Yujie LI ; Wenjing CHEN ; Lan ZHANG ; Yingzhen WU ; Yongjie XU ; Xiaolan WANG ; Junlin HOU ; Liping YANG
China Pharmacy 2024;35(11):1303-1308
OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group, postpartum depression group, and low-dose and high-dose groups of E. ulmoides (1.34, 2.68 g/kg, calculated by crude drug), with 10 rats in each group. Except for the normal group, the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy; at the same time of modeling, the administration groups were given relevant medicine intragastrically, while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test, Morris water maze test and sucrose preference test. Additionally, the levels of corticosterone (CORT) in serum, corticotropin releasing factor (CRF) and urocortin (UCN) in hypothalamus, and adrenocorticotropic hormone (ACTH) in hypophysis were detected; meanwhile, the protein expressions of CRF receptor 1 (CRFR1), CRFR2, and voltage-dependent anion channel 1 (VDAC1) in hippocampal tissue were measured; the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined, and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group, the high-dose group of E. ulmoides showed improvements in appetite, mental state, and hair color in rats; their body weight had increased; the scores of vertical movement, horizontal movement and self-sorting significantly increased; from the 2ed to 4th day avoidance latency significantly shortened, and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目(No.82204789) significantly increased/prolonged (P<0.05); the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum (P<0.05); the levels of CRF, UCN, ACTH and CORT, phagocytic rate, protein expressions of CRFR2 and VDAC1, and the proportion of apoptosis cells in hippocampal tissue were decreased significantly (P<0.05); the proportion of JC-1 high potential cells significantly increased (P<0.05), and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis, decreasing the expression of CRFR2, thereby inhibiting the expression of VDAC1, and decreasing the apoptosis of neuronal cells.
5.Analysis of goitrogenic effect of goitrogen in food
Haowen PAN ; Honglei XIE ; Xin HOU ; Meng ZHAO ; Wenjing CHE ; Jia LI ; Yue SU ; Lanchun LIU ; Zexu ZHANG ; Zongyu YUE ; Peng LIU
Chinese Journal of Endemiology 2024;43(1):77-81
Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.
6.Research progress on the relationship between blood pressure variability and cognitive impairment
Along HOU ; Wenbin CHENG ; Wenjing SUN ; Xiaohan CHEN ; Genru LI ; Jianhua ZHUANG ; You YIN
Chinese Journal of Clinical Medicine 2024;31(4):659-667
Cognitive impairment is a kind of senile disease that leads to the decline of personality and behavior ability of the elderly,which seriously affects the quality of daily life of patients.The prevalence rate of the disease increases year by year with the acceleration of the aging process of the society,and its incidence is affected by many risk factors.At this stage,the curative effect for middle and advanced patients is poor.So early identification and intervention to delay the progression of cognitive impairment have become the focus of relevant research.Blood pressure variability can lead to damage of target organs such as heart,brain tissue and kidney,which is closely related to cognitive impairment.In order to expand a new perspective of early intervention in cognitive impairment,this paper reviews the effects of blood pressure variability on different cognitive impairment and its possible pathogenic mechanism.
7.Formulation and Analysis on the Standard of Construction of Medication Safety Culture
Wenjing HOU ; Su SHEN ; Aiping WEN ; Jin LU ; Jiancun ZHEN ; Wei ZHANG ; Dan MEI ; Zhicheng GONG ; Yubo WU ; Qunhong SHEN ; Weiyi FENG ; Ling TAN ; Yanhua ZHANG ; Fang LIU ; Xiaole ZHANG
Herald of Medicine 2024;43(7):1079-1083
The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.
8.Research Progress in Environment-responsive Nano-drug Delivery System Based on Traditional Chinese Medicine Monomer in Tumor Therapy
Chunyan LYU ; Rui HAN ; Wenyu CUI ; Wenqian WANG ; Xiaoqing HOU ; Wenjing XIN ; Wenjun ZHANG
Herald of Medicine 2024;43(11):1799-1804
Traditional Chinese medicine monomer has certain curative effects in tumor treatment,but its low targeting and difficulty in gathering at the tumor site limit its application.As a new type of drug delivery method,environmentally responsive nano drug delivery system has the advantages of targeted drug delivery,reducing drug side effects,and environmentally responsive release,and has been widely used in tumor treatment.In this paper,by consulting and sorting out the relevant literature,the general situation of traditional Chinese medicine monomers in the treatment of tumors,the classification of environment-responsive traditional Chinese medicine monomer nano drug delivery system,and its application in tumor treatment are summarized in three aspects,to provide ideas for solving the limitations of traditional Chinese medicine monomer in the treatment of tumor.
9.The diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system in adult goiter
Zexu ZHANG ; Zongyu YUE ; Honglei XIE ; Yue SU ; Haowen PAN ; Jia LI ; Wenjing CHE ; Xin HOU ; Meng ZHAO ; Lanchun LIU ; Dandan LI ; Xian XU ; Weidong LI ; Fangang MENG ; Lijun FAN ; Lixiang LIU ; Ming LI ; Peng LIU
Chinese Journal of Endemiology 2024;43(11):922-927
Objective:To study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.
10.Application of qualitative and quantitative analysis of contrast-enhanced ultrasound in the differential diagnosis of pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma
Lihui ZHAO ; Wenjing HOU ; Jing ZHAO ; Jie MU ; Yiran MAO ; Hailing WANG ; Song GAO ; Jian WANG ; Tiansuo ZHAO ; Xi WEI
Chinese Journal of Ultrasonography 2024;33(10):855-861
Objective:To explore the application value of qualitative characteristics and quantitative parameters of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) and non-PDAC presenting as pancreatic solid focal lesions.Methods:A retrospective analysis was conducted on 64 cases of PDAC(the PDAC group) and 52 cases of non-PDAC(the non-PDAC group) who underwent CEUS examination at Tianjin Medical University Cancer Institute and Hospital from July 2022 to June 2023. Clinical characteristics, two-dimensional ultrasound features, CEUS qualitative characteristic, and quantitative parameters were compared between the two groups. ROC curves were plotted, and the Delong test was used to evaluate the diagnostic performance of qualitative and quantitative analyses in distinguishing PDAC from non-PDAC. Binary logistic regression analysis was employed to assess the independent predictors of PDAC.Results:①There were significant differences in serum CA19-9, lesion size, boundary, the main pancreatic duct (MPD) diameter, degree of enhancement and enhancement pattern between the PDAC group and the non-PDAC group (all P<0.05). ②The relative peak intensity (rPE), and relative wash-in and wash-out area under the curve (rWiWoAUC) were lower in the PDAC group than the non-PDAC group, with statistically significant differences(all P<0.001). ③The areas under the curve (AUC) for diagnosing PDAC using enhancement pattern, venous phase(VP) enhancement degree, rPE, and rWiWoAUC were 0.698, 0.707, 0.863, and 0.867, respectively. The AUCs of quantitative parameters were superior to those of qualitative characteristics, with statistically significant differences ( P<0.05). Using CEUS mode B, low VP enhancement, rPE<72.44, and rWiWoAUC<86.59 as cut-off values, the accuracies for diagnosing PDAC were 0.698, 0.741, 0.828, and 0.802, respectively. ④Serum CA19-9, lesion size, MPD diameter, rPE, and rWiWoAUC were independent predictors of PDAC (all P<0.05). Conclusions:CEUS qualitative and quantitative analyses are helpful in the differential diagnosis of PDAC and non-PDAC, with rPE and rWiWoAUC being useful indicators for diagnosing PDAC.

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