1.Effect of Yifei Jianpi Prescription on Lipopolysaccharide-induced Lung Immune Inflammatory Response in Rats Based on STAT1/IRF3 Pathway
Hongjuan YANG ; Yaru YANG ; Yujie YANG ; Zhongbo ZHU ; Quan MA ; Yanlin WU ; Hongmei LI ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):146-155
ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 (STAT1)/interferon regulatory factor 3 (IRF3) signaling pathway in a pneumonia model induced by lipopolysaccharide (LPS) and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group, and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling, the rats were randomly divided into the model group, dexamethasone group (0.5 mg·kg-1), and Yifei Jianpi prescription high-dose (12 mg·kg-1), medium-dose (6 mg·kg-1), and low-dose (3 mg·kg-1) groups, with 10 rats in each group. Treatment was administered once daily, and the normal control and model groups received the same volume of normal saline. After 14 days, flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and the content of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-10 (IL-10) in alveolar lavage fluid (BALF). Hematoxylin-eosin (HE) staining was used to observe lung tissue pathology and score the damage. Thymus weight, spleen weight, and wet-to-dry weight ratio (W/D) were recorded. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of STAT1, IRF3, IL-6, and interferon-alpha (IFN-α) in lung tissues, while Western blot was performed to assess the protein expression of STAT1, IRF3, IL-6, and IFN-α. ResultsCompared with the normal control group, the model group showed significantly increased proportion of B lymphocytes in peripheral blood, decreased proportions of NK cells and CD4+/CD8+ (P<0.05, P<0.01), decreased serum levels of IgG and IgA, significantly increased IgM levels (P<0.01), significantly elevated content of TNF-α, IL-6, and IL-8 in BALF, and significantly decreased IL-10 levels (P<0.01). Lung tissue damage was evident, with significant increases in thymus and spleen weights and a higher W/D ratio (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly upregulated (P<0.05,P<0.01). Compared with the model group, the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood, increased proportions of NK cells and CD4+/CD8+ ratios (P<0.05, P<0.01), significantly increased serum levels of IgG and IgA, significantly decreased IgM levels (P<0.05, P<0.01), significantly reduced levels of TNF-α, IL-6, and IL-8 in BALF, and significantly increased IL-10 levels (P<0.01). Lung tissue damage was alleviated, thymus and spleen weights were significantly reduced, and the W/D ratio was markedly decreased (P<0.01). The mRNA and protein expression of STAT1, IRF3, IFN-α, and IL-6 in lung tissues was significantly downregulated (P<0.05, P<0.01). ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.
2.Effects of Lumbricus Protein on Phenotypic Transformation of Corporal Cavernous Smooth Muscle Cells and Erectile Dysfunction in Rats with Diabetic Erectile Dysfunction
Xiaowei JI ; Aiping ZHANG ; Liming LIU ; Jiashu YANG ; Xiping XING
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):325-333
Objective To investigate the effect of Lumbricus protein on the phenotypic transformation of corporal cavernosum smooth muscle cells(CCSMC)and erectile function in diabetic erectile dysfunction(DMED)rats.Methods Sixty male SD rats with normal erectile function were randomly divided into a blank group,a model group,a Sildelafil group(5 mg·kg-1),and a Lumbricus protein low-,medium-,and high-dose group(45,90,and 180 mg·kg-1),with 10 rats in each group.The diabetic rat model was established by intraperitoneal injection of Streptozotocin(STZ,50 mg·kg-1)combined with high-fat feed feeding;after 8 weeks,the DMED rat model was prepared by neck injection of Apomorphine(APO,100 μg·kg-1).After successful modeling,the rats were administered with a dose of Apomorphine by gavage once a day for 4 weeks.The blood glucose levels and body mass of rats in each group were measured before modeling,on the third day of modeling,and after 4 weeks of drug administration.The intracavernous pressure(ICP)and carotid artery pressure(MAP)were measured by multi-channel physiological recorder,and the ICP/MAP ratio was calculated.The expressions of contractile markers α-smooth muscle actin(α-SMA),smooth muscle myosin heavy chain(SMMHC)and synthetic markers Collagen I and osteopontin(OPN)in corpus cavernosum were detected by immunohistochemistry.The mRNA expression levels of α-SMA,SMMHC and Collagen I in corpus cavernosum were detected by RT-PCR.The protein expression levels of α-SMA,Desmin,Collagen I and OPN in corpus cavernosum were detected by Western Blot.Results Compared with the blank group,the blood glucose levels of the rats in the model group were significantly increased on the third day of modeling and after 4 weeks of administration(P<0.01),and the body mass was significantly decreased after 4 weeks of administration(P<0.01).ICP and ICP/MAP ratio were significantly decreased(P<0.01).The protein expression levels of α-SMA,SMMHC and Desmin in penile corpus cavernosum were significantly decreased(P<0.01),and the protein expression levels of Collagen I and OPN were significantly increased(P<0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly decreased(P<0.01),and the mRNA expression level of Collagen I was significantly increased(P<0.01).Compared with the model group,there was no significant change in blood glucose and body mass of rats in the administration group(P>0.05).ICP and ICP/MAP ratio were significantly increased(P<0.01).The expression levels of α-SMA,SMMHC and Desmin in corpus cavernosum were significantly increased(P<0.01),while the expression levels of Collagen I and OPN were significantly decreased(P<0.01).The mRNA expression levels of α-SMA and SMMHC in corpus cavernosum were significantly increased(P<0.01),and the mRNA expression level of Collagen I was significantly decreased(P<0.01).Conclusion Lumbricus protein can improve the erectile function of DMED rats,and its mechanism may be related to the inhibition of CCSMC from'contractile'to'synthetic(proliferative)'transformation.
3.Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms
Zhixian REN ; Beixian ZHOU ; Linxin WANG ; Jing LI ; Rongping ZHANG ; Xiping PAN
Journal of Southern Medical University 2024;44(6):1070-1078
Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.
4.Exploration on the TCM Pathogenesis of Pulmonary Fibrosis Based on the Theory of"Lung Connecting to Large Intestine"
Yawei DONG ; Zhongbo ZHU ; Fan YANG ; Quan MA ; Hongmei LI ; Yanmei ZHANG ; Lanlan HE ; Xuhui ZHANG ; Xiping LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):19-23
Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".
5.Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms
Zhixian REN ; Beixian ZHOU ; Linxin WANG ; Jing LI ; Rongping ZHANG ; Xiping PAN
Journal of Southern Medical University 2024;44(6):1070-1078
Objective To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone(5-HDF),a compound extracted from Elsholtzia blanda Benth.,against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action.Methods 5-HDF was extracted from Elsholtzia blanda Benth.using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses.In an A549 cell model of H1N1 influenza virus infection(MOI=0.1),the cytotoxicity of 5-HDF was assessed using MTT assay,and its effect on TRAIL and IL-8 expressions was examined using flow cytometry;Western blotting was used to detect the expression levels of inflammatory,apoptosis,and ferroptosis-related proteins.In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 μL H1N1 virus at the median lethal dose,the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight,lung index,gross lung anatomy and lung histopathology were observed.Results 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 μg/mL.In H1N1-infected A549 cells,treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65,lowered the expressions of IL-8,enhanced the expression of anti-ferroptosis proteins(SLC7A11 and GPX4),and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL.In H1N1-infected mice,treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies.Conclusion 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis,inflammatory responses,and apoptosis via upregulating SLC7A11 and GPX4,inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK,and decreasing the expression of cleaved caspase3 and cleaved PARP.
6.Effects of acute lung injury on apoptosis in rat splenic T cells and the interventional effect of Yifei Jianpi formula
Yujie YANG ; Zhongbo ZHU ; Yanmei ZHANG ; Xiping LIU ; Xuhui ZHANG ; Zhiming ZHANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(9):1160-1170
Objective To observe splenic T cell apoptosis and XIAP-associated factor 1(XAF1),FAS,and tumor necrosis factor(TNF)-α protein expression levels in rats with acute lung injury(ALI),and to determine their roles in the protective effect of Yifei Jianpi formula.Methods Sixty male specific pathogen-free SD rats were divided randomly into blank,model,positive control,and high-,medium-,and low-dose Yifei Jianpi formula groups.Rats in the positive control group were given 0.5 g/kg dexamethasone by gavage,and rats in the high-,medium-,and low-dose Yifei Jianpi formula groups were given 12,6,and 3 g/kg Yifei Jianpi formula by gavage,respectively.Rats in the model and blank groups were given equal amounts of saline by gavage.All medications were administered once a day for 14 days.Lung function testing was carried out in all rats.We observed the imaging characteristics of the lungs and changes in the organ index and lung tissue wet/dry weight(W/D)in each group,and detected the pathological changes in lung tissues by hematoxylin-eosin staining.Splenic T-cell subpopulations(CD4+/CD8+)and apoptosis of splenic T-cells were detected by flow cytometry and XAF1,FAS,and TNF-α protein expression levels in the spleen were detected by Western Blot.Results Rats in the model group showed reduced lung function,decreased spleen and thymus organ indexes,and significantly higher W/D of lung tissue(P<0.01).In addition,they had inflammatory exudation and alveolar rupture in the lung tissue,accompanied by thickening of the lung texture and large areas of ground-glass shadows,with a significant decrease in T-cell subsets(CD4+/CD8+)and significant increases in XAF1,FAS,and TNF-α proteins,and in the rate of T-cell apoptosis(P<0.01).Yifei Jianpi formula significantly reduced the W/D spleen of rat lung tissues,significantly increased the thymus organ index(P<0.05,P<0.01)and the T-cell subpopulation(CD4+/CD8+),and significantly decreased the protein expression levels of XAF1,FAS,and TNF-α,and the T-cell apoptosis rate(P<0.05,P<0.01).Conclusions ALI induced up-regulation of XAF1,FAS,and TNF-α protein expression and T-cell apoptosis in the spleen of rats,and Yifei Jianpi formula may protect against ALI by down-regulating these factors.
7.The epidemiological features and relational factors of accidental death among children under 5 years of age in rural Shaanxi Province
Xue YANG ; Baozhu WANG ; Lu GAN ; Min LI ; Xiping YU ; Juan ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):489-492
【Objective】 To explore the epidemiological features and relational factors of accidental death among children under 5 years of age in rural area of Shaanxi Province. 【Methods】 A case-control study was conducted in the research, and children under 5 years old in nine National surveillance counties of Shaanxi were collected. The questionnaire of national survey of accidental injuries among children under 5 years of age was used to investigate the basic information of children, socio-demographic characteristics, child care status, injury occurrence condition. The mean, standard deviation and percentage were used to describe the basic situation and main characteristics of accidental death. The Chi-square test and Logistic regression methods were performed to explore the relational factors of accidental death of children. 【Results】 Of the 25 cases of accidental death of children under the age of five years old, 5 were traffic accidents (20.0%), 9 cases were falling (36.0%), and 11 were suffocation (44.0%). Age distribution showed that children of accidental suffocation were younger, with 90.9% (10 cases) of them under the age of 1 years old. Gender distribution showed that traffic accident deaths occurred to boys. Area distribution showed that falling and suffocation death mainly happened in Hanzhong, while traffic accidents death mainly in Weinan. When the accident happened, 8 caregivers were not on the scene. What was worse, among 17 caregivers who were on the scene of accident, only 4 kept an eye on children. Compared with 25 children in control group, 16 in case group had received health examination, and the difference showed statistical significance (χ2=8.672, P=0.003). Meanwhile, 9 main caregivers were mothers in the case group, compared with 14 in the control group. The Logistic regression analysis showed that compared with fathers, mothers as the children’ main caregivers could positively reduce accidental death of children (OR=0.016, 95% CI: 0.000 3-0.997, P=0.049). 【Conclusion】 To decrease the incidence rate and mortality of accidental death of children under the age of five years old, parenting behavior guidance, health examination, and targeted health education should be taken in Maternal and Child Health Care System as a routine work.
8.Death of hospitalized neonates of different gestational age in Shaanxi Province: a multi-center survey
Yunfan YANG ; Juan ZHANG ; Juanjuan ZHANG ; Xiping YU ; Zhankui LI ; Heqin LI ; Wenping SONG ; Zengfang LIU ; Guanshan YANG ; Huanli GUO
Chinese Journal of Perinatal Medicine 2023;26(5):398-405
Objective:To investigate the current status of hospitalized neonatal death of different gestational ages in Shaanxi Province.Methods:All neonatal deaths in six hospitals in Shaanxi Province from 2016 to 2020 were retrospectively analyzed, and the differences in perinatal complications, the causes of death, and the age at death were compared using Chi-square (or Fisher's exact ) test. Results:(1) Totally, 220 488 neonates were delivered in the obstetric department of the six hospitals during the study period; 71 782 out of them were admitted to the neonatal department. While 424 neonatal death was reported, giving the total hospitalized neonates mortality rate of 5.5‰ (394/71 782), which included 152 deaths of transferred patients ( n=9 103, 16.7‰), 226 premature (53.3%), 196 term (46.2%), and two post-term infants (0.5%). (2) Among mothers of dead neonates, 73.6% were found to have at least one perinatal complication. The most common one was fetal distress (146 cases, 34.4%), followed by gestational diabetes mellitus (113 cases, 26.7%), amniotic fluid abnormalities ( n=73, 17.2%), maternal infectious diseases ( n=71, 16.8%), and hypertensive disorders in pregnancy (HDP) ( n=52, 12.3%). The lower the gestational age, the higher the proportion of multiple pregnancies and assisted reproduction technology applied (Fisher exact test, P<0.05). On the contrary, the higher the gestational age, the higher the cesarean section rate ( χ 2=26.69, P<0.001). HDP was more likely to occur in the gestational age of 28-31 +6 and 32-34 +6 weeks ( χ 2=37.16, P<0.001), and amniotic fluid abnormalities were more likely to occur in those over 37 weeks ( χ 2=27.47, P<0.001). (3) The five leading causes of neonatal death were neonatal respiratory distress syndrome (NRDS, n=100, 23.6%), neonatal asphyxia ( n=88, 20.8%), maternal infectious diseases ( n=80, 18.9%), and birth defects ( n=54, 12.7%), and pulmonary hemorrhage ( n=22, 5.2%). The first three causes of death in term and post-term infants were neonatal asphyxia ( n=65, 32.8%), birth defects ( n=42, 21.2%), and infectious diseases ( n=26, 13.1%). NRDS ( n=83, 36.7%), infectious diseases ( n=54, 23.9%), and neonatal asphyxia ( n=23, 10.2%) were the three leading causes of death of premature babies. (4) Out of the 326 (76.9%) neonatal deaths within seven days after birth, 162 (38.2%) died within 24 h after birth and 164 cases (38.7%) between one to seven days after birth. Conclusions:Most neonatal deaths occurred among preterm ones and within seven days after birth, whose mothers suffered perinatal complications. The causes of neonatal death vary among different gestational age groups.
9.Advantages of contrast-enhanced ultrasound in the localization and diagnostics of sentinel lymph nodes in breast cancer.
Qiuhui YANG ; Yeqin FU ; Jiaxuan WANG ; Hongjian YANG ; Xiping ZHANG
Journal of Zhejiang University. Science. B 2023;24(11):985-997
Sentinel lymph nodes (SLNs) are the first station of lymph nodes that extend from the breast tumor to the axillary lymphatic drainage. The pathological status of these LNs can predict that of the entire axillary lymph node. Therefore, the accurate identification of SLNs is necessary for sentinel lymph node biopsy (SLNB) to replace axillary lymph node dissection (ALND). The quality of life and prognosis of breast cancer patients are related to proper surgical treatment after the precise identification of SLNs. Some of the SLN tracers that have been identified include radioisotope, nano-carbon, indocyanine green (ICG), and methylene blue (MB). However, these tracers have certain limitations, such as pigmentation, radiation dangers, and the requirement for costly detection equipment. Ultrasound contrast agents (UCAs) have good specificity and sensitivity, and thus can compensate for some shortcomings of the mentioned tracers. This technique is also being applied to SLNB in patients with breast cancer, and can even provide an initial judgment on SLN status. Contrast-enhanced ultrasound (CEUS) has the advantages of high distinguishability, simple operation, no radiation harm, low cost, and accurate localization; therefore, it is expected to replace the traditional biopsy methods. In addition, it can significantly enhance the accuracy of SLN localization and shorten the operation time.
Humans
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Female
;
Sentinel Lymph Node/pathology*
;
Breast Neoplasms/pathology*
;
Quality of Life
;
Sentinel Lymph Node Biopsy/methods*
;
Ultrasonography/methods*
;
Lymph Nodes/surgery*
10.Roles of lncRNA in the diagnosis and prognosis of triple-negative breast cancer.
Qiuhui YANG ; Yeqin FU ; Jiaxuan WANG ; Hongjian YANG ; Xiping ZHANG
Journal of Zhejiang University. Science. B 2023;24(12):1123-1140
Breast cancer is a malignant tumor that seriously endangers women's lives. The prognosis of breast cancer patients differs among molecular types. Compared with other subtypes, triple-negative breast cancer (TNBC) has been a research hotspot in recent years because of its high degree of malignancy, strong invasiveness, rapid progression, easy of recurrence, distant metastasis, poor prognosis, and high mortality. Many studies have found that long non-coding RNA (lncRNA) plays an important role in the occurrence, proliferation, migration, recurrence, chemotherapy resistance, and other characteristics of TNBC. Some lncRNAs are expected to become biomarkers in the diagnosis and prognosis of TNBC, and even new targets for its treatment. Based on a PubMed literature search, this review summarizes the progress in research on lncRNAs in TNBC and discusses their roles in TNBC diagnosis, prognosis, and chemotherapy with the hope of providing help for future research.
Humans
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Female
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Triple Negative Breast Neoplasms/genetics*
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RNA, Long Noncoding/genetics*
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Biomarkers, Tumor/genetics*
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Gene Expression Regulation, Neoplastic

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