1.Clinical analysis of endoscopic retrograde cholangiopancreatography and stent implantation for the pancreaticobiliary injuries in children
Xiumin QIN ; Feihong YU ; Hui GUO ; Chunna ZHAO ; Jie WU
Chinese Journal of Pediatrics 2025;63(1):70-74
Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.
2.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
3.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
4.Association of habitual reading and writing postures with common diseases and comorbidities among children and adolescents in Ningxia
WEI Rong, LUO Haiyan, MA Ning, ZHAO Yu, YANG Yi, CHEN Yaogeng
Chinese Journal of School Health 2025;46(5):723-727
Objective:
To investigate the association between habitual reading/writing postures and the co-occurrence of common health conditions (overweight/obesity, visual impairment, hypertension, and scoliosis) and comorbidities among children and adolescents, in order to provide data support for the joint prevention of common diseases and comorbidities among children and adolescents.
Methods:
From September 2021 to June 2022, a multi-stage cluster random sampling method was used to select a total of 4 577 children and adolescents from 16 primary and secondary schools in Ningxia: Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City, and Pingluo County of Shizuishan City. A weighted complex sampling design was used to investigate the association of habitual reading and writing postures with common comorbidities in children and adolescents.
Results:
The prevalence rates of common diseases among children and adolescents in Ningxia were as follows: overweight/obesity was 22.87%, visual impairment was 62.52%, scoliosis was 2.30%, and hypertension was 1.30%. The prevalence of multimorbidity (co-occurrence of ≥2 conditions) among Ningxia children and adolescents was 15.95%. Multivariate unconditional Logistic regression analysis showed that frequent/always collapsing waist and sitting forward with head lowered increased the risk of common comorbidities in children and adolescents ( OR =1.90, P <0.05). Compared with the corresponding reference group, male children and adolescents aged 9 to 12 years and boys had relatively lower risks of overweight/obesity ( OR =0.71, 0.70); the risk of poor vision among children and adolescents aged 9 to 12 years, male, and urban was relatively low ( OR =0.59, 0.60, 0.73)( P < 0.05 ). Children and adolescents who often/always sat leaning to the left or right were at higher risk of poor vision ( OR =1.78); urban children and adolescents had a higher risk of developing scoliosis ( OR =3.71); children and adolescents aged 9 to 12 had a relatively low risk of developing hypertension ( OR =0.09), and children and adolescents who often/always bent their backs and sat forward on their knees had a higher risk of hypertension ( OR =5.03)( P <0.05).
Conclusions
Ningxia has a high incidence of common diseases and multiple diseases among children and adolescents, frequent or always collapsing waist and sitting forward with head lowered is associated with common comorbidities in children and adolescents in Ningxia. Proper postural measures for reading and writing should be carried out as soon as possible to encourage children and adolescents to develop good reading and writing habits for effectively preventing and controlling the occurrence of common diseases.
5.Effect of Tongdu Tiaoshen acupuncture on hippocampal neuronal ferroptosis in depression rats based on SLC7A11/GPX4 pathway.
Tingting QIAN ; Ling ZOU ; Zhi GAO ; Yu WU ; Yanbiao ZHAO ; Nan LI ; Hui LIU ; Meixiang SUN ; Peiyang SUN
Chinese Acupuncture & Moxibustion 2025;45(8):1120-1127
OBJECTIVE:
To observe the effects of Tongdu Tiaoshen acupuncture (acupuncture for unblocking the obstruction in the governor vessel and regulating the spirit) on the depression-like behavior and the hippocampal neuronal ferroptosis mediated by solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway in depression rats, and explore the mechanism of this therapy for depression.
METHODS:
Of 30 male SD rats of SPF grade, 24 rats were selected. According to the random number table, they were divided into a normal group (n=8) and a modeling group (n=16). The rats in the modeling group were subjected to chronic unpredictable mild stress (CUMS) for 28 consecutive days to establish depression model. After modeling, 16 successfully-modeled rats were randomly divided into a model group and an acupuncture group, 8 rats in each one. In the acupuncture group, Tongdu Tiaoshen acupuncture was applied to "Dazhui"(GV14), "Shuigou" (GV26), "Baihui" (GV20) and "Shenting" (GV24). This intervention measure was deliveredonce a day, continuously for 6 days. The intervention discontinued on day 7, and was completed in 4 weeks. Before and after modeling, and after intervention completion, the behavioristics detection was performed using sucrose preference experiment and open field experiment. After intervention, using hematoxylin-eosin (HE) and Nissl staining, the morphology of hippocampal neurons was observed; with Western blot method, the protein expression of GPX4, SLC7A11, Ferritin and acyl-CoA synthetase long-chain family 4 (ACSL4) in hippocampal tissues was detected; with the real-time fluorescence quantitative PCR adopted, the mRNA expression of GPX4, SLC7A11, Ferritin and ACSL4 was detected; and using colorimetry, the hippocampal iron content was determined.
RESULTS:
After modeling, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the model group and the acupuncture group were lower than those in the normal group (P<0.01). After the intervention, the sucrose preference rates, the total distance of movement, the standing times and the boxes of horizontal crossing in the acupuncture group were higher than those in the model group (P<0.01, P<0.05). Compared with the normal group, the number of necrotic cells increased and the number of Nissl bodies decreased in the model group; and when compared with the model group, the neuronal pyknosis and necrosis were ameliorated, the cells were arranged more regularly, the neuronal structure was clear, the matrix was dense, the blood vessels were enriched and the number of Nissl bodies increased in the acupuncture group. In comparison with the normal group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 decreased (P<0.01), it increased in the expression of hippocampal Ferritin and ACSL4 (P<0.01) in the model group. When compared with the model group, in the acupuncture group, the relative expression of protein and mRNA of hippocampal GPX4, SLC7A11 was elevated (P<0.01, P<0.05), it was dropped for hippocampal Ferritin and ACSL4 (P<0.01). In the model group, the hippocampal iron content was elevated when compared with that in the normal group (P<0.01); and it was reduced in the acupuncture group when compared with that in the model group (P<0.05).
CONCLUSION
Tongdu Tiaoshen acupuncture attenuates depression-like behaviors in the depression rats, which may be related to regulating SLC7A11/GPX4 pathway and inhibiting neuronal ferroptosis in the hippocampus.
Animals
;
Ferroptosis
;
Male
;
Hippocampus/cytology*
;
Rats, Sprague-Dawley
;
Rats
;
Depression/enzymology*
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Acupuncture Therapy
;
Neurons/metabolism*
;
Humans
;
Acupuncture Points
;
Amino Acid Transport System y+/genetics*
;
Glutathione Peroxidase/genetics*
6.Eccentric treadmill exercise promotes adaptive hypertrophy of gastrocnemius in rats.
Zhi-Qiang DAI ; Yu KE ; Yan ZHAO ; Ying YANG ; Hui-Wen WU ; Hua-Yu SHANG ; Zhi XIA
Acta Physiologica Sinica 2025;77(3):449-464
The present study aimed to investigate the effects of eccentric treadmill exercise on adaptive hypertrophy of skeletal muscle in rats. Thirty-two 3-month-old Sprague Dawley (SD) rats were selected and randomly assigned to one of the four groups based on their body weights: 2-week quiet control group (2C), 2-week downhill running exercise group (2E), 4-week quiet control group (4C), and 4-week downhill running exercise group (4E). The downhill running protocol for rats in the exercise groups involved slope of -16°, running speed of 16 m/min, training duration of 90 min, and 5 training sessions per week. Twenty-four hours after the final session of training, all the four groups of rats underwent an exhaustion treadmill exercise. After resting for 48 h, all the rats were euthanized and their gastrocnemius muscles were harvested for analysis. HE staining was used to measure the cross-sectional area (CSA) and diameter of muscle fibers. Transmission electron microscope was used to observe the ultrastructural changes in muscle fibers. Purithromycin surface labeling translation method was used to measure protein synthesis rate. Immunofluorescence double labeling was used to detect the colocalization levels of lysosomal-associated membrane protein 2 (Lamp2)-leucyl-tRNA synthetase (LARS) and Lamp2-mammalian target of rapamycin (mTOR). Western blot was used to measure the protein expression levels of myosin heavy chain (MHC) IIb and LARS, as well as the phosphorylation levels of mTOR, p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). The results showed that, compared with the 2C group rats, the 2E group rats showed significant increases in wet weight of gastrocnemius muscle, wet weight/body weight ratio, running distance, running time, pre- and post-exercise blood lactate levels, myofibrillar protein content, colocalization levels of Lamp2-LARS and Lamp2-mTOR, and LARS protein expression. Besides these above changes, compared with the 4C group, the 4E group further exhibited significantly increased fiber CSA, fiber diameter, protein synthesis rate, and phosphorylation levels of mTOR, p70S6K, and 4E-BP1. Compared with the quiet control groups, the exercise groups exhibited ultrastructural damage of rat gastrocnemius muscle, which was more pronounced in the 4E group. These findings suggest that eccentric treadmill exercise may promote mTOR translocation to lysosomal membrane, activating mTOR signaling via up-regulating LARS expression. This, in turn, increases protein synthesis rate through the mTOR-p70S6K-4E-BP1 signaling pathway, promoting protein deposition and inducing adaptive skeletal muscle hypertrophy. Although the ultrastructural changes of skeletal muscle are more pronounced, the relatively long training cycles during short-term exercise periods have a more significant effect on promoting gastrocnemius muscle protein synthesis and adaptive hypertrophy.
Animals
;
Rats, Sprague-Dawley
;
Physical Conditioning, Animal/physiology*
;
Rats
;
Muscle, Skeletal/metabolism*
;
TOR Serine-Threonine Kinases/metabolism*
;
Male
;
Hypertrophy
;
Adaptation, Physiological/physiology*
;
Adaptor Proteins, Signal Transducing/metabolism*
;
Ribosomal Protein S6 Kinases, 70-kDa/metabolism*
;
Intracellular Signaling Peptides and Proteins
7.Huanglian Jiedu Decoction prevents and treats acute liver injury in septic mice via AMPK/SIRT1 autophagy pathway.
Rui-Zhu ZHAO ; Xin-Yue REN ; Yu-Hang WANG ; Ding-Xing FAN ; Shi-Lei LOU ; Hui YAN ; Cong SUN
China Journal of Chinese Materia Medica 2025;50(2):507-514
This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Sirtuin 1/genetics*
;
Male
;
Mice
;
Sepsis/metabolism*
;
Mice, Inbred C57BL
;
Autophagy/drug effects*
;
AMP-Activated Protein Kinases/genetics*
;
Liver/metabolism*
;
Humans
;
Signal Transduction/drug effects*
;
Disease Models, Animal
;
Tumor Necrosis Factor-alpha/genetics*
8.Antidepressant mechanism of Baihe Dihuang Decoction based on metabolomics and network pharmacology.
Chao HU ; Hui YANG ; Hong-Qing ZHAO ; Si-Qi HUANG ; Hong-Yu LIU ; Shui-Han ZHANG ; Lin TANG
China Journal of Chinese Materia Medica 2025;50(1):10-20
The Baihe Dihuang Decoction(BDD) is a representative traditional Chinese medicine formula that has been used to treat depression. This study employed metabolomics and network pharmacology to investigate the mechanism of BDD in the treatment of depression. Fifty male Sprague-Dawley(SD) rats were randomly assigned to the normal control group, model group, fluoxetine group, and high-and low-dose BDD groups. A rat model of depression was established through chronic unpredictable mild stress(CUMS), and the behavioral changes were detected by forced swimming test and open field test. Metabolomics technology was used to analyze the metabolic profiles of serum and hippocampal tissue to screen differential metabolites and related metabolic pathways. Additionally, network pharmacology and molecular docking techniques were used to investigate the key targets and core active ingredients of BDD in improving metabolic abnormalities of depression. A "component-target-metabolite-pathway" regulatory network was constructed. BDD could significantly improve depressive-like behavior in CUMS rats and regulate 12 differential metabolites in serum and 27 differential metabolites in the hippocampus, involving tryptophan metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, tyrosine metabolism, and purine metabolism. Verbascoside, isorbascoside, and regaloside B were the key active ingredients for improving metabolic abnormalities in depression. Epidermal growth factor receptor(EGFR), protooncogene tyrosine-protein kinase(SRC), glycogen synthase kinase 3β(GSK3β), and androgen receptor(AR) were the key core targets for improving metabolic abnormalities of depression. This study offered a preliminary insight into the mechanism of BDD in alleviating metabolic abnormalities of depression through network regulation, providing valuable guidance for its clinical use and subsequent research.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Rats, Sprague-Dawley
;
Rats
;
Metabolomics
;
Depression/genetics*
;
Antidepressive Agents/chemistry*
;
Network Pharmacology
;
Hippocampus/drug effects*
;
Humans
;
Molecular Docking Simulation
;
Behavior, Animal/drug effects*
;
Disease Models, Animal
9.Huotan Jiedu Tongluo Decoction inhibits ferroptosis by regulating Nrf2/GPX4 pathway to ameliorate atherosclerotic lesions in ApoE~(-/-) mice.
Di GAO ; Teng-Hui TIAN ; Ke-Ying YU ; Xiao SHAO ; Wen XUE ; Zhi-Xuan ZHAO ; Yue DENG
China Journal of Chinese Materia Medica 2025;50(7):1908-1919
The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals
;
Ferroptosis/drug effects*
;
Atherosclerosis/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
;
NF-E2-Related Factor 2/genetics*
;
Mice
;
Mice, Inbred C57BL
;
Apolipoproteins E/metabolism*
;
Male
;
Phospholipid Hydroperoxide Glutathione Peroxidase/genetics*
;
Signal Transduction/drug effects*
;
Humans
;
Mice, Knockout
10.Advances in pathogenesis of asthma airway remodeling and intervention mechanism of traditional Chinese medicine.
Ya-Sheng DENG ; Jiang LIN ; Yu-Jiang XI ; Yan-Ping FAN ; Wen-Yue LI ; Yong-Hui LIU ; Zhao-Bing NI ; Xi MING
China Journal of Chinese Materia Medica 2025;50(8):2050-2070
Asthma, a chronic inflammatory airway disease with a high global prevalence, has a complex pathogenesis, in which airway remodeling plays a key role in the chronicity of the disease. Airway remodeling involves a series of pathophysiological changes, including airway epithelial damage, proliferation of mucous glands and goblet cells, subepithelial fibrosis, proliferation and migration of airway smooth muscle cells, and epithelial-mesenchymal transition. These complex pathological changes significantly increase airway resistance and responsiveness, forming an important pathological basis for refractory asthma. Currently, the regulatory mechanisms of airway remodeling focus on signaling pathways and regulatory targets. The signaling pathways include phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), nuclear factor-κB(NF-κB), transforming growth factor-β1(TGF-β1)/Smads, and mitogen-activated protein kinase(MAPK). The regulatory targets include microRNAs(miRNAs), competing endogenous RNAs(ceRNAs), long non-coding RNAs(lncRNAs), and circular RNAs(circRNAs). Key proteins involved in these processes include TGF-β1, silencing information regulator 2-related enzyme 1(SIRT1), chitinase 3-like protein 1(YKL-40), and adenosine deaminase-metalloproteinase 33(ADAM33). In recent years, the potential of traditional Chinese medicine in the treatment of asthma has become increasingly evident. Its active ingredients, extracts, and complexes can inhibit airway remodeling in asthma through multiple pathways, demonstrating a variety of effects, including anti-inflammatory actions, inhibition of smooth muscle cell proliferation and migration, regulation of epithelial-mesenchymal transition, attenuation of fibrosis and basement membrane thickening, reduction of mucus secretion, inhibition of vascular remodeling, modulation of immune imbalance, and antioxidative stress. This paper aims to provide an in-depth analysis of the pathogenesis and therapeutic targets of asthma, offering theoretical support and innovative strategies for clinical research and drug development in the treatment of asthma.
Asthma/pathology*
;
Humans
;
Airway Remodeling/drug effects*
;
Drugs, Chinese Herbal/therapeutic use*
;
Animals
;
Signal Transduction/drug effects*
;
Medicine, Chinese Traditional
;
Transforming Growth Factor beta1/metabolism*


Result Analysis
Print
Save
E-mail