1.Gandouling Regulates PI3K/Akt/mTOR Autophagy Signaling Pathway via LncRNA H19 for Treatment of Wilson Disease Liver Fibrosis
Xin YIN ; Han WANG ; Daiping HUA ; Lanting SUN ; Yunyun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):131-138
ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling (GDL) exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups: the normal group, the model group, the GDL low-, medium-, and high-dose groups (0.24, 0.48, 0.96 g·kg-1), and the penicillamine group (90 mg·kg-1), with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin (HE) staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of hyaluronic acid (HA), laminin (LN), procollagen type-Ⅲ peptide (PC-Ⅲ), and collagen type-Ⅳ (C-Ⅳ). Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 (LncRNA H19), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR). Western blot analysis was performed to assess the expression levels of PI3K, Akt, mTOR, and their phosphorylated forms, as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B (LC3-Ⅱ/LC3-Ⅰ) in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group, the model group exhibited inflammatory cell infiltration in hepatocytes, unclear nuclear boundaries with cell cleavage and necrosis, and collagen fiber deposition around confluent areas. The levels of HA, LN, PC-Ⅲ, and C-Ⅳ were significantly elevated (P<0.01). Transmission electron microscopy revealed an increased number of autophagic vesicles, with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased (P<0.01), and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were reduced (P<0.01), while LncRNA H19 expression was increased (P<0.01), and mRNA expression levels of PI3K, Akt, and mTOR were decreased (P<0.01). After treatment with GDL, the degree of liver fibrosis was significantly improved, with decreased levels of HA, LN, PC-Ⅲ, and C-Ⅳ. The number of autophagic vesicles was significantly reduced, and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower (P<0.01). The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K, Akt, mTOR, p-PI3K, p-Akt, and p-mTOR were elevated (P<0.01), while the expression level of LncRNA H19 was reduced (P<0.01). Furthermore, the mRNA expression levels of PI3K, Akt, and mTOR increased (P<0.05, P<0.01). ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.
2.Effect of Yiqi Wenyang Huoxue Lishui Components on Cardiac Function and Mitochondrial Energy Metabolism in CHF Rats
Hui GAO ; Zeqi YANG ; Xin LIU ; Fan GAO ; Yangyang HAN ; Aiyangzi LU ; Xingchao LIU ; Qiuhong GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):27-36
ObjectiveTo investigate the effects of Yiqi Wenyang Huoxue Lishui components on the cardiac function and mitochondrial energy metabolism in the rat model of chronic heart failure (CHF) and explore the underlying mechanism. MethodsThe rat model of CHF was prepared by transverse aortic constriction (TAC). Eight of the 50 SD rats were randomly selected as the sham group, and the remaining 42 underwent TAC surgery. The 24 SD rats successfully modeled were randomized into model, trimetazidine (6.3 mg·kg-1), and Yiqi Wenyang Huoxue Lishui components (60 mg·kg-1 total saponins of Astragali Radix, 10 mg·kg-1 total phenolic acids of Salviae Miltiorrhizae Radix et Rhizoma, 190 mg·kg-1 aqueous extract of Lepidii Semen, and 100 mg·kg-1 cinnamaldehyde) groups. The rats were administrated with corresponding agents by gavage, and those in the sham and model groups were administrated with the same amount of normal saline at a dose of 10 mL·kg-1 for 8 weeks. Echocardiography was used to examine the cardiac function in rats. Enzyme-linked immunosorbent assay was employed to determine the serum levels of N-terminal pro-B-type natriuretic peptide (NT-ProBNP), hypersensitive troponin(cTnI), creatine kinase (CK), lactate dehydrogenase (LD), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA). The colorimetric assay was employed to measure the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in the myocardial tissue. The pathological changes in the myocardial tissue were observed by hematoxylin-eosin staining and Masson staining. The Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in the myocardial tissue were determined by the colorimetric assay. The ultrastructural changes of myocardial mitochondria were observed by transmission electron microscopy. Western blot was employed to determine the protein levels of ATP synthase subunit delta (ATP5D), glucose transporter 4 (GLUT4), and carnitine palmitoyltransferase-1 (CPT-1). The mitochondrial complex assay kits were used to determine the activities of mitochondrial complexes Ⅰ, Ⅱ, Ⅲ, and Ⅳ. ResultsCompared with the sham group, the model group showed a loosening arrangement of cardiac fibers, fracture and necrosis of partial cardiac fibers, inflammatory cells in necrotic areas, massive blue fibrotic tissue in the myocardial interstitium, increased collagen fiber area and myocardial fibrosis, destroyed mitochondria, myofibril disarrangement, sparse myofilaments, and fractured and reduced cristae. In addition, the rats in the model group showed declined ejection fraction (EF) and fractional shortening (FS), risen left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular end-systolic posterior wall thickness (LVPWs), left ventricular end-diastolic volume (LVVOLd), and left ventricular end-systolic volume (LVVOLs), elevated levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, lowered level of SOD, down-regulated protein levels of GLUT4 and CPT-1, decreased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and declined levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). Compared with the model group, the Yiqi Wenyang Huoxue Lishui components and trimetazidine groups showed alleviated pathological damage of the mitochondria and mycardial tissue, risen EF and FS, declined LVIDd, LVIDs, LVPWd, LVPWs, LVVOLd, and LVVOLs, lowered levels of NT-ProBNP, cTnI, CK, MDA, FFA, and LD, elevated level of SOD, up-regulated protein levels of GLUT4 and CPT-1, increased activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, and respiratory complexes Ⅰ-Ⅳ, and elevated levels of ATP5D, ATP, ADP, and AMP (P<0.05, P<0.01). ConclusionYiqi Wenyang Huoxue Lishui components can improve the cardiac function, reduce myocardial injury, regulate glucose and lipid metabolism, optimize the utilization of substrates, and alleviate the damage of mitochondrial structure and function, thus improving the energy metabolism of the myocardium in the rat model of CHF.
3.Connotation of Traditional Chinese Medicine's Protection of Pulmonary Microvascular Endothelial Cells in Prevention and Treatment of Chronic Obstructive Pulmonary Disease Based on "Lung Collateral Theory"
Jingjing XIN ; Tongxing WANG ; Ningxin HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):221-229
Chronic obstructive pulmonary disease (COPD) is a common disease with a high incidence and mortality rate in the world. It is characterized by chronic inflammation and structural obstruction and is not completely reversible which will lead to shortness of breath caused by air retention and physical exertion. Traditional Chinese medicine proposes the concept of "lung collaterals", which refers to the collateral vessels scattered throughout the lungs and lung system. The lung collaterals include the pulse collaterals and Qi collaterals. The blood circulation in the pulse collaterals belongs to Yin, distributed internally along the way. The Qi circulation in the Qi collateral belongs to Yang and is distributed externally. In western medicine, the pulse collaterals have an identity with large, medium, and small blood vessels, microvessels, and especially microcirculation. The Qi collateral encompasses systems such as the nervous, endocrine, and immune system. Pulmonary microvascular endothelial cells (HPMECs) are an important component of the pulmonary microvascular endothelium. Recent studies have found that HPMECs are the main damaged cells in the pathogenesis of COPD, mediating the occurrence and development of COPD. Traditional Chinese medicine can regulate HPMECs to treat COPD through multiple components, targets, and pathways, and has the advantage of reducing western medicine resistance and many side effects. Based on the "lung collateral theory", this paper focused on HPMECs, and elaborated on the new connotation of traditional Chinese medicine in protecting HPMECs to treat COPD, aiming to provide new insights for the clinical treatment of COPD by protecting HPMECs.
4.Connotation of Traditional Chinese Medicine's Protection of Pulmonary Microvascular Endothelial Cells in Prevention and Treatment of Chronic Obstructive Pulmonary Disease Based on "Lung Collateral Theory"
Jingjing XIN ; Tongxing WANG ; Ningxin HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):221-229
Chronic obstructive pulmonary disease (COPD) is a common disease with a high incidence and mortality rate in the world. It is characterized by chronic inflammation and structural obstruction and is not completely reversible which will lead to shortness of breath caused by air retention and physical exertion. Traditional Chinese medicine proposes the concept of "lung collaterals", which refers to the collateral vessels scattered throughout the lungs and lung system. The lung collaterals include the pulse collaterals and Qi collaterals. The blood circulation in the pulse collaterals belongs to Yin, distributed internally along the way. The Qi circulation in the Qi collateral belongs to Yang and is distributed externally. In western medicine, the pulse collaterals have an identity with large, medium, and small blood vessels, microvessels, and especially microcirculation. The Qi collateral encompasses systems such as the nervous, endocrine, and immune system. Pulmonary microvascular endothelial cells (HPMECs) are an important component of the pulmonary microvascular endothelium. Recent studies have found that HPMECs are the main damaged cells in the pathogenesis of COPD, mediating the occurrence and development of COPD. Traditional Chinese medicine can regulate HPMECs to treat COPD through multiple components, targets, and pathways, and has the advantage of reducing western medicine resistance and many side effects. Based on the "lung collateral theory", this paper focused on HPMECs, and elaborated on the new connotation of traditional Chinese medicine in protecting HPMECs to treat COPD, aiming to provide new insights for the clinical treatment of COPD by protecting HPMECs.
5.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
6.Hepatitis E virus infection among blood donors in Ningbo
Mingxi PENG ; Yiyu LIU ; Huyan MAO ; Dan LIN ; Lu XIN ; Ning SHU ; Jianfeng HAN ; Feng DING
Chinese Journal of Blood Transfusion 2025;38(1):7-12
[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.
7.Targeting fibroblast growth factor receptor 1 signaling to improve bone destruction in rheumatoid arthritis
Haihui HAN ; Lei RAN ; Xiaohui MENG ; Pengfei XIN ; Zheng XIANG ; Yanqin BIAN ; Qi SHI ; Lianbo XIAO
Chinese Journal of Tissue Engineering Research 2025;29(9):1905-1912
BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.
8.Cutting-edge progress of intravascular ultrasound in lower-extremity vascular interventions
Xin GUAN ; Hong HAN ; Huixiong XU
Ultrasonography 2025;44(1):5-18
Lower-extremity vascular disease has a high morbidity rate and often leads to disability and death in its advanced stages. Although angiography-guided endovascular intervention is the primary treatment for peripheral vascular disease, it frequently fails to detect subtle lumen features and falls short of meeting the increasing clinical need for precise management. Intravascular ultrasound (IVUS) merges noninvasive ultrasound imaging with invasive catheterization techniques, providing 360° imaging of the vascular cross-section and delivering accurate information about lesion morphology. IVUS has been crucial in supporting decisionmaking for preoperative assessment, intraoperative monitoring, and postoperative optimization during vascular interventions. This review aims to summarize the latest applications of IVUS in lower-extremity vascular disease, discuss its strengths and limitations, and explore future directions for its use.
9.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
10.Salidroside promotes osteogenic differentiation of MC3T3-E1 cells:an in vitro experiment
Zhaohui LIU ; Xiaoqian HAN ; Xin DUAN ; Pengda GUO ; Yuntao ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(2):231-237
BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

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