1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.Estimation of genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using benchmark dose
Junli LIU ; Yu DING ; Xueqing CHENG ; Zhengli YANG ; Kelei QIAN ; Jing XU ; Yiyun FAN ; Dongsheng YU ; Zhiqing ZHENG ; Jun YANG ; Ning WANG ; Xinyu HONG
Journal of Environmental and Occupational Medicine 2024;41(4):425-430
Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg−1 ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg−1; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg−1) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg−1 and 21.90 mg·kg−1, and those of male mice were calculated to be 58.62 mg·kg−1 and 54.31 mg·kg−1, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg−1 and 11.99 mg·kg−1 for female mice, and 16.28 mg·kg−1 and 10.47 mg·kg−1 for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg−1 and 19.92 mg·kg−1 for female mice, and 24.74 mg·kg−1 and 14.08 mg·kg−1 for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg−1, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.
3.Analysis of micronucleus rate in 394 radiation workers with cytokinesis-block micronucleus method
Haixiang LIU ; Hua ZHAO ; Yu GAO ; Jie ZHANG ; Xueqing ZHANG ; Ying XIA
Chinese Journal of Radiological Health 2024;33(2):129-134
Objective To analyze the micronucleus rate of radiation workers and to provide accurate occupational health monitoring basis in radiation workers exposed to low-level ionizing radiation for a long time. Methods The radiation group consisted of 353 radiation workers who had been exposed to ionizing radiation during work, while the control group consisted of 41 radiation workers who had not yet been exposed to ionizing radiation before work. The cytokinesis-block micronucleus method was used to determine the micronucleus rate. Results The average micronucleus rate in the radiation group was significantly higher than that in the control group (t = −2.95, P < 0.05). In the radiation group, the micronucleus rate gradually increased with age, and the difference was statistically significant (F = 8.36, P < 0.05). The micronucleus rates of workers with > 10 and > 30 years of service were significantly higher than those of workers with < 10 years of service (χ2 = −44.79, −60.47, P < 0.05). The micronucleus rate in females was significantly higher than that in males (t = 3.93, P < 0.05). The micronucleus rates in the diagnostic radiology group and the industrial detection group were significantly higher than that in the control group (t = 3.51, 3.65, P < 0.05). Conclusion The micronucleus rate has increased among the radiation workers exposed to low-level ionizing radiation for a long time. It is necessary to further strengthen occupational health monitoring and radiation protection education for radiation workers, especially the medical workers that constitute the largest population of radiation exposure workers.
4.Research progress on experimental models of idiopathic pulmonary fibrosis
Zhihui LI ; Xueqing YU ; Shuguang YANG ; Ningxia YU ; Danyang ZANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):118-127
Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive interstitial lung disease.IPF incidence is increasing yearly with high mortality and poor prognoses.At present,IPF pathogenesis remains unclear,and its treatments are limited.The experimental model is important to further study IPF pathogenesis and explore effective preventive and therapeutic measures.In recent years,its modeling method have been continuously developed and optimized.This study summarizes the establishment method and research progress of IPF experimental models in recent years to provide ideas and references for preclinical research to select appropriate experimental models.
5.Summary of the first working meeting of the 8th Editorial Committee of Chinese Journal of Nephrology
Miao PENG ; Kekui YANG ; Haiping MAO ; Xueqing YU
Chinese Journal of Nephrology 2024;40(1):1-3
The first working meeting of the 8th Editorial Committee of Chinese Journal of Nephrology was held in Guangzhou, China on November 30, 2023. At the meeting, the list of the 8th Editorial Committee was announced, the work of the journal in the past 5 years was summarized, and the future work of the Editorial Committee was planned and discussed. Jiang Yongmao, former deputy secretary-general of the Chinese Medical Association, Jin Dong, deputy general manager of the Chinese Medical Journals Publishing House Co., Ltd, Lu Quan, editor of the Journal Management Department of Chinese Medical Association, Yu Xueqing, editor-in-chief of the 8th Editorial Committee, Cai Guangyan, Chen Jianghua, Zhao Minghui and Mao Haiping, deputy editor-in-chief of the 8th Editorial Committee, and 69 members of the 8th Editorial Committee, attended the meeting. The meeting came to a successful conclusion, and provided guidance for how to break through the difficulties, publish high-quality content and achieve high-quality development under the new situation.
6.Standard for the management of hyperkalemia—whole-process management mode of multi- department cooperation
Zhiming YE ; Jianfang CAI ; Wei CHEN ; Hong CHENG ; Qiang HE ; Rongshan LI ; Xiangmin LI ; Xinxue LIAO ; Zhiguo MAO ; Huijuan MAO ; Ning TAN ; Gang XU ; Hong ZHAN ; Hao ZHANG ; Jian ZHANG ; Xueqing YU
Chinese Journal of Nephrology 2024;40(3):245-254
Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.
7.Prognosis and risk factors of IgA vasculitis nephritis in children
Xueqing MA ; Yonghua HE ; Jinyun PU ; Wenpei LIANG ; Panpan SHAO ; Jianhua ZHOU ; Yu ZHANG ; Jinhui TANG ; Tonglin LIU ; Huiqing YUAN ; Liru QIU
Chinese Journal of Pediatrics 2024;62(12):1184-1190
Objective:To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children.Methods:A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results:Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ2=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR=5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P=0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions:For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.
8.Erratum to: Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis.
Ming LI ; Xingjie HAO ; Dianchun SHI ; Shanshan CHENG ; Zhong ZHONG ; Lu CAI ; Minghui JIANG ; Lin DING ; Lanbo DING ; Chaolong WANG ; Xueqing YU
Frontiers of Medicine 2024;18(6):1119-1119
9.Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT,p38 MAPK/NF-κB pathways
ZHANG XIAO ; DONG ZHICHENG ; FAN HUI ; YANG QIANKUN ; YU GUILI ; PAN ENZHUANG ; HE NANA ; LI XUEQING ; ZHAO PANPAN ; FU MIAN ; DONG JINGQUAN
Journal of Zhejiang University. Science. B 2023;24(7):617-631
Alcoholic liver disease(ALD)is the most frequent liver disease worldwide,resulting in severe harm to personal health and posing a serious burden to public health.Based on the reported antioxidant and anti-inflammatory capacities of scutellarin(SCU),this study investigated its protective role in male BALB/c mice with acute alcoholic liver injury after oral administration(10,25,and 50 mg/kg).The results indicated that SCU could lessen serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels and improve the histopathological changes in acute alcoholic liver;it reduced alcohol-induced malondialdehyde(MDA)content and increased glutathione peroxidase(GSH-Px),catalase(CAT),and superoxide dismutase(SOD)activity.Furthermore,SCU decreased tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β messenger RNA(mRNA)expression levels,weakened inducible nitric oxide synthase(iNOS)activity,and inhibited nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome activation.Mechanistically,SCU suppressed cytochrome P450 family 2 subfamily E member 1(CYP2E1)upregulation triggered by alcohol,increased the expression of oxidative stress-related nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)pathways,and suppressed the inflammation-related degradation of inhibitor of nuclear factor-κB(NF-κB)-α(IκBα)as well as activation of NF-κB by mediating the protein kinase B(AKT)and p38 mitogen-activated protein kinase(MAPK)pathways.These findings demonstrate that SCU protects against acute alcoholic liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and suppressing inflammation by regulating the AKT,p38 MAPK/NF-κB pathways.
10.Mechanism of Active Components of Chinese Medicine in Treatment of Idiopathic Pulmonary Fibrosis: A Review
Zhihui LI ; Xueqing YU ; Shuguang YANG ; Ningxia YU ; Lili XU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):181-192
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with unknown etiology and poor prognosis. At present, there are few antifibrotic drugs, which have limited efficacy and cause diverse side effects in the treatment of IPF, failing to meet the clinical needs. Therefore, it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that Chinese medicines have remarkable therapeutic effects on IPF and broad application prospects. However, the unclear material basis and mechanism in treating IPF hinders the modernization, internationalization, and clinical application of Chinese medicines. Therefore, it is essential to decipher the mechanism of the active components in Chinese medicines in treating IPF, which has gradually become a hot spot in the research on IPF. Increasing research results have demonstrated that anti-inflammation, anti-oxidation, inhibition of epithelial-mesenchymal transition are involved in the treatment of IPF with these active components, whereas the systematic research and summary remain to be carried out. By reviewing the articles about the treatment of IPF with the active components in Chinese medicines in recent years, this paper summarizes the mechanism and experimental studies and puts forward the existing problems in the research on the mechanism, aiming to provide references for the further basic research on IPF and the development of targerted drugs.

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