1.Shenfu Injection Improve Chronic Heart Failure by Regulates Glycolytic Pathway Mediated by HIF-1α/PFKFB3 Pathway
Ji OUYANG ; Kun LIAN ; Xiaoqian LIAO ; Lichong MENG ; Lin LI ; Zhenyu ZHAO ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):136-145
ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α (HIF-1α)/ 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol (ISO). After successful modeling, the rats were randomly divided into the Sham group, Model group, Shenfu injection (SFI, 6 mL·kg-1) group, and inhibitor (3PO, 35 mg·kg-1) group, according to a random number table, and they were treated for 15 days. Cardiac function was evaluated by echocardiography, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were detected by enzyme-linked immunosorbent assay (ELISA). Fasting body weight and heart weight were measured, and the heart index (HI) was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin (HE) and Masson staining, and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose (GLU), lactic acid (LA), and pyruvic acid (PA). Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway (HIF-1α and PFKFB3), glycolysis-related proteins (HK1, HK2, PKM2, and LDHA), and fibrosis-related proteins [transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), and Collagen type Ⅰ α1 (ColⅠA1)]. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group, the Model group showed significantly decreased left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), interventricular septal thickness (IVSd), and interventricular septal strain (IVSs) (P<0.05), while left ventricular internal dimension at end-diastole (LVDd) and end-systole (LVIDs) were increased (P<0.05). Serum NT-proBNP levels were significantly increased (P<0.01), and body weight was decreased. Heart weight was increased, and the HIT index was increased (P<0.05). Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition, and the fibrosis rate was significantly increased (P<0.05). Serum GLU was decreased (P<0.05), while LA and PA levels were increased (P<0.05). Protein expressions of HIF-1α, PFKFB3, HK1, HK2, PKM2, LDHA, TGF-β1, α-SMA, and ColⅠA1, as well as the mRNA expression of HIF-1α and PFKFB3 were increased (P<0.05). Compared with the Model group, both the SFI group and 3PO groups showed significant improvements in LVEF, LVFS, IVSd, and IVSs (P<0.05) and decreases in LVDd, LVIDs, and NT-proBNP levels (P<0.05). Body weight was significantly increased. Heart weight was significantly decreased, and the HIT index was significantly decreased (P<0.05). Inflammatory cell infiltration, collagen fiber deposition, and the fibrosis rate were significantly decreased (P<0.05). Serum GLU levels were significantly increased (P<0.05), while LA and PA levels were decreased (P<0.05). Expressions of glycolysis-related proteins, fibrosis-related proteins, and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed (P<0.05). ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins, regulating glycolysis, and inhibiting myocardial fibrosis.
2.Visual Analysis of Research Trends and Hotspots in Animal Models of Chronic Heart Failure
Kun LIAN ; Xin LI ; Siyuan HU ; Yuehang XU ; Ji OUYANG ; Zhixi HU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):394-401
Objective To understand the research situation of animal model of chronic heart failure(CHF)based on visualization software and bibliometrics methods,and to explore the research hotspots of animal models of CHF and guide the design of animal experiments and scientific research.Methods Literature related to animal model of CHF included in Web of Science core collection from January 1,2001 to October 10,2022 were retrieved.After reading the full text and obtaining the final included literature,VOSviewer and CiteSpace software were used to analyze the contents of institutions,journals and co-cited journals,authors and co-cited authors,keywords.Results A total of 961 papers were included,and the number of published papers increased steadily.The United States and China are the main research countries.Johns Hopkins University and Harvard University are major research institutions.The most frequently published and cited journals are AM J PHYSIOL-HEART C and CIRCULATION,etc..Schultz Harold D and Sabbah Hani N are more influential in author selection."Myocardial infarction","cardiac hypertrophy",and"rat"are the most frequent keywords,10 clusters and 18 emergent words were formed.Conclusion The research in this field is numerous,high quality but scattered.Commonly used animal models are rodents and dogs.The main modeling methods are surgery and drugs.The main pathological mechanisms are mainly myocardial hypertrophy,oxidative stress,and myocardial fibrosis.
3.Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province
Xinyun ZHU ; Yizhuo XU ; Jie ZHANG ; Xiaole LI ; Jingwen HE ; Chenlu JIA ; Shubo LYU ; Suna LIU ; Yanbo GAO ; Kun MA ; Yunjia OUYANG ; Yihui REN ; Dehua ZHAO
Chinese Journal of Medical Genetics 2024;41(4):461-466
Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.
4.Effects of herbal tea residue supplement on growth performance,serum biochemi-cal and intestinal immune indexes in white feather broilers
Yue GUO ; Kun OUYANG ; Bin LIU ; Bilan CHEN ; Junyi LUO ; Jiajie SUN ; Qianyun XI ; Yongliang ZHANG ; Ting CHEN
Chinese Journal of Veterinary Science 2024;44(7):1534-1544
This experiment aims to investigate the effects of a dietary supplement of herbal tea resi-due on white feather broilers in the prospectives of growth performance,serum indexes and intesti-nal immune indexes.A total of 280 1-day-old white feather broilers with similar body mass and good health were randomly divided into 4 groups with 5 replicates per group and 14 birds per repli-cate.Group Ⅰ(control group)was fed a basal diet.Groups Ⅱ,Ⅲ and Ⅳ were fed a diet supple-mented with 2%,4%and 6%herbal tea residue powder,respectively.The feeding lasted for 49 days,and was divided into 2 phases from 1 to 21 days of age and 22 to 49 days of age.Blood,tissue and mucosa of the duodenum and jejunum were collected on 21 d and 49 d.Total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and the activities of aspartate aminotransferase(AST)and alanine amin-otransferase(ALT)in the serum were examined.The villus height and crypt depth of the jejunum were observed and measured by morphology.The mRNA expression levels of intestinal interleukin-1β(IL-1β),interleukin-2(IL-2),interleukin-4(IL-4),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were determined by qPCR.The results showed that compared with group Ⅰ,the mass of group Ⅲ on 21 d and 49 d significantly increased(P<0.05).The average daily feed intake of 22-49 d and 1-49 d significantly increased(P<0.05).The average daily mass gain of 1-21 d,22-49 d and 1-49 d significantly increased(P<0.05).In the serum of 21 d,compared with group Ⅰ,T-CHO in group Ⅱ significantly decreased(P<0.05).TG in groups Ⅱ,m and Ⅳ significantly de-creased(P<0.05).LDL-C and AST activity in group Ⅳ significantly decreased(P<0.05).In the serum of 49 d,T-CHO in group Ⅲ,LDL-C in group Ⅳ,HDL-C of groups Ⅲ and Ⅳ significantly increased(P<0.05),and the ALT activity of these two groups decreased(P<0.05).AST activity in group Ⅱ significantly decreased(P<0.05).In the duodenum of 21 d,compared with group Ⅰ,the expressions of TNF-α in group Ⅱ was significantly decreased(P<0.05).In the duodenum of 49 d,the expression of IL-10 in group Ⅱ was significantly increased(P<0.05),and the expression of IL-2 in groups Ⅲ and Ⅳ was significantly decreased(P<0.05).In the jejunum of 49 d,the ex-pression of IL-10 in group Ⅱ was increased(P<0.05),and the expression of IL-2 in groups Ⅲand Ⅳ was significantly decreased(P<0.05).In conclusion,dietary herbal tea residue can regulate circulating lipid level and enhance intestinal immunity of white feather broilers without affecting their normal growth performance.This experiment also suggested that the a 2%-4%supplementa-tion of herbal tea residues to white feather broilers was of good effect.
5.Visualization Analysis on Literature of Ligustri Lucidi Fructus from 1994 to 2023
Kun LIAN ; Ji OUYANG ; Yuehang XU ; Lin LI ; Zhixi HU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):70-76
Objective To analyze the research situation and trend of Ligustri Lucidi Fructus through bibliometric method;To provide reference for related research.Methods The literature on Ligustri Lucidi Fructus included in CNKI,VIP,Wanfang Data,CBM,Web of Science and PubMed from January 1,1994 to August 13,2023 was retrieved.NoteExpress 3.6.0.9155 software was used to manage and screen the literature.The publication time trend.CiteSpace 6.2.R4 and VOSviewer 1.6.18.0 software was used to analyze the authors,source journals,research institutions and keywords,and the knowledge map was drawn.Results A total of 795 Chinese papers and 175 English papers were included,and the annual number of published papers fluctuated.Capital Medical University and Hong Kong Polytechnic University published more papers in Chinese and English respectively.The authors with more papers were Liu Renhui and Wong Mansau respectively.The most published journals were Chinese Journal of Experimental Traditional Medical Formulae,Phytotherapy Research,Journal of Ethnopharmacology.The high frequency keywords included oleanolic acid,specnuezhenide,processing,antioxidant,extraction technology and rat.24 clusters and 44 emergent keywords were generated.Conclusion The research focus in this field includes the extraction and purification of oleanolic acid and specnuezhenide,the compatibility of Ligustri Lucidi Fructus with Chinese herbs such as Epimedii Folium and Polygoni Cuspidati Rhizoma et Radix,the effects and mechanism of delaying aging and treating cancer and other diseases,and cultivation and quality control.
6.Changes of spontaneous brain activity in end-stage renal disease patients: A study based on dynamic regional homogeneity
Hang SU ; Zhaoyao LUO ; Hui WANG ; Ronghua HE ; Zhuanqin REN ; Kun ZHANG ; Hongzhe TIAN ; Yuanshuo OUYANG ; Haining LI ; Yuchen ZHANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(3):432-436
【Objective】 To investigate dynamic regional homogeneity (dReHo) abnormality in end-stage renal disease (ESRD) patients by using resting-state functional magnetic resonance imaging (rs-fMRI). 【Methods】 A total of 26 ESRD patients and 26 healthy controls (HC) matched in gender, education level and age were included. Rs-fMRI scanning was performed in all subjects. All the subjects were tested by using auditory verbal learning test Huashan version (AVLT-H) and Montreal Cognitive Assessment (MoCA) to assess cognitive function before collection of MRI data. T-test was used to observe the difference in dReHo at global level between the two groups. Pearson and Spearman correlation analyses were made to estimate the correlation between abnormal brain regions and clinical scales. 【Results】 Compared with HC group, the dReHo value in ESRD patients reduced on the bilateral superior margin gyrus, left insula, left posterior central gyrus, and left putamen (P<0.05, replacement test correction). The dReHo values of left superior margin gyrus (r=-0.534, P=0.005) and left insula in ESRD patients (r=-0.422, P=0.032) were negatively correlated with the LR-S score, and the dReHo value of the left margin was negatively correlated with the SR-S score (r=-0.468, P=0.016). 【Conclusion】 There are abnormal dReHo values in several brain regions in ESRD patients during resting state, which is related to the patients’ cognitive function. The variation of dReHo value provides a new objective imaging basis for evaluating the cognitive function of ESRD patients.
7.Carotid endarterectomy combined with vertebral artery transposition treating vertebral artery V1 segment stenosis combined with ipsilateral carotid artery stenosis
Yuanrui GU ; Zeming ZHOU ; Yangxue SUN ; Yilang QIN ; Chen TIAN ; Jingjing REN ; Chuan TIAN ; Kun FANG ; Wenbin OUYANG ; Ying ZHANG ; Mingyao LUO ; Chang SHU ; Chenxi OUYANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(05):704-709
Objective To explore the treatment outcome of carotid endarterectomy combined with vertebral artery transposition in patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery. Methods From June 2017 to September 2020, patients with severe stenosis to occlusion of the vertebral artery V1 segment and the ipsilateral carotid artery treated with carotid endarterectomy combined with vertebral artery transposition in Fuwai Hospital were retrospectively analyzed. Results Finally 12 patients were enrolled, including 10 males and 2 females with an average age of 67.8±6.0 years. Twelve patients were successfully operated and the follow-up time was 1-3 years. The stenosis degree of the V1 segment of the vertebral artery decreased from 83.5%±11.8% to 24.9%±14.3% (P<0.001). The stenosis degree of carotid artery decreased from 85.6%±11.0% to 0% (P<0.001). Postoperative follow-up showed that the symptoms of symptomatic patients before surgery improved. The 1-year and 3-year patency rates were 100.0%, and there were no peripheral nerve injury complications, perioperative deaths or strokes. Conclusion Carotid endarterectomy combined with vertebral artery transposition can treat ipsilateral carotid artery stenosis and vertebral artery stenosis at the same time, improve blood supply to the brain, improve patients' symptoms and has high promotion value.
8.Treatment of complex acetabular fractures with improved Stoppa combined with Kocher-Langenbeck approach assisted by 3D printing technology.
Lin XU ; Yong-Kun WEI ; Zhen OUYANG ; Wei YIN
China Journal of Orthopaedics and Traumatology 2022;35(11):1015-1019
OBJECTIVE:
To explore the clinical effect of the modified Stoppa combined with Kocher-Langenbeck(K-L) approach and 3D printing technology in the treatment of complex acetabular fractures.
METHODS:
The surgical methods of 70 patients with complex acetabular fractures admitted from April 2013 to July 2019 were retrospectively analyzed. Among them, 25 cases were operated with 3D printing technology(3D printing group) and 45 cases were operated with conventional operation(conventional operation group). The operation time, intraoperative blood loss, intraoperative fluoroscopy times, complications and functional recovery of the hip joint of two groups were recorded.
RESULTS:
There were statistically significant differences between two groups in terms of operation time, intraoperative bleeding volume and intraoperative fluoroscopy times(P<0.01). All patients were followed up for (15.8±3.5) months, and all patients achieved bony healing. There was no significant difference in the results of Matta reduction between two groups(P>0.05). There was no significant difference in Harris score at 6 months after operation between two groups(P>0.05).
CONCLUSION
With the aid of 3D printing technology, the improved Stoppa combined with K-L approach is used to treat complex acetabular fractures. It has certain advantages in helping clinicians to formulate a reasonable operation plan before operation, avoid unnecessary operation and trauma during operation, shorten the operation time and reduce the amount of bleeding during operation. It can improve the safety during the perioperative period, facilitate the accurate reduction of fractures during operation and facilitate the recovery of patients.
Humans
;
Fracture Fixation, Internal/methods*
;
Retrospective Studies
;
Hip Fractures/surgery*
;
Spinal Fractures
;
Printing, Three-Dimensional
9.Modified vertebral-carotid transposition treating stenosis at V1 segment of vertebral artery
Yuanrui GU ; Yangxue SUN ; Yilang QIN ; Chen TIAN ; Jingjing REN ; Chuan TIAN ; Kun FANG ; Wenbin OUYANG ; Ying ZHANG ; Mingyao LUO ; Chang SHU ; Chenxi OUYANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(03):366-370
Objective To investigate the treatment of modified vertebral-carotid transposition (VCT) in patients with severe stenosis or occlusion at V1 segment of vertebral artery. Methods A retrospective study of 13 patients with severe stenosis or occlusion at V1 segment of vertebral artery treated by modified VCT in our hospital from October 2016 to December 2018 was done. There were 10 males and 3 females with an average age of 70.5±7.1 years. Results The operation was successful in this series of patients. The follow-up duration was 1-3 years. The stenosis degree of the V1 segment of the vertebral artery decreased from 86.8%±7.5% to 17.4%±14.5%. All patients achieved remission of symptoms after the surgery. Temporary peripheral nerve injury occurred in 6 patients. Four patients with neurological complications relieved during follow-up. The patency rate was 100.0% at postoperative 1 and 3 years. There was no perioperative death, stroke or re-intervention. Conclusion Modified VCT can precisely restore the distal blood flow of patients with severe stenosis or occlusion at V1 segment of vertebral artery, and relieve their symptoms.
10.Application of subclavian-carotid transposition to patients with proximal subclavian artery occlusion unable to be intervened
Yuanrui GU ; Yangxue SUN ; Chen TIAN ; Mingyao LUO ; Kun FANG ; Chang SHU ; Chenxi OUYANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(09):1005-1009
Objective To investigate the efficacy of subclavian-carotid transposition (SCT) in treating patients with proximal subclavian artery occlusive diseases who were unable to be intervened, such as failure of intervention, congenital malformation and unwillingness to intervention. Methods A retrospective review of 19 patients with proximal subclavian artery occlusion who underwent SCT from May 2016 to December 2018 was done. There were 14 males and 5 females with an average age of 54.05±17.34 years. The advantages and disadvantages of SCT in the treatment of proximal subclavian artery occlusion were analyzed. Results All patients achieved immediate remission of symptoms after surgery. The stenosis degree of the proximal subclavian artery decreased from 100.0%±0.0% to 12.7%±10.1% after surgery. The average blood pressure difference between the unaffected side and the affected side decreased from 11.95±10.60 mm Hg to 0.89±5.75 mm Hg (P<0.01). Peripheral nerve injury occurred in 7 (36.8%) patients. The in-patient cost of subclavian artery occlusion patients who received subclavian artery interventional therapy in our hospital during the corresponding period was 3 392.12 yuan higher than that of the SCT group in average (if eliminating the patients whose cost was far from the average value, the cost of interventional therapy was 4 812.01 yuan higher than that of the SCT group in average). During 1-3 years' follow-up, 6 patients with neurological complication relieved. One- and three-year patency rates were 100.0%. No perioperative stroke, death or re-operation happened. Conclusion SCT is an ideal process for the patients with subclavian artery occlusion who cannot accept subclavian artery interventional therapy.

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