1.Exploration the Immune Regulatory Mechanism of Hedysari Radix Based on Network Pharmacology,Molecular Dynamics,and UPLC-MS/MS
Xudong LUO ; Xinrong LI ; Chengyi LI ; Peng QI ; Tingting LIANG ; Xiaoli FENG ; Xu LI ; Jungang HE ; Xiaocheng WEI ; Ruijuan ZHOU ; Xinming XIE
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):376-383
Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.
2.Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy
LI XIAOCHENG ; XIAO YAQING ; LI PENGFEI ; ZHU YAYUN ; GUO YONGHONG ; BIAN HUIJIE ; LI ZHENG
Journal of Zhejiang University. Science. B 2024;25(6):485-498,中插1-中插2
End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
3.Intravenous ultrasound for evaluating atherosclerotic plaque characteristics of different type traditional Chinese medicine syndrome of coronary heart disease
Guoyou HUANG ; Xiaocheng LI ; Du XIONG
Chinese Journal of Medical Imaging Technology 2024;40(1):51-54
Objective To observe characteristics of atherosclerotic plaque of coronary heart disease(CHD)with different traditional Chinese medicine(TCM)syndrome type based on intravenous ultrasound(IVUS).Methods Data of 116 CHD patients were retrospectively analyzed.The patients were divided into syndrome of blood stasis due to qi deficiency(n=33),syndrome of blockade of phlegm-turbidity(n=42)as well as syndrome of intermin-gled phlegm and blood stasis(n=41)according to TCM syndrome differentiation.IVUS was performed to compare lesion vessel and plaque characteristics among different syndromic types of CHD.Results The lipid pool area,extravascular elastic membrane area,remodeling index,plaque eccentricity index of CHD with syndrome of blood stasis due to qi deficiency were all larger than those of syndrome of blockade of phlegm-turbidity as well as syndrome of intermin-gled phlegm and blood stasis(all P<0.05).The proportion of fibrous-fatty within plaques of syndrome of blood stasis due to qi deficiency was bigger than that of syndrome of intermin-gled phlegm and blood stasis(P<0.05).The lipid pool area,extravascular elastic membrane area and plaque eccentricity index of CHD of syndrome of blockade of phlegm-turbidity were smaller than,while the proportion of necrotic core within plaques was bigger than those of syndrome of intermin-gled phlegm and blood stasis(all P<0.05).Conclusion Atherosclerotic plaque characteristics in CHD with different TCM syndrome types were different,and the plaque stability of syndrome of blood stasis due to qi deficiency was the worst.
4.Mediating effect of positive coping style on disease perception and fear of disease progression in patients after the surgery of pituitary neuroendocrine tumour
Ting LI ; Juzi WANG ; Aihong GAO ; Xiaocheng WANG ; Yinxian LI ; Gangli ZHANG
Modern Clinical Nursing 2024;23(7):10-16
Objective To investigate the status quo of fear of disease progression(FoP)in patients after pituitary neuroendocrine tumour surgery and analyse the medication effects of positive coping style on disease perception and FoP.Methods Convenient sampling method was used to select 345 patients with pituitary neuroendocrine tumours who underwent surgical operations in the neurosurgery department of a Grade IIIA hospital in Shanxi Province from January 2022 to January 2023 as the research objects.A general data questionnaire,disease perception questionnaire,medical coping style questionnaire and fear of progression questionnaire-short form(FoP-Q-SF)were used in the investigation.Pearson correlation was employed to analyse the correlations of the disease perception,active coping style and FoP among the patients.Structural equation models were used to analyse the mediating effects of positive coping styles on disease perception and FoP.Results The FoP score of patients after pituitary neuroendocrine tumour surgery was found at(35.02±4.92).FoP was positively correlated with the disease perception(r=0.672,P<0.01),and negatively with the active coping style(r=-0.679,P<0.01).Positive coping styles were positively correlated with disease perception(r=-0.610,P<0.01).Disease perception not only had a direct effect on FoP,but also had an indirect effect on FoP via active coping style,with an intermediate effect value of 0.202(P<0.001),accounting for 25.5%of total effect.Conclusion Postoperative positive coping style in patients with pituitary neuroendocrine tumour is a mediating variable between the disease perception and FoP.Medical staff should dynamically assess and early identify coping styles of patients and adopt personalised guidance programs,therefore to guide the patients to actively cope with the disease,so as to reduce the negative disease perception and alleviate the fear of disease progression of the patients.
5.Anti-tumor Effect and Mechanism of Effective Components in Hedysari Radix: A Review
Miaoting JIA ; Chengyi LI ; Zhengze QIANG ; Mingwei WANG ; Xiaoli FENG ; Xiaocheng WEI ; Ruijuan ZHOU ; Guangmao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):213-219
Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics, surgery, radiotherapy, or hormone therapy. The treatment process has limitations such as multidrug resistance, non-selective targeting of cancer cells, and drug toxicity. With the development and application of traditional Chinese medicine (TCM), Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation, differentiation, and metastasis, and avoid drug resistance, serving as the focus of current tumor treatment research. Hedysari Radix, one of the genuine medicinal materials in Gansu province, is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation, immune regulation, anti-oxidation, prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties, Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity, scavenging free radicals, and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer, bladder cancer, gastric cancer, breast cancer, and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research, this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis, blocking cell cycle, inhibiting tumor cell proliferation, migration, and invasion, regulating micro mRNA (miRNA), inducing cell autophagy, enhancing immune regulation, as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics, and systematically explained the anti-tumor mechanism of Hedysari Radix active components, aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.
6.Early management after left ventricular assist device implantation in 22 patients: a single center experience
Wei WANG ; Yuan TANG ; Shujie LI ; Chao DU ; Zhihao LI ; Hao WANG ; Xiaocheng LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(9):535-539
Objective:To investigate and summarize the early management experience of 22 patients with end-stage heart failure(ESHF) who underwent left ventricular assist device(LVAD) implantation in an intensive care unit(ICU) in a single center.Methods:Data of 22 patients with ESHF treated with LVAD in the ICU of TEDA International Cardiovascular Hospital from September 2020 to August 2022 were retrospectively analyzed. There were 16 males and 6 females, aged from 20 to 67 years old, with a mean age of(51.0±13.3)years old. There were 21 cases with dilated cardiomyopathy, 1 case with ischemic cardiomyopathy, 6 cases with tricuspid regurgitation, 1 case with intra-aortic balloon pump for cardiogenic shock, and 5 cases with cardiac resynchronization therapy for arrhythmia. After the operation, all patients received restricted fluid therapy, a " stepwise" anticoagulation strategy, and strict blood pressure management. The postoperative complications and treatment process were reviewed, the treatment and management experience were summarized, and the prognosis of the patients was statistically analyzed.Results:All 22 patients survived within 90 days after surgery, and 21 patients(95.5%) recovered well, the pump works fine and there was no hemolysis and thrombosis of LVAD. Major complications included: 1 case of severe pneumonia(4.5%), 2 cases of pericardial tamponade(9.1%), 1 case of intracerebral hemorrhage(4.5%), 1 case of mediastinal infection(4.5%), 5 cases of positive occult blood in gastric juice(22.7%), no cases of right ventricular failure、aortic insufficiency and cerebral infarction. The duration of postoperative mechanical ventilation was 17(8.5, 51.5) h, and the ICU stay was 14(10, 27) days.Conclusion:LVAD is another effective treatment for patients with ESHF in addition to heart transplantation. Good postoperative blood pressure control, " stepwise" anticoagulation strategy and " restrictive" fluid management can reduce postoperative complications in the early phase of post-operation, which is crucial for the prognosis of patients with LVAD.
7.Recent advance in central nervous regulatory mechanism of transcutaneous auricular vagus nerve stimulation in improving cognitive function
Xiaocheng LI ; Lingyan LIANG ; Yichen WEI ; Demao DENG
Chinese Journal of Neuromedicine 2023;22(2):184-188
Vagus nerve stimulation (VNS) is a neuromodulation technique that achieves therapeutic purpose through intermittent and chronic stimulation of vagus nerve afferent fibers, which has a remarkable effect on functional diseases of the central nervous system, and has been approved by FDA for intractable epilepsy, depression and migraine treatments. Transcutaneous auricular vagus nerve stimulation(taVNS) is a new type of non-invasive nerve regulation therapy based on traditional VNS and vagus nerve anatomy, and has a wide range of central regulation; taVNS can improve the cognitive state by regulating functions of cognition-related cerebral cortex and nerve nuclei, regulating inflammatory response, promoting neurotransmitter transmission, and so on, which has a broad application prospect in cognition-related diseases. This paper mainly summarizes the recent advance in central mechanism of taVNS in improving cognitive function.
8.Establishment of the prediction models of malignant brain edema after vascular recanalization in anterior circulation acute large vascular occlusion stroke
Jun CHENG ; Hu LI ; Xiaocheng HUANG ; Haihua WANG
International Journal of Surgery 2022;49(1):15-23,F3
Objective:Based on Logistic regression and XGBoost algorithm, the prediction model of malignant brain edema (MBE) after vascular recanalization of anterior circulation acute great vessel occlusive stroke (ALVOS) was constructed, and the prediction performance was compared.Methods:A retrospective selection of 382 patients with anterior circulation ALVOS who underwent early endovascular treatment (EVT) in our hospital from March 2014 to June 2020 and successfully recanalized the occluded blood vessel was selected. The patients were divided into the training group ( n=267) and the test group ( n=115) according to the ratio of 7∶3 by the random number table method. According to whether the patients had MBE after successful recanalization of the occluded blood vessels, the training group was divided into the MBE group ( n=41) and non-MBE group ( n=226). The baseline data, treatment and brain computed tomography perfusion(CTP) results of MBE group and non-MBE group in training group and test group were compared respectively, including age, admission score of National Institutes of Health Stroke Scale (NIHSS), grade of cerebral collateral circulation, cerebral blood volume, and so on. Logistic regression model and XGBoost algorithm model were used to screen the predictors of MBE in ALVOS patients with occluded vessels successfully recanalized, and the discrimination and calibration of the two models were compared. The measurement data conforming to the normal distribution were expressed as mean ± standard deviation ( ± s), and the independent sample t test was used for comparison between the two groups. Non-normally distributed measurement data were represented by M ( Q1, Q3), using independent sample Mann-Whitney U test. The chi-square test was used to compare the count data between groups. Results:There was no significant difference in baseline data, treatment status, and cranial computed tomography perfusion (CTP) imaging results of the training group and the test group ( P>0.05). The age, admission systolic blood pressure, admission NIHSS score, proportion of hypertension, proportion of cerebral collateral circulation 0-2, proportion of thrombus removal times> 3 times, time from onset to recanalization, and cerebral blood volume (CBV) of MBE group were (68.95±8.04) years old, (146.71±22.73) mmHg, 17(13, 21) min, 87.80%, 82.93%, 68.29%, (365.64±87.83) min, (32.56±5.73) mL/100 g, obvious higher than the non-MBE group [(60.27±7.13) years old, (137.92±19.58) mmHg, 14(10, 18) points, 73.01%, 60.62%, 2.65%, (307.59±74.05) min, (27.49±5.46) mL/100 g] ( P<0.05). The results of Logistic regression model showed that age, NIHSS on admission, grade of cerebral collateral circulation, times of thrombectomy and time from onset to recanalization were the predictors of MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS ( P<0.05). The top five important feature scores of XGBoost algorithm model were cerebral collateral circulation classification 34, embolectomy times 27, onset to vascular recanalization time 25, admission NIHSS score 22, age 16.In the training set, the area under the curve of the Logistic regression model was 0.816(95% CI: 0.749-0.883), and the Hosmer-Lemeshow test showed that χ2=1.547, P=0.438. The area under the curve of the XGBoost algorithm model was 0.856(95% CI: 0.799-0.913), and the Hosmer-Lemeshow test showed that χ2=1.021, P=0.998. Conclusion:Logistic regression model and XGBoost algorithm model had similar prediction performance for MBE after successful recanalization of occluded vessels after EVT in patients with anterior circulation ALVOS, and collateral circulation classification, number of thrombolysis, time from onset to recanalization, NIHSS score on admission, and age could be used as predictors.
9.Analysis of risk factors and construction of diagnosis model for sarcopenia in liver cirrhosis
Jun WANG ; Jintao SUN ; Fengxia LI ; Xiaocheng WANG ; Jingqi BAI ; Tian YANG
Chinese Journal of Clinical Nutrition 2022;30(6):321-327
Objective:To explore the risk factors of sarcopenia in liver cirrhosis and construct a diagnosis model for sarcopenia in cirrhosis.Methods:73 patients with liver cirrhosis hospitalized in Department of Gastroenterology of Shanxi Provincial People's Hospital between June 2021 and June 2022 were included. Common measurements in liver cirrhosis and abdominal CT scans of all patients were collected. The cross-sectional area of skeletal muscle at L3 level was calculated by sliceomatic and the skeletal muscle index (SMI) was subsequently obtained by height standardization. The patients were divided into sarcopenia group and non-sarcopenia group using Asian cut-off per European Working Group on Sarcopenia in Older People-2nd meeting (EWGSOP2) criteria. Risk factors related to sarcopenia in cirrhosis were analyzed and a subsequent diagnosis model was established.Results:among the cirrhotic patients included in the study, the prevalence of sarcopenia was 65.75% (48/73), 47.73% (21/44) in males and 93.10% (27/29) in females, respectively. There were significant differences in age, sex, BMI, liver function grade per Child Pugh classification, etiology, ferritin level, prothrombin time and hemoglobin level between sarcopenia and non-sarcopenia groups (P < 0.05). Age, liver function, sex and ferritin level were closely related to the occurrence of sarcopenia in cirrhosis. A diagnostic model was developed based on these 4 indexes and the area under curve reached up to 95.7%.Conclusion:≥ 60 years old, female, Child-Pugh C grade and ferritin < 29.60 μg/L are independent risk factors for sarcopenia in cirrhosis and the model with these indexes shows good diagnostic value for sarcopenia in cirrhosis.
10.Short-term effect of HeartCon left ventricular assist device on the treatment of 20 adult patients with end-stage heart failure
Wei WANG ; Yu SONG ; Yunqiang ZHANG ; Zhengqing WANG ; Zhigang LIU ; Shujie LI ; Yuan TANG ; Xiaocheng LIU
Chinese Critical Care Medicine 2022;34(12):1258-1262
Objective:To investigate and evaluate the efficacy of HeartCon left ventricular assist device (LVAD) in the treatment of adult patients with end-stage heart failure (ESHF).Methods:A prospective and observational study was conducted. Patients with ESHF who underwent LVAD implantation in the department of cardiac surgery of Teda International Cardiovascular Hospital from September 2020 to August 2021 were selected. The left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) classification, N-terminal pro-B type natriuretic peptide (NT-proBNP), and six minute walk distance (6MWD) before operation and 90 days after operation were compared. The incidence of equipment failures and major adverse events within 90 days after operation were recorded.Results:A total of 20 patients with ESHF were included, with 15 males and 5 females. Patients' age ranged from 20 to 67 years old, with an average of (50.2±13.6) years old. The range of body weight was 49.8-106.1 kg, with an average of (67.9±15.5) kg, and the body surface area (BSA) was from 1.49 to 2.32 m 2, with an average of (17.6±0.22) m 2. The operation process of all the patients were successful. The length of hospital stay ranged from 33 to 90 days, and the average was 56.0 (42.8, 75.0) days. Complications within 90 days after operation as follows, 2 cases with pericardial tamponade (10%), 1 case with cerebral hemorrhage (5%), 1 case with mediastinum infection (5%), 3 cases with acute renal injury (AKI, 15%), 5 cases with gastrointestinal bleeding (25%). There were no mechanical failure of LVAD and hemolysis events, right ventricular failure (RVF), cerebral infarction and death occurred. Compared with preoperative, the LVEDD significantly decreased (mm: 67.50±13.98 vs. 77.40±9.73), LVEF significantly increased (%: 34.80±9.76 vs. 22.70±5.62), NT-proBNP significantly decreased (ng/L: 2 028.65±1 752.05 vs. 4 796.45±4 355.40), 6MWD significantly increased (m: 385.20±144.12 vs. 85.81±63.50) at 90 days after operation, and the differences were statistically significant (all P < 0.05). 18 cases (90%) of the 20 patients reached NYHA classification Ⅰ and 2 cases (10%) reached NYHA classification Ⅱ, which were significantly improved compared with those before surgery (all patients' NYHA classification were Ⅳ before surgery). Conclusion:HeartCon LVAD can effectively improve the life quality of patients with ESHF, which has been proved safe and effective in clinical trials, but its long-term effects and complications need further observation and study.

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