1.Mechanism of Shengmai Injection Against Cerebral Ischemia Based on Proteomics
Jingtong LIU ; Shaowei HU ; Mengli CHANG ; Jing XU ; Qingqing CAI ; Xinghong LI ; Liying TANG ; Huanhuan WANG ; Hongwei WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):57-67
ObjectiveTo evaluate pharmacological effects of Shengmai injection(SMI)on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a sham group, a model group, a low-dose SMI group(3 mL·kg-1), a middle-dose SMI group(6 mL·kg-1), a high-dose SMI group(12 mL·kg-1), and a Ginaton group(4 mL·kg-1)according to the random number table method, with 12 rats in each group. The rat model of cerebral ischemia-reperfusion(MCAO/R)was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion, which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores, cerebral infarction area, hematoxylin-eosin (HE) staining, Nissl staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay (ELISA), Western blot, and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation(OGD/R)-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly decreased density of Nissl bodies and neurons(P<0.01). Compared with the model group, the SMI groups exhibited significantly decreased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly increased density of Nissl bodies and neurons (P<0.05). The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury, and the chloride intracellular channel protein 1 (CLIC1) was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced, compared with those in the model group(P<0.05, P<0.01), and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 (NLRP3) decreased (P<0.01). In addition, the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate(P<0.01) and significantly decreased the intracellular chloride ion concentration(P<0.05). ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.
2.Folic acid treatment regulates C2C12 myoblast diferentiation via JNK/p38 MAPK signaling pathway
Manli SUN ; Haifeng DENG ; Shaoju JIN ; Xudong CHEN ; Xinghong WANG ; Wenjuan FAN
Chinese Journal of Pathophysiology 2024;40(2):317-325
AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P<0.05 or P<0.01),and the rate of EdU positive cells increased(P<0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P<0.05),and the myotube fusion index was raised(P<0.05 or P<0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P<0.05 or P<0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P<0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P<0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P<0.05 or P<0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.
3.Preparation of paeonol nanoemulsion and investigation of vascular endothelial cells uptake
Sibu WANG ; Ying CHEN ; Yang DING ; Ting XIAO ; Wen LIU ; Xiangchun SHEN ; Ling TAO ; Xinghong LUO
Journal of China Pharmaceutical University 2022;53(6):690-697
In order to improve the poor solubility and low bioavailability of paeonol (Pae), paeonol-nanoemulsion (Pae-NE) was prepared, and its effect on uptake of human umbilical vein endothelial cells (HUVECs) was investigated.Pae-NE was prepared by phase inversion composition (PIC), the formulation of Pae-NE was optimized by single factor method and central composite design-response surface method (CCD), and the pharmaceutical properties were further characterized.Moreover, MTT was applied to evaluate the toxicity of Pae-NE on HUVECs, and the cellular uptake efficiency of Pae-NE was detected by fluorescence microscopy and flow cytometry.The results showed that the optimal formulation of Pae-NE was 20 mg of Pae, 55.1 mg of LCT, 144.9 mg of MCT, 600 mg of HS15, and 200 mg of 1,2 propylene glycol.The Pae-NE appearance was a light blue emulsion, and the average particle size is (25.69 ± 0.03) nm, with PDI of 0.182 ± 0.09, Zeta potential of -(4.01 ± 0.30) mV and good stability.The drug loading of Pae-NE was (1.967 ± 0.28) mg/mL and encapsulation rate of (99.36 ± 0.1)%.Pae-NE performed no significant effect on HUVECs growth in the Pae concentration range of 10-1-10-3 μg/mL.Moreover, NE as a drug delivery carrier significantly enhanced the uptake efficiency of Pae on HUVECs.In conclusion, Pae-NE preparation method was simple and stable, and promotes HUVECs uptake efficiency of Pae, suggesting that NE was a better dosage form reference for the lipid-soluble drug of Pae.
4.Preliminary study of clinical application of respiratory navigator-guided stereotactic body radiation therapy of liver malignancies on magnetic resonance linear accelerator
Min LIU ; Xiongfei LIAO ; Bin TANG ; Feng YANG ; Xi FENG ; Jie LI ; Pei WANG ; Sichuan GUO ; Xinghong YAO
Chinese Journal of Radiation Oncology 2022;31(12):1133-1139
Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.
5. Clinical study of ventilated-associated pneumonia after cardiac surgery in adults
Jiaohua YU ; Mengyuan LI ; Hui KE ; Huan WANG ; Xuehui ZHANG ; Xinghong LIU ; Shiyu ZHAO ; Yunfang LIU
Chinese Journal of Practical Nursing 2019;35(17):1324-1329
Objective:
To investigate the epidemiological data of ventilator-associated pneumonia(VAP) occurred in adults after cardiac surgery and exploring the relationship between ventilator-associated pneumonia related factors, and all purpose is to provide strong theoretical advice and technical guidance for prevent the occurrence of ventilator-associated pneumonia in post-cardiac surgery patients.
Methods:
Using literature research method to determine 55 VAP related factors, and 21 nursing experts were selected to conduct 2 rounds of enquiries. Based on the results of the consultation, a retrospective questionnaire was formed. A total of 150 patients who underwent ICU mechanical ventilation after cardiac surgery from September 2016 to August 2017 were retrospectively selected. The related factors of VAP and its etiological characteristics were retrospectively observed.
Results:
Delphi experts consultation results: the response rate two rounds were 86.4% and 100.0% respectively; the coefficient of reliability ascertained the authority of evaluation was 0.857 and 0.903 respectively; Kendall’s
6.Efficacy analysis of neural endoscopic and surgical operation in patients with cerebral hemorrhage induced by hypertension
Clinical Medicine of China 2017;33(4):349-352
Objective To discuss the efficacy of neural endoscopic and surgical operation in patients with cerebral hemorrhage induced by hypertension.Methods Sixty cases with cerebral hemorrhage induced by hypertension admitted at the People′s Hospital of Bortala from January 2015 to June 2016 were divided into the control group(n=32) and research group(n=28) according to cerebral hemorrhage surgical method.The patients of the control group were given conventional surgical operation treatment while the observation group were given neural endoscopic treatment.The operative time and intraoperative blood loss,and situation of hematoma absorption before and after operation and prognosis between the two groups were compared.Results The operative time and intraoperative blood loss of the two groups were respectively (132.6±35.4) min,(49.8±12.3) ml and (236.5±46.2) min,(263.5±49.8) ml,the observation group were obviously lower than that of the control group,the differences were statistically significant(t=6.532,9.548,all P<0.05).The preoperative hematoma volume,postoperative hematoma volume and hematoma clearance of the two groups were respectively (6.8±1.5) ml,(82.7±6.3)% and (16.3±3.1) ml,(57.8±5.2)%,the postoperative hematoma volume of observation group were obviously lower than that of the control group while the hematoma clearance obviously increased,the differences were statistically significant(t=6.584,-5.263,all P<0.05).The ADL assessment in patients of observation group was better than the control group and the death rate was lower than that of control group,the differences were statistically significant(3.6%(1/28) vs.21.9%(7/32),χ2=10.580,4.329,all P<0.05).Conclusion The efficacy of neural endoscopic applied in patients with cerebral hemorrhage induced by hypertension is remarkable,it causes little damage to the body and can obviously improve the effect of prognosis,it is worth popularization and application.
7.Incidence of leukemia in infants in Shanxi Children's Hospital
Xinghong CHANG ; Xiaohuan WANG
Journal of Leukemia & Lymphoma 2017;26(3):181-182,192
Objective To investigate the incidence of leukemia in infants, and to understand the status of this disease in recent years. Methods A total of 5802 children aged median 6 years (0-12 years) with first time bone marrow biopsy from January 2009 to December 2015 were retrospectively analyzed, and the results of bone marrow image analysis were analyzed retrospectively to investigate the incidence of leukemia. Results Of the 5802 cases, 480 (8.27 %) cases were children with leukemia. Among them, 381 (79.38 %) cases were acute lymphocytic leukemia (ALL), 99 (20.62 %) cases were acute myeloid leukemia (AML). The proportion of children with leukemia with first time marrow puncture was 5.33%(40/750), 4.92%(36/731), 7.06%(58/821), 8.34%(78/935), 10.13%(88/868), 10.89%(92/845), and 10.33%(88/852) from 2009 to 2015, respectively. The proportion of male patients per year was more than female, and the incidence in preschool and school-age children was higher [33.75 % (162/480) and 34.79 % (167/480), respectively]. Conclusion The proportion of children's leukemia in children with the first time bone marrow aspiration in Shanxi Children's Hospital increases year by year, and its risk factors need to be further analyzed.
8.Relationship Between Septal Myocardial Metabolism and Left Ventricular Mechanical Synchronization in Patients With Dilated Cardiomyopathy and Left Bundle Branch Block
Xinghong MA ; Lei WANG ; Yong YANG ; Feng GUO ; Daoyu WANG ; Hailong ZHANG ; Qinghai GENG ; Lin GUO ; Wei FANG
Chinese Circulation Journal 2016;31(1):69-72
Objective: To explore the relationship between septal myocardial metabolism and left ventricular mechanical synchronization in patients with dilated cardiomyopathy (DCM) and left bundle branch block (LBBB) by gated 18F-FDG myocardial metabolic imaging.
Methods: A total of 20 consecutive patients diagnosed for DCM with LBBB from 2010-10 to 2013-05 were enrolled, there were 11 male and 9 female at the mean age of (54±11) years. All patients received gated 18F-FDG myocardial metabolic PET imaging. TrueD software was used to determine the maximal standardized 18F-FDG uptake value (S-SUVmax) and the average standardized uptake value (S-SUVavg). QGS software was applied to conduct left ventricular phase analysis and to detect the cardiac function, left ventricular bandwidth (BW), standard deviation of bandwidth (SD), left ventricular end-diastolic volume (LVEDV), LVESV and LVEF. The relationship between 18F-FDG uptake in septal myocardium with the indexes of phase analysis and the indexes of cardiac function was analyzed.
Results: S-SUVmax and S-SUVavg were respectively negatively related to BW (r=-0.44, P<0.05 and r=-0.48, P<0.05);they were also respectively negatively related to SD (r=-0.57, P<0.01 and r=-0.51, P<0.05). While S-SUVmax and S-SUVavg were not really related to LVEDV, LVESV and LVEF, all P>0.05.
Conclusion: In patients of DCM with LBBB, reduced septal myocardial metabolism was closely related to left ventricular mechanical synchronization, gated 18F-FDG myocardial metabolic PET imaging may simultaneously detect both functions, which was important for prognostic evaluation and therapeutic monitoring in clinical practice;phase analysis.
9.Acute Effects of Transforming Growth Factor-β1 on Neuronal Excitability and Involvement in the Pain of Rats with Chronic Pancreatitis.
Xiaoyu ZHANG ; Hang ZHENG ; Hong Yan ZHU ; Shufen HU ; Shusheng WANG ; Xinghong JIANG ; Guang Yin XU
Journal of Neurogastroenterology and Motility 2016;22(2):333-343
BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
Abdomen
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Abdominal Pain
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Action Potentials
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Adult
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Animals
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Blotting, Western
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Calcium
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Diagnosis-Related Groups
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Fires
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Ganglia, Spinal
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Humans
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Hyperalgesia
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Injections, Spinal
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Male
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Membrane Potentials
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Neurons*
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Pancreas
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Pancreatitis, Chronic*
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Rats*
10.Relationship Between Right Ventricular Glucose Metabolism and Right Heart Function in Patients With Dilated Cardiomyopathy
Daoyu WANG ; Lei WANG ; Yong YANG ; Xinghong MA ; Chaowu YAN ; Shihua ZHAO ; Wei FANG
Chinese Circulation Journal 2015;(8):762-765
Objective: To investigate the relationship between right ventricular (RV) glucose metabolism by18F-fludeoxyglucose positron emission tomography (18F-FDG PET) and right heart function in patients with dilated cardiomyopathy (DCM).
Methods: The18F-FDG PET imaging was performed in 34 consecutive DCM patients, with the reference of Herrero method, the corrected RV standard uptake value (cRVSUV), corrected left ventricular standard uptake value (cLVSUV) and the ratio of RV to LV SUV (cR/L) were obtained. And all 34 patients received cardiac magnetic resonance imaging (cMRI) examination within 7 days, the left ventricular ejection fraction (LVEF) and RVEF were automatically calculated with Simpson’s principle. The pulmonary arterial systolic pressure was measured by echocardiography.
Results: The corrected cRVSUV and cR/L by18F-FDG PET were negatively related to RVEF by cMRI, (r=-0.513, P<0.01) and (r=-0.463,P<0.01) respectively, and meanwhile, the corrected cRVSUV and cR/L were also negatively related to LVEF, (r=-0.387,P<0.01 andr=-0.362,P<0.01) respectively.
Conclusion: Increased RV glucose metabolism closely related to RV dysfunction, the18F-FDG uptake value by PET might be used as an index for assessing the right heart function and prognosis in DCM patients.

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