1.Study of the suppressive effect of paeonol on rat cardiac hypertrophy by downregulating endoplasmic reticulum stress in cardiomyocyte
Miao-Miao BIAN ; Chen KONG ; Zi-Qiong WU ; Yu-Qing SUN ; Qi-Long FENG
Chinese Pharmacological Bulletin 2024;40(12):2319-2325
Aim To investigate the effect of paeonol(PAE)on cardiac hypertrophy induced by Angio-tensinogen Ⅱ(Ang Ⅱ)in rats and its mechanism.Methods Forty Sprague-Dawley rats were divided in-to five groups:control group,Ang Ⅱ model group,low concentration paeonol group,middle concentration pae-onol group,high concentration paeonol group.PAE was administered intragastrically(25,50 and 100 mg·kg-1·d-1)for 28 days.The hypertrophic model was established by adding 1 μmol·L-1 Ang Ⅱ to H9c2 cells for 48 hours.Results In Ang Ⅱ-induced rats,PAE improved echocardiography parameters,the cardi-ac hypertrophy index,the mRNA and protein expres-sion levels of ANP and BNP were decreased,and the cardiac fibrosis was alleviated.In vitro,PAE reduced cardiomyocyte hypertrophy and decreased the mRNA and protein expression levels of ANP and BNP in H9c2 cells induced by Ang Ⅱ,at the same time,the expres-sion of endoplasmic reticulum stress marker proteins p-PERK,GRP78,ATF4 and CHOP were decreased and reversed after treatment with the endoplasmic reticulum stress agonist tunicamycin(TN).Conclusion This study suggests that PAE can improve cardiac hypertro-phy by inhibiting endoplasmic reticulum stress,which may be a new drug to delay the development of cardiac hypertrophy.
2.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
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Humans
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Aged
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Natriuretic Peptide, Brain
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Simendan/therapeutic use*
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Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
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Peptide Fragments
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Arrhythmias, Cardiac
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Biomarkers
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Prognosis
3.Expert Consensus on Sepsis Responding Specifically to Traditional Chinese Medicine
Ling-bo KONG ; Jun YAN ; Di ZHANG ; Cai-jun WU ; Tao LI ; Hai-tao LAN ; Jing-feng LIU ; Yang-ping CAI ; Shuo WANG ; Nan GUO ; Xiao-long XU ; Sha-sha HE ; Shu-zhen GUO ; Jia-bo WANG ; Ying QIAN ; Xiao-xiao ZHANG ; Qing-quan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(5):211-218
To give full play to the therapeutic advantages of traditional Chinese medicine (TCM) in sepsis, clarify the entry point of integrated TCM and western medicine, further standardize the clinical treatment of TCM, develop a recognized and integrated treatment protocol of TCM and western medicine, and improve the clinical efficacy on sepsis,the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis, a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response, improving blood coagulation dysfunction, and relieving organ damage. Furthermore, they proposed the treatment protocol with integrated TCM and western medicine, which is expected to provide references for actual clinical treatment and scientific research.
4.Progress in antitumor activity of baicalin
Bang-yan KONG ; Li-bin WEI ; Qing-long GUO
Acta Pharmaceutica Sinica 2021;56(6):1537-1543
Flavonoids baicalin is the main bioactive component extracted from
5.Establishment of an auxiliary diagnosis system of newborn screening for inherited metabolic diseases based on artificial intelligence technology and a clinical trial
Rulai YANG ; Yanling YANG ; Ting WANG ; Weize XU ; Gang YU ; Jianbin YANG ; Qiaoling SUN ; Maosheng GU ; Haibo LI ; Dehua ZHAO ; Juying PEI ; Tao JIANG ; Jun HE ; Hui ZOU ; Xinmei MAO ; Guoxing GENG ; Rong QIANG ; Guoli TIAN ; Yan WANG ; Hongwei WEI ; Xiaogang ZHANG ; Hua WANG ; Yaping TIAN ; Lin ZOU ; Yuanyuan KONG ; Yuxia ZHOU ; Mingcai OU ; Zerong YAO ; Yulin ZHOU ; Wenbin ZHU ; Yonglan HUANG ; Yuhong WANG ; Cidan HUANG ; Ying TAN ; Long LI ; Qing SHANG ; Hong ZHENG ; Shaolei LYU ; Wenjun WANG ; Yan YAO ; Jing LE ; Qiang SHU
Chinese Journal of Pediatrics 2021;59(4):286-293
Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.
6.Lung Protective Mechanism of Compound Kushen Injection on Radiation-induced Pulmonary Injury
Wen-long WANG ; Hong-da LU ; Sheng-you LIN ; Zhang LEI ; Tao YU ; Hong-bin WU ; Qing-zhi KONG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(7):42-49
Objective::To observe the effect of compound Kushen injection on the expressions of transforming growth factor-
7.Effect of emodin on the improvement of drug resistance of gemcitabine in pancreatic cancer cell line by down-regulating the expression of multidrug resistance gene-1
Wen-Long WANG ; Qing-Zhi KONG ; Hong-Da LU ; Zhang LEI ; Tao YU ; Hong-Bin WU ; Dian-Lei LIU
The Chinese Journal of Clinical Pharmacology 2018;34(20):2427-2430
Objective To investigate the effect of emodin on the gemci-tabine-resistant pancreatic cancer cell line SW1990/Gemcitabine (GEM),and explore the potential mechanism of its action .Methods The pancreatic cancer cell line SW1990 was treated by intermittently in-creasing the concentration of gemcitabine in the culture medium for 10 months, and SW1990/GEM cells were obtained.This experiment was di-vided into control group ,emodin group,gemcitabine group and combina-tion group ( emodin +gemcitabine ) .SW1990/GEM and SW1990 cells were treated with emodin ( 10 μmol · L-1) and gemcitabine ( 20 μmol· L-1) alone or those two together in three groups for 48 h, in con-trol group cells were treated with 0.1%DMSO for 48 h.Cell proliferation was analyzed by MTT.Reverse transcription -polymerase chain reaction was performed to analyze the protein and gene expression of multidrug re-sistance gene-1 ( MDR-1) .Flow cytometric was applied to analyze the function of the P-glycoprotein(P-gp).The Rhodamine l23 efflux experiment was applied to assay P -gp function in SW1990/Gemcitabine cells.Results Compared with gemcitabine group , the combination group could significantly inhibit the proliferation of SW1990/GEM cells.Treatment of SW1990/GEM and SW1990 cells with gemcitabine alone could inhibit 13.34%and 36.52%of cell viability,there was significant difference between the two group (P<0.05). The results showed that the SW1990 /GEM cell line had an obvious resistance to gemcitabine compared with the cell line SW 1990.While SW 1990/GEM and SW 1990 cells were treated with gemcitabine combined with emodin , cell via-bility was inhibited to 40.45%and 43.87%, there was no significant difference between the two group .The emodin could enhance the anti -proliferative effect of gemcitabine on drug -resistance cell SW1990/GEM.Compared with gemcitabine group, the combination group could significantly inhibit the expression of MDR-1 gene,and the difference was statistically significant (P<0.05).Conclusion Effect of emodin can down -regulate the expression of MDR -1 and then improve the drug resistance of gemcitabine in pancreatic cancer .
8.Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis.
Xiao-Long DU ; Ling-Shang KONG ; Qing-You MENG ; Aimin QIAN ; Wen-Dong LI ; Hong CHEN ; Xiao-Qiang LI ; Cheng-Long LI
Chinese Medical Journal 2015;128(13):1787-1792
BACKGROUNDCatheter-directed thrombolysis (CDT) has been a mainstay in treating deep venous thrombosis (DVT). However, the optimal dosage of a thrombolytic agent is still controversial. The goal of this study was to evaluate the safety and efficacy of low dosage urokinase with CDT for DVT.
METHODSA retrospective analysis was performed using data from a total of 427 patients with DVT treated with CDT in our single center between July 2009 and December 2012. Early efficacy of thrombolysis was assessed with a thrombus score based on daily venography. The therapeutic safety was evaluated by adverse events. A venography or duplex ultrasound was performed to assess the outcome at 6 months, 1 year and 2 years postoperatively.
RESULTSThe mean total dose of 3.34 (standard deviation [SD] 1.38) million units of urokinase was administered during a mean of 5.18 (SD 2.28) days. Prior to discharge, Grade III (complete lysis) was achieved in 154 (36%) patients; Grade II (50-99% lysis) in 222 (52%); and Grade I (50% lysis) in 51 (12%). The major complications included one intracranial hemorrhage, one hematochezia, five gross hematuria, and one pulmonary embolism. Moreover, no death occurred in the study.
CONCLUSIONSTreatment of low-dose catheter-directed thrombosis is an efficacious and safe therapeutic approach in patients with DVT offering good long-term outcomes and minimal complications.
Adolescent ; Adult ; Aged ; Drug Administration Schedule ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Urokinase-Type Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Venous Thrombosis ; drug therapy ; Young Adult
9.Early multi-disciplinary intervention reduces neurological disability in premature infants.
Guang-Fu CHEN ; Yun-Fang ZHANG ; Mei-Qing CHEN ; Xiao-Li WANG ; Qi LONG ; Qi KONG ; Heng MAO
Chinese Journal of Contemporary Pediatrics 2014;16(1):35-39
OBJECTIVEThis study aimed to evaluate the effectiveness of multi-disciplinary treatment approaches in reducing neurological disabilities in premature infants.
METHODSA total of 117 infants who were born premature in our hospital between March 2008 and February 2010 but had no congenital malformations and no severe neonatal complications, were enrolled in this study. They were randomly allocated to a multi-disciplinary treatment group (n=63) and a control group (n=54). While patients in the control group underwent an early conventional treatment, those in the multi-disciplinary treatment group were subjected to regular development monitoring, neurological examination and screening for brain injury, neuro-nutrition and neurodevelopment therapies, and rehabilitation training.
RESULTSThe incidence rates of abnormalities in posture, reflex, sleep, muscle tone and EEG were significantly lower in the multi-disciplinary treatment group than in the control froup (P<0.05) at corrected postnatal ages of 6-12 months. At corrected postnatal ages of 6, 12, 18 and 24 months, both mental development index (MDI) and psychomotor development index (PDI) scores were significantly higher in the multi-disciplinary treatment group than in the control group (P<0.05). At corrected postnatal age of 3 years, incidence rates of cerebral palsy, language barrier, abnormal muscle tone and hearing impairment were significantly lower in the multi-disciplinary treatment group than in the control group (P<0.05).
CONCLUSIONSEarly multi-disciplinary intervention approaches may significantly improve mental and motor developments and reduce the incidence of cerebral palsy-associated neurological disabilities in premature infants.
Cerebral Palsy ; prevention & control ; Child, Preschool ; Developmental Disabilities ; prevention & control ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; prevention & control ; Male
10.Hepatitis B e antigen from chronic hepatitis B patients induces Th1/Th2 cytokine imbalance in vitro.
Ya-ping HAN ; Jun LI ; Long-feng JIANG ; Qing-qing XU ; Bo LIU ; Li DONG ; Nian CHEN ; Lian-hua KONG ; Fa-ren XIE ; Zu-hu HUANG
Chinese Journal of Hepatology 2013;21(8):584-589
OBJECTIVETo study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).
METHODSPBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.
RESULTSExposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).
CONCLUSIONHBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.
Adult ; Case-Control Studies ; Cells, Cultured ; Female ; Hepatitis B e Antigens ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Interferon-gamma ; immunology ; Interleukin-10 ; immunology ; Interleukin-6 ; immunology ; Leukocytes, Mononuclear ; immunology ; metabolism ; Male ; Middle Aged ; Recombinant Proteins ; immunology ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology

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