1.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
2.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
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Animals
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Mice
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Tripterygium
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Psoriasis/drug therapy*
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Keratinocytes
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Skin Diseases/metabolism*
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Cytokines/metabolism*
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Imiquimod/metabolism*
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Dermatitis/pathology*
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Disease Models, Animal
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Mice, Inbred BALB C
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Skin/metabolism*
3.Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum
Xin WANG ; Yue SHI ; Jin-hui MAN ; Yu-ying HUANG ; Xiao-qin ZHANG ; Ke-lu AN ; Gao-jie HE ; Zi-qi LIU ; Fan-yuan GUAN ; Yu-yan ZHENG ; Xiao-hui WANG ; Sheng-li WEI
Acta Pharmaceutica Sinica 2024;59(1):243-252
Platycodonis Radix is the dry root of
4.Effects of Bushen Huoxue formula on interleukin-17 in rats with recurrent spontaneous abortion
Yao PENG ; Jin CHEN ; Yan LIANG ; Qi YANG ; Li-Mei SHEN ; Xiao-Jian XIA
The Chinese Journal of Clinical Pharmacology 2024;40(13):1928-1932
Objective To observe the effect of Bushen Huoxue formula on interleukin-17(IL-17)in rats with recurrent spontaneous abortion(RSA).Methods RS A model rats were constructed by intraperitoneal injection of estradiol benzoate.Forty RSA model rats were randomly divided into model group,control group and experimental-L,-H groups,with 10 rats per group.Another 10 healthy pregnant rats were set as blank group.The experimental-L,-H groups were given 7.77 and 15.54 g·kg-1 of Bushen Huoxue formula solution by gavage.The control group was given 2.10 mg·kg-1of dydrogesterone solution by gavage.The blank group and the model group were given equal amount of 0.9%NaCl by gavage.The dose of administration for the five groups was 10 mL·kg-1,once a day,for 9 days.The number of live fetuses,embryo loss,and embryo loss rate in each group were observed.The proportion of Th 17 cells in the peripheral blood was detected by flow cytometry.The expression levels of interleukin-6(IL-6),IL-17 and IL-23 proteins in the decidual tissues were detected by Western blotting.Results The number of live fetuses in the experimental-H,control,model and blank groups were 11.50±2.84,11.50±3.10,6.30±1.25 and 12.50±3.24;the number of embryos lost were 1.80±0.42,1.90±0.57,4.90±1.37 and 0;the rates of embryo loss were(14.01±4.52)%,(14.79±6.06)%,(43.50±9.49)%and 0;the proportions of Th17 cells in the peripheral blood were(3.12±0.47)%,(3.10±0.59)%,(5.31±1.16)%and(2.54±0.71)%;the relative expression levels of IL-6 protein were 0.19±0.04,0.18±0.05,0.85±0.16 and 0.11±0.03;the relative expression levels of IL-17 protein were 0.28±0.04,0.29±0.05,0.84±0.12 and 0.09±0.01;the relative expression levels of IL-23 protein were 0.35±0.04,0.34±0.06,0.90±0.11 and 0.08±0.01,respectively.Comparing experimental-H group and model group,comparing control group and blank group,the above indexes were statistically significant(all P<0.05).Conclusion Bushen Huoxue formula can reduce embryo loss,improve placental tissue pathology,reduce Th 17 cell proportion and its related cytokines IL-6,IL-17,IL-23 expression in rats with RSA.
5.A multi-dimensional analysis of pollen broadcasting concerns in Chinese population: a large-scale multi-center cross-sectional survey
Chiyu XU ; Yanshu ZHANG ; Ning LUAN ; Xiangyi LIU ; Dayang QIN ; Hongmin WANG ; Xuping XIAO ; Shuihong ZHOU ; Jie ZHANG ; Ping ZHANG ; Yuqing BAI ; Pengpeng WANG ; Yan QI ; Zhongwu SUN ; Zhuang LIU ; Luo BA ; Wenchao WANG ; Xing LU ; Min WANG ; Rui GUO ; Deyi SUN ; Liyuan TAO ; Li ZHU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(1):2-11
Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.
6.Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing
Li Ya ZHANG ; Zhe Wen SU ; Chen Rui WANG ; Yan LI ; Feng Jun ZHANG ; Hui Sheng LIU ; He Dan HU ; Xiao Chong XU ; Yu Jia YIN ; Kai Qi YIN ; Ying HE ; Fan LI ; Hong Shi FU ; Kai NIE ; Dong Guo LIANG ; Yong TAO ; Tao Song XU ; Feng Chao MA ; Yu Huan WANG
Biomedical and Environmental Sciences 2024;37(3):294-302
Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.
7.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
8.Neoflavonoids from Dalbergia cochinchinensis and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells
Jia-Hui REN ; Qi-Wan ZHENG ; Xiao-Wei MENG ; Yan PANG ; Lan-Ying CHEN ; Rong-Hua LIU
Chinese Traditional Patent Medicine 2024;46(1):126-132
AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.
9.Diagnostic efficacy of optimized T-SPOT.TB in differentiating spinal tu-berculosis from other spinal infection
Ying ZHOU ; Xiao-Jiang HU ; Zhong-Jing JIANG ; Jun-Bao CHEN ; Guang ZHANG ; Hong-Qi ZHANG ; Yan-Bing LI ; Qi-Le GAO
Chinese Journal of Infection Control 2024;23(2):148-154
Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09%)were diagnosed with STB,and 54(40.91%)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68%and 66.67%,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95%CI:1.847-9.974,P<0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56%,higher than 67.42%of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.
10.Value of left ventricular shape index and eccentricity index of gated myocardial perfusion imaging in the evaluation of left ventricular remodeling in patients with myocardial infarction
Xiaoyi XI ; Luxia WANG ; Qi YAO ; Shihao HUANGFU ; Yuxin XIAO ; Zhifang WU ; Ping WU ; Li LI ; Rui YAN ; Yuetao WANG ; Minfu YANG ; Sijin LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):6-11
Objective:To investigate the clinical value of left ventricular shape index (SI) and eccentricity index (EI) in evaluating left ventricular remodeling.Methods:A retrospective analysis was performed on 324 patients (264 males, 60 females, age (62.5±11.8) years) diagnosed with myocardial infarction (MI) and 113 healthy controls (HC; 47 males, 66 females, age (57.8±10.7) years) who received gated myocardial perfusion imaging (GMPI) in First Hospital of Shanxi Medical University from January 2016 to September 2020. SI (end-diastolic SI (EDSI), end-systolic SI (ESSI)), EI and left ventricular function parameters (end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), summed motion score (SMS), summed thickening score (STS), peak ejection rate (PER) and peak filling rate (PFR)) were obtained by quantitative gated SPECT (QGS) software. Propensity score (PS) inverse probability of treatment weighting (IPTW) was used to balance the intergroup covariates. The differences and correlations of EDSI, ESSI, EI and left ventricular function parameters between patients in MI group and HC group were analyzed. ROC curve analysis was used to evaluate the values of EDV, EDSI, ESSI and EI alone and in combination in the assessment of left ventricular systolic function impairment. Data were analyzed by independent-sample t test, Pearson correlation and Spearman rank correlation analyses, and Delong test. Results:After IPTW, EDSI and ESSI in MI group ( n=319) were higher than those in HC group ( n=133; EDSI: 0.66±0.09 vs 0.60±0.06; ESSI: 0.59±0.11 vs 0.47±0.07; t values: 8.05, 14.67, both P<0.001), and EI was lower than that in HC group (0.81±0.06 vs 0.85±0.03; t=-8.93, P<0.001). In both groups, there were significant correlations between EDSI and ESSI ( r values: 0.928, 0.873), between EDSI, ESSI and EI ( r values: from -0.831 to -0.641), between EDSI, ESSI and LVEF ( r values: from -0.627 to -0.201), between ESSI and EDV, ESV and SMS ( rs values: 0.336-0.584), between ESSI and -PER, PFR ( rs values: from -0.406 to -0.402, r values: from -0.352 to -0.325) (all P<0.01). ROC curve analysis showed that EDV (AUC: 0.895) and ESSI (AUC: 0.839) had the highest efficacy in evaluating left ventricular systolic function impairment in MI group and HC group, respectively. EDV-EDSI-ESSI-(1-EI) had higher efficacy in the assessment of impaired left ventricular systolic function in MI group (AUC: 0.956), which was higher than that of EDV or EDV-EDSI or EDV-ESSI or EDV-(1-EI) ( z values: from -2.64 to -2.18, P values: 0.008-0.029); EDV-EDSI-ESSI-(1-EI) also had high efficacy in HC group (AUC: 0.911), which was higher than that of EDV or EDV-EDSI or EDV-(1-EI) ( z values: from -2.60 to -2.43, P values: 0.009-0.015). Conclusions:In MI patients, the increase of SI and the decrease of EI indicate the increase of left ventricular sphericity and the aggravation of left ventricular remodeling. SI and EI have certain clinical application values in evaluating left ventricular morphology, predicting left ventricular remodeling and left ventricular systolic function impairment.

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