AtbHLH29 of Arabidopsis, encoding a bHLH protein, reveals a high similarity to the tomato FER which is proposed as a transcriptional regulator involved in controlling the iron deficiency responses and the iron uptake ...AtbHLH29 of Arabidopsis, encoding a bHLH protein, reveals a high similarity to the tomato FER which is proposed as a transcriptional regulator involved in controlling the iron deficiency responses and the iron uptake in tomato. For identification of its biological functions, AtbHLH29 was introduced into the genome of the tomato FER mutant T3238fer mediated by Agrobacterium tumefaciencs. Transgenic plants were regenerated and the stable integration of AtbHLH29 into their genomes was confirmed by Southern hybridization. Molecular analysis demonstrated that expression of the exogenous AtbHLH29 of Arabidopsis in roots of the FER mutant T3238fer enabled to complement the defect functions of FER. The transgenic plants regained the ability to activate the whole iron deficiency responses and showed normal growth as the wild type under iron-limiting stress. Our transformation data demonstrate that AtbHLH29 is a functional ortholog of the tomato FER and can completely replace FER in controlling the effective iron acquisition in tomato. Except of iron, FER protein was directly or indirectly involved in manganese homeostasis due to that loss functions of FER in T3238fer resulted in strong reduction of Mn content in leaves and the defect function on Mn accumulation in leaves was complemented by expression of AtbHLH29 in the transgenic plants. Identification of the similar biological functions of FER and AtbHLH29, which isolated from two systematically wide-diverged “strategy I” plants, suggests that FER might be a universal gene presented in all strategy I plants in controlling effective iron acquisition system in roots.展开更多
By reducing cysteine-sulfinic acid in oxidized peroxiredoxin, sulfiredoxin （Srx） plays an important role in oxidation stress resistance in yeast and human cells. Here, we report the first molecular and functional ch...By reducing cysteine-sulfinic acid in oxidized peroxiredoxin, sulfiredoxin （Srx） plays an important role in oxidation stress resistance in yeast and human cells. Here, we report the first molecular and functional characterization of Srx homolog from higher plants. Bioinformatic analysis revealed the presence of potential Srx encoding sequences in both monocot and dicot plant species. Putative plant Srx proteins exhibited significant identities to their orthologs from yeast and human, and contained the conserved signature sequence and residues essential for catalysis. However, unlike yeast and human orthologs, plant Srxs were all predicted to possess chloroplast transit peptide in their primary structure. The Srx proteins from Arabidopsis and rice （designated as AtSrx and OsSrx, respectively） complemented functional deficiency of Srx in the SRX1 deletion yeast cells. A GFP fusion protein of AtSrx was targeted to chloroplast in Arabidopsis mesophyll protoplast. AtSrx transcription occurred in both vegetative and reproductive organs, and the highest transcript level was detected in leaves. Under oxidation stress, AtSrx transcript level was substantially increased, which paralleled with enhanced transcription of 2-Cys peroxiredoxins that have been found essential in maintaining chloroplast redox balance. In addition to oxidation stress, osmotic/water deficit or cold treatments also raised AtSrx transcript level. Consistent with above findings, the knock-out mutant of AtSrx was significantly more susceptible to oxidation stress than wild type Arabidopsis plant. Taken together, the results of this work indicate the existence of functional Srx homolog in higher plants that is essential for plants to cope with oxidation stress.展开更多
Previous studies have shown that Arabidopsis equilibrative nucleoside transporters （AtENTs） possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, w...Previous studies have shown that Arabidopsis equilibrative nucleoside transporters （AtENTs） possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, we report further analysis on the nucleoside transport activities and transcriptional patterns of AtENT members. The recombinant proteins of AtENTs 3, 6, and 7, but not those of AtENTs 1, 2, 4, and 8, were found to transport thymidine with high affinity. Contrary to previ- ous suggestion that AtENT 1 may not transport uridine, this work showed that recombinant AtENT 1 was a pH-dependent and high-affinity transporter of uridine. When grown on MS plates, the AtENT3 knockout plants were more tolerant to the cytotoxic uridine analog 5-fluorouridine than wild-type plants and the knockout plants ofAtENT 1 or AtENT6. Con- sistent with this observation, the AtENT3 knockout line exhibited a significantly decreased ability to take up [^3H]uridine via the roots when compared with wild-type plants and the plants with mutated AtENT 1 or AtENT6. This indicates that AtENT3, but not AtENTs 1 and 6, is the main transporter for uridine uptake in Arabidopsis roots. The transcription of AtENTs 1, 3, 4, 6, 7, and 8 was regulated in a complex manner during leaf development and senescence. In contrast, the six AtENT members were coordinately induced during seed germination. This work provides new information on the transport properties of recombinant AtENT proteins and new clues for future studies of the in vivo transport activities and physiological functions of the different ENT proteins in Arabidopsis plants.展开更多
Arachidonic acid cytochrome P-450 （CYP） hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids （20-HETE）, a biologicall...Arachidonic acid cytochrome P-450 （CYP） hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids （20-HETE）, a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adenoassociated viral vector （rAAV） to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley （SD） rats and spontaneously hypertensive rats （SHR）, respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hyperténsion. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV.4A 1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV.anti4A l-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4Al-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys, but 4A l protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxylases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hypertension by blocking expression of CYP 4A in kidneys.展开更多
Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently...Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.展开更多
Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics t...Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3(CVB3)-induced FM in A/J mice,spanning seven distinct time points pre-and post-treatment.Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection.This triggers the activation of macrophages,initiating a cascade of inflammation.Subsequently,pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium,driving tissue damage.We also identified Cd8+effector T cells as key mediators of cardiomyocyte injury.These cells release cytotoxic molecules,particularly IFN-γ,which modulates the expression of Spi1,a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression.Therapeutic interventions targeting the IFN-γ/Spi1 axis demonstrated significant efficacy in FM models.Notably,intravenous immunoglobulin(IVIG)treatment reduced mortality,suppressed viral proliferation,and mitigated the hyperinflammatory state of FM.IVIG therapy also downregulated IFN-γ and Spi1 expression,underscoring its immunomodulatory and therapeutic potential.This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets,paving the way for more effective management strategies for this life-threatening condition.展开更多
DearEditor,SinceDecemberr2019,severeaacute respiratory syndrome coronavirus 2(SARS-CoV-2)has widely spread worldwide,and we have been fighting against coronavirus disease 2019(COVID-19)for more than 4 years[1].Accordi...DearEditor,SinceDecemberr2019,severeaacute respiratory syndrome coronavirus 2(SARS-CoV-2)has widely spread worldwide,and we have been fighting against coronavirus disease 2019(COVID-19)for more than 4 years[1].According to the statistics of the World Health Organization(WHO),more than 775 million individuals have incurred COVID-19,and 7 million deaths have been recorded.展开更多
Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implica...Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis(FM),acute respiratory distress syndrome(ARDS),primary or secondary hemophagocytic lymphohistiocytosis(HLH),cytokine release syndrome(CRS)associated with chimeric antigen receptor-modified T(CAR-T)therapy,and grade Ⅲ to Ⅳ acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.The significant involvement of the JAK-STAT pathway,Toll-like receptors,neutrophil extracellular traps,NLRP3 inflammasome,and other signaling pathways has been recognized in the pathogenesis of CS.Therapies targeting these pathways have been developed or are currently being investigated.While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS,the overall mortality rate of CS resulting from underlying diseases remains high.In the clinical setting,the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation,the preservation of vital organ function,the treatment of the underlying disease,and the provision of life supportive therapy.This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS,elucidates the impact of dysregulated immune cell activation,and delineates the resultant organ injury associated with CS.In addition,we offer insights and current literature on the management of CS in cases of FM,ARDS,systemic inflammatory response syndrome,treatment-induced CRS,HLH,and other related conditions.展开更多
Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium.It is characterized by acute onset,rapid progress and high risk of death.Its pathogenesis involves excessive immune activation of the innate...Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium.It is characterized by acute onset,rapid progress and high risk of death.Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm.According to China’s practical experience,the adoption of the“life support-based comprehensive treatment regimen”(with mechanical circulation support and immunomodulation therapy as the core)can significantly improve the survival rate and long-term prognosis.Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.展开更多
Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid phenylalanine.There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular d...Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid phenylalanine.There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases.In this review,we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln.We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases,such as heart failure,coronary heart disease/atherosclerosis,and cardiac arrhythmia.The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors.Besides,other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln.Moreover,since PAGln is produced across different organs including the intestine,liver,and kidney,the cross-talk among multiple organs focused on the function of this uremic toxic metabolite.Finally,the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.展开更多
CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function...CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in DCM.Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts.Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in vivo.Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts.CFIRL knockdown attenuated these effects.Mechanistically,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate IL-6transcription.IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL knockdown.These findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes.CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.展开更多
lncRNA ZNF593 antisense(ZNF593-AS)transcripts have been implicated in heart failure through the regulation of myocardial contractility.The decreased transcriptional activity of ZNF593-AS has also been detected in card...lncRNA ZNF593 antisense(ZNF593-AS)transcripts have been implicated in heart failure through the regulation of myocardial contractility.The decreased transcriptional activity of ZNF593-AS has also been detected in cardiac hypertrophy.However,the function of ZNF593-AS in cardiac hypertrophy remains unclear.Herein,we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine(PE).In vivo,ZNF593-AS aggravated pressure overload–induced cardiac hypertrophy in knockout mice.By contrast,cardiomyocyte-specific transgenic mice(ZNF593-AS MHC-Tg)exhibited attenuated TAC-induced cardiac hypertrophy.In vitro,vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy,whereas GapmeR-induced inhibition aggravated hypertrophic phenotypes.By using RNA-seq and gene set enrichment analyses,we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2(Mfn2)is a direct target of ZNF593-AS.ZNF593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial function.Therefore,it represents a promising therapeutic target for combating pathological cardiac remodeling.展开更多
This case report described a 61-year-old woman who presented with dizziness,headache,muscle ache,diplopia,and vomiting who lost consciousness.Upon hospital admission,the levels of high-sensitivity cardiac troponin I a...This case report described a 61-year-old woman who presented with dizziness,headache,muscle ache,diplopia,and vomiting who lost consciousness.Upon hospital admission,the levels of high-sensitivity cardiac troponin I and partial pressure of carbon dioxide were increased markedly.Loss of consciousness occurred twice after removal of invasive ventilator support.Coronary angiography demonstrated no stenosis in coronary arteries.Ultrasonography revealed inactivity of respiratory muscles.Oculomotor disturbance and autonomic-nerve dysfunctions were observed.Serum antibody against glutamic acid decarboxylase was positive.The rare phenotypes of persistent stiffness of muscles in the neck,face,bilateral upper and lower limbs were observed.The patient was diagnosed with fulminant myocarditis complicated by Stiff-person syndrome.Immunomodulatory treatment(glucocorticoids and immunoglobulins)elicited satisfactory therapeutic effects.In this case report,it was found that fulminant myocarditis and Stiff-person syndrome shared a common pathogenesis:"cytokine storm".Such patients may benefit from early treatment with immunomodulatory agents.展开更多
The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) ...The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored.We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment.Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled.Conventional echocardiographic measurements were obtained,and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%).Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified,and their changes with time were monitored in 14 FM patients.All patients had severely impaired cardiac function.Steep improvement in LVEF and GLS were observed within 6 days.Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal.In conclusion,FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days.The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.展开更多
In December 2019,an outbreak of novel coronavirus(2019-nCoV)occurred in Wuhan,Hubei Province,China.By February 14,2020,it has led to 66492 confirmed patients in China and high mortality up to^2.96%(1123/37914)in Wuhan...In December 2019,an outbreak of novel coronavirus(2019-nCoV)occurred in Wuhan,Hubei Province,China.By February 14,2020,it has led to 66492 confirmed patients in China and high mortality up to^2.96%(1123/37914)in Wuhan.Here we report the first family case of coronavirus disease 2019(COVID-19)confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid(SHL).This report describes the identification,diagnosis,clinical course,and management of three cases from a family,suggests the expected therapeutic effects of SHL on COVID-19,and warrants further clinical trials.展开更多
The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyz...The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.展开更多
Fulminant myocarditis(FM)is characterized by a rapid progressive decline in cardiac function and a high mortality rate.Since the first report of FM patients in the 1980s,several clinical trials and research studies ha...Fulminant myocarditis(FM)is characterized by a rapid progressive decline in cardiac function and a high mortality rate.Since the first report of FM patients in the 1980s,several clinical trials and research studies have been published increasing our knowledge regarding FM.Currently,the diagnosis of FM depends on various techniques including electrocardiography,echocardiography,endomyocardial biopsy,and cardiac magnetic resonance.The development of mechanical circulation support(MCS)devices and progress in our understanding of the pathophysiological mechanisms underlying FM,treatment regimens have evolved from simple symptomatic treatment to a life support-based comprehensive treatment approach.The core mechanism underlying the development of FM is the occurrence of an inflammatory cytokine storm.This review provides a comprehensive account of the current understanding of FM pathophysiology and knowledge regarding its etiology,pathophysiology,treatments,and outcomes.展开更多
Dear Editor,Patients presenting with acute myocarditis and sudden hemodynamic instability (termed fulminant myocarditis [FM]) still have a high mortality and need for heart transplantation, up to 28% at 60 days.1,2,3 ...Dear Editor,Patients presenting with acute myocarditis and sudden hemodynamic instability (termed fulminant myocarditis [FM]) still have a high mortality and need for heart transplantation, up to 28% at 60 days.1,2,3 Recent scientific statements and expert opinion consensus suggests early use of temporary mechanical circulatory supports (t-MCS).3,4 Specifically, Chinese scientific statement proposed an extensive use of t-MCS combined with immunoregulatory therapy (IT),4 although formal trials are lacking. We present a multicenter, retrospective study to compare the outcome of patients who were treated with t-MCS and IT vs. patients who didn’t receive these treatments. We included patients with the diagnosis of FM based on the presence of viral prodromal signs/symptoms followed by acute onset of severe heart failure (HF) without other relevant differential diagnosis or pre-existing cardiac disorders. Patients who received both t-MCS and IT during hospitalization were classified as t-MCS+IT group.展开更多
We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by...We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard care.The control group was composed of 59 patients who received standard therapy alone.Treatment with SHL was not associated with a difference from standard care in the time to disease recovery.Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL groups.This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.展开更多
Cardiovascular diseases account for approximately 80%of deaths among individuals with diabetes mellitus,with diabetic cardiomyopathy as the major diabetic cardiovascular complication.Hyperglycemia is a symptom that ab...Cardiovascular diseases account for approximately 80%of deaths among individuals with diabetes mellitus,with diabetic cardiomyopathy as the major diabetic cardiovascular complication.Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy,fibrosis,apoptosis,and other pathophysiological changes.Although glycemic control has long been at the center of diabetes therapy,multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes.This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level.This process is now referred to as hyperglycemic memory(HGM)phenomenon.We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.展开更多
基金supported by grants from the Ministry of Science and Technology of China(Grant No.2004AA222110)the National Natural Science Foundation of China(Grant No.30225029).
文摘AtbHLH29 of Arabidopsis, encoding a bHLH protein, reveals a high similarity to the tomato FER which is proposed as a transcriptional regulator involved in controlling the iron deficiency responses and the iron uptake in tomato. For identification of its biological functions, AtbHLH29 was introduced into the genome of the tomato FER mutant T3238fer mediated by Agrobacterium tumefaciencs. Transgenic plants were regenerated and the stable integration of AtbHLH29 into their genomes was confirmed by Southern hybridization. Molecular analysis demonstrated that expression of the exogenous AtbHLH29 of Arabidopsis in roots of the FER mutant T3238fer enabled to complement the defect functions of FER. The transgenic plants regained the ability to activate the whole iron deficiency responses and showed normal growth as the wild type under iron-limiting stress. Our transformation data demonstrate that AtbHLH29 is a functional ortholog of the tomato FER and can completely replace FER in controlling the effective iron acquisition in tomato. Except of iron, FER protein was directly or indirectly involved in manganese homeostasis due to that loss functions of FER in T3238fer resulted in strong reduction of Mn content in leaves and the defect function on Mn accumulation in leaves was complemented by expression of AtbHLH29 in the transgenic plants. Identification of the similar biological functions of FER and AtbHLH29, which isolated from two systematically wide-diverged “strategy I” plants, suggests that FER might be a universal gene presented in all strategy I plants in controlling effective iron acquisition system in roots.
文摘By reducing cysteine-sulfinic acid in oxidized peroxiredoxin, sulfiredoxin （Srx） plays an important role in oxidation stress resistance in yeast and human cells. Here, we report the first molecular and functional characterization of Srx homolog from higher plants. Bioinformatic analysis revealed the presence of potential Srx encoding sequences in both monocot and dicot plant species. Putative plant Srx proteins exhibited significant identities to their orthologs from yeast and human, and contained the conserved signature sequence and residues essential for catalysis. However, unlike yeast and human orthologs, plant Srxs were all predicted to possess chloroplast transit peptide in their primary structure. The Srx proteins from Arabidopsis and rice （designated as AtSrx and OsSrx, respectively） complemented functional deficiency of Srx in the SRX1 deletion yeast cells. A GFP fusion protein of AtSrx was targeted to chloroplast in Arabidopsis mesophyll protoplast. AtSrx transcription occurred in both vegetative and reproductive organs, and the highest transcript level was detected in leaves. Under oxidation stress, AtSrx transcript level was substantially increased, which paralleled with enhanced transcription of 2-Cys peroxiredoxins that have been found essential in maintaining chloroplast redox balance. In addition to oxidation stress, osmotic/water deficit or cold treatments also raised AtSrx transcript level. Consistent with above findings, the knock-out mutant of AtSrx was significantly more susceptible to oxidation stress than wild type Arabidopsis plant. Taken together, the results of this work indicate the existence of functional Srx homolog in higher plants that is essential for plants to cope with oxidation stress.
基金This work was supported by grants from the National Natural Science Foundation of China （39770491） the Chinese Academy of Sciences （KSCX2-SW-304）.
文摘Previous studies have shown that Arabidopsis equilibrative nucleoside transporters （AtENTs） possess transport activities when produced in yeast cells and are differentially expressed in Arabidopsis organs. Herein, we report further analysis on the nucleoside transport activities and transcriptional patterns of AtENT members. The recombinant proteins of AtENTs 3, 6, and 7, but not those of AtENTs 1, 2, 4, and 8, were found to transport thymidine with high affinity. Contrary to previ- ous suggestion that AtENT 1 may not transport uridine, this work showed that recombinant AtENT 1 was a pH-dependent and high-affinity transporter of uridine. When grown on MS plates, the AtENT3 knockout plants were more tolerant to the cytotoxic uridine analog 5-fluorouridine than wild-type plants and the knockout plants ofAtENT 1 or AtENT6. Con- sistent with this observation, the AtENT3 knockout line exhibited a significantly decreased ability to take up [^3H]uridine via the roots when compared with wild-type plants and the plants with mutated AtENT 1 or AtENT6. This indicates that AtENT3, but not AtENTs 1 and 6, is the main transporter for uridine uptake in Arabidopsis roots. The transcription of AtENTs 1, 3, 4, 6, 7, and 8 was regulated in a complex manner during leaf development and senescence. In contrast, the six AtENT members were coordinately induced during seed germination. This work provides new information on the transport properties of recombinant AtENT proteins and new clues for future studies of the in vivo transport activities and physiological functions of the different ENT proteins in Arabidopsis plants.
基金This project Was supported by the National Natural Science Foundation of China(NSFC,No.39870307)National Basic Research Program of China(973 Program,No.G2000056901)KC was the recipient of an Fonds de la recherche en sante du Quebec(FRSQ,Quebec-Canada)-NSFC(China exchange grant).
文摘Arachidonic acid cytochrome P-450 （CYP） hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids （20-HETE）, a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adenoassociated viral vector （rAAV） to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley （SD） rats and spontaneously hypertensive rats （SHR）, respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hyperténsion. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV.4A 1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV.anti4A l-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24 weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4Al-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys, but 4A l protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxylases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension. rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hypertension by blocking expression of CYP 4A in kidneys.
基金grant of National Key Research and Development Program of China(2022YFC3400700)National Natural Science Foundation of China(Nos.82241034,82370397,31971358,U22A20266 and C-0052)+2 种基金Top-Notch Talent Program of Hubei Province and Tongji Hospital(No.2021YBJRC005)Hubei Provincial Key Research and Developmental Program(2022BCA037)Hubei Provincial Natural Science Foundation of China(2017CFB536).
文摘Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.
基金supported by the High-performance Computing Platform of YaZhou Bay Science and Technology City Advanced Computing Center(YZBSTCACC)the National Natural Science Foundation of China(Nos.82330010 and 82241034 to DWW).
文摘Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3(CVB3)-induced FM in A/J mice,spanning seven distinct time points pre-and post-treatment.Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection.This triggers the activation of macrophages,initiating a cascade of inflammation.Subsequently,pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium,driving tissue damage.We also identified Cd8+effector T cells as key mediators of cardiomyocyte injury.These cells release cytotoxic molecules,particularly IFN-γ,which modulates the expression of Spi1,a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression.Therapeutic interventions targeting the IFN-γ/Spi1 axis demonstrated significant efficacy in FM models.Notably,intravenous immunoglobulin(IVIG)treatment reduced mortality,suppressed viral proliferation,and mitigated the hyperinflammatory state of FM.IVIG therapy also downregulated IFN-γ and Spi1 expression,underscoring its immunomodulatory and therapeutic potential.This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets,paving the way for more effective management strategies for this life-threatening condition.
基金supported in part by the projects of National Natural Science Foundation of China(Nos.82100526,82241034,and 82330010)National Key R&D Program of China(No.2024YFC3044500).
文摘DearEditor,SinceDecemberr2019,severeaacute respiratory syndrome coronavirus 2(SARS-CoV-2)has widely spread worldwide,and we have been fighting against coronavirus disease 2019(COVID-19)for more than 4 years[1].According to the statistics of the World Health Organization(WHO),more than 775 million individuals have incurred COVID-19,and 7 million deaths have been recorded.
基金supported by grants from the National High Technology Research and Development Program of China(Grant 2021YFA1101500)the National Natural Science Foundation of China(Nos.82070217,82100401,81873427,82330010,81630010,82473220,81790624,81772477,81201848)+8 种基金the Hubei Provincial Natural Science Foundation(No.2024AFB050)the Fundamental Research Program of Shanxi Province(No.202303021221192)2023 COVID-19 Emergency Project of Shanxi Health Commission(Nos.2023XG001,2023XG005)the Project of Shanxi Bethune Hospital(No.2023xg02)Fundamental Research Program of Shanxi Province(No.202303021211224)the Key Scientific Research Project of COVID-19 Infection Emergency Treatment of Shanxi Bethune Hospital(No.2023xg01)the Four“Batches”Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(2023XM003)the Cancer special Fund research project of Shanxi Bethune Hospital(No.2020-ZL04)External Expert Workshop Fund Program of Shanxi Provincial Health Commission(Proteomics Shanxi studio for Huanghe professor).
文摘Cytokine storm(CS)is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines.This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis(FM),acute respiratory distress syndrome(ARDS),primary or secondary hemophagocytic lymphohistiocytosis(HLH),cytokine release syndrome(CRS)associated with chimeric antigen receptor-modified T(CAR-T)therapy,and grade Ⅲ to Ⅳ acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.The significant involvement of the JAK-STAT pathway,Toll-like receptors,neutrophil extracellular traps,NLRP3 inflammasome,and other signaling pathways has been recognized in the pathogenesis of CS.Therapies targeting these pathways have been developed or are currently being investigated.While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS,the overall mortality rate of CS resulting from underlying diseases remains high.In the clinical setting,the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation,the preservation of vital organ function,the treatment of the underlying disease,and the provision of life supportive therapy.This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS,elucidates the impact of dysregulated immune cell activation,and delineates the resultant organ injury associated with CS.In addition,we offer insights and current literature on the management of CS in cases of FM,ARDS,systemic inflammatory response syndrome,treatment-induced CRS,HLH,and other related conditions.
基金supported in part by the National Natural Science Foundation of China(81790624,81630010)Top-Notch Talent Program of Hubei Province and Tongji Hospital(2021YBJRC005)。
文摘Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium.It is characterized by acute onset,rapid progress and high risk of death.Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm.According to China’s practical experience,the adoption of the“life support-based comprehensive treatment regimen”(with mechanical circulation support and immunomodulation therapy as the core)can significantly improve the survival rate and long-term prognosis.Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.
基金supported by the National Key Research and Development Program of China(No.2022YFC3400700)National Natural Science Foundation of China(Nos.31971358,82370397,U22A20266,and 82100402)+1 种基金Hubei Provincial Key Research and Developmental Program(No.2022BCA037)Hubei Provincial Natural Science Foundation of China(Nos.2017CFB536 and 2022CFB201).
文摘Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid phenylalanine.There are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular diseases.In this review,we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of PAGln.We summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases,such as heart failure,coronary heart disease/atherosclerosis,and cardiac arrhythmia.The underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic receptors.Besides,other possible mechanisms such as inflammatory response and oxidative stress could also be induced by PAGln.Moreover,since PAGln is produced across different organs including the intestine,liver,and kidney,the cross-talk among multiple organs focused on the function of this uremic toxic metabolite.Finally,the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(U22A20266,82170273,81630010)the Fundamental Research Funds for the Central Universities(2019kfy XMBZ035,2021yjs CXCY090)Fundamental Research Funds of Wuhan Innovation Program(2022020801020451)。
文摘CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in DCM.Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts.Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in vivo.Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts.CFIRL knockdown attenuated these effects.Mechanistically,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate IL-6transcription.IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL knockdown.These findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes.CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.
基金supported by grants from the National Natural Science Foundation of China(Nos.82100399,82100400,and 81790624)the project funded by China Postdoctoral Science Foundation(No.2021M701315).
文摘lncRNA ZNF593 antisense(ZNF593-AS)transcripts have been implicated in heart failure through the regulation of myocardial contractility.The decreased transcriptional activity of ZNF593-AS has also been detected in cardiac hypertrophy.However,the function of ZNF593-AS in cardiac hypertrophy remains unclear.Herein,we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine(PE).In vivo,ZNF593-AS aggravated pressure overload–induced cardiac hypertrophy in knockout mice.By contrast,cardiomyocyte-specific transgenic mice(ZNF593-AS MHC-Tg)exhibited attenuated TAC-induced cardiac hypertrophy.In vitro,vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy,whereas GapmeR-induced inhibition aggravated hypertrophic phenotypes.By using RNA-seq and gene set enrichment analyses,we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2(Mfn2)is a direct target of ZNF593-AS.ZNF593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial function.Therefore,it represents a promising therapeutic target for combating pathological cardiac remodeling.
基金supported by the National Nature Science Foundation of China(81790624)Tongji Hospital Clinical Research Flagship Program(2019CR207)NFSC projects(82100510).
文摘This case report described a 61-year-old woman who presented with dizziness,headache,muscle ache,diplopia,and vomiting who lost consciousness.Upon hospital admission,the levels of high-sensitivity cardiac troponin I and partial pressure of carbon dioxide were increased markedly.Loss of consciousness occurred twice after removal of invasive ventilator support.Coronary angiography demonstrated no stenosis in coronary arteries.Ultrasonography revealed inactivity of respiratory muscles.Oculomotor disturbance and autonomic-nerve dysfunctions were observed.Serum antibody against glutamic acid decarboxylase was positive.The rare phenotypes of persistent stiffness of muscles in the neck,face,bilateral upper and lower limbs were observed.The patient was diagnosed with fulminant myocarditis complicated by Stiff-person syndrome.Immunomodulatory treatment(glucocorticoids and immunoglobulins)elicited satisfactory therapeutic effects.In this case report,it was found that fulminant myocarditis and Stiff-person syndrome shared a common pathogenesis:"cytokine storm".Such patients may benefit from early treatment with immunomodulatory agents.
基金The project was supported by the grant from the National Natural Science Foundation of China(Nos.81873535 and 81570367)We thank Dr.Jonathan R.Linder who gave us helpful suggestions in writing the manuscript.
文摘The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored.We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment.Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled.Conventional echocardiographic measurements were obtained,and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%).Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified,and their changes with time were monitored in 14 FM patients.All patients had severely impaired cardiac function.Steep improvement in LVEF and GLS were observed within 6 days.Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal.In conclusion,FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days.The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.
基金This work was supported by Tongji Hospital Clinical Research Flagship Program(No.2019CR207).
文摘In December 2019,an outbreak of novel coronavirus(2019-nCoV)occurred in Wuhan,Hubei Province,China.By February 14,2020,it has led to 66492 confirmed patients in China and high mortality up to^2.96%(1123/37914)in Wuhan.Here we report the first family case of coronavirus disease 2019(COVID-19)confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid(SHL).This report describes the identification,diagnosis,clinical course,and management of three cases from a family,suggests the expected therapeutic effects of SHL on COVID-19,and warrants further clinical trials.
基金supported in part by National Nature Science Foundation of China(Nos.81790624,81700333,81900363,and 81900244)the Deutsche Forschungsgemeinschaft:SFB1039/A6(to I.F.).
文摘The arachidonic acid(AA)pathway plays a key role in cardiovascular biology,carcinogenesis,and many inflammatory diseases,such as asthma,arthritis,etc.Esterified AA on the inner surface of the cell membrane is hydrolyzed to its free form by phospholipase A2 (PLA2),which is in turn further metabolized by cyclooxygenases(COXs)and lipoxygenases(LOXs)and cytochrome P450(CYP)enzymes to a spectrum of bioactive mediators that includes prostanoids,leukotrienes(LTs),epoxyeicosatrienoic acids(EETs),dihydroxyeicosatetraenoic acid(diHETEs),eicosatetraenoic acids(ETEs),and lipoxins(LXs).Many of the latter mediators are considered to be novel preventive and therapeutic targets for cardiovascular diseases(CVD),cancers,and inflammatory diseases.This review sets out to summarize the physiological and pathophysiological importance of the AA metabolizing pathways and outline the molecular mechanisms underlying the actions of AA related to its three main metabolic pathways in CVD and cancer.progression will provide valuable insight for developing new therapeutic drugs for CVD and anti-cancer agents such as inhibitors of EETs or 2J2.Thus,we herein present a synopsis of AA metabolism in human health,cardiovascular and cancer biology,and the signaling pathways involved in these processes.To explore the role of the AA metabolism and potential therapies,we also introduce the current newly clinical studies targeting AA metabolisms in the different disease conditions.
基金supported by grants from the National Natural Science Foundation of China(91839302,81630010,and 81790624)Tongji Hospital Clinical Research Flagship Program(2019CR207)JMS is support by a grant from the Canadian Institutes of Health Sciences(FRN156393).
文摘Fulminant myocarditis(FM)is characterized by a rapid progressive decline in cardiac function and a high mortality rate.Since the first report of FM patients in the 1980s,several clinical trials and research studies have been published increasing our knowledge regarding FM.Currently,the diagnosis of FM depends on various techniques including electrocardiography,echocardiography,endomyocardial biopsy,and cardiac magnetic resonance.The development of mechanical circulation support(MCS)devices and progress in our understanding of the pathophysiological mechanisms underlying FM,treatment regimens have evolved from simple symptomatic treatment to a life support-based comprehensive treatment approach.The core mechanism underlying the development of FM is the occurrence of an inflammatory cytokine storm.This review provides a comprehensive account of the current understanding of FM pathophysiology and knowledge regarding its etiology,pathophysiology,treatments,and outcomes.
基金This work grants from the National Natural Science Foundation of China(No.81790624 and 81630010,82070316)National Key R&D Program of China(NO.2017YFC0909400).
文摘Dear Editor,Patients presenting with acute myocarditis and sudden hemodynamic instability (termed fulminant myocarditis [FM]) still have a high mortality and need for heart transplantation, up to 28% at 60 days.1,2,3 Recent scientific statements and expert opinion consensus suggests early use of temporary mechanical circulatory supports (t-MCS).3,4 Specifically, Chinese scientific statement proposed an extensive use of t-MCS combined with immunoregulatory therapy (IT),4 although formal trials are lacking. We present a multicenter, retrospective study to compare the outcome of patients who were treated with t-MCS and IT vs. patients who didn’t receive these treatments. We included patients with the diagnosis of FM based on the presence of viral prodromal signs/symptoms followed by acute onset of severe heart failure (HF) without other relevant differential diagnosis or pre-existing cardiac disorders. Patients who received both t-MCS and IT during hospitalization were classified as t-MCS+IT group.
基金This work was supported by the National Key R&D Program of China(No.2020YFC0841400)Tongji Hospital Clinical Research Project(Nos.XXGZBDYJ009 and 2019YBKY019).
文摘We conducted a randomized,open-label,parallel-controlled,multicenter trial on the use of Shuanghuanglian(SHL),a traditional Chinese patent medicine,in treating cases of COVID-19.A total of 176 patients received SHL by three doses(56 in low dose,61 in middle dose,and 59 in high dose)in addition to standard care.The control group was composed of 59 patients who received standard therapy alone.Treatment with SHL was not associated with a difference from standard care in the time to disease recovery.Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group(93.4%vs.73.9%,P=0.006).Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia,which was evaluated by density reduction of inflammatory focus from baseline,at day 7(mean difference(95%CI),−46.39(−86.83 to−5.94)HU;P=0.025)and day 14(mean difference(95%CI),−74.21(−133.35 to−15.08)HU;P=0.014).No serious adverse events occurred in the SHL groups.This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
基金supported by grants from the National Natural Science Foundation of China(Nos.81822002,31771264,31800973)the Fundamental Research Funds for the Central Universities(No.2019kfyXMBZ035).
文摘Cardiovascular diseases account for approximately 80%of deaths among individuals with diabetes mellitus,with diabetic cardiomyopathy as the major diabetic cardiovascular complication.Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy,fibrosis,apoptosis,and other pathophysiological changes.Although glycemic control has long been at the center of diabetes therapy,multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes.This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level.This process is now referred to as hyperglycemic memory(HGM)phenomenon.We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
