Sacubitril/valsartan inhibit viral replication and cardiomyocyte apoptosis in mice with CVB3-induced viral myocarditis via PI3K/AKT pathway / 中华微生物学和免疫学杂志

Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.

Characteristic of cardiac and neurological forms of non-polio enterovirus infection

Enterovirus infections (EVI) are ubiquitous and generally present with mild symptoms and have a favorableprognosis with full recovery. But sometimes it can be challenging to diagnose mixed forms of EVI which can result in fatal outcomes. An interesting case report on a patient admitted to the Grodno Regional infectious diseases clinical hospital. The patientwas diagnosed with enteroviral infection. Histological slides of the brain, heart, lung and other systemic organs were prepared on autopsy and are presented in this scientific paper. Generalized EVI in mixed form can cause primary lesions of the brain (destructive edema), the heart (necrotizing cardiomyopathy), and sepsis while also affecting other organ systems. This can lead to unfavorable outcomes similar to that in our case report. Mixed form EVI (meningitis, myocarditis, and sepsis) can progress rapidly towards an adverse course, with the development of severe life-threatening complications. We strongly suggest that mandatory PCR screening for EVI should be carried out in young individuals with sepsis-like diseases and with a fever of unexplained origin at the time of presentation.

Viral Myopericarditis and Viral Encephalitis as manifestations of COVID-19 infection: A case report

Introduction@#Coronavirus disease (COVID-19) is currently a global health crisis and is caused by a new strain of coronavirus. However, emerging literature of case reports noted possible extrapulmonary manifestations of the disease. Because COVID 19 is a relatively new disease, at present, little existing literature tackles the diagnosis and therapeutic management of COVID‐19‐related conditions outside the pulmonary system.@*Case@#A 24-year-old male presented with sudden stiffening of all extremities but non-contrast computed tomography (CT) scan was unremarkable. Chest X-ray revealed interstitial pneumonia and SARS-CoV-2 RT-PCR (OPS/NPS) was positive. Electrocardiogram (ECG) findings showed supraventricular tachycardia and had elevated Troponin I levels. Pertinent physical findings noted were slurring of speech, dysmetria, and vertical nystagmus. The patient was initially treated as a case of Bacterial Abscess versus Viral encephalitis. Pericardial ultrasound revealed small pericardial effusion and was started on Colchicine. Repeat cranial CT scan noted unremarkable results but due to persistence of symptoms, the patient was started with Dexamethasone. On Day 16 of illness, the patient was noted to have full resolution of symptoms. Rapid antibody testing was done which revealed positive for both IgG and IgM hence the patient was discharged with the final diagnosis of Viral Myopericarditis resolved, Viral encephalitis resolved, COVID-19 pneumonia recovered.@*Conclusion@#Extrapulmonary manifestations have been reported increasingly as an atypical presentation of COVID 19 infection. Early recognition of viral myopericarditis and viral encephalitis as a manifestation of COVID 19 can lead to the initiation of proper treatment and management. More reports on these cases can aid future studies on diagnostics and therapeutic approaches during the COVID-19 pandemic.

Application of exosomes in the diagnosis and treatment of cardiovascular diseases / 国际儿科学杂志

The cardiovascular diseases, which have the increasing incidence and high mortality rate, have brought a great impact on people′s lives and health.Being lipid inclusions with 30~150 nm in diameter, exosomes can be secreted by most cells in the body, and proteins, lipids, nucleic acids and other substances derived from those cells are wrapped inside.Exosomes play a variety of biological roles in the communication between cells, such as mediating immune response, inflammatory response, cell migration and differentiation.Research on exosomes has made significant progress, and the roles of exosomes in cardiovascular diseases have consequently attracted more and more attention in recent years.The communication of exosomes between cardiomyocytes and between heart and peripheral tissues has provided new strategies for the diagnosis and treatment of cardiovascular diseases.Application of exosomes in the diagnosis and treatment of cardiovascular diseases such as heart failure, viral myocarditis, Kawasaki disease and dilated cardiomyopathy is summarized in this review.

Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro / 中国中药杂志

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

Non-coding RNAs in viral myocarditis / 生物工程学报

Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.

Protective effect of resolvin D2 on inflammatory response and endoplasmic reticulum stress injury of CVB3-induced viral myocarditis mice and its mechanism / 中华微生物学和免疫学杂志

Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.

Research progress of the immune pathogenesis of viral myocarditis / 国际儿科学杂志

There is no consensus regarding pathogenesis of viral myocarditis in pediatric patients.It makes a big challenge in clinical diagnosis and treatment.The myocyte injury is wildly recognized to be initiated by viral proliferation and secondary host immune response.It may persist and lead to dilated cardiomyopathy.In serious cases, it could even end up with heart failure, cardiogenic shock and sudden death.A growing number of scholars consider that host immune response is the main cause of severe cardiomyopathy.This review outlines the current progress of immune response in viral myocarditis, aiming to assist the clinical diagnosis and treatment.

Research progress of the immune pathogenesis of viral myocarditis / 国际儿科学杂志

There is no consensus regarding pathogenesis of viral myocarditis in pediatric patients.It makes a big challenge in clinical diagnosis and treatment.The myocyte injury is wildly recognized to be initiated by viral proliferation and secondary host immune response.It may persist and lead to dilated cardiomyopathy.In serious cases,it could even end up with heart failure,cardiogenic shock and sudden death.A growing number of scholars consider that host immune response is the main cause of severe cardiomyopathy.This review outlines the current progress of immune response in viral myocarditis,aiming to assist the clinical diagnosis and treatment.

Anti-oxidation and Anti-inflammatory Effect of Yixinshu Capsule in Treatment of Qi-Yin Deficiency in Viral Myocarditis / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Yixinshu capsule for viral myocarditis (VMC) with deficiency of Qi and Yin, and to investigate its antioxidant and anti-inflammatory effect. Method:One hundred and thirty-two patients were randomly divided into control group (66 cases) and observation group (66 cases) by random number table. Patients in two group got comprehensive treatment of Western medicine, i.e. intravenous drip of creatine phosphate injection for 14 days, 1 g/time, 1 time/day. Coenzyme Q10 capsule, 1 grain/time, 3 times/day after meals. Trimetazidine dihydrochloride tablets, 1 tablet/time, 3 times/day during meals. And critically ill patients got intravenous drip of dexamethasone sodium phosphate injection for 14 days, 10-20 mg/time, 1 time/day. The control group took Wenxin granules orally,One bag at a time,3 times/day. Patients in observation group additionally got Yixinshu capsule, 3 grains/time, 3 times/days. The courses of treatment were 8 weeks in both groups. The serum troponin I (cTnI) and creatine phosphokinase (CK-MB) were monitored, and after treatment, the recovery rates of cTnI, CK-MB were recorded. Before and after treatment, the electrocardiogram was observed and the recovery rate after treatment was recorded. Before and after treatment, the scores of deficiency of Qi and Yin were graded, and levels of creatine phosphokinase (CPK), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-17 and IL-35 were detected. Echocardiography, left ventricular ejection fraction (LVEF), cardiac index (CI), and maximum velocity values between early and late diastolic (E/A) were detected. Result:In the analysis of rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.151, P<0.05). Recovery rates of cTnI, CK-MB and electrocardiogram in observation group were 82.26% (51/62), 90.32% (56/62) and 80.65% (50/62), higher than 65.00% (39/60), 73.33% (44/60) and 63.33% (38/60) in control group (P<0.05). Levels of serum cTnI, CK-MB, CPK, HBDH, LDH, AST, MDA, IFN-γ and IL-17 were lower than those in control group (P<0.01), while levels of LVEF, CI, E/A, SOD, GSH-Px, IL-10 and IL-35 were higher than those in control group (P<0.01). Conclusion:On the basis of comprehensive anti-infection treatment, Yixinshu capsule can additional protect myocardium by anti-inflammatory and antioxidant effect, reduce myocardial enzyme, promote the recovery of ECG and cardiac enzyme, improve cardiac function and improve the effect of clinical treatment.

International Clinical Practice Guideline of Traditional Chinese Medicine ‧ Viral Myocarditis / 中国实验方剂学杂志

At present, viral myocarditis is still an important problem to be solved in clinical practice. Traditional Chinese medicine (TCM) has unique advantages in the treatment of this disease. However, there is still a lack of relevant clinical practice guidelines to standardize and guide the diagnosis and treatment of this disease by TCM. Within the framework of relevant laws, regulations and technical guidance documents, International Clinical Practice Guideline of Traditional Chinese Medicine·Viral Myocarditis was developed by consensus of experts through the classification of evidences and recommendation of opinions based on relevant clinical research evidences at home and abroad in recent years. This guideline introduces the diagnosis, etiology, pathogenesis, syndrome differentiation and treatment, acupuncture treatment, prevention and rehabilitation of viral myocarditis. And it will provide guidance for clinicians of TCM and integrated Chinese and western medicine engaged in the prevention and treatment of viral myocarditis.

Clinical Efficacy of Shensuyin in Treating Adult Viral Myocarditis with Syndrome of Insufficiency of Lung-Qi / 中国实验方剂学杂志

Objective: To investigate the efficacy of Shensuyin in treating viralmyocarditis (VMC) with syndrome of insufficiency of lung-qi and the effect on levels of Th17 and Treg cells and relevant factors. Method: One hundred-four VMC cases were regaded as object of study and randomly divided into control group and observation group, with 52 cases in each group. Control group was treated with routine therapy by reference to ‘Chinese Guidelines for Diagnosis and Treatment of Heart Failure 2014’. In addition to the therapy of control group, observation group on the basis of treatment in the control group with Shensuyin, 1 dose/d, bid. One course of treatment was 8 weeks for both groups. Scores of Shensuyin, serum levels of Troponin I (cTnI) and cardiac free fatty acid binding protein (H-FABP), heart function and total efficacy were compared for both groups. Flow cytometry was used to detect peripheral blood levels of Th17 and Treg cells for the two groups. Serum levels of interleukin (IL) -17, IL-21, IL-10 were detected in both groups. Result: After treatment, scores of syndrome of Yin and Yang deficiency (shortness of breath, fatigue, dull chest pain, bad breath, cough) of observation group were obviously lower than those of control group (PPPPPConclusion: In addition to the routine therapy of VMC, the efficacy of Shensuyin has a significant effect in treating VMC with syndrome of lung qi deficiency, and the regulatory effect on levels of Th17 and Treg cells and relevant factors may be one of the effective ways.

Role of autophagy in the pathogenesis of myocarditis / 国际儿科学杂志

Myocarditis refers to diffuse or focal inflammatory cell infiltration of the myocardial interstitium and necrosis or degeneration of adjacent myocardial fiber caused by infection or other causes,which is one of the common diseases that cause the death of infants and adolescents.Viral infection is the main pathogenic factor,but the pathogenesis of myocarditis has not yet been fully elucidated.Autophagy is a highly conservative process of self-digestion,which can provide amino acids,ATP and other substances for cells in the state of inflammation or starvation to help cells survive the energy crisis under excessive stimulation.However,excessive autophagy can promote the replication of viruses,which leads to autophagic death.In recent years,some researchers found that autophagy is closely related to the process of viral myocarditis associated with Coxsackie virus B3.The role of autophagy in the pathogenesis of myocarditis is reviewed in this article.

Effects of Buyang Huanwu Decoction on the Expression of MMPs and TIMPs in Cardiac Tissue of Viral Myocarditis Model Mice / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis （VMC） model mice. METHODS： Male BALb/c mice were randomly divided into control group， model group， positive control group [captopril， 100 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6， 18， 36 g/（kg·d）]， with 24 mice in each group. Except for control group， other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling， control group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d， heart mass to body mass ratio （HW/BW） was measured at 4， 10， 20， 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining， and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining， and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d， relative expressions of MMP-1， MMP-3， MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay， and the ratio of MMPs to TIMPs was calculated. RESULTS： Compared with control group， mice in model group suffered from irritability， arch back， alleviation of stimulation response， reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium， accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW （at different time points of 10-30 d）， myocardial histopathological score （at different time points of 4-30 d）， ratio of type Ⅰ and Ⅲ collagen （at different time points of 4-30 d）， the expression of MMP-1 and MMP-9， ratio of MMPs to TIMPs were increased significantly， while the expression of MMP-3 and TIMP-1 were decreased significantly （P＜0.05）. Compared with model group， above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups （except for 10 d in Buyang huanwu decoction low-dose group）]， myocardial histopathological score （at different time points of 10-30 d in administration groups）， ratio of type Ⅰand Ⅲ collagen （at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group， at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups）， the expression of MMP-1 （positive control group and Buyang huanwu decoction high-dose group） and MMP-9 （administration groups）， ratio of MMPs to TIMPs （administration groups） were decreased significantly， while the expression of MMP-3 （positive control group， Buyang huanwu decoction low-dose and high-dose groups） and TIMP-1 （administration groups） were increased significantly （P＜0.05）. CONCLUSIONS： Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia， regulating the expression of MMPs and TIMPs， improving MMPs/TIMPs imbalance.

Protective effect of diosmetin on viral myocarditis of CVB3-induced suckling mice by regulating macrophage M1/M2 type polarization / 中国药理学与毒理学杂志

Objective: To study the protective effect of diosmetin on viral myocarditis induced by coxsackie virus B3 (CVB3) by regulating macrophage M1/M2 type polarization. Methods: BALB/c suckling mice were given ip 0.1 mL CVB3 virus culture solution of 1×105pfu, which was recorded as DO. After 24 h (D1), diosmetin (Dio) 12.5, 25 and 50 mg·kg-1were ig given, respectively, 7 d in succession. At the end of the experiment, mean arterial pressure (MAP), heart rate (HR), left ventricular systolic pressure (LVSP), expression levels of serum creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB) and myoglobin (Mb) were detected. The peripheral blood was collected to analyze and sort polarization of macrophage M1 and M2 in peripheral blood by flow cytometry. The pathological features of myocardial tissues were analyzed by HE staining and TUNEL staining. Western blotting was performed to detect the expressions of cleaved-caspase 3 and cleaved-caspase 9 in myocardial tissues. Macrophages were sorted from spleen tissues of suckling mice. After macrophages were treated with IFN-y 5 mg·L-1, CVB3 1×105pfu, Dio 20 μmol·L-1, CVB3 (1×105pfu)+Dio 20 μmol·L-1for 24 h, the expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in cells were detected by Western blotting. Results: Compared with normal control group, MAP, HR and LVSP in model group were significantly decreased (P<0.05). Compared with model group, MAP, HR and LVSP were significantly increased in Dio 12.5, 25 and 50 mg·kg-1groups (P<0.05). Compared with normal control group, levels of CK, CK-MB and Mb in serum, and apoptosis rate of cardiomyocytes in model group were significantly increased (P<0.05), so were expression levels of cleaved-caspase 3 and cleaved-caspase 9 in myocardial tissues (P<0.05). Compared with model group, levels of CK, CK-MB and Mb in serum, and apoptosis rate of cardiomyocytes were significantly decreased in Dio 12.5, 25 and 50 mg·kg-1groups (P<0.05), so were expression levels of cleaved-caspase 3 and cleaved-caspase 9 in myocardial tissues (P< 0.05). Compared with normal control group, positive percentages of F4/80+iNOS\F4/80+TLR4+and F4/ 80+CD40+in peripheral blood of model group were significantly increased, while those of F4/80+CD14\ F4/80+Arg-1+ and F4/80+CD206t were significantly decreased (P<0.05). Compared with model group, the former three items in peripheral blood were significantly decreased in Dio 12.5, 25 and 50 mg·kg-1groups, while the latter three items were significantly increased (P<0.05). Both IFN-γ and CVB3 virus could up-regulate the expression of iNOS, and inhibit the expression of Arg-1. The Dio treatment could inhibit the expression of iNOS and up- regulate the expression of Arg-1. Compared with CVB3 virus alone group, the expression of iNOS was decreased, but the expression of Arg-1 was increased in CVB3 + Dio group (P<0.05). Conclusion: Dio can inhibit the activation of M1 type macrophage caused by viral infection, promote its development towards M2 polarization, and improve cardiac function of the viral myocarditis model.

Protective effect of puerarin on viral myocarditis and the underlying mechanism / 国际儿科学杂志

Objective To detect the expression of Nrf2 in mice with viral myocarditis and to investigate the changes and effects of Nrf2 after puerarin (Pue) treatment.Methods A total of 130 BALB/C male mice aged 4 weeks were randomly divided into control group,VMC group,Nrf2 activator group and Pue group (20 mice in each group) with different concentrations.The models were made with Coxsackie B3 virus (CVB3).The mice were sacrificed on day 0,4,7,14 and 28 respectively,and blood and myocardial samples were harvested.Cardiomyocyte apoptosis was detected by flow cytometry.The expression changes of Nrf2,HO-1,Fas,TGF-beta 1 mRNA were detected by real-time PCR and Western blot respectively.Statistical software SPSS19.0 was used to analyze the results.The measurement data was expressed mean ± standard deviation.The paired samples were tested with mean t test.The group data were analyzed with two-way ANOVA.A P value of less than 0.05 was considered to indicate statistical significance.Correlation analysis was performed with Spearman's correlation test.Results Nrf2 mRNA and Nrf2 protein were expressed in all groups.The correlations between Nrf2 and HO-1,Fas and TGF-beta-1 were analyzed according to CPDT or Pue,and the results were consistent with each other.It showed that the relationship between Nrf2 and HO-1,Fas and TGF-beta-1 did not change with intervention measures.The transcription and protein expression of HO1 in CPDT and Pue groups were significantly increased,and were positively correlated with Nrf2 (r =0.969,P ＜0.01).At a certain dose gradient (＜ 45 mg/kg),the transcription and protein expression of HO-1 were dose-dependent;the decreased cardiomyocyte apoptosis was observed in both CPDT and Pue group,while Nrf2 and Fas were negatively correlated (r =-0.968,P ＜ 0.01);at a certain dose gradient,the expression of TGF-beta 1 in CPDT and Pue group decreased with the increase of dose,and Nrf2 and TGF-beta 1 were negatively correlated (r =-0.753,P ＜ 0.01).Conclusion The increased expression of Nrf2 in VMC is involved in the occurrence and development of VMC.Nrf2 has antioxidant effect in VMC by up-regulating the antioxidant enzyme HO-1,has the anti-myocardial APO effect by inhibiting the Fas/FasL signaling pathway,and inhibits myocardial fibrosis by suppressing the expression of TGF-beta 1 protein and transcription.The therapeutic effect of Pue on VMC is to activate Nrf2 to produce antioxidant,anti-apoptotic and anti-fibrotic effects.

Surto de parvovirose cardíaca em filhotes de cães no Brasil / Outbreak of parvoviral myocarditis in puppies in Brazil

Descrevem-se os aspectos epidemiológicos, clínicos, patológicos e imuno-histoquímicos de um surto de parvovirose cardíaca em filhotes de cães. O surto ocorreu em um canil localizado na cidade de Parnamirim, Rio Grande do Norte, região Nordeste do Brasil. De uma ninhada de nove filhotes, um foi natimorto e seis morreram entre 35-57 dias de idade após apresentarem sinais clínicos cardiorrespiratórios com evolução de 10 minutos a três dias. Dos seis filhotes que morreram, dois foram encaminhados para necropsia. No exame macroscópico, ambos os animais apresentaram discreta efusão pericárdica, coração marcadamente globoso, difusa palidez nas superfícies epicárdica e miocárdica e dilatação da cavidade ventricular esquerda. Nos pulmões, observaram-se áreas multifocais avermelhadas na superfície pleural e ao corte fluía líquido espumoso e levemente avermelhado. O fígado estava difusamente aumentado de tamanho, com acentuação do padrão lobular e com áreas pálidas entremeadas por áreas escuras que, ao corte, se aprofundavam ao parênquima. Microscopicamente observou-se miocardite linfohistiocítica, necrosante, associada a fibrose intersticial e corpúsculos de inclusões virais basofílicos intranucleares em cardiomiócitos. Nos pulmões observou-se pneumonia intersticial e edema, e no fígado notou-se degeneração e necrose centrolobular a mediozonal associada à congestão e hemorragia. O diagnóstico foi confirmado por imuno-histoquímica. A forma miocárdica da parvovirose canina pode ocorrer ocasionalmente em filhotes de cadelas que não foram efetivamente vacinadas. Essa forma clínica da doença caracteriza-se por alterações cardiorrespiratórias e morte hiperaguda ou aguda dos animais afetados.(AU)

We describe the epidemiological, clinical, pathological and immunohistochemical aspects of parvoviral myocarditis outbreak in puppies. The outbreak occurred in a kennel located in Parnamirim, Rio Grande do Norte, Northeastern of Brazil. In a litter of nine pups, one was stillbirth and six died between 35-57 days of age after cardiopulmonary clinical signs with evolution of 10 minutes to three days. Of the six puppies that died, two were sent for necropsy. On gross examination, both animals had discreet pericardial effusion, markedly distended heart, diffuse pallor in epicardial and myocardial surfaces and dilation of the left ventricular cavity. The lungs were observed multifocal reddish areas in the pleural surface and at cutting flowed foamed and slightly red liquid. The liver was diffusely increased in size, with lobular standard accentuation and pale areas interspersed with dark areas wich deepened in the parenchyma. Microscopically observed linfohistiocítica myocarditis, necrotizing, associated with interstitial fibrosis and basophilic intranuclear viral inclusions corpuscles in cardiomyocytes. In the lungs there were edema and interstitial pneumonia and in the liver was noted centrilobular to mediozonal degeneration and necrosis associated with congestion and hemorrhage. The diagnosis was confirmed by immunohistochemistry. The parvoviral myocarditis can occasionally occur in puppies of bitches that have not been effectively vaccinated. This clinical form of the disease characterized by cardiorespiratory changes and hyperacute or acute death of the affected animals.(AU)

Shenfu Yangrong Decoction Combined with Routine Western Therapy for Treatment of Viral Myocarditis of Ⅰ– Ⅲ Grades in Children / 中国中医药信息杂志

Objective To observe the efficacy of Shenfu Yangrong Decoction combined with routine Western therapy in the treatment of viral myocarditis (VMC) of Ⅰ– Ⅲ grades in children. Methods Totally 100 cases of VMC children were selected and divided into observation group and control group according to random number table method, with 50 cases in both groups. The control group was treated with routine Western therapy, while the observation group was combined with Shenfu Yangrong Decoction based on the control group, one dosage a day, twice a day, orally. The TCM syndrome scores, the serum levels of interleukin (IL)-17, IL-27 and nuclear factor - κB (NF-κB), the levevs of troponin Ⅰ (cTnⅠ) and cardiac free fatty acid binding protein (H-FABP) before and after treatment in both groups were compared, and the total incidence of adverse reactions during treatment was monitored. Results The total effective rate was 90% (45/50) in the observation group and 74% (37/50) in the control group. The observation group was significantly higher than the control group (χ2=4.336, P=0.037). Compared with before treatment, the scores of the main symptoms, the scores of the secondary symptoms, and the total scores of the two groups decreased significantly after treatment (P＜0.01). Comparing the two groups after treatment, the scores of main symptoms, scores of secondary symptoms and total scores of the observation group were significantly lower than those of the control group (P＜0.05, P＜0.01). Compared with before treatment, serum IL-17, NF-κB, cTnⅠ, H-FABP levels were significantly reduced (P＜0.01), while serum IL-27 levels were significantly increased (P＜0.01) in both group. After treatment, the levels of serum IL-17, NF-κB, cTnⅠ, and H-FABP in the observation group were significantly lower than those in the control group (P＜0.01), and serum IL-27 level in the observation group was significantly higher than in the control group (P＜0.01). The adverse reaction rate was 12% (6/50) in the observation group and 8% (4/50) in the control group, without statistical significance between the two groups (χ2=0.368, P=0.544). Conclusion Shenfu Yangrong Decoction combined with routine Western therapy for the treatment of viral myocarditis children of Ⅰ– Ⅲ grades can effectively reduce the symptoms of patients, inhibit inflammation, reduce myocardial injury, with high safety.

Clinical efficacy of creatine phosphate sodium combined with ribavirin in treating infantile viral myocarditis and its effect on myocardial enzyme levels in children / 吉林大学学报(医学版)

Objective:To investigate the clinical efficacy of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis,and to elucidate its mechanism of the effects on myocardial enzyme levels in the children.Methods:A total of 96 children with viral myocarditis were selected;according to the random number grouping method,they were divided into observation group and control group (n=48).The myocardial enzymes and cardiac troponin Ⅰ (cTnI) of the patients in two groups were detected,and anti-infection,supplementation of electrolytes,and nutritional support for myocardial treatment were performed;then intravenous infusion therapy of ribavirin was used.On this basis,the patients in observation group were given intravenous infusion of creatine phosphate sodium for 14 d.After treatment,the total effective rate of treatment of the patients in two groups,the levels of myocardial enzymes and cTnI and electrocardiogram were compared before and after treatment.Results:The total effective rate of the patients in observation group was 87.50％ (42/48),and it was 70.83％ (34/48) in control group;there was significant difference (x2 =4.04,P=0.04).After treatment,the levels of lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH),aspartate transaminase (AST),creatine phosphokinase (CPK),creatine kinase isoenzyme-MB (CK-MB) and CTnI of the patients in two groups after treatment were lower than before treatment (P＜0.05).The indicators mentioned above of patients in observation group were lower than those in control group (P ＜0.05).The total improvement rate of electrocardiogram in the observation group (89.58％) was significantly higher than that in control group (72.92 ％),and the difference was statistically significant (x2 =4.38,P =0.04).Conclusion:The total effective rate of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis is higher,and they can significantly reduce the levels of myocardial enzymes and improve the cardiac function;it is worth to apply in the clinical treatment.

Clinical efficacy of creatine phosphate sodium combined with ribavirin in treating infantile viral myocarditis and its effect on myocardial enzyme levels in children / 吉林大学学报(医学版)

Objective: To investigate the clinical efficacy of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis, and to elucidate its mechanism of the effects on myocardial enzyme levels in the children. Methods: A total of 96 children with viral myocarditis were selected; according to the random number grouping method, they were divided into observation group and control group (n=48). The myocardial enzymes and cardiac troponin I (cTnl) of the patients in two groups were detected, and anti-infection, supplementation of electrolytes, and nutritional support for myocardial treatment were performed; then intravenous infusion therapy of ribavirin was used. On this basis, the patients in observation group were given intravenous infusion of creatine phosphate sodium for 14 d. After treatment, the total effective rate of treatment of the patients in two groups, the levels of myocardial enzymes and cTnl and electrocardiogram were compared before and after treatment. Results: The total effective rate of the patients in observation group was 87. 50% (42/48), and it was 70. 83% (34/48) in control group; there was significant difference (X2 = 4. 04, P=0. 04). After treatment, the levels of lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), aspartate transaminase (AST), creatine phosphokinase (CPK), creatine kinase isoenzyme-MB (CK-MB) and CTnl of the patients in two groups after treatment were lower than before treatment (P<0. 05). The indicators mentioned above of patients in observation group were lower than those in control group (P < 0.05). The total improvement rate of electrocardiogram in the observation group (89.58%) was significantly higher than that in control group (72.92%), and the difference was statistically significant (X2 = 4. 38, P=0. 04). Conclusion: The total effective rate of creatine phosphate sodium combined with ribavirin in the treatment of infantile viral myocarditis is higher, and they can significantly reduce the levels of myocardial enzymes and improve the cardiac function; it is worth to apply in the clinical treatment.