Unusual presentation of a case of fetal hepatic mass: a case report.

BACKGROUND: Giant hepatic hemangiomas are rare and can cause serious complications that contribute to a high risk of perinatal mortality. The purpose of this article is to review the prenatal imaging features, treatment, pathology, and prognosis of an atypical fetal giant hepatic hemangioma and to discuss the differential diagnosis of fetal hepatic masses. CASE PRESENTATION: A gravida 9, para 0 woman at 32 gestational weeks came to our institution for prenatal ultrasound diagnosis. A complex, heterogeneous hepatic mass measuring 5.2 × 4.1 × 3.7 cm was discovered in the fetus using conventional two-dimensional ultrasound. The mass was solid and had both a high peak systolic velocity (PSV) of the feeding artery and intratumoral venous flow. Fetal magnetic resonance imaging (MRI) revealed a clear, hypointense T1-W and hyperintense T2-W solid hepatic mass. Prenatal diagnosis was very difficult due to the overlap of benign and malignant imaging features on prenatal ultrasound and MRI. Even postnatally, neither contrast-enhanced MRI nor contrast-enhanced computed tomography (CT) was useful in accurately diagnosing this hepatic mass. Due to persistently elevated Alpha-fetoprotein (AFP), a laparotomy was performed. Histopathological examination of the mass showed atypical features such as hepatic sinus dilation, hyperemia, and hepatic chordal hyperplasia. The patient was ultimately diagnosed with a giant hemangioma, and the prognosis was satisfactory. CONCLUSIONS: When a hepatic vascular mass is found in a third trimester fetus a hemangioma should be considered as a possible diagnosis. However, prenatal diagnosis of fetal hepatic hemangiomas can be challenging due to atypical histopathological findings. Imaging and histopathological assays can provide useful information for the diagnosis and treatment of fetal hepatic masses.

Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ.

BACKGROUND: A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction. RESULTS: The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context. CONCLUSIONS: PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.

Expression of ApoA5 and its function in the right ventricular failing and remodeling secondary to pulmonary hypertension.

Right heart failure and right ventricular (RV) remodeling were the main reason for mortality of pulmonary hypertension (PH) patients. Apolipoprotein AV (ApoA5) is a key regulator of plasma triglyceride and have multifunction in several target organs. We detected decreased ApoA5 in serum of patients with PH and both in serum and RV of monocrotaline-induced PH model. Exogenously, overexpression ApoA5 by adenovirus showed protective effects on RV failure and RV fibrosis secondary to PH. In addition, in vitro experiments showed ApoA5 attenuated the activation of fibroblast induced by transforming growth factor ß1 and synthesis and secretion of extracellular matrix by inhibiting focal adhesion kinase-c-Jun N-terminal kinase-Smad3 pathway. Finally, we suggest that ApoA5 may potentially be a pivotal target for RV failure and fibrosis secondary of PH.

Self-Immolative Dye-Doped Polymeric Probe for Precisely Imaging Hydroxyl Radicals by Avoiding Leakage.

For sensing low abundance of biomarkers, utilizing nanocarriers to load dyes is an efficient method to amplify the detected signal. However, the non-specific leak of the internal dyes in this approach is accompanied by false positive signals, resulting in inaccurate signal acquirement. To address this issue, in this work, we reported a novel signal amplification strategy with dye as a scaffold to construct a self-immolative dye-doped polymeric probe (SDPP). In our proposed approach, the dyes were covalently integrated into the main chain of a polymer, which can avoid the non-specific leak of the dye when used in a rigorous biological environment, thus evading the false positive signal. As a prototype of this concept, a SDPP, which responds to hydroxyl radicals (•OH), was rationally fabricated. Upon being activated by •OH, SDPP will liberate the dye through a self-immolative reaction to bind with protein for amplifying the fluorescence signal. Compared with a dye-loaded nanoprobe, SDPP can precisely track intracellular basal •OH levels and visualize the •OH associated with myocarditis in vivo. More importantly, the attempt in this work not only provides an effective molecular tool to investigate the role of •OH in cardiopathy, but also puts forward a new direction to current signal-amplifying strategies for precisely and reliably acquiring the intracellular molecular information.

Soluble epoxide hydrolase inhibitors improve angiogenic function of endothelial progenitor cells via ERK/p38-mediated miR-126 upregulation in myocardial infarction mice after exercise.

It is well established that exercise could protect against myocardial infarction (MI). Previously, we found that epoxyeicosatrienoic acids (EETs) could be induced by exercise and has been found to protect against MI via promoting angiogenic function of endothelial progenitor cells (EPCs). However, the underling mechanism of EETs in promoting EPC functions is unclear. C57BL/6 mice were fed with a novel soluble epoxide hydrolase inhibitor (sEHi), TPPU, to increase EET levels, for 1 week before undergoing MI surgery. Mice were then subjected to exercise training for 4 weeks. Bone marrow-derived EPCs were isolated and cultured in vitro. Exercise upregulated miR-126 expression but downregulated the protein levels of its target gene, Spred1, in EPCs from MI mice. TPPU further enhanced the effects of exercise on EPCs. Spred1 overexpression abolished the protective effects of TPPU on EPC functions. Downregulation of miR-126 by antagomiR-126 impaired the inhibitor effects of TPPU on Spred1 mRNA and protein expression. Additionally, TPPU upregulated miR-126 is partially mediated through ERK/p38 MAPK pathway. This study showed that sEHi promoted miR-126 expression, which might be related to the beneficial effect of sEHi on EPC functions in MI mice under exercise conditions, by increasing ERK and p38 MAPK phosphorylation and inhibiting Spred1.

Isolated ventricular apical hypoplasia: A report of four cases and literature review.

Isolated ventricular apical hypoplasia (IVAH) is a rare congenital cardiac anomaly, with clinical manifestations depending on the age of the patient, ranging from no symptoms in children to congestive heart failure or even malignant tachycardia in adults. Herein, we describe the clinical and anatomical findings in four cases with hypoplasia of the right or left ventricular apex, and we discuss the possible mechanisms and differential diagnosis of this malformation. Echocardiography is a rapidly accessible, low cost, noninvasive technique for the detection and evaluation of IVAH.

Efficacy and Safety of Inorganic Nitrate Versus Placebo Treatment in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is a lack of effective treatments. In this meta-analysis, we assessed the efficacy and safety of inorganic nitrate in patients with HFpEF. METHODS AND RESULTS: We systematically searched PubMed, Embase, and the Cochrane Library from the inception of the database through March 2020. We included randomized controlled trials that compared the efficacy and safety of inorganic nitrate with a placebo in the treatment of patients with HFpEF. The primary outcome of the meta-analysis was exercise capacity (measured as a change in peak oxygen uptake). We also assessed the effect of inorganic nitrate on diastolic function (measured as changes in E/A and E/e', assessed by echocardiography), quality of life (estimated using the Kansas City Cardiomyopathy Questionnaire), and rest and exercise hemodynamics (measured by invasive cardiac catheterization). In the pooled data analysis, there were no significant differences in peak oxygen uptake (mL/kg/min) [mean difference (MD), 0.25; 95% CI, - 0.07 to 0.57], diastolic function [E/A-standardized mean difference (SMD), 0.51; 95% CI, - 0.17 to 1.20; or E/e'-SMD, 0.02; 95% CI, - 0.23 to 0.27], or quality of life. However, a significant change was observed in the rest and exercise hemodynamics between the inorganic nitrate and placebo treatment in HFpEF patients. No study has reported the effect of inorganic nitrate on hospitalization and mortality of patients with HFpEF. CONCLUSIONS: In patients with HFpEF, the use of inorganic nitrate is not associated with improvements in exercise capacity, diastolic function, and quality of life but is associated with significant changes in rest and exercise hemodynamics.

Isolated right ventricular apical hypoplasia characterized by computed tomography and echocardiography.

Isolated right ventricular apical hypoplasia is an unusual congenital heart disease that has been mentioned in only one report to our knowledge. We describe the case of a 62-year-old male patient suffering from recurrent abdominal distention, nausea, and lower extremity edema. The right ventricular morphologic abnormalities as shown by echocardiography and CT were comparable to those of left ventricular apical hypoplasia, suggesting right ventricular apical hypoplasia. However, this speculative diagnosis remains to be confirmed by additional cases. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:82-84, 2018.

[Maternal hepatic venous hemodynamics and cardiac output in normal and fetal growth restricted pregnancies].

OBJECTIVE: To evaluate relationship of maternal hepatic vein Doppler flow parameters and cardiac output (CO) with neonatal birth weight in uncomplicated pregnancies (UP) and pregnancies complicated by fetal growth restriction (FGR) .
 Methods: Hepatic vein impedance index (HVI), venous pulse transit time (VPTT), and CO were measured in women with UP at the 14th-37th weeks and complicated by FGR at the 26th-37th weeks who underwent maternal hepatic hemodynamic and echocardiographic examination during the ultrasonography. After delivery, the birth weight and the birth weight percentile of each neonate in this study were recorded. Correlations among HVI, VPTT, and CO were analyzed.
 Results: In the UP group, HVI, VPTT, and CO changed with the increase of gestation. In the FGR group, HVI was higher, VPTT was shorter, CO and neonatal birth weight were obviously lower than those in the UP at the 26th-37th weeks (P<0.05).
 Conclusion: There is a series of adaptive changes in hepatic venous hemodynamics and CO in UP with the increase of gestation to meet the demand of fetal growth, while the maladaptive changes in hepatic venous hemodynamics and CO in pregnant woman may contribute to FGR.

Contrast-enhanced ultrasound of small cell carcinoma in urinary bladder: a case report and review of literature.

BACKGROUND: Small cell carcinoma of the urinary bladder (SCCB) is a relatively rare malignant bladder tumor, and few reports have investigated the microvasculature of SCCB imaged using contrast-enhanced ultrasound (CEUS). CASE PRESENTATION: A 63-year-old female was admitted to our hospital after experiencing painless gross hematuria for one week. The gray-scale ultrasound (US) demonstrated a 4.8 × 3.4 × 3.6-cm3 hypoechoic mass in the apex of the urinary bladder with a wide base and an irregular surface; the mass did not move with changes in body position. Color Doppler flow imaging (CDFI) showed rich blood flow in the mass. CEUS with low mechanical index (MI) of 0.06 confirmed a highly enhanced 5.0 × 3.3 × 3.8 cm3 mass within the bladder at the apex wall. The time-intensity curves (TICs) showed a wash-in time of 10 s, a time to peak (TTP) of 33 s, a signal intensity (SI) of 62.7% and a wash-out time > 60 s. Finally, the transurethral resection of the bladder tumor (TURBT) was performed, and the pathological examination proved the diagnosis of SCCB. CONCLUSION: CEUS can provide valuable information related to the rich microvasculature of SCCB, which may be helpful in its diagnosis.

Association Between the Left Atrial and Left Atrial Appendages Systole Strain Rate in Patients with Atrial Fibrillation.

BACKGROUND The aim of this research was to explore the association between the left atrial (LA) and left atrial appendages (LAA) systole strain rate (SSR) in patients with atrial fibrillation (AF), and to provide evidence to aid in the assessment of disease progression. MATERIAL AND METHODS A total of 180 patients with AF were selected for the study (130 patients with paroxysmal AF (Par AF) and 50 patients with persistence AF (PerAF).In addition, 60 healthy individuals were selected as a control group. The total and side wall SSRs were calculated. RESULTS The total SSR in the control group was higher than in the ParAF and PerAF groups (2.87±0.45 vs. 2.15±0.56 vs. 1.92±0.62 and 6.24±1.61 vs. 4.45±1.42 vs. 3.66±1.55). The total SSR of LAA was correlated with that of LA in the AF patient groups and the control group; the correlation coefficients were 0.720, 0.563, and 0.421. However, the ratio of total SSR of LAA to that of LA was not significant statistically different among the three groups (2.24±0.41 vs. 2.35±0.58 vs. 2.03±0.56). The posterior wall had the lowest SSRs in the control group and ParAF group. CONCLUSIONS The SSRs of AF patients were lower than that of healthy individuals, and the degree was associated with disease progression. The SSR was different in different side walls, and gradually shorten with disease progression.

BMSCs-derived Exosome CISH Alleviates Myocardial Infarction by Inactivating the NF-κB Pathway to Stimulate Macrophage M2 Polarization.

Current myocardial infarction (MI) treatments are suboptimal, necessitating deeper pathogenesis understanding of MI. This research explored how exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) contribute to MI mitigation and their therapeutic potential. Isolated BMSCs was identified by microscope, flow cytometry, alizarin red and oil red O staining. Exo were identified by TEM, NTA and western blot. HE staining, masson staining, and cardiac function parameters were used to assess the cardiac function in MI mice. TUNEL staining, western blot and qRT-PCR were used to detect apoptosis, inflammatory factors and M1/M2 markers. The NF-κB pathway activation was detected through western blot assays. Immunofluorescence, qRT-PCR, western blot, and flow cytometry were employed to evaluate macrophage polarization. MI mice showed cardiac injury, increased apoptosis and inflammation, while BMSCs-Exo treatment alleviated these effects. In MI mice, the macrophage M1 polarization was increased and the NF-κB pathway was activated, whereas BMSCs-Exo treatment reversed these changes. Furthermore, CISH expression was reduced in MI mice, but was elevated with BMSCs-Exo treatment. In vitro, LPS shifted RAW264.7 cells to M1 phenotype and activated the NF-κB pathway, yet BMSCs-Exo shifted them to M2 phenotype and inhibited the NF-κB pathway. Mechanistically, BMSCs-Exo induced macrophage M2 polarization by transmitting CISH to inhibit NF-κB activation. BMSCs-Exo mitigates MI by transmitting CISH to inhibit the NF-κB pathway, promoting macrophages to M2 type. This implies BMSCs-Exo could be a useful treatment for MI, and CISH could be a potential therapy target.

The fluorescence imaging and precise suppression of bacterial infections in chronic wounds by porphyrin-based metal-organic framework nanorods.

Nano-antibacterial agents can play a critical role in chronic wound management. However, the design of an intelligent nanosystem that can provide both a visual warning of infection and precise sterilization remains a hurdle. Herein, a rod-like porphyrin-based metal-organic framework theranostic nanosystem (Zn-TCPP nanorods) is fabricated via coordination chelation between tetrakis(4-carboxylphenyl)porphyrin and zinc ions. This system can show significant fluorescence activation in response to the local elevated pH shown by chronic wounds, a main indicator of wound infection. Meanwhile, under the guidance of fluorescence imaging, the highly spatiotemporally precise photodynamic inactivation of microorganisms can be carried out without the destruction of surrounding normal cells and nascent cells. The results demonstrated that the Zn-TCPP nanorods were a highly sensitive and reversible probe for sensing alkaline pH levels. Alterations in the fluorescence of the Zn-TCPP nanorods can accurately indicate the infection status and heterogeneity of infection within the wound bed. Under specific light irradiation, the Zn-TCPP nanorods can exterminate 97% of Staphylococcus aureus via the generation of reactive oxygen species (ROS). Assays of extensive wounds demonstrate that the precise fluorescence-imaging-guided suppression of bacterial infection can significantly reduce the mouse mortality rate and accelerate wound healing. This system provides the opportunity for "precision medicine" relating to chronic wounds and some large-area wounds.

[Protective effects of myocardium-targeted nanoparticles loaded L-arginineon on sepsis-induced myocardial injury].

OBJECTIVE: To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium. METHODS: PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. (1) Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. (2) Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability (A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/ß-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/ß-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2-ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2-ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2-ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. CONCLUSIONS: PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.

The inhibition of MyD88 and TRIF signaling serve equivalent roles in attenuating myocardial deterioration due to acute severe inflammation.

Myeloid differentiation factor 88 (MyD88) and Toll or interleukin-1 receptor-domain-containing adaptor-inducing interferon-ß (IFN-ß) (TRIF) are two pivotal downstream adaptors of Toll-like receptors. Activation of MyD88 or TRIF signaling in cardiac immune pathology of severe inflammation negatively influences heart function. In the present study, severe septic cardiac injury was induced in C57BL/6 mice by cecum ligation and puncture (CLP). A total of 64 mice were divided randomly into the following four groups (n=16/group; 8 for observation of survival rate, 8 for heart sample analysis): Sham, CLP, anti-MyD88-CLP and anti-TRIF-CLP. Anti-MyD88 and anti-TRIF antibodies were administered to the respective mice through the tail veins 2 h before CLP. Measurements of cardiac function, including M-modes, velocity vector imaging and cardiac troponin I, were performed. Myocardial inflammatory cytokines were examined by reverse transcription-polymerase chain reaction (RT-PCR), myocardial neutrophil infiltration was measured by a myeloperoxidase activity assay, intracellular adhesion molecule and vascular cell adhesion molecule mRNA expression levels were investigated, and histopathological characteristics were evaluated. Levels of mRNA transcripts encoding genes for apoptosis production and MyD88, TRIF, nuclear factor-κB and IFN regulatory factor 3 were investigated by RT-PCR. Mice challenged with CLP demonstrated deleterious cardiac function, increased levels of interleukin-1ß (IL-1ß), IL-6ß, and tumor necrosis factor-α mRNA, increased neutrophil infiltration, and increased apoptosis. In contrast, mice in the anti-MyD88 CLP and anti-TRIF CLP groups retained cardiac function with reduced cytokine release, decreased neutrophil infiltration, and reduced apoptosis. In addition, there was no significant difference between the anti-MyD88 CLP and anti-TRIF CLP groups. Thus, the present study indicated that MyD88 and TRIF blockades serve notable and equivalent roles in protecting cardiac deterioration from severe sepsis by attenuating cytokine release, reducing neutrophil infiltration and alleviating apoptosis.

Knockout of Toll-like receptor 4 improves survival and cardiac function in a murine model of severe sepsis.

Toll-like receptor 4 (TLR4) is a transmembrane pattern­recognition receptor expressed in immune cells and the heart. Activation of TLR4 signaling during sepsis results in the release of cardiac depression mediators that may impair heart function. The present study aimed to determine whether TLR4 contributes to development of severe sepsis­induced myocardial dysfunction. A cecum ligation and puncture (CLP) procedure was employed to establish severe sepsis models. Wild type (WT) and TLR4 knock­out (TLR4­KO) mice were divided into four groups: WT­sham, TLR4­KO­sham, WT­CLP, and TLR4­KO­CLP. Cardiac function of these animals was evaluated at various time points following the surgical procedure. The expression levels of proinflammatory cytokines in the heart tissues were detected by reverse transcription­semi quantitative polymerase chain reaction (RT­PCR). Myocardial neutrophil and macrophage infiltration were investigated by histopathological examination, as well as a myeloperoxidase activity assay in heart tissue by RT­PCR. Myocardium Fas cell surface death receptor/Fas ligand and caspase­3 were also analyzed by RT­PCR. Additionally, myeloid differentiation primary response 88 M, toll or interleukin­1 receptor­domain­containing adapter­inducing interferon­ß and nuclear factor­κB expression levels were observed in the myocardium of all four groups. WT­CLP mice exhibited increased mortality rates, more severe cardiac dysfunction and had increased levels of interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α in heart tissues and increased neutrophil infiltration compared with TRL4­KO­CLP mice. The present study reported that TLR4 aggravates severe sepsis­induced cardiac impairment by promoting the release of proinflammatory cytokines and neutrophil infiltration in hearts.

[Roles of MyD88 and TRIF in cardiac dysfunction during sepsis].

OBJECTIVE: To investigate the roles of myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-ß (TRIF) in sepsis-induced myocardial dysfunction, and to analyze whether strain rate (SR) can be early sensitive evaluation for septic heart failure. METHODS: Sixty-four healthy male C57BL/6 mice were divided into four groups by random number table (n = 16 in each group): sham group, cecum ligation and puncture (CLP)-induced sepsis model group, anti-MyD88 group and anti-TRIF group. The anti-MyD88 group and anti-TRIF group were injected with 5 µL/g of anti-MyD88 antibody or anti-TRIF antibody through the tail veins 2 hours before CLP. Eight animals in each group were used to observe the survival of 24 hours, and the other 8 myocardial tissues were harvested for examination. The cardiac function was evaluated by echocardiography before and 6 hours and 12 hours after operation. The mRNA expressions of MyD88, TRIF and inflammatory factors in myocardium were measured by polymerase chain reaction (PCR) at 24 hours after operation, and the degree of neutrophils infiltration was detected by myeloperoxidase (MPO) activity. RESULTS: The number of 24-hour survive in anti-MyD88 group and anti-TRIF group were higher than that in CLP group (number: 4, 3 vs. 2, P = 0.044, P = 0.047). Compared with sham group, the cardiac function was significantly decreased, the mRNA expressions of myocardial tissues MyD88, TRIF, interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were significantly increased, and the infiltration of neutrophils were obvious in CLP group. Compared with CLP group, the left ventricular short axis fractional shortening rate (FS) and SR were significantly increased after 12 hours in anti-MyD88 group and anti-TRIF group [FS: (49.52±1.78)%, (49.89±1.49)% vs. (41.11±1.63)%, SR (s-1): 17.63±2.16, 17.85±1.64 vs. 12.55±1.84]; the mRNA expressions of MyD88, TRIF and inflammatory factors were significantly decreased [MyD88 mRNA (A value): 0.463±0.046, 0.505±0.048 vs. 0.638±0.102, TRIF mRNA (A value): 0.413±0.031, 0.410±0.021 vs. 0.625±0.057, IL-1 mRNA (A value): 0.569±0.101, 0.570±0.091 vs. 0.946±0.171, IL-6 mRNA (A value): 0.551±0.143, 0.431±0.157 vs. 0.850±0.194, TNF-α mRNA (A value): 0.471±0.082, 0.444±0.093 vs. 0.707±0.094]; and the infiltration of neutrophils were significantly decreased [MPO (U/L): 62.34±2.60, 60.87±2.40 vs. 73.83±4.90], with statistically significant differences (all P < 0.05). There was no statistical difference in above parameters between the anti-MyD88 group and anti-TRIF group (all P > 0.05). CONCLUSIONS: Blocking MyD88 and TRIF expression play significant and similar roles in protecting cardiac deterioration from sepsis by attenuating cytokine release, reducing neutrophil infiltration. SR can sensitively assess septic cardiac dysfunction.