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Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI.Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models.Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (β = 5.94%; 95% CI: 2.94-8.94; P 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury.The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).

Coronavirus disease 2019 (COVID-19) broke out in December 2019. Due its high morbility and mortality, it is necessary to summarize the clinical characteristics of COVID-19 patients to provide more theoretical basis for future treatment. In the current study, we conducted a retrospective analysis of the clinical characteristics of COVID-19 patients and explored the risk factors for the severity of illness. A total of 101 COVID-19 patients hospitalized in Leishenshan Hospital (Wuhan, China) was classified into three sub-types: moderate (n = 47), severe (n = 36), and critical (n = 18); their clinical data were collected from the Electronic Medical Record. We showed that among the 101 COVID-19 patients, the median age was 62 years (IQR 51–74); 50 (49.5%) patients were accompanied by hypertension, while 25 (24.8%) and 22 (21.8%) patients suffered from diabetes and heart diseases, respectively, with complications. All patients were from Wuhan who had a definite history of exposure to the epidemic area. Multivariate logistic regression analysis revealed that older age, diabetes, chronic liver disease, percentage of neutrophils (N%) > 75%, CRP > 4 mg/L, D-dimer > 0.55 mg/L, IL-2R > 710 U/mL, IL-8 > 62 pg/mL, and IL-10 > 9.1 pg/mL were independent variables associated with severe COVID-19. In conclusion, we have identified the independent risk factors for the severity of COVID-19 pneumonia, including older age, diabetes, chronic liver disease, higher levels of N%, CRP, D-dimer, IL-2R, IL-8, and IL-10, providing evidence for more accurate risk prediction.

Purpose To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients. Methods We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score. Results Overall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09–0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10–0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02–0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15–0.65), as well as among the elderly patients’ age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level. Conclusions Among hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.

Background Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. Purpose To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort. Materials and Methods Participants with STEMI who underwent primary percutaneous coronary intervention and cardiac MRI from 10 sites (EARLY-MYO-CMR registry, clinical trial number NCT03768453) were included. The parent study took place between August 2013 and December 2018. LA longitudinal strain and strain rate parameters were derived from cine cardiac MRI by using an in-house semiautomated method. Major adverse cardiac events (MACEs) were defined as cardiovascular death, myocardial reinfarction, hospitalization for heart failure, and stroke. The association between LA performance and MACE was evaluated by using time-dependent receiver operating characteristic analysis, Kaplan-Meier analysis, and multivariable Cox regression analysis. Results A total of 321 participants (median age, 59 years; age range, 27-75 years; 90% men) were included in this study. During median follow-up of 3.7 years, MACE occurred in 76 participants (23.7%). Participants with impaired reservoir (≤22%) and conduit strain (≤10%) had a higher risk of MACE than those with reservoir strain greater than 22% and conduit strain greater than 10% (P < .001). Reservoir strain (hazard ratio, 0.84; 95% confidence interval: 0.77, 0.91; P < .001) and conduit strain (hazard ratio, 0.81; 95% confidence interval: 0.73, 0.89; P < .001) were independent predictors for MACE after adjustment for known risk factors. Finally, LA reservoir and conduit strains provided incremental prognostic value over traditional outcome predictors (Uno C statistic comparing models, 0.75 vs 0.68; P = .04). Conclusion Assessment of left atrial strain, as a measure of left atrial function, provided incremental prognostic information to established predictors in ST-segment elevation myocardial infarction. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

Direct stenting (DS) without pre-dilatation of the culprit lesion might improve myocardial perfusion and prognosis in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI); however, some studies report conflicting results. We investigated whether DS provides incremental myocardial benefits over conventional stenting (CS) in STEMI patients based on cardiac magnetic resonance imaging (CMR) measures. Reperfused patients who underwent CMR examinations within 1 week of STEMI onset were selected from a multicenter CMR registry of STEMI (NCT: 03768453). Patients were stratified into either a DS or CS group. Each group comprised 137 patients after 1:1 propensity score matching. Major adverse events (MACEs), including death, myocardial re-infarction, re-admission for heart failure, and stroke were noted during a median period of 44 months (interquartile range 32-58 months). DS was associated with larger (p = 0.007) and shorter (p = 0.005) stent sizes than CS. DS and CS achieved comparable angiographic TIMI-3 flow grades (p = 0.86) and myocardial blush grades (p = 0.70). There were no group differences regarding the incidence of CMR manifestations of microvascular dysfunction, including microvascular obstruction (MVO) (p = 0.89) and intramyocardial hemorrhage (p = 0.47), the extent of MVO (p = 0.21), infarction size (p = 0.83), or left ventricular ejection fraction (p = 0.57). Kaplan-Meier analysis revealed similar risks of MACEs (log rank p = 0.909), which occurred in 23.4% of DS and 26.3% of CS patients (p = 0.576). DS did not show any incremental benefits over CS on myocardial impairments as evaluated using CMR.Clinical Trial Registration: Clinicaltrials.gov, NCT: 03768453.

Cyprinid herpesvirus 2 is a DNA virus that is a concern for the aquaculture worldwide. Here, the challenge of CyHV-2 infection was conducted in gibel carp at a host susceptible temperature (25 ℃) and a less-susceptible temperature (15 ℃). The viral replication and expression of antiviral genes were analyzed by real time PCR, and the activities of antioxidative enzymes in serum were also examined. Results showed that CyHV-2 was in normal proliferative in 25 ℃ group, while the growth was inhibited in 15 ℃ group. Moreover, IFNφ1 and Mx were highly expressed from 12 hpi to 48 hpi in both groups, but the 15 ℃ group showed quicker and stronger response. TNF-α and IL-1β showed early upregulation at 12 hpi followed by a sharp decline in both groups. Fatty acid synthase (FAS) and Caspase-8 showed a higher expression level in 15 ℃ group than that in 25 ℃ group during 48-96 hpi. Furthermore, the activities of antioxidant enzymes (SOD and CAT) in 15 ℃ group were higher than those in 25 ℃ group at late infection. Thus, water temperature affected the immune response against CyHV-2 infection, which may ultimately lead to host survival in the less-susceptible temperatures.

Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. Methods A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. Results Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. Conclusions Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).

CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China OnBehalf Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University Background：The prognostic value of Peak Early Diastolic Strain Rate (PEDSR) measured by Cardiac Magnetic Resonance (CMR) in ST-Elevation Myocardial Infarction (STEMI) is not clear. Methods：420 first-STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453) and 40 normal people were enrolled and followed up. The patients received timely percutaneous coronary intervention (PCI) within 12h and CMR within 1 week (median,5 days; range, 2-7 days) after infarction. LV circumferential, radial, longitudinal PEDSR and other routine CMR parameters were measured. Clinical end point was a composite major adverse cardiovascular events (MACEs) including cardiovascular death, re-infarction and re-hospitalization for heart failure. Results：During follow-up (median: 52 months, inter-quartile range: 29–78 months), 73 (17.4%) patients experienced a MACE event. Compared with normal people, STEMI patients had lower PEDSR (circumf. PEDSR 0.77 vs. 1.27%/s, P 50.28% (P = 0.003) but not in reduced LVEF patients (P = 0.204). PEDSR is also incremental to LVEF (Continuous NRI 0.515 [95%CI 0.268-0.763], P Conclusions：CMR-derived PEDSR can significantly predict MACEs with the discriminative power not inferior to LVEF, LVIS and LVMVO. Circumf. PEDSR ≤ 0.665%/s is an independent predictive factor of MACEs and is incremental in the prognostic risk stratification of STEMI.

Background: Percutaneous left atrial appendage occlusion (LAAO) provides an alternative for poor candidates for long-term oral anticoagulation (OAC). To prevent device-related thrombosis (DRT), OAC should be continued for the first 45 days to allow complete endothelialization post-LAAO implantation. Whereas, evidence is limited on the feasibility and safety of direct oral anticoagulants (DOACs) used after LAAO. Methods: This was a retrospective observational single-center study of AF patients undergoing LAAO with a Watchman device and receiving either low-dose dabigatran (110mg twice daily) or warfarin in the peri- and post-procedural period for 45 days. Transesophageal echocardiography was scheduled to perform at 6 weeks, 6 months, and 12 months after the procedure to assess the stability of the device and to detect DRT. Incidence of thromboembolic and bleeding events were also evaluated during the follow-up period. Results: There were a total of 84 patients who successfully underwent Watchman implantation, with 38 patients (45.2%) receiving low-dose dabigatran and 46 patients (54.8%) using warfarin post-LAAO. Peri-procedural complications occurred in 10 patients, with 3 patients in the dabigatran group and 7 patients in the warfarin group (7.9% vs. 15.2%, p = 0.30). During the 12-month follow-up, 1 patient experienced major bleeding and 16 patients suffered minor bleeding in the warfarin group, while 5 patients treated with dabigatran had minor bleeding (34.8% vs. 13.2%, p = 0.02). Besides, 6 DRT (15.8%) were detected in dabigatran groups, and the incidence was higher than in the warfarin group (15.8% vs. 2.2%, p = 0.03). No DRT-related ischemic events were found. Conclusions: This study suggested that short-term low-dose dabigatran (110 mg twice daily) could significantly decrease the risk of bleeding compared with warfarin at the expense of increased risk of DRT post-LAAO. Therefore, low-dose dabigatran should be used with caution for post-implant anticoagulation of LAAO. Further studies are urgently needed on the feasibility and safety of DOACs post-LAAO.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become global pandemic and resulted in considerable morbidity and mortality since December 2019. Information on the incidence of myocardial injury remains scarce. METHODS: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platform were searched to identify studies that reported the myocardial injury data in COVID-19 patients. Random-effects meta-analyses were used to derive the pooled incidence and relative risks (RRs) of myocardial injury. Variations by disease severity were examined by subgroup analyses. Sensitivity analyses were performed to strengthen the results. Meta-regression was applied to explore the risk factors associated with myocardial injury. RESULTS: A total of 53 studies involving 7,679 patients were included. The pooled incidence of myocardial injury was 21% [95% confidence interval (CI), 17–25%; I(2), 96.5%]. The highest incidence of myocardial injury was found in non-survivors (66%; 95 CI%, 54–78%; I(2), 85.7%), followed by severe patients (43%; 95 CI%, 33–53%; I(2), 93.0%) and non-severe patients (11%; 95 CI%, 7–15%; I(2), 95.2%). Higher risk of myocardial injury was detected in severe patients than non-severe patients (RR, 5.74; 95% CI, 3.74–8.79; I(2), 86.8%). All the sensitivity analyses confirmed the robustness of primacy results. CONCLUSIONS: This meta-analysis showed that myocardial injury occurred in 21% of COVID-19 patients. An elevated rate was observed in non-survivors (66%) and severe patients (43%). Severe patients had a 4.74-fold increase in the risk of myocardial injury than non-severe patients. Aggressive strategy may be considered for COVID-19 patients at high risk of myocardial injury.

BACKGROUNDIncreasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients.METHODSWe conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020.RESULTSOf 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0–69.0%), with most (44/86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test).CONCLUSIONSTypical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.CLINICAL TRIAL REGISTRATIONUnique identifier: NCT04352842.

Two types of titanium/steel composite plates with the same thickness were manufactured by parallel explosive welding and double vertical explosive welding and rolling, respectively. The comparative analysis of microstructure showed that the interface of double vertical explosive welding plate (B plate) tended to be straight while the interface of parallel explosive welding plate (A plate) was wavy bonding. Defects near the interface of B plate were extruded, and the thickness of the diffusion layer of B plate was thicker under the effects of preheating temperature and press-working. Comparative tests of mechanical properties indicated that the tensile shear strength of B plate was lower while its micro-hardness was higher. Specimens of these two types of plates were neither separated nor cracked after bending up to 180° in the three-point bending test. From the microstructural observation of tensile fracture characteristics, A plate had strong toughness fracture while B plate had mainly ductile fracture with cleavage fracture as the supplement. Macroscopically, the tensile strength of the latter was 7.9% less than that of the former. However, both satisfied the Chinese standard of tensile strength.

Background: Timely primary percutaneous coronary intervention (PPCI) cannot be offered to all patients with ST-segment–elevation myocardial infarction (STEMI). Pharmaco-invasive (PhI) strategy has been proposed as a valuable alternative for eligible patients with STEMI. We conducted a randomized study to compare the efficacy and safety of a PhI strategy with half-dose fibrinolytic regimen versus PPCI in patients with STEMI. Methods: The EARLY-MYO trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment–Elevation Myocardial Infarction) was an investigator-initiated, prospective, multicenter, randomized, noninferiority trial comparing a PhI strategy with half-dose alteplase versus PPCI in patients with STEMI 18 to 75 years of age presenting ≤6 hours after symptom onset but with an expected PCI-related delay. The primary end point of the study was complete epicardial and myocardial reperfusion after PCI, defined as thrombolysis in myocardial infarction flow grade 3, thrombolysis in myocardial infarction myocardial perfusion grade 3, and ST-segment resolution ≥70%. We also measured infarct size and left ventricular ejection fraction with cardiac magnetic resonance and recorded 30-day clinical and safety outcomes. Results: A total of 344 patients from 7 centers were randomized to PhI (n=171) or PPCI (n=173). PhI was noninferior (and even superior) to PPCI for the primary end point (34.2% versus 22.8%, P noninferiority P superiority =0.022), with no significant differences in the frequency of the individual components of the combined end point: thrombolysis in myocardial infarction flow 3 (91.3% versus 89.2%, P =0.580), thrombolysis in myocardial infarction myocardial perfusion grade 3 (65.8% versus 62.9%, P =0.730), and ST-segment resolution ≥70% (50.9% versus 45.5%, P =0.377). Infarct size (23.3%±11.3% versus 25.8%±13.7%, P =0.101) and left ventricular ejection fraction (52.2%±11.0% versus 51.4%±12.0%, P =0.562) were similar in both groups. No significant differences occurred in 30-day rates of total death (0.6% versus 1.2%, P =1.0), reinfarction (0.6% versus 0.6%, P =1.0), heart failure (13.5% versus 16.2%, P =0.545), major bleeding events (0.6% versus 0%, P =0.497), or intracranial hemorrhage (0% versus 0%), but minor bleeding (26.9% versus 11.0%, P Conclusions: For patients with STEMI presenting ≤6 hours after symptom onset and with an expected PCI-related delay, a PhI strategy with half-dose alteplase and timely PCI offers more complete epicardial and myocardial reperfusion when compared with PPCI. Adequately powered trials with this reperfusion strategy to assess clinical and safety outcomes are warranted. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01930682.

The influence of explosive charge thickness on the quality of explosive welding of dissimilar metals was investigated. The lower limit law should be followed in the course of explosive welding. Three welding experiments of stainless steel (410S) and steel (Q345R) were carried out in three different kinds of explosive charge thicknesses, namely 15, 25 and 35 mm. Interfaces of morphology and mechanical properties of three samples were observed and tested. It was found that micro and small wavy bonding is mainly formed for charge thickness of 15 mm whose strength is the highest with minor deformation and few defects in the interface; small and middle wavy bonding are mainly formed for charge thickness of 25 mm whose strength is comparatively mediocre; big wavy bonding is mainly formed for charge thickness of 35 mm whose strength is the lowest. The cause of high bonding strength of the micro and small wavy interface was analyzed and verified on the basis of the results of Electron Probe Micro-Analyzer (EPMA) tests of three selected samples.

Isolated left ventricular non-compaction (LVNC) is a rare cardiomyopathy that leads to severe clinical complications. This study is to investigate whether or not prolonged QTc is a good indicator for evaluating the severity of fibrosis and predicting the prognosis of LVNC, and if native T1 can be used to quantify the fibrosis. 32 LVNC patients and 14 healthy controls with matched age and sex were examined by CMR and ECG to acquire native T1, QTc interval, and ECG abnormalities. 18 LVNC patients had normal QTc and 14 LVNC patients had prolonged QTc. The mean native T1 value of the normal controls, normal QTc and prolonged QTc patients was 1096.0 ± 41.5, 1141.98 ± 45.46, and 1182.67 ± 42.02 ms, respectively. One-way ANVOA showed significant differences in native T1 among three groups (F = 14.9, p

Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.

OBJECTIVES This study evaluated quantitative flow ratio (QFR) to predict microvascular dysfunction (MVD) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND QFR is a novel approach for the rapid computation of fractional flow reserve based on three-dimensional quantitative coronary angiography. We hypothesized that QFR computation could be used to predict MVD after STEMI. METHODS Indexes such as contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and hyperemic flow velocity (HFV) were calculated in 130 STEMI patients with culprit lesion with ≥50% diameter stenosis and TIMI flow grade 2/3 in the spontaneously recanalized culprit artery on initial angiography. MVD was defined as microvascular obstruction determined by contrast-enhanced cardiac magnetic resonance at a median of 5 days after percutaneous coronary intervention. RESULTS Patients were divided into the MVD group (76/130, 58.5%) and non-MVD group (54/130, 41.5%). Patients with MVD had higher cQFR-fQFR value (0.080 ± 0.058 vs. 0.038 ± 0.039, p

Background: Idiopathic membranous nephropathy (IMN), one of the most common causes resulting into nephrotic syndrome in adults, is usually clinically treated with steroids and/or other immunosuppressive agents. However, the treatment on the patients with IMN coexisting with type 2 diabetes mellitus (DM) is still challenging. There are few convincing literatures available on the efficacy and safety of therapeutic regimens in this subgroup of patients to guide clinical practice. Methods: We retrospectively collected and analyzed the data of twenty-three patients who underwent renal biopsies between January 2013 and March 2018 in our institute and were diagnosed with IMN coexisting with type 2 DM. Nine patients received prednisone combining with tacrolimus and mycophenolate mofetil (group 1), while 14 patients received prednisone and intravenous cyclophosphamide (group 2). The primary endpoint was measured by percentage of patients achieved complete remission (CR) or partial remission (PR), the secondary endpoints included changes of urinary protein excretion from baseline and treatment-related adverse events. Results: The remission rates were compared between the group 1 and the group 2 at both 6 months (44.4% versus 50%, P>0.05 ) and 12 months (77.8% versus 64.3%, P>0.05 ). Significant decrease in urinary protein excretion was observed in both groups during treatment, which was significantly greater in group 1 than that in group 2. No significant renal impairment was observed during the follow-up period. Infections and worsening glycemic control were the most common adverse effects of two therapy. Patients treated with prednisone plus cyclophosphamide were more likely to develop worsening diabetes, while infections tended to be more common in patients treated with prednisone combining with tacrolimus and mycophenolate mofetil. Conclusions: The combination therapy of prednisone, tacrolimus and mycophenolate mofetil is one of the effective and safe options for patients with IMN and type 2 DM.

The effect of glucagon-like peptide-1 (GLP-1) treatment in patients with type 2 diabetes mellitus (T2DM) remains controversial. The purpose of this study was to compare the effect of GLP-1 and placebo/conventional antidiabetic agents on cardiovascular risk in T2DM patients. PubMed, EmBase and the Cochrane Library were searched to identify its eligible studies as well as manual searches for the reliability of this study. All eligible trials were performed in T2DM patients who received GLP-1 therapy or placebo/conventional antidiabetic agents. The reported outcomes included major cardiovascular events (MACE), and total mortality. Of 490 identified studies, we included 13 trials reporting data on 11,943 T2DM patients. Overall, the pooled results suggested that GLP-1 therapy has no or little effect on MACE (RR: 0.99; 95% CI: 0.88-1.12; P=0.872) and total mortality (RR: 0.90; 95% CI: 0.70-1.15; P=0.399). Furthermore, sensitivity analysis indicated that GLP-1 was associated with lower incidence of total mortality (RR: 0.28; 95% CI: 0.08-0.93; P=0.037). We concluded that GLP-1 therapy was not associated with MACE and total mortality compared with placebo or antidiabetic agents.

// Jie Gao 1, * , Xinghan Liu 2, * , Linting Wei 1, * , Dan Niu 3 , Jiali Wei 4 , Li Wang 1 , Heng Ge 1 , Meng Wang 2 , Qiaoling Yu 5 , Tianbo Jin 6 , Tian Tian 2 , Zhijun Dai 2 , Rongguo Fu 1 1 Department of Nephrology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China 2 Department of Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China 3 Department of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China 4 Department of Nephrology, Hainan general hospital, Haikou 570311, China 5 Department of Pathology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China 6 National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi’an 710069, China * These authors have contributed equally to this work Correspondence to: Jie Gao, email: gxej_cn@sina.com Rongguo Fu, email: pipifu@126.com Keywords: monocyte chemoattractant protein-1, IgA nephropathy, polymorphism, risk, case-control study Received: September 16, 2016 Accepted: October 12, 2016 Published: October 24, 2016 ABSTRACT Monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2 stimulate inflammation response by activating and recruiting monocytes/macrophages. MCP-1 and CCR2 polymorphisms were reported to be associated with various diseases. To explore the relationship between MCP-1 and CCR2 polymorphisms and IgA nephropathy (IgAN), we conducted this case-control study by enrolling 351 IgAN patients and 310 health controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate potential associations of MCP-1 and CCR2 polymorphisms with susceptibility and clinical parameters of IgAN. No statistical differences between IgAN group and the control group in the MCP-1 -2518 and CCR2 +190 genotypic groups were observed ( P > 0.05). Individuals with MCP-1 -2518 GG genotypes had a higher blood pressure (GG vs. AA+AG: OR = 1.79, 95% CI = 1.07-2.99, P = 0.026) and Lee’s grade (GG vs. AA+AG: OR = 2.05, 95% CI = 1.19-3.54, P = 0.009; GG vs. AA: OR = 2.24, 95% CI = 1.19-4.20, P = 0.01), compared with patients with AA/AG genotypes. A significant association between CCR2 +190 polymorphism and Lee’s grades was observed (GA+AA vs. GG: OR = 2.66, 95% CI = 1.63-4.35, P < 0.001; GA vs. AA+GG: OR = 2.27, 95% CI = 1.39-3.70, P = 0.001). Our results indicated that MCP-1 and CCR2 polymorphisms may influence the progression of IgAN, but not increase/decrease its susceptibility.