The heart is one of the organs most vulnerable to sepsis. This review describes the general characteristics of sepsis-induced cardiomyopathy and the main pathogenesis of myocardial dysfunction in sepsis. Levosimendan is a novel drug for treatment of sepsis-induced myocardial dysfunction. This review also elaborates on the pathogenesis of levosimendan, including the mechanisms of its anti-inflammatory effects, improvement of myocardial ischaemia, increased synthesis of nitric oxide, vascular endothelial cell protection, increased myocardial contractility, improved diastolic function, and inhibition of hypoxia-inducible factor-1α expression. Many clinical studies have proven that levosimendan effectively prevents myocardial dysfunction in sepsis. In addition to the widespread use of levosimendan in patients with heart failure, the role of levosimendan in the treatment of patients with sepsis-induced cardiomyopathy will be increasingly studied and applied in the future.

Background. Sepsis is a life-threatening condition and a systemic inflammatory response syndrome (SIRS) driven by infection. This study aimed at investigating the expression of microRNA-103 (miR-103) in sepsis patients, evaluating its diagnostic value, and exploring the regulatory effect of miR-103 on LPS-induced inflammation in monocytes. Methods. Expression of miR-103 was measured using quantitative real-time PCR. A receiver operating characteristics curve was plotted to evaluate the diagnostic vale of miR-103. Serum and cell supernatant levels of proinflammatory cytokines were analyzed using ELISA. The interaction between miR-103 and Toll-like receptors 4 (TLR4) was analyzed using luciferase reporter assay. The effect of miR-103 on inflammation was examined in LPS-treated monocytes. Results. Serum expression of miR-103 was decreased in noninfectious SIRS and sepsis patients compared with healthy controls, and the lowest expression value was observed in sepsis patients (all P<0.05). Serum levels of miR-103 have considerable diagnostic accuracy in distinguishing sepsis patients from SIRS patients and healthy controls. A negative correlation was found between miR-103 and inflammatory responses in sepsis patients. TLR4 was demonstrated to be a direct target of miR-103 and was negatively regulated by miR-103 in monocytes. The promoted inflammatory responses by LPS in monocytes were reversed by the overexpression of miR-103. Conclusion. All the data revealed that serum decreased miR-103 in sepsis patients serves as a promising noninvasive diagnostic biomarker and may be involved in the pathogenesis of sepsis by regulating inflammatory responses via targeting TLR4.

BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identifi ed for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). RESULTS: Sixteen RCTs involving 1,334 patients were identifi ed. Compared with the atropineor penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also signifi cantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. CONCLUSION: Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Introduction: Heart failure (HF) disproportionately burdens Black Americans. The contributions of impairments in cardiovascular (CV) and non-cardiovascular (non-CV) function to incident HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction in this group remain unclear. Methods: Among 4,356 Black participants in the Jackson Heart Study (JHS) free of prevalent HF at visit 1 (2000-2004), multivariable Cox proportional hazard models were employed to assess the associations of measures of CV and non-CV organ function with incident HF, HFpEF, and HFrEF over a median follow-up of 13 years. Systems considered included: CV: left ventricular (LV) structure (mass index; LVMI), LV systolic function (LVEF), LV diastolic function (left atrial diameter; LAD), systemic arterial function (pulse pressure; PP); Non-CV: pulmonary function (percent predicted FEV1; ppFEV1), renal function (eGFR), body composition (waist circumference), and dysglycemia (hemoglobin A1c; HbA1c). Model covariates included age, sex, hypertension, diabetes, smoking status, and coronary disease history. Results: Average age was 54±13 years and 64% were women. Over median 13 (IQR 12-14) years follow-up, incident HF occurred in 315 participants (152 HFpEF, 134 HFrEF, 29 unknown LVEF). In multivariable models incorporating measures reflecting each organ system, significant predictors of incident HFpEF included greater LAD, higher PP, lower ppFEV1, lower eGFR, larger waist circumference, and higher HbA1c (Figure). Predictors of incident HFrEF included greater LVMI, lower LVEF, and lower eGFR. eGFR was the only independent predictor of both HFpEF and HFrEF. Conclusion: Subclinical impairments in CV and non-CV organ function differentially associate with risk of incident HFpEF and HFrEF among Black Americans. These findings support partially distinct mechanisms underlying HFrEF and HFpEF, and a greater contribution of multisystem non-cardiac impairments to HFpEF in particular.