SummaryThe pulmonary inflammatory response and pulmonary dysfunction after cardiopulmonary bypass is a major problem in patients undergoing cardiac surgery. Propofol has anti-inflammatory and immunomodulatory properties which may attenuate this response. Thirty patients undergoing cardiopulmonary bypass were randomly assigned to receive saline (control group) or propofol (propofol group). Pulmonary thoracic compliance, respiratory index, malondialdehyde and interleukin-8 concentrations and intrapulmonary polymorphonucleocyte sequestration were measured at pre-bypass and 5, 30, 60, 90 and 120 min after unclamping the aorta. Plasma levels of interleukin-8, malondialdehyde and the respiratory index increased and reached peaks 30 min after unclamping in both groups. However, in the propofol group the increases were less than in the control group (p < 0.01). Intrapulmonary polymorphonucleocytes sequestration in the propofol group was less than in the control group 5 min after unclamping (p < 0.0001). Pulmonary thoracic compliance decreased significantly after unclamping in both groups, but the reduction was less in the propofol group (p < 0.01). These findings suggest that propofol administered during bypass could reduce the severity of pulmonary dysfunction. Pulmonary dysfunction is common after cardiopulmonary bypass (CPB). The clinical manifestations range from subclinical functional changes to full-blown adult respiratory distress syndrome (ARDS) seen in 2% of cases and which carries a 50% mortality rate [1]. System inflammatory response syndrome (SIRS) is the main cause of pulmonary dysfunction after CPB [2]. Although many strategies to attenuate SIRS have been developed [3], it has not been completely prevented and remains a significant contributor to pulmonary dysfunction after surgery [2,4,5].SIRS is mainly caused by the contact of blood with the non-endothelialised surface of CPB circuits activating multiple plasma protein cascades and blood cells, resulting in increased production of inflammatory mediators and activation of vascular endothelium [3,4]. Activated polymorphonucleocytes (PMNs) sequestered in the lung in response to chemotactic factor interleukin-8 (IL-8) may result in widespread pulmonary inflammatory response and injury through the release of harmful oxygen free radicals and specific enzymes [6,7]. Thus, inhibition of IL-8 release and PMNs sequestration in the lung is a key strategy to control the pulmonary inflammatory response.Propofol is structurally similar to endogenous antioxidant a-tocoferol (vitamin E) and possesses multiple anti-inflammatory [8][9][10] and immunomodulatory properties [11]. Experimental evidence suggests that propofol is a valuable pharmacological tool to treat pulmonary dysfunction related to CPB [12]. However, these studies are in vitro and may not be relevant to the clinical scenario. Hence, we undertook a prospective,

In this study, we investigated the role ofhistone deacetylase 4 (HDAC4) and MEG3/miR-125a-5p/interferonregulatoryfactor 1 (IRF1) on vascular smooth muscle cell (VSMCs)proliferation. Platelet derived growth factor (PDGF)-BB was used toinduce the proliferation and migration of VSMCs. The expressionsof MEG3, miR-125a-5p, HDAC4 and IRF1in VSMCs were detectedby qRT-PCR and western blot, respectively. ChIP assay was usedto determine the relationship between MEG3 and HDAC4. Doubleluciferase reporter assay was used to test the regulation betweenmiR-125-5p and IRF1. Results showed that PDGF-BB decreasedthe expression of MEG3 and IRF1, while increased the expressionof miR-125a-5p and HDAC4. In addition, HDAC4 knockdowninhibited the proliferation and migration of VSMCs via upregulatingMEG3 and downregulating miR-125a-5p. MiR-125a-5p inhibitorcould repress the proliferation and migration of VSMCs andalleviate intimal hyperplasia (IH) by directly upregulating IRF1expression. These results suggested that HDAC4 interferenceinhibited PDGF-BB-induced VSMCs proliferation via regulatingMEG3/miR-125a-5p/IRF1 axis, and then alleviated IH.

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Background Although frailty is a common geriatric syndrome in old adults, a simple method to assess the degree of frailty in a person has not yet been established. In this study we have tried to establish the association between calf circumference (CC) and frailty among older Chinese people. Methods We used the data obtained from the 2014 edition of the Chinese Longitudinal Healthy Longevity Survey; 1216 participants aged ≥60 years were included for the study. Body mass index, CC and waist circumference measurement data, and laboratory test results were collected. Frailty status was measured using the frailty index (FI). Participants were then classified into non-frail (FI < 0.25) and frail (FI ≥ 0.25) groups. Results There were 874 participants (71.9%) in the non-frail group and 342 (28.1%) in the frail group. The CC was significantly different between the two groups (31.54 ± 4.16 versus 28.04 ± 4.53, P < 0.001). Logistic regression analysis revealed that CC (odds ratio = 0.947, 95% confidence interval: 0.904–0.993, P = 0.023) was an independent impact factor associated with frailty. The CC value of 28.5 cm was considered the best cut-off value in women with area under the curve (AUC) was 0.732 (P < 0.001) and 29.5 cm in men with AUC was 0.592 (P = 0.004);We created a simple prediction model for frailty that included age,sex and CC:$$\textrm{Logit}(P)=-9.756+0.123\ast \textrm{Age}-0.512\ast \textrm{Sex}\left(\textrm{man}=1,\textrm{woman}=0\right)-0.053\ast \textrm{CC},$$ Logit ( P ) = - 9.756 + 0.123 * Age - 0.512 * Sex man = 1 , woman = 0 - 0.053 * CC , P = elogit(P) /1 + elogit(P), and AUC is 0.849 (P < 0.001). Conclusions CC is a convenient and predictable marker of frailty in older adults.