Abstract Acute ischemic stroke (AIS) results in high mortality, especially among patients admitted to the intensive care unit. Previous research has shown the relationship of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with stroke. However, unlike in heart disease, few research has related NT-proBNP with severity and prognosis of patients with AIS in the intensive care unit. This study aimed to investigate the relation between NT-proBNP, which is widely used in heart disease, and the short-term mortality of patients with AIS in critical care unit. This retrospective study was based on Medical Information Mart for Intensive Care (MIMIC)-IV. The main outcome was defined as mortality in seven days and the secondary outcomes were defined as ventricular tachycardia and performance of endotracheal tube. Patients diagnosed with acute ischemic stroke and acute cerebral infarction were extracted based on the 9th and 10th versions of ICD codes. If the patient was treated multiple times in the ICU, only the data of the first admission to the ICU will be taken for research and analysis. The level of NT-proBNP was significantly associated with 7-day all-cause mortality in patients with AIS, the HR was 1.84 ([95% CI, 1.11–3.07], P = 0.019). After excluding patients with heart failure, NT-proBNP showed significant association with 7-day all-cause mortality, the HR was 2.71 ([95% CI, 1.15–6.37], P = 0.022). There was no significant association between NT-proBNP and secondary outcomes. In patients with AIS in intensive care unit, higher levels of NT-proBNP related with a higher mortality. NT-proBNP might serve as a biomarker that help to predict the short-term mortality among the patients with AIS in intensive care unit.
Abstract Background : Lung cancer is the leading cause of cancer-related death worldwide. Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer. Traditional anticancer therapies involving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) have been proven beneficial in the treatment of patients with EGFR mutations. However, patients with EGFR wild-type NSCLC usually fail to respond to EGFR-TKIs. Enhancer of zeste homolog 2 ( EZH2 ), a key molecule of the PRC2 complex, plays an important role in epigenetic regulation and is overexpressed in various tumors. EZH2 inhibitors sensitize various types of tumor cells to antitumor drugs. Therefore, this study aimed to investigate whether the EZH2 inhibitors GSK343 and DZNep, whencombined with gefitinib, can reverse EGFR-TKI resistance in EGFR wild-type NSCLC. Methods : EZH2 expression was evaluated using the RNA sequencing dataset of NSCLC patients (502 lung squamous cell carcinoma cases including 49 paracancerous lung tissues and 513 lung adenocarcinoma cases including 59 paracancerous lung tissues) from The Cancer Genome Atlas (TCGA). We simultaneously also verified EZH2 expressionin 40 NSCLC samples and their corresponding paracancerous lung tissues from our institution via quantitative PCR. The lung adenocarcinoma cell lines A549 and H1299 were treated with EZH2 -specific small interfering RNA or EZH2 inhibitors and subjected to analyses of cell viability and apoptosis as well as of EGFR pathway protein expressions by western blotting. Results: EZH2 was upregulated in human NSCLC tissues and was correlated with poor prognosis in patients with lung adenocarcinoma based on data from both TCGA and our institution. Both EZH2 inhibitors sensitized A549 and H1299 cells to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted stronger inhibitory effects on tumor activity, cell proliferation, and cell migration than single drug administration in vitro and in vivo . Conclusion: Co-administration of EZH2 inhibitors with EGFR-TKIs may be feasible for the treatment of EGFR wild-type NSCLC in patients who refuse traditional chemotherapy.
The presence of allergic rhinitis (AR) is an increased risk factor for the occurrence of bronchial asthma (BA). Nerve growth factor (NGF), in addition to its key role in the development and differentiation of neurons, may also be an important inflammatory factor in AR and BA. However, the pathogenesis of the progression of AR to BA remains to be elucidated. The present study aimed to investigate the ability of NGF to mediate nasobronchial interactions and explore possible underlying molecular mechanisms. In the present study, an AR mouse model was established and histology of nasal mucosa tissue injury was determined. The level of phenylethanolamine N‑methyl transferase in adrenal medulla was determined by immunofluorescence. Primary adrenal medullary chromaffin cells (AMCCs) were isolated and cultured from the adrenal medulla of mice. The expression levels of synaptophysin (SYP), STAT1, JAK1, p38 and ERK in NGF‑treated and untreated AMCCs were detected by reverse‑transcription‑quantitative PCR and western blotting. The epinephrine (EPI) and norepinephrine (NE) concentrations were measured by ELISA. It was found that the expression of SYP in AMCCs was enhanced in the presence of NGF, whereas, the concentration of EPI decreased significantly under the same conditions. Furthermore, NGF mediated the phenotypic and functional changes of AMCCs, resulting in decreased EPI secretion via JAK1/STAT1, p38 and ERK signaling. In conclusion, these findings could provide novel evidence for the role of NGF in regulating neuroendocrine mechanisms.
<b>Objective</b> We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among Chinese population aged 40 years or older. <p><b>Research design and methods </b>Baseline lifestyle information, waist circumference, blood pressure, lipid profiles and glycemic status were obtained in a nationwide, multicenter, prospective study of 170 240 participants. During the up to 5 years of follow-up, we detected 7 847 diabetes according to the American Diabetes Association 2010 criteria and 3 520 cardiovascular events including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure.</p> <p><b>Results: </b>Based on 36.13% (population-attributable fraction, PAF) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status.</p> <p><b>Conclusions: </b>We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status.</p>
Recent evidence indicates that prednisone can potentiate renal responsiveness to diuretics in heart failure (HF). However, the optimal dose of prednisone is not known.Thirty-eight patients with symptomatic HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/d, n = 8), medium-dose (30 mg/d, n = 10), or high-dose prednisone (60 mg/d, n = 10), for 10 days. During this time, we recorded the 24-hour urinary output and the 24-hour urinary sodium excretion, at baseline, on day 5 and day 10. We also monitored the change in the concentration of serum creatinine, angiotensin II, aldosterone, high-sensitive C-reactive protein, tumor necrosis factor-α, interleukin 1β, and interleukin 6.Low-dose prednisone significantly enhanced urine output. However, the effects of medium- and high-dose prednisone on urine output were less obvious. As for renal sodium excretion, high-dose prednisone induced a more potent natriuresis than low-dose prednisone. Despite the potent diuresis and natriuresis induced by prednisone, serum creatinine, angiotensin II, and aldosterone levels were not elevated. These favorable effects were not associated with an inflammatory suppression by glucocorticoids.Only low-dose prednisone significantly enhanced urine output. However, high-dose prednisone induced a more potent renal sodium excretion than low-dose prednisone.
The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to exert cardioprotective effects against acute myocardial infarction (AMI) due to ischemic injury. However, the mechanisms responsible for these effects are not yet fully understood. In this study, we investigated whether sodium hydrogen sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. For this purpose, we utilized an in vivo rat model of AMI by occluding the left anterior descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally), the GSK-3β inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1% dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The results demonstrated that the administration of medium- and high-dose NaHS and SB216763 significantly improved rat cardiac function, as evidenced by an increase in the mean arterial pressure, left ventricular developed pressure, contraction and relaxation rates, as well as a decrease in left ventricular end-diastolic pressure. In addition, the administration of NaHS and SB216763 attenuated myocardial injury as reflected by a decrease in apoptotic cell death and in the serum lactate dehydrogenase concentrations, and prevented myocardial structural changes. The administration of NaHS and SB216763 increased the concentrations of phosphorylated (p-)GSK-3β, the p-GSK-3β/t-GSK-3β ratio and downstream protein β-catenin. Moreover, western blot and immunohistochemical analyses of apoptotic signaling pathway proteins further established the cardioprotective potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the downregulation of Bax expression, and a decrease in the number of TUNEL-positive stained cells. These findings suggest that hydrosulfide exerts cardioprotective effects against AMI-induced apoptosis through the GSK-3β/β-catenin signaling pathway.
To evaluate the effects of high and low levels of PEEP on ICU patients without ARDS.We searched public databases (including PubMed, EMBASE, Cochrane Library and Clinicaltrial.gov). The Cochrane Risk of Bias Assessment tool was used to evaluate the quality of the included studies.We included 2307 patients from 24 trials. Although no significant difference was found between high and low PEEP applications in in-hospital mortality (risk ratio[RR] 0.98, 95% confidence interval[CI] [0.81, 1.19], P = 0.87), high PEEP indeed decreased the incidence of ARDS, hypoxemia, and increased the level of PaO2/FIO2. In addition, although the overall results did not reveal any advantages of high PEEP in terms of secondary outcomes regarding 28-day mortality, the duration of ventilation, atelectasis, pulmonary barotrauma, hypotension, and so forth, the subgroup analysis concerning the level of low PEEP (ZEEP or not) and patient type (postoperative or medical ones) yielded different results. The TSA results suggested that more RCTs are needed.Although ventilation with high PEEP in ICU patients without ARDS may not reduce in-hospital mortality, the decreased incidences of ARDS and hypoxemia and the improvement in PaO2/FIO2 were found in the high PEEP arm.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)